{"query": "How much impact do masks have on preventing the spread of the COVID-19?", "hits": [{"content": "Title: Masking the general population might attenuate COVID-19 outbreaks Content: The effect of masking the general population on a COVID-19 epidemic is estimated by computer simulation using two separate state-of-the-art web-based softwares, one of them calibrated for the SARS-CoV-2 virus. The questions addressed are these: 1. Can mask use by the general population limit the spread of SARS-CoV-2 in a country? 2. What types of masks exist, and how elaborate must a mask be to be effective against COVID-19? 3. Does the mask have to be applied early in an epidemic? 4. A brief general discussion of masks and some possible future research questions regarding masks and SARS-CoV-2. Results are as follows: (1) The results indicate that any type of mask, even simple home-made ones, may be effective. Masks use seems to have an effect in lowering new patients even the protective effect of each mask (here dubbed\"one-mask protection\") is low. Strict adherence to mask use does not appear to be critical. However, increasing the one-mask protection to>50% was found to be advantageous. Masks seemed able to reduce overflow of capacity, e.g. of intensive care. As the default parameters of the software included another intervention, it seems possible to combine mask and other interventions. (2) Masks do seem to reduce the number of new cases even if introduced at a late stage in an epidemic. However, early implementation helps reduce the cumulative and total number of cases. (3) The simulations suggest that it might be possible to eliminate a COVID-19 outbreak by widespread mask use during a limited period. The results from these simulations are encouraging, but do not necessarily represent the real-life situation, so it is suggested that clinical trials of masks are now carried out while continuously monitoring effects and side-effects.", "qid": 44, "docid": "ugkxxaeb", "rank": 1, "score": 0.8257986307144165}, {"content": "Title: Brief research report: Bidirectional impact of imperfect mask use on reproduction number of COVID-19: A next generation matrix approach() Content: The use of masks as a means of reducing transmission of COVID-19 outside healthcare settings has proved controversial. Masks are thought to have two modes of effect: they prevent infection with COVID-19 in wearers; and prevent transmission by individuals with subclinical infection. We used a simple next-generation matrix approach to estimate the conditions under which masks would reduce the reproduction number of COVID-19 under a threshold of 1. Our model takes into account the possibility of assortative mixing, where mask users interact preferentially with other mask users. We make 3 key observations: 1. Masks, even with suboptimal efficacy in both prevention of acquisition and transmission of infection, could substantially decrease the reproduction number for COVID-19 if widely used. 2. Widespread masking may be sufficient to suppress epidemics where R has been brought close to 1 via other measures (e.g., distancing). 3. \u201cAssortment\u201d within populations (the tendency for interactions between masked individuals to be more likely than interactions between masked and unmasked individuals) would rapidly erode the impact of masks. As such, mask uptake needs to be fairly universal to have an effect. This simple model suggests that widespread uptake of masking could be determinative in suppressing COVID-19 epidemics in regions with R(t) at or near 1.", "qid": 44, "docid": "dt2pew66", "rank": 2, "score": 0.8256139755249023}, {"content": "Title: A simple model to show the relative risk of viral aerosol infection and the benefit of wearing masks in different settings with implications for Covid-19 . Content: Background . Widespread use of masks in the general population is being used in many countries for Covid-19 . There has been reluctance on the part of the WHO and some governments to recommend this . Methodology . A basic model has been constructed to show the relative risk of aerosol from normal breathing in various situations together with the benefit from use of masks which is multiplicative . Results . Social distancing at 2 metres is validated but in confined areas is time limited and the use of masks in the absence of extremely good ventilation is important. Where social distancing is not possible at all times or an infectious person is in a confined area for a prolonged period there is a higher risk of infection requiring protection . Conclusions . The use of masks should be factored into models and used at an early stage as widespread use of more efficient masks could have a large impact on control and spread of infection . Public health planning requires stockpiling masks and encouraging everyone to have suitable masks in their household when supplies are normalised . The use of a cloth mask will be better than no protection at all .", "qid": 44, "docid": "sqr11fpv", "rank": 3, "score": 0.8086904287338257}, {"content": "Title: Face Masks Considerably Reduce Covid-19 Cases in Germany Content: We use the synthetic control method to analyze the effect of face masks on the spread of Covid-19 in Germany. Our identification approach exploits regional variation in the point in time when face masks became compulsory. Depending on the region we analyse, we find that face masks reduced the cumulative number of registered Covid-19 cases between 2.3% and 13% over a period of 10 days after they became compulsory. Assessing the credibility of the various estimates, we conclude that face masks reduce the daily growth rate of reported infections by around 40%.", "qid": 44, "docid": "yx9oa2ra", "rank": 4, "score": 0.8045148849487305}, {"content": "Title: The effect of behavior of wearing masks on epidemic dynamics Content: Recently, COVID-19 has attracted a lot of attention of researchers from different fields. Wearing masks is a frequently adopted precautionary measure. In this paper, we investigate the effect of behavior of wearing masks on epidemic dynamics in the context of COVID-19. At each time, every susceptible individual chooses whether to wear a mask or not in the next time step, which depends on an evaluation of the potential costs and perceived risk of infection. When the cost of infection is high, the majority of the population choose to wear masks, where global awareness plays a significant role. However, if the mask source is limited, global awareness may give rise to a negative result. In this case, more mask source should be allocated to the individuals with high risk of infection.", "qid": 44, "docid": "2iokkog5", "rank": 5, "score": 0.8027182817459106}, {"content": "Title: The use of facemasks may not lead to an increase in hand-face contact Content: Advocacy of the use of facemasks by the public as a measure against the spread of COVID-19 is controversial, with some healthcare professionals arguing that the use of a face mask may increase the rate at which people touch their faces, due to readjusting the mask. We assessed the facial touching behaviour of bus passengers in China before and after the outbreak of COVID-19 and found that wearing a face mask does not increase the number of hand-face contacts and is likely, therefore, to have a positive beneficial effect on suppressing the spread of COVID-19 within populations when used in conjunction with social distancing measures.", "qid": 44, "docid": "gaujhk7z", "rank": 6, "score": 0.8004345893859863}, {"content": "Title: The use of facemasks may not lead to an increase in hand\u2013face contact Content: Advocacy of the use of facemasks by the public as a measure against the spread of COVID\u201019 is controversial, with some healthcare professionals arguing that the use of a face mask may increase the rate at which people touch their faces, due to readjusting the mask. We assessed the facial touching behaviour of bus passengers in China before and after the outbreak of COVID\u201019 and found that wearing a face mask does not increase the number of hand\u2010face contacts and is likely, therefore, to have a positive beneficial effect on suppressing the spread of COVID\u201019 within populations when used in conjunction with social distancing measures.", "qid": 44, "docid": "8g2v5cku", "rank": 7, "score": 0.7965711355209351}, {"content": "Title: Face mask use in the general population and optimal resource allocation during the COVID-19 pandemic Content: The ongoing novel coronavirus disease (COVID-19) pandemic has rapidly spread in early 2020, causing tens of thousands of deaths, over a million cases and widespread socioeconomic disruption. With no vaccine available and numerous national healthcare systems reaching or exceeding capacity, interventions to limit transmission are urgently needed. While there is broad agreement that travel restrictions and closure of non-essential businesses and schools are beneficial in limiting local and regional spread, recommendations around the use of face masks for the general population are less consistent internationally. In this study, we examined the role of face masks in mitigating the spread of COVID-19 in the general population, using epidemic models to estimate the total reduction of infections and deaths under various scenarios. In particular, we examined the optimal deployment of face masks when resources are limited, and explored a range of supply and demand dynamics. We found that face masks, even with a limited protective effect, can reduce infections and deaths, and can delay the peak time of the epidemic. We consistently found that a random distribution of masks in the population was a suboptimal strategy when resources were limited. Prioritizing coverage among the elderly was more beneficial, while allocating a proportion of available resources for diagnosed infected cases provided further mitigation under a range of scenarios. In summary, face mask use, particularly for a pathogen with relatively common asymptomatic carriage, can effectively provide some mitigation of transmission, while balancing provision between vulnerable healthy persons and symptomatic persons can optimize mitigation efforts when resources are limited.", "qid": 44, "docid": "qdamvwxl", "rank": 8, "score": 0.7965478897094727}, {"content": "Title: To mask or not to mask: Modeling the potential for face mask use by the general public to curtail the COVID-19 pandemic Content: Face mask use by the general public for limiting the spread of the COVID-19 pandemic is controversial, though increasingly recommended, and the potential of this intervention is not well understood. We develop a compartmental model for assessing the community-wide impact of mask use by the general, asymptomatic public, a portion of which may be asymptomatically infectious. Model simulations, using data relevant to COVID-19 dynamics in the US states of New York and Washington, suggest that broad adoption of even relatively ineffective face masks may meaningfully reduce community transmission of COVID-19 and decrease peak hospitalizations and deaths. Moreover, mask use decreases the effective transmission rate in nearly linear proportion to the product of mask effectiveness (as a fraction of potentially infectious contacts blocked) and coverage rate (as a fraction of the general population), while the impact on epidemiologic outcomes (death, hospitalizations) is highly nonlinear, indicating masks could synergize with other non-pharmaceutical measures. Notably, masks are found to be useful with respect to both preventing illness in healthy persons and preventing asymptomatic transmission. Hypothetical mask adoption scenarios, for Washington and New York state, suggest that immediate near universal (80%) adoption of moderately (50%) effective masks could prevent on the order of 17\u201345% of projected deaths over two months in New York, while decreasing the peak daily death rate by 34\u201358%, absent other changes in epidemic dynamics. Even very weak masks (20% effective) can still be useful if the underlying transmission rate is relatively low or decreasing: In Washington, where baseline transmission is much less intense, 80% adoption of such masks could reduce mortality by 24\u201365% (and peak deaths 15\u201369%), compared to 2\u20139% mortality reduction in New York (peak death reduction 9\u201318%). Our results suggest use of face masks by the general public is potentially of high value in curtailing community transmission and the burden of the pandemic. The community-wide benefits are likely to be greatest when face masks are used in conjunction with other non-pharmaceutical practices (such as social-distancing), and when adoption is nearly universal (nation-wide) and compliance is high.", "qid": 44, "docid": "qi1henyy", "rank": 9, "score": 0.7930253744125366}, {"content": "Title: To mask or not to mask: Modeling the potential for face mask use by the general public to curtail the COVID-19 pandemic Content: Face mask use by the general public for limiting the spread of the COVID-19 pandemic is controversial, though increasingly recommended, and the potential of this intervention is not well understood. We develop a compartmental model for assessing the community-wide impact of mask use by the general, asymptomatic public, a portion of which may be asymptomatically infectious. Model simulations, using data relevant to COVID-19 dynamics in the US states of New York and Washington, suggest that broad adoption of even relatively ineffective face masks may meaningfully reduce community transmission of COVID-19 and decrease peak hospitalizations and deaths. Moreover, mask use decreases the effective transmission rate in nearly linear proportion to the product of mask effectiveness (as a fraction of potentially infectious contacts blocked) and coverage rate (as a fraction of the general population), while the impact on epidemiologic outcomes (death, hospitalizations) is highly nonlinear, indicating masks could synergize with other non-pharmaceutical measures. Notably, masks are found to be useful with respect to both preventing illness in healthy persons and preventing asymptomatic transmission. Hypothetical mask adoption scenarios, for Washington and New York state, suggest that immediate near universal (80%) adoption of moderately (50%) effective masks could prevent on the order of 17--45% of projected deaths over two months in New York, while decreasing the peak daily death rate by 34--58%, absent other changes in epidemic dynamics. Even very weak masks (20% effective) can still be useful if the underlying transmission rate is relatively low or decreasing: In Washington, where baseline transmission is much less intense, 80% adoption of such masks could reduce mortality by 24--65% (and peak deaths 15--69%), compared to 2--9% mortality reduction in New York (peak death reduction 9--18%). Our results suggest use of face masks by the general public is potentially of high value in curtailing community transmission and the burden of the pandemic. The community-wide benefits are likely to be greatest when face masks are used in conjunction with other non-pharmaceutical practices (such as social-distancing), and when adoption is nearly universal (nation-wide) and compliance is high.", "qid": 44, "docid": "28utunid", "rank": 10, "score": 0.7906749844551086}, {"content": "Title: Who is wearing a mask? Gender-, age-, and location-related differences during the COVID-19 pandemic Content: Masks are an effective tool in combatting the spread of COVID-19 but wearing them remains controversial and has not been studied in the United States. To understand the demographics of mask wearers in the US, we observed shoppers (n = 5517) entering retail stores. 41.5% of the observed sample wore a mask. The odds of an individual wearing a mask increased significantly with age, and was also 1.5x greater for females than males. Additionally, the odds of observing a mask on an urban or suburban shopper were ~4x that for rural areas. Thus, gender, age, and location factor into whether American shoppers wear a mask or face covering. Regardless, all demographics wore masks at substantially lesser rates than required to stop the spread of COVID-19.", "qid": 44, "docid": "f4uh73j7", "rank": 11, "score": 0.7868831157684326}, {"content": "Title: Reply to Zhang et al.: Slowing the rate of spread of COVID-19 Content: Zhang et al. (2020) reported that mandating face coverings in public is necessary to decrease the rate of new COVID-19 infections. We present a counterexample that disproves this finding. We agree with Zhang et al. that masks can be an important element in reducing virus transmission and that widespread use may be essential for returning to full activity. However, their analysis neglects the potential importance of physical distancing for limiting COVID-19 transmission by misattributing its effect to mask requirements. A full suite of epidemiological tools is necessary in these challenging times.", "qid": 44, "docid": "8t8psk46", "rank": 12, "score": 0.785131573677063}, {"content": "Title: Mask use during COVID-19: A risk adjusted strategy() Content: In the context of Coronavirus Disease (2019) (COVID-19) cases globally, there is a lack of consensus across cultures on whether wearing face masks is an effective physical intervention against disease transmission. This study 1) illustrates transmission routes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); 2) addresses controversies surrounding the mask from perspectives of attitude, effectiveness, and necessity of wearing the mask with evidence that the use of mask would effectively interrupt the transmission of infectious diseases in both hospital settings and community settings; and 3) provides suggestion that the public should wear the mask during COVID-19 pandemic according to local context. To achieve this goal, government should establish a risk adjusted strategy of mask use to scientifically publicize the use of masks, guarantee sufficient supply of masks, and cooperate for reducing health resources inequities.", "qid": 44, "docid": "iaiosjlu", "rank": 13, "score": 0.7847244739532471}, {"content": "Title: Mask use during COVID-19: A risk adjusted strategy Content: In the context of Coronavirus Disease (2019) (COVID-19) cases globally, there is a lack of consensus across cultures on whether wearing face masks is an effective physical intervention against disease transmission. This study 1) illustrates transmission routes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); 2) addresses controversies surrounding the mask from perspectives of attitude, effectiveness, and necessity of wearing the mask with evidence that the use of mask would effectively interrupt the transmission of infectious diseases in both hospital settings and community settings; and 3) provides suggestion that the public should wear the mask during COVID-19 pandemic according to local context. To achieve this goal, government should establish a risk adjusted strategy of mask use to scientifically publicize the use of masks, guarantee sufficient supply of masks, and cooperate for reducing health resources inequities.", "qid": 44, "docid": "6tod4abn", "rank": 14, "score": 0.7847244739532471}, {"content": "Title: Universal Masking is Urgent in the COVID-19 Pandemic: SEIR and Agent Based Models, Empirical Validation, Policy Recommendations Content: We present two models for the COVID-19 pandemic predicting the impact of universal face mask wearing upon the spread of the SARS-CoV-2 virus--one employing a stochastic dynamic network based compartmental SEIR (susceptible-exposed-infectious-recovered) approach, and the other employing individual ABM (agent-based modelling) Monte Carlo simulation--indicating (1) significant impact under (near) universal masking when at least 80% of a population is wearing masks, versus minimal impact when only 50% or less of the population is wearing masks, and (2) significant impact when universal masking is adopted early, by Day 50 of a regional outbreak, versus minimal impact when universal masking is adopted late. These effects hold even at the lower filtering rates of homemade masks. To validate these theoretical models, we compare their predictions against a new empirical data set we have collected that includes whether regions have universal masking cultures or policies, their daily case growth rates, and their percentage reduction from peak daily case growth rates. Results show a near perfect correlation between early universal masking and successful suppression of daily case growth rates and/or reduction from peak daily case growth rates, as predicted by our theoretical simulations. Our theoretical and empirical results argue for urgent implementation of universal masking. As governments plan how to exit societal lockdowns, it is emerging as a key NPI; a\"mouth-and-nose lockdown\"is far more sustainable than a\"full body lockdown\", on economic, social, and mental health axes. An interactive visualization of the ABM simulation is at http://dek.ai/masks4all. We recommend immediate mask wearing recommendations, official guidelines for correct use, and awareness campaigns to shift masking mindsets away from pure self-protection, towards aspirational goals of responsibly protecting one's community.", "qid": 44, "docid": "m5udub60", "rank": 15, "score": 0.7837308049201965}, {"content": "Title: Efficacy of face mask in preventing respiratory virus transmission: a systematic review and meta-analysis Content: Background: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. Results: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24-0.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11-0.37) and 47% (OR = 0.53, 95% CI = 0.36-0.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials, case-control studies and retrospective studies. Conclusions: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak.", "qid": 44, "docid": "ropgq7tr", "rank": 16, "score": 0.7832973003387451}, {"content": "Title: Efficacy of face mask in preventing respiratory virus transmission: A systematic review and meta-analysis Content: BACKGROUND: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. RESULTS: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24-0.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11-0.37) and 47% (OR = 0.53, 95% CI = 0.36-0.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials and observational studies. CONCLUSIONS: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak.", "qid": 44, "docid": "b4znk2wr", "rank": 17, "score": 0.7827433347702026}, {"content": "Title: Efficacy of face mask in preventing respiratory virus transmission: A systematic review and meta-analysis Content: BACKGROUND: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. RESULTS: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24\u20130.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11\u20130.37) and 47% (OR = 0.53, 95% CI = 0.36\u20130.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials and observational studies. CONCLUSIONS: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak.", "qid": 44, "docid": "x9sfgtim", "rank": 18, "score": 0.7825070023536682}, {"content": "Title: Importance of face masks for COVID-19 - a call for effective public education Content: Considerable debates about the general community use of face masks for protection against COVID-19 stemmed out from differing views taken by health authorities. Misconceptions and stigmatization towards the use of face masks may hinder the containment of the COVID-19 pandemic. We address this previous debate by analyzing the advice on the community use of masks across different credible health authorities: countries that promoted the use of masks acknowledged that masks are effective, but also explained the importance of their proper use along with other hygiene measures. In contrast, authorities that recommended against the community use of masks mainly cited shortage of supplies, the argument that the public do not have the adequate skills to wear them, or that wearing masks might reduce compliance with other important behaviors. We suggest promoting effective behavioral changes in personal protective measures by teaching microbiological knowledge instead of just listing out the \"dos-and-don'ts\".", "qid": 44, "docid": "wee1133a", "rank": 19, "score": 0.7816693782806396}, {"content": "Title: Importance of face masks for COVID-19 \u2013 a call for effective public education Content: Considerable debates about the general community use of face masks for protection against COVID-19 stemmed out from differing views taken by health authorities. Misconceptions and stigmatization towards the use of face masks may hinder the containment of the COVID-19 pandemic. We address this previous debate by analyzing the advice on the community use of masks across different credible health authorities: countries that promoted the use of masks acknowledged that masks are effective, but also explained the importance of their proper use along with other hygiene measures. In contrast, authorities that recommended against the community use of masks mainly cited shortage of supplies, the argument that the public do not have the adequate skills to wear them, or that wearing masks might reduce compliance with other important behaviors. We suggest promoting effective behavioral changes in personal protective measures by teaching microbiological knowledge instead of just listing out the \u201cdos-and-don\u2019ts\u201d.", "qid": 44, "docid": "p2ufydgs", "rank": 20, "score": 0.7809469103813171}, {"content": "Title: Teach, and teach and teach: does the average citizen use masks correctly during daily activities? Results from an observational study with more than 12,000 participants Content: COVID-19 is a new disease with no treatment and no vaccine so far. The pandemic is still growing in many areas. Among the core measures to prevent disease spread is the use of face masks. We observed 12,588 people in five Brazilian cities within the Baixada Santista metropolitan area. Even though this is densely populated region and heavily impacted by COVID-19 with a high risk population, only 45.1% of the observed population wore in face masks in a correct way, and another 15.5% simply did not use masks at all. The remainder used masks incorrectly, which is evidence of the worst scenario of people believing that they are protected when they are not. This is among the first studies, to the best of our knowledge, that measures real life compliance with face masks during this COVID-19 pandemic. It is our conclusion that it is paramount to first control the virus before allowing people back in the streets. We should not assume that people will wear masks properly. Equally important is to instruct and sensitize people on how to use face masks and why it is important.", "qid": 44, "docid": "ej76fsxa", "rank": 21, "score": 0.7780901193618774}, {"content": "Title: A modelling framework to assess the likely effectiveness of facemasks in combination with 'lock-down' in managing the COVID-19 pandemic Content: COVID-19 is characterized by an infectious presymptomatic period,when newly infected individuals can unwittingly infect others We are interested in what benefits facemasks could offer as a nonpharmaceutical intervention, especially in the settings where high-technology interventions, such as contact tracing using mobile apps or rapid case detection via molecular tests, are not sustainable Here, we report the results of two mathematical models and show that facemask use by the public could make a major contribution to reducing the impact of the COVID-19 pandemic Our intention is to provide a simple modelling framework to examine the dynamics of COVID-19 epidemics when facemasks are worn by the public, with or without imposed 'lock-down' periods Our results are illustrated for a number of plausible values for parameter ranges describing epidemiological processes and mechanistic properties of facemasks, in the absence of current measurements for these values We show that, when facemasks are used by the public all the time (not just from when symptoms first appear), the effective reproduction number, Re, can be decreased below 1, leading to the mitigation of epidemic spread Under certain conditions, when lock-down periods are implemented in combination with 100% facemask use, there is vastly less disease spread, secondary and tertiary waves are flattened and the epidemic is brought under control The effect occurs even when it is assumed that facemasks are only 50% effective at capturing exhaled virus inoculum with an equal or lower efficiency on inhalation Facemask use by the public has been suggested to be ineffective because wearers may touch their facesmore often, thus increasing the probability of contracting COVID-19 For completeness, our models show that facemask adoption provides population-level benefits, even in circumstances where wearers are placed at increased risk At the time of writing, facemask use by the public has not been recommended in many countries, but a recommendation for wearing face-coverings has just been announced for Scotland Even if facemask use began after the start of the first lock-down period, our results show that benefits could still accrue by reducing the risk of the occurrence of further COVID-19 waves We examine the effects of different rates of facemask adoption without lock-down periods and show that, even at lower levels of adoption, benefits accrue to the facemask wearers These analyses may explain why some countries, where adoption of facemask use by the public is around 100%, have experienced significantly lower rates of COVID-19 spread and associated deaths We conclude that facemask use by the public, when used in combination with physical distancing or periods of lock-down, may provide an acceptable way of managing the COVID- 19 pandemic and re-opening economic activity These results are relevant to the developed as well as the developing world, where large numbers of people are resource poor, but fabrication of home-made, effective facemasks is possible A key message from our analyses to aid the widespread adoption of facemasks would be: 'my mask protects you, your mask protects me' [ABSTRACT FROM AUTHOR] Copyright of Proceedings of the Royal Society A: Mathematical, Physical & Engineering Sciences is the property of Royal Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )", "qid": 44, "docid": "30pl5tx3", "rank": 22, "score": 0.7719488143920898}, {"content": "Title: Universal Masking during Covid-19 Pandemic - Current Evidence and Controversies Content: The emergence of coronavirus disease 19 pandemic and novel research on the high transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised controversies over the use of face masks to prevent community transmission. Specific regulations need to be fulfilled to use a face mask as part of the personal protective equipment and high quality of evidence supporting its use to prevent respiratory viral infections, including SARS-CoV-2, is lacking. However, its widespread use is becoming a standard practice in some countries and discrepancies between health authorities on their policy have led to controversy. The aim of this review is to provide an outlook on recent research in this matter and areas of opportunity.", "qid": 44, "docid": "fdkqs3rg", "rank": 23, "score": 0.7714024186134338}, {"content": "Title: UNIVERSAL MASKING DURING COVID-19 PANDEMIC - CURRENT EVIDENCE AND CONTROVERSIES. Content: The emergence of coronavirus disease 19 pandemic and novel research on the high transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised controversies over the use of face masks to prevent community transmission. Specific regulations need to be fulfilled to use a face mask as part of the personal protective equipment and high quality of evidence supporting its use to prevent respiratory viral infections, including SARS-CoV-2, is lacking. However, its widespread use is becoming a standard practice in some countries and discrepancies between health authorities on their policy have led to controversy. The aim of this review is to provide an outlook on recent research in this matter and areas of opportunity.", "qid": 44, "docid": "cvulb9t6", "rank": 24, "score": 0.7714024186134338}, {"content": "Title: The history and value of face masks Content: In the human population, social contacts are a key for transmission of bacteria and viruses. The use of face masks seems to be critical to prevent the transmission of SARS-CoV-2 for the period, in which therapeutic interventions are lacking. In this review, we describe the history of masks from the middle age to modern times.", "qid": 44, "docid": "jyju71r1", "rank": 25, "score": 0.7711495161056519}, {"content": "Title: Impact of population mask wearing on Covid-19 post lockdown Content: COVID-19, caused by SARS-CoV2 is a rapidly spreading global pandemic. Although precise transmission routes and dynamics are unknown, SARS-CoV2 is thought primarily to spread via contagious respiratory droplets. Unlike with SARS-CoV, maximal viral shedding occurs in the early phase of illness, and this is supported by models that suggest 40-80% of transmission events occur from pre- and asymptomatic individuals. One widely-discussed strategy to limit transmission of SARS-CoV2, particularly from presymptomatic individuals, has been population-level wearing of masks. Modelling for pandemic influenza suggests some benefit in reducing total numbers infected with even 50% mask-use. COVID-19 has a higher hospitalization and mortality rate than influenza, and the impacts on these parameters, and critically, at what point in the pandemic trajectory mask-use might exert maximal benefit are completely unknown. We derived a simplified SIR model to investigate the effects of near-universal mask-use on COVID-19 assuming 8 or 16% mask efficacy. We decided to model, in particular, the impact of masks on numbers of critically-ill patients and cumulative mortality, since these are parameters that are likely to have the most severe consequences in the COVID-19 pandemic. Whereas mask use had a relatively minor benefit on critical-care and mortality rates when transmissibility (Reff) was high, the reduction on deaths was dramatic as the effective R approached 1, as might be expected after aggressive social-distancing measures such as wide-spread lockdowns. One major concern with COVID-19 is its potential to overwhelm healthcare infrastructures, even in resource-rich settings, with one third of hospitalized patients requiring critical-care. We incorporated this into our model, increasing death rates for when critical-care resources have been exhausted. Our simple model shows that modest efficacy of masks could avert substantial mortality in this scenario. Importantly, the effects on mortality became hyper-sensitive to mask-wearing as the effective R approaches 1, i.e. near the tipping point of when the infection trajectory is expected to revert to exponential growth, as would be expected after effective lockdown. Our model suggests that mask-wearing might exert maximal benefit as nations plan their post-lockdown strategies and suggests that mask-wearing should be included in further more sophisticated models of the current pandemic.", "qid": 44, "docid": "uc37poce", "rank": 26, "score": 0.7707676291465759}, {"content": "Title: Understanding the Impact of Face Mask Usage Through Epidemic Simulation of Large Social Networks Content: Evidence from the 2003 SARS epidemic and 2009 H1N1 pandemic shows that face masks can be an effective non-pharmaceutical intervention in minimizing the spread of airborne viruses. Recent studies have shown that using face masks is correlated to an individual\u2019s age and gender, where females and older adults are more likely to wear a mask than males or youths. There are only a few studies quantifying the impact of using face masks to slow the spread of an epidemic at the population level, and even fewer studies that model their impact in a population where the use of face masks depends upon the age and gender of the population. We use a state-of-the-art agent-based simulation to model the use of face masks and quantify their impact on three levels of an influenza epidemic and compare different mitigation scenarios. These scenarios involve changing the demographics of mask usage, the adoption of mask usage in relation to a perceived threat level, and the combination of masks with other non-pharmaceutical interventions such as hand washing and social distancing. Our results shows that face masks alone have limited impact on the spread of influenza. However, when face masks are combined with other interventions such as hand sanitizer, they can be more effective. We also observe that monitoring social internet systems can be a useful technique to measure compliance. We conclude that educating the public on the effectiveness of masks to increase compliance can reduce morbidity and mortality.", "qid": 44, "docid": "14x4uqq7", "rank": 27, "score": 0.7706689834594727}, {"content": "Title: The Effect of Mask Use on the Spread of Influenza During a Pandemic Content: Face masks have traditionally been used in general infection control, but their efficacy at the population level in preventing transmission of influenza viruses has not been studied in detail. Data from published clinical studies indicate that the infectivity of influenza A virus is probably very high, so that transmission of infection may involve low doses of virus. At low doses, the relation between dose and the probability of infection is approximately linear, so that the reduction in infection risk is proportional to the reduction in exposure due to particle retention of the mask. A population transmission model was set up to explore the impact of population\u2010wide mask use, allowing estimation of the effects of mask efficacy and coverage (fraction of the population wearing masks) on the basic reproduction number and the infection attack rate. We conclude that population\u2010wide use of face masks could make an important contribution in delaying an influenza pandemic. Mask use also reduces the reproduction number, possibly even to levels sufficient for containing an influenza outbreak.", "qid": 44, "docid": "mfb2or98", "rank": 28, "score": 0.767084002494812}, {"content": "Title: Do Face Masks Create a False Sense of Security? A COVID-19 Dilemma Content: Face masks have become an emblem of the public response to COVID-19, with many governments mandating their use in public spaces. The logic is that face masks are low cost and might help prevent some transmission. However, from the start, the assumption that face masks are \"low cost\" was questioned. Early on, there were warnings of the opportunity cost of public use of medical masks given shortages of personal protective equipment for healthcare providers. This led to recommendations for cloth masks and other face coverings, with little evidence of their ability to prevent transmission. However, there may also be a high cost to these recommendations if people rely on face masks in place of other more effective ways to break transmission, such as staying home. We use SafeGraph smart device location data to show that the representative American in states that have face mask mandates spent 20-30 minutes less time at home, and increase visits to a number of commercial locations, following the mandate. Since the reproductive rate of SAR-COV2, the pathogen that causes COVID-19 is hovering right around one, such substitution behavior could be the difference between controlling the epidemic and a resurgence of cases.", "qid": 44, "docid": "1c3fpazy", "rank": 29, "score": 0.7670358419418335}, {"content": "Title: Revisi\u00f3n r\u00e1pida del uso de cubrebocas quir\u00fargicos en \u00e1mbito comunitario e infecciones respiratorias agudas./ [Rapid review of the use of community-wide surgical masks and acute respiratory infections] Content: OBJECTIVE: To assess the effectiveness of using surgical masks in community settings to reduce the probability of infection by SARS-CoV-2 or other acute viral respiratory infection, compared to not using surgical masks. MATERIALS AND METHODS: We followed the Cochrane rapid review methodology. The search strategy encompasses one academic database and pre-prints until April 1, 2020. Titles and abstracts were reviewed by one investigator. The full text review was divided among three researchers. The results were synthesized in a narrative way. RESULTS: 713 manuscripts were identified, of which 21 met the inclusion criteria. Of six systematic reviews, four found no reduction in the probability of transmission. Experimental home studies found no differences in the probability of contagion associated with the use of mouth masks. Only one modeling study estimated a 20% reduction in the incidence of acute respiratory disease, assuming that 10 to 50% of the population use the surgical masks correctly. CONCLUSIONS: The scientific evidence is inconclusive to recommend or discourage the use of surgical masks at the population level. Considering the potential negative effects, official recommendations should await for the results of natural experiments currently occurring in countries that have recommended the use of face masks at the population level.", "qid": 44, "docid": "gy9u32i2", "rank": 30, "score": 0.7668366432189941}, {"content": "Title: Comprehensive review of mask utility and challenges during the COVID-19 pandemic Content: Masks are widely discussed during the course of the ongoing COVID-19 pandemic Most hospitals have implemented universal masking for their healthcare workers, and the Center for Disease Control currently advises even the general public to wear cloth masks when outdoors The pertinent need for masks arises from plausible dissemination of the SARS-CoV-2 through close contacts, as well as the possibility of virus transmission from asymptomatic, pre-symptomatic, and mildly symptomatic individuals Given current global shortages in personal protective equipment, the efficacy of various types of masks: N95 respirators, surgical masks, and cloth masks are researched To accommodate limited supplies, techniques for extended use, reuse, and sterilization of masks are strategized However, masks alone may not greatly slow down the COVID-19 pandemic unless they are coupled with adequate social distancing, diligent hand hygiene, and other proven preventive measures", "qid": 44, "docid": "7qj00qi9", "rank": 31, "score": 0.7663338780403137}, {"content": "Title: Comprehensive review of mask utility and challenges during the COVID-19 pandemic. Content: Masks are widely discussed during the course of the ongoing COVID-19 pandemic. Most hospitals have implemented universal masking for their healthcare workers, and the Center for Disease Control currently advises even the general public to wear cloth masks when outdoors. The pertinent need for masks arises from plausible dissemination of the SARS-CoV-2 through close contacts, as well as the possibility of virus transmission from asymptomatic, pre-symptomatic, and mildly symptomatic individuals. Given current global shortages in personal protective equipment, the efficacy of various types of masks: N95 respirators, surgical masks, and cloth masks are researched. To accommodate limited supplies, techniques for extended use, reuse, and sterilization of masks are strategized. However, masks alone may not greatly slow down the COVID-19 pandemic unless they are coupled with adequate social distancing, diligent hand hygiene, and other proven preventive measures.", "qid": 44, "docid": "3ttcfhm3", "rank": 32, "score": 0.7647614479064941}, {"content": "Title: Professional and Home-Made Face Masks Reduce Exposure to Respiratory Infections among the General Population Content: BACKGROUND: Governments are preparing for a potential influenza pandemic. Therefore they need data to assess the possible impact of interventions. Face-masks worn by the general population could be an accessible and affordable intervention, if effective when worn under routine circumstances. METHODOLOGY: We assessed transmission reduction potential provided by personal respirators, surgical masks and home-made masks when worn during a variety of activities by healthy volunteers and a simulated patient. PRINCIPAL FINDINGS: All types of masks reduced aerosol exposure, relatively stable over time, unaffected by duration of wear or type of activity, but with a high degree of individual variation. Personal respirators were more efficient than surgical masks, which were more efficient than home-made masks. Regardless of mask type, children were less well protected. Outward protection (mask wearing by a mechanical head) was less effective than inward protection (mask wearing by healthy volunteers). CONCLUSIONS/SIGNIFICANCE: Any type of general mask use is likely to decrease viral exposure and infection risk on a population level, in spite of imperfect fit and imperfect adherence, personal respirators providing most protection. Masks worn by patients may not offer as great a degree of protection against aerosol transmission.", "qid": 44, "docid": "umvrwgaw", "rank": 33, "score": 0.7639659643173218}, {"content": "Title: [Rapid review of the use of community-wide surgical masks and acute respiratory infections]. Content: OBJECTIVE To assess the effectiveness of using surgical masks in community settings to reduce the probability of infection by SARS-CoV-2 or other acute viral respiratory infection, compared to not using surgical masks. MATERIALS AND METHODS We followed the Cochrane rapid review methodology. The search strategy encompasses one academic database and pre-prints until April 1, 2020. Titles and abstracts were reviewed by one investigator. The full text review was divided among three researchers. The results were synthesized in a narrative way. RESULTS 713 manuscripts were identified, of which 21 met the inclusion criteria. Of six systematic reviews, four found no reduction in the probability of transmission. Experimental home studies found no differences in the probability of contagion associated with the use of mouth masks. Only one modeling study estimated a 20% reduction in the incidence of acute respiratory disease, assuming that 10 to 50% of the population use the surgical masks correctly. CONCLUSIONS The scientific evidence is inconclusive to recommend or discourage the use of surgical masks at the population level. Considering the potential negative effects, official recommendations should await for the results of natural experiments currently occurring in countries that have recommended the use of face masks at the population level.", "qid": 44, "docid": "1r6eg1hh", "rank": 34, "score": 0.7638161182403564}, {"content": "Title: A RAPID SYSTEMATIC REVIEW OF THE EFFICACY OF FACE MASKS AND RESPIRATORS AGAINST CORONAVIRUSES AND OTHER RESPIRATORY TRANSMISSIBLE VIRUSES FOR THE COMMUNITY, HEALTHCARE WORKERS AND SICK PATIENTS Content: ABSTRACT Background The pandemic of COVID-19 is growing, and a shortage of masks and respirators has been reported globally. Policies of health organizations for healthcare workers are inconsistent, with a change in policy in the US for universal face mask use. The aim of this study was to review the evidence around the efficacy of masks and respirators for healthcare workers, sick patients and the general public. Methods A systematic review of randomized controlled clinical trials on use of respiratory protection by healthcare workers, sick patients and community members was conducted. Articles were searched on Medline and Embase using key search terms. Results A total of 19 randomised controlled trials were included in this study \u2013 8 in community settings, 6 in healthcare settings and 5 as source control. Most of these randomised controlled trials used different interventions and outcome measures. In the community, masks appeared to be more effective than hand hygiene alone, and both together are more protective. Randomised controlled trials in health care workers showed that respirators, if worn continually during a shift, were effective but not if worn intermittently. Medical masks were not effective, and cloth masks even less effective. When used by sick patients randomised controlled trials suggested protection of well contacts. Conclusion The study suggests that community mask use by well people could be beneficial, particularly for COVID-19, where transmission may be pre-symptomatic. The studies of masks as source control also suggest a benefit, and may be important during the COVID-19 pandemic in universal community face mask use as well as in health care settings. Trials in healthcare workers support the use of respirators continuously during a shift. This may prevent health worker infections and deaths from COVID-19, as aerosolisation in the hospital setting has been documented.", "qid": 44, "docid": "h7ftu3ax", "rank": 35, "score": 0.7631993293762207}, {"content": "Title: A rapid systematic review of the efficacy of face masks and respirators against coronaviruses and other respiratory transmissible viruses for the community, healthcare workers and sick patients Content: BACKGROUND: The pandemic of COVID-19 is growing, and a shortage of masks and respirators has been reported globally. Policies of health organizations for healthcare workers are inconsistent, with a change in policy in the US for universal face mask use. The aim of this study was to review the evidence around the efficacy of masks and respirators for healthcare workers, sick patients and the general public. METHODS: A systematic review of randomized controlled clinical trials on use of respiratory protection by healthcare workers, sick patients and community members was conducted. Articles were searched on Medline and Embase using key search terms. RESULTS: A total of 19 randomised controlled trials were included in this study - 8 in community settings, 6 in healthcare settings and 5 as source control. Most of these randomised controlled trials used different interventions and outcome measures. In the community, masks appeared to be effective with and without hand hygiene, and both together are more protective. Randomised controlled trials in health care workers showed that respirators, if worn continually during a shift, were effective but not if worn intermittently. Medical masks were not effective, and cloth masks even less effective. When used by sick patients randomised controlled trials suggested protection of well contacts. CONCLUSION: The study suggests that community mask use by well people could be beneficial, particularly for COVID-19, where transmission may be pre-symptomatic. The studies of masks as source control also suggest a benefit, and may be important during the COVID-19 pandemic in universal community face mask use as well as in health care settings. Trials in healthcare workers support the use of respirators continuously during a shift. This may prevent health worker infections and deaths from COVID-19, as aerosolisation in the hospital setting has been documented.", "qid": 44, "docid": "in16u4pm", "rank": 36, "score": 0.7613532543182373}, {"content": "Title: Mathematical assessment of the impact of non-pharmaceutical interventions on curtailing the 2019 novel Coronavirus Content: A pandemic of a novel Coronavirus emerged in December of 2019 (COVID-19), causing devastating public health impact across the world. In the absence of a safe and effective vaccine or antivirals, strategies for controlling and mitigating the burden of the pandemic are focused on non-pharmaceutical interventions, such as social-distancing, contact-tracing, quarantine, isolation, and the use of face-masks in public. We develop a new mathematical model for assessing the population-level impact of the aforementioned control and mitigation strategies. Rigorous analysis of the model shows that the disease-free equilibrium is locally-asymptotically stable if a certain epidemiological threshold, known as the reproduction number (denoted by [Formula: see text]), is less than unity. Simulations of the model, using data relevant to COVID-19 transmission dynamics in the US state of New York and the entire US, show that the pandemic burden will peak in mid and late April, respectively. The worst-case scenario projections for cumulative mortality (based on the baseline levels of anti-COVID non-pharmaceutical interventions considered in the study) decrease dramatically by 80% and 64%, respectively, if the strict social-distancing measures implemented are maintained until the end of May or June, 2020. The duration and timing of the relaxation or termination of the strict social-distancing measures are crucially-important in determining the future trajectory of the COVID-19 pandemic. This study shows that early termination of the strict social-distancing measures could trigger a devastating second wave with burden similar to those projected before the onset of the strict social-distancing measures were implemented. The use of efficacious face-masks (such as surgical masks, with estimated efficacy [Formula: see text] 70%) in public could lead to the elimination of the pandemic if at least 70% of the residents of New York state use such masks in public consistently (nationwide, a compliance of at least 80% will be required using such masks). The use of low efficacy masks, such as cloth masks (of estimated efficacy less than 30%), could also lead to significant reduction of COVID-19 burden (albeit, they are not able to lead to elimination). Combining low efficacy masks with improved levels of the other anti-COVID-19 intervention strategies can lead to the elimination of the pandemic. This study emphasizes the important role social-distancing plays in curtailing the burden of COVID-19. Increases in the adherence level of social-distancing protocols result in dramatic reduction of the burden of the pandemic, and the timely implementation of social-distancing measures in numerous states of the US may have averted a catastrophic outcome with respect to the burden of COVID-19. Using face-masks in public (including the low efficacy cloth masks) is very useful in minimizing community transmission and burden of COVID-19, provided their coverage level is high. The masks coverage needed to eliminate COVID-19 decreases if the masks-based intervention is combined with the strict social-distancing strategy.", "qid": 44, "docid": "41gd7rug", "rank": 37, "score": 0.7601123452186584}, {"content": "Title: Low-cost measurement of facemask efficacy for filtering expelled droplets during speech Content: Mandates for mask use in public during the recent COVID-19 pandemic, worsened by global shortage of commercial supplies, have led to widespread use of homemade masks and mask alternatives. It is assumed that wearing such masks reduces the likelihood for an infected person to spread the disease, but many of these mask designs have not been tested in practice. We have applied a simple optical measurement method to evaluate the efficacy of masks to reduce the transmission of respiratory droplets during regular speech. We compare a variety of commonly available mask types and observe that some mask types approach the performance of standard surgical masks, while some mask alternatives, such as neck fleece or bandanas, offer very little protection. Our measurement setup is inexpensive and can be built and operated by non-experts, allowing for rapid evaluation of mask performance during speech, sneezing, or coughing.", "qid": 44, "docid": "oyxxji7r", "rank": 38, "score": 0.7581966519355774}, {"content": "Title: The face mask: How a real protection becomes a psychological symbol during Covid-19? Content: 'The Mask' has become a byword and a precious possession universally. Except for its use by the medical fraternity, answers to the common questions-whether it provides enough protection, which type is optimal for the general public and who really needs to don it, remain poorly understood. For a frontline healthcare worker, wearing mask is a necessity as an important person protection equipment, it is perhaps the most-powerful psychological symbol for the general public. Surprisingly, it even undermines all other recommended practices of infection control and breaking the transmission chain of Covid-19, like hand washing, personal hygiene and social distancing. 'The mask' has evolved with time and yet there is a need to further improve the design for safety, tolerability and comfort. In this review we present the journey of face mask, originating from the first masks aimed at stopping the bad smell to its industrial use to its all-important place in the medical field. Various types of face masks, their filtration efficiency, reusability and current recommendations for their use are presented.", "qid": 44, "docid": "svtux4dk", "rank": 39, "score": 0.7581439018249512}, {"content": "Title: The Face Mask How a Real Protection becomes a Psychological Symbol during Covid-19? Content: 'The Mask' has become a byword and a precious possession universally. Except for its use by the medical fraternity, answers to the common questions-whether it provides enough protection, which type is optimal for the general public and who really needs to don it, remain poorly understood. For a frontline healthcare worker, wearing mask is a necessity as an important person protection equipment, it is perhaps the most-powerful psychological symbol for the general public. Surprisingly, it even undermines all other recommended practices of infection control and breaking the transmission chain of Covid-19, like hand washing, personal hygiene and social distancing. 'The mask' has evolved with time and yet there is a need to further improve the design for safety, tolerability and comfort. In this review we present the journey of face mask, originating from the first masks aimed at stopping the bad smell to its industrial use to its all-important place in the medical field. Various types of face masks, their filtration efficiency, reusability and current recommendations for their use are presented.", "qid": 44, "docid": "uq6kj3qi", "rank": 40, "score": 0.7581439018249512}, {"content": "Title: Mathematical assessment of the impact of non-pharmaceutical interventions on curtailing the 2019 novel Coronavirus Content: A novel Coronavirus pandemic emerged in December of 2019, causing devastating public health impact across the world. In the absence of a safe and effective vaccine or antiviral, strategies for mitigating the burden of the pandemic are focused on non-pharmaceutical interventions, such as social-distancing, contact-tracing, quarantine, isolation and the use of face-masks in public. We develop a new mathematical model for assessing the population-level impact of these mitigation strategies. Simulations of the model, using data relevant to COVID-19 transmission in New York state and the entire US, show that the pandemic will peak in mid and late April, respectively. The worst-case scenario projections for cumulative mortality (based on the baseline levels of anti-COVID non-pharmaceutical interventions considered in the study) in New York State and the entire US decrease dramatically by 80% and 64%, respectively, if the strict social-distancing measures implemented are maintained until the end of May or June, 2020. This study shows that early termination of strict social-distancing could trigger a devastating second wave with burden similar to that projected before the onset of strict social-distance. The use of efficacious face-masks (efficacy greater than 70%) could lead to the elimination of the pandemic if at least 70% of the residents of New York state use such masks consistently (nationwide, a compliance of at least 80% will be required using such masks). The use of low efficacy masks, such as cloth masks (of efficacy less than 30%), could also lead to significant reduction of COVID-19 burden (albeit, they are not able to lead to elimination). Combining low efficacy masks with improved levels of other anti-COVID-19 intervention measures can lead to elimination of the pandemic. The mask coverage needed to eliminate COVID-19 decreases if mask-use is combined with strict social-distancing.", "qid": 44, "docid": "6gsg0u53", "rank": 41, "score": 0.7580284476280212}, {"content": "Title: Widespread use of face masks in public may slow the spread of SARS CoV-2: an ecological study Content: Background The reasons for the large differences between countries in the sizes of their SARS CoV2 epidemics is unknown. Individual level studies have found that the use of face masks was protective for the acquisition and transmission of a range of respiratory viruses including SARS CoV1. We hypothesized that population level usage of face masks may be negatively associated SARS CoV2 spread. Methods At a country level, linear regression was used to assess the association between COVID19 diagnoses per inhabitant and the national promotion of face masks in public (coded as a binary variable), controlling for the age of the COVID19 epidemic and testing intensity. Results Eight of the 49 countries with available data advocated wearing face masks in public: China, Czechia, Hong Kong, Japan, Singapore, South Korea, Thailand and Malaysia. In multivariate analysis face mask use was negatively associated with number of COVID19 cases/inhabitant (coef. -326, 95% CI -601- -51, P=0.021). Testing intensity was positively associated with COVID-19 cases (coef. 0.07, 95% CI 0.05-0.08, P<0.001). Conclusion Whilst these results are susceptible to residual confounding, they do provide ecological level support to the individual level studies that found face mask usage to reduce the transmission and acquisition of respiratory viral infections.", "qid": 44, "docid": "5wsj003j", "rank": 42, "score": 0.7575303316116333}, {"content": "Title: The use of facemasks by the general population to prevent transmission of Covid 19 infection: A systematic review. Content: Background The pandemic of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), has become a serious worldwide public health emergency. This systematic review aims to summarize the available evidence regarding the role of face mask in community settings in slowing the spread of respiratory viruses such as SARS- CoV-2. Methods The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used for this review. A literature search using PUBMED, Google Scholar, and Cochrane database were performed using Medical subject heading (MeSH) words from the year 2000-2020. The articles focused on the use of masks and N95 respirators in healthcare workers were excluded. Results A total of 305 records were identified, out of which 14 articles were included in the review based upon quality and eligibility criteria. All the articles mentioned about the role of face masks in preventing the spread of respiratory viruses like influenza, SARS, and SARS-CoV-2, in the community or experimental setting. Studies also suggested that early initiation of face mask usage was more effective. Masks were also reported to be more effective in viruses that transmit easily from asymptomatic individuals, as is now known in SARS-CoV-2. Conclusion Theoretical, experimental, and clinical evidence suggested that usage of face masks in a general population offered significant benefit in preventing the spread of respiratory viruses especially in the pandemic situation, but its utility is limited by inconsistent adherence to mask usage.", "qid": 44, "docid": "f7rcijh4", "rank": 43, "score": 0.7573826909065247}, {"content": "Title: Face masks for all and all for face masks in the COVID-19 pandemic: community level production to face the global shortage and shorten the epidemic Content: The current COVID-19 pandemic caused a global shortage of medical masks, leaving most exposed health personnel without appropriate protection.Since the beginning of the outbreak, the WHO has revised several times the recommendations on general use of facemasks. In various countries, the public was advised to wear facemasks, in order to ensure them to healthcare workers. Until recently, WHO recommended to limit the use of facemasks to symptomatic people and advised against off-standard solutions. Moreover, recommendations differ among and within countries, causing public confusion and individual initiative.There is wide consensus that universal appropriate use of masks may contribute both to contain the epidemic and to reduce the burden on national procurement, if a community production approach is followed. Especially in low-middle income countries, due to the scarce capacity of national industrial production or import, the use of masks produced at community level may become the only viable option.For the purpose ad hoc guidelines will be needed.Current knowledge and experience call for further and updated review of global and national guidelines in order to provide clear and consistent criteria to ensure the widest availability and appropriate use of facial protection, bearing in mind populations in socio-economic disadvantaged settings.", "qid": 44, "docid": "sd7ozaif", "rank": 44, "score": 0.7566570043563843}, {"content": "Title: Face masks for all and all for face masks in the COVID-19 pandemic: community level production to face the global shortage and shorten the epidemic. Content: The current COVID-19 pandemic caused a global shortage of medical masks, leaving most exposed health personnel without appropriate protection.Since the beginning of the outbreak, the WHO has revised several times the recommendations on general use of facemasks. In various countries, the public was advised to wear facemasks, in order to ensure them to healthcare workers. Until recently, WHO recommended to limit the use of facemasks to symptomatic people and advised against off-standard solutions. Moreover, recommendations differ among and within countries, causing public confusion and individual initiative.There is wide consensus that universal appropriate use of masks may contribute both to contain the epidemic and to reduce the burden on national procurement, if a community production approach is followed. Especially in low-middle income countries, due to the scarce capacity of national industrial production or import, the use of masks produced at community level may become the only viable option.For the purpose ad hoc guidelines will be needed.Current knowledge and experience call for further and updated review of global and national guidelines in order to provide clear and consistent criteria to ensure the widest availability and appropriate use of facial protection, bearing in mind populations in socio-economic disadvantaged settings.", "qid": 44, "docid": "krh7p1tg", "rank": 45, "score": 0.7566568851470947}, {"content": "Title: Coronavirus epidemic: prediction and controlling measures Content: The COVID-19 outbreak has caused over 1.7 million (still increasing) confirmed cases globally as of April 10th, 2020. The levels of spread and severity of the virus lead to a wide-spread political and economic turmoil. We believe that two critical contributing factors need to be taken into account by the authorities to make effective decisions for controlling the spread of the virus: (i) being familiar with the most effective controlling measures and (ii) having a mathematical model to predict the spread of the virus. In this study, we provided information regarding both of these crucial factors. First, we investigated the importance of different measures such as quarantine, isolation, face mask, social distancing, etc. in controlling the virus in various countries. We then present a mathematical model to predict the spread of the virus in different countries. Our prediction shows an excellent match with the actual data up to now.", "qid": 44, "docid": "ivb8tm4c", "rank": 46, "score": 0.7556591033935547}, {"content": "Title: 'Masking the evidence': perspectives of the COVID-19 pandemic Content: The COVID-19 pandemic presents a severe and acute public health emergency around the world. The event of the pandemic has seen an upsurge in the general public wearing of disposable surgical masks (DSM) and other types of face masks. The World Health Organisation of mask wearing has been widely debated in the press a(WHO) have changed their advice, to now recommend the routine wearing of fabric masks by the general public as a means of preventing the spread of COVID-19 (WHO 2020a).", "qid": 44, "docid": "sjenehbl", "rank": 47, "score": 0.754815936088562}, {"content": "Title: Comparative efficacy of the front-line anti-HBV drugs in nucleos(t)ide analogue-naive chronic hepatitis B: A protocol for systematic review and network meta-analysis Content: BACKGROUND: During the COVID-19 period, there was a huge gap in the understanding of masks between east and west. At the same time, the mechanism of the mask and the effect after use, also appeared differences. The Objective of this Meta-analysis is to systematically evaluate the efficacy of masks for influenza in the community. METHODS: The Web of Science, PubMed, The Cochrane Library, EMBASE and Clinical Trials will be electronically searched to collect randomized controlled trials regarding the efficacy of masks for influenza in the community through Apr 2020. Two researchers independently screened and evaluated the obtained studies and extracted the outcome indexes. Revman 5.3 software will be used for the meta-analysis. RESULTS: The outbreak is continuing, and we need to be prepared for a long fight. If masks are effective, we need to promote their use as soon as possible. If masks are ineffective, strong evidence should be given. This is an urgent task and our team will finish it as soon as possible. CONCLUSION: Provide stronger evidence to solve the problem, should we wear masks or not right now.", "qid": 44, "docid": "29vynklv", "rank": 48, "score": 0.754149854183197}, {"content": "Title: The efficacy of masks for influenza-like illness in the community: A protocol for systematic review and meta-analysis Content: BACKGROUND: During the COVID-19 period, there was a huge gap in the understanding of masks between east and west. At the same time, the mechanism of the mask and the effect after use, also appeared differences. The Objective of this Meta-analysis is to systematically evaluate the efficacy of masks for influenza in the community. METHODS: The Web of Science, PubMed, The Cochrane Library, EMBASE and Clinical Trials will be electronically searched to collect randomized controlled trials regarding the efficacy of masks for influenza in the community through Apr 2020. Two researchers independently screened and evaluated the obtained studies and extracted the outcome indexes. Revman 5.3 software will be used for the meta-analysis. RESULTS: The outbreak is continuing, and we need to be prepared for a long fight. If masks are effective, we need to promote their use as soon as possible. If masks are ineffective, strong evidence should be given. This is an urgent task and our team will finish it as soon as possible. CONCLUSION: Provide stronger evidence to solve the problem, should we wear masks or not right now.", "qid": 44, "docid": "p8lu5mc0", "rank": 49, "score": 0.754149854183197}, {"content": "Title: Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis Content: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and is spread person-to-person through close contact. We aimed to investigate the effects of physical distance, face masks, and eye protection on virus transmission in health-care and non-health-care (eg, community) settings. METHODS: We did a systematic review and meta-analysis to investigate the optimum distance for avoiding person-to-person virus transmission and to assess the use of face masks and eye protection to prevent transmission of viruses. We obtained data for SARS-CoV-2 and the betacoronaviruses that cause severe acute respiratory syndrome, and Middle East respiratory syndrome from 21 standard WHO-specific and COVID-19-specific sources. We searched these data sources from database inception to May 3, 2020, with no restriction by language, for comparative studies and for contextual factors of acceptability, feasibility, resource use, and equity. We screened records, extracted data, and assessed risk of bias in duplicate. We did frequentist and Bayesian meta-analyses and random-effects meta-regressions. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. This study is registered with PROSPERO, CRD42020177047. FINDINGS: Our search identified 172 observational studies across 16 countries and six continents, with no randomised controlled trials and 44 relevant comparative studies in health-care and non-health-care settings (n=25 697 patients). Transmission of viruses was lower with physical distancing of 1 m or more, compared with a distance of less than 1 m (n=10 736, pooled adjusted odds ratio [aOR] 0\u00b718, 95% CI 0\u00b709 to 0\u00b738; risk difference [RD] \u221210\u00b72%, 95% CI \u221211\u00b75 to \u22127\u00b75; moderate certainty); protection was increased as distance was lengthened (change in relative risk [RR] 2\u00b702 per m; p(interaction)=0\u00b7041; moderate certainty). Face mask use could result in a large reduction in risk of infection (n=2647; aOR 0\u00b715, 95% CI 0\u00b707 to 0\u00b734, RD \u221214\u00b73%, \u221215\u00b79 to \u221210\u00b77; low certainty), with stronger associations with N95 or similar respirators compared with disposable surgical masks or similar (eg, reusable 12\u201316-layer cotton masks; p(interaction)=0\u00b7090; posterior probability >95%, low certainty). Eye protection also was associated with less infection (n=3713; aOR 0\u00b722, 95% CI 0\u00b712 to 0\u00b739, RD \u221210\u00b76%, 95% CI \u221212\u00b75 to \u22127\u00b77; low certainty). Unadjusted studies and subgroup and sensitivity analyses showed similar findings. INTERPRETATION: The findings of this systematic review and meta-analysis support physical distancing of 1 m or more and provide quantitative estimates for models and contact tracing to inform policy. Optimum use of face masks, respirators, and eye protection in public and health-care settings should be informed by these findings and contextual factors. Robust randomised trials are needed to better inform the evidence for these interventions, but this systematic appraisal of currently best available evidence might inform interim guidance. FUNDING: World Health Organization.", "qid": 44, "docid": "8ko7mmu3", "rank": 50, "score": 0.7538312673568726}, {"content": "Title: \u2018Masking the evidence\u2019: perspectives of the COVID\u201019 pandemic Content: The COVID\u201019 pandemic presents a severe and acute public health emergency around the world. The event of the pandemic has seen an upsurge in the general public wearing of disposable surgical masks (DSM) and other types of face masks. The World Health Organisation of mask wearing has been widely debated in the press a(WHO) have changed their advice, to now recommend the routine wearing of fabric masks by the general public as a means of preventing the spread of COVID\u201019 (WHO 2020a).", "qid": 44, "docid": "f9syysdw", "rank": 51, "score": 0.7537393569946289}, {"content": "Title: Mathematical assessment of the impact of non-pharmaceutical interventions on curtailing the 2019 novel Coronavirus Content: A pandemic of a novel Coronavirus emerged in December of 2019 (COVID-19), causing devastating public health impact across the world. In the absence of a safe and effective vaccine or antivirals, strategies for controlling and mitigating the burden of the pandemic are focused on non-pharmaceutical interventions, such as social-distancing, contact-tracing, quarantine, isolation, and the use of face-masks in public. We develop a new mathematical model for assessing the population-level impact of the aforementioned control and mitigation strategies. Rigorous analysis of the model shows that the disease-free equilibrium is locally-asymptotically stable if a certain epidemiological threshold, known as the reproduction number (denoted by \u00e2\u0084\u009bc), is less than unity. Simulations of the model, using data relevant to COVID-19 transmission dynamics in the US state of New York and the entire US, show that the pandemic burden will peak in mid and late April, respectively. The worst-case scenario projections for cumulative mortality (based on the baseline levels of anti-COVID non-pharmaceutical interventions considered in the study) decrease dramatically by 80% and 64%, respectively, if the strict social-distancing measures implemented are maintained until the end of May or June, 2020. The duration and timing of the relaxation or termination of the strict social-distancing measures are crucially-important in determining the future trajectory of the COVID-19 pandemic. This study shows that early termination of the strict social-distancing measures could trigger a devastating second wave with burden similar to those projected before the onset of the strict social-distancing measures were implemented. The use of efficacious face-masks (such as surgical masks, with estimated efficacy &#8805; 70%) in public could lead to the elimination of the pandemic if at least 70% of the residents of New York state use such masks in public consistently (nationwide, a compliance of at least 80% will be required using such masks). The use of low efficacy masks, such as cloth masks (of estimated efficacy less than 30%), could also lead to significant reduction of COVID-19 burden (albeit, they are not able to lead to elimination). Combining low efficacy masks with improved levels of the other anti-COVID-19 intervention strategies can lead to the elimination of the pandemic. This study emphasizes the important role social-distancing plays in curtailing the burden of COVID-19. Increases in the adherence level of social-distancing protocols result in dramatic reduction of the burden of the pandemic, and the timely implementation of social-distancing measures in numerous states of the US may have averted a catastrophic outcome with respect to the burden of COVID-19. Using face-masks in public (including the low efficacy cloth masks) is very useful in minimizing community transmission and burden of COVID-19, provided their coverage level is high. The masks coverage needed to eliminate COVID-19 decreases if the masks-based intervention is combined with the strict social-distancing strategy.", "qid": 44, "docid": "1yo8win8", "rank": 52, "score": 0.7531144618988037}, {"content": "Title: Associations between wearing masks, washing hands, and social distancing practices, and risk of COVID-19 infection in public: a cohort-based case-control study in Thailand Content: Objective. To investigate whether wearing masks, washing hands and social distancing practices are associated with lower risk of COVID-19 infection. Design. A retrospective cohort-based case-control study. All participants were retrospectively interviewed by phone about their preventive measures against COVID-19 infection. Setting. Thailand, using the data from contact tracing of COVID-19 patients associated with nightclub, boxing stadium and state enterprise office clusters from the Surveillance Rapid Response Team, Department of Disease Control, Ministry of Public Health. Contacts were tested for COVID-19 using PCR assays per national contact tracing guidelines. Participants. A cohort of 1,050 asymptomatic contacts of COVID-19 patients between 1 and 31 March 2020. Main outcome measures. Diagnosis of COVID-19 by 21 April 2020. Odds ratios for COVID-19 infection and population attributable fraction were calculated. Exposure. The study team retrospectively asked about wearing masks, washing hands, and social distancing practices during the contact period through telephone interviews. Results. Overall, 211 (20%) were diagnosed with COVID-19 by 21 Apr 2020 (case group) while 839 (80%) were not (control group). Fourteen percent of cases (29/210) and 24% of controls (198/823) reported wearing either non-medical or medical masks all the time during the contact period. Wearing masks all the time (adjusted odds ratio [aOR] 0.23; 95%CI 0.09-0.60) was associated with lower risk of COVID-19 infections compared to not wearing masks, while wearing masks sometimes (aOR 0.87; 95%CI 0.41-1.84) was not. Shortest distance of contact >1 meter (aOR 0.15; 95%CI 0.04-0.63), duration of close contact [\u2264]15 minutes (aOR 0.24; 95%CI 0.07-0.90) and washing hands often (aOR 0.33; 95%CI 0.13-0.87) were significantly associated with lower risk of infection. Sharing a cigarette (aOR 3.47; 95%CI 1.09-11.02) was associated with higher risk of infection. Type of mask was not independently associated with risk of infection. Those who wore masks all the time were more likely to wash hands and practice social distancing. We estimated that if everyone wore a mask all the time, washed hands often, did not share a dish, cup or cigarette, had shortest distance of contact >1 meter and had duration of close contact [\u2264]15 minutes, cases would have been reduced by 84%. Conclusions. Our findings support consistently wearing non-medical masks, washing hands, and social distancing in public to prevent COVID-19 infections.", "qid": 44, "docid": "l8y9r8cp", "rank": 53, "score": 0.7530938982963562}, {"content": "Title: Aerosol-generating procedures in head and neck surgery \u2013 can we improve practice after COVID-19? Content: The COVID-19 pandemic has had a dramatic impact on international medicine practice. The propensity for head and neck surgery to generate aerosols needs special consideration over and above simply adopting personal protective equipment. This study sought to interrogate the literature and evaluate whether which additional measures might provide benefit if routinely adopted in minimising viral transmission.", "qid": 44, "docid": "afjb7az9", "rank": 54, "score": 0.7530235052108765}, {"content": "Title: Aerosol-generating procedures in head and neck surgery - can we improve practice after COVID-19? Content: The COVID-19 pandemic has had a dramatic impact on international medicine practice. The propensity for head and neck surgery to generate aerosols needs special consideration over and above simply adopting personal protective equipment. This study sought to interrogate the literature and evaluate whether which additional measures might provide benefit if routinely adopted in minimising viral transmission.", "qid": 44, "docid": "t6ppntpi", "rank": 55, "score": 0.7530233860015869}, {"content": "Title: Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis Content: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and is spread person-to-person through close contact. We aimed to investigate the effects of physical distance, face masks, and eye protection on virus transmission in health-care and non-health-care (eg, community) settings. METHODS: We did a systematic review and meta-analysis to investigate the optimum distance for avoiding person-to-person virus transmission and to assess the use of face masks and eye protection to prevent transmission of viruses. We obtained data for SARS-CoV-2 and the betacoronaviruses that cause severe acute respiratory syndrome, and Middle East respiratory syndrome from 21 standard WHO-specific and COVID-19-specific sources. We searched these data sources from database inception to May 3, 2020, with no restriction by language, for comparative studies and for contextual factors of acceptability, feasibility, resource use, and equity. We screened records, extracted data, and assessed risk of bias in duplicate. We did frequentist and Bayesian meta-analyses and random-effects meta-regressions. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. This study is registered with PROSPERO, CRD42020177047. FINDINGS: Our search identified 172 observational studies across 16 countries and six continents, with no randomised controlled trials and 44 relevant comparative studies in health-care and non-health-care settings (n=25\u00e2\u0080\u0088697 patients). Transmission of viruses was lower with physical distancing of 1 m or more, compared with a distance of less than 1 m (n=10\u00e2\u0080\u0088736, pooled adjusted odds ratio [aOR] 0\u00b718, 95% CI 0\u00b709 to 0\u00b738; risk difference [RD] -10\u00b72%, 95% CI -11\u00b75 to -7\u00b75; moderate certainty); protection was increased as distance was lengthened (change in relative risk [RR] 2\u00b702 per m; pinteraction=0\u00b7041; moderate certainty). Face mask use could result in a large reduction in risk of infection (n=2647; aOR 0\u00b715, 95% CI 0\u00b707 to 0\u00b734, RD -14\u00b73%, -15\u00b79 to -10\u00b77; low certainty), with stronger associations with N95 or similar respirators compared with disposable surgical masks or similar (eg, reusable 12-16-layer cotton masks; pinteraction=0\u00b7090; posterior probability >95%, low certainty). Eye protection also was associated with less infection (n=3713; aOR 0\u00b722, 95% CI 0\u00b712 to 0\u00b739, RD -10\u00b76%, 95% CI -12\u00b75 to -7\u00b77; low certainty). Unadjusted studies and subgroup and sensitivity analyses showed similar findings. INTERPRETATION: The findings of this systematic review and meta-analysis support physical distancing of 1 m or more and provide quantitative estimates for models and contact tracing to inform policy. Optimum use of face masks, respirators, and eye protection in public and health-care settings should be informed by these findings and contextual factors. Robust randomised trials are needed to better inform the evidence for these interventions, but this systematic appraisal of currently best available evidence might inform interim guidance. FUNDING: World Health Organization.", "qid": 44, "docid": "zzumi9h5", "rank": 56, "score": 0.7523487210273743}, {"content": "Title: Can wearing face masks in public affect transmission route and viral load in COVID-19? Content: The mandatory face mask wearing was implemented in the Czech Republic and Slovakia shortly after the COVID-19 outbreak in Central Europe. So far, the number of COVID-19-associated deaths per 100,000 individuals is far lower in these countries as compared with other neighbouring or close countries. The use of face masks in public may not protect the general public from contracting the virus, however, presumptively decreases the viral load and contributes to a favourable clinical outcome in COVID-19 disease. A certain time is required for antigen-specific T cells and B cells to fully develop. Obligatory face mask wearing in public favours the virus transmission through oral mucosa and/or conjunctival epithelium, which enables the adaptive immune responses to evolve. In the case of inhalation of high loads of SARS-CoV-2, the time for the development of fully protective adaptive immune responses seems to be insufficient. Then, a less specific and more damaging innate immune response prevails.", "qid": 44, "docid": "p93u753c", "rank": 57, "score": 0.7523103952407837}, {"content": "Title: Adolescents\u2019 face mask usage and contact transmission in novel Coronavirus Content: The global outbreak of coronavirus has become an international public health threat. Prevention is of paramount importance to contain its spread. This study observes face mask wearing behavior and contact transmission problems in Taiwan. Teachers track student status in class. In addition to measuring body temperature and regular disinfection, classrooms require ventilation wear mask, provide alcohol spray and avoid sharing the microphone. Both questionnaire surveys and experimental were utilized. A total of 160 adults residing in Taiwan participated in the survey. The dye simulated the possible virus area on the mask surface during usage. Subjects were required to complete a questionnaire and simulate the spread of contact transmission when using a computer. Eighty-one % of respondents reported consistent use of surgical masks several times a day. They reported taking their masks off in relatively safe areas. Most people reported using one mask per day and storing the masks in their pockets. As a result, masks surface become a contamination source. In the contact experiment, ten adults were requested to don and doff a surgical mask while doing a word processing task. The extended contamination areas were recorded and identified by image analysis. The results show an average contamination area of the workspace is significant 530 cm(2). When the hand touches the surface of the mask, it may spread the virus to the subsequent contact area.", "qid": 44, "docid": "clidl6v1", "rank": 58, "score": 0.7522817254066467}, {"content": "Title: Identifying airborne transmission as the dominant route for the spread of COVID-19 Content: Various mitigation measures have been implemented to fight the coronavirus disease 2019 (COVID-19) pandemic, including widely adopted social distancing and mandated face covering. However, assessing the effectiveness of those intervention practices hinges on the understanding of virus transmission, which remains uncertain. Here we show that airborne transmission is highly virulent and represents the dominant route to spread the disease. By analyzing the trend and mitigation measures in Wuhan, China, Italy, and New York City, from January 23 to May 9, 2020, we illustrate that the impacts of mitigation measures are discernable from the trends of the pandemic. Our analysis reveals that the difference with and without mandated face covering represents the determinant in shaping the pandemic trends in the three epicenters. This protective measure alone significantly reduced the number of infections, that is, by over 78,000 in Italy from April 6 to May 9 and over 66,000 in New York City from April 17 to May 9. Other mitigation measures, such as social distancing implemented in the United States, are insufficient by themselves in protecting the public. We conclude that wearing of face masks in public corresponds to the most effective means to prevent interhuman transmission, and this inexpensive practice, in conjunction with simultaneous social distancing, quarantine, and contact tracing, represents the most likely fighting opportunity to stop the COVID-19 pandemic. Our work also highlights the fact that sound science is essential in decision-making for the current and future public health pandemics.", "qid": 44, "docid": "9ye2okm5", "rank": 59, "score": 0.7515344619750977}, {"content": "Title: Medical mask or N95 respirator: When and how to use? Content: COVID-19 pandemic is now a global threat on human health reaching up to 2 million infected people all around the World. Since its first recognition in Wuhan, many topics were discussed intensively about COVID-19, both in the public and scientific community. Personal protective equipments and especially masks were among the hottest topics during this pandemic. Regardless of which mask is used, performing hand hygiene frequently with an alcohol-based hand rub or with soap and water if hands are dirty; is the most effective preventive measure for COVID-19. The type of mask used when caring for COVID-19 patients will vary according to the setting, type of personnel/person, and activity. Although the main transmission route for COVID-19 is droplets, during aerosol generating procedures airborne transmission may occur. Keeping the distancing and medical masks and eye protection during close contact efficiently protects against respiratory diseases transmitted via droplets. Airborne precautions include goggles and respiratory protection with the use of an N95 or an equivalent mask respirator to prevent airborne transmission.", "qid": 44, "docid": "6wxjm7m0", "rank": 60, "score": 0.7507126927375793}, {"content": "Title: Medical mask or N95 respirator: When and how to use? Content: COVID-19 pandemic is now a global threat to human health reaching up to 2 million infected people all around the world. Since its first recognition in Wuhan, many topics were discussed intensively about COVID-19, both in the public and scientific community. Personal protective equipment, especially masks, has been among the hottest topics during this pandemic. Regardless of which mask is used, performing hand hygiene frequently with an alcohol-based hand rub or with soap and water if hands are dirty is the most effective preventive measure for COVID-19. The type of mask used when caring for COVID-19 patients will vary according to the setting, type of personnel/person, and activity. Although the main transmission route for COVID-19 is droplets, during aerosol generating procedures airborne transmission may occur. Keeping the distancing and medical masks and eye protection during close contact efficiently protects against respiratory diseases transmitted via droplets. Airborne precautions include goggles and respiratory protection with the use of an N95 or an equivalent mask respirator to prevent airborne transmission.", "qid": 44, "docid": "r1oqwdkz", "rank": 61, "score": 0.7490964531898499}, {"content": "Title: An apparatus for nondestructive and rapid comparison of mask approaches in defense against infected respiratory aerosols Content: At the front lines of the world's response to the COVID-19 pandemic are hero-clinicians facing a lack of critical supplies including protective medical grade breathing masks and filtering materials. At the same time, the general public is now being advised to wear masks to help stop the spread. As a result, in the absence of centrally coordinated production and distribution efforts, supply chains for masks, respirators, and materials for advanced filtration technology are immensely burdened. Here we describe experimental efforts to nondestructively quantify three vital characteristics of mask approaches: breathability, material filtration effectiveness, and sensitivity to fit. We focus on protection against water aerosols $>$0.3$\\mu$m using off-the-shelf particulate, flow, and pressure sensors, permitting rapid comparative evaluation of these three properties. We present and discuss both the pressure drop and the particle transmission as a function of flow to permit comparison of relative protection for a set of proposed filter and mask designs. The design considerations of the testing apparatus can be reproduced by university laboratories and medical facilities and used for rapid local quality control of respirator masks which are of uncertified origin, monitoring the long-term effects of various disinfection schemes, and evaluating improvised products not designed or marketed for filtration.", "qid": 44, "docid": "jkoegawm", "rank": 62, "score": 0.7484533786773682}, {"content": "Title: To mask or not to mask children to overcome COVID-19 Content: It has been reported that asymptomatic people can transmit the new coronavirus disease 2019 (COVID-19) and become important sources of COVID-19. To reduce the role of asymptomatic or poorly symptomatic people in COVID-19, universal use of face masks in addition to hand hygiene and safety distance seems extremely useful. Consequently, preparing the healthy child to use face masks is strongly needed. To obtain maximal compliance, reasons for mask wearing without attempts of removing must be clearly explained. Moreover, child\u2019s will must not be forced. Conclusion: On the basis of clinical findings, we think that the universal use of facial masks seems necessary when people have to go out in their everyday lives. In addition to the availability of masks of different sizes capable of adapting perfectly to the face, it is necessary that the use of masks in children is preceded by a strong parental work and school lessons on this issue and other hygiene topics with the main aim to obtain child cooperation.", "qid": 44, "docid": "ahhrs3sy", "rank": 63, "score": 0.7484232783317566}, {"content": "Title: What proportion of healthcare worker masks carry virus? A systematic review Content: BACKGROUND: Concerns have been raised by healthcare organisations in New Zealand that routine mask use by healthcare workers (HCW) may increase the risk of transmission of SARS-CoV-2 through increased face touching. Routine mask use by frontline HCW was not recommended when seeing 'low risk' patients. The aim of this review was to determine the carriage of respiratory viruses on facemasks used by HCW. METHODS: A systematic review was conducted with structured searches of medical and allied health databases. Two authors independently screened articles for inclusion, with substantial agreement (k=0.66, 95%CI 0.54 to 0.79). Studies that at least one author recommended for full text review were reviewed in full for inclusion. Two authors independently extracted data from included studies including the setting, method of analysis and results. There was exact agreement on the proportion of virus detected on masks. RESULTS: 1233 titles were retrieved, 47 underwent full text review and five studies reported in four articles were included. The studies were limited by small numbers and failure to test all eligible masks in some studies. The proportion in each study ranged from 0 (95% CI 0-10) to 25% (95%CI 8-54). No study reported clinical respiratory illness as a result of virus on the masks. CONCLUSIONS: Although limited, current evidence suggests that viral carriage on the outer surface of surgical masks worn by HCW treating patients with clinical respiratory illness is low and there was not strong evidence to support the assumption that mask use may increase the risk of viral transmission. This article is protected by copyright. All rights reserved.", "qid": 44, "docid": "s8bwq0d5", "rank": 64, "score": 0.7452943325042725}, {"content": "Title: What proportion of healthcare worker masks carry virus? A systematic review Content: BACKGROUND: Concerns have been raised by healthcare organisations in New Zealand that routine mask use by healthcare workers (HCW) may increase the risk of transmission of SARS\u2010CoV\u20102 through increased face touching. Routine mask use by frontline HCW was not recommended when seeing \u2018low risk\u2019 patients. The aim of this review was to determine the carriage of respiratory viruses on facemasks used by HCW. METHODS: A systematic review was conducted with structured searches of medical and allied health databases. Two authors independently screened articles for inclusion, with substantial agreement (k=0.66, 95%CI 0.54 to 0.79). Studies that at least one author recommended for full text review were reviewed in full for inclusion. Two authors independently extracted data from included studies including the setting, method of analysis and results. There was exact agreement on the proportion of virus detected on masks. RESULTS: 1233 titles were retrieved, 47 underwent full text review and five studies reported in four articles were included. The studies were limited by small numbers and failure to test all eligible masks in some studies. The proportion in each study ranged from 0 (95% CI 0\u201010) to 25% (95%CI 8\u201054). No study reported clinical respiratory illness as a result of virus on the masks. CONCLUSIONS: Although limited, current evidence suggests that viral carriage on the outer surface of surgical masks worn by HCW treating patients with clinical respiratory illness is low and there was not strong evidence to support the assumption that mask use may increase the risk of viral transmission. This article is protected by copyright. All rights reserved.", "qid": 44, "docid": "6m9g3bdr", "rank": 65, "score": 0.7448558807373047}, {"content": "Title: The use of face masks during the COVID\u201019 pandemic in Poland: A survey study of 2315 young adults Content: Face masks wearing during the coronavirus disease 2019 (COVID\u201019) pandemic became ubiquitous. The aim of our study was to assess the use of face masks among young adults during the current viral pandemic. The survey was based on specially created Google Forms and posted on numerous Facebook groups for young people in Poland. Seven days were considered as a recall period. A total of 2315 answers were obtained, 2307 were finally analysis, as eight questionnaires were removed because of data incompleteness. 60.4% of responders declared using the face masks. Those who reported an atopic predisposition wore face masks significantly (P = .007) more commonly (65.5% and 57.7%, respectively). Cloth masks (46.2%) appeared to be most popular ones, followed by surgical masks (39.2%), respirators (N95 and FFP) (13.3%), half\u2010face elastomeric respirators (0.8%) and full\u2010face respirators (0.4%). Females significantly more frequently (P = .0001) used cloth masks; respirators, half\u2010face elastomeric respirators and full\u2010face respirators were used more commonly by males (P < .0001, P = .001 and P = .001, respectively). 23.9% of responders who used single\u2010use mask wore it again. Moreover, 73.6% participants declared mask decontamination; however, the procedures were not always appropriate. We suggest that our results may be of help in construction of general public education campaigns on the proper use of face masks.", "qid": 44, "docid": "9lgg5gya", "rank": 66, "score": 0.7446084022521973}, {"content": "Title: Facial protection in the era of COVID-19: A narrative review Content: We live in extraordinary times, where COVID-19 pandemic has brought the whole world to a screeching halt. Tensions and contradictions that surround the pandemic ridden world include the availability, and the lack thereof, various facial protection measures to mitigate the viral spread. Here, we comprehensively explore the different types of facial protection measures, including masks, needed both for the public and the healthcare workers (HCW). We discuss the anatomy, the critical issues of disinfection and reusability of masks, the alternative equipment available for the protection of the facial region from airborne diseases, such as face shields and powered air-purifying respirators (PAPR), and the skin health impact of prolonged wearing of facial protection by HCW. Clearly, facial protection, either in the form of masks or alternates, appears to have mitigated the pandemic as seen from the minimal COVID-19 spread in countries where public mask wearing is strictly enforced. On the contrary, the healthcare systems, that appear to have been unprepared for emergencies of this nature, should be appropriately geared to handle the imbalance of supply and demand of personal protective equipment including face masks. These are two crucial lessons we can learn from this tragic experience.", "qid": 44, "docid": "6n5gnow1", "rank": 67, "score": 0.7444121837615967}, {"content": "Title: Sustainable and resilient strategies for touristic cities against COVID-19: an agent-based approach Content: Touristic cities will suffer from COVID-19 emergency because of its economic impact on their communities. The first emergency phases involved a wide closure of such areas to support\"social distancing\"measures (i.e. travels limitation; lockdown of (over)crowd-prone activities). In the second phase, individual's risk-mitigation strategies (facial masks) could be properly linked to\"social distancing\"to ensure re-opening touristic cities to visitors. Simulation tools could support the effectiveness evaluation of risk-mitigation measures to look for an economic and social optimum for activities restarting. This work modifies an existing Agent-Based Model to estimate the virus spreading in touristic areas, including tourists and residents' behaviours, movement and virus effects on them according to a probabilistic approach. Consolidated proximity-based and exposure-time-based contagion spreading rules are included according to international health organizations and previous calibration through experimental data. Effects of tourists' capacity (as\"social distancing\"-based measure) and other strategies (i.e. facial mask implementation) are evaluated depending on virus-related conditions (i.e. initial infector percentages). An idealized scenario representing a significant case study has been analysed to demonstrate the tool capabilities and compare the effectiveness of those solutions. Results show that\"social distancing\"seems to be more effective at the highest infectors' rates, although represents an extreme measure with important economic effects. This measure loses its full effectiveness (on the community) as the infectors' rate decreases and individuals' protection measures become predominant (facial masks). The model could be integrated to consider other recurring issues on tourist-related fruition and schedule of urban spaces and facilities (e.g. cultural/leisure buildings).", "qid": 44, "docid": "t6q7jhtf", "rank": 68, "score": 0.7432954907417297}, {"content": "Title: Cloth Masks May Prevent Transmission of COVID-19: An Evidence-Based, Risk-Based Approach Content: As the COVID-19 pandemic progressed across the world, governments, international agencies, policymakers, and public health officials began recommending widespread use of nonmedical cloth masks to reduce the transmission of SARS-CoV-2. The authors of this article suggest that there is convincing evidence to support this recommendation.", "qid": 44, "docid": "8je46886", "rank": 69, "score": 0.7432781457901001}, {"content": "Title: Impact of self-imposed prevention measures and short-term government intervention on mitigating and delaying a COVID-19 epidemic Content: Background: With new cases of COVID-19 surging around the world, many countries have to prepare for moving beyond the containment phase. Prediction of the effectiveness of non-case-based interventions for mitigating, delaying or preventing the epidemic is urgent, especially for countries affected by the ongoing seasonal influenza activity. Methods: We developed a transmission model to evaluate the impact of self-imposed prevention measures (handwashing, mask-wearing, and social distancing) due to the spread of COVID-19 awareness and of short-term government-imposed social distancing on the peak number of diagnoses, attack rate and time until the peak number of diagnoses. Findings: For fast awareness spread in the population, self-imposed measures can significantly reduce the attack rate, diminish and postpone the peak number of diagnoses. A large epidemic can be prevented if the efficacy of these measures exceeds 50%. For slow awareness spread, self-imposed measures reduce the peak number of diagnoses and attack rate but do not affect the timing of the peak. Early implementation of short-term government interventions can only delay the peak (by at most 7 months for a 3-month intervention). Interpretation: Handwashing, mask-wearing and social distancing as a reaction to information dissemination about COVID-19 can be effective strategies to mitigate and delay the epidemic. We stress the importance of rapidly spreading awareness on the use of these self-imposed prevention measures in the population. Early-initiated short-term government-imposed social distancing can buy time for healthcare systems to prepare for an increasing COVID-19 burden. Keywords: SARS-CoV-2, COVID-19, mathematical model, prevention measures, mitigation, epidemic control, disease awareness, social distancing, handwashing, mask-wearing", "qid": 44, "docid": "xfjexm5b", "rank": 70, "score": 0.7425378561019897}, {"content": "Title: Mask is the possible key for self\u2010isolation in COVID\u201019 pandemic Content: Ma's research shows N95 masks, medical masks, even homemade masks could block at least 90% of the virus in aerosols(1). This study puts the debate on whether the public wear masks back on the table. Recently Science interviewed Dr. Gao, director\u2010general of Chinese Center for Disease Control and Prevention (CDC). This article is protected by copyright. All rights reserved.", "qid": 44, "docid": "p5hljkkm", "rank": 71, "score": 0.7423242926597595}, {"content": "Title: Community Use Of Face Masks And COVID-19: Evidence From A Natural Experiment Of State Mandates In The US Content: State policies mandating public or community use of face masks or covers in mitigating novel coronavirus disease (COVID-19) spread are hotly contested. This study provides evidence from a natural experiment on effects of state government mandates in the US for face mask use in public issued by 15 states plus DC between April 8 and May 15. The research design is an event study examining changes in the daily county-level COVID-19 growth rates between March 31, 2020 and May 22, 2020. Mandating face mask use in public is associated with a decline in the daily COVID-19 growth rate by 0.9, 1.1, 1.4, 1.7, and 2.0 percentage-points in 1-5, 6-10, 11-15, 16-20, and 21+ days after signing, respectively. Estimates suggest as many as 230,000-450,000 COVID-19 cases possibly averted By May 22, 2020 by these mandates. The findings suggest that requiring face mask use in public might help in mitigating COVID-19 spread. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].", "qid": 44, "docid": "h2ahzau7", "rank": 72, "score": 0.7422598600387573}, {"content": "Title: Community Use Of Face Masks And COVID-19: Evidence From A Natural Experiment Of State Mandates In The US. Content: State policies mandating public or community use of face masks or covers in mitigating novel coronavirus disease (COVID-19) spread are hotly contested. This study provides evidence from a natural experiment on effects of state government mandates in the US for face mask use in public issued by 15 states plus DC between April 8 and May 15. The research design is an event study examining changes in the daily county-level COVID-19 growth rates between March 31, 2020 and May 22, 2020. Mandating face mask use in public is associated with a decline in the daily COVID-19 growth rate by 0.9, 1.1, 1.4, 1.7, and 2.0 percentage-points in 1-5, 6-10, 11-15, 16-20, and 21+ days after signing, respectively. Estimates suggest as many as 230,000-450,000 COVID-19 cases possibly averted By May 22, 2020 by these mandates. The findings suggest that requiring face mask use in public might help in mitigating COVID-19 spread. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].", "qid": 44, "docid": "9b6cepf4", "rank": 73, "score": 0.7422598600387573}, {"content": "Title: Correspondence: Angiotensin-converting enzyme 2 coated nanoparticles containing respiratory masks, chewing gums and nasal filters may be used for protection against COVID-19 infection Content: \u2022 World has encountered a novel pandemic called as COVID-19. \u2022 All people need protective items such as masks and gloves worldwide. \u2022 Preventing COVID-19 infection has become the most important issue. \u2022 ACE2 containing nanomaterials may be used in the respiratory masks, gloves and clothes. \u2022 Using nanotechnology to prevent this pandemic may be hope for fighting against COVID-19.", "qid": 44, "docid": "g477u9k1", "rank": 74, "score": 0.7422291040420532}, {"content": "Title: Physical interventions to interrupt or reduce the spread of respiratory viruses. Part 1 - Face masks, eye protection and person distancing: systematic review and meta-analysis Content: Abstract OBJECTIVE: To examine the effectiveness of eye protection, face masks, or person distancing on interrupting or reducing the spread of respiratory viruses. DESIGN: Update of a Cochrane review that included a meta-analysis of observational studies during the SARS outbreak of 2003. DATA SOURCES: Eligible trials from the previous review; search of Cochrane Central Register of Controlled Trials, PubMed, Embase and CINAHL from October 2010 up to 1 April 2020; and forward and backward citation analysis. DATA SELECTION: Randomised and cluster-randomised trials of people of any age, testing the use of eye protection, face masks, or person distancing against standard practice, or a similar physical barrier. Outcomes included any acute respiratory illness and its related consequences. DATA EXTRACTION AND ANALYSIS: Six authors independently assessed risk of bias using the Cochrane tool and extracted data. We used a generalised inverse variance method for pooling using a random-effects model and reported results with risk ratios and 95% Confidence Intervals (CI). RESULTS: We included 15 randomised trials investigating the effect of masks (14 trials) in healthcare workers and the general population and of quarantine (1 trial). We found no trials testing eye protection. Compared to no masks there was no reduction of influenza-like illness (ILI) cases (Risk Ratio 0.93, 95%CI 0.83 to 1.05) or influenza (Risk Ratio 0.84, 95%CI 0.61-1.17) for masks in the general population, nor in healthcare workers (Risk Ratio 0.37, 95%CI 0.05 to 2.50). There was no difference between surgical masks and N95 respirators: for ILI (Risk Ratio 0.83, 95%CI 0.63 to 1.08), for influenza (Risk Ratio 1.02, 95%CI 0.73 to 1.43). Harms were poorly reported and limited to discomfort with lower compliance. The only trial testing quarantining workers with household ILI contacts found a reduction in ILI cases, but increased risk of quarantined workers contracting influenza. All trials were conducted during seasonal ILI activity. CONCLUSIONS: Most included trials had poor design, reporting and sparse events. There was insufficient evidence to provide a recommendation on the use of facial barriers without other measures. We found insufficient evidence for a difference between surgical masks and N95 respirators and limited evidence to support effectiveness of quarantine. Based on observational evidence from the previous SARS epidemic included in the previous version of our Cochrane review we recommend the use of masks combined with other measures.", "qid": 44, "docid": "1vcc1khg", "rank": 75, "score": 0.741898238658905}, {"content": "Title: The role of community-wide wearing of face mask for control of coronavirus disease 2019 (COVID-19) epidemic due to SARS-CoV-2 Content: BACKGROUND: Face mask usage by the healthy population in the community to reduce risk of transmission of respiratory viruses remains controversial. We assessed the effect of community-wide mask usage to control coronavirus disease 2019 (COVID-19) in Hong Kong Special Administrative Region (HKSAR). METHODS: Patients presenting with respiratory symptoms at outpatient clinics or hospital wards were screened for COVID-19 per protocol. Epidemiological analysis was performed for confirmed cases, especially persons acquiring COVID-19 during mask-off and mask-on settings. The incidence of COVID-19 per million population in HKSAR with community-wide masking was compared to that of non-mask-wearing countries which are comparable with HKSAR in terms of population density, healthcare system, BCG vaccination and social distancing measures but not community-wide masking. Compliance of face mask usage in the HKSAR community was monitored. FINDINGS: Within first 100 days (31 December 2019 to 8 April 2020), 961 COVID-19 patients were diagnosed in HKSAR. The COVID-19 incidence in HKSAR (129.0 per million population) was significantly lower (p<0.001) than that of Spain (2983.2), Italy (2250.8), Germany (1241.5), France (1151.6), U.S. (1102.8), U.K. (831.5), Singapore (259.8), and South Korea (200.5). The compliance of face mask usage by HKSAR general public was 96.6% (range: 95.7% to 97.2%). We observed 11 COVID-19 clusters in recreational 'mask-off' settings compared to only 3 in workplace 'mask-on' settings (p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.036 by Chi square test of goodness-of-fit). CONCLUSION: Community-wide mask wearing may contribute to the control of COVID-19 by reducing the amount of emission of infected saliva and respiratory droplets from individuals with subclinical or mild COVID-19.", "qid": 44, "docid": "wiel6zen", "rank": 76, "score": 0.7417223453521729}, {"content": "Title: Waste Not, Want Not: Re-Usability of N95 Masks Content: As the spread of COVID-19 illnesses continues to escalate amidst a substandard supply of protective equipment for health care providers, the question of extended use or reuse of N95 masks has emerged. As well, the relative effectiveness of the N95 compared to other mask types have been entertained. A recent article by Abd-Elsayed and Karri aim to put these topics into focus. Additionally, personal correspondence between Drs. Richard Prielipp (University of Minnesota Department of Anesthesiology) and Peter Tsai (inventor of the N95 mask) offers perspectives on managing the reuse of this central element of protective equipment.", "qid": 44, "docid": "u6vpa1ih", "rank": 77, "score": 0.7417111992835999}, {"content": "Title: Strategy of using personal protective equipment during aerosol generating medical procedures with COVID-19 Content: \u2022 Compared the effectiveness and cost-effectiveness between masks and respirators for the COVID-19 transmission; \u2022 Discussed the strategy to avoid severe nosocomial infection through aerosol-generating medical procedures; \u2022 Suggestions for healthcare workers to choose proper personal protective equipment.", "qid": 44, "docid": "62pnddks", "rank": 78, "score": 0.7416044473648071}, {"content": "Title: Mathematical Modeling of the Effectiveness of Facemasks in Reducing the Spread of Novel Influenza A (H1N1) Content: On June 11, 2009, the World Health Organization declared the outbreak of novel influenza A (H1N1) a pandemic. With limited supplies of antivirals and vaccines, countries and individuals are looking at other ways to reduce the spread of pandemic (H1N1) 2009, particularly options that are cost effective and relatively easy to implement. Recent experiences with the 2003 SARS and 2009 H1N1 epidemics have shown that people are willing to wear facemasks to protect themselves against infection; however, little research has been done to quantify the impact of using facemasks in reducing the spread of disease. We construct and analyze a mathematical model for a population in which some people wear facemasks during the pandemic and quantify impact of these masks on the spread of influenza. To estimate the parameter values used for the effectiveness of facemasks, we used available data from studies on N95 respirators and surgical facemasks. The results show that if N95 respirators are only 20% effective in reducing susceptibility and infectivity, only 10% of the population would have to wear them to reduce the number of influenza A (H1N1) cases by 20%. We can conclude from our model that, if worn properly, facemasks are an effective intervention strategy in reducing the spread of pandemic (H1N1) 2009.", "qid": 44, "docid": "36bfeoqv", "rank": 79, "score": 0.7406957149505615}, {"content": "Title: Estimated effectiveness of symptom and risk screening to prevent the spread of COVID-19 Content: Traveller screening is being used to limit further spread of COVID-19 following its recent emergence, and symptom screening has become a ubiquitous tool in the global response. Previously, we developed a mathematical model to understand factors governing the effectiveness of traveller screening to prevent spread of emerging pathogens (Gostic et al., 2015). Here, we estimate the impact of different screening programs given current knowledge of key COVID-19 life history and epidemiological parameters. Even under best-case assumptions, we estimate that screening will miss more than half of infected people. Breaking down the factors leading to screening successes and failures, we find that most cases missed by screening are fundamentally undetectable, because they have not yet developed symptoms and are unaware they were exposed. Our work underscores the need for measures to limit transmission by individuals who become ill after being missed by a screening program. These findings can support evidence-based policy to combat the spread of COVID-19, and prospective planning to mitigate future emerging pathogens.", "qid": 44, "docid": "7zt3bc3a", "rank": 80, "score": 0.740613579750061}, {"content": "Title: COVID\u201019: Face masks and human\u2010to\u2010human transmission Content: In December 2019, transmission of the novel coronavirus (SARS-CoV-2) that causes coronavirus disease 2019(COVID-19) occurred in Wuhan, China1 .And later the virus began to be transmitted from person to person2 .Face masks are a type of personal protective equipment used to prevent the spread of respiratory infections\uff0cit may be effective at helping prevent transmission of respiratory viruses and bacteria3 .Here, we share a case of face masks are be used to prevent the transmission of COVID-19 infection.", "qid": 44, "docid": "wni08lks", "rank": 81, "score": 0.7400236129760742}, {"content": "Title: Rationeel gebruik van ademhalingsbeschermingsmaskers./ [Rational use of respiratory protective equipment: advice for health care professionals in time of COVID-19] Content: The current COVID-19 pandemic has led to a worldwide shortage of respiratory protective equipment. In order to offer maximum protection against infection for all healthcare workers, we need to optimise our use of the available equipment. This article provides practical advice on which type of mask is indicated in what specific situation, what requirements the mask should meet and how to optimise the local workflow, including the re-use of masks after decontamination.", "qid": 44, "docid": "31fnbch7", "rank": 82, "score": 0.7400013208389282}, {"content": "Title: [Rational use of respiratory protective equipment: advice for health care professionals in time of COVID-19]. Content: The current COVID-19 pandemic has led to a worldwide shortage of respiratory protective equipment. In order to offer maximum protection against infection for all healthcare workers, we need to optimise our use of the available equipment. This article provides practical advice on which type of mask is indicated in what specific situation, what requirements the mask should meet and how to optimise the local workflow, including the re-use of masks after decontamination.", "qid": 44, "docid": "nk95dyln", "rank": 83, "score": 0.7400013208389282}, {"content": "Title: Impact of non-pharmaceutical interventions against COVID-19 in Europe: a quasi-experimental study Content: The current epidemic of COVID-19 is unparalleled in recent history as are the social distancing interventions that have led to a significant halt on the economic and social life of so many countries. However, there is very little empirical evidence about which social distancing measures have the most impact. We report a quasi-experimental study of the impact of various interventions for control of the outbreak. Data on case numbers and deaths were taken from the daily published figures by the European Centre for Disease Control and dates of initiation of various control strategies from the Institute of Health Metrics and Evaluation website and published sources. Our primary analyses were modelled in R using Bayesian generalised additive mixed models (GAMM). We found that closure of education facilities, prohibiting mass gatherings and closure of some non-essential businesses were associated with reduced incidence whereas stay at home orders, closure of all non-businesses and requiring the wearing of facemasks or coverings in public was not associated with any independent additional impact. Our results could help inform strategies for coming out of lockdown.", "qid": 44, "docid": "3yi44xfe", "rank": 84, "score": 0.7397798299789429}, {"content": "Title: The more I fear about COVID-19, the more I wear medical masks: A survey on risk perception and medical masks uses Content: The legal behaviors in using medical masks in public have been finally promulgated by the Vietnamese Government after 47 days since the WHO declared the Public Health Emergency of International Concern (PHEIC) due to the COVID-19 pandemic. From a sample of 345 Vietnamese respondents aged from 15 to 47 years, this brief note found that the risk perception of COVID-19 danger significantly increases the likelihood of wearing the medical masks. In addition, there is a weak evidence about the differences in age under the COVID-19 outbreaks. More noticeably, those who use masks before COVID-19 pandemic tend to maintain their behaviors. Our results offer the insightful into Vietnamese citizens responses in terms of using medical masks; even the uses of this method are still controversial. Our results are robust by performing Exploratory Factor Analysis for five features and further regressions.", "qid": 44, "docid": "tfspedf1", "rank": 85, "score": 0.7396968007087708}, {"content": "Title: How Efficient Can Non-Professional MasksSuppress COVID-19 Pandemic? Content: The coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can be transmitted via respiratory secretions. Since there are currently no specific therapeutics or vaccines available against the SARS-CoV-2, the commen nonpharmaceutical interventions (NPIs) are still the main measures to curb the COVID-19 epidemic. Face mask wearing is one important measure to suppress the pandemic. In order to know how efficient is face mask wearing in reducing the pandemic even with low efficiency non-professional face masks, we exploit physical abstraction to model the non-professional face masks made from cotton woven fabrics and characterize them by a parameter virus penetration rate (VPR){gamma}. Monte Carlo simulations exhibit that the effective reproduction number R of COVID-19 or similar pandemics can be approximately reduced by factor {gamma}4 with respect to the basic reproduction number R0,if the face masks with 70% <{gamma}< 90% are universally applied for the entire network. Furthermore, thought experiments and practical exploitation examples in country-level and city-level are enumerated and discussed to support our discovery in this study and indicate that the outbreak of a COVID-19 like pandemic can be even suppressed by the low efficiency non-professional face masks.", "qid": 44, "docid": "1yf1ae1d", "rank": 86, "score": 0.7396965026855469}, {"content": "Title: Aerosol blocking assessment by different types of fabrics for homemade respiratory masks: spectroscopy and imaging study Content: During the COVID-19 pandemic, there is no agreement, until the current date, about the recommendations of homemade face mask use for the general population, and one of the reasons is a lack of information about their real protective rule on spreading aerosols and viruses. This is a comparative study regarding the relative efficiencies of commercial respiratory masks (medical masks) and homemade fabric masks, which may guide authorities across the globe, following the 'Advice on the use of masks in the context of COVID-19', by the World Health Organization. We described two optical methodologies for charactering respiratory masks. It happens that the aerosol scattering coefficient is linear as a function of its concentration inside the mask chamber. Quantitative optical properties of scattering for a large batch fabrication of masks were demonstrated, making the mask N95 suitable for use as a reference standard.", "qid": 44, "docid": "0lndg8s2", "rank": 87, "score": 0.7390220165252686}, {"content": "Title: Disposable masks: Disinfection and sterilization for reuse, and non-certified manufacturing, in the face of shortages during the COVID-19 pandemic Content: The COVID-19 pandemic is posing a huge global health threat. To deal with this problem, in addition to research and work in the medical field, the main health measures being taken in the workplace and at home involve the establishment of safety protocols, which include distance measures, hygiene and the use of personal protective equipment, such as masks, etc. The WHO still does not recommend the use of masks for the general population. However, their successful use in China, South Korea and the Czech Republic has encouraged their widespread use, and the shortage that already existed. This has caused that companies and individuals are looking at the best way to reuse them, and to manufacture, homemade or not, of non-certified masks. This paper is based on two objectives: to consult the scientific literature to identify the main strategies for disinfecting them, and to determine the effectiveness of non-certified disposable masks. A rapid review has been conducted in which the main publications and other information available online have been analyzed. Results showed that the most promising methods are those that use hydrogen peroxide vapor, ultraviolet radiation, moist heat, dry heat and ozone gas. Soapy water, alcohol, bleach immersion, ethylene oxide, ionizing radiation, microwave, high temperature, autoclave or steam are not fully recommended. Regarding the effectiveness of surgical masks compared to PPE, the former have been seen to be slightly less effective than PPE. As for other types of masks the effectiveness of homemade or non-certified masks is very low.", "qid": 44, "docid": "lncsfohg", "rank": 88, "score": 0.7385300993919373}, {"content": "Title: Efficacy of hydrogel patches in preventing facial skin damage caused by mask compression in fighting against coronavirus disease\u20102019: a short\u2010term, self\u2010controlled study Content: During the recent ongoing coronavirus disease\u20102019 (COVID\u201019) outbreak, healthcare workers around the world are fighting at the front lines of this epidemic, as well as the dermatologists. Our previous research revealed that long\u2010term wearing of N95 masks could lead to various facial skin lesions, which might affect their routine work and mental health. More importantly, severe skin lesions (e.g. ulcers) might put them in danger of being infected. Generally, hydrogels have been used to treat patients with pressure ulcers.", "qid": 44, "docid": "tg5oa58i", "rank": 89, "score": 0.7384320497512817}, {"content": "Title: The use of face masks during the COVID-19 pandemic in Poland: a survey study of 2315 young adults Content: Face masks wearing during the COVID-19 pandemic became ubiquitous. The aim of our study was to assess the use of face masks among young adults during the current viral pandemic. The survey was based on specially created Google Forms and posted on numerous Facebook groups for young people in Poland. Seven days were considered as a recall period. 2315 answers were obtained, 2307 were finally analysis, as 8 questionnaires were removed because of data incompleteness. 60.4% of responders declared using the face masks. Those who reported an atopic predisposition wore face masks significantly (P = 0.007) more commonly (65.5% and 57.7%, respectively). Cloth masks (46.2%) appeared to be most popular ones, followed by surgical masks (39.2%), respirators (N95 and FFP) (13.3%), half-face elastomeric respirators (0.8%) and full-face respirators (0.4%). Females significantly more frequently (P = 0.0001) used cloth masks; respirators, half-face elastomeric respirators and full-face respirators were used more commonly by males (P < 0.0001, P = 0.001 and P = 0.001, respectively). 23.9% of responders who used single-use staff wore it again. Moreover, 73.6% participants declared masks decontamination, however the procedures were not always appropriate. We suggest that our results may be of help in construction of general public education campaigns on the proper use of face masks. This article is protected by copyright. All rights reserved.", "qid": 44, "docid": "br6f9ig9", "rank": 90, "score": 0.7383730411529541}, {"content": "Title: The scientific rationale for the use of simple masks or improvised facial coverings to trap exhaled aerosols and possibly reduce the breathborne spread of COVID-19 Content: The medical community agrees that breathborne infectious materials can be spread with exhaled aerosols and that asymptomatic people, i.e., those showing no symptoms, could be unknowingly infectious. With the current worldwide pandemic of the respiratory coronavirus disease 2019 (COVID-19), various health bodies and governments are recommending that the population wear some form of mask or improvised facial covers while out in public in an effort to reduce the spread of disease . The general concept is that more accessible masks or mask-like materials (scarves, bandanas, etc.) could serve to reduce the amount of infectious aerosol from infected people, and reduce the viral load in the environment. This editorial addresses the underlying scientific rationale that such inexpensive or improvised could indeed serve to reduce the emissions of infectious aerosol by the mechanism of surface adhesion and particle kinetics in addition to the filtration effect.", "qid": 44, "docid": "m17j5u0y", "rank": 91, "score": 0.7378076910972595}, {"content": "Title: Lockdown exit strategies and risk of a second epidemic peak: a stochastic agent-based model of SARS-CoV-2 epidemic in France Content: Most European countries have responded to the COVID-19 threat by nationwide implementation of barrier measures and lockdown. However, assuming that population immunity will build up through the epidemic, it is likely to rebound once these measures are relaxed, possibly leading to a second or multiple repeated lockdowns. In this report, we present results of epidemiological modelling that has helped inform policy making in France. We used a stochastic agent-based microsimulation model of the COVID-19 epidemic in France, and examined the potential impact of post-quarantine measures, including social distancing, mask-wearing, and shielding of the population the most vulnerable to severe COVID-19 infection, on the disease's cumulative incidence and mortality, and on ICU-bed occupancy. The model calibrated well and variation of model parameter values had little impact on outcome estimates. While quarantine is effective in containing the viral spread, it would be unlikely to prevent a rebound of the epidemic once lifted, regardless of its duration. Both social distancing and mask-wearing, although effective in slowing the epidemic and in reducing mortality, would also be ineffective in ultimately preventing the overwhelming of ICUs and a second lockdown. However, these measures coupled with shielding of vulnerable people would be associated with better outcomes, including lower cumulative incidence, mortality, and maintaining an adequate number of ICU beds to prevent a second lockdown. Benefits would nonetheless be markedly reduced if these measures were not applied by most people or not maintained for a sufficiently long period, as herd immunity progressively establishes in the less vulnerable population.", "qid": 44, "docid": "smndijko", "rank": 92, "score": 0.7377457022666931}, {"content": "Title: Facemasks and similar barriers to prevent respiratory illness such as COVID-19: A rapid systematic review Content: The current pandemic of COVID-19 has lead to conflicting opinions on whether wearing facemasks outside of health care facilities protects against the infection. To better understand the value of wearing facemasks we undertook a rapid systematic review of existing scientific evidence about development of respiratory illness, linked to use of facemasks in community settings. METHODS: We included all study designs. There were 31 eligible studies (including 12 RCTs). Narrative synthesis and random-effects meta-analysis of attack rates for primary and secondary prevention in 28 studies were performed. Results were reported by design, setting and type of face barrier in primary prevention, and by who wore the facemask (index patient or well contacts) in secondary prevention trials. The preferred outcome was influenza-like illness (ILI) but similar outcomes were pooled with ILI when ILI was unavailable. GRADE quality assessment was based on RCTs with support from observational studies. RESULTS: Where specific information was available, most studies reported about use of medical grade (surgical paper masks). In 3 RCTs, wearing a facemask may very slightly reduce the odds of developing ILI/respiratory symptoms, by around 6% (OR 0.94, 95% CI 0.75 to 1.19, I2 29%, low certainty evidence). Greater effectiveness was suggested by observational studies. When both house-mates and an infected household member wore facemasks the odds of further household members becoming ill may be modestly reduced by around 19% (OR 0.81, 95%CI 0.48 to 1.37, I 2 45%, 5 RCTs, low certainty evidence). The protective effect was very small if only the well person(OR 0.93, 95% CI 0.68 to 1.28, I2 11%, 2 RCTs, low uncertainty evidence) or the infected person wore the facemask (very low certainty evidence). DISCUSSION: Based on the RCTs we would conclude that wearing facemasks can be very slightly protective against primary infection from casual community contact, and modestly protective against household infections when both infected and uninfected members wear facemasks. However, the RCTs often suffered from poor compliance and controls using facemasks. Across observational studies the evidence in favour of wearing facemasks was stronger. We expect RCTs to under-estimate the protective effect and observational studies to exaggerate it. The evidence is not sufficiently strong to support widespread use of facemasks as a protective measure against COVID-19. However, there is enough evidence to support the use of facemasks for short periods of time by particularly vulnerable individuals when in transient higher risk situations. Further high quality trials are needed to assess when wearing a facemask in the community is most likely to be protective.", "qid": 44, "docid": "844229sb", "rank": 93, "score": 0.7376056909561157}, {"content": "Title: Rational use of face mask in a tertiary care hospital setting during COVID-19 pandemic: An observational study Content: Masks play a role in the protection of health-care workers (HCWs) from acquiring respiratory infections, including coronavirus disease 2019 (COVID-19) in health-care settings. This observational study was conducted among 382 HCWs in a tertiary care setting over a period of 1 month. Descriptive analysis was done to assess the rational and recommended use of masks/respirators during COVID-19 pandemic using a structured observation checklist as a survey tool. A total of 374 HCWs were included, 64.9% of whom were using face masks rationally as mentioned per risk area categorization with a predominance of triple-layered mask during all 4 weeks. Overall, 64.1% used masks correctly. Clear guidelines and strategies can help to increase the compliance of HCWs with rational use of face masks.", "qid": 44, "docid": "57zwd3y6", "rank": 94, "score": 0.7370878458023071}, {"content": "Title: Rational use of face mask in a tertiary care hospital setting during COVID-19 pandemic: An observational study. Content: Masks play a role in the protection of health-care workers (HCWs) from acquiring respiratory infections, including coronavirus disease 2019 (COVID-19) in health-care settings. This observational study was conducted among 382 HCWs in a tertiary care setting over a period of 1 month. Descriptive analysis was done to assess the rational and recommended use of masks/respirators during COVID-19 pandemic using a structured observation checklist as a survey tool. A total of 374 HCWs were included, 64.9% of whom were using face masks rationally as mentioned per risk area categorization with a predominance of triple-layered mask during all 4 weeks. Overall, 64.1% used masks correctly. Clear guidelines and strategies can help to increase the compliance of HCWs with rational use of face masks.", "qid": 44, "docid": "t2e4bxsu", "rank": 95, "score": 0.7370878458023071}, {"content": "Title: Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community Settings: A Living Rapid Review Content: BACKGROUND: Recommendations on masks for preventing coronavirus disease 2019 (COVID-19) vary. PURPOSE: To examine the effectiveness of N95, surgical, and cloth masks in community and health care settings for preventing respiratory virus infections, and effects of reuse or extended use of N95 masks. DATA SOURCES: Multiple electronic databases, including the World Health Organization COVID-19 database and medRxiv preprint server (2003 through 14 April 2020; surveillance through 2 June 2020), and reference lists. STUDY SELECTION: Randomized trials of masks and risk for respiratory virus infection, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and observational studies of mask use and coronavirus infection risk were included. New evidence will be incorporated by using living review methods. DATA EXTRACTION: One reviewer abstracted data and assessed methodological limitations; a second reviewer provided verification. DATA SYNTHESIS: 39 studies (18 randomized controlled trials and 21 observational studies; 33 867 participants) were included. No study evaluated reuse or extended use of N95 masks. Evidence on SARS-CoV-2 was limited to 2 observational studies with serious limitations. Community mask use was possibly associated with decreased risk for SARS-CoV-1 infection in observational studies. In high- or moderate-risk health care settings, observational studies found that risk for infection with SARS-CoV-1 and Middle East respiratory syndrome coronavirus probably decreased with mask use versus nonuse and possibly decreased with N95 versus surgical mask use. Randomized trials in community settings found possibly no difference between N95 versus surgical masks and probably no difference between surgical versus no mask in risk for influenza or influenza-like illness, but compliance was low. In health care settings, N95 and surgical masks were probably associated with similar risks for influenza-like illness and laboratory-confirmed viral infection; clinical respiratory illness had inconsistency. Bothersome symptoms were common. LIMITATIONS: There were few SARS-CoV-2 studies, observational studies have methodological limitations, and the review was done by using streamlined methods. CONCLUSION: Evidence on mask effectiveness for respiratory infection prevention is stronger in health care than community settings. N95 respirators might reduce SARS-CoV-1 risk versus surgical masks in health care settings, but applicability to SARS-CoV-2 is uncertain. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.", "qid": 44, "docid": "kshjqsdj", "rank": 96, "score": 0.7369657754898071}, {"content": "Title: Knowledge, Attitude, and Practices of Healthcare Workers Regarding the Use of Face Mask to Limit the Spread of the New Coronavirus Disease (COVID-19) Content: Introduction Many countries including Pakistan are currently using face masks in their pandemic control plans. Being highly prevalent, the correct use of these masks is particularly important, as an incorrect use and disposal may actually increase the rate of transmission. The purpose of this study was to investigate the knowledge, attitude, and practices of healthcare workers (HCWs) in wearing a surgical face mask to limit the spread of the new coronavirus disease 2019 (COVID-19). Materials and Methods This survey was conducted by interviewing HCWs using a questionnaire consisting of the basic demographic characteristics, and the knowledge, attitude, and practices regarding the use of surgical face mask to limit the new COVID-19 exposure. Each correct answer was scored 1 and each incorrect answer scored 0. The total number of questions was 16, and the final score was calculated and then labeled according to the percentage (out of 16) of correct responses as good (>80%), moderate (60-80%), and poor (<60%). Results A total of 392 participants with a mean age of 42.37 \u00b1 13.34 years (341 males and 51 females) were included in the study. The overall final results were good in 138 (35.2%), moderate in 178 (45.4%), and poor in 76 (19.3%). Around 43.6% of participants knew about the correct method of wearing the masks, 68.9% knew that there are three layers, 53% stated that the middle layer act as a filter media barrier, and 75.5% knew the recommended maximum duration of wearing it. The majority (88.2%) of participants knew that a cloth face mask is not much effective, around 79.8% knew that used face mask cannot be re-used, and 44.8% knew about the yellow-coded bag for disposal. Conclusions Knowledge, attitude, and practice of HCWs regarding the use of face masks were found to be inadequate. Studied HCWs had a positive attitude but moderate-to-poor level of knowledge and practice regarding the use of face mask. HCWs and general public awareness campaigns regarding the proper use of face mask by utilizing all social media available resources would be helpful during this pandemic.", "qid": 44, "docid": "0javg3m8", "rank": 97, "score": 0.7368782162666321}, {"content": "Title: The N-95 mask: invaluable ally in the battle against the COVID-19 pandemic Content: The present COVID-19 pandemic, caused by the airborne SARS-CoV-2 virus, has highlighted the vital importance of appropriate personal protective equipment for all exposed health care workers The single most important part of this armor is the N-95 mask With the awareness that the virus is spread by both droplets and through the aerosolized route, the N-95 provides protection that a surgical mask cannot match This timely review looks at the special advantages that an N-95 offers over a surgical mask with specific reference to the COVID-19 epidemic It also emphasizes the crucial importance of ensuring quality masks with a proper fit Finally, with acute scarcities of N-95 masks being reported from hospitals globally, it reviews recent literature which attempts to prolong the life of these masks with extended use, reuse and decontamination of used masks", "qid": 44, "docid": "i1w2snyy", "rank": 98, "score": 0.7368302345275879}, {"content": "Title: The role of community-wide wearing of face mask for control of coronavirus disease 2019 (COVID-19) epidemic due to SARS-CoV-2 Content: Abstract Background Face mask usage by the healthy population in the community to reduce risk of transmission of respiratory viruses remains controversial. We assessed the effect of community-wide mask usage to control coronavirus disease 2019 (COVID-19) in Hong Kong Special Administrative Region (HKSAR). Methods Patients presenting with respiratory symptoms at outpatient clinics or hospital wards were screened for COVID-19 per protocol. Epidemiological analysis was performed for confirmed cases, especially persons acquiring COVID-19 during mask-off and mask-on settings. The incidence of COVID-19 per-million-population in HKSAR with community-wide masking was compared to that of non-mask-wearing countries which are comparable with HKSAR in terms of population density, healthcare system, BCG vaccination and social distancing measures but not community-wide masking. Compliance of face mask usage in the HKSAR community was monitored. Findings Within first 100 days (31 December 2019 to 8 April 2020), 961 COVID-19 patients were diagnosed in HKSAR. The COVID-19 incidence in HKSAR (129.0 per-million-population) was significantly lower (p<0.001) than that of Spain (2983.2), Italy (2250.8), Germany (1241.5), France (1151.6), U.S. (1102.8), U.K. (831.5), Singapore (259.8), and South Korea (200.5). The compliance of face mask usage by HKSAR general public was 96.6% (range: 95.7% to 97.2%). We observed 11 COVID-19 clusters in recreational \u2018mask-off\u2019 settings compared to only 3 in workplace \u2018mask-on\u2019 settings (p = 0.036 by Chi square test of goodness-of-fit). Conclusion Community-wide mask wearing may contribute to the control of COVID-19 by reducing virus shedding in saliva and respiratory droplets from individuals with subclinical or mild COVID-19.", "qid": 44, "docid": "9mn6trtn", "rank": 99, "score": 0.7364284992218018}, {"content": "Title: Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community Settings: A Living Rapid Review Content: BACKGROUND: Recommendations on masks for preventing coronavirus disease 2019 (COVID-19) vary. PURPOSE: To examine the effectiveness of N95, surgical, and cloth masks in community and health care settings for preventing respiratory virus infections, and effects of reuse or extended use of N95 masks. DATA SOURCES: Multiple electronic databases, including the World Health Organization COVID-19 database and medRxiv preprint server (2003 through 14 April 2020; surveillance through 2 June 2020), and reference lists. STUDY SELECTION: Randomized trials of masks and risk for respiratory virus infection, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and observational studies of mask use and coronavirus infection risk were included. New evidence will be incorporated by using living review methods. DATA EXTRACTION: One reviewer abstracted data and assessed methodological limitations; a second reviewer provided verification. DATA SYNTHESIS: 39 studies (18 randomized controlled trials and 21 observational studies; 33 867 participants) were included. No study evaluated reuse or extended use of N95 masks. Evidence on SARS-CoV-2 was limited to 2 observational studies with serious limitations. Community mask use was possibly associated with decreased risk for SARS-CoV-1 infection in observational studies. In high- or moderate-risk health care settings, observational studies found that risk for infection with SARS-CoV-1 and Middle East respiratory syndrome coronavirus probably decreased with mask use versus nonuse and possibly decreased with N95 versus surgical mask use. Randomized trials in community settings found possibly no difference between N95 versus surgical masks and probably no difference between surgical versus no mask in risk for influenza or influenza-like illness, but compliance was low. In health care settings, N95 and surgical masks were probably associated with similar risks for influenza-like illness and laboratory-confirmed viral infection; clinical respiratory illness had inconsistency. Bothersome symptoms were common. LIMITATIONS: There were few SARS-CoV-2 studies, observational studies have methodological limitations, and the review was done by using streamlined methods. CONCLUSION: Evidence on mask effectiveness for respiratory infection prevention is stronger in health care than community settings. N95 respirators might reduce SARS-CoV-1 risk versus surgical masks in health care settings, but applicability to SARS-CoV-2 is uncertain. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. Update Alerts: The authors have specified in the Methods section the interval and stop date for updates to this Living Review. As Annals receives updates, they will appear in the Comments section of the article on Annals.org. Reader inquiries about updates that are not available at approximately the specified intervals should be submitted as Comments to the article.", "qid": 44, "docid": "j0lpy07l", "rank": 100, "score": 0.7362123727798462}]}
{"query": "How has the COVID-19 pandemic impacted mental health?", "hits": [{"content": "Title: Caring for patients with posttraumatic stress and substance use disorders during the COVID-19 pandemic Content: Although COVID-19 is a physical illness, it has had large impacts on mental health. For many individuals, social distancing has led to social isolation; individuals with posttraumatic stress disorder and substance use disorders are at a particular risk for negative outcomes due to the global pandemic. Here, we discuss the impacts we have noticed and procedures we have implemented to care for this population during the pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "pfrnlvda", "rank": 1, "score": 0.8790720105171204}, {"content": "Title: Caring for patients with posttraumatic stress and substance use disorders during the COVID-19 pandemic. Content: Although COVID-19 is a physical illness, it has had large impacts on mental health. For many individuals, social distancing has led to social isolation; individuals with posttraumatic stress disorder and substance use disorders are at a particular risk for negative outcomes due to the global pandemic. Here, we discuss the impacts we have noticed and procedures we have implemented to care for this population during the pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "7uodxlrz", "rank": 2, "score": 0.8790720105171204}, {"content": "Title: Coping with Mental Health Challenges During COVID-19 Content: The ongoing pandemic of COVID-19 is a global challenge which resulted in significant morbidity and mortality worldwide. It has also adversely affected the economy and social integrity. There is rising concern about the mental health challenges of the general population, COVID-19-infected patients, close contacts, elderly, children and health professionals. This chapter focusses on various mental health challenges during the COVID-19 pandemic.", "qid": 45, "docid": "50palac7", "rank": 3, "score": 0.8713893294334412}, {"content": "Title: Mental Health and the COVID19 Pandemic Content: With the advent of the COVID-19 pandemic we have witnessed the greatest global challenge in a generation. The full extent of the mental health impact is, as yet, unknown, but is anticipated to be severe and enduring. In this Special Issue dedicated to mental health and the COVID-19 pandemic, we aim to lay the foundation for an improved understanding of how COVID-19 is affecting mental health services both in Ireland and globally. This Special Issue highlights how the mental health effects of COVID-19 stretch to almost every element of society. The issue includes perspectives from several countries across multiple disciplines and healthcare settings. The drive for rapid innovation and service development is clearly evident throughout, and provides hope that by working collaboratively we can positively impact population mental health in the months and years ahead.", "qid": 45, "docid": "wbwd7m5w", "rank": 4, "score": 0.869912326335907}, {"content": "Title: Mental Health and the COVID19 Pandemic. Content: With the advent of the COVID-19 pandemic we have witnessed the greatest global challenge in a generation. The full extent of the mental health impact is, as yet, unknown, but is anticipated to be severe and enduring. In this Special Issue dedicated to mental health and the COVID-19 pandemic, we aim to lay the foundation for an improved understanding of how COVID-19 is affecting mental health services both in Ireland and globally. This Special Issue highlights how the mental health effects of COVID-19 stretch to almost every element of society. The issue includes perspectives from several countries across multiple disciplines and healthcare settings. The drive for rapid innovation and service development is clearly evident throughout, and provides hope that by working collaboratively we can positively impact population mental health in the months and years ahead.", "qid": 45, "docid": "hze88sr4", "rank": 5, "score": 0.869912326335907}, {"content": "Title: [COVID-19 Concerns and Worries in Patients with Mental Illness]. Content: OBJECTIVE This study examines the impact of the COVID-19 pandemic and the lock-down on patients with mental illness. METHODS Patients in inpatient or outpatient psychiatric treatment received a questionnaire, examining psychological distress and psychiatric care during the COVID-19 pandemic. RESULTS More than half of the patients indicated that the state of emergency had a negative impact on their mental illness. Severely ill patients were more affected. CONCLUSION Patients with mental illness are a particularly vulnerable group in the current crisis. Psychiatric and psychotherapeutic care needs to be adapted accordingly; the specific burden and distress needs to be examined actively in patients from all diagnostic groups.", "qid": 45, "docid": "96wi5b3a", "rank": 6, "score": 0.8693133592605591}, {"content": "Title: The impact of the COVID-19 pandemic on suicide rates Content: Multiple lines of evidence indicate that the COVID-19 pandemic has profound psychological and social effects. The psychological sequelae of the pandemic will probably persist for months and years to come. Studies indicate that the COVID-19 pandemic is associated with distress, anxiety, fear of contagion, depression, and insomnia in the general population and among health care professionals. Social isolation, anxiety, fear of contagion, uncertainty, chronic stress, and economic difficulties may lead to the development or exacerbation of depressive, anxiety, substance use, and other psychiatric disorders in vulnerable populations including individuals with pre-existing psychiatric disorders and people who reside in high COVID-19 prevalence areas. Stress-related psychiatric conditions including mood and substance use disorders are associated with suicidal behavior. COVID-19 survivors may also be at elevated suicide risk. The COVID-19 crisis may increase suicide rates during and after the pandemic. Mental health consequences of the COVID-19 crisis including suicidal behavior are likely to be present for a long time and peak later than the actual pandemic. To reduce suicides during the COVID-19 crisis it is imperative to decrease stress, anxiety, fears and loneliness in the general population. There should be traditional and social media campaigns to promote mental health and reduce distress. Active outreach is necessary, especially for people with a history of psychiatric disorders, COVID-19 survivors, and older adults. Research studies are needed of how mental health consequences can be mitigated during and after the COVID-19 pandemic.", "qid": 45, "docid": "y9vx7coj", "rank": 7, "score": 0.86829674243927}, {"content": "Title: The coronavirus (COVID-19) pandemic's impact on mental health Content: Throughout the world, the public is being informed about the physical effects of SARS-CoV-2 infection and steps to take to prevent exposure to the coronavirus and manage symptoms of COVID-19 if they appear. However, the effects of this pandemic on one's mental health have not been studied at length and are still not known. As all efforts are focused on understanding the epidemiology, clinical features, transmission patterns, and management of the COVID-19 outbreak, there has been very little concern expressed over the effects on one's mental health and on strategies to prevent stigmatization. People's behavior may greatly affect the pandemic's dynamic by altering the severity, transmission, disease flow, and repercussions. The present situation requires raising awareness in public, which can be helpful to deal with this calamity. This perspective article provides a detailed overview of the effects of the COVID-19 outbreak on the mental health of people.", "qid": 45, "docid": "5cmcri6u", "rank": 8, "score": 0.8675626516342163}, {"content": "Title: COVID-19 and mental health: A review of the existing literature Content: Abstract The COVID-19 pandemic is a major health crisis affecting several nations, with over 720,000 cases and 33,000 confirmed deaths reported to date. Such widespread outbreaks are associated with adverse mental health consequences. Keeping this in mind, existing literature on the COVID-19 outbreak pertinent to mental health was retrieved via a literature search of the PubMed database. Published articles were classified according to their overall themes and summarized. Preliminary evidence suggests that symptoms of anxiety and depression (16\u201328%) and self-reported stress (8%) are common psychological reactions to the COVID-19 pandemic, and may be associated with disturbed sleep. A number of individual and structural variables moderate this risk. In planning services for such populations, both the needs of the concerned people and the necessary preventive guidelines must be taken into account. The available literature has emerged from only a few of the affected countries, and may not reflect the experience of persons living in other parts of the world. In conclusion, subsyndromal mental health problems are a common response to the COVID-19 pandemic. There is a need for more representative research from other affected countries, particularly in vulnerable populations.", "qid": 45, "docid": "o72unm3q", "rank": 9, "score": 0.8655524253845215}, {"content": "Title: COVID-19 and mental health: A review of the existing literature Content: The COVID-19 pandemic is a major health crisis affecting several nations, with over 720,000 cases and 33,000 confirmed deaths reported to date. Such widespread outbreaks are associated with adverse mental health consequences. Keeping this in mind, existing literature on the COVID-19 outbreak pertinent to mental health was retrieved via a literature search of the PubMed database. Published articles were classified according to their overall themes and summarized. Preliminary evidence suggests that symptoms of anxiety and depression (16-28%) and self-reported stress (8%) are common psychological reactions to the COVID-19 pandemic, and may be associated with disturbed sleep. A number of individual and structural variables moderate this risk. In planning services for such populations, both the needs of the concerned people and the necessary preventive guidelines must be taken into account. The available literature has emerged from only a few of the affected countries, and may not reflect the experience of persons living in other parts of the world. In conclusion, subsyndromal mental health problems are a common response to the COVID-19 pandemic. There is a need for more representative research from other affected countries, particularly in vulnerable populations.", "qid": 45, "docid": "6gtgohci", "rank": 10, "score": 0.8650458455085754}, {"content": "Title: Psychological Intervention and COVID-19: What We Know So Far and What We Can Do Content: The coronavirus COVID-19 and the global pandemic has already had a substantial disruptive impact on society, posing major challenges to the provision of mental health services in a time of crisis, and carrying the spectre of an increased burden to mental health, both in terms of existing psychiatric disorder, and emerging psychological distress from the pandemic. In this paper we provide a framework for understanding the key challenges for psychologically informed mental health care during and beyond the pandemic. We identify three groups that can benefit from psychological approaches to mental health, and/or interventions relating to COVID-19. These are (i) healthcare workers engaged in frontline response to the pandemic and their patients; (ii) individuals who will experience the emergence of new mental health distress as a function of being diagnosed with COVID-19, or losing family and loved ones to the illness, or the psychological effects of prolonged social distancing; and (iii) individuals with existing mental health conditions who are either diagnosed with COVID-19 or whose experience of social distancing exacerbates existing vulnerabilities. Drawing on existing literature and our own experience of adapting treatments to the crisis we suggest a number of salient points to consider in identifying risks and offering support to all three groups. We also offer a number of practical and technical considerations for working psychotherapeutically with existing patients where COVID-19 restrictions have forced a move to online or technologically mediated delivery of psychological interventions.", "qid": 45, "docid": "9qh7efs4", "rank": 11, "score": 0.8647504448890686}, {"content": "Title: Current and Future Challenges in the Delivery of Mental Healthcare during COVID-19 Content: The USA is in the midst of the COVID-19 pandemic. We assess the impact of COVID-19 on psychiatric symptoms in healthcare workers, those with psychiatric comorbidities, and the general population. We highlight the challenges ahead and discuss the increased relevance of telepsychiatry. We analyzed all available literature available as of March 25, 2020, on PubMed, Ovid Medline, and PsychInfo. We utilized the MeSH term \u201ccovid AND (psychiatry OR mental health)\u201d and included all articles. Duplicates were removed resulting in 32 articles, of which 19 are cited. Four additional references are included to examine suicide data. During the review process, an additional 7 articles were identified which are also included. Frontline healthcare workers are currently experiencing increased psychiatric symptoms and this is more severe in females and nurses. Non-frontline healthcare workers, as well as the general population, are experiencing vicarious traumatization. People with psychiatric comorbidities, and the general population, face increased psychiatric symptom burden. Migrant workers, the elderly, children, and the homeless may be disproportionately impacted. Suicide rates may be impacted. The COVID-19 pandemic has resulted in a severe disruption to the delivery of mental healthcare. Psychiatric facilities are facing unprecedented disruptions in care provision as they struggle to manage an infected population with comorbid psychiatric symptoms. Telepsychiatry is a flawed but reasonable solution to increase the availability of mental healthcare during COVID-19.", "qid": 45, "docid": "y2vgo55k", "rank": 12, "score": 0.864176869392395}, {"content": "Title: Psychiatric Symptoms Related to the COVID-19 Pandemic Content: The COVID-19 pandemic and the consequential societal changes are likely to have major health consequences way beyond those caused by the virus infection. One of the medical fields that may experience significant consequences of the pandemic is that of psychiatry. Importantly, individuals who already live with mental disorders may be particularly vulnerable to the psychological stress associated with the pandemic. However, data on how the COVID-19 pandemic affects this group of people is largely absent from the literature. Here, we report data from a quality development project conducted at the psychiatric services of the Central Denmark Region (CDR), which has a catchment area of approximately 1.3 million people covered by five psychiatric hospitals providing inpatient and outpatient treatment of all types of mental disorders. Based on a manual screening of all clinical notes from the period from February 1st to March 23rd 2020 that contained at least one of the following words: corona, COVID, virus, epidemic, pandemic, and contaminate/contamination (including compound words), we found 1357 notes from 918 adult patients that described pandemic-related psychopathology (symptoms that appeared to be caused/deteriorated by the pandemic and/or its societal consequences). To our knowledge, this is the first investigation of COVID-19 pandemic-related psychopathology from a large psychiatric treatment setting. The results clearly suggest that this phenomenon exists among individuals with mental illness. However, as the data from this investigation stems from standard clinical practice where the patients were not systematically assessed for pandemic-related psychopathology, we cannot speak to its overall prevalence. Nevertheless, we believe that our findings underline the necessity of taking urgent action to mitigate the negative effects of the COVID-19 pandemic on patients with mental disorders. A low-cost intervention would be to simply discuss the ongoing pandemic and its societal consequences with patients seeking care in psychiatric settings - as this may lead to relief of pandemic-related symptoms via general comforting, and clarification of misunderstandings/false beliefs regarding the pandemic.", "qid": 45, "docid": "gy90nvir", "rank": 13, "score": 0.863411545753479}, {"content": "Title: Early impacts of the COVID-19 pandemic on mental health care and on people with mental health conditions: framework synthesis of international experiences and responses Content: Purpose The COVID-19 pandemic has many potential impacts on people with mental health conditions and on mental health care, including direct consequences of infection, effects of infection control measures and subsequent societal changes. We aimed to map early impacts of the pandemic on people with pre-existing mental health conditions and services they use, and to identify individual and service-level strategies adopted to manage these. Methods We searched for relevant material in the public domain published before 30 April 2020, including papers in scientific and professional journals, published first person accounts, media articles, and publications by governments, charities and professional associations. Search languages were English, French, German, Italian, Spanish, and Mandarin Chinese. Relevant content was retrieved and summarised via a rapid qualitative framework synthesis approach. Results We found 872 eligible sources from 29 countries. Most documented observations and experiences rather than reporting research data. We found many reports of deteriorations in symptoms, and of impacts of loneliness and social isolation and of lack of access to services and resources, but sometimes also of resilience, effective self-management and peer support. Immediate service challenges related to controlling infection, especially in inpatient and residential settings, and establishing remote working, especially in the community. We summarise reports of swiftly implemented adaptations and innovations, but also of pressing ethical challenges and concerns for the future. Conclusion Our analysis captures the range of stakeholder perspectives and experiences publicly reported in the early stages of the COVID-19 pandemic in several countries. We identify potential foci for service planning and research.", "qid": 45, "docid": "uyebygdm", "rank": 14, "score": 0.8632969260215759}, {"content": "Title: The coronavirus (COVID\u201019) pandemic's impact on mental health Content: Throughout the world, the public is being informed about the physical effects of SARS\u2010CoV\u20102 infection and steps to take to prevent exposure to the coronavirus and manage symptoms of COVID\u201019 if they appear. However, the effects of this pandemic on one's mental health have not been studied at length and are still not known. As all efforts are focused on understanding the epidemiology, clinical features, transmission patterns, and management of the COVID\u201019 outbreak, there has been very little concern expressed over the effects on one's mental health and on strategies to prevent stigmatization. People's behavior may greatly affect the pandemic's dynamic by altering the severity, transmission, disease flow, and repercussions. The present situation requires raising awareness in public, which can be helpful to deal with this calamity. This perspective article provides a detailed overview of the effects of the COVID\u201019 outbreak on the mental health of people.", "qid": 45, "docid": "0n5n7p4b", "rank": 15, "score": 0.8612996339797974}, {"content": "Title: A population mental health perspective on the impact of COVID-19 Content: The global pandemic of coronavirus disease 2019 (COVID-19) has resulted in massive societal, economic, and environmental impacts that have both short- and long-term mental health influences. This commentary serves to tie existing literature on mental health and COVID-19 to the clinical experiences of a psychologist working in the Canadian hospital sector. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "6ngsyo8o", "rank": 16, "score": 0.8611665964126587}, {"content": "Title: A population mental health perspective on the impact of COVID-19. Content: The global pandemic of coronavirus disease 2019 (COVID-19) has resulted in massive societal, economic, and environmental impacts that have both short- and long-term mental health influences. This commentary serves to tie existing literature on mental health and COVID-19 to the clinical experiences of a psychologist working in the Canadian hospital sector. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "4q1j6g44", "rank": 17, "score": 0.8611665964126587}, {"content": "Title: Impact on mental health care and on mental health service users of the COVID-19 pandemic: a mixed methods survey of UK mental health care staff Content: Purpose: The COVID-19 pandemic has potential to disrupt and burden the mental health care system, and to magnify inequalities experienced by mental health service users. Methods: We investigated staff reports regarding the impact of the COVID-19 pandemic in its early weeks on mental health care and mental health service users in the UK using a mixed methods online survey. Recruitment channels included professional associations and networks, charities and social media. Quantitative findings were reported with descriptive statistics, and content analysis conducted for qualitative data. Results: 2,180 staff from a range of sectors, professions and specialties participated. Immediate infection control concerns were highly salient for inpatient staff, new ways of working for community staff. Multiple rapid adaptations and innovations in response to the crisis were described, especially remote working. This was cautiously welcomed but found successful in only some clinical situations. Staff had specific concerns about many groups of service users, including people whose conditions are exacerbated by pandemic anxieties and social disruptions; people experiencing loneliness, domestic abuse and family conflict; those unable to understand and follow social distancing requirements; and those who cannot engage with remote care. Conclusion: This overview of staff concerns and experiences in the early COVID-19 pandemic suggests directions for further research and service development: we suggest that how to combine infection control and a therapeutic environment in hospital, and how to achieve effective and targeted tele-health implementation in the community, should be priorities. The limitations of our convenience sample must be noted.", "qid": 45, "docid": "mfetvz49", "rank": 18, "score": 0.8597433567047119}, {"content": "Title: COVID-19 Pandemic: Impact on psychiatric care in the United States Content: The World Health Organization declared the coronavirus outbreak a pandemic on March 11, 2020. Infection by the SARS-CoV2 virus leads to the COVID-19 disease which can be fatal, especially in older patients with medical co-morbidities. The impact to the US healthcare system has been disruptive, and the way healthcare services are provided has changed drastically. Here, we present a compilation of the impact of the COVID-19 pandemic on psychiatric care in the US, in the various settings: outpatient, emergency room, inpatient units, consultation services, and the community. We further present effects seen on psychiatric physicians in the setting of new and constantly evolving protocols where adjustment and flexibility have become the norm, training of residents, leading a team of professionals with different expertise, conducting clinical research, and ethical considerations. The purpose of this paper is to provide examples of \"how to\" processes based on our current front-line experiences and research to practicing psychiatrists and mental health clinicians, inform practitioners about national guidelines affecting psychiatric care during the pandemic, and inform health care policy makers and health care systems about the challenges and continued needs of financial and administrative support for psychiatric physicians and mental health systems.", "qid": 45, "docid": "nxqa2wis", "rank": 19, "score": 0.8588182926177979}, {"content": "Title: Living with PTSD amid a global pandemic Content: The COVID-19 pandemic has demonstrated itself to be a considerable stressor, especially for those individuals coping with a preexisting mental health disorder. This article contains clinical observations and reflections from two practicing psychologists regarding the impact of the COVID-19 pandemic and associated social conditions on clients with posttraumatic stress disorder. Observations include changes in trauma-related symptom manifestations and therapeutic process issues, particularly in response to social isolation. The authors encourage specific therapeutic considerations and offer suggestions for adapting treatment with regard to these early observations. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "247r7fd3", "rank": 20, "score": 0.8565336465835571}, {"content": "Title: Living with PTSD amid a global pandemic. Content: The COVID-19 pandemic has demonstrated itself to be a considerable stressor, especially for those individuals coping with a preexisting mental health disorder. This article contains clinical observations and reflections from two practicing psychologists regarding the impact of the COVID-19 pandemic and associated social conditions on clients with posttraumatic stress disorder. Observations include changes in trauma-related symptom manifestations and therapeutic process issues, particularly in response to social isolation. The authors encourage specific therapeutic considerations and offer suggestions for adapting treatment with regard to these early observations. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "zn0m48q4", "rank": 21, "score": 0.8565336465835571}, {"content": "Title: Psychological interventions during COVID-19: Challenges for low and middle income countries Content: At the start of 2020, the 2019 coronavirus disease (COVID-19), originating from China has spread to the world. There have been increasing numbers of confirmed cases and deaths around the globe. The COVID-19 pandemic has paved the way for considerable psychological and psychosocial morbidity among the general public and health care providers. An array of guidelines has been put forward by multiple agencies for combating mental health challenges. This paper addresses some of the mental health challenges faced by low and middle income countries (LMIC). It is worthwhile to note that these are challenges at the current stage of the pandemic and may change with the course of the pandemic itself.", "qid": 45, "docid": "obrmy0zf", "rank": 22, "score": 0.855353593826294}, {"content": "Title: The scope of mental health research during the COVID-19 pandemic and its aftermath Content: The effects of the COVID-19 pandemic on population mental health are unknown. We need to understand the scale of any such impact in different sections of the population, who is most affected and how best to mitigate, prevent and treat any excess morbidity. We propose a coordinated and interdisciplinary mental health science response.", "qid": 45, "docid": "ilk9u1a8", "rank": 23, "score": 0.8547689914703369}, {"content": "Title: COVID-19 Pandemic: Impact on Psychiatric Care in the United States, a Review Content: Abstract The World Health Organization declared the coronavirus outbreak a pandemic on March 11, 2020. Infection by the SARS-CoV2 virus leads to the COVID-19 disease which can be fatal, especially in older patients with medical co-morbidities. The impact to the US healthcare system has been disruptive, and the way healthcare services are provided has changed drastically. Here, we present a compilation of the impact of the COVID-19 pandemic on psychiatric care in the US, in the various settings: outpatient, emergency room, inpatient units, consultation services, and the community. We further present effects seen on psychiatric physicians in the setting of new and constantly evolving protocols where adjustment and flexibility have become the norm, training of residents, leading a team of professionals with different expertise, conducting clinical research, and ethical considerations. The purpose of this paper is to provide examples of \u201chow to\u201d processes based on our current front-line experiences and research to practicing psychiatrists and mental health clinicians, inform practitioners about national guidelines affecting psychiatric care during the pandemic, and inform health care policy makers and health care systems about the challenges and continued needs of financial and administrative support for psychiatric physicians and mental health systems.", "qid": 45, "docid": "td9syerz", "rank": 24, "score": 0.8547661900520325}, {"content": "Title: Impact of the COVID-19 Pandemic on Adult Mental Health Content: The outbreak of the Novel Coronavirus (COVID-19) in December 2019 has progressed to the status of a global pandemic, with countries across the seven continents adversely affected and the number of human cases exceeding two million. With no available vaccine, the treatment is primarily symptomatic for those affected and preventative for those at risk. Most countries have taken action to curtail the spread of COVID-19 through measures such as lockdowns, social distancing and voluntary self-isolation. Whilst necessary, such measures and the disease itself, may have an adverse impact on mental health. In view of research from previous pandemic crises, it is known that such situations are likely to increase stress levels and have negative psychiatric effects. The impact is likely to be felt by the general public, sufferers of COVID-19, their families and friends, persons with pre-existing mental health conditions and healthcare workers.", "qid": 45, "docid": "880lwnde", "rank": 25, "score": 0.8546122908592224}, {"content": "Title: Mental Health and Psychosocial Challenges in the COVID-19 Pandemic: Food for Thought for Cardiovascular Health Care Professionals Content: Background The coronavirus disease (COVID-19) pandemic has produced substantial health challenges from the perspective of both its direct health complications and the disruption to delivery of standard care for individuals with a range of acute and chronic health issues. In parallel, the widespread application of social isolation initiatives in most countries raises the potential for significant mental health consequences and psychosocial impacts. This has major implications for cardiovascular health care professionals and the management of their patients. Challenges The COVID-19 pandemic and associated physical isolation practices are likely to result in a range of mental health and psychosocial challenges. In addition to an increasing incidence of anxiety, depression, suicidal ideation and post-traumatic stress, the pandemic may also witness an increase in substance abuse, domestic violence and relationship discord. The consequences of these complications will be further magnified, when considering their potential effect on cardiovascular disease and its management. Purpose This statement aims to summarise some of the potential mental health and psychosocial challenges that may arise in the setting of the COVID-19 pandemic.", "qid": 45, "docid": "pf1f9fhc", "rank": 26, "score": 0.8518450260162354}, {"content": "Title: Why all COVID-19 Hospitals should have Mental Health Professionals: The importance of mental health in a worldwide crisis! Content: Abstract COVID-19 pandemic has led to a worldwide crisis. At present, everyone is focusing on the prevention of COVID-19 infection, preparing and discussing issues related to physical health consequences. However, it is important to understand that the life-threatening negative physical health consequences are going to be faced by a few, but everyone is going to face the negative mental health consequences of the pandemic. At various places COVID-19 hospitals are being established, to address the physical health consequences of the pandemic. However, mental health professionals have not been very actively involved in the management of people going through this pandemic. This viewpoint discusses the mental health consequences of the pandemic for the health care workers, people who are undergoing quarantine, people who are admitted to the COVID-19 hospitals, and those who have recovered from the infection. The article also highlights the mental health needs of people at different levels and the kind of interventions, which may be carried out.", "qid": 45, "docid": "2q7fb55t", "rank": 27, "score": 0.8505092859268188}, {"content": "Title: Mental Health and Psychosocial Challenges in the COVID-19 Pandemic: Food for Thought for Cardiovascular Health Care Professionals Content: BACKGROUND: The coronavirus disease (COVID-19) pandemic has produced substantial health challenges from the perspective of both its direct health complications and the disruption to delivery of standard care for individuals with a range of acute and chronic health issues. In parallel, the widespread application of social isolation initiatives in most countries raises the potential for significant mental health consequences and psychosocial impacts. This has major implications for cardiovascular health care professionals and the management of their patients. CHALLENGES: The COVID-19 pandemic and associated physical isolation practices are likely to result in a range of mental health and psychosocial challenges. In addition to an increasing incidence of anxiety, depression, suicidal ideation and post-traumatic stress, the pandemic may also witness an increase in substance abuse, domestic violence and relationship discord. The consequences of these complications will be further magnified, when considering their potential effect on cardiovascular disease and its management. PURPOSE: This commentary aims to summarise some of the potential mental health and psychosocial challenges that may arise in the setting of the COVID-19 pandemic.", "qid": 45, "docid": "d7vo3l8e", "rank": 28, "score": 0.8494074940681458}, {"content": "Title: What lies ahead: Elevated concerns for the ongoing suicide pandemic Content: The genesis and global spread of coronavirus disease 2019 (COVID-19) has resulted in significant health concerns amid societies that were ill-equipped for such a formidable opponent. The COVID-19 pandemic has illuminated systemic health disparities and weaknesses within our health care and political systems. With aggressive but necessary interventions to thwart the instantaneous reproduction number, we have simultaneously introduced risk factors for new and exacerbated mental health concerns. Suicide, an ongoing pandemic whose rates are higher than they have been in the past 50 years, is one of these concerns as we navigate COVID-19 deaths and fears surrounding its spread. This article aims to briefly describe in retrospect some of the historical pandemics and their downstream consequences as well as present what may lie ahead in terms of anxiety, depression, and suicidal behaviors. This applies not only to frontline health care workers but also the public at large, who may very well experience long-term stressor- and trauma-related consequences through ongoing exposure to a virus that is not only potentially fatal but may have taken the lives of loved ones. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "h2tcrh1q", "rank": 29, "score": 0.8492673635482788}, {"content": "Title: What lies ahead: Elevated concerns for the ongoing suicide pandemic. Content: The genesis and global spread of coronavirus disease 2019 (COVID-19) has resulted in significant health concerns amid societies that were ill-equipped for such a formidable opponent. The COVID-19 pandemic has illuminated systemic health disparities and weaknesses within our health care and political systems. With aggressive but necessary interventions to thwart the instantaneous reproduction number, we have simultaneously introduced risk factors for new and exacerbated mental health concerns. Suicide, an ongoing pandemic whose rates are higher than they have been in the past 50 years, is one of these concerns as we navigate COVID-19 deaths and fears surrounding its spread. This article aims to briefly describe in retrospect some of the historical pandemics and their downstream consequences as well as present what may lie ahead in terms of anxiety, depression, and suicidal behaviors. This applies not only to frontline health care workers but also the public at large, who may very well experience long-term stressor- and trauma-related consequences through ongoing exposure to a virus that is not only potentially fatal but may have taken the lives of loved ones. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "tfx7tx9i", "rank": 30, "score": 0.8492673635482788}, {"content": "Title: Mental Health Consequences during the Initial Stage of the 2020 Coronavirus Pandemic (COVID-19) in Spain Content: The pandemic caused by Covid-19 has been an unprecedented social and health emergency worldwide. This is the first study in the scientific literature reporting the psychological impact of the Covid-19 outbreak in a sample of the Spanish population. A cross-sectional study was conducted through an online survey of 3480 people. The presence of depression, anxiety and post-traumatic stress disorder (PTSD) was evaluated with screening tests from 14 March. Sociodemographic and Covid-19-related data was collected. Additionally, spiritual well-being, loneliness, social support, discrimination and sense of belonging were assessed. Descriptive analyses were carried out and linear regression models compiled. The 18.7% of the sample revealed depressive, 21.6% anxiety and 15.8% PTSD symptoms. Being in the older age group, having economic stability and the belief that adequate information had been provided about the pandemic were negatively related to depression, anxiety and PTSD. However, female gender, previous diagnoses of mental health problems or neurological disorders, having symptoms associated with the virus, or those with a close relative infected were associated with greater symptomatology in all three variables. Predictive models revealed that the greatest protector for symptomatology was spiritual well-being, while loneliness was the strongest predictor of depression, anxiety and PTSD. The impact on our mental health caused by the pandemic and the measures adopted during the first weeks to deal with it are evident. In addition, it is possible to identify the need of greater psychological support in general and in certain particularly vulnerable groups.", "qid": 45, "docid": "h0ex5siq", "rank": 31, "score": 0.847946047782898}, {"content": "Title: Mental health consequences during the initial stage of the 2020 Coronavirus pandemic (COVID-19) in Spain Content: The pandemic caused by Covid-19 has been an unprecedented social and health emergency worldwide. This is the first study in the scientific literature reporting the psychological impact of the Covid-19 outbreak in a sample of the Spanish population. A cross-sectional study was conducted through an online survey of 3480 people. The presence of depression, anxiety and post-traumatic stress disorder (PTSD) was evaluated with screening tests from 14 March. Sociodemographic and Covid-19-related data was collected. Additionally, spiritual well-being, loneliness, social support, discrimination and sense of belonging were assessed. Descriptive analyses were carried out and linear regression models compiled. The 18.7% of the sample revealed depressive, 21.6% anxiety and 15.8% PTSD symptoms. Being in the older age group, having economic stability and the belief that adequate information had been provided about the pandemic were negatively related to depression, anxiety and PTSD. However, female gender, previous diagnoses of mental health problems or neurological disorders, having symptoms associated with the virus, or those with a close relative infected were associated with greater symptomatology in all three variables. Predictive models revealed that the greatest protector for symptomatology was spiritual well-being, while loneliness was the strongest predictor of depression, anxiety and PTSD. The impact on our mental health caused by the pandemic and the measures adopted during the first weeks to deal with it are evident. In addition, it is possible to identify the need of greater psychological support in general and in certain particularly vulnerable groups.", "qid": 45, "docid": "n2pw9uts", "rank": 32, "score": 0.847946047782898}, {"content": "Title: Why all COVID-19 hospitals should have mental health professionals: The importance of mental health in a worldwide crisis! Content: COVID-19 pandemic has led to a worldwide crisis. At present, everyone is focusing on the prevention of COVID-19 infection, preparing and discussing issues related to physical health consequences. However, it is important to understand that the life-threatening negative physical health consequences are going to be faced by a few, but everyone is going to face the negative mental health consequences of the pandemic. At various places COVID-19 hospitals are being established, to address the physical health consequences of the pandemic. However, mental health professionals have not been very actively involved in the management of people going through this pandemic. This viewpoint discusses the mental health consequences of the pandemic for the health care workers, people who are undergoing quarantine, people who are admitted to the COVID-19 hospitals, and those who have recovered from the infection. The article also highlights the mental health needs of people at different levels and the kind of interventions, which may be carried out.", "qid": 45, "docid": "74ovl7ls", "rank": 33, "score": 0.8476952314376831}, {"content": "Title: Mental Health Treatment for Front-Line Clinicians During and After the Coronavirus Disease 2019 (COVID-19) Pandemic: A Plea to the Medical Community Content: The COVID-19 pandemic has placed front-line health care professionals\u2014who were already at higher risk for negative effects of chronic stress before the pandemic\u2014at even greater risk for depression and anxiety. This article reminds us of the importance of mutual support and caring for our own mental health, including seeking help from our mental health colleagues when needed.", "qid": 45, "docid": "vzmlkk79", "rank": 34, "score": 0.8476310968399048}, {"content": "Title: COVID-19 Pandemia and Public and Global Mental Health from the Perspective of Global Health Securit Content: The Coronavirus disease 2019 (COVID-19) pandemic emerged in Wuhan, China and has spread all over the world and has caused huge threats to health and lives. It has affected different frontiers of lives and induced many psychiatric individual and collective problems such as panic, anxiety, depression, post-traumatic stress disorders, suspiciousness, infodemia, cacophony, xenophobia, racisms, etc. The COVID-19 outbreak has induced public and global mental health crisis as well as a huge psycho-social experiment. Psychiatry and other mental health sciences can play very useful role in supporting the well-being of COVID-19 patients and their families, healthcare personnel and the society. For successful fighting with present and future pandemics we have to learn more about psychiatric and psychological aspects of COVID-19 from the perspectives of public and global mental health.", "qid": 45, "docid": "u81fflce", "rank": 35, "score": 0.8474863767623901}, {"content": "Title: COVID-19 Pandemia and Public and Global Mental Health from the Perspective of Global Health Securit. Content: The Coronavirus disease 2019 (COVID-19) pandemic emerged in Wuhan, China and has spread all over the world and has caused huge threats to health and lives. It has affected different frontiers of lives and induced many psychiatric individual and collective problems such as panic, anxiety, depression, post-traumatic stress disorders, suspiciousness, infodemia, cacophony, xenophobia, racisms, etc. The COVID-19 outbreak has induced public and global mental health crisis as well as a huge psycho-social experiment. Psychiatry and other mental health sciences can play very useful role in supporting the well-being of COVID-19 patients and their families, healthcare personnel and the society. For successful fighting with present and future pandemics we have to learn more about psychiatric and psychological aspects of COVID-19 from the perspectives of public and global mental health.", "qid": 45, "docid": "1vehveqk", "rank": 36, "score": 0.8474863767623901}, {"content": "Title: Adolescent psychiatric disorders during the COVID-19 pandemic and lockdown Content: The aim of this paper was to review the literature on adolescent psychiatric disorders related to the COVID-19 pandemic and lockdown. Stressful life events, extended home confinement, brutal grief, intrafamilial violence, overuse of the Internet and social media are factors that could influence the mental health of adolescents during this period. The COVID-19 pandemic could result in increased psychiatric disorders such as Post-Traumatic Stress, Depressive, and Anxiety Disorders, as well as grief-related symptoms. Adolescents with psychiatric disorders are at risk of a break or change in their care and management; they may experience increased symptoms. The COVID-19 pandemic and lockdown may have a negative impact on the mental health of adolescents, although there is still no data on the long term impact of this crisis. Adolescents\u2019 individual, familial, and social vulnerability, as well as individual and familial coping abilities, are factors related to adolescent mental health in times of crisis. Adolescents are often vulnerable and require careful consideration by caregivers and healthcare system adaptations to allow for mental health support despite the lockdown. Research on adolescent psychiatric disorders in times of pandemics is necessary, as such a global situation could be prolonged or repeated.", "qid": 45, "docid": "h8s1c5my", "rank": 37, "score": 0.8462457656860352}, {"content": "Title: The Nature and Treatment of Pandemic-Related Psychological Distress Content: The COVID-19 crisis has created a \u201cmental health pandemic\u201d throughout the world. Scientific data are not available to fully understand the nature of the resulting mental health impact given the very recent onset of the pandemic, nevertheless, there is a need to act immediately to develop psychotherapeutic strategies that may alleviate pandemic-related distress. The psychological distress, in particular fear and sadness, is a function of the pandemic\u2019s negative impact upon people\u2019s ability to meet their most basic needs (e.g., physical safety, financial security, social connection, participation in meaningful activities). This paper presents evidence-based cognitive behavioral strategies that should prove useful in reducing the emotional suffering associated with the COVID crisis.", "qid": 45, "docid": "3q0ujnjq", "rank": 38, "score": 0.8460985422134399}, {"content": "Title: Psychological Interventions during COVID-19: Challenges for low and middle income countries Content: Abstract At the start of 2020, the 2019 coronavirus disease (COVID-19), originating from China has spread to the world. There have been increasing numbers of confirmed cases and deaths around the globe. The COVID-19 pandemic has paved the way for considerable psychological and psychosocial morbidity among the general public and health care providers. An array of guidelines has been put forward by multiple agencies for combating mental health challenges. This paper addresses some of the mental health challenges faced by low and middle income countries (LMIC). It is worthwhile to note that these are challenges at the current stage of the pandemic and may change with the course of the pandemic itself.", "qid": 45, "docid": "hn6oao66", "rank": 39, "score": 0.8460148572921753}, {"content": "Title: Adolescent psychiatric disorders during the COVID-19 pandemic and lockdown Content: The aim of this paper was to review the literature on adolescent psychiatric disorders related to the COVID-19 pandemic and lockdown. Stressful life events, extended home confinement, brutal grief, intrafamilial violence, overuse of the Internet and social media are factors that could influence the mental health of adolescents during this period. The COVID-19 pandemic could result in increased psychiatric disorders such as Post-Traumatic Stress, Depressive, and Anxiety Disorders, as well as grief-related symptoms. Adolescents with psychiatric disorders are at risk of a break or change in their care and management; they may experience increased symptoms. The COVID-19 pandemic and lockdown may have a negative impact on the mental health of adolescents, although there is still no data on the long term impact of this crisis. Adolescents' individual, familial, and social vulnerability, as well as individual and familial coping abilities, are factors related to adolescent mental health in times of crisis. Adolescents are often vulnerable and require careful consideration by caregivers and healthcare system adaptations to allow for mental health support despite the lockdown. Research on adolescent psychiatric disorders in times of pandemics is necessary, as such a global situation could be prolonged or repeated.", "qid": 45, "docid": "2uaylezt", "rank": 40, "score": 0.8459922671318054}, {"content": "Title: The Impact of Quarantine and Physical Distancing Following COVID-19 on Mental Health: Study Protocol of a Multicentric Italian Population Trial Content: The COVID-19 pandemic and its related containment measures\u2014mainly physical distancing and isolation\u2014are having detrimental consequences on the mental health of the general population worldwide. In particular, frustration, loneliness, and worries about the future are common reactions and represent well-known risk factors for several mental disorders, including anxiety, affective, and post-traumatic stress disorders. The vast majority of available studies have been conducted in China, where the pandemic started. Italy has been severely hit by the pandemic, and the socio-cultural context is completely different from Eastern countries. Therefore, there is the need for methodologically rigorous studies aiming to evaluate the impact of COVID-19 and quarantine measures on the mental health of the Italian population. In fact, our results will help us to develop appropriate interventions for managing the psychosocial consequences of pandemic. The \u201cCOVID-IT-mental health trial\u201d is a no-profit, not-funded, national, multicentric, cross-sectional population-based trial which has the following aims: a) to evaluate the impact of COVID-19 pandemic and its containment measures on mental health of the Italian population; b) to identify the main areas to be targeted by supportive long-term interventions for the different categories of people exposed to the pandemic. Data will be collected through a web-platform using validated assessment tools. Participants will be subdivided into four groups: a) Group 1\u2014COVID-19 quarantine group. This group includes the general population which are quarantined but not isolated, i.e., those not directly exposed to contagion nor in contact with COVID-19+ individuals; b) Group 2\u2014COVID-19+ group, which includes isolated people directly/indirectly exposed to the virus; c) Group 3\u2014COVID-19 healthcare staff group, which includes first- and second-line healthcare professionals; d) Group 4\u2014COVID-19 mental health, which includes users of mental health services and all those who had already been diagnosed with a mental disorder. Mental health services worldwide are not prepared yet to manage the short- and long-term consequences of the pandemic. It is necessary to have a clear picture of the impact that this new stressor will have on mental health and well-being in order to develop and disseminate appropriate interventions for the general population and for the other at-risk groups.", "qid": 45, "docid": "vl5zhxyh", "rank": 41, "score": 0.842811107635498}, {"content": "Title: A global needs assessment in times of a global crisis: world psychiatry response to the COVID-19 pandemic Content: The COVID-19 pandemic has stunned the global community with marked social and psychological ramifications. There are key challenges for psychiatry that require urgent attention to ensure mental health well-being for all \u2013 COVID-19-positive patients, healthcare professionals, first responders, people with psychiatric disorders and the general population. This editorial outlines some of these challenges and research questions, and serves as a preliminary framework of what needs to be addressed. Mental healthcare should be an integral component of healthcare policy and practice towards COVID-19. Collaborative efforts from psychiatric organisations and their members are required to maximise appropriate clinical and educational interventions while minimising stigma.", "qid": 45, "docid": "2d897k8x", "rank": 42, "score": 0.8416473865509033}, {"content": "Title: Flattening the mental ill-health curve: the importance of primary prevention in managing the mental health impacts of COVID19 Content: The COVID19 pandemic is one the biggest challenges the global community has faced. The threat of the virus coupled with the impacts of the social and economic shut-down measures required to slow its spread, already appear to be impacting on people's mental health and wellbeing. Over the weeks, months and years ahead it is likely that many countries will experience a \u2018wave\u2019 of COVID19 related mental disorders as a result of an increase in risk factors linked to the pandemic such as social isolation; child-maltreatment; intimate partner violence; unemployment; housing and income stress; workplace trauma; and grief and loss. The \u2018two-pronged\u2019 approach used to deal with COVID19, provides an excellent blueprint for managing its mental health impacts as well. Nations must focus on preventing the occurrence of new cases of mental disorders as well as strengthening their mental healthcare response to support people who become mentally unwell. A focus on primary prevention is particularly important to \u2018flatten the curve\u2019 and avoid a surge in incidence of mental disorders stemming from the COVID19 pandemic. Many evidence-based interventions designed to prevent common disorders are already available and should be scaled-up. These interventions include parenting programs, social and emotional learning programs, self-care strategies, and workplace mental wellbeing programs, among others.", "qid": 45, "docid": "pl5hyzwp", "rank": 43, "score": 0.840402364730835}, {"content": "Title: Risk, resilience, psychological distress, and anxiety at the beginning of the COVID-19 pandemic in Germany Content: BACKGROUND: The current COVID-19 pandemic comes with multiple psychological stressors due to health-related, social, economic, and individual consequences and may cause psychological distress. The aim of this study was to screen the population in Germany for negative impact on mental health in the current COVID-19 pandemic and to analyze possible risk and protective factors. METHODS: A total of 6,509 people took part in an online survey in Germany from 27 March to 6 April. The questionnaire included demographic information and ascertained psychological distress, anxiety and depressive symptoms, and risk and protective factors. RESULTS: In our sample, over 50% expressed suffering from anxiety and psychological distress regarding the COVID-19 pandemic. Participants spent several hours per day thinking about COVID-19 (M = 4.45). Psychological and social determinants showed stronger associations with anxiety regarding COVID-19 than experiences with the disease. CONCLUSIONS: The current COVID-19 pandemic does cause psychological distress, anxiety, and depression for large proportions of the general population. Strategies such as maintaining a healthy lifestyle and social contacts, acceptance of anxiety and negative emotions, fostering self-efficacy, and information on where to get medical treatment if needed, seem of help, while substance abuse and suppression of anxiety and negative emotions seem to be associated with more psychological burden.", "qid": 45, "docid": "ku7hatk8", "rank": 44, "score": 0.8401304483413696}, {"content": "Title: Heterogeneous mental health consequences of COVID-19: Costs and benefits Content: In this commentary, I argue that the mental health impact of COVID-19 will show substantial variation across individuals, contexts, and time. Further, one key contributor to this variation will be the proximal and long-term impact of COVID-19 on the social environment. In addition to the mental health costs of the pandemic, it is likely that a subset of people will experience improved social and mental health functioning. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "ingq7m2m", "rank": 45, "score": 0.840044379234314}, {"content": "Title: Heterogeneous mental health consequences of COVID-19: Costs and benefits. Content: In this commentary, I argue that the mental health impact of COVID-19 will show substantial variation across individuals, contexts, and time. Further, one key contributor to this variation will be the proximal and long-term impact of COVID-19 on the social environment. In addition to the mental health costs of the pandemic, it is likely that a subset of people will experience improved social and mental health functioning. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "u02vjcjs", "rank": 46, "score": 0.840044379234314}, {"content": "Title: Impact of the COVID-19 pandemic on patients with pre-existing anxiety disorders attending secondary care Content: OBJECTIVES: To examine the psychological and social impact of the COVID-19 pandemic on patients with established anxiety disorders during a period of stringent mandated social restrictions. METHODS: Semi-structured interviews were conducted with 30 individuals attending the Galway-Roscommon Mental Health Services with an International Classification of Diseases diagnosis of an anxiety disorder to determine the impact of the COVID-19 restrictions on anxiety and mood symptoms, social and occupational functioning and quality of life. RESULTS: Twelve (40.0%) participants described COVID-19 restrictions as having a deleterious impact on their anxiety symptoms. Likert scale measurements noted that the greatest impact of COVID-19 related to social functioning (mean = 4.5, SD = 2.9), with a modest deleterious effect on anxiety symptoms noted (mean = 3.8, SD = 2.9). Clinician rated data noted that 8 (26.7%) participants had disimproved and 14 (46.7%) participants had improved since their previous clinical review, prior to commencement of COVID-19 restrictions. Conditions associated with no 'trigger', such as generalised anxiety disorder, demonstrated a non-significant increase in anxiety symptoms compared to conditions with a 'trigger', such as obsessive compulsive disorder. Psychiatric or physical comorbidity did not substantially impact on symptomatology secondary to COVID-19 mandated restrictions. CONCLUSIONS: The psychological and social impact of COVID-19 restrictions on individuals with pre-existing anxiety disorders has been modest with only minimal increases in symptomatology or social impairment noted.", "qid": 45, "docid": "hcyoshrs", "rank": 47, "score": 0.8400221467018127}, {"content": "Title: Mental Health Status of the General Population during the COVID-19 Pandemic: A Cross-sectional National Survey in Japan Content: The ongoing COVID-19 pandemic may have detrimental mental health consequences. However, as yet, there is limited understanding of its impact on the mental health of the general population. The aim of this study is to examine the mental health of the Japanese general population by conducting the first systematic survey during the pandemic (N=1,000), with a particular focus on identifying the most vulnerable groups. Results from logistic regression analyses showed that the mental health of young and middle-aged individuals was significantly worse than that of older individuals during the pandemic. There was also some indication that individuals who were not currently working were significantly more likely to report a high level of anxiety and depressive symptoms. Part-time and temporary contract-based workers were also more likely to suffer from anxiety disorder. Our results highlight that monitoring the mental health of younger and economically vulnerable individuals may be especially important. In addition, they also indicate that population mental health might not only be affected by the direct health consequences of COVID-19, but also by the economic ramifications of the pandemic.", "qid": 45, "docid": "wpxrzjzx", "rank": 48, "score": 0.8397695422172546}, {"content": "Title: Utilization of Teleconsultation: Mitigation in Handling Mental Disorders in the COVID-19 Era Content: The COVID-19 pandemic has caused many undesirable effects, including death. The COVID-19 outbreak occurred suddenly, and many countries were ill prepared to face it. Community behaviour has been altered due to the pandemic. Uncertainty surrounding the disease triggered panic buying; public panic caused additional worry about limited food supplies, and thus demand increased. World economies have also felt the impacts of the COVID-19 outbreak. Owing to the measures put in place to address the spread of COVID-19, many service providers and industries were closed, resulting in financial losses, and the risk of unemployment was elevated, which inevitably increased negative emotions in individuals. A psychosocial consequence of the COVID-19 pandemic is worldwide fear. Because psychological defence is a supporting factor for the recovery of COVID-19 patients, it is important to encourage prevention of mental stress. Psychotherapy is able to provide counselling services to the community through teleconsultation. Strengthening psychological defences can help countries fight against this disease.", "qid": 45, "docid": "7vowrme2", "rank": 49, "score": 0.8395193815231323}, {"content": "Title: Impact of the COVID-19 pandemic on patients with pre-existing anxiety disorders attending secondary care Content: OBJECTIVES: To examine the psychological and social impact of the COVID-19 pandemic on patients with established anxiety disorders during a period of stringent mandated social restrictions. METHODS: Semi-structured interviews were conducted with 30 individuals attending the Galway-Roscommon Mental Health Services with an International Classification of Diseases diagnosis of an anxiety disorder to determine the impact of the COVID-19 restrictions on anxiety and mood symptoms, social and occupational functioning and quality of life. RESULTS: Twelve (40.0%) participants described COVID-19 restrictions as having a deleterious impact on their anxiety symptoms. Likert scale measurements noted that the greatest impact of COVID-19 related to social functioning (mean = 4.5, SD = 2.9), with a modest deleterious effect on anxiety symptoms noted (mean = 3.8, SD = 2.9). Clinician rated data noted that 8 (26.7%) participants had disimproved and 14 (46.7%) participants had improved since their previous clinical review, prior to commencement of COVID-19 restrictions. Conditions associated with no \u2018trigger\u2019, such as generalised anxiety disorder, demonstrated a non-significant increase in anxiety symptoms compared to conditions with a \u2018trigger\u2019, such as obsessive compulsive disorder. Psychiatric or physical comorbidity did not substantially impact on symptomatology secondary to COVID-19 mandated restrictions. CONCLUSIONS: The psychological and social impact of COVID-19 restrictions on individuals with pre-existing anxiety disorders has been modest with only minimal increases in symptomatology or social impairment noted.", "qid": 45, "docid": "o3qipyqw", "rank": 50, "score": 0.8392919301986694}, {"content": "Title: Risk, resilience, psychological distress, and anxiety at the beginning of the COVID\u201019 pandemic in Germany Content: BACKGROUND: The current COVID\u201019 pandemic comes with multiple psychological stressors due to health\u2010related, social, economic, and individual consequences and may cause psychological distress. The aim of this study was to screen the population in Germany for negative impact on mental health in the current COVID\u201019 pandemic and to analyze possible risk and protective factors. METHODS: A total of 6,509 people took part in an online survey in Germany from 27 March to 6 April. The questionnaire included demographic information and ascertained psychological distress, anxiety and depressive symptoms, and risk and protective factors. RESULTS: In our sample, over 50% expressed suffering from anxiety and psychological distress regarding the COVID\u201019 pandemic. Participants spent several hours per day thinking about COVID\u201019 (M = 4.45). Psychological and social determinants showed stronger associations with anxiety regarding COVID\u201019 than experiences with the disease. CONCLUSIONS: The current COVID\u201019 pandemic does cause psychological distress, anxiety, and depression for large proportions of the general population. Strategies such as maintaining a healthy lifestyle and social contacts, acceptance of anxiety and negative emotions, fostering self\u2010efficacy, and information on where to get medical treatment if needed, seem of help, while substance abuse and suppression of anxiety and negative emotions seem to be associated with more psychological burden.", "qid": 45, "docid": "e1htl489", "rank": 51, "score": 0.8389831781387329}, {"content": "Title: Experiences of American older adults with pre-existing depression during the beginnings of the COVID-19 pandemic: a multi-city, mixed-methods study Content: OBJECTIVE: To determine the effect of the COVID-19 pandemic on the mental health of older adults with pre-existing major depressive disorder (MDD). PARTICIPANTS: Participants were 73 community-living older adults with pre-existing MDD (mean age 69 [SD 6]) in Los Angeles, New York, Pittsburgh, and St Louis. DESIGN AND MEASUREMENTS: During the first two months of the pandemic, we interviewed participants with a semi-structured qualitative interview evaluating access to care, mental health, quality of life, and coping. We also assessed depression, anxiety, and suicidality with validated scales and compared scores before and during the pandemic. RESULTS: Five themes from the interviews highlight the experience of older adults with MDD: (1) They are more concerned about the risk of contracting the virus than the risks of isolation. (2) They exhibit resilience to the stress and isolation of physical distancing. (3) Most are not isolated socially, with virtual contact with friends and family. (4) Their quality of life is lower, and they worry their mental health will suffer with continued physical distancing. (5) They are outraged by an inadequate governmental response to the pandemic. Depression, anxiety, and suicidal ideation symptom scores did not differ from scores before the pandemic. CONCLUSIONS: Most older adults with pre-existing MDD show resilience in the first two months of the COVID-19 pandemic but have concerns about the future. Policies and interventions to provide access to medical services and opportunities for social interaction are needed to help to maintain mental health and quality of life as the pandemic continues.", "qid": 45, "docid": "tqtqf7k5", "rank": 52, "score": 0.8386414051055908}, {"content": "Title: Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms Content: The coronavirus disease 19 (COVID-19) pandemic is a significant psychological stressor in addition to its tremendous impact on every facet of individuals' lives and organizations in virtually all social and economic sectors worldwide. Fear of illness and uncertainty about the future precipitate anxiety- and stress-related disorders, and several groups have rightfully called for the creation and dissemination of robust mental health screening and treatment programs for the general public and front-line healthcare workers. However, in addition to pandemic-associated psychological distress, the direct effects of the virus itself (several acute respiratory syndrome coronavirus; SARS-CoV-2), and the subsequent host immunologic response, on the human central nervous system (CNS) and related outcomes are unknown. We discuss currently available evidence of COVID-19 related neuropsychiatric sequelae while drawing parallels to past viral pandemic-related outcomes. Past pandemics have demonstrated that diverse types of neuropsychiatric symptoms, such as encephalopathy, mood changes, psychosis, neuromuscular dysfunction, or demyelinating processes, may accompany acute viral infection, or may follow infection by weeks, months, or longer in recovered patients. The potential mechanisms are also discussed, including viral and immunological underpinnings. Therefore, prospective neuropsychiatric monitoring of individuals exposed to SARS-CoV-2 at various points in the life course, as well as their neuroimmune status, are needed to fully understand the long-term impact of COVID-19, and to establish a framework for integrating psychoneuroimmunology into epidemiologic studies of pandemics.", "qid": 45, "docid": "8yjdeyog", "rank": 53, "score": 0.8372143507003784}, {"content": "Title: The impact of the COVID-19 pandemic on the mental health of healthcare professionals Content: INTRODUCTION: Healthcare professionals (HPs) have been confronted by unprecedented traumatic experiences during the COVID-19 pandemic, especially in countries that had not experienced similar epidemic outbreaks in recent years. AIM: To analyze the impact of the COVID-19 pandemic on the mental health of HPs. METHOD: We comprehensively reviewed the studies published in MEDLINE (PubMed), Web of Science and Google Scholar between December 2019 and May 2020. RESULTS: Most studies report a high prevalence of anxiety and depressive symptoms among HPs that can be associated with: a) COVID-19 exposure; b) epidemiological issues; c) material resources; d) human resources; and e) personal factors. The role of certain variables, before, during and after the pandemic, remains unexplored. Longitudinal studies will help elucidate which factors are associated with a higher risk of developing long-lasting negative effects. Qualitative studies may contribute to understanding the influence of individual and social narratives in HPs' distress. CONCLUSION: A deeper analysis on the individual, institutional, political and socio-cultural factors, meanings and values influencing HPs distress and resilience during the COVID-19 pandemic is needed.", "qid": 45, "docid": "t9t2qlw4", "rank": 54, "score": 0.8369719982147217}, {"content": "Title: Pandemics and Psychiatry: repositioning research in context of COVID-19 Content: The current Covid-19 pandemic is posing an unprecedented threat to global well-being and its mental health consequences are just becoming understood. While the crisis has led to a temporary halt in a lot of ongoing or planned psychiatric research, this pandemic is a natural experiment that can help the field to repurpose research to better understand the causes, presentations and outcome trajectories as well as treatments in psychiatry. Inter-disciplinary collaborations between researchers are needed to rapidly develop and share the emerging new knowledge of the mental health implications of Covid-19, This will help mount an effective response to the current as well as future pandemics.", "qid": 45, "docid": "pkw2cjej", "rank": 55, "score": 0.8369710445404053}, {"content": "Title: Pandemics and psychiatry: Repositioning research in context of COVID-19 Content: The current Covid-19 pandemic is posing an unprecedented threat to global well-being and its mental health consequences are just becoming understood. While the crisis has led to a temporary halt in a lot of ongoing or planned psychiatric research, this pandemic is a natural experiment that can help the field to repurpose research to better understand the causes, presentations and outcome trajectories as well as treatments in psychiatry. Inter-disciplinary collaborations between researchers are needed to rapidly develop and share the emerging new knowledge of the mental health implications of Covid-19, This will help mount an effective response to the current as well as future pandemics.", "qid": 45, "docid": "ijeeck3i", "rank": 56, "score": 0.8369710445404053}, {"content": "Title: Editorial Perspective: COVID\u201019 pandemic\u2010related psychopathology in children and adolescents with mental illness Content: The coronavirus disease (COVID\u201019) pandemic is likely to have negative health consequences way beyond those caused by the virus per se \u2013 including significant psychological distress. Children and adolescents who already live with a mental illness may be particularly vulnerable to the distress associated with the pandemic \u2013 due to, for example, fear of the virus as well as the significant societal changes launched to minimize spread of the virus (social distancing and quarantine). In this editorial perspective, we (a) provide data on COVID\u201019 pandemic\u2010related psychopathology in children and adolescents from a large psychiatric treatment setting in Denmark, (b) give advice on how the likely harmful effects of the COVID\u201019 pandemic on the mental health of children and adolescents may be minimized, and (c) propose six lines of research into pandemic\u2010related psychopathology with emphasis on children and adolescents. Finally, we underline the necessity of politicians, health authorities, and funding bodies supporting these research initiatives here and now.", "qid": 45, "docid": "21bghq0n", "rank": 57, "score": 0.836514949798584}, {"content": "Title: Keep mental health in mind Content: A surge in mental-health problems related to the COVID-19 pandemic is on the horizon. The time to prepare and prevent another health-crisis wave is now.", "qid": 45, "docid": "flgtmdfb", "rank": 58, "score": 0.8363816738128662}, {"content": "Title: The COVID\u201019 pandemic is a crisis and opportunity for bipolar disorder Content: The ongoing COVID\u201019 pandemic has to date infected more than one million people and led to tens of thousands of deaths across the globe. Thus, many governments have imposed regional or national mass shelters\u2010in\u2010place in an effort to slow its rapid spread. In this global health emergency, special attention should be paid to the potential impact of the measures taken to combat the pandemic on patients with bipolar disorders (BDs).", "qid": 45, "docid": "ttir73l5", "rank": 59, "score": 0.8345699310302734}, {"content": "Title: The need for Early Intervention for Psychosis to persist throughout the covid-19 pandemic and beyond Content: In the last three decades, Early Intervention for psychosis services have been established worldwide and have resulted in superior symptomatic and functional outcomes for people affected by psychotic disorders. These improved outcomes are a result of reducing delays to treatment and the provision of specialized, holistic interventions. The covid-19 pandemic poses significant challenges to the delivery of these services, such as undetected cases or long delays to treatment. Furthermore, the covid-19 pandemic will likely increase the mental health needs of communities, including the incidence of psychotic disorders. In this perspective piece, we provide suggestions as to how early intervention for psychosis services can adapt within this environment, such as utilizing novel technologies. Finally, we argue that despite the economic consequences of the pandemic, the funding for mental health services, including early intervention services, should be increased in line with the need for these services during and beyond the pandemic.", "qid": 45, "docid": "of8i5aaf", "rank": 60, "score": 0.8339524269104004}, {"content": "Title: The need for Early Intervention for Psychosis to persist throughout the covid-19 pandemic and beyond. Content: In the last three decades, Early Intervention for psychosis services have been established worldwide and have resulted in superior symptomatic and functional outcomes for people affected by psychotic disorders. These improved outcomes are a result of reducing delays to treatment and the provision of specialized, holistic interventions. The covid-19 pandemic poses significant challenges to the delivery of these services, such as undetected cases or long delays to treatment. Furthermore, the covid-19 pandemic will likely increase the mental health needs of communities, including the incidence of psychotic disorders. In this perspective piece, we provide suggestions as to how early intervention for psychosis services can adapt within this environment, such as utilizing novel technologies. Finally, we argue that despite the economic consequences of the pandemic, the funding for mental health services, including early intervention services, should be increased in line with the need for these services during and beyond the pandemic.", "qid": 45, "docid": "eq75a87f", "rank": 61, "score": 0.8339524269104004}, {"content": "Title: Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms Content: Abstract The coronavirus disease 19 (COVID-19) pandemic is a significant psychological stressor in addition to its tremendous impact on every facet of individuals\u2019 lives and organizations in virtually all social and economic sectors worldwide. Fear of illness and uncertainty about the future precipitate anxiety- and stress-related disorders, and several groups have rightfully called for the creation and dissemination of robust mental health screening and treatment programs for the general public and front-line healthcare workers. However, in addition to pandemic-associated psychological distress, the direct effects of the virus itself (several acute respiratory syndrome coronavirus; SARS-CoV-2), and the subsequent host immunologic response, on the human central nervous system (CNS) and related outcomes are unknown. We discuss currently available evidence of COVID-19 related neuropsychiatric sequelae while drawing parallels to past viral pandemic-related outcomes. Past pandemics have demonstrated that diverse types of neuropsychiatric symptoms, such as encephalopathy, mood changes, psychosis, neuromuscular dysfunction, or demyelinating processes, may accompany acute viral infection, or may follow infection by weeks, months, or longer in recovered patients. The potential mechanisms are also discussed, including viral and immunological underpinnings. Therefore, prospective neuropsychiatric monitoring of individuals exposed to SARS-CoV-2 at various points in the life course, as well as their neuroimmune status, are needed to fully understand the long-term impact of COVID-19, and to establish a framework for integrating psychoneuroimmunology into epidemiologic studies of pandemics.", "qid": 45, "docid": "stnva6pv", "rank": 62, "score": 0.8337842226028442}, {"content": "Title: Multidisciplinary research priorities for the COVID-19 pandemic: a call for action for mental health science Content: The coronavirus disease 2019 (COVID-19) pandemic is having a profound effect on all aspects of society, including mental health and physical health. We explore the psychological, social, and neuroscientific effects of COVID-19 and set out the immediate priorities and longer-term strategies for mental health science research. These priorities were informed by surveys of the public and an expert panel convened by the UK Academy of Medical Sciences and the mental health research charity, MQ: Transforming Mental Health, in the first weeks of the pandemic in the UK in March, 2020. We urge UK research funding agencies to work with researchers, people with lived experience, and others to establish a high level coordination group to ensure that these research priorities are addressed, and to allow new ones to be identified over time. The need to maintain high-quality research standards is imperative. International collaboration and a global perspective will be beneficial. An immediate priority is collecting high-quality data on the mental health effects of the COVID-19 pandemic across the whole population and vulnerable groups, and on brain function, cognition, and mental health of patients with COVID-19. There is an urgent need for research to address how mental health consequences for vulnerable groups can be mitigated under pandemic conditions, and on the impact of repeated media consumption and health messaging around COVID-19. Discovery, evaluation, and refinement of mechanistically driven interventions to address the psychological, social, and neuroscientific aspects of the pandemic are required. Rising to this challenge will require integration across disciplines and sectors, and should be done together with people with lived experience. New funding will be required to meet these priorities, and it can be efficiently leveraged by the UK's world-leading infrastructure. This Position Paper provides a strategy that may be both adapted for, and integrated with, research efforts in other countries.", "qid": 45, "docid": "d8aa0ro1", "rank": 63, "score": 0.833747923374176}, {"content": "Title: The COVID-19 Global Pandemic: Implications for People With Schizophrenia and Related Disorders Content: The coronavirus disease-19 (COVID-19) global pandemic has already had an unprecedented impact on populations around the world, and is anticipated to have a disproportionate burden on people with schizophrenia and related disorders. We discuss the implications of the COVID-19 global pandemic with respect to: (1) increased risk of infection and poor outcomes among people with schizophrenia, (2) anticipated adverse mental health consequences for people with schizophrenia, (3) considerations for mental health service delivery in inpatient and outpatient settings, and (4) potential impact on clinical research in schizophrenia. Recommendations emphasize rapid implementation of measures to both decrease the risk of COVID-19 transmission and maintain continuity of clinical care and research to preserve safety of both people with schizophrenia and the public.", "qid": 45, "docid": "q1sybzej", "rank": 64, "score": 0.833004891872406}, {"content": "Title: Mental health and psychosocial well-being during the COVID-19 pandemic: the invisible elephant in the room Content: The novel SARS-CoV-2 coronavirus pandemic has emerged as a truly formidable threat to humankind\u2019s existence. In the wake of the massively volatile global situation created by COVID-19, it is vital to recognize that the trauma it causes can affect people in different ways, at the individual and collective levels, resulting in mental health challenges for many. Although mental health problems account for about one-third of the world\u2019s disability among adults, these issues tend to be under-addressed and overlooked in society and are closely associated with deadly disease outbreaks. In large scale outbreaks, the mental health problems experienced are not limited to infected persons but also extend to involve frontline health workers and community members alike. While it is crucial to limit the spread of infections during an outbreak, previous experience suggests that mental and behavioural health interventions should be fully included in public health response strategies.", "qid": 45, "docid": "ypgor52g", "rank": 65, "score": 0.8326131701469421}, {"content": "Title: COVID-19 related stress exacerbates common physical and mental pathologies and affects treatment (Review) Content: COVID-19 pandemic has caused a global public health emergency resulting in unprecedented individual and societal fear and anxiety. The stress surrounding this biothreat appears to have clinical implications in all aspects of medicine, both in mental and physical health spheres. The impact of COVID-19 related anxiety in Cardiology, Paediatrics, Oncology, Dermatology, Neurology and Mental Health and how it affects treatments is discussed. Moreover, the need for introducing novel communication and therapeutic approaches is highlighted in the new landscape of the COVID-19 era.", "qid": 45, "docid": "j7novgyb", "rank": 66, "score": 0.8324373960494995}, {"content": "Title: Mental health considerations for children & adolescents in COVID-19 Pandemic Content: Children are not indifferent to the significant psychological impact of the COVID-19 Pandemic. They experience fears, uncertainties, substantial changes to their routines, physical and social isolation alongside high level of parental stress. Understanding their emotions and responses is essential to properly address their needs during this pandemic. In this article, we highlight children\u2019s vulnerability, provide an overview of common symptoms of distress in different age groups, and summarize the interventions and resources available to promote child mental health and wellbeing during these challenging times. We advocate that prioritizing mental health including child & adolescent mental health is an essential component of any universal, community led response to COVID-19 Pandemic.", "qid": 45, "docid": "6iuekyie", "rank": 67, "score": 0.8324307203292847}, {"content": "Title: Levels and predictors of anxiety, depression and health anxiety during COVID-19 pandemic in Turkish society: The importance of gender. Content: BACKGROUND The COVID-19 pandemic is having negative effects on societies' mental health. Both the pandemic and the measures taken to combat it can affect individuals' mental health. AIMS The purpose of this study was to evaluate the levels of depression, anxiety and health anxiety in Turkish society during the COVID-19 pandemic, and to examine the factors affecting these. METHOD The study was performed using an online questionnaire. Participants were asked to complete a sociodemographic data form, the Hospital Anxiety and Depression Scale (HADS) and the Health Anxiety Inventory (HAI). The effects on depression, anxiety and health anxiety levels of factors such as age, sex, marital status, living with an individual aged above 60, the presence of a new Coronavirus+ patient among friends or relatives, previous and current psychiatric illness and presence of accompanying chronic disease were then investigated. RESULTS In terms of HADS cut-off points, 23.6% (n = 81) of the population scored above the depression cut-off point, and 45.1% (n = 155) scored above the cut-off point for anxiety. In regression analysis, female gender, living in urban areas and previous psychiatric illness history were found as risk factors for anxiety; living in urban areas was found as risk factor for depression; and female gender, accompanying chronic disease and previous psychiatric history were found as risk factors for health anxiety. CONCLUSION The results of this cross-sectional study suggest that the groups most psychologically affected by the COVID-19 pandemic are women, individuals with previous psychiatric illness, individuals living in urban areas and those with an accompanying chronic disease. Priority might therefore be attached to these in future psychiatric planning.", "qid": 45, "docid": "64zz84u7", "rank": 68, "score": 0.83221435546875}, {"content": "Title: Fear and agony of the pandemic leading to stress and mental illness: An emerging crisis in the novel coronavirus (COVID-19) outbreak Content: The outbreak of novel Coronavirus (COVID-19), later named as a pandemic affecting nearly 210 countries and territories has led to negative emotions of fear and agony in the general population and healthcare staff professionals. The healthcare regulators and the governments have imposed emergencies and lockdowns in their countries which has led to an adverse effect on the mental health of people ultimately leading to a rise in anxiety, depression, and associated mental illness. The fear and uncertainty increased by the COVID-19 crisis are putting extreme pressure on our finite resources. This report aims to synthesis the dilemma of mental illness as a result of pandemic and initiates suggestions to help the general public, healthcare professionals, and workers mitigate the negative emotions to improve the mental wellbeing in this detached period of isolation.", "qid": 45, "docid": "2sr3lgol", "rank": 69, "score": 0.8317508697509766}, {"content": "Title: Fear and agony of the pandemic leading to stress and mental illness: An emerging crisis in the novel coronavirus (COVID-19) outbreak. Content: The outbreak of novel Coronavirus (COVID-19), later named as a pandemic affecting nearly 210 countries and territories has led to negative emotions of fear and agony in the general population and healthcare staff professionals. The healthcare regulators and the governments have imposed emergencies and lockdowns in their countries which has led to an adverse effect on the mental health of people ultimately leading to a rise in anxiety, depression, and associated mental illness. The fear and uncertainty increased by the COVID-19 crisis are putting extreme pressure on our finite resources. This report aims to synthesis the dilemma of mental illness as a result of pandemic and initiates suggestions to help the general public, healthcare professionals, and workers mitigate the negative emotions to improve the mental wellbeing in this detached period of isolation.", "qid": 45, "docid": "20bgev65", "rank": 70, "score": 0.8317508697509766}, {"content": "Title: Mental Health Policy in the Era of COVID-19 Content: The response to the global COVID-19 pandemic has important ramifications for mental health systems and the patients they serve. This article describes significant changes in mental health policy prompted by the COVID-19 crisis across five major areas: legislation, regulation, financing, accountability, and workforce development. Special considerations for mental health policy are discussed, including social determinants of health, innovative technologies, and research and evaluation. These extraordinary advances provide an unprecedented opportunity to evaluate the effects of mental health policies that may be adopted in the post-COVID-19 era in the United States.", "qid": 45, "docid": "rw5a8tkj", "rank": 71, "score": 0.8314874172210693}, {"content": "Title: Mental Health Policy in the Era of COVID-19. Content: The response to the global COVID-19 pandemic has important ramifications for mental health systems and the patients they serve. This article describes significant changes in mental health policy prompted by the COVID-19 crisis across five major areas: legislation, regulation, financing, accountability, and workforce development. Special considerations for mental health policy are discussed, including social determinants of health, innovative technologies, and research and evaluation. These extraordinary advances provide an unprecedented opportunity to evaluate the effects of mental health policies that may be adopted in the post-COVID-19 era in the United States.", "qid": 45, "docid": "zg8l6std", "rank": 72, "score": 0.8314874172210693}, {"content": "Title: Predictors of Mental Health during the early Covid-19 Pandemic in the US: role of economic concerns, health worries and social distancing Content: Objective: To assess mental health in the US adult population in the Covid-19 pandemic and explore the roles of economic concerns, health worries and social distancing in shaping mental health outcomes. Methods: We analyze online survey data from the \"Understanding America Study\" (UAS) that is representative of the US adult population and covers the period of March 10-31st 2020 (sample size: 6436). Results: About 29% (CI:27.4-.30.4%) of the US adult population reported some depression/anxiety symptoms over the study period, with symptoms deteriorating over the month of March. Worsening mental health was most strongly associated with concerns about the economic consequences of the pandemic, while concerns about the potential impact of the virus on respondents' own health and the practice of social distancing also predicted the presence of depression and anxiety symptoms, albeit less strongly. Conclusions: Our findings point towards a major mental health crisis unfolding simultaneously with the pandemic in the US. They also highlight the importance of economic countermeasures and social policy for mitigating the impact of Covid-19 on adult mental health in the US over and above an effective public health response.", "qid": 45, "docid": "omv50b7j", "rank": 73, "score": 0.8313695192337036}, {"content": "Title: Depression and Anxiety in Hong Kong during COVID-19 Content: It has been three months since the first confirmed case of coronavirus disease 2019 (COVID-19) in Hong Kong, and people now have a more complete picture of the extent of the pandemic. Therefore, it is time to evaluate the impacts of COVID-19 on mental health. The current population-based study aimed to evaluate the depression and anxiety of people in Hong Kong during the COVID-19 pandemic. Respondents were randomly recruited and asked to complete a structured questionnaire, including the patient health questionnaire-9 (PHQ-9), the generalized anxiety disorder-7 (GAD-7), the global rating of change scale and items related to COVID-19. Of the 500 respondents included in the study, 19% had depression (PHQ-9 score \u2265 10) and 14% had anxiety (GAD score \u2265 10). In addition, 25.4% reported that their mental health had deteriorated since the pandemic. Multiple logistic regression analysis found that not experiencing the SARS outbreak in 2003, being worried about being infected by COVID-19, being bothered by having not enough surgical masks and being bothered by not being able to work from home were associated with a poorer mental health status. Psychological support, such as brief, home-based psychological interventions, should be provided to citizens during the pandemic.", "qid": 45, "docid": "vdf441lf", "rank": 74, "score": 0.8313340544700623}, {"content": "Title: The German COVID-19 Survey on Mental Health: Primary Results Content: Abstract First cases of COVID-19 were reported in Wuhan, China in early December 2019. Preliminary data from China indicated a substantial impact on mental health by the pandemic and its associated lockdown measures. Such measures are unprecedented for the majority of people and may affect their lives tremendously. The current survey was developed to assess mental health in response to the lockdown in Germany. Methods We conducted a web-based self-report survey including various aspects of mental health (e.g. PHQ-D, PHQ-4, WHO-5 and comparative questions on a 5-point Likert scale concerning sleep, irritability & interpersonal violence). First wave data were taken during the height of lockdown measures in Germany from 1 April to 15 April 2020. Results A total of 3,545 volunteers took part in this cross-sectional survey. Mean age was 40.36 years (SD = 11.70; 83.1% female, 15.2% male). Acute or chronic disease was reported by 36.7% (physical) and 24.7% (mental) of subjects. Participants scored mild severity distress in the PHQ stress module. Depression and anxiety as assessed by PHQ-4 was significantly higher than in reference samples. The mean well-being score (WHO-5) was 50.7, thus pointing towards possible signs of depression. Furthermore, we found significant gender differences for anxiety and depression with women showing higher levels. 45.3% of participants reported worsened sleep, increased levels of irritation, anger and aggression compared to pre-pandemic times. Most importantly, 5% of all participants reported experiencing interpersonal violence (IPV). Discussion This is one of the first and largest surveys on mental health during the COVID-19 pandemic in a European society reflecting a relatively well educated and financially secure sample. Yet, there is evidence for a substantial mental burden with increased levels of stress, anxiety, depressive symptoms, sleep disturbance and irritability. Most importantly and also most concerning is the finding of a one-month prevalence of 5% IPV. We think it is of vital importance to continuously monitor the mental health of the general public during this pandemic and its aftermath and to carefully screen for IPV and its risk factors such as stress, sleep problems and anger.", "qid": 45, "docid": "ov0x3dho", "rank": 75, "score": 0.831024706363678}, {"content": "Title: Bipolar disorder, COVID\u201019, and the risk of relapse Content: The novel coronavirus disease (COVID\u201019) pandemic represents a global health crisis which can directly or indirectly affect the mental health of millions of people around the world. There are certain aspects of this pandemic, and of the measures necessary for this control, which are of particular concern for patients with bipolar disorders, particularly as regards the risk of relapse.", "qid": 45, "docid": "gvluu83h", "rank": 76, "score": 0.8310149312019348}, {"content": "Title: Addressing collegiate mental health amid COVID-19 pandemic Content: College students encounter unique challenges leading to poor mental health in the wake of the COVID-19 outbreak. Before the pandemic started, one in five college students experienced one or more diagnosable mental disorders worldwide. The fact that the COVID-19 pandemic affects collegiate mental health underscores the urgent need to understand these challenges and concerns in order to inform the development of courses of action and public health messaging that can better support college students in this crisis. This article provides recommendations that prepare higher education institutions and health professionals for addressing collegiate mental health needs and challenges posed by COVID-19.", "qid": 45, "docid": "9lxwi3j8", "rank": 77, "score": 0.8309712409973145}, {"content": "Title: Mental Health Effects of COVID-19 Pandemia: A Review of Clinical and Psychological Traits Content: OBJECTIVE: As the coronavirus (COVID-19) pandemic sweeps across the world, it is causing widespread concern, fear and stress, all of which are natural and normal reactions to the changing and uncertain situation that everyone finds themselves in. METHODS: In this general review, we examined the literature about the psychological effects of COVID-19 pandemia. In total 65 papers were reviewed using the Medline computer database. Only publications in English were selected. RESULTS: Children are likely to be experiencing worry, anxiety and fear and older people are also those with underlying health conditions, having been identified as more vulnerable to COVID-19, can be extremely frightening and very fear-inducing. China and several other countries took strict isolation measures. Medical staff and affiliated healthcare workers (staff) are under both physical and psychological pressure. CONCLUSION: The COVID-19 pandemic is exceptional. Its effect will likely be imprinted on each individual involved. Extensive stressors will emerge or become worsened. Many medical staff workers will be harmfully psychologically affected.", "qid": 45, "docid": "9jl89mry", "rank": 78, "score": 0.8305413722991943}, {"content": "Title: Psychological impact of anti-Asian stigma due to the COVID-19 pandemic: A call for research, practice, and policy responses Content: The COVID-19 pandemic is linked to a rise in stigma and discrimination against Chinese and other Asians, which is likely to have a negative impact on mental health, especially when combined with additional outbreak-related stressors. We discuss the need to consider the potential harms of these anti-Asian sentiments during both the height of the pandemic and longer-term recovery through (a) research-examining how it affects mental health and recovery; (b) practice-implementing evidence-based stigma reduction initiatives; and (c) policy-coordinating federal response to anti-Asian racism including investment in mental health services and community-based efforts. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "hlbjrkqp", "rank": 79, "score": 0.8300087451934814}, {"content": "Title: Psychological impact of anti-Asian stigma due to the COVID-19 pandemic: A call for research, practice, and policy responses. Content: The COVID-19 pandemic is linked to a rise in stigma and discrimination against Chinese and other Asians, which is likely to have a negative impact on mental health, especially when combined with additional outbreak-related stressors. We discuss the need to consider the potential harms of these anti-Asian sentiments during both the height of the pandemic and longer-term recovery through (a) research-examining how it affects mental health and recovery; (b) practice-implementing evidence-based stigma reduction initiatives; and (c) policy-coordinating federal response to anti-Asian racism including investment in mental health services and community-based efforts. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "q1ywk5vc", "rank": 80, "score": 0.8300087451934814}, {"content": "Title: Dimensions and modulators of behavioural and mental-health changes during the Covid-19 pandemic: an N=343,017 study Content: BACKGROUND The effects of the Covid-19 pandemic on mental health remain unclear. To mitigate the risks and capitalise on opportunities for positive change, we must understand how the impact has been mediated by sociodemographics, mental disorders, personality traits, life circumstances and the coping measures people choose to take. METHODS Data were collected from 376,987 members of the general public, predominantly in the UK, between late December 2019 and May 2020. Interaction models examined differences in sociodemographic distributions of mood and anxiety for 233,268 people in January vs. 109,749 in May. Factor analysis of a comprehensive instrument determined the dimensionality of self-perceived pandemic-driven change in wellbeing, outlook and behaviour for 74,830 participants in May. Linear modelling identified demographic, contextual, clinical, and trait predictors of pandemic impact. Topic modelling distilled prevalent advice from free-text responses. RESULTS Anxiety, depression and insomnia changed markedly in demographically-mediated ways. Untoward changes were larger for older adults. Benefits were greater for younger adults. Social connectedness was negatively affected across most mental and neurological conditions. There were disorder-specific changes in other domains, e.g., heightened conflict at home for attention-deficit hyperactivity disorder and heightened anxiety for obsessive-compulsive disorder. Psychiatric symptoms, personality traits, occupational variables and living conditions were amongst the strongest predictors of pandemic impact. Frontline health workers, carers of vulnerable older adults, and disabled or sheltered adults were disproportionately affected. Fifty advice topics were identified from free-text, the prevalence of which covaried with subpopulation, context and traits. CONCLUSIONS The general public report positive and negative consequences of the pandemic. Particular subsets of people have heightened risk of untoward effects whereas other groups appear resilient. To be valid and effective, studies seeking to quantify, predict or mitigate the impact of pandemics on mental health should apply holistic approaches, combining multiple psycho-socio-economic factors.", "qid": 45, "docid": "oxs7qc0f", "rank": 81, "score": 0.8298797607421875}, {"content": "Title: COVID-19 and people with intellectual disability: impacts of a pandemic Content: The impacts of the COVID-19 pandemic affect all groups in society. People with intellectual disability (ID) are especially vulnerable to the physical, mental and social effects of the pandemic. Cognitive impairments can limit understanding of information to protect them relying on carers to be vigilant on their behalf during quarantine. Restrictions on usual activities are likely to induce mental stress especially among those who are autistic leading to an escalation in challenging behaviours, risk of placement breakdown and increased the use of psychotropic medication. People with ID are vulnerable to exploitation by others where the usual community supports no longer function to protect them. In future pandemics, it is important that lessons are learned from the impacts COVID-19 have on people with ID. Collecting the evidence through a rigorous approach should help to empower people with ID and their carers to face future outbreaks of infectious diseases.", "qid": 45, "docid": "03aubqeb", "rank": 82, "score": 0.8298759460449219}, {"content": "Title: Levels and predictors of anxiety, depression and health anxiety during COVID-19 pandemic in Turkish society: The importance of gender Content: BACKGROUND: The COVID-19 pandemic is having negative effects on societies' mental health. Both the pandemic and the measures taken to combat it can affect individuals' mental health. AIMS: The purpose of this study was to evaluate the levels of depression, anxiety and health anxiety in Turkish society during the COVID-19 pandemic, and to examine the factors affecting these. METHOD: The study was performed using an online questionnaire. Participants were asked to complete a sociodemographic data form, the Hospital Anxiety and Depression Scale (HADS) and the Health Anxiety Inventory (HAI). The effects on depression, anxiety and health anxiety levels of factors such as age, sex, marital status, living with an individual aged above 60, the presence of a new Coronavirus+ patient among friends or relatives, previous and current psychiatric illness and presence of accompanying chronic disease were then investigated. RESULTS: In terms of HADS cut-off points, 23.6% (n = 81) of the population scored above the depression cut-off point, and 45.1% (n = 155) scored above the cut-off point for anxiety. In regression analysis, female gender, living in urban areas and previous psychiatric illness history were found as risk factors for anxiety; living in urban areas was found as risk factor for depression; and female gender, accompanying chronic disease and previous psychiatric history were found as risk factors for health anxiety. CONCLUSION: The results of this cross-sectional study suggest that the groups most psychologically affected by the COVID-19 pandemic are women, individuals with previous psychiatric illness, individuals living in urban areas and those with an accompanying chronic disease. Priority might therefore be attached to these in future psychiatric planning.", "qid": 45, "docid": "6pv0c1iu", "rank": 83, "score": 0.8296923637390137}, {"content": "Title: Prevalence of stress, anxiety, depression among the general population during the COVID-19 pandemic: a systematic review and meta-analysis Content: BACKGROUND: The COVID-19 pandemic has had a significant impact on public mental health. Therefore, monitoring and oversight of the population mental health during crises such as a panedmic is an immediate priority. The aim of this study is to analyze the existing research works and findings in relation to the prevalence of stress, anxiety and depression in the general population during the COVID-19 pandemic. METHOD: In this systematic review and meta-analysis, articles that have focused on stress and anxiety prevalence among the general population during the COVID-19 pandemic were searched in the Science Direct, Embase, Scopus, PubMed, Web of Science (ISI) and Google Scholar databases, without a lower time limit and until May 2020. In order to perform a meta-analysis of the collected studies, the random effects model was used, and the heterogeneity of studies was investigated using the I(2) index. Moreover. data analysis was conducted using the Comprehensive Meta-Analysis (CMA) software. RESULTS: The prevalence of stress in 5 studies with a total sample size of 9074 is obtained as 29.6% (95% confidence limit: 24.3\u201335.4), the prevalence of anxiety in 17 studies with a sample size of 63,439 as 31.9% (95% confidence interval: 27.5\u201336.7), and the prevalence of depression in 14 studies with a sample size of 44,531 people as 33.7% (95% confidence interval: 27.5\u201340.6). CONCLUSION: COVID-19 not only causes physical health concerns but also results in a number of psychological disorders. The spread of the new coronavirus can impact the mental health of people in different communities. Thus, it is essential to preserve the mental health of individuals and to develop psychological interventions that can improve the mental health of vulnerable groups during the COVID-19 pandemic.", "qid": 45, "docid": "8ab8rugv", "rank": 84, "score": 0.8290676474571228}, {"content": "Title: Research in counselling and psychotherapy Post\u2010COVID\u201019 Content: The COVID\u201019 pandemic brings to light many areas the field of counselling and psychotherapy may need to address in future research. We outline several issues stemming from or exacerbated by the pandemic and offer suggestions for future research to address the mental health needs of those impacted. Our suggestions focus on five domains: (a) the health and well\u2010being of helping professionals, (b) the infodemic, (c) discrimination and minority stress, (d) spiritual and existential dynamics in mental health and (e) couple and family stress and resilience. We aim to provide a multi\u2010systemic perspective of mental health and well\u2010being in the time of COVID\u201019, as well as encourage current and future studies to incorporate these suggestions to advance the health and well\u2010being of our communities through evidence\u2010based treatment approaches.", "qid": 45, "docid": "74en8bkt", "rank": 85, "score": 0.8290220499038696}, {"content": "Title: Commentary on the coronavirus pandemic: Anticipating a fourth wave in the opioid epidemic Content: Experiencing the COVID-19 pandemic simultaneously with the U.S. opioid epidemic is anticipated to have a profound mental health impact on some of our most vulnerable populations. Recent federal and state regulatory changes have been made under the state of emergency in order to ameliorate the some of the challenges faced in maintaining access to substance use and addiction services during such times. There are currently considerable limitations in quantifying the impact of COVID-19 among those with substance use disorders, however, it is imperative that health care systems continue to serve this population in order to prevent associated morbidity and mortality. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "h6gb99fw", "rank": 86, "score": 0.829020619392395}, {"content": "Title: Commentary on the coronavirus pandemic: Anticipating a fourth wave in the opioid epidemic. Content: Experiencing the COVID-19 pandemic simultaneously with the U.S. opioid epidemic is anticipated to have a profound mental health impact on some of our most vulnerable populations. Recent federal and state regulatory changes have been made under the state of emergency in order to ameliorate the some of the challenges faced in maintaining access to substance use and addiction services during such times. There are currently considerable limitations in quantifying the impact of COVID-19 among those with substance use disorders, however, it is imperative that health care systems continue to serve this population in order to prevent associated morbidity and mortality. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "41rn0fdg", "rank": 87, "score": 0.829020619392395}, {"content": "Title: The impact of the COVID-19 outbreak on the medico-legal and human rights of psychiatric patients Content: The COVID-19 pandemic has raised significant concerns for population mental health and the effective provision of mental health services in the light of increased demands and barriers to service delivery [1]. Particular attention is being directed toward the possible neuropsychiatric sequelae of both COVID-19 and of the stringent societal mitigation steps deployed by national governments, concerns that are informed by historical increases in the incidence of psychotic disorders following influenza pandemics [2]. However, so far there has been scant attention paid to other important areas of psychiatry during COVID-19, including medico-legal aspects and human rights. In this paper, we discuss the legal implications for psychiatry of the COVID-19 pandemic and report a novel situation in which psychiatric patients may experience diminution of their statutory protections. We believe that this represents a paradigm shift in psychiatric care and that the consideration of the fundamental rights of psychiatric patients as \"less important\" than infection control measures compel mental health professionals to \"advocate for patients and their caregivers\" in this time of crisis [1].", "qid": 45, "docid": "wx30gugb", "rank": 88, "score": 0.8289233446121216}, {"content": "Title: Depression and Anxiety in Hong Kong during COVID-19 Content: It has been three months since the first confirmed case of coronavirus disease 2019 (COVID-19) in Hong Kong, and people now have a more complete picture of the extent of the pandemic. Therefore, it is time to evaluate the impacts of COVID-19 on mental health. The current population-based study aimed to evaluate the depression and anxiety of people in Hong Kong during the COVID-19 pandemic. Respondents were randomly recruited and asked to complete a structured questionnaire, including the patient health questionnaire-9 (PHQ-9), the generalized anxiety disorder-7 (GAD-7), the global rating of change scale and items related to COVID-19. Of the 500 respondents included in the study, 19% had depression (PHQ-9 score &#8805; 10) and 14% had anxiety (GAD score &#8805; 10). In addition, 25.4% reported that their mental health had deteriorated since the pandemic. Multiple logistic regression analysis found that not experiencing the SARS outbreak in 2003, being worried about being infected by COVID-19, being bothered by having not enough surgical masks and being bothered by not being able to work from home were associated with a poorer mental health status. Psychological support, such as brief, home-based psychological interventions, should be provided to citizens during the pandemic.", "qid": 45, "docid": "bqeu51ch", "rank": 89, "score": 0.8285991549491882}, {"content": "Title: Covid-19, Mental Health and Psychological First Aid Content: Crises such as the global pandemic of Covid-19 (coronavirus) elicit a range of responses from individuals and societies adversely affecting physical and emotional well-being. This article provides an overview of factors elicited in response to Covid-19 and their impact on immunity, physical health, mental health and wellbeing. Certain groups, such as individuals with mental illness, are especially vulnerable, so it is important to maximise the supports available to this population and their families during the pandemic. More broadly, the World Health Organization recommends \"Psychological First Aid\" as a useful technique that can help many people in a time of crisis.", "qid": 45, "docid": "ljsoikhk", "rank": 90, "score": 0.828531801700592}, {"content": "Title: Covid-19, Mental Health and Psychological First Aid. Content: Crises such as the global pandemic of Covid-19 (coronavirus) elicit a range of responses from individuals and societies adversely affecting physical and emotional well-being. This article provides an overview of factors elicited in response to Covid-19 and their impact on immunity, physical health, mental health and wellbeing. Certain groups, such as individuals with mental illness, are especially vulnerable, so it is important to maximise the supports available to this population and their families during the pandemic. More broadly, the World Health Organization recommends \"Psychological First Aid\" as a useful technique that can help many people in a time of crisis.", "qid": 45, "docid": "j7c7hk2h", "rank": 91, "score": 0.828531801700592}, {"content": "Title: Multidisciplinary research priorities for the COVID-19 pandemic: a call for action for mental health science Content: Summary The coronavirus disease 2019 (COVID-19) pandemic is having a profound effect on all aspects of society, including mental health and physical health. We explore the psychological, social, and neuroscientific effects of COVID-19 and set out the immediate priorities and longer-term strategies for mental health science research. These priorities were informed by surveys of the public and an expert panel convened by the UK Academy of Medical Sciences and the mental health research charity, MQ: Transforming Mental Health, in the first weeks of the pandemic in the UK in March, 2020. We urge UK research funding agencies to work with researchers, people with lived experience, and others to establish a high level coordination group to ensure that these research priorities are addressed, and to allow new ones to be identified over time. The need to maintain high-quality research standards is imperative. International collaboration and a global perspective will be beneficial. An immediate priority is collecting high-quality data on the mental health effects of the COVID-19 pandemic across the whole population and vulnerable groups, and on brain function, cognition, and mental health of patients with COVID-19. There is an urgent need for research to address how mental health consequences for vulnerable groups can be mitigated under pandemic conditions, and on the impact of repeated media consumption and health messaging around COVID-19. Discovery, evaluation, and refinement of mechanistically driven interventions to address the psychological, social, and neuroscientific aspects of the pandemic are required. Rising to this challenge will require integration across disciplines and sectors, and should be done together with people with lived experience. New funding will be required to meet these priorities, and it can be efficiently leveraged by the UK's world-leading infrastructure. This Position Paper provides a strategy that may be both adapted for, and integrated with, research efforts in other countries.", "qid": 45, "docid": "knlc3bxh", "rank": 92, "score": 0.8283148407936096}, {"content": "Title: Adjustment and coronavirus: How to prepare for COVID-19 pandemic-related adjustment disorder worldwide? Content: As the 2019 novel coronavirus (COVID-19) is spreading worldwide in 2020, there is a growing concern about the impact of the pandemic on mental health. Multiple stressors associated with the pandemic, such as health-related stressors, job loss, and work-related stressors, could increase the prevalence of adjustment disorders worldwide. The present article acknowledges adjustment disorder as a highly relevant mental health outcome of the pandemic that should be addressed by mental health professionals. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 45, "docid": "3yikeq42", "rank": 93, "score": 0.8279858827590942}, {"content": "Title: Three challenges that the COVID-19 pandemic represents for psychiatry Content: The evolving COVID-19 pandemic and its likely consequences add to the already substantial psychosocial burden caused by global problems, existential threats and heightened uncertainty, which are increasingly confronting communities worldwide. Here we briefly outline three challenges for clinical psychiatry and research, related to coping with the social epidemiology of negative moods, stress and socially mediated traumatic experiences brought on by these adverse developments.", "qid": 45, "docid": "62yih8td", "rank": 94, "score": 0.827634871006012}, {"content": "Title: Acute mental health responses during the COVID-19 pandemic in Australia Content: The acute and long-term mental health impacts of the COVID-19 pandemic are unknown. The current study examined the acute mental health responses to the COVID-19 pandemic in 5070 adult participants in Australia, using an online survey administered during the peak of the outbreak in Australia (27th March to 7th April 2020). Self-report questionnaires examined COVID-19 fears and behavioural responses to COVID-19, as well as the severity of psychological distress (depression, anxiety and stress), health anxiety, contamination fears, alcohol use, and physical activity. 78% of respondents reported that their mental health had worsened since the outbreak, one quarter (25.9%) were very or extremely worried about contracting COVID-19, and half (52.7%) were worried about family and friends contracting COVID-19. Uncertainty, loneliness and financial worries (50%) were common. Rates of elevated psychological distress were higher than expected, with 62%, 50%, and 64% of respondents reporting elevated depression, anxiety and stress levels respectively, and one in four reporting elevated health anxiety in the past week. Participants with self-reported history of a mental health diagnosis had significantly higher distress, health anxiety, and COVID-19 fears than those without a prior mental health diagnosis. Demographic (e.g., non-binary or different gender identity; Aboriginal and Torres Strait Islander status), occupational (e.g., being a carer or stay at home parent), and psychological (e.g., perceived risk of contracting COVID-19) factors were associated with distress. Results revealed that precautionary behaviours (e.g., washing hands, using hand sanitiser, avoiding social events) were common, although in contrast to previous research, higher engagement in hygiene behaviours was associated with higher stress and anxiety levels. These results highlight the serious acute impact of COVID-19 on the mental health of respondents, and the need for proactive, accessible digital mental health services to address these mental health needs, particularly for those most vulnerable, including people with prior history of mental health problems. Longitudinal research is needed to explore long-term predictors of poor mental health from the COVID-19 pandemic.", "qid": 45, "docid": "fzusgbww", "rank": 95, "score": 0.8276050686836243}, {"content": "Title: Mapping population mental health concerns related to COVID-19 and the consequences of physical distancing: a Google trends analysis Content: Background: The 2020 Coronavirus pandemic is a major international public health challenge. Governments have taken public health protection measures to reduce the spread of the virus through non-pharmalogical measures. The impact of the pandemic and the public health response on individual and population mental health is unknown. Methods: We used Google Trends data (1 Jan 2020 - 30 Mar 2020) to investigate the impact of the pandemic and government measures to curb it on people\u2019s concerns, as indexed by changes in search frequency for topics indicating mental distress, social and economic stressors and mental health treatment-seeking. We explored the changes of key topics in Google trends in Italy, Spain, USA, UK, and Worldwide in relation to sentinel events during the pandemic. Results: Globally there appears to be significant concerns over the financial and work-related consequences of the pandemic, with some evidence that levels of fear are rising. Conversely relative searching for topics related to depression and suicide fell after the pandemic was announced, with some evidence that searches for the latter have risen recently. Concerns over education and access to medication appear to be particular social stressors. Whilst searches for face-to-face treatments have declined, those for self-care have risen. Conclusions: Monitoring Google trends shows promise as a means of tracking changing public concerns. In weeks to come it may enable policy makers to assess the impact of their interventions including those aiming to limit negative consequences, such as government funded financial safety nets.", "qid": 45, "docid": "9659rpgy", "rank": 96, "score": 0.8272401094436646}, {"content": "Title: Psychotic relapse from COVID-19 quarantine, a case report Content: \u2022 The coronavirus disease 2019 (COVID-19), first reported on December 31(st), 2019 in China, has currently spread worldwide and became pandemic on March 11(th). \u2022 Besides causing an emotional impact in people affected, COVID-19 pandemic could specially affect people with previous mental health conditions, resulting in relapses or worsening of an already existing mental health condition because of high susceptibility to stress compared with the general population. \u2022 Worldwide, in different countries, among them Spain, it has been necessary to adopt confinement measures to preserve public health. These measures might represent to an extra stressful situation, particularly in vulnerable patients, such as those suffering from psychotic disorders. \u2022 This case report highlights the importance to developing specific support programs for this vulnerable population in an unprecedented situation such us the COVID-19 crisis. The role of telemedicine it has been suggested for that purpose.", "qid": 45, "docid": "0fhl7muq", "rank": 97, "score": 0.8267390131950378}, {"content": "Title: CoViD-19 and stress in the pandemic: \"sanity is not statistical\" Content: CoViD-19 pandemic is causing serious consequences on mental health, consequences that are considered that bad that World Health Organization has affirmed that mental health defence is priority in this particular moment of development of pandemic. In light of this alertness, what we are interested in approaching in this work, is the specific stress condition caused by pandemic, which underlies and precedes the described classification of diseases and which is going towards an increase in the entire world, including . The stress caused by pandemic is a new condition in comparison with what is known in clinical practice and with what is included in the classification of mental disorder. The ongoing stress condition and the mixture of different types of unconventional stress, which not only hits the present but also disrupts the future, create an entirely new form of clinical condition given by pandemic.", "qid": 45, "docid": "csi7x7w8", "rank": 98, "score": 0.8264837861061096}, {"content": "Title: CoViD-19 and stress in the pandemic: \"sanity is not statistical\". Content: CoViD-19 pandemic is causing serious consequences on mental health, consequences that are considered that bad that World Health Organization has affirmed that mental health defence is priority in this particular moment of development of pandemic. In light of this alertness, what we are interested in approaching in this work, is the specific stress condition caused by pandemic, which underlies and precedes the described classification of diseases and which is going towards an increase in the entire world, including . The stress caused by pandemic is a new condition in comparison with what is known in clinical practice and with what is included in the classification of mental disorder. The ongoing stress condition and the mixture of different types of unconventional stress, which not only hits the present but also disrupts the future, create an entirely new form of clinical condition given by pandemic.", "qid": 45, "docid": "ykb23itb", "rank": 99, "score": 0.8264837861061096}, {"content": "Title: The impact of the COVID-19 pandemic on the mental health of healthcare professionals Content: INTRODUCTION: Healthcare professionals (HPs) have been confronted by unprecedented traumatic experiences during the novel coronavirus disease (COVID-19) pandemic, especially in countries that had not experienced similar epidemic outbreaks in recent years. AIM: To analyze the impact of the COVID-19 pandemic on the mental health of HPs. METHOD: We comprehensively reviewed the studies published in MEDLINE (PubMed), Web of Science and Google Scholar between December 2019 and May 2020. RESULTS: Most studies report a high prevalence of anxiety and depressive symptoms among HPs that can be associated with: (i) COVID-19 exposure; (ii) epidemiological issues; (iii) material resources; (iv) human resources; and (v) personal factors. The role of certain variables, before, during and after the pandemic, remains unexplored. Longitudinal studies will help elucidate which factors are associated with a higher risk of developing long-lasting negative effects. Qualitative studies may contribute to understanding the influence of individual and social narratives in HPs\u2019 distress. CONCLUSION: A deeper analysis on the individual, institutional, political and socio-cultural factors, meanings and values influencing HPs distress and resilience during the COVID-19 pandemic is needed.", "qid": 45, "docid": "5mq7h8ng", "rank": 100, "score": 0.8264124989509583}]}
{"query": "what evidence is there for dexamethasone as a treatment for COVID-19?", "hits": [{"content": "Title: Transcatheter drug delivery through bronchial artery for COVID-19: is it fiction or could it come true? Content: More than 1,200 active or recruiting clinical trials for novel coronavirus disease 2019 (COVID-19) treatments and vaccines are registered. Many drugs have shown promise for treatment of COVID-19. Nevertheless, up to date, no drugs have been confirmed as a definitive treatment for COVID-19. Trials such as the SOLIDARITY and RECOVERY are ongoing, and first results were announced in favour of therapy with dexamethasone with a significant trend showing greatest benefit among those patients requiring ventilation. The drawbacks of these trials include exposing the patients to drugs with well-documented systemic adverse effects or unknown complications of novel therapies without proof of clinical benefit. We present here the hypothesis that bronchial artery infusion could be an alternative for systemic drug infusion in COVID-19 trials with superadded benefits of high drug concentration and low systemic adverse effects. The concept of this idea has many uncertainties and no current clinical data to support. Perhaps, the technique should be first applied in animal models to determine its safety and calculate the effective dose of the drugs. Guidelines and reviews of pharmacotherapy for COVID-19 should be implemented for this fiction to come true.", "qid": 46, "docid": "ylcaw0vi", "rank": 1, "score": 0.844261646270752}, {"content": "Title: Rapid Radiological Worsening and Cytokine Storm Syndrome in COVID-19 Pneumonia Content: BACKGROUND: In June 2020, a large randomised controlled clinical trial in the UK found that dexamethasone was effective in reducing the number of deaths in patients with severe coronavirus disease 2019 (COVID-19). CASE DESCRIPTION: We describe a patient with rapid worsening of COVID-19 pneumonia and its dramatic improvement under corticosteroids. DISCUSSION: Corticosteroids could be useful in patients with an inflammatory profile, considering that acute respiratory distress syndrome may be the consequence of cytokine storm syndrome. LEARNING POINTS: One of the main pathophysiological hypotheses for severe COVID-19 pneumonia is inappropriate immunological hyperactivation. Corticosteroid therapy may be useful in these patients.", "qid": 46, "docid": "gc8770l9", "rank": 2, "score": 0.8432036638259888}, {"content": "Title: Role of corticosteroid in the management of COVID-19: A systemic review and a Clinician\u2019s perspective Content: BACKGROUND AND AIMS: Interest in corticosteroid therapy in COVID-19 has been rekindled after the results from Randomized Evaluation of COVid-19 thERapY (RECOVERY) Trial. However, the World health Organization has not recommended corticosteroid in the treatment of COVID-19. We sought to conduct a systematic review on the role of corticosteroid in the management of patients of COVID-19. METHODS: A systematic electronic search of PubMed, Cochrane and MedRxiv database using specific keywords was made up till June 17, 2020. Full text of all the original articles with supplementary appendix that fulfilled the inclusion criteria were retrieved and a detailed analysis of results were represented. RESULTS: Of the 5 studies (4 retrospective studies and 1 quasi-prospective study) conducted for evaluating the role of corticosteroids, 3 studies have shown benefit, while 2 studies shown no benefit and there was a suggestion of significant harm in critical cases in one sub-study. RECOVERY trial is the only randomized controlled trial that has shown a significant reduction of death by 35% in ventilated patients and by 20% amongst patients on supplemental oxygen therapy with the dexamethasone, although no benefit was observed in mild cases. CONCLUSIONS: While the results from retrospective studies are heterogenous and difficult to infer of a definitive protective benefit with corticosteroids, RECOVERY trial found a significantly better outcome with dexamethasone, mostly in severe cases. Nonetheless, more studies are needed to replicate the outcome shown in RECOVERY trial for a substantial conclusion.", "qid": 46, "docid": "zi86r481", "rank": 3, "score": 0.8417515754699707}, {"content": "Title: Role of corticosteroid in the management of COVID-19: A systemic review and a Clinician's perspective Content: BACKGROUND AND AIMS: Interest in corticosteroid therapy in COVID-19 has been rekindled after the results from Randomized Evaluation of COVid-19 thERapY (RECOVERY) Trial. However, the World health Organization has not recommended corticosteroid in the treatment of COVID-19. We sought to conduct a systematic review on the role of corticosteroid in the management of patients of COVID-19. METHODS: A systematic electronic search of PubMed, Cochrane and MedRxiv database using specific keywords was made up till June 17, 2020. Full text of all the original articles with supplementary appendix that fulfilled the inclusion criteria were retrieved and a detailed analysis of results were represented. RESULTS: Of the 5 studies (4 retrospective studies and 1 quasi-prospective study) conducted for evaluating the role of corticosteroids, 3 studies have shown benefit, while 2 studies shown no benefit and there was a suggestion of significant harm in critical cases in one sub-study. RECOVERY trial is the only randomized controlled trial that has shown a significant reduction of death by 35% in ventilated patients and by 20% amongst patients on supplemental oxygen therapy with the dexamethasone, although no benefit was observed in mild cases. CONCLUSIONS: While the results from retrospective studies are heterogenous and difficult to infer of a definitive protective benefit with corticosteroids, RECOVERY trial found a significantly better outcome with dexamethasone, mostly in severe cases. Nonetheless, more studies are needed to replicate the outcome shown in RECOVERY trial for a substantial conclusion.", "qid": 46, "docid": "hswuwtod", "rank": 4, "score": 0.8417515754699707}, {"content": "Title: A critical evaluation of glucocorticoids in the management of severe COVID-19 Content: The viral infection by SARS-CoV-2 has irrevocably altered the life of the majority of human beings, challenging national health systems worldwide, and pushing researchers to rapidly find adequate preventive and treatment strategies. No therapies have been shown effective with the exception of dexamethasone, a glucocorticoid that was recently proved to be the first life-saving drug in this disease. Remarkably, around 20 % of infected people develop a severe form of COVID-19, giving rise to respiratory and multi-organ failures requiring subintensive and intensive care interventions. This phenomenon is due to an excessive immune response that damages pulmonary alveoli, leading to a cytokine and chemokine storm with systemic effects. Indeed glucocorticoids' role in regulating this immune response is controversial, and they have been used in clinical practice in a variety of countries, even without a previous clear consensus on their evidence-based benefit.", "qid": 46, "docid": "bhkmax7s", "rank": 5, "score": 0.8410561084747314}, {"content": "Title: Short-Term Dexamethasone in Sars-CoV-2 Patients. Content: BACKGROUND Dexamethasone, a synthetic glucocorticoid, has anti-inflammatory and immunosuppressive properties. There is a hyperinflammatory response involved in the clinical course of patients with pneumonia due to SARS-CoV-2. To date, there has been no definite therapy for COVID-19. We reviewed the charts of SARS-CoV-2 patients with pneumonia and moderate to severely elevated CRP and worsening hypoxemia who were treated with early, short-term dexamethasone. METHODS We describe a series of 21 patients who tested positive for SARS-CoV-2 and were admitted to The Miriam Hospital in Providence, RI, and were treated with a short course of dexamethasone, either alone or in addition to current investigative therapies. RESULTS CRP levels decreased significantly following the start of dexamethasone from mean initial levels of 129.52 to 40.73 mg/L at time of discharge. 71% percent of the patients were discharged home with a mean length of stay of 7.8 days. None of the patients had escalation of care, leading to mechanical ventilation. Two patients were transferred to inpatient hospice facilities on account of persistent hypoxemia, in line with their documented goals of care. CONCLUSIONS A short course of systemic corticosteroids among inpatients with SARS-CoV-2 with hypoxic respiratory failure was well tolerated, and most patients had improved outcomes. This limited case series may not offer concrete evidence towards the benefit of corticosteroids in COVID-19. However, patients' positive response to short-term corticosteroids demonstrates that they may help blunt the severity of inflammation and prevent a severe hyperinflammatory phase, in turn reducing the length of stay, ICU admissions, and healthcare costs.", "qid": 46, "docid": "ztd7awzv", "rank": 6, "score": 0.8358616828918457}, {"content": "Title: Short-Term Corticosteroids in SARS-CoV2 Patients: Hospitalists' Perspective Content: Background: Dexamethasone, a synthetic glucocorticoid, has anti-inflammatory and immunosuppressive properties. There is a hyperinflammatory response involved in the clinical course of patients with pneumonia due to SARS-CoV2. To date, there has been no definite therapy for COVID-19. We reviewed the charts of SARS-CoV2 patients with pneumonia and moderate to severely elevated CRP and worsening hypoxemia who were treated with early, short-term dexamethasone. Methods: We describe a series of 21 patients who tested positive for SARS-CoV2 and were admitted to The Miriam Hospital in Providence and were treated with a short course of dexamethasone, either alone or in addition to current investigative therapies. Results: CRP levels decreased significantly following the start of dexamethasone from mean initial levels of 129.52 to 40.73 mg/L at time of discharge. 71% percent of the patients were discharged home with a mean length of stay of 7.8 days. None of the patients had escalation of care, leading to mechanical ventilation. Two patients were transferred to inpatient hospice facilities on account of persistent hypoxemia, in line with their documented goals of care. Conclusions: A short course of systemic corticosteroids among inpatients with SARS-CoV2 with hypoxic respiratory failure was well tolerated, and most patients had improved outcomes. This limited case series may not offer concrete evidence towards the benefit of corticosteroids in COVID-19. However, patients positive response to short-term corticosteroids demonstrates that they may help blunt the severity of inflammation and prevent a severe hyperinflammatory phase, in turn reducing the length of stay, ICU admissions, and healthcare costs.", "qid": 46, "docid": "oqgw6ao6", "rank": 7, "score": 0.8354017734527588}, {"content": "Title: COVID-19 and treatment with NSAIDs and corticosteroids: should we be limiting their use in the clinical setting? Content: Given the current SARS-CoV-2 (COVID-19) pandemic, the availability of reliable information for clinicians and patients is paramount. There have been a number of reports stating that non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids may exacerbate symptoms in COVID-19 patients. Therefore, this review aimed to collate information available in published articles to identify any evidence behind these claims with the aim of advising clinicians on how best to treat patients. This review found no published evidence for or against the use of NSAIDs in COVID-19 patients. Meanwhile, there appeared to be some evidence that corticosteroids may be beneficial if utilised in the early acute phase of infection, however, conflicting evidence from the World Health Organisation surrounding corticosteroid use in certain viral infections means this evidence is not conclusive. Given the current availability of literature, caution should be exercised until further evidence emerges surrounding the use of NSAIDs and corticosteroids in COVID-19 patients.", "qid": 46, "docid": "0uengr9t", "rank": 8, "score": 0.8347682952880859}, {"content": "Title: Dexamethasone for COVID-19? Not so fast Content: Recent announcements indicated, without sharing any distinct published set of results, that the corticosteroid dexamethasone may reduce mortality of severe COVID-19 patients only. The recent Coronavirus [severe acute respiratory syndrome (SARS)-CoV-2]-associated multiorgan disease, called COVID-19, has high morbidity and mortality due to autoimmune destruction of the lungs stemming from the release of a storm of pro-inflammatory cytokines. Defense against this Corona virus requires activated T cells and specific antibodies. Instead, cytokines are responsible for the serious sequelae of COVID-19 that damage the lungs. Dexamethasone is a synthetic corticosteroid approved by the FDA 1958 as a broad-spectrum immunosuppressor and it is about 30 times as active and with longer duration of action (2-3 days) than cortisone. Dexamethasone would limit the production of and damaging effect of the cytokines, but will also inhibit the protective function of T cells and block B cells from making antibodies, potentially leading to increased plasma viral load that will persist after a patient survives SARS. Moreover, dexamethasone would block macrophages from clearing secondary, nosocomial, infections. Hence, dexamethasone may be useful for the short-term in severe, intubated, COVID-19 patients, but could be outright dangerous during recovery since the virus will not only persist, but the body will be prevented from generating protective antibodies. Instead, a pulse of intravenous dexamethasone may be followed by administration of nebulized triamcinolone (6 times as active as cortisone) to concentrate in the lungs only. These corticosteroids could be given together with the natural flavonoid luteolin because of its antiviral and anti-inflammatory properties, especially its ability to inhibit mast cells, which are the main source of cytokines in the lungs. At the end, we should remember that \"The good physician treats the disease; the great physician treats the patient who has the disease\" [Sir William Osler's (1849-1919)].", "qid": 46, "docid": "6q0y3ewu", "rank": 9, "score": 0.8304824233055115}, {"content": "Title: Dexamethasone for COVID-19? Not so fast. Content: Recent announcements indicated, without sharing any distinct published set of results, that the corticosteroid dexamethasone may reduce mortality of severe COVID-19 patients only. The recent Coronavirus [severe acute respiratory syndrome (SARS)-CoV-2]-associated multiorgan disease, called COVID-19, has high morbidity and mortality due to autoimmune destruction of the lungs stemming from the release of a storm of pro-inflammatory cytokines. Defense against this Corona virus requires activated T cells and specific antibodies. Instead, cytokines are responsible for the serious sequelae of COVID-19 that damage the lungs. Dexamethasone is a synthetic corticosteroid approved by the FDA 1958 as a broad-spectrum immunosuppressor and it is about 30 times as active and with longer duration of action (2-3 days) than cortisone. Dexamethasone would limit the production of and damaging effect of the cytokines, but will also inhibit the protective function of T cells and block B cells from making antibodies, potentially leading to increased plasma viral load that will persist after a patient survives SARS. Moreover, dexamethasone would block macrophages from clearing secondary, nosocomial, infections. Hence, dexamethasone may be useful for the short-term in severe, intubated, COVID-19 patients, but could be outright dangerous during recovery since the virus will not only persist, but the body will be prevented from generating protective antibodies. Instead, a pulse of intravenous dexamethasone may be followed by administration of nebulized triamcinolone (6 times as active as cortisone) to concentrate in the lungs only. These corticosteroids could be given together with the natural flavonoid luteolin because of its antiviral and anti-inflammatory properties, especially its ability to inhibit mast cells, which are the main source of cytokines in the lungs. At the end, we should remember that \"The good physician treats the disease; the great physician treats the patient who has the disease\" [Sir William Osler's (1849-1919)].", "qid": 46, "docid": "br3ahtf7", "rank": 10, "score": 0.8304824233055115}, {"content": "Title: A critical evaluation of glucocorticoids in the treatment of severe COVID-19 Content: The viral infection by SARS-CoV-2, has revolutionized the life of the majority of human beings, challenging national health systems worldwide, and pushing researchers to rapidly find adequate preventive and treatment strategies. No therapies have been shown effective, with the exception of dexamethasone, a glucocorticoid that was recently proved to be the first life-saving drug in this disease. Remarkably, around 20% of infected people develop a severe form of COVID-19, giving rise to respiratory and multi-organ failures requiring subintensive and intensive care interventions. This phenomenon is due to an excessive immune response that damages pulmonary alveoli, leading to a cytokine and chemokine storm with systemic effects. Indeed glucocorticoids\u2019 role in regulating this immune response is controversial, and they have been used in clinical practice in a variety of countries, even without a previous clear consensus on their evidence-based benefit.", "qid": 46, "docid": "m2b836k8", "rank": 11, "score": 0.825462818145752}, {"content": "Title: Short-Term Dexamethasone in Sars-CoV-2 Patients Content: BACKGROUND: Dexamethasone, a synthetic glucocorticoid, has anti-inflammatory and immunosuppressive properties There is a hyperinflammatory response involved in the clinical course of patients with pneumonia due to SARS-CoV-2 To date, there has been no definite therapy for COVID-19 We reviewed the charts of SARS-CoV-2 patients with pneumonia and moderate to severely elevated CRP and worsening hypoxemia who were treated with early, short-term dexamethasone METHODS: We describe a series of 21 patients who tested positive for SARS-CoV-2 and were admitted to The Miriam Hospital in Providence, RI, and were treated with a short course of dexamethasone, either alone or in addition to current investigative therapies RESULTS: CRP levels decreased significantly following the start of dexamethasone from mean initial levels of 129 52 to 40 73 mg/L at time of discharge 71% percent of the patients were discharged home with a mean length of stay of 7 8 days None of the patients had escalation of care, leading to mechanical ventilation Two patients were transferred to inpatient hospice facilities on account of persistent hypoxemia, in line with their documented goals of care CONCLUSIONS: A short course of systemic corticosteroids among inpatients with SARS-CoV-2 with hypoxic respiratory failure was well tolerated, and most patients had improved outcomes This limited case series may not offer concrete evidence towards the benefit of corticosteroids in COVID-19 However, patients' positive response to short-term corticosteroids demonstrates that they may help blunt the severity of inflammation and prevent a severe hyperinflammatory phase, in turn reducing the length of stay, ICU admissions, and healthcare costs", "qid": 46, "docid": "fqh77aaa", "rank": 12, "score": 0.8241024613380432}, {"content": "Title: Pros and cons of corticosteroid therapy for COVID-19 patients Content: In December 2019, an outbreak of severe pneumonia was reported in Wuhan, China. Later described as COVID-19 (coronavirus disease 2019), this infection caused by a virus from the Coronaviridae family (SARS-CoV-2) has spread globally. Effective therapies for this new disease are urgently needed. In this short communication, we will evaluate the use of corticosteroids as an adjunctive pharmacological therapy in the management of COVID-19 and describe its pros and cons in light of the latest available evidence.", "qid": 46, "docid": "mza0oz89", "rank": 13, "score": 0.8240329027175903}, {"content": "Title: Use of Corticosteroids in Coronavirus Disease 2019 Pneumonia: A Systematic Review of the Literature Content: The aim was to investigate the effectiveness of glucocorticoid therapy in patients with COVID-19. A systematic search of the literature across nine databases was conducted from inception until 15th March 2020, following the PRISMA guidelines. Patients with a validated diagnosis of COVID-19 and using corticosteroids were included, considering all health outcomes. Four studies with 542 Chinese participants were included. Two studies reported negative findings regarding the use of corticosteroids in patients with COVID-19, i.e., corticosteroids had a detrimental impact on clinical outcomes. One study reported no significant association between the use of corticosteroids and clinical outcomes. However, one study, on 201 participants with different stages of pneumonia due to COVID-19, found that in more severe forms, the administration of methylprednisolone significantly reduced the risk of death by 62%. The literature to date does not fully support the routine use of corticosteroids in COVID-19, but some findings suggest that methylprednisolone could lower mortality rate in more severe forms of the condition.", "qid": 46, "docid": "ypeibwje", "rank": 14, "score": 0.8203153610229492}, {"content": "Title: Pharmacologicaltreatment of COVID-19: lights and shadows Content: At the end of December 2019, a novel coronavirus, the severe acute respiratory syndrome coronavirus 2, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China and then the entire world, forcing the World Health Organization to make the assessment that the coronavirus disease (COVID-19) can be characterized as a pandemic, the first ever caused by a coronavirus. To date, clinical evidence and guidelines based on reliable data and randomized clinical trials for the treatment of COVID-19 are lacking. In the absence of definitive management protocols, many treatments for COVID-19 are currently being evaluated and tested worldwide. Some of these options were soon abandoned due to ineffectiveness, while others showed promising results. The basic treatments are mainly represented by antiviral drugs, even if the evidence is not satisfactory. Among the antivirals, the most promising appears to be remdesivir. Corticosteroids and tocilizumab seem to guarantee positive results in selected patients so far, although the timing of starting therapy and the most appropriate therapeutic schemes remain to be clarified. Efficacy of the other drugs is still uncertain, and they are currently used as a cocktail of treatments in the absence of definitive guidelines. What will represent the real solution to the enormous problem taking place worldwide is the identification of a safe and effective vaccine, for which enormous efforts and investments are underway.", "qid": 46, "docid": "o29773cz", "rank": 15, "score": 0.8197400569915771}, {"content": "Title: Therapeutic Management of COVID-19 Patients: A systematic review Content: Background: SARS-CoV-2 is the cause of the COVID-19 that has been declared a global pandemic by the WHO in 2020. The COVID-19 treatment guidelines vary in each country, and yet there is no approved therapeutic for COVID-19. Aims of the study: this review aimed to report any evidence of therapeutics used for the management of COVID-19 patients in clinical practice since the emergence of the virus. Methods: A systematic review protocol was developed based on PRISMA Statement. Articles for review were selected from electronic databases (Embase, Medline and Google Scholar). Readily accessible peer-reviewed full articles in English published from December 1 st , 2019 to March 26 th , 2020 were included. The search terms included combinations of: COVID, SARS-COV-2, glucocorticoids, convalescent plasma, antiviral, antibacterial. There were no restrictions on the type of study design eligible for inclusion. Results: As of March 26, 2020, of the initial manuscripts identified (n=449) articles. Forty-one studies were included, of which clinical trials (n=3), (case reports n=7), case series (n=10), retrospective (n=11) and prospective (n=10) observational studies. Thirty-six studies were conducted in China (88%). The most common mentioned and reported medicine in this systematic review was corticosteroids (n=25), followed by Lopinavir (n=21) and oseltamivir (n=16). Conclusions: This is the first systematic review up to date related to the therapeutics used in COVID-19 patients. Only forty-one research articles on COVID-19 and therapeutics were found eligible to be included, most conducted in China, corticosteroid therapy was found to be the most used medicine in these studies.", "qid": 46, "docid": "w02mylsc", "rank": 16, "score": 0.8195930123329163}, {"content": "Title: Therapeutic Management of COVID-19 Patients: A systematic review Content: Abstract Background SARS-CoV-2 is the causative agent of COVID-19; that has been declared a global pandemic by the WHO in 2020. The COVID-19 treatment guidelines vary in each country, and yet there is no approved therapeutic for COVID-19. Aims of the study this review aimed to report any evidence of therapeutics used for the management of COVID-19 patients in clinical practice since the emergence of the virus. Methods A systematic review protocol was developed based on PRISMA Statement. Articles for review were selected from electronic databases (Embase, Medline and Google Scholar). Readily accessible peer-reviewed, full articles in English published from December 1st , 2019 to March 26th , 2020 were included. The search terms included combinations of: COVID, SARS-COV-2, glucocorticoids, convalescent plasma, antiviral and antibacterial. There were no restrictions on the type of study design eligible for inclusion. Results As of March 26th, 2020, of the initial manuscripts identified (n=449); forty-one studies were included. These consisted of clinical trials (n=3), case reports (n=7), case series (n=10), retrospective (n=11) and prospective (n=10) observational studies. Thirty-six studies were conducted in China (88%). The most commonly reported medicine in this systematic review was corticosteroids (n=25), followed by Lopinavir (n=21) and Oseltamivir (n=16). Conclusions This is the first systematic review to date related to the therapeutics used in COVID-19 patients. Only 41 research articles on COVID-19 and therapeutics were found eligible to be included, most conducted in China. Corticosteroid therapy was found to be the most studied medicine in the literature.", "qid": 46, "docid": "uxl8liil", "rank": 17, "score": 0.8191196918487549}, {"content": "Title: Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report Content: Background: Coronavirus disease 2019 (COVID-19) is associated with diffuse lung damage. Corticosteroids may modulate immune-mediated lung injury and reducing progression to respiratory failure and death. Methods: The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, adaptive, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of dexamethasone 6 mg given once daily for up to ten days vs. usual care alone. The primary outcome was 28-day mortality. Results: 2104 patients randomly allocated to receive dexamethasone were compared with 4321 patients concurrently allocated to usual care. Overall, 454 (21.6%) patients allocated dexamethasone and 1065 (24.6%) patients allocated usual care died within 28 days (age-adjusted rate ratio [RR] 0.83; 95% confidence interval [CI] 0.74 to 0.92; P<0.001). The proportional and absolute mortality rate reductions varied significantly depending on level of respiratory support at randomization (test for trend p<0.001): Dexamethasone reduced deaths by one-third in patients receiving invasive mechanical ventilation (29.0% vs. 40.7%, RR 0.65 [95% CI 0.51 to 0.82]; p<0.001), by one-fifth in patients receiving oxygen without invasive mechanical ventilation (21.5% vs. 25.0%, RR 0.80 [95% CI 0.70 to 0.92]; p=0.002), but did not reduce mortality in patients not receiving respiratory support at randomization (17.0% vs. 13.2%, RR 1.22 [95% CI 0.93 to 1.61]; p=0.14). Conclusions: In patients hospitalized with COVID-19, dexamethasone reduced 28-day mortality among those receiving invasive mechanical ventilation or oxygen at randomization, but not among patients not receiving respiratory support.", "qid": 46, "docid": "ocguwlam", "rank": 18, "score": 0.8176823854446411}, {"content": "Title: IL-6 Inhibitors in the Treatment of Serious COVID-19: A Promising Therapy? Content: At present, there are no proven agents for treatment of coronavirus disease (COVID-19). The available evidence has not allowed guidelines to clearly recommend any drugs outside the context of clinical trials. The novel coronavirus SARS-CoV-2 that causes COVID-19 invokes a hyperinflammatory state driven by multiple cells and mediators like interleukin (IL)-1, IL-6, IL-12, and IL-18, tumor necrosis factor alpha (TNF&#945;), etc. Considering the proven role of cytokine dysregulation in causing this hyperinflammation in the lungs with IL-6 being a key driver, particularly in seriously ill COVID-19 patients, it is crucial to further explore selective cytokine blockade with drugs like the IL-6 inhibitors tocilizumab, sarilumab, and siltuximab. These targeted monoclonal antibodies can dampen the downstream IL-6 signaling pathways, which can lead to decreased cell proliferation, differentiation, oxidative stress, exudation, and improve clinical outcomes in patients with evident features of cytokine-driven inflammation like persistent fever, dyspnea and elevated markers. Preliminary evidence has come for tocilizumab from some small studies, and interim analysis of a randomized controlled trial; the latter also being available for sarilumab. International guidelines do include IL-6 inhibitors as one of the options available for severe or critically ill patients. There has been increased interest in evaluating these drugs with a series of clinical trials being registered and conducted in different countries. The level of investigation though perhaps needs to be further intensified as there is a need to focus on therapeutic options that can prove to be 'life-saving' as the number of COVID-19 fatalities worldwide keeps increasing alarmingly. IL-6 inhibitors could be one such treatment option, with generation of more evidence and completion of a larger number of systematic studies.", "qid": 46, "docid": "z91sksce", "rank": 19, "score": 0.8173441886901855}, {"content": "Title: COVID-19: An Update on the Epidemiological, Clinical, Preventive and Therapeutic Evidence and Guidelines of Integrative Chinese-Western Medicine for the Management of 2019 Novel Coronavirus Disease Content: As of 22 February 2020, more than 77662 cases of confirmed COVID-19 have been documented globally with over 2360 deaths. Common presentations of confirmed cases include fever, fatigue, dry cough, upper airway congestion, sputum production, shortness of breath, myalgia/arthralgia with lymphopenia, prolonged prothrombin time, elevated C-reactive protein, and elevated lactate dehydrogenase. The reported severe/critical case ratio is approximately 7-10% and median time to intensive care admission is 9.5-10.5 days with mortality of around 1-2% varied geographically. Similar to outbreaks of other newly identified virus, there is no proven regimen from conventional medicine and most reports managed the patients with lopinavir/ritonavir, ribavirin, beta-interferon, glucocorticoid and supportive treatment with remdesivir undergoing clinical trial. In China, Chinese medicine is proposed as a treatment option by national and provincial guidelines with substantial utilization. We reviewed the latest national and provincial clinical guidelines, retrospective cohort studies, and case series regarding the treatment of COVID-19 by add-on Chinese medicine. We have also reviewed the clinical evidence generated from SARS and H1N1 management with hypothesized mechanisms and latest in silico findings to identify candidate Chinese medicines for the consideration of possible trials and management. Given the paucity of strongly evidence-based regimens, the available data suggest that Chinese medicine could be considered as an adjunctive therapeutic option in the management of COVID-19.", "qid": 46, "docid": "hgsqd42a", "rank": 20, "score": 0.8138365745544434}, {"content": "Title: COVID-19: An Update on the Epidemiological, Clinical, Preventive and Therapeutic Evidence and Guidelines of Integrative Chinese-Western Medicine for the Management of 2019 Novel Coronavirus Disease. Content: As of 22 February 2020, more than 77662 cases of confirmed COVID-19 have been documented globally with over 2360 deaths. Common presentations of confirmed cases include fever, fatigue, dry cough, upper airway congestion, sputum production, shortness of breath, myalgia/arthralgia with lymphopenia, prolonged prothrombin time, elevated C-reactive protein, and elevated lactate dehydrogenase. The reported severe/critical case ratio is approximately 7-10% and median time to intensive care admission is 9.5-10.5 days with mortality of around 1-2% varied geographically. Similar to outbreaks of other newly identified virus, there is no proven regimen from conventional medicine and most reports managed the patients with lopinavir/ritonavir, ribavirin, beta-interferon, glucocorticoid and supportive treatment with remdesivir undergoing clinical trial. In China, Chinese medicine is proposed as a treatment option by national and provincial guidelines with substantial utilization. We reviewed the latest national and provincial clinical guidelines, retrospective cohort studies, and case series regarding the treatment of COVID-19 by add-on Chinese medicine. We have also reviewed the clinical evidence generated from SARS and H1N1 management with hypothesized mechanisms and latest in silico findings to identify candidate Chinese medicines for the consideration of possible trials and management. Given the paucity of strongly evidence-based regimens, the available data suggest that Chinese medicine could be considered as an adjunctive therapeutic option in the management of COVID-19.", "qid": 46, "docid": "gizxnw4n", "rank": 21, "score": 0.8138365745544434}, {"content": "Title: IL-6 Inhibitors in the Treatment of Serious COVID-19: A Promising Therapy? Content: At present, there are no proven agents for treatment of coronavirus disease (COVID-19). The available evidence has not allowed guidelines to clearly recommend any drugs outside the context of clinical trials. The novel coronavirus SARS-CoV-2 that causes COVID-19 invokes a hyperinflammatory state driven by multiple cells and mediators like interleukin (IL)-1, IL-6, IL-12, and IL-18, tumor necrosis factor alpha (TNF\u03b1), etc. Considering the proven role of cytokine dysregulation in causing this hyperinflammation in the lungs with IL-6 being a key driver, particularly in seriously ill COVID-19 patients, it is crucial to further explore selective cytokine blockade with drugs like the IL-6 inhibitors tocilizumab, sarilumab, and siltuximab. These targeted monoclonal antibodies can dampen the downstream IL-6 signaling pathways, which can lead to decreased cell proliferation, differentiation, oxidative stress, exudation, and improve clinical outcomes in patients with evident features of cytokine-driven inflammation like persistent fever, dyspnea and elevated markers. Preliminary evidence has come for tocilizumab from some small studies, and interim analysis of a randomized controlled trial; the latter also being available for sarilumab. International guidelines do include IL-6 inhibitors as one of the options available for severe or critically ill patients. There has been increased interest in evaluating these drugs with a series of clinical trials being registered and conducted in different countries. The level of investigation though perhaps needs to be further intensified as there is a need to focus on therapeutic options that can prove to be \u2018life-saving\u2019 as the number of COVID-19 fatalities worldwide keeps increasing alarmingly. IL-6 inhibitors could be one such treatment option, with generation of more evidence and completion of a larger number of systematic studies.", "qid": 46, "docid": "s5lailkp", "rank": 22, "score": 0.8127002716064453}, {"content": "Title: The use of corticosteroids for COVID-19 infection Content: The SARS-CoV-2 pandemic is continuing relentlessly in many parts of the world and has resulted in the outpouring of literature on various aspects of the infection, including studies and recommendations regarding the optimal treatment of infected patients. Not surprisingly, the use of corticosteroids in the management of such patients has featured prominently in many of these publications. There is considerable debate in the literature as to the likely benefits, as well as the potential detrimental effects of corticosteroid therapy in general viral respiratory infections and, in particular, COVID-19 infections. While the definitive answer may need to await the results of ongoing randomised, controlled trials recent studies suggest that corticosteroid use in COVID-19 cases with hypoxaemia may benefit from low-dose corticosteroid therapy.", "qid": 46, "docid": "y6fvjsjl", "rank": 23, "score": 0.8125571012496948}, {"content": "Title: Initial experience with short-course corticosteroids in a small cohort of adults with severe COVID-19 in a tertiary care hospital in India Content: Abstract Severe COVID 19 disease is associated with high morbidity and mortality with limited therapeutic options. The role of glucocorticoids in treatment of COVID 19 has been riddled with controversy. The study site has been using glucocorticoids in patients with severe COVID 19 since the first few patients of COVID 19 that were admitted. In the initial cohort of 7 patients with severe COVID disease, use of methylprednisolone in a dose of 30 mg twice daily was associated with rapid improvement in oxygenation and decline in CRP levels. While six patients made a complete clinical recovery, one patient died. There were no secondary infections.", "qid": 46, "docid": "ma6gmwgl", "rank": 24, "score": 0.8122298121452332}, {"content": "Title: Letter to the editor: efficacy of different methods of combination regimen administrations including dexamethasone, intravenous immunoglobulin, and interferon-beta to treat critically ill COVID-19 patients: a structured summary of a study protocol for a randomized controlled trial Content: OBJECTIVES: There is little information about Coronavirus Disease 2019 (COVID-19) management for critically ill patients. Most of these patients develop acute respiratory distress syndrome (ARDS) due to excessive inflammatory response and the ensuing cytokine storm. Anti-inflammatory drugs including corticosteroids can be used to effectively reduce the effect of this cytokine storm and lung damage. However, corticosteroids can have side effects, so simultaneous administration of immunoglobulin (IV-IG) and interferon-beta can help manage treatment using corticosteroids. Therefore, we designed a trial to test our hypothesis that early administration of dexamethasone in combination with IV-IG and interferon-beta can reduce the effect of the cytokine storm in critically ill patients COVID-19. TRIAL DESIGN: A phase two multi-center randomized controlled trial (RCT) with three parallel arms (1:1:1 ratio). PARTICIPANTS: They will be hospitalized patients with severe COVID-19 who have positive RT-PCR test and have blood oxygen saturation levels (SpO2) less than 90% and respiratory rate higher than 24 per minute or have involvement of more than 50% of their lung when viewed using computed tomography (CT)-scan. The age range of patients will be 18-70 years old. EXCLUSION CRITERIA: the need for intubation; allergy, intolerance, or contraindication to any study drug including dexamethasone, IV-IG, and interferon-beta; pregnancy or lactation; known HIV positive or active hepatitis B or C. The study will be conducted in several hospitals of the Golestan province, Iran. INTERVENTION AND COMPARATOR: The study subjects will be randomly allocated to three treatment arms: two experimental groups (two arms: Intervention 1 and Intervention 2) and one Control Group, which will be matched for age and sex using frequency matching method. Each eligible patient in the control arm will receive the standard treatment for COVID-19 based on WHO guidelines and the Ministry of the Health and Medical Education (MOHME) of Iran. Each patient in the Intervention Group 1 will receive the standard treatment for COVID-19 and dexamethasone, at the first 24 hours' time of admission. The intervention begins with the administration of dexamethasone based on the SpO2 levels. If the level of SpO2 does not improve after 24 hours, IV-IG (400 mg/kg once daily for 5 days) and interferon-beta (7 doses every other day) will be prescribed along with dexamethasone administration. In Intervention Group 2, the administration of dexamethasone will be started within the first 24 hours' time of admission and will be continued for 48-72 hours and then the SpO2 level will be checked. Then, if the level of SpO2 has not improved after that time, IV-IG and interferon-beta will be prescribed as the same dosage as Group 1. If the percentages of the SpO2 level are between 85 and 90/ 80 and 85/ 75 and 80/ less than 75, the dosages will be 4 mg every 12 hours/ 4 mg every 8 hours/ 8 mg every 12 hours/ 8 mg every 8 hours, respectively. According to the WHO recommendation, all participants will have the best available supportive care with full monitoring. MAIN OUTCOMES: Primary: An increase in the SpO2 level to reach more than 90% in each case, which will be assessed by the oximeter. Secondary: The duration of hospital stays; intubation status and the percentage of patients who are free of mechanical ventilation; the mortality rates during hospitalization and one month after the admission time. RANDOMISATION: Participants will be allocated into either control or intervention groups with a 1:1:1 allocation ratio using a computer random number generator to generate a table of random numbers for simple randomization. BLINDING (MASKING): The project's principal investigator (PI) is unblinded. However, the PI will not analyse the data and interpret the results. An unblinded researcher (a pharmacist) will cover the drug's bottles with aluminium foil and prepare them interventions and control drugs in a syringe with a code so that patients are blinded. This person will have no patients contact. The staff and nurses, caring for the patients, will be unblinded for each study group due to the nature of this study. The staff that take outcome measurements will be blinded. The laboratory technicians will also be blinded as well as the statistical team. These study statisticians will have access to coded data and will analyse the data labelled as group X, group Y, and group Z. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The target sample size will be 105 critically ill COVID-19 patients, who will be allocated randomly to the three trial arms with 35 patients in each group. TRIAL STATUS: Recruitment is ongoing. The study began on April 18 2020 and will be completed June 19 2020. This summary describes protocol version 1; April 2 2020. TRIAL REGISTRATION: https://www.irct.ir/. Identifier: IRCT20120225009124N4 version 1; Registration date: April 2 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The full protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.", "qid": 46, "docid": "mapu4r1z", "rank": 25, "score": 0.8109323978424072}, {"content": "Title: Therapeutic potential of ciclesonide inahalation for COVID-19 pneumonia: Report of three cases Content: No specific and effective anti-viral treatment has been approved for COVID-19 so far. Systemic corticosteroid has been sometimes administered to severe infectious diseases combined with the specific treatment. However, as lack of the specific anti-SARS-CoV-2 drug, systemic steroid treatment has not been recommended for COVID-19. We report here three cases of the COVID-19 pneumonia successfully treated with ciclesonide inhalation. Rationale of the treatment is to mitigate the local inflammation with inhaled steroid that stays in the lung and to inhibit proliferation of the virus by antiviral activity. Larger and further studies are warranted to confirm the result of these cases.", "qid": 46, "docid": "3mxfew35", "rank": 26, "score": 0.810870885848999}, {"content": "Title: COVID-19-associated ARDS treated with DEXamethasone (CoDEX): Study design and rationale for a randomized trial. Content: OBJECTIVES: The infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) spreads worldwide and is considered a pandemic. The most common manifestation of SARS-CoV2 infection (Coronavirus disease 2019 - COVID-19) is viral pneumonia with varying degrees of respiratory compromise and up to 40% of hospitalized patients might develop Acute Respiratory Distress Syndrome (ARDS). Several clinical trials evaluated the role of corticosteroids in non-COVID-19 ARDS with conflicting results. We designed a trial to evaluate the effectiveness of early intravenous dexamethasone administration on the number of days alive and free of mechanical ventilation within 28 days after randomization in adult patients with moderate or severe ARDS due to confirmed or probable COVID-19. METHODS: This is a pragmatic, prospective, randomized, stratified, multicenter, open-label, controlled trial including 350 patients with early-onset (less than 48h before randomization) moderate or severe ARDS, defined by the Berlin criteria, due to COVID-19. Eligible patients will be randomly allocated to either standard treatment plus dexamethasone (intervention group) or standard treatment without dexamethasone (control group). Patients in the intervention group will receive dexamethasone 20mg IV once daily for 5 days, followed by dexamethasone 10mg IV once daily for additional 5 days or until Intensive Care Unit (ICU) discharge, whichever occurs first. The primary outcome is ventilator-free days within 28 days after randomization, defined as days alive and free from invasive mechanical ventilation. Secondary outcomes are all-cause mortality rates at day 28, evaluation of the clinical status at day 15 assessed with a 6-level ordinal scale, mechanical ventilation duration from randomization to day 28, Sequential Organ Failure Assessment (SOFA) Score evaluation at 48h, 72h and 7 days and ICU-free days within 28. ETHICS AND DISSEMINATION: This trial was approved by the Brazilian National Committee of Ethics in Research (Comissao Nacional de Etica em Pesquisa - CONEP) and National Health Surveillance Agency (ANVISA). An independent data monitoring committee will perform interim analyses and evaluate adverse events throughout the trial. Results will be submitted for publication after enrolment and follow-up are complete.", "qid": 46, "docid": "dgy7qbl5", "rank": 27, "score": 0.8101671934127808}, {"content": "Title: Letter to the editor: efficacy of different methods of combination regimen administrations including dexamethasone, intravenous immunoglobulin, and interferon-beta to treat critically ill COVID-19 patients: a structured summary of a study protocol for a randomized controlled trial Content: OBJECTIVES: There is little information about Coronavirus Disease 2019 (COVID-19) management for critically ill patients. Most of these patients develop acute respiratory distress syndrome (ARDS) due to excessive inflammatory response and the ensuing cytokine storm. Anti-inflammatory drugs including corticosteroids can be used to effectively reduce the effect of this cytokine storm and lung damage. However, corticosteroids can have side effects, so simultaneous administration of immunoglobulin (IV-IG) and interferon-beta can help manage treatment using corticosteroids. Therefore, we designed a trial to test our hypothesis that early administration of dexamethasone in combination with IV-IG and interferon-beta can reduce the effect of the cytokine storm in critically ill patients COVID-19. TRIAL DESIGN: A phase two multi-center randomized controlled trial (RCT) with three parallel arms (1:1:1 ratio). PARTICIPANTS: They will be hospitalized patients with severe COVID-19 who have positive RT-PCR test and have blood oxygen saturation levels (SpO(2)) less than 90% and respiratory rate higher than 24 per minute or have involvement of more than 50% of their lung when viewed using computed tomography (CT)-scan. The age range of patients will be 18-70 years old. Exclusion criteria: the need for intubation; allergy, intolerance, or contraindication to any study drug including dexamethasone, IV-IG, and interferon-beta; pregnancy or lactation; known HIV positive or active hepatitis B or C. The study will be conducted in several hospitals of the Golestan province, Iran. INTERVENTION AND COMPARATOR: The study subjects will be randomly allocated to three treatment arms: two experimental groups (two arms: Intervention 1 and Intervention 2) and one Control Group, which will be matched for age and sex using frequency matching method. Each eligible patient in the control arm will receive the standard treatment for COVID-19 based on WHO guidelines and the Ministry of the Health and Medical Education (MOHME) of Iran. Each patient in the Intervention Group 1 will receive the standard treatment for COVID-19 and dexamethasone, at the first 24 hours\u2019 time of admission. The intervention begins with the administration of dexamethasone based on the SpO(2) levels. If the level of SpO(2) does not improve after 24 hours, IV-IG (400 mg/kg once daily for 5 days) and interferon-beta (7 doses every other day) will be prescribed along with dexamethasone administration. In Intervention Group 2, the administration of dexamethasone will be started within the first 24 hours\u2019 time of admission and will be continued for 48-72 hours and then the SpO(2) level will be checked. Then, if the level of SpO(2) has not improved after that time, IV-IG and interferon-beta will be prescribed as the same dosage as Group 1. If the percentages of the SpO(2) level are between 85 and 90/ 80 and 85/ 75 and 80/ less than 75, the dosages will be 4 mg every 12 hours/ 4 mg every 8 hours/ 8 mg every 12 hours/ 8 mg every 8 hours, respectively. According to the WHO recommendation, all participants will have the best available supportive care with full monitoring. MAIN OUTCOMES: Primary: An increase in the SpO(2) level to reach more than 90% in each case, which will be assessed by the oximeter. Secondary: The duration of hospital stays; intubation status and the percentage of patients who are free of mechanical ventilation; the mortality rates during hospitalization and one month after the admission time. RANDOMISATION: Participants will be allocated into either control or intervention groups with a 1:1:1 allocation ratio using a computer random number generator to generate a table of random numbers for simple randomization. BLINDING (MASKING): The project's principal investigator (PI) is unblinded. However, the PI will not analyse the data and interpret the results. An unblinded researcher (a pharmacist) will cover the drug\u2019s bottles with aluminium foil and prepare them interventions and control drugs in a syringe with a code so that patients are blinded. This person will have no patients contact. The staff and nurses, caring for the patients, will be unblinded for each study group due to the nature of this study. The staff that take outcome measurements will be blinded. The laboratory technicians will also be blinded as well as the statistical team. These study statisticians will have access to coded data and will analyse the data labelled as group X, group Y, and group Z. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The target sample size will be 105 critically ill COVID-19 patients, who will be allocated randomly to the three trial arms with 35 patients in each group. TRIAL STATUS: Recruitment is ongoing. The study began on April 18 2020 and will be completed June 19 2020. This summary describes protocol version 1; April 2 2020. TRIAL REGISTRATION: https://www.irct.ir/. Identifier: IRCT20120225009124N4 version 1; Registration date: April 2 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The full protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.", "qid": 46, "docid": "t9c26eld", "rank": 28, "score": 0.8095927238464355}, {"content": "Title: Routine antiemetic prophylaxis with dexamethasone during COVID-19: Should oncologists reconsider? Content: The ongoing pandemic caused by severe acute respiratory syndrome (SARS) coronavirus type 2 (SARS-CoV-2, also known as COVID-19) has caused unprecedented strain on the global healthcare system, causing thousands of deaths worldwide. Patients with underlying conditions such as cancer are at substantial risk of acquiring and dying from this novel coronavirus. Numerous reports have shown that infection with SARS-CoV-2 causes depletion of B- and T-lymphocytes, including CD4 and CD8 T-cells, and is associated with severe illness and death and that patients with higher lymphocyte levels may have better outcomes. Dexamethasone, a widely prescribed antiemetic for acute and delayed nausea and vomiting from a variety of cancer drugs, causes B and T cell depletion, which may augment immunosuppression. Since it seems that lymphocytes are vital in the immune response to novel coronavirus, oncologists should reconsider the routine use of prophylactic dexamethasone in uninfected patients, to avoid inducing lymphopenia, which may increase risk of infection or lead to inferior outcomes if a cancer patient subsequently becomes infected. Since many cancer drugs and malignant diseases inherently cause lymphopenia, further reduction of lymphocytes with dexamethasone should be avoided if possible and if safe and effective alternative antiemetics are available during the COVID-19 crisis.", "qid": 46, "docid": "pec5ezyy", "rank": 29, "score": 0.8094017505645752}, {"content": "Title: Heparin as a Therapy for COVID-19: Current Evidence and Future Possibilities Content: Coronavirus Disease 2019 (COVID-19), the clinical syndrome associated with infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has impacted nearly every country in the world. Despite an unprecedented focus of scientific investigation, there is a paucity of evidence-based pharmacotherapies against this disease. Due to this lack of data-driven treatment strategies, broad variations in practice patterns have emerged. Observed hypercoagulability in COVID-19 patients has created debate within the critical care community on the therapeutic utility of heparin. We seek to provide an overview of the data supporting the therapeutic use of heparin, both unfractionated and low molecular weight, as an anticoagulant for the treatment of SARS-CoV-2 infection. Additionally, we review preclinical evidence establishing biological plausibility for heparin and synthetic heparin-like drugs as therapies for COVID-19 through anti-viral and anti-inflammatory effects. Finally, we discuss known adverse effects and theoretical off-target effects that may temper enthusiasm for the adoption of heparin as a therapy in COVID-19 without confirmatory prospective randomized controlled trials. Despite previous failures of anticoagulants in critical illness, plausibility of heparin for COVID-19 is sufficiently robust to justify urgent randomized controlled trials to determine the safety and effectiveness of this therapy.", "qid": 46, "docid": "qywsgpia", "rank": 30, "score": 0.8072630763053894}, {"content": "Title: Heparin as a Therapy for COVID-19: Current Evidence and Future Possibilities. Content: Coronavirus Disease 2019 (COVID-19), the clinical syndrome associated with infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has impacted nearly every country in the world. Despite an unprecedented focus of scientific investigation, there is a paucity of evidence-based pharmacotherapies against this disease. Due to this lack of data-driven treatment strategies, broad variations in practice patterns have emerged. Observed hypercoagulability in COVID-19 patients has created debate within the critical care community on the therapeutic utility of heparin. We seek to provide an overview of the data supporting the therapeutic use of heparin, both unfractionated and low molecular weight, as an anticoagulant for the treatment of SARS-CoV-2 infection. Additionally, we review preclinical evidence establishing biological plausibility for heparin and synthetic heparin-like drugs as therapies for COVID-19 through anti-viral and anti-inflammatory effects. Finally, we discuss known adverse effects and theoretical off-target effects that may temper enthusiasm for the adoption of heparin as a therapy in COVID-19 without confirmatory prospective randomized controlled trials. Despite previous failures of anticoagulants in critical illness, plausibility of heparin for COVID-19 is sufficiently robust to justify urgent randomized controlled trials to determine the safety and effectiveness of this therapy.", "qid": 46, "docid": "ixnyny8d", "rank": 31, "score": 0.8072630763053894}, {"content": "Title: Towards treatment planning of COVID-19: Rationale and hypothesis for the use of multiple immunosuppressive agents: anti-antibodies, immunoglobulins, and corticosteroids Content: Abstract The novel coronavirus, SARS-CoV2, can cause a potentially fatal disease, COVID-19, in humans. Here, we will provide an overview of therapeutic options for COVID-19. Plasma from patients recovered from COVID-19 that contains antibodies against SARS-CoV2 has shown promising results in patients with severe COVID-19. Also, IVIG, combined with moderate-dose of corticosteroids, might improve patient outcomes. Evidence links COVID-19 to variable degrees of inflammation. Studies show that the use of corticosteroids might accelerate recovery from COVID-19. There are, however, no controlled clinical trials that show whether the use of corticosteroids can reduce COVID-19-related death. Also, the pro-inflammatory cytokine IL6 is the best-documented cytokine in COVID-19 correlated with severity, criticality, viral load, and prognosis of patients with COVID-19. Tocilizumab, a monoclonal antibody against IL6, could confer clinical benefit in patients with high IL6 levels. Essential elements that process SARS-CoV2 cell entry and specific characteristics that allow SARS-CoV2 to escape the immune system have the potential as targets for COVID-19 therapy.", "qid": 46, "docid": "2705en59", "rank": 32, "score": 0.806647539138794}, {"content": "Title: Therapeutic potential of ciclesonide inahalation for COVID-19 pneumonia: Report of three cases Content: Abstract No specific and effective anti-viral treatment has been approved for COVID-19 so far. Systemic corticosteroid has been sometimes administered to severe infectious diseases combined with the specific treatment. However, as lack of the specific anti-SARS-CoV-2 drug, systemic steroid treatment has not been recommended for COVID-19. We report here three cases of the COVID-19 pneumonia successfully treated with ciclesonide inhalation. Rationale of the treatment is to mitigate the local inflammation with inhaled steroid that stays in the lung and to inhibit proliferation of the virus by antiviral activity. Larger and further studies are warranted to confirm the result of these cases.", "qid": 46, "docid": "uuor5hck", "rank": 33, "score": 0.8062347769737244}, {"content": "Title: Pharmacotherapy in COVID-19; A narrative review for emergency providers Content: INTRODUCTION: The COVID-19 pandemic has been particularly challenging due to a lack of established therapies and treatment guidelines. With the rapid transmission of disease, even the off-label use of available therapies has been impeded by limited availability. Several antivirals, antimalarials, and biologics are being considered for treatment at this time. The purpose of this literature review is to synthesize the available information regarding treatment options for COVID-19 and serve as a resource for health care professionals. OBJECTIVES: This narrative review was conducted to summarize the effectiveness of current therapy options for COVID-19 and address the controversial use of non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs). PubMed and SCOPUS were queried using a combination of the keywords \"COVID 19,\" \"SARS-CoV-2,\" and \"treatment.\" All types of studies were evaluated including systematic reviews, case-studies, and clinical guidelines. DISCUSSION: There are currently no therapeutic drugs available that are directly active against SARS-CoV-2; however, several antivirals (remdesivir, favipiravir) and antimalarials (chloroquine, hydroxychloroquine) have emerged as potential therapies. Current guidelines recommend combination treatment with hydroxychloroquine/azithromycin or chloroquine, if hydroxychloroquine is unavailable, in patients with moderate disease, although these recommendations are based on limited evidence. Remdesivir and convalescent plasma may be considered in critical patients with respiratory failure; however, access to these therapies may be limited. Interleukin-6 (IL-6) antagonists may be used in patients who develop evidence of cytokine release syndrome (CRS). Corticosteroids should be avoided unless there is evidence of refractory septic shock, acute respiratory distress syndrome (ARDS), or another compelling indication for their use. ACE inhibitors and ARBs should not be discontinued at this time and ibuprofen may be used for fever. CONCLUSION: There are several ongoing clinical trials that are testing the efficacy of single and combination treatments with the drugs mentioned in this review and new agents are under development. Until the results of these trials become available, we must use the best available evidence for the prevention and treatment of COVID-19. Additionally, we can learn from the experiences of healthcare providers around the world to combat this pandemic.", "qid": 46, "docid": "4ehhtkfn", "rank": 34, "score": 0.8058516979217529}, {"content": "Title: Corticosteroid therapy in ENT in the context of the COVID-19 pandemic Content: ABSTRACT This consensus statement about the indications and modalities of corticosteroid treatment in the context of the COVID-19 pandemic was jointly written by experts from the French Association of Otology and Oto-Neurology (AFON) and from the French Society of Otorhinolaryngology, Head and Neck Surgery (SFORL). There is currently not enough data in favour of danger or benefit from corticosteroids in COVID-19, so until this matter is resolved it is advisable to limit their indications to the most serious clinical pictures for which it is well established that this type of treatment has a positive impact on the progression of symptoms. In Grade V and VI Bell's palsy according to the House-Brackmann grading system, a week\u2019s course of oral corticosteroids is recommended. Corticosteroid therapy is also recommended in cases of sudden hearing loss of more than 60 dB, either in the form of intratympanic injections or a week\u2019s course of oral medication. In rhinology, there is no indication for systemic corticosteroid therapy in the current situation. However, patients are advised to continue with their local corticosteroid therapy in the form of a nasal spray or by inhalation. Treatments with corticosteroid nasal sprays can still be prescribed if there is no alternative.", "qid": 46, "docid": "wtnol2tl", "rank": 35, "score": 0.8055257797241211}, {"content": "Title: Towards treatment planning of COVID-19: Rationale and hypothesis for the use of multiple immunosuppressive agents: Anti-antibodies, immunoglobulins, and corticosteroids Content: The novel coronavirus, SARS-CoV2, can cause a potentially fatal disease, COVID-19, in humans. Here, we will provide an overview of therapeutic options for COVID-19. Plasma from patients recovered from COVID-19 that contains antibodies against SARS-CoV2 has shown promising results in patients with severe COVID-19. Also, IVIG, combined with moderate-dose of corticosteroids, might improve patient outcomes. Evidence links COVID-19 to variable degrees of inflammation. Studies show that the use of corticosteroids might accelerate recovery from COVID-19. There are, however, no controlled clinical trials that show whether the use of corticosteroids can reduce COVID-19-related death. Also, the pro-inflammatory cytokine IL6 is the best-documented cytokine in COVID-19 correlated with severity, criticality, viral load, and prognosis of patients with COVID-19. Tocilizumab, a monoclonal antibody against IL6, could confer clinical benefit in patients with high IL6 levels. Essential elements that process SARS-CoV2 cell entry and specific characteristics that allow SARS-CoV2 to escape the immune system have the potential as targets for COVID-19 therapy.", "qid": 46, "docid": "glmni128", "rank": 36, "score": 0.805328905582428}, {"content": "Title: Pharmacotherapy in COVID-19; A narrative review for emergency providers Content: INTRODUCTION: The COVID-19 pandemic has been particularly challenging due to a lack of established therapies and treatment guidelines. With the rapid transmission of disease, even the off-label use of available therapies has been impeded by limited availability. Several antivirals, antimalarials, and biologics are being considered for treatment at this time. The purpose of this literature review is to synthesize the available information regarding treatment options for COVID-19 and serve as a resource for health care professionals. OBJECTIVES: This narrative review was conducted to summarize the effectiveness of current therapy options for COVID-19 and address the controversial use of non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs). PubMed and SCOPUS were queried using a combination of the keywords \u201cCOVID 19,\u201d \u201cSARS-CoV-2,\u201d and \u201ctreatment.\u201d All types of studies were evaluated including systematic reviews, case-studies, and clinical guidelines. DISCUSSION: There are currently no therapeutic drugs available that are directly active against SARS-CoV-2; however, several antivirals (remdesivir, favipiravir) and antimalarials (chloroquine, hydroxychloroquine) have emerged as potential therapies. Current guidelines recommend combination treatment with hydroxychloroquine/azithromycin or chloroquine, if hydroxychloroquine is unavailable, in patients with moderate disease, although these recommendations are based on limited evidence. Remdesivir and convalescent plasma may be considered in critical patients with respiratory failure; however, access to these therapies may be limited. Interleukin-6 (IL-6) antagonists may be used in patients who develop evidence of cytokine release syndrome (CRS). Glucocorticoids should be avoided unless there is evidence of refractory septic shock, acute respiratory distress syndrome (ARDS), or another compelling indication for their use. ACE inhibitors and ARBs should not be discontinued at this time and ibuprofen may be used for fever. CONCLUSION: There are several ongoing clinical trials that are testing the efficacy of single and combination treatments with the drugs mentioned in this review and new agents are under development. Until the results of these trials become available, we must use the best available evidence for the prevention and treatment of COVID-19. Additionally, we can learn from the experiences of healthcare providers around the world to combat this pandemic.", "qid": 46, "docid": "9ryu9ady", "rank": 37, "score": 0.8040018677711487}, {"content": "Title: COVID-19 and Headache Medicine: A Narrative Review of Non-Steroidal Anti-Inflammatory Drug (NSAID) and Corticosteroid Use Content: OBJECTIVE: To summarize the current literature on non-steroidal anti-inflammatory drug and corticosteroid use during the coronavirus disease 2019 (COVID-19) pandemic, recognizing that these are commonly used treatments in the field of headache medicine. BACKGROUND: The use of non-steroidal anti-inflammatory drugs and corticosteroids in patients during the COVID-19 pandemic has been a controversial topic within the medical community and international and national health organizations. Lay press and social media outlets have circulated opinions on this topic despite the fact that the evidence for or against the use of these medications is sparse. In the field of headache medicine, these medications are used commonly and both patients and clinicians may have questions or hesitations pertaining to their use during the COVID-19 pandemic. METHODS: A detailed search of the scientific and popular literature was performed. RESULTS: There is limited literature pertaining to the safety of non-steroidal anti-inflammatory drugs and corticosteroids during the COVID-19 pandemic. To date, there are no clear scientific data that preclude the use of non-steroidal anti-inflammatory drugs in the general population who may acquire COVID-19 or in those acutely infected with the virus. Several health organizations have concluded that treatment with corticosteroids during active infection should be avoided due to concerns of prolonged viral shedding in the respiratory tract and the lack of survival benefit based on the data from past coronaviruses and influenza virus; specific exceptions exist including treatment for underlying asthma or chronic obstructive pulmonary disease, septic shock, and acute respiratory distress syndrome. CONCLUSION: Scientific information regarding the COVID-19 pandemic is constantly evolving, and limited or contradictory information can lead to confusion for both patients and clinicians. It is recommended that prior to prescribing non-steroidal anti-inflammatory drugs and steroids for the treatment of headache, clinicians have open discussions with their patients about the potential risks and benefits of using these medications during the COVID-19 pandemic. This manuscript summarizes the currently available evidence and understanding about these risks and benefits to help clinicians navigate such discussions.", "qid": 46, "docid": "i44s4vqr", "rank": 38, "score": 0.8038856983184814}, {"content": "Title: Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review Content: Importance: The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection. Observations: No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19. Conclusions and Relevance: The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.", "qid": 46, "docid": "yth9hh5q", "rank": 39, "score": 0.8036236763000488}, {"content": "Title: Role of adjunctive treatment strategies in COVID-19 and a review of international and national clinical guidelines Content: The coronavirus disease (COVID-19) pandemic has led to a global struggle to cope with the sheer numbers of infected persons, many of whom require intensive care support or eventually succumb to the illness. The outbreak is managed by a combination of disease containment via public health measures and supportive care for those who are affected. To date, there is no specific anti-COVID-19 treatment. However, the urgency to identify treatments that could turn the tide has led to the emergence of several investigational drugs as potential candidates to improve outcome, especially in the severe to critically ill. While many of these adjunctive drugs are being investigated in clinical trials, professional bodies have attempted to clarify the setting where the use of these drugs may be considered as off-label or compassionate use. This review summarizes the clinical evidence of investigational adjunctive treatments used in COVID-19 patients as well as the recommendations of their use from guidelines issued by international and national organizations in healthcare.", "qid": 46, "docid": "4ea77hqx", "rank": 40, "score": 0.8034136295318604}, {"content": "Title: Expanded Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) as a Therapeutic Strategy in Managing Critically Ill COVID-19 Patients: The Case for Compassionate Use Content: COVID-19 has affected the United States leading to a national emergency with health care and economic impact, propelling the country into a recession with disrupted lifestyles not seen in recent history. COVID-19 is a serious illness leading to multiple deaths in various countries including the United States. Several million Americans satisfy the Center for Disease Control and Prevention (CDC) criteria for being high risk. Unfortunately, the available supply of medical beds and equipment for mechanical ventilation are much less than is projected to be needed. The World Health Organization (WHO) and multiple agencies led by the CDC in the United States have attempted to organize intensive outbreak investigation programs utilizing appropriate preventive measures, evaluation, and treatment. The clinical spectrum of COVID-19 varies from asymptomatic forms to conditions encompassing multiorgan and systemic manifestations in terms of septic shock, and multiple organ dysfunction (MOD) syndromes. The presently approved treatments are supportive but not curative for the disease. There are multiple treatments being studied. These include vaccines, medications Remdesivir and hydroxychloroquine and potentially combination therapy. Finally, expanded umbilical cord mesenchymal stem cells or (UC-MSCs) may have a role and are being studied. The cure of COVID-19 is essentially dependent on the patients' own immune system. When the immune system is over activated in an attempt to kill the virus, this can lead to the production of a large number of inflammatory factors, resulting in severe cytokine storm. The cytokine storm may induce organ damage followed by the edema, dysfunction of air exchange, acute respiratory distress syndrome (ARDS), acute cardiac injury, and secondary infection, which may lead to death. Thus, at this point, the avoidance of the cytokine storm may be the key for the treatment of HCOV-19 infected patients.In China, where there was limited availability of effective modalities to manage COVID-19 several patients were treated with expanded UC-MSCs. Additionally, the Italian College of Anesthesia, Analgesia, Resuscitation and Intensive Care have reported guidelines to treat coronavirus patients with stem cells in the hope of decreasing the number of patients going to the ICU, and, also relatively quickly getting them out of ICU. In this manuscript, we describe the urgent need for various solutions, pathogenesis of coronavirus and the clinical evidence for treatment of COVID-19 with stem cells. The limited but emerging evidence regarding UC MSC in managing COVID-19 suggests that it might be considered for compassionate use in critically ill patients to reduce morbidity and mortality in the United States. The administration and Coronavirus Task Force might wish to approach the potential of expanded UC-MSCs as an evolutionary therapeutic strategy in managing COVID-19 illness with a 3-pronged approach: If proven safe and effective on a specific and limited basis 1. Minimize regulatory burden by all agencies so that critically ill COVID-19 patients will have access regardless of their financial circumstance.2. Institute appropriate safeguards to avoid negative consequences from unscrupulous actors.3. With proper informed consent from patients or proxy when necessary, and subject to accumulation of data in that cohort, allow the procedure to be initiated in critically ill patients who are not responding to conventional therapies.KEY WORDS: Coronavirus, COVID-19, cytokine storm, multiorgan failure, expanded umbilical cord mesenchymal stem cells.", "qid": 46, "docid": "aplbtvfd", "rank": 41, "score": 0.8033089637756348}, {"content": "Title: Expanded Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) as a Therapeutic Strategy in Managing Critically Ill COVID-19 Patients: The Case for Compassionate Use. Content: COVID-19 has affected the United States leading to a national emergency with health care and economic impact, propelling the country into a recession with disrupted lifestyles not seen in recent history. COVID-19 is a serious illness leading to multiple deaths in various countries including the United States. Several million Americans satisfy the Center for Disease Control and Prevention (CDC) criteria for being high risk. Unfortunately, the available supply of medical beds and equipment for mechanical ventilation are much less than is projected to be needed. The World Health Organization (WHO) and multiple agencies led by the CDC in the United States have attempted to organize intensive outbreak investigation programs utilizing appropriate preventive measures, evaluation, and treatment. The clinical spectrum of COVID-19 varies from asymptomatic forms to conditions encompassing multiorgan and systemic manifestations in terms of septic shock, and multiple organ dysfunction (MOD) syndromes. The presently approved treatments are supportive but not curative for the disease. There are multiple treatments being studied. These include vaccines, medications Remdesivir and hydroxychloroquine and potentially combination therapy. Finally, expanded umbilical cord mesenchymal stem cells or (UC-MSCs) may have a role and are being studied. The cure of COVID-19 is essentially dependent on the patients' own immune system. When the immune system is over activated in an attempt to kill the virus, this can lead to the production of a large number of inflammatory factors, resulting in severe cytokine storm. The cytokine storm may induce organ damage followed by the edema, dysfunction of air exchange, acute respiratory distress syndrome (ARDS), acute cardiac injury, and secondary infection, which may lead to death. Thus, at this point, the avoidance of the cytokine storm may be the key for the treatment of HCOV-19 infected patients.In China, where there was limited availability of effective modalities to manage COVID-19 several patients were treated with expanded UC-MSCs. Additionally, the Italian College of Anesthesia, Analgesia, Resuscitation and Intensive Care have reported guidelines to treat coronavirus patients with stem cells in the hope of decreasing the number of patients going to the ICU, and, also relatively quickly getting them out of ICU. In this manuscript, we describe the urgent need for various solutions, pathogenesis of coronavirus and the clinical evidence for treatment of COVID-19 with stem cells. The limited but emerging evidence regarding UC MSC in managing COVID-19 suggests that it might be considered for compassionate use in critically ill patients to reduce morbidity and mortality in the United States. The administration and Coronavirus Task Force might wish to approach the potential of expanded UC-MSCs as an evolutionary therapeutic strategy in managing COVID-19 illness with a 3-pronged approach: If proven safe and effective on a specific and limited basis\u20261. Minimize regulatory burden by all agencies so that critically ill COVID-19 patients will have access regardless of their financial circumstance.2. Institute appropriate safeguards to avoid negative consequences from unscrupulous actors.3. With proper informed consent from patients or proxy when necessary, and subject to accumulation of data in that cohort, allow the procedure to be initiated in critically ill patients who are not responding to conventional therapies.KEY WORDS: Coronavirus, COVID-19, cytokine storm, multiorgan failure, expanded umbilical cord mesenchymal stem cells.", "qid": 46, "docid": "e98a5ed5", "rank": 42, "score": 0.8033089637756348}, {"content": "Title: Reducing dexamethasone antiemetic prophylaxis during the COVID-19 pandemic: recommendations from Ontario, Canada Content: PURPOSE: People with cancer face an elevated risk of infection and severe sequelae from COVID-19. Dexamethasone is commonly used for antiemetic prophylaxis with systemic therapy for cancer. However, dexamethasone is associated with increased risk of viral and respiratory infections, and causes lymphopenia, which is associated with worse outcomes during COVID-19 infections. Our purpose was to minimize dexamethasone exposure during antiemetic prophylaxis for systemic therapy for solid tumors during the COVID-19 pandemic, while maintaining control of nausea and emesis. METHODS: We convened an expert panel to systematically review the literature and formulate consensus recommendations. RESULTS: No studies considered the impact of dexamethasone-based antiemetic regimens on the risk and severity of COVID-19 infection. Expert consensus recommended modifications to the 2019 Cancer Care Ontario Antiemetic Recommendations. CONCLUSION: Clinicians should prescribe the minimally effective dose of dexamethasone for antiemetic prophylaxis. Single-day dexamethasone dosing is recommended over multi-day dosing for regimens with high emetogenic risk excluding high-dose cisplatin, preferably in combination with palonosetron, netupitant, and olanzapine. For regimens with low emetogenic risk, 5-HT(3) antagonists are recommended over dexamethasone.", "qid": 46, "docid": "gd6dd4qm", "rank": 43, "score": 0.8015570640563965}, {"content": "Title: Reducing dexamethasone antiemetic prophylaxis during the COVID-19 pandemic: recommendations from Ontario, Canada Content: PURPOSE: People with cancer face an elevated risk of infection and severe sequelae from COVID-19. Dexamethasone is commonly used for antiemetic prophylaxis with systemic therapy for cancer. However, dexamethasone is associated with increased risk of viral and respiratory infections, and causes lymphopenia, which is associated with worse outcomes during COVID-19 infections. Our purpose was to minimize dexamethasone exposure during antiemetic prophylaxis for systemic therapy for solid tumors during the COVID-19 pandemic, while maintaining control of nausea and emesis. METHODS: We convened an expert panel to systematically review the literature and formulate consensus recommendations. RESULTS: No studies considered the impact of dexamethasone-based antiemetic regimens on the risk and severity of COVID-19 infection. Expert consensus recommended modifications to the 2019 Cancer Care Ontario Antiemetic Recommendations. CONCLUSION: Clinicians should prescribe the minimally effective dose of dexamethasone for antiemetic prophylaxis. Single-day dexamethasone dosing is recommended over multi-day dosing for regimens with high emetogenic risk excluding high-dose cisplatin, preferably in combination with palonosetron, netupitant, and olanzapine. For regimens with low emetogenic risk, 5-HT3 antagonists are recommended over dexamethasone.", "qid": 46, "docid": "b8p4l0yp", "rank": 44, "score": 0.8015083074569702}, {"content": "Title: The COVID-19 pandemic: is our medicine still evidence-based? Content: There is no randomized controlled trial that demonstrated the efficacy of antiviral therapy against COVID-19 yet. However, physicians are prescribing different drugs to a large part of COVID-19 population in the hope they will cure them. This does not reflect the evidence-based medicine approach. What we need is more evidence-based knowledge about what routine care practices we should to apply to ameliorate symptoms of patients and fight COVID-19 pathology.", "qid": 46, "docid": "x82yaoxc", "rank": 45, "score": 0.8000686168670654}, {"content": "Title: COVID\u201019: A review of therapeutics under investigation Content: The COVID\u201019 outbreak has disrupted global health care networks and caused thousands of deaths and an international economic downturn. Multiple drugs are being used on patients with COVID\u201019 based on theoretical and in vitro therapeutic targets. Several of these therapies have been studied, but many have limited evidence behind their use, and clinical trials to evaluate their efficacy are either ongoing or have not yet begun. This review summarizes the existing evidence for medications currently under investigation for treatment of COVID\u201019, including remdesivir, chloroquine/hydroxychlorquine, convalescent plasma, lopinavir/ritonavir, IL\u20106 inhibitors, corticosteroids, and angiotensin\u2010converting enzyme inhibitors.", "qid": 46, "docid": "j2u0ny2u", "rank": 46, "score": 0.7988792657852173}, {"content": "Title: Medikamentoznoe lechenie koronavirusnoi bolezni COVID-19: sushchestvuet li dokazatel'naya baza?/ [Drug treatment of coronavirus disease COVID-19: evidence exists?] Content: The article provides a review of foreign literature for 2020 on existing methods of drug treatment of coronavirus disease COVID-19. To date, in the treatment of COVID-19 in different countries, a little more than 10 drugs are used. The largest number of studies on the testing of these drugs is carried out by scientists from China, the USA, and European countries. It should be noted that among these drugs there is not a single new drug developed specifically for the treatment of COVID-19, the recommended and used drugs have previously been used to treat, as a rule, diseases of the viral etiology, less often another pathology. These suggestions are often based on analogy, the hypothesis of their supposed effectiveness for COVID-19. It can be assumed that a brake on the development of a drug specific for coronavirus disease is a poor knowledge of the pathogenesis of virus invasion in the body's adhesives and the development of complications. The review provides detailed literature data on drugs such as hydroxychloroquine / chloroquine, lopinavir/natinavir, remdesivir, ACE inhibitors and angiotensin converting enzyme receptor blockers, tissue plasminogen activator, as well as plasma transfusion transfusions.", "qid": 46, "docid": "xax8g2yd", "rank": 47, "score": 0.7987837195396423}, {"content": "Title: [Drug treatment of coronavirus disease COVID-19: evidence exists?] Content: The article provides a review of foreign literature for 2020 on existing methods of drug treatment of coronavirus disease COVID-19. To date, in the treatment of COVID-19 in different countries, a little more than 10 drugs are used. The largest number of studies on the testing of these drugs is carried out by scientists from China, the USA, and European countries. It should be noted that among these drugs there is not a single new drug developed specifically for the treatment of COVID-19, the recommended and used drugs have previously been used to treat, as a rule, diseases of the viral etiology, less often another pathology. These suggestions are often based on analogy, the hypothesis of their supposed effectiveness for COVID-19. It can be assumed that a brake on the development of a drug specific for coronavirus disease is a poor knowledge of the pathogenesis of virus invasion in the body's adhesives and the development of complications. The review provides detailed literature data on drugs such as hydroxychloroquine / chloroquine, lopinavir/natinavir, remdesivir, ACE inhibitors and angiotensin converting enzyme receptor blockers, tissue plasminogen activator, as well as plasma transfusion transfusions.", "qid": 46, "docid": "ec5a65l8", "rank": 48, "score": 0.7987837195396423}, {"content": "Title: Potential specific therapies in COVID-19 Content: COVID-19 has grown into a global pandemic that has strained healthcare throughout the world. There is a sense of urgency in finding a cure for this deadly virus. In this study, we reviewed the empiric options used in common practice for COVID-19, based on the literature available online, with an emphasis on human experiences with these treatments on severe acute respiratory syndrome-associated coronavirus (SARS-COV-1) and other viruses. Convalescent blood products are the most promising potential treatment for use in COVID-19. The use of chloroquine or hydroxychloroquine (HCQ), remdesivir, and tocilizumab are some of the other promising potential therapies; however, they are yet to be tested in randomized clinical trials (RCTs). The use of lopinavir-ritonavir did not prove beneficial in a large RCT. The use of corticosteroids should be avoided in COVID-19 pneumonia unless used for other indications, based on the suggestion of harm in patients with SARS-COV-1 and Middle Eastern Respiratory Syndrome (MERS) infection. The reviews of this paper are available via the supplemental material section.", "qid": 46, "docid": "agdec3vz", "rank": 49, "score": 0.7985920310020447}, {"content": "Title: Consensus statement. Corticosteroid therapy in ENT in the context of the COVID-19 pandemic Content: This consensus statement about the indications and modalities of corticosteroid treatment in the context of the COVID-19 pandemic was jointly written by experts from the French Association of Otology and Oto-Neurology (AFON) and from the French Society of Otorhinolaryngology, Head and Neck Surgery (SFORL). There is currently not enough data in favour of danger or benefit from corticosteroids in COVID-19, so until this matter is resolved it is advisable to limit their indications to the most serious clinical pictures for which it is well established that this type of treatment has a positive impact on the progression of symptoms. In Grade V and VI Bell's palsy according to the House-Brackmann grading system, a week's course of oral corticosteroids is recommended. Corticosteroid therapy is also recommended in cases of sudden hearing loss of more than 60dB, either in the form of intratympanic injections or a week's course of oral medication. In rhinology, there is no indication for systemic corticosteroid therapy in the current situation. However, patients are advised to continue with their local corticosteroid therapy in the form of a nasal spray or by inhalation. Treatments with corticosteroid nasal sprays can still be prescribed if there is no alternative. Finally, systemic or local corticosteroid therapy is not indicated for bacterial ENT infections.", "qid": 46, "docid": "ekvyyo5k", "rank": 50, "score": 0.7976974844932556}, {"content": "Title: Pharmacological development of the potential adjuvant therapeutic agents against coronavirus disease 2019 Content: As the coronavirus disease 2019 (COVID-19, also called severe acute respiratory syndrome coronavirus-2, SARSCoV-2) outbreak accelerates, vigorous and diverse efforts were made in developing treatment strategies. In addition to direct acting agents, increasing evidence showed some potential adjuvant therapies with promising efficacy against COVID-19. These therapies include immunomodulators (i.e. intravenous immunoglobulin, thymosin &#945;-1, IL-6, tocilizumab, cyclosporine, thalidomide, fingolimod), Chinese medicines (i.e. glycyrrhizin, baicalin, Xuebijing), anti-vascular endothelial growth factors (bevacizumab), estrogen modulating drugs, statins and nutritional supplements (i.e. vitamin A, B, C, D, E and zinc). This article reviewed the pharmacological development of potential adjuvants for COVID-19 treatment.", "qid": 46, "docid": "s457bak7", "rank": 51, "score": 0.7975056171417236}, {"content": "Title: Novel Stem Cells and Nucleic Acid-Based Vaccine Trials Against Viral Outbreak: A Systematic Evaluation During COVID-2019 Pandemic Content: The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak, the cause of coronavirus disease (COVID-19), has influenced health globally. So far, there are no established management options and prophylaxis for those who have been exposed to SARS-CoV-2, and those who develop COVID-19. Documented scientific evidences in similar viral outbreaks in past suggested few therapy regimens. These rather have not shown promising results in management of current pandemic. So, in the current review, we are exploring novel treatment strategies and therapies that are being explored and are in clinical and preclinical stages of research. To explore more about the same, we directed our search towards stem cell based, DNA based, or RNA based vaccines against COVID-19 under development by various universities, institutes or pharmaceutical companies. The current scientific literature and database search were performed by exploring various Trials registry (NIH: https://clinicaltrials.gov/ and https://www.coronavirus.gov) and Chinese clinical trial registry http://www.chictr.org.cn/) and for preclinical trials various University, Institutions, Pharmaceutical companies websites and news bulletins along with google search were checked routinely from 3rd March 2020 to 16 May 2020. The term \u201cStem Cell therapy and COVID-19\u201d, \u201cMesenchymal stem cell and corona 2019 virus\u201d, \u201cDNA Vaccines and COVID-19, RNA Vaccines and COVID-19\u201d and \u201cCell-based therapy with SARS-CoV-2, University/Institutions and COVID-19 research\u201d were used. The vaccine trials (Stem Cells/DNA/RNA) which were cancelled were not included in this review. Similarly, few others like repurposing of drugs, Nano Vaccines, other miscellaneous trials of Herbs, Music therapy etc., were also excluded. In the present review, we have included the various novel therapies like stem cell therapy, DNA or RNA vaccines which are under development and if proven successful may have a lasting impact on the health industry.", "qid": 46, "docid": "ajd9renr", "rank": 52, "score": 0.7973573207855225}, {"content": "Title: Efficacy and safety of corticosteroids in COVID-19 based on evidence for COVID-19, other coronavirus infections, influenza, community-acquired pneumonia and acute respiratory distress syndrome: a systematic review and meta-analysis Content: BACKGROUND: Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses. METHODS: We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects. RESULTS: In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non-COVID-19 populations (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio [HR] 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia. INTERPRETATION: Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality.", "qid": 46, "docid": "r8rd5f2j", "rank": 53, "score": 0.7972582578659058}, {"content": "Title: Balancing evidence and frontline experience in the early phases of the COVID-19 pandemic: current position of the Italian Society of anti-infective therapy (SITA) and the Italian Society of Pulmonology (SIP) Content: Abstract Background SARS-CoV-2 is the causative agent of coronavirus disease 2019 (COVID-19), which has rapidly become epidemic in Italy and other European countries. The disease spectrum ranges from asymptomatic/mildly symptomatic presentations to acute respiratory failure. At the present time the absolute number of severe cases requiring ventilator support is reaching or even surpassing the intensive care unit bed capacity in the most affected regions and countries. Objectives To narratively summarize the available literature on the management of COVID-19, in the attempt to combine current evidence and frontline opinions and provide balanced answers to pressing clinical questions. Sources Inductive PubMed search for publications relevant to the topic. Content The available literature and the authors\u2019 frontline-based opinion are summarized in brief narrative answers to selected clinical questions, plus a conclusive statement for each answer. Implications Many off-label antiviral and anti-inflammatory drugs are currently being administered to patients with COVID-19. Physicians must be aware that, being not supported by high-level evidence, these treatments may often be ethically justifiable only in those worsening patients unlikely to improve only with supportive care, and who cannot be enrolled in randomized clinical trials (RCT). Access to well-designed RCT should be expanded as much as possible, being the most secure way to change for the better our approach to COVID-19 patients.", "qid": 46, "docid": "p5cz7t52", "rank": 54, "score": 0.7970565557479858}, {"content": "Title: Efficacy and safety of corticosteroids in COVID-19 based on evidence for COVID-19, other coronavirus infections, influenza, community-acquired pneumonia and acute respiratory distress syndrome: a systematic review and meta-analysis. Content: BACKGROUND Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses. METHODS We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects. RESULTS In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non-COVID-19 populations (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio [HR] 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia. INTERPRETATION Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality.", "qid": 46, "docid": "ivm2d5rl", "rank": 55, "score": 0.7965598106384277}, {"content": "Title: Current Status of the COVID-19 Outbreak and Emerging Management through Pharmaceutical Therapeutic Strategy. Content: The latest SARS COV2 coronavirus contributes to a pandemic of millions of COVID-19. Because there is no defensive immunity in humans and a virus can overcome inborn immune reaction, it can propagate unhindered, mostly in tissues contaminated. No unique therapies for COVID-19 contaminated patients are available at this time. The insights learned from previous respiratory viral infection control have given guidance into COVID-19 therapy. Several complementary treatments have been tentatively introduced in hospital environments such as immune-modulators, antiviral, convalescent plasma transfusions and natural products. In COVID-19 patients, some of these therapies have provided substantial curative benefits. Moreover, numerous studies and clinical trials are being carried out in order to determine the efficacy of current pharmaceutical and natural products and establish possible therapeutic strategies for producing novel COVID-19 medicines. We summarized and defined the modes of mechanism, protection and efficacy on existing therapeutic strategies for diseases linked to COVID-19 infection.", "qid": 46, "docid": "kpdfkl4e", "rank": 56, "score": 0.7963769435882568}, {"content": "Title: Rethinking the role of hydroxychloroquine in the treatment of COVID-19 Content: There are currently no proven or approved treatments for coronavirus disease 2019 (COVID-19). Early anecdotal reports and limited in vitro data led to the significant uptake of hydroxychloroquine (HCQ), and to lesser extent chloroquine (CQ), for many patients with this disease. As an increasing number of patients with COVID-19 are treated with these agents and more evidence accumulates, there continues to be no high-quality clinical data showing a clear benefit of these agents for this disease. Moreover, these agents have the potential to cause harm, including a broad range of adverse events including serious cardiac side effects when combined with other agents. In addition, the known and potent immunomodulatory effects of these agents which support their use in the treatment of auto-immune conditions, and provided a component in the original rationale for their use in patients with COVID-19, may, in fact, undermine their utility in the context of the treatment of this respiratory viral infection. Specifically, the impact of HCQ on cytokine production and suppression of antigen presentation may have immunologic consequences that hamper innate and adaptive antiviral immune responses for patients with COVID-19. Similarly, the reported in vitro inhibition of viral proliferation is largely derived from the blockade of viral fusion that initiates infection rather than the direct inhibition of viral replication as seen with nucleoside/tide analogs in other viral infections. Given these facts and the growing uncertainty about these agents for the treatment of COVID-19, it is clear that at the very least thoughtful planning and data collection from randomized clinical trials are needed to understand what if any role these agents may have in this disease. In this article, we review the datasets that support or detract from the use of these agents for the treatment of COVID-19 and render a data informed opinion that they should only be used with caution and in the context of carefully thought out clinical trials, or on a case-by-case basis after rigorous consideration of the risks and benefits of this therapeutic approach.", "qid": 46, "docid": "87uhx3pt", "rank": 57, "score": 0.7963277697563171}, {"content": "Title: Update for Anaesthetists on Clinical Features of COVID-19 Patients and Relevant Management Content: When preparing for the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the coronavirus infection disease (COVID-19) questions arose regarding various aspects concerning the anaesthetist. When reviewing the literature it became obvious that keeping up-to-date with all relevant publications is almost impossible. We searched for and summarised clinically relevant topics that could help making clinical decisions. This is a subjective analysis of literature concerning specific topics raised in our daily practice (e.g., clinical features of COVID-19 patients; ventilation of the critically ill COVID-19 patient; diagnostic of infection with SARS-CoV-2; stability of the virus; Covid-19 in specific patient populations, e.g., paediatrics, immunosuppressed patients, patients with hypertension, diabetes mellitus, kidney or liver disease; co-medication with non-steroidal anti-inflammatory drugs (NSAIDs); antiviral treatment) and we believe that these answers help colleagues in clinical decision-making. With ongoing treatment of severely ill COVID-19 patients other questions will come up. While respective guidelines on these topics will serve clinicians in clinical practice, regularly updating all guidelines concerning COVID-19 will be a necessary, although challenging task in the upcoming weeks and months. All recommendations during the current extremely rapid development of knowledge must be evaluated on a daily basis, as suggestions made today may be out-dated with the new evidence available tomorrow.", "qid": 46, "docid": "cfqfchk4", "rank": 58, "score": 0.7962064743041992}, {"content": "Title: Etoposid-based therapy for severe forms of COVID-19 Content: Abstract The new coronavirus infection COVID-19 has quickly become a global health emergency. Mortality is principally due to severe Acute Respiratory Distress Syndrome (ARDS) which relays only on supportive treatment. Numerous pathological, clinical and laboratory findings rise the similarity between moderate to severe COVID-19 and haemophagocytic lymphohistiocytosis (HLH). Etoposide-based protocol including dexametasone is the standard of care for secondary HLH. The protocol has been successfully used in HLHs that are secondary to EBV and H1N1 infections by inducing complete response and pronged survival. These observations prompt to consider this cytotoxic therapy in HLH associated to moderately severe to severe forms of COVID-19.", "qid": 46, "docid": "3i6pnheg", "rank": 59, "score": 0.7961646914482117}, {"content": "Title: Pharmacological development of the potential adjuvant therapeutic agents against coronavirus disease 2019. Content: As the coronavirus disease 2019 (COVID-19, also called severe acute respiratory syndrome coronavirus-2, SARSCoV-2) outbreak accelerates, vigorous and diverse efforts were made in developing treatment strategies. In addition to direct acting agents, increasing evidence showed some potential adjuvant therapies with promising efficacy against COVID-19. These therapies include immunomodulators (i.e. intravenous immunoglobulin, thymosin \u03b1-1, IL-6, tocilizumab, cyclosporine, thalidomide, fingolimod), Chinese medicines (i.e. glycyrrhizin, baicalin, Xuebijing), anti-vascular endothelial growth factors (bevacizumab), estrogen modulating drugs, statins and nutritional supplements (i.e. vitamin A, B, C, D, E and zinc). This article reviewed the pharmacological development of potential adjuvants for COVID-19 treatment.", "qid": 46, "docid": "rtvbf6aw", "rank": 60, "score": 0.7955325841903687}, {"content": "Title: Comparative Efficacy and Safety of Pharmacological Managements for Hospitalized COVID-19 Patients: Protocol for Systematic Review and Trade-Off Network Meta-Analysis. Content: Coronavirus-Disease 2019 (COVID-19) is the clinical disease caused by the SARS-CoV-2 virus, the infectious agent causing the ongoing pandemic that has impacted the lives of hundreds of millions of people in almost every nation worldwide. It is a potentially fatal disease to many vulnerable patients including the elderly and those with chronic illnesses; but because this virus is a novel one, there are no firmly established treatment protocols. Many treatment methods are being investigated worldwide, and scientific conclusions drawn from these endeavors are crucial for healthcare professionals in combating this disease. In this network meta-analysis, we focus specifically on the pharmacologic agents that have been investigated for the treatment of COVID-19 and aim to produce a comprehensive picture of the evidence from current data in order to produce relevant insights on the comparative efficacy and safety profiles of various pharmacologic agents against COVID-19.", "qid": 46, "docid": "30h09e1k", "rank": 61, "score": 0.7954208254814148}, {"content": "Title: Balancing evidence and frontline experience in the early phases of the COVID-19 pandemic: current position of the Italian Society of Anti-infective Therapy (SITA) and the Italian Society of Pulmonology (SIP) Content: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which has rapidly become epidemic in Italy and other European countries. The disease spectrum ranges from asymptomatic/mildly symptomatic presentations to acute respiratory failure. At the present time the absolute number of severe cases requiring ventilator support is reaching or even surpassing the intensive care unit bed capacity in the most affected regions and countries. OBJECTIVES: To narratively summarize the available literature on the management of COVID-19 in order to combine current evidence and frontline opinions and to provide balanced answers to pressing clinical questions. SOURCES: Inductive PubMed search for publications relevant to the topic. CONTENT: The available literature and the authors' frontline-based opinion are summarized in brief narrative answers to selected clinical questions, with a conclusive statement provided for each answer. IMPLICATIONS: Many off-label antiviral and anti-inflammatory drugs are currently being administered to patients with COVID-19. Physicians must be aware that, as they are not supported by high-level evidence, these treatments may often be ethically justifiable only in those worsening patients unlikely to improve only with supportive care, and who cannot be enrolled onto randomized clinical trials. Access to well-designed randomized controlled trials should be expanded as much as possible because it is the most secure way to change for the better our approach to COVID-19 patients.", "qid": 46, "docid": "w8yb5bfa", "rank": 62, "score": 0.7953239679336548}, {"content": "Title: Rethinking the role of hydroxychloroquine in the treatment of COVID\u201019 Content: There are currently no proven or approved treatments for coronavirus disease 2019 (COVID\u201019). Early anecdotal reports and limited in vitro data led to the significant uptake of hydroxychloroquine (HCQ), and to lesser extent chloroquine (CQ), for many patients with this disease. As an increasing number of patients with COVID\u201019 are treated with these agents and more evidence accumulates, there continues to be no high\u2010quality clinical data showing a clear benefit of these agents for this disease. Moreover, these agents have the potential to cause harm, including a broad range of adverse events including serious cardiac side effects when combined with other agents. In addition, the known and potent immunomodulatory effects of these agents which support their use in the treatment of auto\u2010immune conditions, and provided a component in the original rationale for their use in patients with COVID\u201019, may, in fact, undermine their utility in the context of the treatment of this respiratory viral infection. Specifically, the impact of HCQ on cytokine production and suppression of antigen presentation may have immunologic consequences that hamper innate and adaptive antiviral immune responses for patients with COVID\u201019. Similarly, the reported in vitro inhibition of viral proliferation is largely derived from the blockade of viral fusion that initiates infection rather than the direct inhibition of viral replication as seen with nucleoside/tide analogs in other viral infections. Given these facts and the growing uncertainty about these agents for the treatment of COVID\u201019, it is clear that at the very least thoughtful planning and data collection from randomized clinical trials are needed to understand what if any role these agents may have in this disease. In this article, we review the datasets that support or detract from the use of these agents for the treatment of COVID\u201019 and render a data informed opinion that they should only be used with caution and in the context of carefully thought out clinical trials, or on a case\u2010by\u2010case basis after rigorous consideration of the risks and benefits of this therapeutic approach.", "qid": 46, "docid": "75vvix5o", "rank": 63, "score": 0.7950365543365479}, {"content": "Title: COVID-19 and Headache Medicine: A Narrative Review of Non-Steroidal Anti-Inflammatory Drug (NSAID) and Corticosteroid Use. Content: OBJECTIVE To summarize the current literature on non-steroidal anti-inflammatory drug and corticosteroid use during the coronavirus disease 2019 (COVID-19) pandemic, recognizing that these are commonly used treatments in the field of headache medicine. BACKGROUND The use of non-steroidal anti-inflammatory drugs and corticosteroids in patients during the COVID-19 pandemic has been a controversial topic within the medical community and international and national health organizations. Lay press and social media outlets have circulated opinions on this topic despite the fact that the evidence for or against the use of these medications is sparse. In the field of headache medicine, these medications are used commonly and both patients and clinicians may have questions or hesitations pertaining to their use during the COVID-19 pandemic. METHODS A detailed search of the scientific and popular literature was performed. RESULTS There is limited literature pertaining to the safety of non-steroidal anti-inflammatory drugs and corticosteroids during the COVID-19 pandemic. To date, there are no clear scientific data that preclude the use of non-steroidal anti-inflammatory drugs in the general population who may acquire COVID-19 or in those acutely infected with the virus. Several health organizations have concluded that treatment with corticosteroids during active infection should be avoided due to concerns of prolonged viral shedding in the respiratory tract and the lack of survival benefit based on the data from past coronaviruses and influenza virus; specific exceptions exist including treatment for underlying asthma or chronic obstructive pulmonary disease, septic shock, and acute respiratory distress syndrome. CONCLUSION Scientific information regarding the COVID-19 pandemic is constantly evolving, and limited or contradictory information can lead to confusion for both patients and clinicians. It is recommended that prior to prescribing non-steroidal anti-inflammatory drugs and steroids for the treatment of headache, clinicians have open discussions with their patients about the potential risks and benefits of using these medications during the COVID-19 pandemic. This manuscript summarizes the currently available evidence and understanding about these risks and benefits to help clinicians navigate such discussions.", "qid": 46, "docid": "oooat8xj", "rank": 64, "score": 0.7948453426361084}, {"content": "Title: Mesenchymal Stem Cell Therapy for COVID-19: Present or Future Content: \"COVID-19\" is the word that certainly isn't forgotten by everybody who lives in the first half of the twenty-first century. COVID-19, as a pandemic, has led many researchers from different biomedical fields to find solutions or treatments to manage the pandemic. However, no standard treatment for this disease has been discovered to date. Probably, preventing the severe acute respiratory infection form of COVID-19 as the most dangerous phase of this disease can be helpful for the treatment and reduction of the death rate. In this regard, mesenchymal stem cells (MSCs)-based immunomodulation treatment has been proposed as a suitable therapeutic approach and several clinical trials have begun. Recently, MSCs according to their immunomodulatory and regenerative properties attract attention in clinical trials. After the intravenous transplantation of MSCs, a significant population of cells accumulates in the lung, which they alongside immunomodulatory effect could protect alveolar epithelial cells, reclaim the pulmonary microenvironment, prevent pulmonary fibrosis, and cure lung dysfunction. Given the uncertainties in this area, we reviewed reported clinical trials and hypotheses to provide useful information to researchers and those interested in stem cell therapy. In this study, we considered this new approach to improve patient's immunological responses to COVID-19 using MSCs and discussed the aspects of this proposed treatment. However, currently, there are no approved MSC-based approaches for the prevention and/or treatment of COVID-19 patients but clinical trials ongoing.", "qid": 46, "docid": "s94gdcmc", "rank": 65, "score": 0.7946314215660095}, {"content": "Title: Vademecum for the treatment of people with COVID-19. Edition 2.0, 13 March 2020 Content: The spread of COVID-19 epidemic in Italy, and particularly in Lombardy determined the need to standardize the therapeutic approach in order to offer the same indications for all hospitals in Lombardy. However, no specific drug has been previously approved for the COVID-19 treatment. The Lombardy Section of the Italian Society of Infectious and Tropical Diseases provided this \u00abvademecum\u00bc with the aim to explore the current evidence about the drugs likely to be efficacious in the treatment of COVID-19. Moreover, a multidisciplinary group including critical care specialists has been created in order to provide indications about supporting measures and the use of steroids. A new grading scale has been proposed to help patients' stratification according to the severity of the respiratory conditions. Lastly, a collaborating group with immunologists and rheumatologists has been built with the aim of providing some guidance about the use of tocilizumab, a promising option for the treatment of the hyperinflammatory state occurring in most patients affected by COVID-19.", "qid": 46, "docid": "kpw0e9a7", "rank": 66, "score": 0.7943317890167236}, {"content": "Title: Current evidence for directed and supportive investigational therapies against COVID-19 Content: Coronavirus disease 2019 (COVID-19) is a global health crisis. There is currently a great need for effective and safe therapies directed at the disease, but no drugs are presently registered for use in COVID-19. Several directed therapies have been proposed, and most are still in clinical trials. Currently available published, peer-reviewed results mostly involve small sample sizes with study limitations restricting the interpretation of the findings. Many trials currently published also do not have a control group, limiting the interpretation of the effect of the intervention. Investigational directed therapies as well as investigational supportive therapies against COVID-19 are reviewed here. Chloroquine and hydroxychloroquine show promise as directed therapies, but current trial results are conflicting. Lopinavir/ritonavir also shows potential, but was started late in the disease course in most trials. No randomised controlled evidence is currently available for remdesivir and favipiravir. Corticosteroid use is not recommended for directed therapy against COVID-19, and the role of tocilizumab is currently unclear, based on limited evidence. Early initiation of investigational directed therapies may provide benefit in selected patients. The results from larger randomised controlled trials will clarify the place of these therapies in COVID-19 treatment.", "qid": 46, "docid": "f33eb1nf", "rank": 67, "score": 0.793992280960083}, {"content": "Title: Evidence based management guideline for the COVID-19 pandemic - Review article Content: COVID-19 has now been declared a pandemic. To date, COVID-19 has affected over 2.5 million people worldwide, resulting in over 170,000 reported deaths. Numerous preventative strategies and non-pharmaceutical interventions have been employed to mitigate the spread of disease including careful infection control, the isolation of patients, and social distancing. Management is predominantly focused on the provision of supportive care, with oxygen therapy representing the major treatment intervention. Medical therapy involving corticosteroids and antivirals have also been encouraged as part of critical management schemes. However, there is at present no specific antiviral recommended for the treatment of COVID-19, and no vaccine is currently available. Despite the strategic implementation of these measures, the number of new reported cases continues to rise at a profoundly alarming rate. As new findings emerge, there is an urgent need for up-to-date management guidelines. In response to this call, we review what is currently known regarding the management of COVID-19, and offer an evidence-based review of current practice.", "qid": 46, "docid": "2697ts31", "rank": 68, "score": 0.7929443120956421}, {"content": "Title: Natural History of COVID-19 and Current Knowledge on Treatment Therapeutic Options Content: Despite intense research there is currently no effective vaccine available against the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in the later 2019 and responsible for the COVID-19 pandemic. This infectious and communicable disease has become one of the major public health challenges in the world. The clinical management of COVID-19 has been limited to infection prevention and control measures associated with supportive care such as supplemental oxygen and mechanical ventilation. Meanwhile efforts to find an effective treatment to inhibit virus replication, mitigate the symptoms, increase survival and decrease mortality rate are ongoing. Several classes of drugs, many of them already in use for other diseases, are being evaluated based on the body of clinical knowledge obtained from infected patients regarding to the natural history and evolution of the infection. Herein we will provide an updated overview of the natural history and current knowledge on drugs and therapeutic agents being tested for the prevention and treatment of COVID-19. These include different classes of drugs such as antiviral agents (chloroquine, ivermectin, nitazoxanide, hydroxychloroquine, lopinavir, remdesivir, tocilizumab), supporting agents (Vitamin C, Vitamin D, azithromycin, corticosteroids) and promising investigational vaccines. Considering the controversies and excessive number of compounds being tested and reported in the literature we hope that this review can provide useful and updated consolidated information on potential drugs used to prevent, control and treat COVID-19 patients worldwide.", "qid": 46, "docid": "rirzes0m", "rank": 69, "score": 0.7929089665412903}, {"content": "Title: Thalidomide-Revisited: Are COVID-19 Patients Going to Be the Latest Victims of Yet Another Theoretical Drug-Repurposing? Content: The coronavirus disease 2019 (COVID-19) pandemic is a worldwide threatening health issue. The progression of this viral infection occurs in the airways of the lungs with an exaggerated inflammatory response referred to as the \"cytokine storm\" that can lead to lethal lung injuries. In the absence of an effective anti-viral molecule and until the formulation of a successful vaccine, anti-inflammatory drugs might offer a complementary tool for controlling the associated complications of COVID-19 and thus decreasing the subsequent fatalities. Drug repurposing for several molecules has emerged as a rapid temporary solution for COVID-19. Among these drugs is Thalidomide; a historically emblematic controversial molecule that harbors an FDA approval for treating erythema nodosum leprosum (ENL) and multiple myeloma (MM). Based on just one-case report that presented positive outcomes in a patient treated amongst others with Thalidomide, two clinical trials on the efficacy and safety of Thalidomide in treating severe respiratory complications in COVID-19 patients were registered. Yet, the absence of substantial evidence on Thalidomide usage in that context along with the discontinued studies on the efficiency of this drug in similar pulmonary diseases, might cause a significant obstacle for carrying out further clinical evaluations. Herein, we will discuss the theoretical effectiveness of Thalidomide in attenuating inflammatory complications that are encountered in COVID-19 patients while pinpointing the lack of the needed evidences to move forward with this drug.", "qid": 46, "docid": "0i6qoc53", "rank": 70, "score": 0.7924289703369141}, {"content": "Title: Mesenchymal Stem Cell Therapy for COVID-19: Present or Future Content: \u201cCOVID-19\u201d is the word that certainly isn\u2019t forgotten by everybody who lives in the first half of the twenty-first century. COVID-19, as a pandemic, has led many researchers from different biomedical fields to find solutions or treatments to manage the pandemic. However, no standard treatment for this disease has been discovered to date. Probably, preventing the severe acute respiratory infection form of COVID-19 as the most dangerous phase of this disease can be helpful for the treatment and reduction of the death rate. In this regard, mesenchymal stem cells (MSCs)-based immunomodulation treatment has been proposed as a suitable therapeutic approach and several clinical trials have begun. Recently, MSCs according to their immunomodulatory and regenerative properties attract attention in clinical trials. After the intravenous transplantation of MSCs, a significant population of cells accumulates in the lung, which they alongside immunomodulatory effect could protect alveolar epithelial cells, reclaim the pulmonary microenvironment, prevent pulmonary fibrosis, and cure lung dysfunction. Given the uncertainties in this area, we reviewed reported clinical trials and hypotheses to provide useful information to researchers and those interested in stem cell therapy. In this study, we considered this new approach to improve patient\u2019s immunological responses to COVID-19 using MSCs and discussed the aspects of this proposed treatment. However, currently, there are no approved MSC-based approaches for the prevention and/or treatment of COVID-19 patients but clinical trials ongoing.", "qid": 46, "docid": "t7wlz9lj", "rank": 71, "score": 0.7924149036407471}, {"content": "Title: Systemic autoimmune diseases, anti-rheumatic therapies, COVID-19 infection risk and patient outcomes Content: As of June 10th 2020 about 7.2 million individuals have tested positive for, and more than 410,000 have died due to COVID-19. In this review we outline the pathophysiology that underpins the potential use of anti-rheumatic therapies for severe COVID-19 infection and summarize the current evidence regarding the risk and outcome of COVID-19 in patients with systemic autoimmune diseases. Thus far there is no convincing evidence that any disease-modifying anti-rheumatic drug (conventional synthetic, biologic or targeted synthetic) including hydroxychloroquine, may protect against severe COVID-19 infection; answers about their possible usefulness in the management of the cytokine storm associated with severe COVID-9 infection will only arise from ongoing randomized controlled trials. Evidence on COVID-19 risk and outcome in patients with systemic autoimmune diseases is extremely limited; thus, any conclusions would be unsafe and should be seen with great caution. At present, the risk and severity (hospitalization, intensive care unit admission and death) of COVID-19 infection in people with autoimmune diseases do not appear particularly dissimilar to the general population, with the possible exception of hospitalization in patients exposed to high glucocorticoid doses. At this stage it is impossible to draw any conclusions for differences in COVID-19 risk and outcome between different autoimmune diseases and between the various immunomodulatory therapies used for them. More research in the field is obviously required, including as a minimum careful and systematic epidemiology and appropriately controlled clinical trials.", "qid": 46, "docid": "e02y93f6", "rank": 72, "score": 0.792272686958313}, {"content": "Title: Associations between immune-suppressive and stimulating drugs and novel COVID-19\u2014a systematic review of current evidence Content: BACKGROUND: Cancer and transplant patients with COVID-19 have a higher risk of developing severe and even fatal respiratory diseases, especially as they may be treated with immune-suppressive or immune-stimulating drugs. This review focuses on the effects of these drugs on host immunity against COVID-19. METHODS: Using Ovid MEDLINE, we reviewed current evidence for immune-suppressing or -stimulating drugs: cytotoxic chemotherapy, low-dose steroids, tumour necrosis factor\u03b1 (TNF\u03b1) blockers, interlukin-6 (IL-6) blockade, Janus kinase (JAK) inhibitors, IL-1 blockade, mycophenolate, tacrolimus, anti-CD20 and CTLA4-Ig. RESULTS: 89 studies were included. Cytotoxic chemotherapy has been shown to be a specific inhibitor for severe acute respiratory syndrome coronavirus in in vitro studies, but no specific studies exist as of yet for COVID-19. No conclusive evidence for or against the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of COVID-19 patients is available, nor is there evidence indicating that TNF\u03b1 blockade is harmful to patients in the context of COVID-19. COVID-19 has been observed to induce a pro-inflammatory cytokine generation and secretion of cytokines, such as IL-6, but there is no evidence of the beneficial impact of IL-6 inhibitors on the modulation of COVID-19. Although there are potential targets in the JAK-STAT pathway that can be manipulated in treatment for coronaviruses and it is evident that IL-1 is elevated in patients with a coronavirus, there is currently no evidence for a role of these drugs in treatment of COVID-19. CONCLUSION: The COVID-19 pandemic has led to challenging decision-making about treatment of critically unwell patients. Low-dose prednisolone and tacrolimus may have beneficial impacts on COVID-19. The mycophenolate mofetil picture is less clear, with conflicting data from pre-clinical studies. There is no definitive evidence that specific cytotoxic drugs, low-dose methotrexate for auto-immune disease, NSAIDs, JAK kinase inhibitors or anti-TNF\u03b1 agents are contraindicated. There is clear evidence that IL-6 peak levels are associated with severity of pulmonary complications.", "qid": 46, "docid": "za3qypgg", "rank": 73, "score": 0.7922388315200806}, {"content": "Title: Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. Content: Importance The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection. Observations No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19. Conclusions and Relevance The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.", "qid": 46, "docid": "8cvjsisw", "rank": 74, "score": 0.7920621633529663}, {"content": "Title: Vademecum for the treatment of people with COVID-19. Edition 2.0, 13 March 2020. Content: The spread of COVID-19 epidemic in Italy, and particularly in Lombardy determined the need to standardize the therapeutic approach in order to offer the same indications for all hospitals in Lombardy. However, no specific drug has been previously approved for the COVID-19 treatment. The Lombardy Section of the Italian Society of Infectious and Tropical Diseases provided this \u00abvademecum\u00bb with the aim to explore the current evidence about the drugs likely to be efficacious in the treatment of COVID-19. Moreover, a multidisciplinary group including critical care specialists has been created in order to provide indications about supporting measures and the use of steroids. A new grading scale has been proposed to help patients' stratification according to the severity of the respiratory conditions. Lastly, a collaborating group with immunologists and rheumatologists has been built with the aim of providing some guidance about the use of tocilizumab, a promising option for the treatment of the hyperinflammatory state occurring in most patients affected by COVID-19.", "qid": 46, "docid": "vozfv7gj", "rank": 75, "score": 0.7919648885726929}, {"content": "Title: Can cell therapies halt cytokine storm in severe COVID-19 patients? Content: A pilot study of COVID-19 patients treated with mesenchymal stem cells demonstrates safety. Mesenchymal stromal cell (MSC) therapies, which have been explored for decades as a treatment for inflammatory diseases, are now being called into action to combat the cytokine storm induced by COVID-19. The severity of COVID-19 may be due in part to the patient's response to the infection. In some patients, the virus induces an outpouring of inflammatory mediators that leads to swelling, inflammatory infiltration, and reduced gas exchange in the alveoli of the lungs. To combat this cytokine storm, over 20 clinical trials aiming to treat COVID-19 with MSCs have been registered with ClinicalTrials.gov. Leng et al. recently conducted a pilot study of MSC transplantation in 10 patients in China. All patients tested positive for SARS-CoV-2 by polymerase chain reaction and had fever, shortness of breath, cough, and oxygen saturation at rest &lt;95%. Seven of the patients received intravenous infusions of allogeneic MSCs while three received saline as a placebo control. All seven MSC treated patients experienced resolution of symptoms while one of the placebo-treated patients went on to develop ARDS and another died. The response of the most severely ill patient treated with MSCs was monitored throughout recovery. Of note, C-reactive protein levels dropped 10-fold after MSC treatment, suggesting a drop in systemic inflammation. Analysis of cytokine levels before and after treatment revealed that MSC treatment, but not placebo, was associated with a halt in the increase of serum tumor necrosis factor\u2013\u03b1 and an increase in anti-inflammatory interleukin-10 concentrations in the serum. Although this study is not designed to make definitive claims regarding the efficacy of MSC therapy for COVID-19 or the mechanisms by which MSCs may function to prevent or treat cytokine storm, it does provide important safety data and hints of efficacy that have motivated further exploration of MSCs as a treatment for COVID-19. Of particular note is a randomized, multicenter, placebo-controlled, Phase 2/3 trial enrolling 240 patients being conducted through a public-private partnership between the U.S. National Institutes of Health\u2013funded Cardiothoracic Surgical Trials Network and Mesoblast. As multiple clinical trials are launched around the world, we should not have to wait long to determine if MSCs are a viable and effective treatment option for severe COVID-19.", "qid": 46, "docid": "c9qbnonk", "rank": 76, "score": 0.7917053699493408}, {"content": "Title: Thalidomide-Revisited: Are COVID-19 Patients Going to Be the Latest Victims of Yet Another Theoretical Drug-Repurposing? Content: The coronavirus disease 2019 (COVID-19) pandemic is a worldwide threatening health issue. The progression of this viral infection occurs in the airways of the lungs with an exaggerated inflammatory response referred to as the \u201ccytokine storm\u201d that can lead to lethal lung injuries. In the absence of an effective anti-viral molecule and until the formulation of a successful vaccine, anti-inflammatory drugs might offer a complementary tool for controlling the associated complications of COVID-19 and thus decreasing the subsequent fatalities. Drug repurposing for several molecules has emerged as a rapid temporary solution for COVID-19. Among these drugs is Thalidomide; a historically emblematic controversial molecule that harbors an FDA approval for treating erythema nodosum leprosum (ENL) and multiple myeloma (MM). Based on just one-case report that presented positive outcomes in a patient treated amongst others with Thalidomide, two clinical trials on the efficacy and safety of Thalidomide in treating severe respiratory complications in COVID-19 patients were registered. Yet, the absence of substantial evidence on Thalidomide usage in that context along with the discontinued studies on the efficiency of this drug in similar pulmonary diseases, might cause a significant obstacle for carrying out further clinical evaluations. Herein, we will discuss the theoretical effectiveness of Thalidomide in attenuating inflammatory complications that are encountered in COVID-19 patients while pinpointing the lack of the needed evidences to move forward with this drug.", "qid": 46, "docid": "urgh8zhs", "rank": 77, "score": 0.7916325330734253}, {"content": "Title: Treatment Considerations for COVID-19: A Critical Review of the Evidence (or Lack Thereof) Content: Abstract The novel severe acute respiratory syndrome coronavirus 2 is causing a worldwide pandemic that may lead to a highly morbid and potentially fatal coronavirus disease-19 (COVID-19). There is currently no drug that has been proven as an effective therapy for COVID-19. Several candidate drugs are being considered and evaluated for treatment. This includes clinically-available drugs, such as chloroquine, hydroxychloroquine, and lopinavir/ritonavir, which are being repurposed for the treatment of COVID-19. Novel experimental therapies, such as remdesivir and favipiravir, are also actively being investigated for antiviral efficacy. Clinically-available and investigational immunomodulators, such as the IL-6 inhibitors tocilizumab and sarilumab and the anti-GMCSF lenzilumab, are being tested for their anticipated effect in counteracting the pro-inflammatory cytokine environment that characterizes severe and critical COVID-19. This review article examines the evidence behind the potential use of these leading drug candidates for the treatment of COVID-19. The authors conclude, based on this review, that there is still no high-quality evidence to support any of these proposed drug therapies. The authors, therefore, encourage the enrollment of eligible patients to multiple ongoing clinical trials that assess the efficacy and safety of these candidate therapies. Until the results of controlled trials are available, none of the suggested therapeutics is clinically proven as an effective therapy for COVID-19.", "qid": 46, "docid": "iymmf4k6", "rank": 78, "score": 0.7915332913398743}, {"content": "Title: COVID-19 Treatment: Close to a Cure? \u2013 A Rapid Review of Pharmacotherapies for the Novel Coronavirus Content: Currently, there is no approved therapy for COVID-19. The World Health Organization therefore endorse supportive care only. However, frontline clinicians and researchers have been experimenting with several virus-based and host-based therapeutics since the outbreak in China. China's National Health Commission has issued the first COVID-19 Treatment Guideline with therapy suggestions (7(th) edition attached) which inspired following clinical studies worldwide. Major therapeutics are evaluated in this review. Key evidence from in vitro researches, animal models and clinical researches in emerging coronaviruses are examined. Antiviral therapies remdesivir, lopinavir/ritonavir and umifenovir, if considered, could be initiated before the peak of viral replication for optimal outcomes. Ribavirin may be beneficial as an add-on therapy and is ineffective as a monotherapy. Corticosteroids use should be limited to indicating comorbidities. IVIG is not recommended due to lack of data in COVID-19. Xuebijing may benefit patients with complications of bacterial pneumonia or sepsis. The efficacy of interferon is unclear due to conflicting outcomes in coronavirus studies. Chloroquine and hydroxychloroquine have shown in vitro inhibition of SARS-CoV-2, and the studies on clinical efficacy and whether the benefits outweigh the risk of dysrhythmias remain inconclusive. For patients who developed cytokine release syndrome, interleukin-6 inhibitors may be beneficial.", "qid": 46, "docid": "369kax2m", "rank": 79, "score": 0.7911680340766907}, {"content": "Title: Review of Emerging Pharmacotherapy for the Treatment of Coronavirus Disease 2019 Content: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into an emergent global pandemic. Coronavirus disease 2019 (COVID-19) can manifest on a spectrum of illness from mild disease to severe respiratory failure requiring intensive care unit admission. As the incidence continues to rise at a rapid pace, critical care teams are faced with challenging treatment decisions. There is currently no widely accepted standard of care in the pharmacologic management of patients with COVID-19. Urgent identification of potential treatment strategies is a priority. Therapies include novel agents available in clinical trials or through compassionate use, and other drugs, repurposed antiviral and immunomodulating therapies. Many have demonstrated in vitro or in vivo potential against other viruses that are similar to SARS-CoV-2. Critically ill patients with COVID-19 have additional considerations related to adjustments for organ impairment and renal replacement therapies, complex lists of concurrent medications, limitations with drug administration and compatibility, and unique toxicities that should be evaluated when utilizing these therapies. The purpose of this review is to summarize practical considerations for pharmacotherapy in patients with COVID-19, with the intent of serving as a resource for health care providers at the forefront of clinical care during this pandemic.", "qid": 46, "docid": "2o4oagps", "rank": 80, "score": 0.7910590171813965}, {"content": "Title: Evidence Based Management Guideline for the COVID-19 Pandemic - Review article Content: ABSTRACT COVID-19 has now been declared a pandemic. To date, COVID-19 has affected over 944,181 people worldwide, resulting in over 47,312 reported deaths. Numerous preventative strategies and non-pharmaceutical interventions have been employed to mitigate the spread of disease including careful infection control, the isolation of patients, and social distancing. Management is predominantly focused on the provision of supportive care, with oxygen therapy representing the major treatment intervention. Medical therapy involving corticosteroids and antivirals have also been encouraged as part of critical management schemes. However, there is at present no specific antiviral recommended for the treatment of COVID-19, and no vaccine is currently available. Despite the strategic implementation of these measures, the number of new reported cases continues to rise at a profoundly alarming rate. As new findings emerge, there is an urgent need for up-to-date management guidelines. In response to this call, we review what is currently known regarding the management of COVID-19, and offer an evidence-based review of current practice.", "qid": 46, "docid": "ver7x3lx", "rank": 81, "score": 0.7909213304519653}, {"content": "Title: Outpatient treatment of COVID-19 with steroids in the phase of mild pneumonia without the need for admission as an opportunity to modify the course of the disease: A structured summary of a randomised controlled trial Content: OBJECTIVES: The aim of this study is to explore the effectiveness and safety of oral corticosteroids (prednisone) in the treatment of early stage SARS-Cov-2 pneumonia in patients who do not yet meet hospital admission criteria. TRIAL DESIGN: Randomized clinical trial, controlled, open, parallel group, to evaluate the effectiveness of steroids in adult patients with confirmed COVID-19, with incipient pulmonary involvement, without hospital admission criteria. Patients will be stratified by the presence or not of radiological data on pneumonia. PARTICIPANTS: We will include patients with early stage SARS-Cov-2 pneumonia who do not meet hospital admission criteria from the reference hospital, the Hospital Universitario de Burgos, in the region of Castilla y Le\u00f3n, Spain. Patients will be followed-up by specialist physicians and Primary Health Care professionals. INCLUSION CRITERIA: - Men and women. - Age between 18 and 75 years old. - Diagnosed SARS-CoV-2 infection, by PCR and/or IgM+ antibody test and/or antigen test. - Clinical diagnosis of lung involvement: (respiratory symptoms +/- pathological auscultation +/- O2 desaturation) - Chest X-ray with mild-moderate alterations or normal. - Patients who give their verbal informed consent in front of witnesses, which will be reflected in the patients' medical records. EXCLUSION CRITERIA: - Oxygen desaturation below 93% or P02 < 62. - Moderate-severe dyspnea or significant respiratory or general deterioration that makes admission advisable. - Chest X-ray with multifocal infiltrates. - Insulin-dependent diabetes with poor control or glycaemia in the emergency room test greater than 300 mg/ml (fasting or not). - Other significant comorbidities: Severe renal failure (creatinine clearance < 30 mL/min); cirrhosis or chronic liver disease, poorly controlled hypertension. - Heart rhythm disturbances (including prolonged QT). - Severe immunosuppression (HIV infection, long-term use of immunosuppressive agents); cancer. - Pregnant or breast-feeding women. - Patients under use of glucocorticoids for other diseases. - History of allergy or intolerance to any of the drugs in the study (prednisone, azithromycin or hydroxychloroquine). - Patients who took one or more of the study drugs in the 7 days prior to study inclusion. - Patients taking non-suppressible drugs with risk of QT prolongation or significant interactions. - Patients unwilling or unable to participate until study completion. - Participation in another study. INTERVENTION AND COMPARATOR: Eligible patients will be randomized to receive standard outpatient treatment only (group 1) or standard outpatient treatment plus prednisone (group 2). - Group 1: paracetamol 1 g/8 h (on demand) + hydroxychloroquine 400 mg/12h the first day, 200 mg/12 h for 4 days + azithromycin 500 mg/24h for 5 days. - Group 2: paracetamol 1 g/8 h (on demand) + hydroxychloroquine 400 mg/12h the first day, 200 mg/12 h for 4 days + azithromycin 500 mg/24h for 5 days + prednisone 60 mg / 24 h for 3 days, 30 mg / 24 h for 3 days and 15 mg / 24 h for 3 days. MAIN OUTCOMES: If the patient requires ambulatory observation, according to the protocol established in this respect in the Emergency Department, meets all the criteria for inclusion and none for exclusion, data will be taken by the person responsible on the data collection sheet. The main result is admission after 30 days. Secondary outcomes are 30-day ICU admission and hospital stay. The safety variable will be the occurrence of clinical symptoms or delirium related to the steroids. Also, the possible decompensations of diabetes will be measured. All tests will be on an intention-to-treat basis. RANDOMISATION: Treatment will be assigned according to stratified randomization by the presence or absence of radiological data of lung involvement (previously performed by random sequence 1:1 generated with Epidat and kept hidden by opaque, sealed envelopes, which will only be opened after inclusion and basal measurement). BLINDING (MASKING): Participants, caregivers and personnel responsible for outcomes measurement will not be blinded to group assignment, once the patient is included and the basal measurement performed, as per protocol design. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The percentage of patients with incipient lung involvement is unknown, but given that pulmonary involvement already exists it is estimated to be around 20%. We consider that the intervention could reduce this percentage to 5%, so the necessary sample size would be 200 subjects (100 per group), with a power of 80% and an estimated loss percentage of 10%. TRIAL STATUS: The protocol with code TAC-COVID-19, version 2.0 on date: April 16, 2020 is approved by the Spanish Drug Agency (AEMPS) and the local Ethics Committee. The trial is in the recruitment phase. Recruitment began 19 April, 2020 and is anticipated to be complete by April 2021. TRIAL REGISTRATION: The trial was registered under the title \"OUTPATIENT TREATMENT OF EARLY PULMONARY COVID19 WITH CORTICOSTEROIDS AS AN OPPORTUNITY TO MODIFY THE COURSE OF THE DISEASE\" with EudraCT number 2020-001622-64 , registered on 3 April 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.", "qid": 46, "docid": "bmnmwobu", "rank": 82, "score": 0.790794312953949}, {"content": "Title: Part II. High-dose methotrexate with leucovorin rescue for severe COVID-19: An immune stabilization strategy for SARS-CoV-2 induced \u2018PANIC\u2019 attack() Content: Here, in Part II of a duology on the characterization and potential treatment for COVID-19, we characterize the application of an innovative treatment regimen for the prevention of the transition from mild to severe COVID-19, as well as detail an intensive immunotherapy intervention hypothesis. We propose as a putative randomized controlled trial that high-dose methotrexate with leucovorin (HDMTX-LR) rescue can abolish \u2018PANIC\u2019, thereby \u2018left-shifting\u2019 severe COVID-19 patients to the group majority of those infected with the SARS-CoV-2 virus, who are designated as having mild, even asymptomatic, disease. HDMTX-LR is endowed with broadly pleiotropic properties and is a repurposed, generic, inexpensive, and widely available agent which can be administered early in the course of severe COVID-19 thus rescuing the critical and irreplaceable gas-exchange alveoli. Further, we describe a preventative treatment intervention regimen for those designated as having mild to moderate COVID-19 disease, but who exhibit features which herald the transition to the severe variant of this novel Coronavirus. Both of our proposed hypothesis-driven questions should be urgently subjected to rigorous assessment in the context of randomized controlled trials, in order to confirm or refute the contention that the approaches characterized herein, are in fact capable of exerting mitigating, if not abolishing, effects upon the SARS-CoV-2 triggering of the \u2018PANIC Attack\u2019. Confirmation of our immunotherapy hypothesis would have far-reaching ramifications for the current pandemic, along with yielding invaluable lessons from which we can more effectively prepare for the next challenge to global health.", "qid": 46, "docid": "qzime3u2", "rank": 83, "score": 0.7901395559310913}, {"content": "Title: Psoriasis and COVID 19: A narrative review with treatment considerations Content: COVID\u201019 is a highly contagious respiratory infection caused by severe acute respiratory syndrome coronavirus 2. COVID\u201019 outbreak, has been declared a pandemic by the World Health Organization on March, 2020. The pandemic has affected the management of psoriasis, not only for those who are under treatment but also for those who are about to begin a new therapy to control their disease. An increasing number of studies in the current literature have focused on the relationship between psoriasis and COVID 19 from different perspectives. This narrative review includes searching the PubMed and Web of Science databases using the keywords \"psoriasis,\u201d, \u201cpsoriatic arthritis\u201d, \"coronavirus\", \"COVID 19\" and \"SARS\u2010Cov\u20102\". The search was supplemented by manual searching of reference lists of included articles. A total of 11 relevant original investigations and 6 case studies was identified. The search was updated in May 2019. Due to the absence of randomized controlled trials, it is not likely to have a robust evidence\u2010based approach to psoriasis management in the era of COVID\u201019. However, current literature may provide some clues for safety considerations. Conventional immunosuppressive therapies such as methotrexate and cyclosporine, and anti TNF agents should not be preferred due to increased risk of infection, especially in high\u2010risk areas. The use of cyclosporine may pose additional risk due to the side effect of hypertension, which has been reported to be associated with susceptibility to severe COVID\u201019. Considering that current literature has provide no conclusive evidence that biologics increase the risk of COVID\u201019, withdrawal of these agents should be reserved for patients with COVID 19 symptoms. The treatment approach should be personalized, considering the advantages and disadvantages for each case separately. This article is protected by copyright. All rights reserved.", "qid": 46, "docid": "u8h0py48", "rank": 84, "score": 0.7900994420051575}, {"content": "Title: COVID-19 Treatment: Close to a Cure? - A Rapid Review of Pharmacotherapies for the Novel Coronavirus Content: Currently, there is no approved therapy for COVID-19. The World Health Organization therefore endorse supportive care only. However, frontline clinicians and researchers have been experimenting with several virus-based and host-based therapeutics since the outbreak in China. China's National Health Commission has issued the first COVID-19 Treatment Guideline with therapy suggestions (7th edition attached) which inspired following clinical studies worldwide. Major therapeutics are evaluated in this review. Key evidence from in vitro researches, animal models and clinical researches in emerging coronaviruses are examined. Antiviral therapies remdesivir, lopinavir/ritonavir and umifenovir, if considered, could be initiated before the peak of viral replication for optimal outcomes. Ribavirin may be beneficial as an add-on therapy and is ineffective as a monotherapy. Corticosteroids use should be limited to indicating comorbidities. IVIG is not recommended due to lack of data in COVID-19. Xuebijing may benefit patients with complications of bacterial pneumonia or sepsis. The efficacy of interferon is unclear due to conflicting outcomes in coronavirus studies. Chloroquine and hydroxychloroquine have shown in vitro inhibition of SARS-CoV-2, and the studies on clinical efficacy and whether the benefits outweigh the risk of dysrhythmias remain inconclusive. For patients who developed cytokine release syndrome, interleukin-6 inhibitors may be beneficial.", "qid": 46, "docid": "ptoyu3in", "rank": 85, "score": 0.7900222539901733}, {"content": "Title: Emerging patterns of hypercoagulability associated with critical COVID-19: A review Content: Abstract While the COVID-19 pandemic sweeps the world, much evidence is being gathered regarding its novel pathological mechanisms. It is the authors\u2019 clinical experience that patients in the intensive care unit suffering from COVID-19 are extremely pro-coagulable, with venous and arterial thromboembolism frequently observed, and losses of vascular access lines and filtration circuits to thrombosis now commonplace. Here, we explore the evidence for hypercoagulability in this group, presenting evidence of both a localised pulmonary hypercoagulability, and a systemic hypercoagulability resulting in thrombosis distant to the pulmonary vasculature. Furthermore, we discuss the possible risk factors exacerbated by, or selected for in COVID-19. We review the available evidence for use of plasma D-dimer as a prognostic marker, exploring the possibility that it acts as a marker of a COVID-19-associated hypercoagulability. We review the evidence for a pro-coagulant subtype of disseminated intravascular coagulation, discussing its clinical significance. Finally, we discuss the current evidence surrounding treatment of COVID-19 hypercoagulability, including prophylactic and treatment-dose heparin, thrombolytic agents, antiplatelet agents, and direct thrombin inhibitors, among others. We suggest areas in which further investigation is urgently needed to reduce the startling incidence of thrombosis in this group, a complication no doubt contributing to morbidity and mortality.", "qid": 46, "docid": "9khivobg", "rank": 86, "score": 0.789954662322998}, {"content": "Title: Outpatient treatment of COVID-19 with steroids in the phase of mild pneumonia without the need for admission as an opportunity to modify the course of the disease: A structured summary of a randomised controlled trial Content: OBJECTIVES: The aim of this study is to explore the effectiveness and safety of oral corticosteroids (prednisone) in the treatment of early stage SARS-Cov-2 pneumonia in patients who do not yet meet hospital admission criteria. TRIAL DESIGN: Randomized clinical trial, controlled, open, parallel group, to evaluate the effectiveness of steroids in adult patients with confirmed COVID-19, with incipient pulmonary involvement, without hospital admission criteria. Patients will be stratified by the presence or not of radiological data on pneumonia. PARTICIPANTS: We will include patients with early stage SARS-Cov-2 pneumonia who do not meet hospital admission criteria from the reference hospital, the Hospital Universitario de Burgos, in the region of Castilla y Le\u00f3n, Spain. Patients will be followed-up by specialist physicians and Primary Health Care professionals. Inclusion criteria: - Men and women. - Age between 18 and 75 years old. - Diagnosed SARS-CoV-2 infection, by PCR and/or IgM+ antibody test and/or antigen test. - Clinical diagnosis of lung involvement: (respiratory symptoms +/- pathological auscultation +/- O2 desaturation) - Chest X-ray with mild-moderate alterations or normal. - Patients who give their verbal informed consent in front of witnesses, which will be reflected in the patients\u2019 medical records. Exclusion criteria: - Oxygen desaturation below 93% or P0(2) < 62. - Moderate-severe dyspnea or significant respiratory or general deterioration that makes admission advisable. - Chest X-ray with multifocal infiltrates. - Insulin-dependent diabetes with poor control or glycaemia in the emergency room test greater than 300 mg/ml (fasting or not). - Other significant comorbidities: Severe renal failure (creatinine clearance < 30 mL/min); cirrhosis or chronic liver disease, poorly controlled hypertension. - Heart rhythm disturbances (including prolonged QT). - Severe immunosuppression (HIV infection, long-term use of immunosuppressive agents); cancer. - Pregnant or breast-feeding women. - Patients under use of glucocorticoids for other diseases. - History of allergy or intolerance to any of the drugs in the study (prednisone, azithromycin or hydroxychloroquine). - Patients who took one or more of the study drugs in the 7 days prior to study inclusion. - Patients taking non-suppressible drugs with risk of QT prolongation or significant interactions. - Patients unwilling or unable to participate until study completion. - Participation in another study. INTERVENTION AND COMPARATOR: Eligible patients will be randomized to receive standard outpatient treatment only (group 1) or standard outpatient treatment plus prednisone (group 2). - Group 1: paracetamol 1 g/8 h (on demand) + hydroxychloroquine 400 mg/12h the first day, 200 mg/12 h for 4 days + azithromycin 500 mg/24h for 5 days. - Group 2: paracetamol 1 g/8 h (on demand) + hydroxychloroquine 400 mg/12h the first day, 200 mg/12 h for 4 days + azithromycin 500 mg/24h for 5 days + prednisone 60 mg / 24 h for 3 days, 30 mg / 24 h for 3 days and 15 mg / 24 h for 3 days. MAIN OUTCOMES: If the patient requires ambulatory observation, according to the protocol established in this respect in the Emergency Department, meets all the criteria for inclusion and none for exclusion, data will be taken by the person responsible on the data collection sheet. The main result is admission after 30 days. Secondary outcomes are 30-day ICU admission and hospital stay. The safety variable will be the occurrence of clinical symptoms or delirium related to the steroids. Also, the possible decompensations of diabetes will be measured. All tests will be on an intention-to-treat basis. RANDOMISATION: Treatment will be assigned according to stratified randomization by the presence or absence of radiological data of lung involvement (previously performed by random sequence 1:1 generated with Epidat and kept hidden by opaque, sealed envelopes, which will only be opened after inclusion and basal measurement). BLINDING (MASKING): Participants, caregivers and personnel responsible for outcomes measurement will not be blinded to group assignment, once the patient is included and the basal measurement performed, as per protocol design. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The percentage of patients with incipient lung involvement is unknown, but given that pulmonary involvement already exists it is estimated to be around 20%. We consider that the intervention could reduce this percentage to 5%, so the necessary sample size would be 200 subjects (100 per group), with a power of 80% and an estimated loss percentage of 10%. TRIAL STATUS: The protocol with code TAC-COVID-19, version 2.0 on date: April 16, 2020 is approved by the Spanish Drug Agency (AEMPS) and the local Ethics Committee. The trial is in the recruitment phase. Recruitment began 19 April, 2020 and is anticipated to be complete by April 2021. TRIAL REGISTRATION: The trial was registered under the title \u201cOUTPATIENT TREATMENT OF EARLY PULMONARY COVID19 WITH CORTICOSTEROIDS AS AN OPPORTUNITY TO MODIFY THE COURSE OF THE DISEASE\u201d with EudraCT number 2020-001622-64, registered on 3 April 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.", "qid": 46, "docid": "woyysdvo", "rank": 87, "score": 0.7892768383026123}, {"content": "Title: The Rationale for Potential Pharmacotherapy of COVID-19 Content: On 11 March 2020, the coronavirus disease (COVID-19) was defined by the World Health Organization as a pandemic. Severe acute respiratory syndrome-2 (SARS-CoV-2) is the newly evolving human coronavirus infection that causes COVID-19, and it first appeared in Wuhan, China in December 2019 and spread rapidly all over the world. COVID-19 is being increasingly investigated through virology, epidemiology, and clinical management strategies. There is currently no established consensus on the standard of care in the pharmacological treatment of COVID-19 patients. However, certain medications suggested for other diseases have been shown to be potentially effective for treating this infection, though there has yet to be clear evidence. Therapies include new agents that are currently tested in several clinical trials, in addition to other medications that have been repurposed as antiviral and immune-modulating therapies. Previous high-morbidity human coronavirus epidemics such as the 2003 SARS-CoV and the 2012 Middle East respiratory syndrome coronavirus (MERS-CoV) prompted the identification of compounds that could theoretically be active against the emerging coronavirus SARS-CoV-2. Moreover, advances in molecular biology techniques and computational analysis have allowed for the better recognition of the virus structure and the quicker screening of chemical libraries to suggest potential therapies. This review aims to summarize rationalized pharmacotherapy considerations in COVID-19 patients in order to serve as a tool for health care professionals at the forefront of clinical care during this pandemic. All the reviewed therapies require either additional drug development or randomized large-scale clinical trials to be justified for clinical use.", "qid": 46, "docid": "ro1wrvf8", "rank": 88, "score": 0.7889127731323242}, {"content": "Title: Treatment of SARS-CoV-2 with high dose oral zinc salts: A report on four patients Content: Coronavirus 2019 (COVID-19) is a pandemic with substantial mortality and no accepted therapy. We report here on four consecutive outpatients with clinical characteristics (CDC case definition) of and/or laboratory-confirmed COVID-19 who were treated with high dose zinc salt oral lozenges. All four patients experienced significant improvement in objective and symptomatic disease measures after one day of high dose therapy suggesting that zinc therapy was playing a role in clinical recovery. A mechanism for zinc's effects is proposed based on previously published studies on SARS- CoV-1, and randomized controlled trials assessing zinc shortening of common cold duration. The limited sample size and study design preclude a definitive statement about the effectiveness of zinc as a treatment for COVID-19 but suggest the variables to be addressed to confirm these initial findings in future trials.", "qid": 46, "docid": "rgt1h046", "rank": 89, "score": 0.7886619567871094}, {"content": "Title: Treatment of SARS-CoV-2 with high dose oral zinc salts: A report on four patients. Content: Coronavirus 2019 (COVID-19) is a pandemic with substantial mortality and no accepted therapy. We report here on four consecutive outpatients with clinical characteristics (CDC case definition) of and/or laboratory-confirmed COVID-19 who were treated with high dose zinc salt oral lozenges. All four patients experienced significant improvement in objective and symptomatic disease measures after one day of high dose therapy suggesting that zinc therapy was playing a role in clinical recovery. A mechanism for zinc's effects is proposed based on previously published studies on SARS- CoV-1, and randomized controlled trials assessing zinc shortening of common cold duration. The limited sample size and study design preclude a definitive statement about the effectiveness of zinc as a treatment for COVID-19 but suggest the variables to be addressed to confirm these initial findings in future trials.", "qid": 46, "docid": "w3jmi043", "rank": 90, "score": 0.7886619567871094}, {"content": "Title: Effectiveness and Safety of Glucocorticoids to Treat COVID-19: A Rapid Review and Meta-Analysis Content: Background: Glucocorticoids are widely used in the treatment of various pulmonary inflammatory diseases, but they are also often accompanied by significant adverse reactions. Published guidelines point out that low dose and short duration systemic glucocorticoid therapy may be considered for patients with rapidly progressing COVID-19 while the evidence is still limited. Methods: We comprehensively searched electronic databases and supplemented the screening by conducting a manual search. We included RCTs and cohort studies evaluating the effectiveness and safety of glucocorticoids in children and adults with COVID-19, SARS and MERS, and conducted meta-analyses of the main indicators that were identified in the studies. Results: Our search retrieved 23 studies, including one RCT and 22 cohort studies, with a total of 13,815 patients. In adults with COVID-19, the use of systemic glucocorticoid did not reduce mortality (RR=2.00, 95% CI: 0.69 to 5.75, I 2=90.9%) or the duration of lung inflammation (WMD=-1 days, 95% CI: -2.91 to 0.91), while a significant reduction was found in the duration of fever (WMD=-3.23 days, 95% CI: -3.56 to -2.90). In patients with SARS, glucocorticoids also did not reduce the mortality (RR=1.52, 95% CI: 0.89 to 2.60, I2=84.6%), duration of fever (WMD=0.82 days, 95% CI: -2.88 to 4.52, I2=97.9%) or duration of lung inflammation absorption (WMD=0.95 days, 95% CI: -7.57 to 9.48, I2=94.6%). The use of systemic glucocorticoid therapy prolonged the duration of hospital stay in all patients (COVID-19, SARS and MERS). Conclusions: Glucocorticoid therapy was found to reduce the duration of fever, but not mortality, duration of hospitalization or lung inflammation absorption. Long-term use of high-dose glucocorticoids increased the risk of adverse reactions such as coinfections, so routine use of systemic glucocorticoids for patients with COVID-19 cannot be recommend. Keywords: COVID-19; glucocorticoids; meta-analysis; rapid review", "qid": 46, "docid": "935r7w01", "rank": 91, "score": 0.7880622148513794}, {"content": "Title: A COVID-19 pandemic guideline in evidence-based medicine Content: Data sources This review article scrutinised 16 clinical studies (clinical trials and observational studies) concerning coronavirus disease of 2019 (COVID-19). Additionally, 18 guidelines about the COVID-19 were reviewed and the key points were represented in this study. Study selection The review included human trials, in-vitro studies, review articles, and credible news reports about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 complications, treatment guidelines, management strategies, and epidemiological features. There were no exclusion criteria reported in this review and the included information was in English and Chinese languages. Data extraction and synthesis A descriptive review of the literature was conducted, taking a comprehensive approach. The paper consisted of three main parts: introduction, presentation, and management. The introduction part presented basic information about the SARS-CoV-2, its evolution and transmission, and the course of disease. The presentation section introduced the signs and symptoms, diagnosis, high risk groups, and complications of COVID-19. Eventually, some evidence was presented about the prevention, medical management, and measuring responses to the treatments in the management section. Results Based on the results of this study, non-pharmaceutical interventions, including strict social isolation and distancing measures, might reduce the spread of the SARS-CoV-2 by nearly 99.3 percent (reproduction number mitigating from 406 to 2.5 in 30 days). In the supportive management section, monitoring vital signs and neonatal feeding were stated as the most important factors to consider. For symptomatic neonates, medical management and intervention were mentioned as essential. It was claimed that for adults with mild infection, the best option would be home quarantine with further medical monitoring or hospitalisation if required. The following sequence was also suggested as early supportive therapy and monitoring: intravenous fluid administration, oxygen therapy, and application of corticosteroids. Management of critical patients with critical COVID-19 included admission to intensive care unit, use of continuous positive airway pressure and bi-level positive airway pressure in certain circumstances, endotracheal intubation, invasive mechanical ventilation, extracorporeal membrane oxygenation, and fluid resuscitation and vasopressors. Additionally, this study suggested oseltamivir, iopinavir, remdesivir, chloroquine, baricitinib, ruxolitinib, and fedratinib as possible drugs to help manage COVID-19. A soaring c-reactive protein level and decreased albumin content in the blood were reported to be associated with a deteriorating status in COVID-19 patients. To keep the number of exposures to a minimum, two separate viral clearance tests taken at least 24 hours apart, were stated as necessary laboratory results before the discharge of patients with COVID-19. Conclusions The study warns about possible exponential spread of COVID-19 and proposes to adhering to tighter restrictions of social distancing. Besides the clinical guidelines presented within the study, it also encourages further up-to-date and evidence-based management guidelines for patients with COVID-19.", "qid": 46, "docid": "dnshqna6", "rank": 92, "score": 0.7880369424819946}, {"content": "Title: A COVID-19 pandemic guideline in evidence-based medicine Content: Data sources This review article scrutinised 16 clinical studies (clinical trials and observational studies) concerning coronavirus disease of 2019 (COVID-19). Additionally, 18 guidelines about the COVID-19 were reviewed and the key points were represented in this study.Study selection The review included human trials, in-vitro studies, review articles, and credible news reports about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 complications, treatment guidelines, management strategies, and epidemiological features. There were no exclusion criteria reported in this review and the included information was in English and Chinese languages.Data extraction and synthesis A descriptive review of the literature was conducted, taking a comprehensive approach. The paper consisted of three main parts: introduction, presentation, and management. The introduction part presented basic information about the SARS-CoV-2, its evolution and transmission, and the course of disease. The presentation section introduced the signs and symptoms, diagnosis, high risk groups, and complications of COVID-19. Eventually, some evidence was presented about the prevention, medical management, and measuring responses to the treatments in the management section.Results Based on the results of this study, non-pharmaceutical interventions, including strict social isolation and distancing measures, might reduce the spread of the SARS-CoV-2 by nearly 99.3 percent (reproduction number mitigating from 406 to 2.5 in 30 days). In the supportive management section, monitoring vital signs and neonatal feeding were stated as the most important factors to consider. For symptomatic neonates, medical management and intervention were mentioned as essential. It was claimed that for adults with mild infection, the best option would be home quarantine with further medical monitoring or hospitalisation if required. The following sequence was also suggested as early supportive therapy and monitoring: intravenous fluid administration, oxygen therapy, and application of corticosteroids. Management of critical patients with critical COVID-19 included admission to intensive care unit, use of continuous positive airway pressure and bi-level positive airway pressure in certain circumstances, endotracheal intubation, invasive mechanical ventilation, extracorporeal membrane oxygenation, and fluid resuscitation and vasopressors. Additionally, this study suggested oseltamivir, iopinavir, remdesivir, chloroquine, baricitinib, ruxolitinib, and fedratinib as possible drugs to help manage COVID-19. A soaring c-reactive protein level and decreased albumin content in the blood were reported to be associated with a deteriorating status in COVID-19 patients. To keep the number of exposures to a minimum, two separate viral clearance tests taken at least 24 hours apart, were stated as necessary laboratory results before the discharge of patients with COVID-19.Conclusions The study warns about possible exponential spread of COVID-19 and proposes to adhering to tighter restrictions of social distancing. Besides the clinical guidelines presented within the study, it also encourages further up-to-date and evidence-based management guidelines for patients with COVID-19.", "qid": 46, "docid": "1fm9smfr", "rank": 93, "score": 0.7880369424819946}, {"content": "Title: Treatment algorithm for COVID-19: a multidisciplinary point of view Content: The novel coronavirus (Sars-CoV-2) pandemic has spread rapidly, from December to the end of March, to 185 countries, and there have been over 3,000,000 cases identified and over 200,000 deaths. For a proportion of hospitalized patients, death can occur within a few days, mainly for adult respiratory distress syndrome or multi-organ dysfunction syndrome. In these patients, clinical signs and symptoms, as well as laboratory abnormalities, suggest a cytokine storm syndrome in response to the viral infection. No current targeted treatment is yet available for COVID-19, an unknown disease up to 2 months ago, which challenges doctors and researchers to find new drugs or reallocate other treatments for these patients. Since the beginning of the COVID-19 outbreak, a growing body of information on diagnostic and therapeutic strategies has emerged, mainly based on preliminary experience on retrospective studies or small case series. Antivirals, antimalarials, corticosteroids, biotechnological and small molecules, convalescent plasma and anticoagulants are among the drugs proposed for the treatment or in tested for COVID-19. Given the complexity of this new condition, a multidisciplinary management seems to be the best approach. Sharing and integrating knowledge between specialists, to evaluate the correct timing and setting of every treatment, could greatly benefit our patients. We reviewed the literature, combining it with our experiences and our specialist knowledge, to propose a management algorithm, correlating the clinical features with laboratory and imaging findings to establish the right timing for each treatment.", "qid": 46, "docid": "ik5rdhlo", "rank": 94, "score": 0.7878570556640625}, {"content": "Title: The role of corticosteroids in the management of critically ill patients with coronavirus disease 2019 (COVID-19): A meta-analysis Content: Objective: There are no controlled studies on the role of systemic corticosteroids (CS) in patients with coronavirus disease 2019 (COVID-19). In the absence of high-quality evidence, understandably the recommendations from various organizations are cautious. Several randomized controlled trials are underway but shall take time to conclude. We therefore undertook a meta-analysis to ascertain the role of CS in the management of critically ill patients with COVID-19. Data Sources: Electronic databases, including Pubmed, Cochrane library and Embase, were searched, using the keywords of interest and the PICO search technique, from inception to 12th April 2020. Study Selection: Studies highlighting the use of CS in coronavirus infection with severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome (MERS) and COVID-19 were selected based on pre-determined inclusion criteria. Data extraction: Data was extracted into an excel sheet and transferred to comprehensive meta-analysis software version 3, Biostat Inc., Englewood, NJ, USA, for analysis. Data synthesis: Five studies with SARS-CoV-2 infection were included in the meta-analysis. The rate ratio (RR) for mortality in patients with SARS-CoV-2 infection was 1.26 (95% CI: 0.96-1.65, I2: 74.46), indicating lack of benefit of CS therapy on mortality in critically ill patients with COVID-19. The RR for mortality on analysis of the three studies that particularly reported on patients with significant pulmonary compromise secondary to SARS-CoV-2 infection was neutral (RR: 0.91, 95% CI: 0.63-1.33, I2: 63.38). Conclusions: The use of CS in critically ill patients with COVID-19 did not improve or worsen mortality. Pending further information from controlled studies, CS can be used in critically ill patients with COVID-19 with critical illness related corticosteroid insufficiency and moderate to severe ARDS without the risk of increased mortality.", "qid": 46, "docid": "w4ze158q", "rank": 95, "score": 0.7878494262695312}, {"content": "Title: The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19 Content: Abstract The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has posed the world at a pandemic risk. Coronavirus-19 disease (COVID-19) is an infectious disease caused by SARS-CoV-2, which causes pneumonia, requires intensive care unit hospitalization in about 10% of cases and can lead to a fatal outcome. Several efforts are currently made to find a treatment for COVID-19 patients. So far, several anti-viral and immunosuppressive or immunomodulating drugs have demonstrated some efficacy on COVID-19 both in vitro and in animal models as well as in cases series. In COVID-19 patients a pro-inflammatory status with high levels of interleukin (IL)-1B, IL-1 receptor (R)A and tumor necrosis factor (TNF)-\u03b1 has been demonstrated. Moreover, high levels of IL-6 and TNF-\u03b1 have been observed in patients requiring intensive-care-unit hospitalization. This provided rationale for the use of anti-rheumatic drugs as potential treatments for this severe viral infection. Other agents, such as hydroxychloroquine and chloroquine might have a direct anti-viral effect. The anti-viral aspect of immunosuppressants towards a variety of viruses has been known since long time and it is herein discussed in the view of searching for a potential treatment for SARS-CoV-2 infection.", "qid": 46, "docid": "29h189tx", "rank": 96, "score": 0.7875943183898926}, {"content": "Title: Review of Emerging Pharmacotherapy for the Treatment of Coronavirus Disease 2019 Content: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) has evolved into an emergent global pandemic. Coronavirus disease 2019 (COVID\u201019) can manifest on a spectrum of illness from mild disease to severe respiratory failure requiring intensive care unit admission. As the incidence continues to rise at a rapid pace, critical care teams are faced with challenging treatment decisions. There is currently no widely accepted standard of care in the pharmacologic management of patients with COVID\u201019. Urgent identification of potential treatment strategies is a priority. Therapies include novel agents available in clinical trials or through compassionate use, and other drugs, repurposed antiviral and immunomodulating therapies. Many have demonstrated in vitro or in vivo potential against other viruses that are similar to SARS\u2010CoV\u20102. Critically ill patients with COVID\u201019 have additional considerations related to adjustments for organ impairment and renal replacement therapies, complex lists of concurrent medications, limitations with drug administration and compatibility, and unique toxicities that should be evaluated when utilizing these therapies. The purpose of this review is to summarize practical considerations for pharmacotherapy in patients with COVID\u201019, with the intent of serving as a resource for health care providers at the forefront of clinical care during this pandemic.", "qid": 46, "docid": "bsdk64t1", "rank": 97, "score": 0.7875251770019531}, {"content": "Title: Anti-Coagulant and Anti-Platelet Therapy in the COVID-19 Patient: A Best Practices Quality Initiative Across a Large Health System. Content: The coronavirus disease 2019 (COVID-19) pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has challenged health care systems and physicians worldwide to attempt to provide the best care to their patients with an evolving understanding of this unique pathogen. This disease and its worldwide impact have sparked tremendous interest in the epidemiology, pathogenesis, and clinical consequences of COVID-19. This accumulating body of evidence has centered around case series and often empiric therapies as controlled trials are just getting underway. What is clear is that patients appear to be at higher risk for thrombotic disease states including acute coronary syndrome (ACS), venous thromboembolism (VTE) such as deep vein thrombosis (DVT) or pulmonary embolism (PE), or stroke. Patients with underlying cardiovascular disease are also at higher risk for morbidity and mortality if infected. These patients are commonly treated with anticoagulation and/or antiplatelet medications and less commonly thrombolysis during hospitalization, potentially with great benefit but management of these medications can be difficult in potentially critically ill patients.In this paper, we review the current guidelines, consensus statements, and emerging evidence for a wide range of cardiovascular disease states with special focus on anticoagulant and antiplatelet therapy. Our goal is to provide guidance for treatment of the cardiovascular patient with COVID-19 in the face of a rapidly evolving understanding of this virus and its complications.Preamble:Anticoagulant and antiplatelet therapies are a major cause of inpatient morbidity and mortality. This is amplified in critically ill patients. COVID-19 patients present special challenges due to rapidly changing clinical status. In an effort to align practice patterns across a large health system (Jefferson Health 2,622 staffed inpatient beds and 319 intensive care unit (ICU) beds across 14 facilities), a task force was assembled to address the utilization of anti-thrombotic and anti-platelet therapy in COVID-19 positive or suspected patients. The task force incorporated experts in Cardiology, Vascular Medicine, Hematology, Vascular Surgery, Pharmacy, and Vascular Neurology. Current guidelines, consensus documents, and policy documents from specialty organizations were used to formulate health system recommendations. Our deliberations and treatment recommendations are summarized here.Objective:To provide guidance to the utilization of antithrombotic and antiplatelet therapies in patients with known or suspected COVID-19.", "qid": 46, "docid": "h2zwlyz7", "rank": 98, "score": 0.7874711751937866}, {"content": "Title: Endocrine and metabolic aspects of the COVID-19 pandemic Content: COVID-19 infection has tremendously impacted our daily clinical practice as well as our social living organization. Virtually all organs and biological systems suffer from this new coronavirus infection, either because the virus targets directly specific tissues or because of indirect effects. Endocrine diseases are not an exception and some of endocrine organs are at risk of direct or indirect lesion by COVID-19. Although there is still no evidence of higher predisposition to contract the infection in patients with diabetes and/or obesity, the coexistence of these conditions contributes to a worse prognosis because both conditions confer an impaired immunologic system. Cytokines storm can be amplified by these two latter conditions thereby leading to multisystemic failure and death. Glycaemic control has been demonstrated to be crucial to avoiding long hospital stays, ICU requirement and also prevention of excessive mortality. Endocrine treatment modifications as a consequence of COVID-19 infection are required in a proactive manner, in order to avoid decompensation and eventual hospital admission. This is the case of diabetes and adrenal insufficiency in which prompt increase of insulin dosage and substitutive adrenal steroids through adoption of the sick day\u2019s rules should be warranted, as well as easy contact with the health care provider through telematic different modalities. New possible endocrinological targets of COVID-19 have been recently described and warrant a full study in the next future.", "qid": 46, "docid": "ylfc9iro", "rank": 99, "score": 0.7873733043670654}, {"content": "Title: Three novel prevention, diagnostic, and treatment options for COVID-19 urgently necessitating controlled randomized trials Content: PURPOSE: Asymptomatic or minimally symptomatic infection with COVID-19 can result in silent transmission to large numbers of individuals, resulting in expansion of the pandemic with a global increase in morbidity and mortality. New ways of screening the general population for COVID-19 are urgently needed along with novel effective prevention and treatment strategies. HYPOTHESIS: A hypothetical three-part prevention, diagnostic, and treatment approach based on an up-to-date scientific literature review for COVID-19 is proposed. Regarding diagnosis, a validated screening questionnaire and digital app for COVID-19 could help identify individuals who are at risk of transmitting the disease, as well as those at highest risk for poor clinical outcomes. Global implementation and online tracking of vital signs and scored questionnaires that are statistically validated would help health authorities properly allocate essential health care resources to test and isolate those at highest risk for transmission and poor outcomes. Second, regarding prevention, no validated protocols except for physical distancing, hand washing, and isolation exist, and recently ivermectin has been published to have anti-viral properties against COVID-19. A randomized trial of ivermectin, and/or nutraceuticals that have been published to support immune function including glutathione, vitamin C, zinc, and immunomodulatory supplements (3,6 Beta glucan) could be beneficial in preventing transmission or lessening symptomatology but requires statistical validation. Third, concerning treatment, COVID-19 induced inflammation and \"cytokine storm syndrome\" with hemophagocytic lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS) have resulted in extreme morbidity and mortality in those with certain comorbidities, secondary to \"acute respiratory distress syndrome\" (ARDS) and multiorgan dysfunction with disseminated intravascular coagulation (DIC). Deficiency in red blood cell, serum and alveolar glutathione has been published in the medical literature for ARDS, as well as viral and bacterial pneumonias, resulting from increased levels of free radical/oxidative stress. A randomized controlled trial of blocking NF-&#954;B and cytokine formation using glutathione precursors (N-acetyl-cysteine [NAC] and alpha lipoic acid) and PO/IV glutathione with associated anti-viral effects should be performed, along with an evaluation of Nrf2 activators (curcumin, sulforaphane glucosinolate) which have been scientifically proven to lower inflammation. Since high mortality rates from sepsis induced DIC due to COVID-19 infection has also been associated with thrombotic events and elevated levels of D-dimer, randomized controlled trials of using anticoagulant therapy with heparin is urgently required. This is especially important in patients on ventilators who have met certain sepsis induced coagulopathy (SIC) criteria. The use of acetazolamide with or without sildenafil also needs to be explored with or without heparin, since increased oxygen delivery to vital organs through prevention of thrombosis/pulmonary emboli along with carbonic anhydrase inhibition may help increase oxygenation and prevent adverse clinical outcomes. CONCLUSION AND IMPLICATIONS: A three-part prevention, diagnostic, and treatment plan is proposed for addressing the severe complications of COVID-19. Digital monitoring of symptoms to clinically diagnose early exposure and response to treatment; prevention with ivermectin as well as nutritional therapies that support a healthy immune response; treatment with anti-inflammatory therapies that block NF-&#954;B and activate Nrf2 pathways, as well as novel therapies that address COVID-19 pneumonia and ARDS with DIC including anticoagulation and/or novel respiratory therapies with or without acetazolamide and sildenafil. These three broad-based interventions urgently need to be subjected to randomized, controlled trials.", "qid": 46, "docid": "k1zlmd2k", "rank": 100, "score": 0.7873176336288452}]}
{"query": "what are the health outcomes for children who contract COVID-19?", "hits": [{"content": "Title: Managing COVID-19 disease in pediatric patients Content: Children are less likely to be infected with SARS-CoV-2 than adults and often have a milder course of COVID-19 disease and a lower case fatality rate. Children account for an estimated 1% to 5% of those diagnosed with COVID-19. Even so, preschool-aged children, infants, and children with underlying health conditions may still be at risk for severe disease and complications. Unique aspects of COVID-19 presentation and disease course in children and possible vertical transmission to newborns from COVID-19-positive mothers are discussed.", "qid": 47, "docid": "4f8v0tou", "rank": 1, "score": 0.8215926885604858}, {"content": "Title: Coronavirus disease 2019 (COVID-19) in children and/or adolescents: a meta-analysis Content: BACKGROUND: To assess the overall prevalence of clinical signs, symptoms, and radiological findings in children and/or adolescents with COVID-19. METHODS: We systematically researched in PubMed, Scopus and Web of Science databases observational studies describing COVID-19 in children and/or adolescents until April 11, 2020. Data regarding clinical and radiological features were extracted from eligible studies and meta-analysis was performed using random-effects modeling. RESULTS: We examined 19 eligible studies for a total of 2855 children and/or adolescents with COVID-19. Approximately 47% of subjects had fever (95% confidence interval [CI] 22-72%; I2 = 98.6%), 37% cough (95%CI 15-63%; I2 = 98.6%), 4% diarrhea (95%CI 0-12%; I2 = 92.2%), 2% nasal congestion (95%CI 0-7%; I2 = 87.7%), 1% dyspnea (95%CI 0-7%; I2 = 91.5%) and 0% abdominal pain (95%CI 0-1%; I2 = 76.3%). Subjects presented mild symptoms in 79% (95%CI 65-91%; I2 = 93.5%) of cases, whereas only 4% (95%CI 1-9%; I2 = 76.4%) were critical. Among those with pneumonia on computed tomography, 26.4% (95%CI 13-41%; I2 = 80.8%) presented a unilateral involvement, 16% (95%CI 5-29%, I2 = 81.2%) had bilateral involvement and 9% (95%CI 0-24%; I2 = 88.7%) had interstitial pneumonia. CONCLUSIONS: Children and/or adolescents tend to have a mild COVID-19 course with a good prognosis. IMPACT: Compared to adults, children and/or adolescents tend to have a mild COVID-19 course with a good prognosis.This study provides new and consistence information on the clinical and radiological characteristics of COVID-19 in pediatrics.This study may help to fight COVID-19 in pediatric population.", "qid": 47, "docid": "hw4kgs6h", "rank": 2, "score": 0.8197200298309326}, {"content": "Title: Clinical Features and Outcome of SARS-CoV-2 Infection in Children: A Systematic Review and Meta-analysis. Content: BACKGROUND AND OBJECTIVE Knowledge about COVID-19 in children is limited due to the paucity of reported data. The pediatric age group comprises only less than 5% of total COVID-19 worldwide, therefore, large studies in this population are unlikely in the immediate future. Hence, we planned to synthesize the current data that will help in a better understanding of COVID-19 in children. METHODS Four different electronic databases (MEDLINE, EMBASE, Web of Science, and CENTRAL) were searched for articles related to COVID-19 in the pediatric population. We included studies reporting disease characteristics and outcomes of COVID-19 in patients aged less than 19 years. We performed a random-effect meta-analysis to provide pooled estimates of various disease characteristics. RESULTS 27 studies (4857 patients) fulfilling the eligibility criteria were included in this systematic review, from a total of 883 records. About half of the patients had each of fever and cough, 11% (6-17%) had fast breathing, and 6-13% had gastrointestinal manifestations. Most of the patients had mild to moderate disease, and only 4% had a severe or critical illness. Leukopenia was the commonest reported laboratory abnormality. CONCLUSION Even among the symptomatic COVID-19 cases, severe manifestations are seen in very few children. Though fever and respiratory symptoms are most common, many children also have gastrointestinal manifestations.", "qid": 47, "docid": "6zqp53tk", "rank": 3, "score": 0.8180912733078003}, {"content": "Title: Clinical Features and Outcome of SARS-CoV-2 Infection in Children: A Systematic Review and Meta-analysis Content: BACKGROUND AND OBJECTIVE: Knowledge about COVID-19 in children is limited due to the paucity of reported data. The pediatric age group comprises only less than 5% of total COVID-19 worldwide, therefore, large studies in this population are unlikely in the immediate future. Hence, we planned to synthesize the current data that will help in a better understanding of COVID-19 in children. METHODS: Four different electronic databases (MEDLINE, EMBASE, Web of Science, and CENTRAL) were searched for articles related to COVID-19 in the pediatric population. We included studies reporting disease characteristics and outcomes of COVID-19 in patients aged less than 19 years. We performed a random-effect meta-analysis to provide pooled estimates of various disease characteristics. RESULTS: 27 studies (4857 patients) fulfilling the eligibility criteria were included in this systematic review, from a total of 883 records. About half of the patients had each of fever and cough, 11% (6-17%) had fast breathing, and 6-13% had gastrointestinal manifestations. Most of the patients had mild to moderate disease, and only 4% had a severe or critical illness. Leukopenia was the commonest reported laboratory abnormality. CONCLUSION: Even among the symptomatic COVID-19 cases, severe manifestations are seen in very few children. Though fever and respiratory symptoms are most common, many children also have gastrointestinal manifestations.", "qid": 47, "docid": "z6trtz8s", "rank": 4, "score": 0.8179727792739868}, {"content": "Title: Coronavirus disease 2019 (COVID-19) in children and/or adolescents: a meta-analysis. Content: BACKGROUND To assess the overall prevalence of clinical signs, symptoms, and radiological findings in children and/or adolescents with COVID-19. METHODS We systematically researched in PubMed, Scopus and Web of Science databases observational studies describing COVID-19 in children and/or adolescents until April 11, 2020. Data regarding clinical and radiological features were extracted from eligible studies and meta-analysis was performed using random-effects modeling. RESULTS We examined 19 eligible studies for a total of 2855 children and/or adolescents with COVID-19. Approximately 47% of subjects had fever (95% confidence interval [CI] 22-72%; I2 = 98.6%), 37% cough (95%CI 15-63%; I2 = 98.6%), 4% diarrhea (95%CI 0-12%; I2 = 92.2%), 2% nasal congestion (95%CI 0-7%; I2 = 87.7%), 1% dyspnea (95%CI 0-7%; I2 = 91.5%) and 0% abdominal pain (95%CI 0-1%; I2 = 76.3%). Subjects presented mild symptoms in 79% (95%CI 65-91%; I2 = 93.5%) of cases, whereas only 4% (95%CI 1-9%; I2 = 76.4%) were critical. Among those with pneumonia on computed tomography, 26.4% (95%CI 13-41%; I2 = 80.8%) presented a unilateral involvement, 16% (95%CI 5-29%, I2 = 81.2%) had bilateral involvement and 9% (95%CI 0-24%; I2 = 88.7%) had interstitial pneumonia. CONCLUSIONS Children and/or adolescents tend to have a mild COVID-19 course with a good prognosis. IMPACT Compared to adults, children and/or adolescents tend to have a mild COVID-19 course with a good prognosis. This study provides new and consistence information on the clinical and radiological characteristics of COVID-19 in pediatrics. This study may help to fight COVID-19 in pediatric population.", "qid": 47, "docid": "8cc26phd", "rank": 5, "score": 0.815456748008728}, {"content": "Title: Managing COVID-19 Iinfection in pediatric patients. Content: Children are less likely to be infected with SARS-CoV-2 than adults and often have a milder course of illness and a lower case fatality rate. Children account for an estimated 1% to 5% of those diagnosed with COVID-19.1 Even so, pre-school-aged children, infants, and children with underlying health conditions may still be at risk for severe disease and complications.2 Unique aspects of COVID-19 presentation and course in children and possible vertical transmission to newborns from COVID-19-positive mothers are discussed.", "qid": 47, "docid": "yxatsk8l", "rank": 6, "score": 0.8140832781791687}, {"content": "Title: Coronavirus Disease 2019 (COVID-19) in Children - What We Know So Far and What We Do Not Content: Pediatric coronavirus disease-19 (COVID-19) infection is relatively mild when compared to adults, and children are reported to have a better prognosis. Mortality in children appears rare. Clinical features of COVID-19 in children include fever and cough, but a large proportion of infected children appears to be asymptomatic and may contribute to transmission. It remains unclear why children and young adults are less severely affected than older individuals, but this might involve differences in immune system function in the elderly and/or differences in the expression/function of the cellular receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)- Angiotensin converting enzyme 2 (ACE2). Laboratory findings and chest imaging may not be specific in children with COVID-19. Diagnosis is by Reverse transcriptase-Polymerase chain reaction (RT-PCR) testing of upper or lower respiratory tract secretions. This review additionally considers COVID-19 in immunosuppressed children, and also suggests a management algorithm for the few children who appear to present with life threatening infection, including the potential use of antiviral and immunomodulatory treatment. The most significant threat to global child health from SARS-CoV-2 is unlikely to be related to COVID 19 in children, but rather the socio-economic consequences of a prolonged pandemic.", "qid": 47, "docid": "18q23z8l", "rank": 7, "score": 0.8137872219085693}, {"content": "Title: COVID-19 in Children with Brain-Based Developmental Disabilities: A Rapid Review Content: Background. The prevalence of symptomatic COVID-19 in children remains low to date. In just a few months, COVID-19 has affected millions of people worldwide, and as of the date of this publication, the pandemic continues. Based on the current available evidence, children do not appear to be at higher risk of contracting COVID-19 than adults. However, children with neurological and neuromuscular conditions are vulnerable to the respiratory complications of other viral infections. Objectives. To assess whether children with brain-based developmental disabilities were more likely to develop COVID-19 and have complications or poorer outcomes following infection. Methods. We conducted a two-week rapid review on studies with primary data regarding children aged between zero and 18 years old with brain-based developmental disabilities, or who were at risk of developing such disabilities, with confirmed or suspected COVID-19. We performed our literature searches on April 18, 2020. Results. Our search strategy identified 538 individual records, of which four were included in our review. Of the 50 COVID-19 pediatric patients reported in the included studies, a total of seven children were at risk of developing brain-based disabilities. Symptoms ranged in severity. However, generally, patients were discharged or saw improvements in their symptoms by the end of the study period. No deaths were reported. Discussion. Our study highlights a knowledge gap regarding the impact of COVID-19 in children with brain-based developmental disabilities.", "qid": 47, "docid": "wjbh1z8y", "rank": 8, "score": 0.8134438395500183}, {"content": "Title: Characteristic of COVID-19 infection in pediatric patients: early findings from two Italian Pediatric Research Networks Content: Detailed data on clinical presentations and outcomes of children with COVID-19 in Europe are still lacking. In this descriptive study, we report on 130 children with confirmed COVID-19 diagnosed by 28 centers (mostly hospitals), in 10 regions in Italy, during the first months of the pandemic. Among these, 67 (51.5%) had a relative with COVID-19 while 34 (26.2%) had comorbidities, with the most frequent being respiratory, cardiac, or neuromuscular chronic diseases. Overall, 98 (75.4%) had an asymptomatic or mild disease, 11 (8.5%) had moderate disease, 11 (8.5%) had a severe disease, and 9 (6.9%) had a critical presentation with infants below 6 months having significantly increased risk of critical disease severity (OR 5.6, 95% CI 1.3 to 29.1). Seventy-five (57.7%) children were hospitalized, 15 (11.5%) needed some respiratory support, and nine (6.9%) were treated in an intensive care unit. All recovered.Conclusion:This descriptive case series of children with COVID-19, mostly encompassing of cases enrolled at hospital level, suggest that COVID-19 may have a non-negligible rate of severe presentations in selected pediatric populations with a relatively high rates of comorbidities. More studies are needed to further understand the presentation and outcomes of children with COVID-19 in children with special needs. What is Known: \u00e2\u0080\u00a2 There is limited evidence on the clinical presentation and outcomes of children with COVID-19 in Europe, and almost no evidence on characteristics and risk factors of severe cases. What is New: \u00e2\u0080\u00a2 Among a case series of 130 children, mostly diagnosed at hospital level, and with a relatively high rate (26.2%) of comorbidities, about three-quarter had an asymptomatic or mild disease. \u00e2\u0080\u00a2 However, 57.7% were hospitalized, 11.5% needed some respiratory support, and 6.9% were treated in an intensive care unit.", "qid": 47, "docid": "u7arfoym", "rank": 9, "score": 0.8130617141723633}, {"content": "Title: Characteristic of COVID-19 infection in pediatric patients: early findings from two Italian Pediatric Research Networks Content: Detailed data on clinical presentations and outcomes of children with COVID-19 in Europe are still lacking. In this descriptive study, we report on 130 children with confirmed COVID-19 diagnosed by 28 centers (mostly hospitals), in 10 regions in Italy, during the first months of the pandemic. Among these, 67 (51.5%) had a relative with COVID-19 while 34 (26.2%) had comorbidities, with the most frequent being respiratory, cardiac, or neuromuscular chronic diseases. Overall, 98 (75.4%) had an asymptomatic or mild disease, 11 (8.5%) had moderate disease, 11 (8.5%) had a severe disease, and 9 (6.9%) had a critical presentation with infants below 6 months having significantly increased risk of critical disease severity (OR 5.6, 95% CI 1.3 to 29.1). Seventy-five (57.7%) children were hospitalized, 15 (11.5%) needed some respiratory support, and nine (6.9%) were treated in an intensive care unit. All recovered. Conclusion:This descriptive case series of children with COVID-19, mostly encompassing of cases enrolled at hospital level, suggest that COVID-19 may have a non-negligible rate of severe presentations in selected pediatric populations with a relatively high rates of comorbidities. More studies are needed to further understand the presentation and outcomes of children with COVID-19 in children with special needs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00431-020-03683-8) contains supplementary material, which is available to authorized users.", "qid": 47, "docid": "62ic8r0s", "rank": 10, "score": 0.809059202671051}, {"content": "Title: What we know so far about Coronavirus Disease 2019 in children: A meta-analysis of 551 laboratory-confirmed cases Content: AIM: To summarize what we know so far about coronavirus disease (COVID-19) in children. METHOD: We searched PubMed, Scientific Electronic Library Online, and Latin American and Caribbean Center on Health Sciences Information from 1 January 2020 to 4 May 2020. We selected randomized trials, observational studies, case series or case reports, and research letters of children ages birth to 18 years with laboratory-confirmed COVID-19. We conducted random-effects meta-analyses to calculate the weighted mean prevalence and 95% confidence interval (CI) or the weighted average means and 95% CI. RESULT: Forty-six articles reporting 551 cases of COVID-19 in children (aged 1 day-17.5 years) were included. Eighty-seven percent (95% CI: 77%-95%) of patients had household exposure to COVID-19. The most common symptoms and signs were fever (53%, 95% CI: 45%-61%), cough (39%, 95% CI: 30%-47%), and sore throat/pharyngeal erythema (14%, 95% CI: 4%-28%); however, 18% (95% CI: 11%-27%) of cases were asymptomatic. The most common radiographic and computed tomography (CT) findings were patchy consolidations (33%, 95% CI: 23%-43%) and ground glass opacities (28%, 95% CI: 18%-39%), but 36% (95% CI: 28%-45%) of patients had normal CT images. Antiviral agents were given to 74% of patients (95% CI: 52%-92%). Six patients, all with major underlying medical conditions, needed invasive mechanical ventilation, and one of them died. CONCLUSION: Previously healthy children with COVID-19 have mild symptoms. The diagnosis is generally suspected from history of household exposure to COVID-19 case. Children with COVID-19 and major underlying condition are more likely to have severe/critical disease and poor prognosis, even death.", "qid": 47, "docid": "dqjwcm0i", "rank": 11, "score": 0.8060112595558167}, {"content": "Title: Clinical characteristics of children with COVID-19: a rapid review and meta-analysis. Content: Background Most guidelines on COVID-19 published so far include recommendations for patients regardless of age. Clinicians need a more accurate understanding of the clinical characteristics of children with COVID-19. Methods We searched studies reporting clinical characteristics in children with COVID-19 published until March 31, 2020. We screened the literature, extracted the data and evaluated the risk of bias and quality of evidence of the included studies. We combined some of the outcomes (symptoms) in a single-arm meta-analysis using a random-effects model. Results Our search retrieved 49 studies, including 25 case reports, 23 case series and one cohort study, with a total of 1,667 patients. Our meta-analysis showed that most children with COVID-19 have mild symptoms. Eighty-three percent of the children were within family clusters of cases, and 19% had no symptoms. At least 7% with digestive symptoms. The main symptoms of children were fever [48%, 95% confidence interval (CI): 39%, 56%] and cough (39%, 95% CI: 30%, 48%). The lymphocyte count was below normal level in only 15% (95% CI: 8%, 22%) of children which is different from adult patients. 66% (95% CI: 55%, 77%) of children had abnormal findings in CT imaging. Conclusions Most children with COVID-19 have only mild symptoms, and many children are asymptomatic. Fever and cough are the most common symptoms in children. Vomiting and diarrhea were not common in children. The lymphocyte count is usually within the normal range in children.", "qid": 47, "docid": "n0r2imd4", "rank": 12, "score": 0.80511474609375}, {"content": "Title: Novel coronavirus infection (COVID-19) in children younger than one year: A systematic review of symptoms, management and outcomes Content: AIM: The aim of this systematic review was to evaluate the clinical characteristics of COVID-19 in neonates and children under one year of age. METHODS: A systematic literature review of the MEDLINE, PubMed, CINAHL, Embase and EBSCO databases was carried out for studies from January 1, 2020, to April 7, 2020. We included all papers that addressed clinical manifestations, laboratory results, imaging findings and outcomes in infants and neonates. RESULTS: Our search identified 77 peer-reviewed papers, and 18 papers covering 160 infants were reviewed. One paper was from Vietnam, and the other 17 were from China: eight were cross-sectional studies, eight were case reports, one was a case series, and one was a prospective cohort study. The most common clinical symptoms were fever (54%) and cough (33%). Most infants were treated symptomatically, with frequent use of various empirical medications. Infants and neonates tended to have more severe COVID-19 disease than older children: 11 (7%) were admitted to intensive care and one infant died. The mortality rate was 0.006%, with favourable outcomes in most cases. CONCLUSION: Infants and neonates were more vulnerable to more severe COVID-19 disease than older children, but morbidity and mortality were low.", "qid": 47, "docid": "1n3t23ag", "rank": 13, "score": 0.8049563765525818}, {"content": "Title: Coronavirus Disease (COVID-19) in Children - What We Know So Far and What We Do Not? Content: Pediatric coronavirus disease - 19 (COVID-19) infection is relatively mild when compared to adults, and children are reported to have a better prognosis Mortality in children appears rare Clinical features of COVID-19 in children include fever and cough, but a large proportion of infected children appears to be asymptomatic and may contribute to transmission It remains unclear why children and young adults are less severely affected than older individuals, but this might involve differences in immune system function in the elderly and/or differences in the expression/function of the cellular receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) - Angiotensin converting enzyme 2 (ACE2) Laboratory findings and chest imaging may not be specific in children with COVID-19 Diagnosis is by Reverse transcriptase-Polymerase chain reaction (RT-PCR) testing of upper or lower respiratory tract secretions This review additionally considers COVID-19 in immunosuppressed children, and also suggests a management algorithm for the few children who appear to present with life threatening infection, including the potential use of antiviral and immunomodulatory treatment The most significant threat to global child health from SARS-CoV-2 is unlikely to be related to COVID 19 in children, but rather the socio-economic consequences of a prolonged pandemic", "qid": 47, "docid": "03vy3uaj", "rank": 14, "score": 0.8026577234268188}, {"content": "Title: Clinical Characteristics of Children with Coronavirus Disease 2019 in Hubei, China Content: Since December 2019, COVID-19 has occurred unexpectedly and emerged as a health problem worldwide. Despite the rapidly increasing number of cases in subsequent weeks, the clinical characteristics of pediatric cases are rarely described. A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province. A total of 25 confirmed pediatric cases of COVID-19 were collected. The demographic data, epidemiological history, underlying diseases, clinical manifestations, laboratory and radiological data, treatments, and outcomes were analyzed. Of 25 hospitalized patients with COVID-19, the boy to girl ratio was 1.27:1. The median age was 3 years. COVID-19 cases in children aged <3 years, 3.6 years, and \u22656-years patients were 10 (40%), 6 (24%), and 9 (36%), respectively. The most common symptoms at onset of illness were fever (13 [52%]), and dry cough (11 [44%]). Chest CT images showed essential normal in 8 cases (33.3%), unilateral involvement of lungs in 5 cases (20.8%), and bilateral involvement in 11 cases (45.8%). Clinical diagnoses included upper respiratory tract infection (n=8), mild pneumonia (n=15), and critical cases (n=2). Two critical cases (8%) were given invasive mechanical ventilation, corticosteroids, and immunoglobulin. The symptoms in 24 (96%) of 25 patients were alleviated and one patient had been discharged. It was concluded that children were susceptible to COVID-19 like adults, while the clinical presentations and outcomes were more favorable in children. However, children less than 3 years old accounted for majority cases and critical cases lied in this age group, which demanded extra attentions during home caring and hospitalization treatment.", "qid": 47, "docid": "ou80n3p3", "rank": 15, "score": 0.8022288084030151}, {"content": "Title: Clinical Characteristics of Children with COVID-19: A Rapid Review and Meta-Analysis Content: Abstract Background: Most guidelines on COVID-19 published so far include recommendations for patients regardless of age. Clinicians need a more accurate understanding of the clinical characteristics of children with COVID-19. Methods: We searched studies reporting clinical characteristics in children with COVID-19 published until March 31, 2020. We screened the literature, extracted the data and evaluated the risk of bias and quality of evidence of the included studies. We combined some of the outcomes (symptoms) in a single-arm meta-analysis using a random-effects model. Results: Our search retrieved 49 studies, including 25 case reports, 23 case series and one cohort study, with a total of 1667 patients. Our meta-analysis showed that most children with COVID-19 have mild symptoms. Eighty-three percent of the children were within family clusters of cases, and 19% had no symptoms. At least 7% with digestive symptoms. The main symptoms of children were fever (48%, 95% confidence interval [CI]: 39%, 56%) and cough (39%, 95% CI: 30%, 48%). The lymphocyte count was below normal level in only 15% [95% CI: 8%, 22%] of children which is different from adult patients. 66% [95% CI: 55%, 77%] of children had abnormal findings in CT imaging. Conclusions: Most children with COVID-19 have only mild symptoms, and many children are asymptomatic. Fever and cough are the most common symptoms in children. Vomiting and diarrhea were not common in children. The lymphocyte count is usually within the normal range in children.", "qid": 47, "docid": "jsjxdmi2", "rank": 16, "score": 0.8014094233512878}, {"content": "Title: Clinical Characteristics of Children with Coronavirus Disease 2019 in Hubei, China Content: Since December 2019, COVID-19 has occurred unexpectedly and emerged as a health problem worldwide. Despite the rapidly increasing number of cases in subsequent weeks, the clinical characteristics of pediatric cases are rarely described. A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province. A total of 25 confirmed pediatric cases of COVID-19 were collected. The demographic data, epidemiological history, underlying diseases, clinical manifestations, laboratory and radiological data, treatments, and outcomes were analyzed. Of 25 hospitalized patients with COVID-19, the boy to girl ratio was 1.27:1. The median age was 3 years. COVID-19 cases in children aged <3 years, 3.6 years, and &#8805;6-years patients were 10 (40%), 6 (24%), and 9 (36%), respectively. The most common symptoms at onset of illness were fever (13 [52%]), and dry cough (11 [44%]). Chest CT images showed essential normal in 8 cases (33.3%), unilateral involvement of lungs in 5 cases (20.8%), and bilateral involvement in 11 cases (45.8%). Clinical diagnoses included upper respiratory tract infection (n=8), mild pneumonia (n=15), and critical cases (n=2). Two critical cases (8%) were given invasive mechanical ventilation, corticosteroids, and immunoglobulin. The symptoms in 24 (96%) of 25 patients were alleviated and one patient had been discharged. It was concluded that children were susceptible to COVID-19 like adults, while the clinical presentations and outcomes were more favorable in children. However, children less than 3 years old accounted for majority cases and critical cases lied in this age group, which demanded extra attentions during home caring and hospitalization treatment.", "qid": 47, "docid": "ioauiuu5", "rank": 17, "score": 0.8002350330352783}, {"content": "Title: Pediatric COVID-19: Systematic review of the literature Content: OBJECTIVES: There is limited data regarding the demographics and clinical features of SARS-CoV-2 infection in children. This information is especially important as pneumonia is the single leading cause of death in children worldwide. This Systematic Review aims to elucidate a better understanding of the global impact of COVID-19 on the pediatric population. METHODS: A systematic review of the literature was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to gain insight into pediatric COVID-19 epidemiology. Specifically, Pubmed and Google Scholar databases were searched to identify any relevant article with a focus on Pediatric Covid 19, Pediatric Covid-19, Pediatric SARS-COV-2, and Pediatric Coronavirus 19. References within the included articles were reviewed. All articles that met criteria where analyzed for demographics, clinical, laboratory, radiographic, treatment and outcomes data. RESULTS: Ten studies including two case series and 8 retrospective chart reviews, altogether describing a total of 2914 pediatric patients with COVID-19 were included in this systematic review. Of the patients whose data was available, 56% were male, the age range was 1\u00e2\u0080\u00afday to 17\u00e2\u0080\u00afyears, 79% were reported to have no comorbidities, and of the 21% with comorbidities, the most common were asthma, immunosupression, and cardiovascular disease. Of pediatric patients that were tested and positive for an infection with SARS-CoV-2, patients were asymptomatic, 14.9% of the time. Patients presented with cough (48%), fever (47%) and sore throat/pharyngitis (28.6%), more commonly than with upper respiratory symptoms/rhinorrhea/sneezing/nasal congestion (13.7%), vomiting/nausea (7.8%) and diarrhea (10.1%). Median lab values including those for WBC, lymphocyte count and CRP, were within the reference ranges with the exception of procalcitonin levels, which were slightly elevated in children with COVID-19 (median procalcitonin levels ranged from 0.07 to 0.5\u00e2\u0080\u00afng/mL. Computed tomography (CT) results suggest that unilateral CT imaging findings are present 36% of cases while 64% of pediatric patients with COVID-19 had bilateral findings. Of the studies with age specific hospitalization data available, 27.0% of patients hospitalized were infants under 1\u00e2\u0080\u00afyear of age. Various treatment regimens including interferon, antivirals, and hydroxychloroquine therapies have been trialed on the pediatric population but there are currently no studies showing efficacy of one regimen over the other. The mortality rate of children that were hospitalized with COVID-19 was 0.0018%. CONCLUSION: In contrast to adults, most infected children appear to have a milder course and have better outcomes overall. Additional care may be needed for children with comorbidities and younger children. This review also suggests that unilateral CT chest imaging findings were seen in 36.4% pediatric COVID-19 patients. This is particularly concerning as the work-up of pediatric patients with cough may warrant a bronchoscopy to evaluate for airway foreign bodies. Extra precautions need to be taken with personal protective equipment for these cases, as aerosolizing procedures may be a method of viral transmission. LEVEL OF EVIDENCE: 4 (Systematic Review).", "qid": 47, "docid": "fmmm8itx", "rank": 18, "score": 0.7999714612960815}, {"content": "Title: Coronavirus Disease 2019 (COVID-19) in Children: Vulnerable or Spared? A Systematic Review Content: The ongoing pandemic of coronavirus disease 2019 (COVID-19) has affected people from all cultures, religions, gender, and age groups around the world. In the last few months, several studies have been conducted on various aspects of COVID-19. Our goal was to see if the pediatric population is vulnerable to this infection. In this review, we conducted extensive research mainly by using the PubMed database. We used Medical Subject Headings (MeSH) and associated keywords to engage in an extensive search focussing on COVID-19 in the pediatric population. We discovered that most of the studies were from China, and some of them were in the Chinese language. However, English translations of many of the studies were available. For accessing the relevant statistical data, we relied on the World Health Organization (WHO) resources and the official website of the Ontario Government (ontario.ca). Most of the studies showed that the virus has affected the pediatric population. However, we found some differences among these studies regarding the severity of symptoms in children affected by COVID-19. While a few studies stated that the virus has presented with milder symptoms in the pediatric population, some studies have presented data of children who have suffered life-threatening complications due to COVID-19. Although the data is limited, we have been able to conclude from the studies we reviewed that COVID-19 does indeed affect children the same way as any other age group. Moreover, children can act as carriers of the virus and can endanger the lives of other individuals. Besides, neonates and infants can easily acquire the infection from family members without having any exposure to the outside world. Hence, utmost care should be taken while handling this population. More trials and studies should be conducted to analyze the impact of early diagnosis of infection in children and its management.", "qid": 47, "docid": "62cyo5kj", "rank": 19, "score": 0.798738420009613}, {"content": "Title: Pediatric COVID-19: Systematic review of the literature. Content: OBJECTIVES There is limited data regarding the demographics and clinical features of SARS-CoV-2 infection in children. This information is especially important as pneumonia is the single leading cause of death in children worldwide. This Systematic Review aims to elucidate a better understanding of the global impact of COVID-19 on the pediatric population. METHODS A systematic review of the literature was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to gain insight into pediatric COVID-19 epidemiology. Specifically, Pubmed and Google Scholar databases were searched to identify any relevant article with a focus on Pediatric Covid 19, Pediatric Covid-19, Pediatric SARS-COV-2, and Pediatric Coronavirus 19. References within the included articles were reviewed. All articles that met criteria where analyzed for demographics, clinical, laboratory, radiographic, treatment and outcomes data. RESULTS Ten studies including two case series and 8 retrospective chart reviews, altogether describing a total of 2914 pediatric patients with COVID-19 were included in this systematic review. Of the patients whose data was available, 56% were male, the age range was 1 day to 17 years, 79% were reported to have no comorbidities, and of the 21% with comorbidities, the most common were asthma, immunosupression, and cardiovascular disease. Of pediatric patients that were tested and positive for an infection with SARS-CoV-2, patients were asymptomatic, 14.9% of the time. Patients presented with cough (48%), fever (47%) and sore throat/pharyngitis (28.6%), more commonly than with upper respiratory symptoms/rhinorrhea/sneezing/nasal congestion (13.7%), vomiting/nausea (7.8%) and diarrhea (10.1%). Median lab values including those for WBC, lymphocyte count and CRP, were within the reference ranges with the exception of procalcitonin levels, which were slightly elevated in children with COVID-19 (median procalcitonin levels ranged from 0.07 to 0.5 ng/mL. Computed tomography (CT) results suggest that unilateral CT imaging findings are present 36% of cases while 64% of pediatric patients with COVID-19 had bilateral findings. Of the studies with age specific hospitalization data available, 27.0% of patients hospitalized were infants under 1 year of age. Various treatment regimens including interferon, antivirals, and hydroxychloroquine therapies have been trialed on the pediatric population but there are currently no studies showing efficacy of one regimen over the other. The mortality rate of children that were hospitalized with COVID-19 was 0.0018%. CONCLUSION In contrast to adults, most infected children appear to have a milder course and have better outcomes overall. Additional care may be needed for children with comorbidities and younger children. This review also suggests that unilateral CT chest imaging findings were seen in 36.4% pediatric COVID-19 patients. This is particularly concerning as the work-up of pediatric patients with cough may warrant a bronchoscopy to evaluate for airway foreign bodies. Extra precautions need to be taken with personal protective equipment for these cases, as aerosolizing procedures may be a method of viral transmission. LEVEL OF EVIDENCE 4 (Systematic Review).", "qid": 47, "docid": "4pwxplhh", "rank": 20, "score": 0.7982860803604126}, {"content": "Title: Consensus statement of the Italian society of pediatric allergy and immunology for the pragmatic management of children and adolescents with allergic or immunological diseases during the COVID-19 pandemic Content: The COVID-19 pandemic has surprised the entire population. The world has had to face an unprecedented pandemic. Only, Spanish flu had similar disastrous consequences. As a result, drastic measures (lockdown) have been adopted worldwide. Healthcare service has been overwhelmed by the extraordinary influx of patients, often requiring high intensity of care. Mortality has been associated with severe comorbidities, including chronic diseases. Patients with frailty were, therefore, the victim of the SARS-COV-2 infection. Allergy and asthma are the most prevalent chronic disorders in children and adolescents, so they need careful attention and, if necessary, an adaptation of their regular treatment plans. Fortunately, at present, young people are less suffering from COVID-19, both as incidence and severity. However, any age, including infancy, could be affected by the pandemic. Based on this background, the Italian Society of Pediatric Allergy and Immunology has felt it necessary to provide a Consensus Statement. This expert panel consensus document offers a rationale to help guide decision-making in the management of children and adolescents with allergic or immunologic diseases.", "qid": 47, "docid": "pw3vszh0", "rank": 21, "score": 0.7979786396026611}, {"content": "Title: Consensus statement of the Italian society of pediatric allergy and immunology for the pragmatic management of children and adolescents with allergic or immunological diseases during the COVID-19 pandemic Content: The COVID-19 pandemic has surprised the entire population. The world has had to face an unprecedented pandemic. Only, Spanish flu had similar disastrous consequences. As a result, drastic measures (lockdown) have been adopted worldwide. Healthcare service has been overwhelmed by the extraordinary influx of patients, often requiring high intensity of care. Mortality has been associated with severe comorbidities, including chronic diseases. Patients with frailty were, therefore, the victim of the SARS-COV-2 infection. Allergy and asthma are the most prevalent chronic disorders in children and adolescents, so they need careful attention and, if necessary, an adaptation of their regular treatment plans. Fortunately, at present, young people are less suffering from COVID-19, both as incidence and severity. However, any age, including infancy, could be affected by the pandemic.Based on this background, the Italian Society of Pediatric Allergy and Immunology has felt it necessary to provide a Consensus Statement. This expert panel consensus document offers a rationale to help guide decision-making in the management of children and adolescents with allergic or immunologic diseases.", "qid": 47, "docid": "31njngcs", "rank": 22, "score": 0.7979786396026611}, {"content": "Title: COVID-19 in 7780 pediatric patients: A systematic review Content: BACKGROUND: Studies summarizing the clinical picture of COVID-19 in children are lacking. This review characterizes clinical symptoms, laboratory, and imaging findings, as well as therapies provided to confirmed pediatric cases of COVID-19. METHODS: Adhering to PRISMA guidelines, we searched four medical databases (PubMed, LitCovid, Scopus, WHO COVID-19 database) between December 1, 2019 to May 14, 2020 using the keywords \u201cnovel coronavirus\u201d, \u201cCOVID-19\u201d or \u201cSARS-CoV-2\u201d. We included published or in press peer-reviewed cross-sectional, case series, and case reports providing clinical signs, imaging findings, and/or laboratory results of pediatric patients who were positive for COVID-19. Risk of bias was appraised through the quality assessment tool published by the National Institutes of Health. PROSPERO registration # CRD42020182261. FINDINGS: We identified 131 studies across 26 countries comprising 7780 pediatric patients. Although fever (59\u00b71%) and cough (55\u00b79%) were the most frequent symptoms 19\u00b73% of children were asymptomatic. Patchy lesions (21\u00b70%) and ground-glass opacities (32\u00b79%) depicted lung radiograph and computed tomography findings, respectively. Immunocompromised children or those with respiratory/cardiac disease comprised the largest subset of COVID-19 children with underlying medical conditions (152 of 233 individuals). Coinfections were observed in 5.6% of children and abnormal laboratory markers included serum D-dimer, procalcitonin, creatine kinase, and interleukin-6. Seven deaths were reported (0\u00b709%) and 11 children (0\u00b714%) met inclusion for multisystem inflammatory syndrome in children. INTERPRETATION: This review provides evidence that children diagnosed with COVID-19 have an overall excellent prognosis. Future longitudinal studies are needed to confirm our findings and better understand which patients are at increased risk for developing severe inflammation and multiorgan failure. FUNDING: Parker B. Francis and pilot grant from 2R25-HL126140. Funding agencies had no involvement in the study.", "qid": 47, "docid": "xv7vuypd", "rank": 23, "score": 0.7979275584220886}, {"content": "Title: What we know so far about Coronavirus Disease 2019 in children: A meta\u2010analysis of 551 laboratory\u2010confirmed cases Content: AIM: To summarize what we know so far about coronavirus disease (COVID\u201019) in children. METHOD: We searched PubMed, Scientific Electronic Library Online, and Latin American and Caribbean Center on Health Sciences Information from 1 January 2020 to 4 May 2020. We selected randomized trials, observational studies, case series or case reports, and research letters of children ages birth to 18 years with laboratory\u2010confirmed COVID\u201019. We conducted random\u2010effects meta\u2010analyses to calculate the weighted mean prevalence and 95% confidence interval (CI) or the weighted average means and 95% CI. RESULT: Forty\u2010six articles reporting 551 cases of COVID\u201019 in children (aged 1 day\u201017.5 years) were included. Eighty\u2010seven percent (95% CI: 77%\u201095%) of patients had household exposure to COVID\u201019. The most common symptoms and signs were fever (53%, 95% CI: 45%\u201061%), cough (39%, 95% CI: 30%\u201047%), and sore throat/pharyngeal erythema (14%, 95% CI: 4%\u201028%); however, 18% (95% CI: 11%\u201027%) of cases were asymptomatic. The most common radiographic and computed tomography (CT) findings were patchy consolidations (33%, 95% CI: 23%\u201043%) and ground glass opacities (28%, 95% CI: 18%\u201039%), but 36% (95% CI: 28%\u201045%) of patients had normal CT images. Antiviral agents were given to 74% of patients (95% CI: 52%\u201092%). Six patients, all with major underlying medical conditions, needed invasive mechanical ventilation, and one of them died. CONCLUSION: Previously healthy children with COVID\u201019 have mild symptoms. The diagnosis is generally suspected from history of household exposure to COVID\u201019 case. Children with COVID\u201019 and major underlying condition are more likely to have severe/critical disease and poor prognosis, even death.", "qid": 47, "docid": "hit7rs6q", "rank": 24, "score": 0.7978403568267822}, {"content": "Title: Reduced inflammatory responses to SARS-CoV-2 infection in children presenting to hospital with COVID19 in China Content: Background Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children is associated with better outcomes than in adults. The inflammatory response to COVID-19 infection in children remains poorly characterised. Methods We retrospectively analysed the medical records of 127 laboratory-confirmed COVID-19 patients aged 1 month to 16 years from Wuhan and Jingzhou of Hubei Province. Patients presented between January 25th and March 24th 2020. Information on clinical features, laboratory results, plasma cytokines/chemokines and lymphocyte subsets were analysed. Findings Children admitted to hospital with COVID-19 were more likely to be male (67.7%) and the median age was 7.3 [IQR 4.9] years. All but one patient with severe disease was aged under 2 and the majority (5/7) had significant co-morbidities. Despite 53% having viral pneumonia on CT scanning only 2 patients had low lymphocyte counts and no differences were observed in the levels of plasma proinflammatory cytokines, including interleukin (IL)-2, IL-4, IL-6, tumour necrosis factor (TNF)-alpha; and interferon (IFN)-gamma; between patients with mild, moderate or severe disease. Interpretations We demonstrated that the immune responses of children to COVID-19 infection is significantly different from that seen in adults. Our evidence suggests that SARS-CoV-2 does not trigger a robust inflammatory response or \"cytokine storm\" in children with COVID-19, and this may underlie the generally better outcomes seen in children with this disease. These data also imply anti-cytokine therapies may not be effective in children with moderate COVID-19.", "qid": 47, "docid": "y6ssshea", "rank": 25, "score": 0.7974984645843506}, {"content": "Title: Clinical characteristics of 182 pediatric COVID-19 patients with different severities and allergic status Content: BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has made widespread impact recently. We aim to investigate the clinical characteristics of COVID-19 children with different severities and allergic status. METHODS: Data extracted from the electronical medical records, including demographics, clinical manifestations, comorbidities, laboratory and immunological results and radiological images of 182 hospitalized COVID-19 children were summarized and analyzed. RESULTS: The median age was 6 years old, ranging from 3 days to 15 years, and there were more boys (male-female ratio about 2:1) within the studied 182 patients. Most of the children were infected by family members. Fever (43.4%) and dry cough (44.5%) were common symptoms, and gastrointestinal manifestations accounted for 11.0%, including diarrhea, abdominal discomfort and vomiting. 71.4% had abnormal chest computed tomography (CT) scan images, and typical signs of pneumonia were ground-glass opacity and local patchy shadowing on admission. Laboratory results were mostly within normal ranges, and only a small ratio of lymphopenia (3.9%) and eosinopenia (29.5%) were observed. The majority (97.8%) of infected children were not severe, and 24 (13.2%) of them had asymptomatic infections. Compared to children without pneumonia(manifested as asymptomatic and acute upper respiratory infection), children with pneumonia were associated with higher percentages of the comorbidity history, symptoms of fever and cough, and increased levels of serum procalcitonin, alkaline phosphatase and serum interleukins (IL)-2, IL-4, IL-6, IL-10 and TNF-&#945;.There were no differences of treatments, duration of hospitalization, time from first positive to first negative nucleic acid testing and outcomes between children with mild pneumonia and without pneumonia. All the hospitalized COVID-19 children had recovered except one death due to intussusception and sepsis. In 43 allergic children with COVID-19, allergic rhinitis (83.7%) was the major disease, followed by drug allergy, atopic dermatitis, food allergy and asthma. Demographics and clinical features were not significantly different between allergic and non-allergic groups. Allergic patients showed less increase in acute phase reactants, procalcitonin, D-dimer and aspartate aminotransferase levels compared to all patients. Immunological profiles including circulating T, B and NK lymphocyte subsets, total immunoglobulin and complement levels and serum cytokines did not show any difference in allergic and pneumonia groups. Neither eosinophil counts nor serum total immunoglobulin E (IgE) levels showed a significant correlation with other immunological measures, such as other immunoglobulins, complements, lymphocyte subsets numbers and serum cytokine levels. CONCLUSION: Pediatric COVID-19 patients tended to have a mild clinical course. Patients with pneumonia had higher proportion of fever and cough and increased inflammatory biomarkers than those without pneumonia. There was no difference between allergic and non-allergic COVID-19 children in disease incidence, clinical features, laboratory and immunological findings. Allergy was not a risk factor for developing and severity of SARS-CoV-2 infection and hardly influenced the disease course of COVID-19 in children.", "qid": 47, "docid": "m63b9ekk", "rank": 26, "score": 0.7963441610336304}, {"content": "Title: Clinical characteristics of 182 pediatric COVID\u201019 patients with different severities and allergic status Content: BACKGROUND: The pandemic of coronavirus disease 2019 (COVID\u201019) caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) infection has made widespread impact recently. We aim to investigate the clinical characteristics of COVID\u201019 children with different severities and allergic status. METHODS: Data extracted from the electronical medical records, including demographics, clinical manifestations, comorbidities, laboratory and immunological results and radiological images of 182 hospitalized COVID\u201019 children were summarized and analyzed. RESULTS: The median age was 6 years old, ranging from 3 days to 15 years, and there were more boys (male\u2010female ratio about 2:1) within the studied 182 patients. Most of the children were infected by family members. Fever (43.4%) and dry cough (44.5%) were common symptoms, and gastrointestinal manifestations accounted for 11.0%, including diarrhea, abdominal discomfort and vomiting. 71.4% had abnormal chest computed tomography (CT) scan images, and typical signs of pneumonia were ground\u2010glass opacity and local patchy shadowing on admission. Laboratory results were mostly within normal ranges, and only a small ratio of lymphopenia (3.9%) and eosinopenia (29.5%) were observed. The majority (97.8%) of infected children were not severe, and 24 (13.2%) of them had asymptomatic infections. Compared to children without pneumonia(manifested as asymptomatic and acute upper respiratory infection), children with pneumonia were associated with higher percentages of the comorbidity history, symptoms of fever and cough, and increased levels of serum procalcitonin, alkaline phosphatase and serum interleukins (IL)\u20102, IL\u20104, IL\u20106, IL\u201010 and TNF\u2010\u03b1.There were no differences of treatments, duration of hospitalization, time from first positive to first negative nucleic acid testing and outcomes between children with mild pneumonia and without pneumonia. All the hospitalized COVID\u201019 children had recovered except one death due to intussusception and sepsis. In 43 allergic children with COVID\u201019, allergic rhinitis (83.7%) was the major disease, followed by drug allergy, atopic dermatitis, food allergy and asthma. Demographics and clinical features were not significantly different between allergic and non\u2010allergic groups. Allergic patients showed less increase in acute phase reactants, procalcitonin, D\u2010dimer and aspartate aminotransferase levels compared to all patients. Immunological profiles including circulating T, B and NK lymphocyte subsets, total immunoglobulin and complement levels and serum cytokines did not show any difference in allergic and pneumonia groups. Neither eosinophil counts nor serum total immunoglobulin E (IgE) levels showed a significant correlation with other immunological measures, such as other immunoglobulins, complements, lymphocyte subsets numbers and serum cytokine levels. CONCLUSION: Pediatric COVID\u201019 patients tended to have a mild clinical course. Patients with pneumonia had higher proportion of fever and cough and increased inflammatory biomarkers than those without pneumonia. There was no difference between allergic and non\u2010allergic COVID\u201019 children in disease incidence, clinical features, laboratory and immunological findings. Allergy was not a risk factor for developing and severity of SARS\u2010CoV\u20102 infection and hardly influenced the disease course of COVID\u201019 in children.", "qid": 47, "docid": "gdzx3vlt", "rank": 27, "score": 0.7959445118904114}, {"content": "Title: COVID-19 bei hospitalisierten Kindern und Jugendlichen: Ein systematischer Review zu publizierten Fallserien (Stand 31.03.2020) und erste Daten aus Deutschland./ [COVID-19 in hospitalized children and adolescents] Content: Background: The clinical knowledge about the course, complications and treatment of COVID-19 in children and adolescents is so far limited. Aim: This systematic review summarizes the current scientific evidence regarding the clinical presentation of COVID-19 in hospitalized children based on available case series from China. In addition, first data from a nationwide pediatric hospital survey conducted by the German Society for Pediatric Infectious Diseases (DGPI) are presented. Methods: This study evaluated 12 case series from China with 6-2143 children infected with SARS-CoV\u00ad2, which were identified by a literature search in PubMed up to 31 March 2020. The database of the German nationwide DGPI COVID-19 survey was accessed on 6 April 2020. Results: The median patient age in the case series was between 2 and 7 years and 18-45% were infants <1 year of age. The duration of hospital stay was 5-20 days. Most commonly reported symptoms were fever and cough; in 40-100% of cases involvement of the lower respiratory tract was reported, usually confirmed by computed tomography (CT). Severe and critical courses of disease were reported in up to 8% of the children including 2 fatalities. So far the German DGPI COVID-19 survey reported 33 hospitalized children up to 6 April 2020, mostly with upper airway infections. Of these children, 45% were infants and 32% had an underlying medical condition. So far 3 children (9%) needed admission to an intensive care unit. Conclusion: COVID-19 in hospitalized children usually presented as an uncomplicated febrile upper airway infection or mild pneumonia. Severe cases or fatalities rarely occurred in children. Information on neonates and children with underlying chronic conditions as well as on therapeutic and preventive measures are urgently needed.", "qid": 47, "docid": "pt03w0wa", "rank": 28, "score": 0.7937135696411133}, {"content": "Title: COVID-19 bei hospitalisierten Kindern und Jugendlichen: Ein systematischer Review zu publizierten Fallserien (Stand 31.03.2020) und erste Daten aus Deutschland Content: BACKGROUND: The clinical knowledge about the course, complications and treatment of COVID-19 in children and adolescents is so far limited. AIM: This systematic review summarizes the current scientific evidence regarding the clinical presentation of COVID-19 in hospitalized children based on available case series from China. In addition, first data from a nationwide pediatric hospital survey conducted by the German Society for Pediatric Infectious Diseases (DGPI) are presented. METHODS: This study evaluated 12 case series from China with 6\u20132143 children infected with SARS-CoV\u20112, which were identified by a literature search in PubMed up to 31 March 2020. The database of the German nationwide DGPI COVID-19 survey was accessed on 6 April 2020. RESULTS: The median patient age in the case series was between 2 and 7 years and 18\u201345% were infants <1 year of age. The duration of hospital stay was 5\u201320 days. Most commonly reported symptoms were fever and cough; in 40\u2013100% of cases involvement of the lower respiratory tract was reported, usually confirmed by computed tomography (CT). Severe and critical courses of disease were reported in up to 8% of the children including 2 fatalities. So far the German DGPI COVID-19 survey reported 33 hospitalized children up to 6 April 2020, mostly with upper airway infections. Of these children, 45% were infants and 32% had an underlying medical condition. So far 3 children (9%) needed admission to an intensive care unit. CONCLUSION: COVID-19 in hospitalized children usually presented as an uncomplicated febrile upper airway infection or mild pneumonia. Severe cases or fatalities rarely occurred in children. Information on neonates and children with underlying chronic conditions as well as on therapeutic and preventive measures are urgently needed.", "qid": 47, "docid": "i154l4tu", "rank": 29, "score": 0.7932208776473999}, {"content": "Title: SARS-CoV-2 (COVID-19): What do we know about children? A systematic review Content: BACKGROUND: Few paediatric cases of COVID-19 have been reported and we know little about the epidemiology in children, though more is known about other coronaviruses. We aimed to understand the infection rate, clinical presentation, clinical outcomes and transmission dynamics for SARS-CoV-2, in order to inform clinical and public health measures. METHODS: We undertook a rapid systematic review and narrative synthesis of all literature relating to SARS-CoV-2 in paediatric populations. The search terms also included SARS-CoV and MERS-CoV. We searched three databases and the COVID-19 resource centres of eleven major journals and publishers. English abstracts of Chinese language papers were included. Data were extracted and narrative syntheses conducted. RESULTS: 24 studies relating to COVID-19 were included in the review. Children appear to be less affected by COVID-19 than adults by observed rate of cases in large epidemiological studies. Limited data on attack rate indicate that children are just as susceptible to infection. Data on clinical outcomes are scarce but include several reports of asymptomatic infection and a milder course of disease in young children, though radiological abnormalities are noted. Severe cases are not reported in detail and there are little data relating to transmission. CONCLUSIONS: Children appear to have a low observed case rate of COVID-19 but may have similar rates to adults of infection with SARS-CoV-2. This discrepancy may be because children are asymptomatic or too mildly infected to draw medical attention, be tested and counted in observed cases of COVID-19.", "qid": 47, "docid": "998lscmk", "rank": 30, "score": 0.7922245264053345}, {"content": "Title: Preliminary epidemiological analysis on children and adolescents with novel coronavirus disease 2019 outside Hubei Province, China: an observational study utilizing crowdsourced data Content: Background: The outbreak of coronavirus disease 2019 (COVID-19) continues to expand across the world. Though both the number of cases and mortality rate in children and adolescents is reported to be low in comparison to adults, limited data has been reported on the outbreak with respect to pediatric patients. To elucidate information, we utilized crowdsourced data to perform a preliminary epidemiologic analysis of pediatric patients with COVID-19 Methods: In this observational study, data was collected from two open-access, line list crowdsourced online databases. Pediatric cases of COVID-19 were defined as patients \u226419 years of age with a laboratory confirmed diagnosis. The primary outcomes were case counts and cumulative case counts. Secondary outcomes included days between symptoms onset and first medical care and days between first medical care and reporting. Tertiary outcomes were rate of travel to Wuhan, rate of infected family members and rates of symptoms. Results: A total of 82 patients were included. The median age was 10 [IQR: 5-15] years. Patients from mainland China (outside Hubei) accounted for 46.3% of cases, while the remaining 53.7% of cases were international. Males and females accounted for 52.4% and 32.9% of cases, respectively, with the remaining 14.6% being designated as unknown. A male skew persisted across subgroup analyses by age group (p=1.0) and location (inside/outside China) (p=0.22). While the number of reported international cases has been steadily increasing over the study period, the number of reported cases in China rapidly decreased from the start point. The median reporting delay was 3 [IQR: 2-4.8] days. The median delay between symptom onset and first seeking medical care was 1 [IQR: 0-3.25] day. In international cases, time to first seeking medical care was a median of 2.5 days longer than in China (p=0.04). When clinical features were reported, fever was the most common presentation (68.0%), followed by cough (36.0%). Conclusions: The number of reported international pediatric COVID-19 cases is rapidly increasing. COVID-19 infections are, to-date, more common in males than females in both the children and adolescent age groups. Additionally, this male predominance remains the case both inside and outside of China. Crowdsourced data enabled early analysis of epidemiologic variables in pediatric patients with COVID-19. Further data sharing is required to enable analyses that are required to understand the course of this infection in children.", "qid": 47, "docid": "j58f1lwa", "rank": 31, "score": 0.7917906641960144}, {"content": "Title: Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China Dong Y, Mo X, Hu Y, et al. Pediatrics. 2020; doi: 10.1542/peds.2020-0702. Content: Novel coronavirus (SARS-CoV-2, which causes COVID-19) is a pandemic with many countries employing massive public health responses. Little is known about the severity of illness in the pediatric population. This study sought to identify demographic information and severity of disease in pediatric patients with COVID-19. This was a retrospective study conducted on patients less than 18 years who were suspected or confirmed to have COVID-19 and were reported to the Chinese Centers for Disease Control (China CDC). Children were considered high risk and suspected if they had positive exposure to an endemic area or a confirmed case of COVID-19. High suspicion also included those with fever, respiratory symptoms, digestive symptoms, or fatigue, normal or low white blood cell count and increased C-reactive protein, or abnormal chest radiography, or those at lower risk for whom influenza or other respiratory illnesses were ruled out. Confirmed cases were defined as having a nasopharyngeal swab or blood sample positive via PCR or a genetic sampling of respiratory secretions or blood consistent with SARS-CoV-2. Once identified, patients were categorized by severity of disease using clinical features as well as laboratory and radiographic findings. Severity categories included asymptomatic (no symptoms but positive test), mild (mild respiratory symptoms and normal lung exam), moderate (pneumonia, fever, and cough but without hypoxemia or respiratory distress), severe (above symptoms as well as oxygen saturation less than 92% and respiratory distress), or critical disease (acute respiratory failure, acute respiratory distress syndrome, shock, or other life-threatening organ dysfunction). There were 2143 patients included who were suspected (65.9%) or confirmed (34.1%) to have COVID-19. Median age was 7 years (IQR 2-13) and the majority (56.6%) were male. The median time from onset of symptoms to presentation was 2 days (range 0-42). Nearly all were categorized as asymptomatic (4.4%), mild (50.9%), or moderate (38.8%) severity, leaving only 5.9% as severe or critical. Looking at breakdown by age, infants made up the highest proportion of severe or critical disease (32%) with preschool ages (1-5 years) next with 28.8%. Half (7) of the 13 critical patients were under 1 year old. No significant differences were seen between male or female patients. There was one death in the sample: a 14-year old boy. Limitations included lack of clinical characteristics, as only data from the Chinese CDC was used rather than electronic medical records from individual patients. Additionally the majority of cases were suspected, not confirmed, and some of the children remained hospitalized at the end of the study therefore severity of disease may not be accurate. The authors concluded that COVID-19 caused infection in all ages without obvious gender differences, however younger children appeared to have higher severity of disease. Comment: This is the largest cohort of pediatric COVID-19 patients to date. This study is based on the China CDC dataset and is limited to the variables that are reported to the CDC. We cannot assume children in the United States will be affected similarly. Overall, this dataset suggests that critical disease is rare in children with COVID-19. Emergency physicians should use caution with infants and young children, however, as they appear to be at highest risk of severe disease and may need closer observation in the emergency department or inpatient admission.", "qid": 47, "docid": "h93g5hvf", "rank": 32, "score": 0.791365385055542}, {"content": "Title: Clinical manifestations of children with COVID-19: A systematic review Content: BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak is an unprecedented global public health challenge, leading to thousands of deaths every day worldwide. Despite the epidemiological importance, clinical patterns of children with COVID-19 remain unclear. The aim of this study was to describe the clinical, laboratorial, and radiological characteristics of children with COVID-19. METHODS: The Medline database was searched between December 1st 2019 and April 6th 2020. No language restrictions were applied. Inclusion criteria were (a) studied patients younger than 18 years old; (b) presented original data from cases of COVID-19 confirmed by reverse-transcription polymerase chain reaction; and (c) contained descriptions of clinical manifestations, laboratory tests, or radiological examinations. RESULTS: A total of 38 studies (1124 cases) were included. From all the cases, 1117 had their severity classified: 14.2% were asymptomatic, 36.3% were mild, 46.0% were moderate, 2.1% were severe, and 1.2% were critical. The most prevalent symptom was fever (47.5%), followed by cough (41.5%), nasal symptoms (11.2%), diarrhea (8.1%), and nausea/vomiting (7.1%). One hundred forty-five (36.9%) children were diagnosed with pneumonia and 43 (10.9%) upper airway infections were reported. Reduced lymphocyte count was reported in 12.9% of cases. Abnormalities in computed tomography were reported in 63.0% of cases. The most prevalent abnormalities reported were ground-glass opacities, patchy shadows, and consolidations. Only one death was reported. CONCLUSIONS: Clinical manifestations of children with COVID-19 differ widely from adult cases. Fever and respiratory symptoms should not be considered a hallmark of COVID-19 in children.", "qid": 47, "docid": "e6br6v2d", "rank": 33, "score": 0.7912482619285583}, {"content": "Title: Coronavirus (COVID-19) infection in children at a specialist centre: outcome and implications of underlying high-risk comorbidities in a paediatric population Content: Background: There is evolving evidence of significant differences in severity and outcomes of coronavirus disease 2019 (COVID-19) in children compared to adults. Underlying medical conditions associated with increased risk of severe disease are based on adult data, but have been applied across all ages resulting in large numbers of families undertaking social shielding (vulnerable group). We conducted a retrospective analysis of children with suspected COVID-19 at a Specialist Childrens Hospital to determine outcomes based on COVID-19 testing status and underlying health vulnerabilities. Methods: Routine clinical data were extracted retrospectively from the Institutions Electronic Health Record system and Digital Research Environment for patients with suspected and confirmed COVID-19 diagnoses. Data were compared between Sars-CoV-2 positive and negative patients (CoVPos / CoVNeg respectively), and in relation to presence of underlying health vulnerabilities based on Public Health England guidance. Findings: Between 1st March and 15th May 2020, 166 children (<18 years of age) presented to a specialist childrens hospital with clinical features of possible COVID-19 infection. 65 patients (39.2%) tested positive for SARS-CoV-2 virus. CoVPos patients were older (median 9 [0.9-14] years vs median 1 [0.1-5.7.5] years respectively, p<0.001). There was a significantly reduced proportion of vulnerable cases (47.7% vs 72.3%, p=0.002), but no difference in proportion of vulnerable patients requiring ventilation (61% vs 64.3%, p = 0.84) between CoVPos and CoVNeg groups. However, a significantly lower proportion of CoVPos patients required mechanical ventilation support compared to CoVNeg patients (27.7 vs 57.4%, p<0.001). Mortality was not significantly different between CoVPos and CoVNeg groups (1.5 vs 4% respectively, p=0.67) although there were no direct COVID-19 related deaths in this highly preselected paediatric population. Interpretation: COVID-19 infection may be associated with severe disease in childhood presenting to a specialist hospital, but does not appear significantly different in severity to other causes of similar clinical presentations. In children presenting with pre-existing COVID-19 vulnerable medical conditions at a specialist centre, there does not appear to be significantly increased risk of either contracting COVID-19 or severe complications, apart from those undergoing chemotherapy, who are over-represented.", "qid": 47, "docid": "15zj660u", "rank": 34, "score": 0.7912306785583496}, {"content": "Title: Coronavirus disease 2019 in children: Characteristics, antimicrobial treatment, and outcomes Content: BACKGROUND: At present, coronavirus disease 2019 (COVID-19) has spread in many countries. We conducted this study to help pediatricians understand the conditions of COVID-19 in children. METHODS: We retrospectively summarized the characteristics, treatment and outcomes of pediatric cases in Wuhan Children's Hospital which was the only designated hospital for children with COVID-19 in Hubei Province. A Cox proportional hazards regression analysis was used to evaluate factors associated with clinical outcomes. RESULTS: As of February 29, 75 children had been discharged, of which only one was has severe pneumonia and one was critical cases. Children younger than 2 years were more susceptible to COVID-19. All patients have received interferon-&#945; nebulization, and eight cases including the severe and critical cases were co-administrated ribavirin. Five patients with mild pneumonia were given arbidol. Twenty-three patients were given traditional Chinese medicine (TCM). The average length of stay (LOS) and the time of SARS-CoV-2 clearance were 10.57 and 6.39 days, respectively. None of the factors was associated with LOS or time of SARS-CoV-2 clearance. CONCLUSIONS: The severity of COVID-19 in pediatric cases were milder than adults. The efficacy of the antiviral therapy in children with COVID-19 remains to be evaluated.", "qid": 47, "docid": "t4tg0o8o", "rank": 35, "score": 0.7905019521713257}, {"content": "Title: Children with coronavirus disease 2019: A review of demographic, clinical, laboratory, and imaging features in pediatric patients Content: There is a current outbreak of coronavirus disease 2019 (COVID-19), with a global spread. With the rapid increase in the number of infections, an increase is observed in the number of children with COVID-19. Most research findings are regarding adult cases, which are not always transferrable to children. Evidence-based studies are still expected to formulate clinical decisions for pediatric patients. In this review, we included 2597 pediatric patients that reported recently and evaluated the demographic, clinical, laboratory, and imaging features of children with COVID-19. We found that even lymphopenia was the most common lab finding in adults; it infrequently occurred in children (9.8%). Moreover, elevated creatine kinase MB isoenzyme was much more commonly observed in children (27.0%) than that in adults, suggesting that heart injury would be more likely to occur in pediatric patients. Our analysis may contribute to determine the spectrum of disease in children and to develop strategies to control the disease transmission.", "qid": 47, "docid": "8jfsrsmf", "rank": 36, "score": 0.7899110317230225}, {"content": "Title: Disease and age-related inequalities in paediatric research, funding and communication: lessons from the COVID-19 pandemic Content: COVID-19 has already caused millions of infections, thousands of deaths and countless indirect and poorly estimated consequences on other diseases and the global economy. All ages are potentially susceptible, but the virus has had a lower direct impact on children, with fewer severe cases and low mortality rates. However, the reasons for this are still unclear and we cannot rule out children's role in transmitting the disease. The serious impact that restrictive measures have had on children's lives have not been fully considered. Because children are less affected by COVID-19, the scientific community, health agencies and governments have not focused much attention on them during this pandemic.", "qid": 47, "docid": "w3hgmfzb", "rank": 37, "score": 0.7893447875976562}, {"content": "Title: Impact of COVID-19 on Pediatric Asthma: Practice Adjustments and Disease Burden Content: BACKGROUND: It is unclear whether asthma may affect susceptibility or severity of coronavirus disease 2019 (COVID-19) in children and how pediatric asthma services worldwide have responded to the pandemic. OBJECTIVE: To describe the impact of the COVID-19 pandemic on pediatric asthma services and on disease burden in their patients. METHODS: An online survey was sent to members of the Pediatric Asthma in Real Life think tank and the World Allergy Organization Pediatric Asthma Committee. It included questions on service provision, disease burden, and the clinical course of confirmed cases of COVID-19 infection among children with asthma. RESULTS: Ninety-one respondents, caring for an estimated population of more than 133,000 children with asthma, completed the survey. COVID-19 significantly impacted pediatric asthma services: 39% ceased physical appointments, 47% stopped accepting new patients, and 75% limited patients' visits. Consultations were almost halved to a median of 20 (interquartile range, 10-25) patients per week. Virtual clinics and helplines were launched in most centers. Better than expected disease control was reported in 20% (10%-40%) of patients, whereas control was negatively affected in only 10% (7.5%-12.5%). Adherence also appeared to increase. Only 15 confirmed cases of COVID-19 were reported among the population; the estimated incidence is not apparently different from the reports of general pediatric cohorts. CONCLUSIONS: Children with asthma do not appear to be disproportionately affected by COVID-19. Outcomes may even have improved, possibly through increased adherence and/or reduced exposures. Clinical services have rapidly responded to the pandemic by limiting and replacing physical appointments with virtual encounters.", "qid": 47, "docid": "qilgtp4w", "rank": 38, "score": 0.7892535924911499}, {"content": "Title: Clinical Features and the Treatment of Children with COVID\u201019: A Case Series from Wenzhou, China Content: The clinical features and treatment of children with COVID\u201019 is unclear and understudied. Here, three children with COVID\u201019 infection, ages 2 to 12 years, were prospectively followed from hospital admission to discharge. We provide information and experience with treatment of pediatric cases with confirmed COVID\u201019 infection. This article is protected by copyright. All rights reserved.", "qid": 47, "docid": "swxr5t3e", "rank": 39, "score": 0.7882939577102661}, {"content": "Title: Novel Coronavirus Infection (COVID\u201019) in Children Younger Than One Year: A Systematic Review of Symptoms, Management and Outcomes Content: AIM: This aim of this systematic review and meta\u2010analysis was to evaluate the clinical characteristics of COVID\u201019 in neonates and children under one year of age. METHODS: A systematic literature review of the MEDLINE, PubMed, CINAHL, Embase and EBSCO databases was carried out for studies from 1 January to 7 April 2020. We included all papers that addressed clinical manifestations, laboratory results, imaging findings and outcomes in infants and neonates. RESULTS: Our search identified 77 peer\u2010reviewed papers and 18 papers covering 160 infants were reviewed. One paper was from Vietnam and the other 17 were from China: eight were cross\u2010sectional studies, eight were case reports, one was a case series and one was a prospective cohort study. The most common clinical symptoms were fever (54%) and cough (33%). Most infants were treated symptomatically, with frequent use of various empirical medications. Infants and neonates tended to have more severe COVID\u201019 disease than older children: 11 (7%) were admitted to intensive care and one infant died. The mortality rate was 0.006%, with favourable outcomes in most cases. CONCLUSION: Infants and neonates were more vulnerable to more severe COVID\u201019 disease than older children, but morbidity and mortality were low.", "qid": 47, "docid": "y8lctk6k", "rank": 40, "score": 0.7882376909255981}, {"content": "Title: Coronavirus Disease (COVID-19) and Pediatric Patients: A Review of Epidemiology, Symptomatology, Laboratory and Imaging Results to Guide the Development of a Management Algorithm Content: Coronavirus disease (COVID-19) has been declared a worldwide pandemic. Compared to adults, there has been a significantly smaller number of reported cases of COVID-19 in the pediatric population, although the incidence is increasing every day. This article looks to review specific epidemiological factors, symptomatology, laboratory and imaging workup, and other relevant metrics derived from the limited published literature that are specific to the pediatric population, to provide a review for the pediatric practitioner and guide, in part, the creation of a clinical algorithm for the management of COVID-19 in the pediatric population that can be utilized by pediatric institutions.", "qid": 47, "docid": "1nijgf3k", "rank": 41, "score": 0.7876452207565308}, {"content": "Title: Severe and fatal forms of COVID-19 in children Content: OBJECTIVES: The aim of this study was to describe severe forms of novel coronavirus disease 2019 in children, including patient characteristics, clinical, laboratory, and imaging findings, as well as the disease management and outcomes. METHODS: This was a retrospective, single-center, observational study conducted in a pediatric intensive and high-dependency care unit (PICU, HDU) in an urban hospital in Paris. All patients, aged from 1 month to 18 years, admitted for confirmed or highly suspected SARS-CoV-2 were included. RESULTS: We analyzed the data of 27 children. Comorbidities (n=19, 70%) were mainly neurological (n=7), respiratory, (n=4), or sickle cell disease (n=4). SARS-CoV-2 PCR results were positive in 24 children (nasopharyngeal swabs). The three remaining children had a chest CT scan consistent with COVID-19. Respiratory involvement was observed in 24 patients (89%). Supportive treatments were invasive mechanical ventilation (n=9), catecholamine (n=4), erythropheresis (n=4), renal replacement therapy (n=1), and extracorporeal membrane oxygenation (n=1). Five children died, of whom three were without past medical history. CONCLUSION: This study highlighted the large spectrum of clinical presentation and time course of disease progression as well as the non-negligible occurrence of pediatric life-threatening and fatal cases of COVID-19 mostly in patients with comorbidities. Additional laboratory investigations are needed to further analyze the mechanism underlying the variability of SARS-Cov-2 pathogenicity in children.", "qid": 47, "docid": "zi23n8b4", "rank": 42, "score": 0.7875474691390991}, {"content": "Title: Neurotropic mechanisms in COVID-19 and their potential influence on neuropsychological outcomes in children Content: Children have shown more physical resilience to COVID-19 than adults, but there is a cohort of vulnerable infants and young children who may experience disease burden, both in the acute phase and chronically. Children may have had early undocumented exposure to COVID-19. Even when the risk of exposure was known, developmental variables may have made the avoidance of physical proximity difficult for children. Preliminary hypotheses concerning neurotropic factors have been documented by researchers. Children with COVID-19 and comorbid physical or mental disorders may be vulnerable to exacerbations of neurotropic factors and comorbidities, the neural impact of which has been documented for other coronaviruses. Researchers are investigating COVID-19 symptom descriptions, neurotropic mechanisms at the genomic and transcriptomatic levels, neurological manifestations, and the impact of comorbid health complications. Neuropsychologists need information concerning the likely impact of COVID-19 on children. With a view toward that goal, this article provides recommendations for some initial updates in neuropsychology practice.", "qid": 47, "docid": "1wrwxb9b", "rank": 43, "score": 0.7868567109107971}, {"content": "Title: Clinical characteristics of a case series of children with coronavirus disease 2019 Content: We reported the clinical characteristics of a case series of 10 patients with coronavirus disease 2019 (COVID-19) aged from 1 year to 18 years. Seven patients had contact with confirmed COVID-19 family members before onset. Fever (4 [40.0%]) and cough (3 [30.0%]) were the most common symptoms. No patient showed leucopenia and lymphopenia on admission. Pneumonia was observed in chest CT images in 5 (50.0%) patients. Five (50.0%) patients received antiviral treatment. No patient had severe complications or developed a severe illness in our study. Our study indicated that COVID-19 children present less severe symptoms and have better outcomes.", "qid": 47, "docid": "nb08i303", "rank": 44, "score": 0.7865960597991943}, {"content": "Title: Flash survey on severe acute respiratory syndrome coronavirus-2 infections in paediatric patients on anticancer treatment Content: INTRODUCTION: Since the beginning of COVID-19 pandemic, it is known that the severe course of the disease occurs mostly among the elderly, whereas it is rare among children and young adults. Comorbidities, in particular, diabetes and hypertension, clearly associated with age, besides obesity and smoke, are strongly associated with the need for intensive treatment and a dismal outcome. A weaker immunity of the elderly has been proposed as a possible explanation of this uneven age distribution. Thus, there is concern that children treated for cancer may allso be at risk for an unfavourable course of infection. Along the same line, anecdotal information from Wuhan, China, mentioned a severe course of COVID-19 in a child treated for leukaemia. AIM AND METHODS: We made a flash survey on COVID-19 incidence and severity among children on anticancer treatment. Respondents were asked by email to fill in a short Web-based survey. RESULTS: We received reports from 25 countries, where approximately 10,000 patients at risk are followed up. At the time of the survey, more than 200 of these children were tested, nine of whom were positive for COVID-19. Eight of the nine cases had asymptomatic to mild disease, and one was just diagnosed with COVID-19. We also discuss preventive measures that are in place or should be taken and treatment options in immunocompromised children with COVID-19. CONCLUSION: Thus, even children receiving anticancer chemotherapy may have a mild or asymptomatic course of COVID-19. While we should not underestimate the risk of developing a more severe course of COVID-19 than that observed here, the intensity of preventive measures should not cause delays or obstructions in oncological treatment.", "qid": 47, "docid": "vz4c270q", "rank": 45, "score": 0.7864840030670166}, {"content": "Title: Neurotropic mechanisms in COVID-19 and their potential influence on neuropsychological outcomes in children. Content: Children have shown more physical resilience to COVID-19 than adults, but there is a cohort of vulnerable infants and young children who may experience disease burden, both in the acute phase and chronically. Children may have had early undocumented exposure to COVID-19. Even when the risk of exposure was known, developmental variables may have made the avoidance of physical proximity difficult for children. Preliminary hypotheses concerning neurotropic factors have been documented by researchers. Children with COVID-19 and comorbid physical or mental disorders may be vulnerable to exacerbations of neurotropic factors and comorbidities, the neural impact of which has been documented for other coronaviruses. Researchers are investigating COVID-19 symptom descriptions, neurotropic mechanisms at the genomic and transcriptomatic levels, neurological manifestations, and the impact of comorbid health complications. Neuropsychologists need information concerning the likely impact of COVID-19 on children. With a view toward that goal, this article provides recommendations for relevant for some initial updates in neuropsychology practice.", "qid": 47, "docid": "lbsacgr7", "rank": 46, "score": 0.7863270044326782}, {"content": "Title: Potential effectiveness and safety of antiviral agents in children with coronavirus disease 2019: a rapid review and meta-analysis. Content: Background The COVID-19 outbreak presents a new, life-threatening disease. Our aim was to assess the potential effectiveness and safety of antiviral agents for COVID-19 in children. Methods Electronic databases (MEDLINE, Embase, Web of Science, the Cochrane library, CBM, CNKI, and Wanfang Data) from their inception to March 31, 2020 were searched for randomized controlled trials (RCTs), clinical controlled trials and cohort studies of interventions with antiviral agents for children (less than 18 years of age) with COVID-19. Results A total of 23 studies with 6,008 patients were included. There was no direct evidence and all of evidence were indirect. The risks of bias in all studies were moderate to high in general. The effectiveness and safety of antiviral agents for children with COVID-19 is uncertain: For adults with COVID-19, lopinavir/ritonavir had no effect on mortality [risk ratio (RR) =0.77; 95% confidence interval (CI), 0.45 to 1.30]. Arbidol and hydroxychloroquine (HCQ) had no benefit on probability of negative PCR test (RR =1.27; 95% CI, 0.93 to 1.73; RR =0.93; 95% CI, 0.73 to 1.18) respectively. For adults with SARS, interferon was associated with reduced corticosteroid dose [weighted mean difference (WMD) = -0.14 g; 95% CI, -0.21 to -0.07] but had no effect on mortality (RR =0.72; 95% CI, 0.28 to 1.88); ribavirin did not reduce mortality (RR =0.68; 95% CI, 0.43 to 1.06) and was associated with high risk of severe adverse reactions; and oseltamivir had no effect on mortality (RR =0.87; 95% CI, 0.55 to 1.38). Ribavirin combined with interferon was also not effective in adults with MERS and associated with adverse reactions. Conclusions There is no evidence showing the effectiveness of antiviral agents for children with COVID-19, and the clinical efficacy of existing antiviral agents is still uncertain. We do not suggest clinical routine use of antivirals for COVID-19 in children, with the exception of clinical trials.", "qid": 47, "docid": "pp7w0ikh", "rank": 47, "score": 0.7859588861465454}, {"content": "Title: Children with coronavirus disease 2019: A review of demographic, clinical, laboratory, and imaging features in pediatric patients Content: There is a current outbreak of coronavirus disease 2019 (COVID\u201019), with a global spread. With the rapid increase in the number of infections, an increase is observed in the number of children with COVID\u201019. Most research findings are regarding adult cases, which are not always transferrable to children. Evidence\u2010based studies are still expected to formulate clinical decisions for pediatric patients. In this review, we included 2597 pediatric patients that reported recently and evaluated the demographic, clinical, laboratory, and imaging features of children with COVID\u201019. We found that even lymphopenia was the most common lab finding in adults; it infrequently occurred in children (9.8%). Moreover, elevated creatine kinase MB isoenzyme was much more commonly observed in children (27.0%) than that in adults, suggesting that heart injury would be more likely to occur in pediatric patients. Our analysis may contribute to determine the spectrum of disease in children and to develop strategies to control the disease transmission.", "qid": 47, "docid": "ythil22o", "rank": 48, "score": 0.7857838273048401}, {"content": "Title: Clinical characteristics and outcome of SARS-CoV-2 infection in Italian pediatric oncology patients: a study from the Infectious Diseases Working Group of the AIEOP. Content: BACKGROUND Little is known as yet about the outcome of SARS-CoV-2 infection in children being treated for cancer. METHODS We collected information on the clinical characteristics and outcomes of a cohort of 29 children (16 females and 13 males, median age 7 years, range [0-16]) diagnosed with SARS-CoV-2 infection while on chemotherapy/immunotherapy (N=26), or after stem cell transplantation (N=3) during the peak of the epidemic in Italy. These patients suffered from leukemia (N=16), lymphoma (N=3), solid tumors (N=10), and Langerhans cell histiocytosis (N=1). RESULTS The course of the disease was mild in all cases, with only 12 children developing symptoms (pneumonia in 3 cases), and none needing intensive care. Fifteen patients were hospitalized, including 7 asymptomatic patients. Nine patients (including 5 with no symptoms) were given hydroxychloroquine, and 3 of them were also given lopinavir/ritonavir. CONCLUSIONS SARS-CoV-2 infection seems to take a milder clinical course in children than in adults with cancer. Specific SARS-CoV-2 treatment seems unnecessary for most children. In the light of our findings, and albeit with the necessary caution, we suggest avoiding major changes to planned anticancer treatments in pediatric patients acquiring COVID-19.", "qid": 47, "docid": "rznp2fuy", "rank": 49, "score": 0.7853165864944458}, {"content": "Title: Clinical characteristics and outcome of SARS-CoV-2 infection in Italian pediatric oncology patients: a study from the Infectious Diseases Working Group of the AIEOP Content: BACKGROUND: Little is known as yet about the outcome of SARS-CoV-2 infection in children being treated for cancer. METHODS: We collected information on the clinical characteristics and outcomes of a cohort of 29 children (16 females and 13 males, median age 7 years, range [0-16]) diagnosed with SARS-CoV-2 infection while on chemotherapy/immunotherapy (N=26), or after stem cell transplantation (N=3) during the peak of the epidemic in Italy. These patients suffered from leukemia (N=16), lymphoma (N=3), solid tumors (N=10), and Langerhans cell histiocytosis (N=1). RESULTS: The course of the disease was mild in all cases, with only 12 children developing symptoms (pneumonia in 3 cases), and none needing intensive care. Fifteen patients were hospitalized, including 7 asymptomatic patients. Nine patients (including 5 with no symptoms) were given hydroxychloroquine, and 3 of them were also given lopinavir/ritonavir. CONCLUSIONS: SARS-CoV-2 infection seems to take a milder clinical course in children than in adults with cancer. Specific SARS-CoV-2 treatment seems unnecessary for most children. In the light of our findings, and albeit with the necessary caution, we suggest avoiding major changes to planned anticancer treatments in pediatric patients acquiring COVID-19.", "qid": 47, "docid": "f1697rdp", "rank": 50, "score": 0.7852661609649658}, {"content": "Title: Pediatric Otolaryngology Divisional and Institutional Preparatory Response at Seattle Children's Hospital after COVID-19 Regional Exposure Content: Coronavirus disease 2019 (COVID-19) is a novel coronavirus resulting in high mortality in the adult population but low mortality in the pediatric population. The role children and adolescents play in COVID-19 transmission is unclear, and it is possible that healthy pediatric patients serve as a reservoir for the virus. This article serves as a summary of a single pediatric institution's response to COVID-19 with the goal of protecting both patients and health care providers while providing ongoing care to critically ill patients who require urgent interventions. A significant limitation of this commentary is that it reflects a single institution's joint effort at a moment in time but does not take into consideration future circumstances that could change practice patterns. We still hope dissemination of our overall response at this moment, approximately 8 weeks after our region's first adult case, may benefit other pediatric institutions preparing for COVID-19.", "qid": 47, "docid": "9g1d5vpa", "rank": 51, "score": 0.7850273847579956}, {"content": "Title: Pediatric Otolaryngology Divisional and Institutional Preparatory Response at Seattle Children's Hospital after COVID-19 Regional Exposure. Content: Coronavirus disease 2019 (COVID-19) is a novel coronavirus resulting in high mortality in the adult population but low mortality in the pediatric population. The role children and adolescents play in COVID-19 transmission is unclear, and it is possible that healthy pediatric patients serve as a reservoir for the virus. This article serves as a summary of a single pediatric institution's response to COVID-19 with the goal of protecting both patients and health care providers while providing ongoing care to critically ill patients who require urgent interventions. A significant limitation of this commentary is that it reflects a single institution's joint effort at a moment in time but does not take into consideration future circumstances that could change practice patterns. We still hope dissemination of our overall response at this moment, approximately 8 weeks after our region's first adult case, may benefit other pediatric institutions preparing for COVID-19.", "qid": 47, "docid": "nzd8qg7l", "rank": 52, "score": 0.7850273847579956}, {"content": "Title: Coronavirus Disease 2019 in Children: Characteristics, Antimicrobial Treatment, and Outcomes Content: Abstract Background At present, coronavirus disease 2019 (COVID-19) has spread in many countries. We conducted this study to help paediatricians To help pediatricians understand the conditions of COVID-19 in children, we conducted this study. Methods We retrospectively summarized the characteristics, treatment and outcomes of pediatric cases in Wuhan children's hospital which was the only designated hospital for children with COVID-19 in Hubei Province. A Cox proportional hazards regression analysis was used to evaluate factors associated with clinical outcomes. Results As of February 29, 75 children had been discharged, of which only one was has severe pneumonia and one was critical cases. Children younger than 2 years were more susceptible to COVID-19. All patients have received interferon-\u03b1 nebulization, and eight cases including the severe and critical cases were co-administrated ribavirin. Five patients with mild pneumonia were given arbidol. Twenty-three patients were given traditional Chinese medicine (TCM). The average length of stay (LOS) and the time of SARS-CoV-2 clearance were 10.57 and 6.39 days, respectively. None of the factors was associated with LOS or time of SARS-CoV-2 clearance. Conclusions The severity of COVID-19 in pediatric cases were milder than adults. The efficacy of the antiviral therapy in children with COVID-19 remains to be evaluated.", "qid": 47, "docid": "11es4w0u", "rank": 53, "score": 0.7849225997924805}, {"content": "Title: Children Hospitalized With Severe COVID-19 in Wuhan Content: BACKGROUND: Novel coronavirus disease (COVID-19) is spreading globally. Little is known about the risk factors for the clinical outcomes of COVID-19 in children. METHODS: A retrospective case-control study was taken in children with severe acute respiratory syndrome coronary virus-2 infection in Wuhan Children's Hospital. Risk factors associated with the development of COVID-19 and progression were collected and analyzed. RESULTS: Eight of 260 children diagnosed with severe COVID-19 pneumonia were included in the study. Thirty-five children with COVID-19 infection matched for age, sex and date of admission, and who classified as non-severe type, were randomly selected from the hospital admissions. For cases with severe pneumonia caused by COVID-19, the most common symptoms were dyspnea (87.5%), fever (62.5%) and cough (62.5%). In laboratory, white blood cells count was significantly higher in severe children than non-severe children. Levels of inflammation bio-makers such as hsCRP, IL-6, IL-10 and D-dimer elevated in severe children compared with non-severe children on admission. The level of total bilirubin and uric acid clearly elevated in severe children compared with non-severe children on admission. All of severe children displayed the lesions on chest CT, more lung segments were involved in severe children than in non-severe children, which was only risk factor associated with severe COVID-19 pneumonia in multivariable analysis. CONCLUSIONS: More than 3 lung segments involved were associated with greater risk of development of severe COVID-19 in children. Moreover, the possible risk of the elevation of IL-6, high total bilirubin and D-dimer with univariable analysis could identify patients to be severe earlier.", "qid": 47, "docid": "9cr0bk2a", "rank": 54, "score": 0.7841475009918213}, {"content": "Title: Clinical manifestations of children with COVID\u201019: A systematic review Content: BACKGROUND: The coronavirus disease 2019 (COVID\u201019) outbreak is an unprecedented global public health challenge, leading to thousands of deaths every day worldwide. Despite the epidemiological importance, clinical patterns of children with COVID\u201019 remain unclear. The aim of this study was to describe the clinical, laboratorial, and radiological characteristics of children with COVID\u201019. METHODS: The Medline database was searched between December 1st 2019 and April 6th 2020. No language restrictions were applied. Inclusion criteria were (a) studied patients younger than 18 years old; (b) presented original data from cases of COVID\u201019 confirmed by reverse\u2010transcription polymerase chain reaction; and (c) contained descriptions of clinical manifestations, laboratory tests, or radiological examinations. RESULTS: A total of 38 studies (1124 cases) were included. From all the cases, 1117 had their severity classified: 14.2% were asymptomatic, 36.3% were mild, 46.0% were moderate, 2.1% were severe, and 1.2% were critical. The most prevalent symptom was fever (47.5%), followed by cough (41.5%), nasal symptoms (11.2%), diarrhea (8.1%), and nausea/vomiting (7.1%). One hundred forty\u2010five (36.9%) children were diagnosed with pneumonia and 43 (10.9%) upper airway infections were reported. Reduced lymphocyte count was reported in 12.9% of cases. Abnormalities in computed tomography were reported in 63.0% of cases. The most prevalent abnormalities reported were ground\u2010glass opacities, patchy shadows, and consolidations. Only one death was reported. CONCLUSIONS: Clinical manifestations of children with COVID\u201019 differ widely from adult cases. Fever and respiratory symptoms should not be considered a hallmark of COVID\u201019 in children.", "qid": 47, "docid": "5nw3828d", "rank": 55, "score": 0.7840235233306885}, {"content": "Title: Clinical Manifestations of Children with COVID-19: a Systematic Review Content: Context: The coronavirus disease 2019 (COVID-19) outbreak is an unprecedented global public health challenge, leading to thousands of deaths every day worldwide. Despite the epidemiological importance, clinical patterns of children with COVID-19 remain unclear. Objective: To describe the clinical, laboratorial and radiological characteristics of children with COVID-19. Data Sources: The Medline database was searched between December 1st 2019 and March 30th 2020. Study Selection: Inclusion criteria were: (1) studied patients younger than 18 years old; (2) presented original data from cases of COVID-19 confirmed by reverse-transcription polymerase chain reaction; and (3) contained descriptions of clinical manifestations, laboratory tests or radiological examinations. Data Extraction: Number of cases, gender, age, clinical manifestations, laboratory tests, radiological examinations and outcomes. Results: A total of 34 studies (1,118 cases) were included. From all the cases, 1,111 had their severity classified: 14.3% were asymptomatic, 36.4% were mild, 46.0% were moderate, 2.2% were severe and 1.2% were critical. The most prevalent symptom was fever (16.3%), followed by cough (14.4%), nasal symptoms (3.6%), diarrhea (2.7%) and nausea/vomiting (2.5%). One hundred forty-five (12.9%) children were diagnosed with pneumonia and 43 (3.8%) upper airway infections were reported. Reduced lymphocyte count were reported in 13.1% of cases. Abnormalities on computed tomography was reported in 62.7% of cases. The most prevalent abnormalities reported were ground glass opacities, patchy shadows and consolidations. Only one death was reported. Conclusions: Clinical manifestations of children with COVID-19 differ widely from adults cases. Fever and respiratory symptoms should not be considered a hallmark of COVID-19 in children.", "qid": 47, "docid": "r3cqvf0c", "rank": 56, "score": 0.7839623093605042}, {"content": "Title: Renal involvement in children with COVID-19 infection Content: Perhaps when China reported its first cases of the novel coronavirus in December 2019, few would predict that it would overwhelm the majority of the global community The first reports conveyed that the rate of infection and death from this virus among children is rare However, evidence showed that there is no particular age range for the disease and children, infants and even neonates may be infected Although COVID-19 primarily targets the host's respiratory system, complications in other organs such as heart, kidney and liver have been observed as well This mini-review attempts to consider the publications focused on the COVID-19 infection among children with emphasis on renal involvement and the treatment approach of this complication", "qid": 47, "docid": "dd69ms7k", "rank": 57, "score": 0.7836495637893677}, {"content": "Title: Clinical Characteristics of Children with COVID-19 Content: BACKGROUND: In December 2019, the infection caused by 2019 novel coronavirus (COVID-19) led to an outbreak in Wuhan, situated in the Hubei Province of China. Following this, there has been a rapid increase in the number of cases. On 12th March 2020, there were over 100,000 confirmed cases and almost 4,300 deaths worldwide. The clinical profile of children with COVID-19 is unknown due to the few number of cases reported. Currently, available data suggest they may have a milder form of illness. METHODS: A review of the literature published from June 2019 to March 2020 was undertaken to evaluate the clinical presentation, management and outcomes of COVID-19 in in children. Data sources included EMBASE, MEDLINE, Cochrane library, ISI Web of Knowledge and references within identified articles. RESULTS: We identified 303 potential studies, and 295 were excluded for reasons including duplicates, experimental studies and case reports. Eight studies were eligible for inclusion, including a total of 820 paediatric cases of COVID-19. Asymptomatic cases represented 14.3% (n = 117) of the total number of cases identified, and thus the remaining 85.7% (n = 703) experienced symptoms. Fever was the commonest symptom in 53.9% (n = 48) of cases, followed by cough in 39.3% (n = 35) of cases, and rhinorrhoea or pharyngeal congestion in 13.5% (n = 12) of cases. Diarrhoea and sore throats were less common symptoms, 7.9% (n = 7) and 9.0% (n = 8) respectively. Other symptoms, including fatigue, headache and dizziness were rare. CONCLUSION: Children are disproportionately affected by COVID-19 and are more likely to run a milder cause of illness following this infection compared to adults. This outbreak only started 3 months ago, therefore, further population wide studies are needed to validate these findings.", "qid": 47, "docid": "fg0lcl64", "rank": 58, "score": 0.7836102247238159}, {"content": "Title: Impact of COVID -19 on children: special focus on the psychosocial aspect Content: Although medical literature shows that children are minimally susceptible to 2019-Corona virus disease (COVID-19), they are hit the hardest by psychosocial impact of this pandemic. Being quarantined in homes and institutions may impose greater psychological burden than the physical sufferings caused by the virus. School closure, lack of outdoor activity, aberrant dietary and sleeping habits are likely to disrupt children's usual lifestyle and can potentially promote monotony, distress, impatience, annoyance and varied neuropsychiatric manifestations. Incidences of domestic violence, child abuse, adulterated online contents are on the rise. Children of single parent and frontline workers suffer unique problems. The children from marginalized communities are particularly susceptible to the infection and may suffer from extended ill-consequences of this pandemic, such as child labor, child trafficking, child marriage, sexual exploitation and death etc. Parents, pediatricians, psychologists, social workers, hospital authorities, government and non-governmental organizations have important roles to play to mitigate the psychosocial ill-effects of COVID-19 on children and adolescents. To provide the basic amenities, social security, medical care, and to minimize the educational inequities among the children of the different strata of the society are foremost priorities.", "qid": 47, "docid": "k30mv20e", "rank": 59, "score": 0.7832992076873779}, {"content": "Title: Impact of COVID -19 on children: special focus on the psychosocial aspect. Content: Although medical literature shows that children are minimally susceptible to 2019-Corona virus disease (COVID-19), they are hit the hardest by psychosocial impact of this pandemic. Being quarantined in homes and institutions may impose greater psychological burden than the physical sufferings caused by the virus. School closure, lack of outdoor activity, aberrant dietary and sleeping habits are likely to disrupt children's usual lifestyle and can potentially promote monotony, distress, impatience, annoyance and varied neuropsychiatric manifestations. Incidences of domestic violence, child abuse, adulterated online contents are on the rise. Children of single parent and frontline workers suffer unique problems. The children from marginalized communities are particularly susceptible to the infection and may suffer from extended ill-consequences of this pandemic, such as child labor, child trafficking, child marriage, sexual exploitation and death etc. Parents, pediatricians, psychologists, social workers, hospital authorities, government and non-governmental organizations have important roles to play to mitigate the psychosocial ill-effects of COVID-19 on children and adolescents. To provide the basic amenities, social security, medical care, and to minimize the educational inequities among the children of the different strata of the society are foremost priorities.", "qid": 47, "docid": "q0ubeurh", "rank": 60, "score": 0.7832992076873779}, {"content": "Title: Disease and age\u2010related inequalities in paediatric research, funding and communication: lessons from the COVID\u201019 pandemic Content: COVID\u201019 has already caused millions of infections, thousands of deaths and countless indirect and poorly estimated consequences on other diseases and the global economy. All ages are potentially susceptible, but the virus has had a lower direct impact on children, with fewer severe cases and low mortality rates. However, the reasons for this are still unclear and we cannot rule out children\u2019s role in transmitting the disease. The serious impact that restrictive measures have had on children\u2019s lives have not been fully considered. Because children are less affected by COVID\u201019, the scientific community, health agencies and governments have not focused much attention on them during this pandemic.", "qid": 47, "docid": "todyvwsj", "rank": 61, "score": 0.7824772596359253}, {"content": "Title: COVID19: potential cardiovascular issues in pediatric patients. Content: The novel severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) has rapidly spread worldwide with increasing hospitalization and mortality rate. Ongoing studies and accumulated data are de- tailing the features and the effects of the new coronavirus disease 19 (COVID 19) in the adult population, and cardiovascular involvement is emerging as the most significant and life-threatening complication, with an in- creased risk of morbidity and mortality in patients with underlying cardiovascular disease. At present, though the limited data on the effects of COVID 19 in pediatric patients, children seem to count for a little proportion of SARS-COV 2 infection, and present with less severe disease and effects However infants and toddlers are at risk of developing critical course. The disease has a range of clinical presentations in children, for which the potential need for further investigation of myocardial injury and cardiovascular issues should be kept in mind to avoid misdiagnosing severe clinical entities. Overlapping with Kawasaki disease is a concern, particularly the incomplete and atypical form. We aim to summarize the initial considerations and potential cardiovascular implications of COVID-19 for children and patients with congenital heart disease.", "qid": 47, "docid": "9jr7ekbu", "rank": 62, "score": 0.782349705696106}, {"content": "Title: COVID19: potential cardiovascular issues in pediatric patients Content: The novel severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) has rapidly spread worldwide with increasing hospitalization and mortality rate. Ongoing studies and accumulated data are de- tailing the features and the effects of the new coronavirus disease 19 (COVID 19) in the adult population, and cardiovascular involvement is emerging as the most significant and life-threatening complication, with an in- creased risk of morbidity and mortality in patients with underlying cardiovascular disease. At present, though the limited data on the effects of COVID 19 in pediatric patients, children seem to count for a little proportion of SARS-COV 2 infection, and present with less severe disease and effects However infants and toddlers are at risk of developing critical course. The disease has a range of clinical presentations in children, for which the potential need for further investigation of myocardial injury and cardiovascular issues should be kept in mind to avoid misdiagnosing severe clinical entities. Overlapping with Kawasaki disease is a concern, particularly the incomplete and atypical form. We aim to summarize the initial considerations and potential cardiovascular implications of COVID-19 for children and patients with congenital heart disease.", "qid": 47, "docid": "18zt8b8g", "rank": 63, "score": 0.7823496460914612}, {"content": "Title: Covid-19 in children: A brief overview after three months experience Content: Severe Acute Respiratory Syndrome - Coronavirus - 2 (SARS-CoV-2) and its related Coronavirus Disease - 19 (COVID-19) has become a health emergency worldwide. The medical community has been concerned since the beginning of the outbreak about the potential impact of COVID-19 in children, especially in those with underlying chronic diseases. Fortunately, COVID-19 has been reported to be less severe in children than in adults. However, epidemiologic and clinical data are scarce. Children show unique features of SARS-CoV-2 involvement that may account for the low rate of infection and death in this age group. The purpose of this review is to summarize the most relevant evidence of COVID-19 in children highlighting similarities and differences with adults.", "qid": 47, "docid": "fuhvsy2j", "rank": 64, "score": 0.7819274663925171}, {"content": "Title: Covid-19 in children: A brief overview after three months experience. Content: Severe Acute Respiratory Syndrome - Coronavirus - 2 (SARS-CoV-2) and its related Coronavirus Disease - 19 (COVID-19) has become a health emergency worldwide. The medical community has been concerned since the beginning of the outbreak about the potential impact of COVID-19 in children, especially in those with underlying chronic diseases. Fortunately, COVID-19 has been reported to be less severe in children than in adults. However, epidemiologic and clinical data are scarce. Children show unique features of SARS-CoV-2 involvement that may account for the low rate of infection and death in this age group. The purpose of this review is to summarize the most relevant evidence of COVID-19 in children highlighting similarities and differences with adults.", "qid": 47, "docid": "5gvpjxxp", "rank": 65, "score": 0.7819274663925171}, {"content": "Title: Potential Effectiveness and Safety of Antiviral Agents in Children with Coronavirus Disease 2019: A Rapid Review and Meta-Analysis Content: Background: The COVID-19 outbreak presents a new, life-threatening disease. Our aim was to assess the potential effectiveness and safety of antiviral agents for COVID-19 in children. Methods: Electronic databases from their inception to March, 31 2020 were searched for randomized controlled trials, clinical controlled trials and cohort studies of interventions with antiviral agents for children (less than 18 years of age) with COVID-19. Results: A total of 23 studies of indirect evidence with 6008 patients were included. The risks of bias in all studies were moderate to high in general. The effectiveness and safety of antiviral agents for children with COVID-19 is uncertain: For adults with COVID-19, lopinavir/ritonavir had no effect on mortality (risk ratio [RR]= 0.77, 95% confidence interval [CI] 0.45 to 1.30) and probability of negative PCR test (RR=0.98, 95 CI% 0.82 to 1.18). Arbidol had no benefit on probability of negative PCR test (RR=1.27, 95% CI 0.93 to 1.73). Hydroxychloroquine was not associated with increasing the probability of negative PCR result (RR=0.93, 95% CI 0.73 to 1.18). For adults with SARS, interferon was associated with reduced corticosteroid dose (weighted mean difference [WMD]=-0.14 g, 95% CI -0.21 to -0.07) but had no effect on mortality (RR=0.72, 95% CI 0.28 to 1.88); ribavirin did not reduce mortality (RR=0.68, 95% CI % 0.43 to 1.06) and was associated with high risk of severe adverse reactions; and oseltamivir had no effect on mortality (RR=0.87, 95% CI 0.55 to 1.38). Ribavirin combined with interferon was also not effective in adults with MERS and associated with adverse reactions. Conclusions: There is no evidence showing the effectiveness of antiviral agents for children with COVID-19, and the clinical efficacy of existing antiviral agents is still uncertain. We do not suggest clinical routine use of antivirals for COVID-19 in children, with the exception of clinical trials. Keywords: Antiviral agents; children; COVID-19; meta-analysis; rapid review.", "qid": 47, "docid": "xuo2jrfq", "rank": 66, "score": 0.781851053237915}, {"content": "Title: Risks to Children under-five in India from COVID-19 Content: Objective: The novel coronavirus, COVID-19, has rapidly emerged to become a global pandemic and is known to cause a high risk to patients over the age of 70 and those with co-morbidities, such as hypertension and diabetes. Though children are at comparatively lower risk compared to adults, the Indian population has a large young demographic that is likely to be at higher risk due to exposure to pollution, malnutrition and poor access to medical care. We aimed to quantify the potential impact of COVID-19 on Indias child population. Methods: We combined district family household survey data with data from the COVID-19 outbreak in China to analyze the potential impact of COVID-19 on children under the age of 5, under three different scenarios; each of which assumed the prevalence of infection to be 0.5%, 1%, or 5%. Results: We find that in the lowest prevalence scenario, across the most populous 18 Indian states, asymptomatic, non-hospitalized symptomatic and hospitalized symptomatic cases could reach 87,200, 412,900 and 31,900, respectively. In a moderate prevalence scenario, these figures reach 174,500, 825,800, and 63,800, and in the worst case, high prevalence scenario these cases could climb as high as 872,200, 4,128,900 and 319,700. Conclusion: These estimates show COVID-19 has the potential to pose a substantial threat to Indias large population of children, particularly those suffering from malnutrition and exposure to indoor air pollution, who may have limited access to health services.", "qid": 47, "docid": "jm2dtrav", "rank": 67, "score": 0.7817696332931519}, {"content": "Title: Financial Burden of Hospitalization of Children with Coronavirus Disease 2019 under the National Health Insurance Service in Korea Content: Coronavirus disease 2019 (COVID-19) has resulted in an ongoing pandemic; however, the socioeconomic burden of COVID-19 treatment in the pediatric population remains unclear. Thus, the aim of this study was to determine the hospitalization periods and medical costs among children with COVID-19. In total, 145 billing statements for pediatric patients receiving healthcare services because of COVID-19 from February 1, 2020 to March 31, 2020 were used. The study showed that individual treatment costs for children with COVID-19 are approximately USD 2,192 under the Korean National Health Insurance Service System. This study revealed the differences in cost among age groups, determined by the type of hospital wherein admission occurred, as a trend of increasing age, increasing hospitalization time, and increasing cost was observed. Tailored COVID-19 treatment strategies by age group may lower costs and increase the effectiveness of resource allocation.", "qid": 47, "docid": "pcyfx7t4", "rank": 68, "score": 0.7814487218856812}, {"content": "Title: Pediatric Asthma & Coronavirus (COVID-19)-Clinical Presentation in an Asthmatic Child\u2014Case Report Content: Pandemic coronavirus (COVID-19) is a novel virus that causes severe pneumonia. Elderly people with co-morbidities are at risk of severe disease. Symptoms are generally milder in children. We present an asthmatic 12-year old girl with cough, wheeze, and mild pneumonia due to COVID-19. Reverse transcription (RT) polymerase chain reaction (PCR) confirmed COVID-19 on nasopharyngeal sample. Chest radiograph revealed bronchopneumonia. Frequent salbutamol inhalers were administered for treatment. Case was discharged home 2 days following hospitalization. COVID-19 may present with mild pneumonia in children or with an exacerbation of asthma in asthmatic children. Additional observations of clinical presentations of COVID-19 in children are recommended.", "qid": 47, "docid": "nec12z61", "rank": 69, "score": 0.7808958292007446}, {"content": "Title: The Risk of Children Hospitalized With Severe COVID-19 in Wuhan. Content: BACKGROUND Novel coronavirus disease (COVID-19) is spreading globally. Little is known about the risk factors for the clinical outcomes of COVID-19 in children. METHODS A retrospective case-control study was taken in children with severe acute respiratory syndrome coronary virus-2 infection in Wuhan Children's Hospital. Risk factors associated with the development of COVID-19 and progression were collected and analyzed. RESULTS Eight out of 260 children diagnosed with severe COVID-19 pneumonia were included in the study. Thirty-five children with COVID-19 infection matched for age, sex and date of admission, and who classified as non-severe type, were randomly selected from the hospital admissions. For cases with severe pneumonia caused by COVID-19, the most common symptoms were dyspnea (87.5%), fever (62.5%) and cough (62.5%). In laboratory, white blood cells count was significantly higher in severe children than non-severe children. Levels of inflammation bio-makers such as hsCRP, IL-6, IL-10 and D-dimer elevated in severe children compared with non-severe children on admission. The level of total bilirubin and uric acid clearly elevated in severe children compared with non-severe children on admission. All of severe children displayed the lesions on chest CT, more lung segments were involved in severe children than in non-severe children, which was only risk factor associated with severe COVID-19 pneumonia in multivariable analysis. CONCLUSIONS More than 3 lung segments involved were associated with greater risk of development of severe COVID-19 in children. Moreover, the possible risk of the elevation of IL-6, high total bilirubin and D-dimer with univariable analysis could identify patients to be severe earlier.", "qid": 47, "docid": "l5n0r5g9", "rank": 70, "score": 0.77982497215271}, {"content": "Title: Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study Content: BACKGROUND: Since December, 2019, an outbreak of coronavirus disease 2019 (COVID-19) has spread globally. Little is known about the epidemiological and clinical features of paediatric patients with COVID-19. METHODS: We retrospectively retrieved data for paediatric patients (aged 0-16 years) with confirmed COVID-19 from electronic medical records in three hospitals in Zhejiang, China. We recorded patients' epidemiological and clinical features. FINDINGS: From Jan 17 to March 1, 2020, 36 children (mean age 8\u00b73 [SD 3\u00b75] years) were identified to be infected with severe acute respiratory syndrome coronavirus 2. The route of transmission was by close contact with family members (32 [89%]) or a history of exposure to the epidemic area (12 [33%]); eight (22%) patients had both exposures. 19 (53%) patients had moderate clinical type with pneumonia; 17 (47%) had mild clinical type and either were asymptomatic (ten [28%]) or had acute upper respiratory symptoms (seven [19%]). Common symptoms on admission were fever (13 [36%]) and dry cough (seven [19%]). Of those with fever, four (11%) had a body temperature of 38\u00b75\u00b0C or higher, and nine (25%) had a body temperature of 37\u00b75-38\u00b75\u00b0C. Typical abnormal laboratory findings were elevated creatine kinase MB (11 [31%]), decreased lymphocytes (11 [31%]), leucopenia (seven [19%]), and elevated procalcitonin (six [17%]). Besides radiographic presentations, variables that were associated significantly with severity of COVID-19 were decreased lymphocytes, elevated body temperature, and high levels of procalcitonin, D-dimer, and creatine kinase MB. All children received interferon alfa by aerosolisation twice a day, 14 (39%) received lopinavir-ritonavir syrup twice a day, and six (17%) needed oxygen inhalation. Mean time in hospital was 14 (SD 3) days. By Feb 28, 2020, all patients were cured. INTERPRETATION: Although all paediatric patients in our cohort had mild or moderate type of COVID-19, the large proportion of asymptomatic children indicates the difficulty in identifying paediatric patients who do not have clear epidemiological information, leading to a dangerous situation in community-acquired infections. FUNDING: Ningbo Clinical Research Center for Children's Health and Diseases, Ningbo Reproductive Medicine Centre, and Key Scientific and Technological Innovation Projects of Wenzhou.", "qid": 47, "docid": "12sakknb", "rank": 71, "score": 0.7796884775161743}, {"content": "Title: Psychopathological problems related to the COVID\u201019 pandemic and possible prevention with music therapy Content: COVID-19 is having a profound effect on societies worldwide and the impact that it is having on children cannot be underestimated. Although Brodin (1) stated that the disease tends to be mild in children, psychopathological considerations allow us to assume that the pandemic will have a high risk of long-term paediatric psychiatric sequelae and interdisciplinary preventative measures are needed.", "qid": 47, "docid": "0mxv8h06", "rank": 72, "score": 0.7793892621994019}, {"content": "Title: Children are unlikely to be the main drivers of the COVID-19 pandemic - A systematic review Content: AIM: Many countries have closed schools and kindergartens to minimise COVID-19, but the role that children play in disease transmission is unclear. METHODS: A systematic literature review of the MEDLINE and EMBASE databases and medRxiv/bioRxiv preprint servers to 11 May 2020 identified published and unpublished papers on COVID-19 transmission by children. RESULTS: We identified 700 scientific papers and letters and 47 full texts were studied in detail. Children accounted for a small fraction of COVID-19 cases and mostly had social contacts with peers or parents, rather than older people at risk of severe disease. Data on viral loads were scarce, but indicated that children may have lower levels than adults, partly because they often have fewer symptoms, and this should decrease the transmission risk. Household transmission studies showed that children were rarely the index case and case studies suggested that children with COVID-19 seldom caused outbreaks. However, it is highly likely that children can transmit the SARS-COV-2 virus, which causes COVID-19, and even asymptomatic children can have viral loads. CONCLUSION: Children are unlikely to be the main drivers of the pandemic. Opening up schools and kindergartens is unlikely to impact COVID-19 mortality rates in older people.", "qid": 47, "docid": "tm9uso6w", "rank": 73, "score": 0.7787455320358276}, {"content": "Title: Severe and fatal forms of COVID-19 in children Content: ABSTRACT OBJECTIVES: The aim of this study was to describe severe forms of novel coronavirus disease 2019 in children, including patient characteristics, clinical, laboratory, and imaging findings, as well as the disease management and outcomes. METHODS: This was a retrospective, single-center, observational study conducted in a pediatric intensive and high-dependency care unit (PICU, HDU) in an urban hospital in Paris. All patients, aged from 1 month to 18 years, admitted for confirmed or highly suspected SARS-CoV-2 were included. RESULTS: We analyzed the data of 27 children. Comorbidities (n = 19, 70 %) were mainly neurological (n = 7), respiratory, (n = 4), or sickle cell disease (n = 4). SARS-CoV-2 PCR results were positive in 24 children (nasopharyngeal swabs). The three remaining children had a chest CT scan consistent with COVID-19. Respiratory involvement was observed in 24 patients (89%). Supportive treatments were invasive mechanical ventilation (n = 9), catecholamine (n = 4), erythropheresis (n = 4), renal replacement therapy (n = 1), and extracorporeal membrane oxygenation (n = 1). Five children died, of whom three were without past medical history. CONCLUSION: This study highlighted the large spectrum of clinical presentation and time course of disease progression as well as the non-negligible occurrence of pediatric life-threatening and fatal cases of COVID-19 mostly in patients with comorbidities. Additional laboratory investigations are needed to further analyze the mechanism underlying the variability of SARS-Cov-2 pathogenicity in children", "qid": 47, "docid": "z1wihwga", "rank": 74, "score": 0.7768362760543823}, {"content": "Title: Serial Computed Tomography Findings in a Child with Coronavirus Disease (COVID-19) Pneumonia Content: Computed tomography (CT) manifestations and treatment of children with COVID-19 are still unclear. We report serial CT findings of a child with COVID-19 pneumonia who recovered without any sequelae.", "qid": 47, "docid": "njea7o4p", "rank": 75, "score": 0.7767519950866699}, {"content": "Title: Infection control practices in children during COVID-19 pandemic: differences from adults Content: BACKGROUND: Limited studies have been published on practices and management of COVID-19 in children. Despite the fact that COVID-19 rarely caused any severe disease in children, the asymptomatic children might be playing an important role for spreading COVID-19 in healthcare facilities. This review aimed at sharing our experience of how to handle patients with COVID-19 in a pediatric referral and tertiary care hospital to prevent the possible transmissions to the healthcare workers (HCWs). METHODS: This review sought to identify infection control practices measures during COVID-19 pandemic comes from our daily practice combined with the most recent guidelines with the new experience and information. RESULTS: Prevention the transmission of COVID-19 to the HCWs, four primary themes should be taken into consideration; (1) ongoing education and importance of the organization of the healthcare facility, (2) proper clinical triage and isolation of the suspected or confirmed COVID-19 patients in the outpatient clinics and in the emergency departments, (3) necessity of the organization of the COVID-19 wards, and (4) utilization of personal protective equipment. CONCLUSIONS: Infection control precautions to prevent the possible transmissions to HCWs as well as the other patients and their caregivers from children with COVID-19 are very critical. If sufficient precautions are not taken, healthcare settings may serve as additional source of transmission and spread of COVID-19 in the society.", "qid": 47, "docid": "satufg9w", "rank": 76, "score": 0.7764168977737427}, {"content": "Title: Favourable outcome of coronavirus disease 2019 in a 1\u2010year\u2010old girl with acute myeloid leukaemia and severe treatment\u2010induced immunosuppression Content: Since the beginning of coronavirus disease 2019 (COVID-19) pandemic outbreak, it has emerged that the clinical course and outcome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is definitely more favourable in children than in adults.1 Few cases of infection in children with cancer are described; also in these patients, except for one reported case,2 the disease was largely asymptomatic.3 Nevertheless, the management of COVID-19 in young patients with comorbidities, particularly cancer, remains a challenge for the clinician; further data are required to optimize the clinical approach to these cases.", "qid": 47, "docid": "4cz2hziz", "rank": 77, "score": 0.7763485908508301}, {"content": "Title: The Epidemiology of SARS-CoV-2 in a Pediatric Healthcare Network in the United States Content: BACKGROUND: Understanding the prevalence and clinical presentation of COVID-19 in pediatric patients can help healthcare providers and systems prepare and respond to this emerging pandemic. METHODS: Retrospective case series of patients tested for SARS-CoV-2 across a pediatric healthcare network, including the clinical features and outcomes of those with positive test results. RESULTS: Of 7,256 unique children tested for SARS-CoV-2, 424 (5.8%) tested positive. Patients 18-21 years of age had the highest test positive rate (11.2%) while those 1-5 years of age had the lowest (3.9%). By race, 10.6% (226/2132) of Black children tested positive vs. 3.3% (117/3592) of White children. Of those with an indication for testing, 21.1% (371/1756) of patients with reported exposures or clinical symptoms tested positive vs. 3.8% (53/1410) of those undergoing pre-procedural or pre-admission testing. Of the 424 patients who tested positive for SARS-CoV-2, 182 (42.9%) had no comorbid medical conditions, 87 (20.5%) had asthma, 55 (13.0% had obesity, and 38 (9.0%) had mental health disorders. Overall, 52.1% had cough, 51.2% fever, and 14.6% shortness of breath. Seventy-seven (18.2%) SARS-CoV-2 positive patients were hospitalized, of which 24 (31.2%) required any respiratory support. SARS-CoV-2-targeted antiviral therapy was given to 9 patients, and immunomodulatory therapy to 18 patients. Twelve (2.8%) SARS-CoV-2 positive patients developed critical illness requiring mechanical ventilation and 2 patients required extracorporeal membrane oxygenation. Two patients died. CONCLUSIONS: In this large cohort of pediatric patients tested for SARS-CoV-2, the rate of infection was low, but varied by testing indication. The majority of cases were mild, few children had critical illness, and two patients died.", "qid": 47, "docid": "dqll7wmr", "rank": 78, "score": 0.7759221792221069}, {"content": "Title: Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center\u2019s observational study Content: BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was first detected in Wuhan, Hubei, China. People of all ages are susceptible to SARS-CoV-2 infection. No information on severe pediatric patients with COVID-19 has been reported. We aimed to describe the clinical features of severe pediatric patients with COVID-19. METHODS: We included eight severe or critically ill patients with COVID-19 who were treated at the Intensive Care Unit (ICU), Wuhan Children\u2019s Hospital from January 24 to February 24. We collected information including demographic data, symptoms, imaging data, laboratory findings, treatments and clinical outcomes of the patients with severe COVID-19. RESULTS: The onset age of the eight patients ranged from 2 months to 15 years; six were boys. The most common symptoms were polypnea (8/8), followed by fever (6/8) and cough (6/8). Chest imaging showed multiple patch-like shadows in seven patients and ground-glass opacity in six. Laboratory findings revealed normal or increased whole blood counts (7/8), increased C-reactive protein, procalcitonin and lactate dehydrogenase (6/8), and abnormal liver function (4/8). Other findings included decreased CD16 + CD56 (4/8) and Th/Ts*(1/8), increased CD3 (2/8), CD4 (4/8) and CD8 (1/8), IL-6 (2/8), IL-10 (5/8) and IFN-\u03b3 (2/8). Treatment modalities were focused on symptomatic and respiratory support. Two critically ill patients underwent invasive mechanical ventilation. Up to February 24, 2020, three patients remained under treatment in ICU, the other five recovered and were discharged home. CONCLUSIONS: In this series of severe pediatric patients in Wuhan, polypnea was the most common symptom, followed by fever and cough. Common imaging changes included multiple patch-like shadows and ground-glass opacity; and a cytokine storm was found in these patients, which appeared more serious in critically ill patients.", "qid": 47, "docid": "tt2q5mgs", "rank": 79, "score": 0.7757495641708374}, {"content": "Title: Flash Survey on SARS-CoV-2 Infections in Pediatric Patients on anti-Cancer Treatment Content: Abstract Introduction Since the beginning of COVID-19 pandemics, it is known that the severe course of the disease occurs mostly among elderly, whereas it is rare among children and young adults. Comorbidities, in particular diabetes and hypertension, clearly associated with age, besides obesity and smoke are strongly associated with the need of intensive treatment and a dismal outcome. A weaker immunity of the elderly has been proposed as a possible explanation of this uneven age distribution. Along the same line, anecdotal information from Wuhan, China mentioned a severe course of COVID-19 in a child treated for leukemia. Aim and methods We made a flash survey on COVID19 incidence and severity among children on anticancer treatment. Respondents were asked by email to fill in a short web based survey. Results We received reports from 25 countries, where approximately 10,000 patients at risk are followed. At the time of the survey, over 200 of these children were tested, nine of whom were positive for COVID-19. Eight of the nine cases had asymptomatic to mild disease and one was just diagnosed with COVID-19. We also discuss preventive measures that are in place or should be taken as well as treatment options in immunocompromised children with COVID-19. Conclusion Thus, even children receiving anti-cancer chemotherapy may have a mild or asymptomatic course of COVID-19. While we should not underestimate the risk of developing a more severe course of COVID-19 than observed here, the intensity of preventive measures should not cause delays or obstructions in oncological treatment.", "qid": 47, "docid": "9d5g5xaw", "rank": 80, "score": 0.7754756212234497}, {"content": "Title: Pathophysiology of COVID-19: Why Children Fare Better than Adults? Content: The world is facing Coronavirus Disease-2019 (COVID-19) pandemic, which is causing a large number of deaths and burden on intensive care facilities. It is caused by Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) originating in Wuhan, China. It has been seen that fewer children contract COVID-19 and among infected, children have less severe disease. Insights in pathophysiological mechanisms of less severity in children could be important for devising therapeutics for high-risk adults and elderly. Early closing of schools and day-care centers led to less frequent exposure and hence, lower infection rate in children. The expression of primary target receptor for SARS-CoV-2, i.e. angiotensin converting enzyme-2 (ACE-2), decreases with age. ACE-2 has lung protective effects by limiting angiotensin-2 mediated pulmonary capillary leak and inflammation. Severe COVID-19 disease is associated with high and persistent viral loads in adults. Children have strong innate immune response due to trained immunity (secondary to live-vaccines and frequent viral infections), leading to probably early control of infection at the site of entry. Adult patients show suppressed adaptive immunity and dysfunctional over-active innate immune response in severe infections, which is not seen in children. These could be related to immune-senescence in elderly. Excellent regeneration capacity of pediatric alveolar epithelium may be contributing to early recovery from COVID-19. Children, less frequently, have risk factors such as co-morbidities, smoking, and obesity. But young infants and children with pre-existing illnesses could be high risk groups and need careful monitoring. Studies describing immune-pathogenesis in COVID-19 are lacking in children and need urgent attention.", "qid": 47, "docid": "g592dfyz", "rank": 81, "score": 0.7752127647399902}, {"content": "Title: Children are unlikely to be the main drivers of the COVID\u201019 pandemic \u2013 a systematic review Content: AIM: Many countries have closed schools and kindergartens to minimise COVID\u201019, but the role that children play in disease transmission is unclear. METHODS: A systematic literature review of the MEDLINE and EMBASE databases and medRxiv/bioRxiv preprint servers to 11 May 2020 identified published and unpublished papers on COVID\u201019 transmission by children. RESULTS: We identified 700 scientific papers and letters and 47 full texts were studied in detail. Children accounted for a small fraction of COVID\u201019 cases and mostly had social contacts with peers or parents, rather than older people at risk of severe disease. Data on viral loads were scarce, but indicated that children may have lower levels than adults, partly because they often have fewer symptoms, and this should decrease the transmission risk. Household transmission studies showed that children were rarely the index case and case studies suggested that children with COVID\u201019 seldom caused outbreaks. However, it is highly likely that children can transmit the SARS\u2010COV\u20102 virus, which causes COVID\u201019, and even asymptomatic children can have viral loads. CONCLUSION: Children are unlikely to be the main drivers of the pandemic. Opening up schools and kindergartens is unlikely to impact COVID\u201019 mortality rates in older people.", "qid": 47, "docid": "5azti19e", "rank": 82, "score": 0.7751284837722778}, {"content": "Title: COVID-19 in children: Epidemiology, presentation, diagnosis and management Content: The new pandemic coronavirus disease (COVID-19) has affected children, including neonates, who mostly comprise of approximately 2% of total confirmed cases. Most children are asymptomatic or have mild disease and much lower mortality compared to adults for yet unknown reasons. Recovery from illness has largely been universal and <2% have severe disease requiring intensive care. Standardised guidelines from initial studies are now available for diagnosis, treatment, and prevention. Treatment is mostly supportive with no recommendations for any specific drugs so far. As the pandemic evolves, it is expected that more children will be diagnosed and treated with evolving newer regimens. Research should now focus on early diagnosis, better drugs for children, intensive care modalities, and a universal vaccine. New developments will help in better prevention asides from the other precautionary measures already being practiced.", "qid": 47, "docid": "yekcr5ka", "rank": 83, "score": 0.7750840187072754}, {"content": "Title: COVID-19 in children: Epidemiology, presentation, diagnosis and management. Content: The new pandemic coronavirus disease (COVID-19) has affected children, including neonates, who mostly comprise of approximately 2% of total confirmed cases. Most children are asymptomatic or have mild disease and much lower mortality compared to adults for yet unknown reasons. Recovery from illness has largely been universal and <2% have severe disease requiring intensive care. Standardised guidelines from initial studies are now available for diagnosis, treatment, and prevention. Treatment is mostly supportive with no recommendations for any specific drugs so far. As the pandemic evolves, it is expected that more children will be diagnosed and treated with evolving newer regimens. Research should now focus on early diagnosis, better drugs for children, intensive care modalities, and a universal vaccine. New developments will help in better prevention asides from the other precautionary measures already being practiced.", "qid": 47, "docid": "ni4ck8w4", "rank": 84, "score": 0.7750838994979858}, {"content": "Title: Clinical characteristics and diagnostic challenges of pediatric COVID-19: A systematic review and meta-analysis Content: BACKGROUND/PURPOSE: Current studies on pediatric coronavirus disease 2019 (COVID-19) are rare. The clinical characteristics and spectrum are still unknown. Facing this unknown and emerging pathogen, we aimed to collect current evidence about COVID-19 in children. METHODS: We performed a systematic review in PubMed and Embase to find relevant case series. Because some reports were published in Chinese journals, the journals and publications of the Chinese Medical Association related to COVID-19 were completely reviewed. A random effects model was used to pool clinical data in the meta-analysis. RESULTS: Nine case series were included. In the pooled data, most of patients (75%) had a household contact history. The disease severity was mainly mild to moderate (98%). Only 2 children (2%) received intensive care. Fever occurred in 59% of the patients, while cough in 46%. Gastrointestinal symptoms (12%) were uncommon. There are 26% children are asymptomatic. The most common radiographic finding was ground glass opacities (48%). Currently, there is no evidence of vertical transmission to neonates born to mothers with COVID-19. Compared with the most relevant virus, SARS-CoV, SARS-CoV-2 causes less severe disease. CONCLUSION: COVID-19 has distinct features in children. The disease severity is mild. Current diagnosis is based mainly on typical ground glass opacities on chest CT, epidemiological suspicion and contact tracing.", "qid": 47, "docid": "qqb433od", "rank": 85, "score": 0.7750815153121948}, {"content": "Title: Clinical characteristics of COVID-19 in children: Are they similar to those of SARS? Content: Although the number of SARS-CoV-2 infections has been rising amid the current pandemic of COVID-19, the low infection rate of SARS-CoV-2 in children has been low. By examining the clinical data available in the public domain, the present work clarifies the clinical presentations in children with COVID-19 in China. Statistical significance tests and adjusted odds ratios estimation were performed on the children (age below 18) and adults (age 18 or above) cohorts in China. SARS-CoV and SARS-CoV-2 shared similar clinical features. Lower respiratory tract infection was less prominent in children as evidenced by the relatively low prevalence in chest pain/discomfort and dyspnea. Similar to SARS, younger children had a less aggressive clinical course, compared with adolescents. While fewer symptoms were observed in children compared to adults, there is not yet sufficient evidence to conclude shorter hospital stay in children.", "qid": 47, "docid": "ra237kyx", "rank": 86, "score": 0.7749393582344055}, {"content": "Title: Clinical characteristics and diagnostic challenges of pediatric COVID-19: A systematic review and meta-analysis Content: Background/Purpose Current studies on pediatric coronavirus disease 2019 (COVID-19) are rare. The clinical characteristics and spectrum are still unknown. Facing this unknown and emerging pathogen, we aimed to collect current evidence about COVID-19 in children. Methods We performed a systematic review in PubMed and Embase to find relevant case series. Because some reports were published in Chinese journals, the journals and publications of the Chinese Medical Association related to COVID-19 were completely reviewed. A random effects model was used to pool clinical data in the meta-analysis. Results Nine case series were included. In the pooled data, most of patients (75%) had a household contact history. The disease severity was mainly mild to moderate (98%). Only 2 children (2%) received intensive care. Fever occurred in 59% of the patients, while cough in 46%. Gastrointestinal symptoms (12%) were uncommon. There are 26% children are asymptomatic. The most common radiographic finding was ground glass opacities (48%). Currently, there is no evidence of vertical transmission to neonates born to mothers with COVID-19. Compared with the most relevant virus, SARS-CoV, SARS-CoV-2 causes less severe disease. Conclusion COVID-19 has distinct features in children. The disease severity is mild. Current diagnosis is based mainly on typical ground glass opacities on chest CT, epidemiological suspicion and contact tracing.", "qid": 47, "docid": "xwlzq3m3", "rank": 87, "score": 0.7746262550354004}, {"content": "Title: Clinical Characteristics and Outcomes of Hospitalized and Critically Ill Children and Adolescents with Coronavirus Disease 2019 (COVID-19) at a Tertiary Care Medical Center in New York City Content: OBJECTIVE: To describe the clinical profiles and risk factors for critical illness in hospitalized children and adolescents with COVID-19. STUDY DESIGN: Children 1 month to 21 years with COVID-19 from a single tertiary care children's hospital between March 15-April 13, 2020 were included. Demographic and clinical data were collected. RESULTS: 67 children tested positive for COVID-19; 21 (31.3%) were managed as outpatients. Of 46 admitted patients, 33 (72%) were admitted to the general pediatric medical unit and 13 (28%) to the pediatric intensive care unit (PICU). Obesity and asthma were highly prevalent but not significantly associated with PICU admission (p=0.99). Admission to the PICU was significantly associated with higher C-reactive protein, procalcitonin, and pro-B type natriuretic peptide levels and platelet counts (p<0.05 for all). Patients in the PICU were more likely to require high-flow nasal cannula (p=0.0001) and were more likely to have received Remdesivir through compassionate release (p<0.05). Severe sepsis and septic shock syndromes were observed in 7 (53.8%) PICU patients. Acute respiratory distress syndrome (ARDS) was observed in 10 (77%) PICU patients, 6 of whom (46.2%) required invasive mechanical ventilation for a median of 9 days. Of the 13 patients in the PICU, 8 (61.5%) were discharged home, and 4 (30.7%) patients remain hospitalized on ventilatory support at day 14. One patient died after withdrawal of life-sustaining therapy because of metastatic cancer. CONCLUSIONS: We describe a higher than previously recognized rate of severe disease requiring PICU admission in pediatric patients admitted to the hospital with COVID-19.", "qid": 47, "docid": "t5fpm082", "rank": 88, "score": 0.7745181322097778}, {"content": "Title: Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study Content: Summary Background Since December, 2019, an outbreak of coronavirus disease 2019 (COVID-19) has spread globally. Little is known about the epidemiological and clinical features of paediatric patients with COVID-19. Methods We retrospectively retrieved data for paediatric patients (aged 0\u201316 years) with confirmed COVID-19 from electronic medical records in three hospitals in Zhejiang, China. We recorded patients' epidemiological and clinical features. Findings From Jan 17 to March 1, 2020, 36 children (mean age 8\u00b73 [SD 3\u00b75] years) were identified to be infected with severe acute respiratory syndrome coronavirus 2. The route of transmission was by close contact with family members (32 [89%]) or a history of exposure to the epidemic area (12 [33%]); eight (22%) patients had both exposures. 19 (53%) patients had moderate clinical type with pneumonia; 17 (47%) had mild clinical type and either were asymptomatic (ten [28%]) or had acute upper respiratory symptoms (seven [19%]). Common symptoms on admission were fever (13 [36%]) and dry cough (seven [19%]). Of those with fever, four (11%) had a body temperature of 38\u00b75\u00b0C or higher, and nine (25%) had a body temperature of 37\u00b75\u201338\u00b75\u00b0C. Typical abnormal laboratory findings were elevated creatine kinase MB (11 [31%]), decreased lymphocytes (11 [31%]), leucopenia (seven [19%]), and elevated procalcitonin (six [17%]). Besides radiographic presentations, variables that were associated significantly with severity of COVID-19 were decreased lymphocytes, elevated body temperature, and high levels of procalcitonin, D-dimer, and creatine kinase MB. All children received interferon alfa by aerosolisation twice a day, 14 (39%) received lopinavir\u2013ritonavir syrup twice a day, and six (17%) needed oxygen inhalation. Mean time in hospital was 14 (SD 3) days. By Feb 28, 2020, all patients were cured. Interpretation Although all paediatric patients in our cohort had mild or moderate type of COVID-19, the large proportion of asymptomatic children indicates the difficulty in identifying paediatric patients who do not have clear epidemiological information, leading to a dangerous situation in community-acquired infections. Funding Ningbo Clinical Research Center for Children's Health and Diseases, Ningbo Reproductive Medicine Centre, and Key Scientific and Technological Innovation Projects of Wenzhou.", "qid": 47, "docid": "dmrtsxik", "rank": 89, "score": 0.7744947671890259}, {"content": "Title: Clinical Characteristics of 5 COVID-19 Cases With Non-respiratory Symptoms as the First Manifestation in Children Content: An outbreak of the novel coronavirus disease 2019 (COVID-19) occurred in Wuhan, China, in December 2019, which then rapidly spread to more than 80 countries. However, detailed information on the characteristics of COVID-19 in children is still scarce. Five patients with non-respiratory symptoms as the first manifestation were hospitalized from the emergency department, and were later confirmed to have COVID-19, between 23 January and 20 February 2020, at the Wuhan Children's Hospital. SARS-CoV-2 nucleic acid detection was positive for all the patients. Four of the patients were male and one was female, and their ages ranged from 2-months to 5.6 years. All lived in Wuhan. One patient had a clear history of exposure to SARS-CoV-2, one had a suspected history of exposure, while the others had no exposure history. For three of the five patients, the primary onset disease required an emergency operation or treatment, and included intussusception, acute suppurative appendicitis perforation with local peritonitis, and traumatic subdural hemorrhage with convulsion, while for the other two it was acute gastroenteritis (including one patient with hydronephrosis and a stone in his left kidney). During the course of the disease, four of the five patients had a fever, whereas one case had no fever or cough. Two patients had leukopenia, and one also had lymphopenia. In the two cases of severe COVID-19, the levels of CRP, PCT, serum ferritin, IL-6, and IL-10 were significantly increased, whereas the numbers of CD3+, CD4+, CD8+ T lymphocytes, and CD16 + CD56 natural killer cells were decreased. We also found impaired liver, kidney, and myocardial functions; the presence of hypoproteinemia, hyponatremia, and hypocalcemia; and, in one case, abnormal coagulation function. Except for one patient who had a rotavirus infection, all patients tested negative for common pathogens, including the influenza virus, parainfluenza virus, respiratory syncytial virus, adenovirus, enterovirus, mycoplasma, Chlamydia, and Legionella. Chest CT images of all the patients showed patches or ground-glass opacities in the lung periphery or near the pleura, even large consolidations. This case series is the first report to describe the clinical features of COVID-19 with non-respiratory symptoms as the first manifestation in children.", "qid": 47, "docid": "g4250q6l", "rank": 90, "score": 0.7743983268737793}, {"content": "Title: Clinical characteristics of a case series of children with coronavirus disease 2019 Content: We reported the clinical characteristics of a case series of 10 patients with coronavirus disease 2019 (COVID\u201019) aged from 1 year to 18 years. Seven patients had contact with confirmed COVID\u201019 family members before onset. Fever (4 [40.0%]) and cough (3 [30.0%]) were the most common symptoms. No patient showed leucopenia and lymphopenia on admission. Pneumonia was observed in chest CT images in 5 (50.0%) patients. Five (50.0%) patients received antiviral treatment. No patient had severe complications or developed a severe illness in our study. Our study indicated that COVID\u201019 children present less severe symptoms and have better outcomes.", "qid": 47, "docid": "gmo6big4", "rank": 91, "score": 0.7742329239845276}, {"content": "Title: Clinical Characteristics and Outcomes of Hospitalized and Critically Ill Children and Adolescents with Coronavirus Disease 2019 (COVID-19) at a Tertiary Care Medical Center in New York City Content: OBJECTIVE: To describe the clinical profiles and risk factors for critical illness in hospitalized children and adolescents with COVID-19. STUDY DESIGN: Children 1 month to 21 years with COVID-19 from a single tertiary care children\u2019s hospital between March 15-April 13, 2020 were included. Demographic and clinical data were collected. RESULTS: 67 children tested positive for COVID-19; 21 (31.3%) were managed as outpatients. Of 46 admitted patients, 33 (72%) were admitted to the general pediatric medical unit and 13 (28%) to the pediatric intensive care unit (PICU). Obesity and asthma were highly prevalent but not significantly associated with PICU admission (p=0.99). Admission to the PICU was significantly associated with higher C-reactive protein, procalcitonin, and pro-B type natriuretic peptide levels and platelet counts (p<0.05 for all). Patients in the PICU were more likely to require high-flow nasal cannula (p=0.0001) and were more likely to have received Remdesivir through compassionate release (p<0.05). Severe sepsis and septic shock syndromes were observed in 7 (53.8%) PICU patients. Acute respiratory distress syndrome (ARDS) was observed in 10 (77%) PICU patients, 6 of whom (46.2%) required invasive mechanical ventilation for a median of 9 days. Of the 13 patients in the PICU, 8 (61.5%) were discharged home, and 4 (30.7%) patients remain hospitalized on ventilatory support at day 14. One patient died after withdrawal of life-sustaining therapy because of metastatic cancer. CONCLUSIONS: We describe a higher than previously recognized rate of severe disease requiring PICU admission in pediatric patients admitted to the hospital with COVID-19.", "qid": 47, "docid": "0ifsyct7", "rank": 92, "score": 0.7739256620407104}, {"content": "Title: Impact of COVID-19 on pediatric asthma: practice adjustments and disease burden. Content: Abstract Background It is unclear whether asthma may affect susceptibility or severity of the Coronavirus Disease 2019 (COVID-19) in children and how pediatric asthma services worldwide have responded to the pandemic. Objective To describe the impact of the COVID-19 pandemic on pediatric asthma services and on disease burden in their patients. Methods An online survey was sent to members of the Pediatric Asthma in Real Life (PeARL) think-tank and the World Allergy Organization Pediatric Asthma Committee. It included questions on service provision, disease burden and on the clinical course of confirmed cases of COVID-19 infection among children with asthma. Results Ninety-one respondents, caring for an estimated population of >133,000 children with asthma, completed the survey. COVID-19 significantly impacted pediatric asthma services: 39% ceased physical appointments, 47% stopped accepting new patients, 75% limited patients visits. Consultations were almost halved to a median of 20 (IQR: 10-25) patients per week. Virtual clinics and helplines were launched in most centers. Better than expected disease control was reported in 20% (10-40%) of patients, while control was negatively affected in only 10% (7.5-12.5%). Adherence also appeared to increase. Only 15 confirmed cases of COVID-19 were reported among the population; the estimated incidence is not apparently different from the reports of general pediatric cohorts. Conclusion Children with asthma do not appear to be disproportionately affected by COVID-19. Outcomes may even have improved, possibly through increased adherence and/or reduced exposures. Clinical services have rapidly responded to the pandemic by limiting and replacing physical appointments with virtual encounters.", "qid": 47, "docid": "90hm8i3c", "rank": 93, "score": 0.7734711170196533}, {"content": "Title: COVID-19 in Children: An Ample Review Content: The aim of this review was to describe the current knowledge about coronavirus disease 2019 (COVID-19, which is caused by severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) in children, from epidemiological, clinical, and laboratory perspectives, including knowledge on the disease course, treatment, and prognosis. An extensive literature search was performed to identify papers on COVID-19 (SARS-CoV-2 infection) in children, published between January 1, 2020 and April 1, 2020. There were 44 relevant papers on COVID-19 in children. The results showed that COVID-19 occurs in 0.39\u201312.3% of children. Clinical signs and symptoms are comparable to those in adults, but milder forms and a large percentage of asymptomatic carriers are found among children. Elevated inflammatory markers are associated with complications and linked to various co-infections. Chest computed tomography (CT) scans in children revealed structural changes similar to those found in adults, with consolidations surrounded by halos being somewhat specific for children with COVID-19. The recommended treatment includes providing symptomatic therapy, with no specific drug recommendations for children. The prognosis is much better for children compared to adults. This review highlights that COVID-19 in children is similar to the disease in the adult population, but with particularities regarding clinical manifestations, laboratory test results, chest imaging, and treatment. The prognosis is much better for children compared to adults, but with the progression of the pandemic; the cases in children might change in the future.", "qid": 47, "docid": "8du0s33p", "rank": 94, "score": 0.7731557488441467}, {"content": "Title: COVID-19 PICU guidelines: for high- and limited-resource settings Content: Fewer children than adults have been affected by the COVID-19 pandemic, and the clinical manifestations are distinct from those of adults. Some children particularly those with acute or chronic comorbidities are likely to develop critical illness. Recently, a Multisystem Inflammatory Syndrome (MIS-C) has been described in children with these patients often requiring care in the Pediatric ICU. An international collaboration was formed to review the available evidence and develop evidence-based guidelines for the care of critically ill children with SARS-CoV-2 infection. Where the evidence was lacking, those gaps were replaced with consensus-based guidelines. This process has generated 44 recommendations related to pediatric COVID-19 patients presenting with respiratory distress or failure, sepsis or septic shock, cardiopulmonary arrest, MIS-C, or those requiring adjuvant therapies, or ECMO. Evidence to explain the milder disease patterns in children and the potential to use repurposed antiviral drugs, anti-inflammatory or antithrombotic therapies are also described. Brief summaries of pediatric SARS-CoV-2 infection in different regions of the world are included since few registries are capturing these data globally. These guidelines seek to harmonize the standards and strategies for intensive care that critically ill children with COVID-19 receive across the world. IMPACT: At the time of publication, this is the latest evidence for managing critically ill children infected with SARS-CoV-2.Referring to these guidelines can decrease the morbidity and potentially the mortality of children effected by COVID-19 and its sequalae.These guidelines can be adapted to both high- and limited-resource settings.", "qid": 47, "docid": "mt84vlbw", "rank": 95, "score": 0.7731324434280396}, {"content": "Title: COVID-19 PICU guidelines: for high- and limited-resource settings. Content: Fewer children than adults have been affected by the COVID-19 pandemic, and the clinical manifestations are distinct from those of adults. Some children particularly those with acute or chronic comorbidities are likely to develop critical illness. Recently, a Multisystem Inflammatory Syndrome (MIS-C) has been described in children with these patients often requiring care in the Pediatric ICU. An international collaboration was formed to review the available evidence and develop evidence-based guidelines for the care of critically ill children with SARS-CoV-2 infection. Where the evidence was lacking, those gaps were replaced with consensus-based guidelines. This process has generated 44 recommendations related to pediatric COVID-19 patients presenting with respiratory distress or failure, sepsis or septic shock, cardiopulmonary arrest, MIS-C, or those requiring adjuvant therapies, or ECMO. Evidence to explain the milder disease patterns in children and the potential to use repurposed antiviral drugs, anti-inflammatory or antithrombotic therapies are also described. Brief summaries of pediatric SARS-CoV-2 infection in different regions of the world are included since few registries are capturing these data globally. These guidelines seek to harmonize the standards and strategies for intensive care that critically ill children with COVID-19 receive across the world. IMPACT: At the time of publication, this is the latest evidence for managing critically ill children infected with SARS-CoV-2.Referring to these guidelines can decrease the morbidity and potentially the mortality of children effected by COVID-19 and its sequalae.These guidelines can be adapted to both high- and limited-resource settings.", "qid": 47, "docid": "yno07x0l", "rank": 96, "score": 0.7731324434280396}, {"content": "Title: Infection control practices in children during COVID-19 pandemic: Differences from adults Content: BACKGROUND: Limited studies have been published on practices and management of Coronavirus Disease 2019 (COVID-19) in children. Despite the fact that COVID-19 rarely caused any severe disease in children, the asymptomatic children might be playing an important role for spreading COVID-19 in healthcare facilities. This review aimed at sharing our experience of how to handle patients with COVID-19 in a pediatric referral and tertiary care hospital to prevent the possible transmissions to the healthcare workers (HCWs). METHODS: This review sought to identify infection control practices measures during COVID-19 pandemic comes from our daily practice combined with the most recent guidelines with the new experience and information. RESULTS: Prevention the transmission of COVID-19 to the HCWs, 4 primary themes should be taken into consideration; (1) ongoing education and importance of the organization of the healthcare facility, (2) proper clinical triage and isolation of the suspected or confirmed COVID-19 patients in the outpatient clinics and in the emergency departments, (3) necessity of the organization of the COVID-19 wards, and (4) utilization of personal protective equipment. CONCLUSIONS: Infection control precautions to prevent the possible transmissions to HCWs as well as the other patients and their caregivers from children with COVID-19 are very critical. If sufficient precautions are not taken, healthcare settings may serve as additional source of transmission and spread of COVID-19 in the society.", "qid": 47, "docid": "q1zyesvx", "rank": 97, "score": 0.7718740701675415}, {"content": "Title: Children with Coronavirus Disease 2019 (COVID-19): A Review of Demographic, Clinical, Laboratory and Imaging Features in 2,597 Pediatric Patients Content: An epidemic of coronavirus disease 2019 (COVID-19) has been spreading worldwide. With the rapid increase in the number of infections, children with COVID-19 appear to be rising. Most research findings regarding adult cases, which are not always transferrable to children. Evidence-based studies are still expected to formulate clinical decisions for pediatric patients. In this review, we evaluated the demographic, clinical, laboratory and imaging features from 2,597 pediatric patients of COVID-19 that reported recently. We found that even lymphopenia was the most common lab finding in adults, it infrequently occurred in children (9.8%). Moreover, elevated creatine kinase MB isoenzyme (CK-MB) was much more commonly observed in children (27.0%) than that in adults, suggesting that heart injury would be more likely to happen in pediatric patients. Our analysis may contribute to determine the spectrum of disease in children, as well as to develop strategies to control the disease transmission. This article is protected by copyright. All rights reserved.", "qid": 47, "docid": "fmijknz0", "rank": 98, "score": 0.7718155980110168}, {"content": "Title: Novel coronavirus disease (COVID-19) in children Content: Coronavirus disease (COVID-19) was firstly reported at the end of 2019. The disease rapidly spread all around the world in a few months and was declared a worldwide pandemic by WHO in March 2020. By April 9, there were 1,436,198 confirmed COVID-19 cases in the world, nearly with 6% mortality rate. This novel infectious disease causes respiratory tract illness that may generally occur as mild upper respiratory tract disease or pneumonia. In older patients and/or patients with underlying conditions, it may result in acute respiratory distress syndrome, multi organ failure and even death. According to the current literature, children account approximately for 1%\u00ad5% of diagnosed COVID-19 cases. Generally, COVID-19 seems to be a less severe disease for children than adults. Approximately 90% of pediatric patients are diagnosed as asymptomatic, mild, or moderate disease. However, up to 6.7% of cases may be severe. Severe illness is generally seen in patients smaller than 1 year of age and patients who have underlying disesases. The epidemiological and clinical patterns of COVID-19 and treatment approaches in pediatric patients still remain unclear although many pediatric reports are published. This review aims to summarize the current epidemics, clinical presentations, diagnosis, and treatment of COVID-19 in pediatric patients.", "qid": 47, "docid": "epoo8mj4", "rank": 99, "score": 0.771116316318512}, {"content": "Title: Chest computed tomography in children with COVID-19 respiratory infection Content: BACKGROUND: Infection with COVID-19 is currently rare in children. OBJECTIVE: To describe chest CT findings in children with COVID-19. MATERIALS AND METHODS: We studied children at a large tertiary-care hospital in China, during the period from 28 January 2019 to 8 February 2020, who had positive reverse transcriptase polymerase chain reaction (RT-PCR) for COVID-19. We recorded findings at any chest CT performed in the included children, along with core clinical observations. RESULTS: We included five children from 10 months to 6 years of age (mean 3.4 years). All had had at least one CT scan after admission. Three of these five had CT abnormality on the first CT scan (at 2 days, 4 days and 9 days, respectively, after onset of symptoms) in the form of patchy ground-glass opacities; all normalised during treatment. CONCLUSION: Compared to reports in adults, we found similar but more modest lung abnormalities at CT in our small paediatric cohort.", "qid": 47, "docid": "xoz96rjz", "rank": 100, "score": 0.771023154258728}]}
{"query": "what are the benefits and risks of re-opening schools in the midst of the COVID-19 pandemic?", "hits": [{"content": "Title: Children of COVID-19: pawns, pathfinders or partners? Content: Countries throughout the world are counting the health and socioeconomic costs of the COVID-19 pandemic, including the strategies necessary to contain it. Profound consequences from social isolation are beginning to emerge, and there is an urgency about charting a path to recovery, albeit to a \u2018new normal\u2019 that mitigates them. Children have not suffered as much from the direct effects of COVID-19 infection as older adults. Still, there is mounting evidence that their health and welfare are being adversely affected. Closure of schools has been a critical component of social isolation but has a far broader impact than the diminution of educational opportunities, as important as these are. Reopening of schools is therefore essential to recovery, with some countries already tentatively implementing it. Children\u2019s interests are vital considerations in any recovery plan, but the question remains as to how to address them within the context of how society views children; should they be regarded as pawns, pathfinders or partners in this enterprise?", "qid": 48, "docid": "gdz63spj", "rank": 1, "score": 0.8113362193107605}, {"content": "Title: Children and the COVID-19 pandemic Content: As a result of the COVID-19 pandemic, many school districts have closed for the remainder of the academic year. These closures are unfortunate because, for many students, schools are their only source of trauma-informed care and supports. When schools reopen, they must develop a comprehensive plan to address the potential mental health needs of their students. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 48, "docid": "17a70tu9", "rank": 2, "score": 0.8111362457275391}, {"content": "Title: Children and the COVID-19 pandemic. Content: As a result of the COVID-19 pandemic, many school districts have closed for the remainder of the academic year. These closures are unfortunate because, for many students, schools are their only source of trauma-informed care and supports. When schools reopen, they must develop a comprehensive plan to address the potential mental health needs of their students. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 48, "docid": "4nv1kedt", "rank": 3, "score": 0.8111361861228943}, {"content": "Title: Children of COVID-19: pawns, pathfinders or partners? Content: Countries throughout the world are counting the health and socioeconomic costs of the COVID-19 pandemic, including the strategies necessary to contain it. Profound consequences from social isolation are beginning to emerge, and there is an urgency about charting a path to recovery, albeit to a 'new normal' that mitigates them. Children have not suffered as much from the direct effects of COVID-19 infection as older adults. Still, there is mounting evidence that their health and welfare are being adversely affected. Closure of schools has been a critical component of social isolation but has a far broader impact than the diminution of educational opportunities, as important as these are. Reopening of schools is therefore essential to recovery, with some countries already tentatively implementing it. Children's interests are vital considerations in any recovery plan, but the question remains as to how to address them within the context of how society views children; should they be regarded as pawns, pathfinders or partners in this enterprise?", "qid": 48, "docid": "gyilcbr7", "rank": 4, "score": 0.8081223964691162}, {"content": "Title: COVID-19 Related School Closings and Risk of Weight Gain Among Children. Content: The COVID-19 pandemic is causing substantial morbidity and mortality, straining health care systems, shutting down economies, and closing school districts. While it is a priority to mitigate its immediate impact, we want to call attention to the pandemic's longer-term effect on children's health: COVID-19, via these school closures, may exacerbate the epidemic of childhood obesity and increase disparities in obesity risk. In many areas of the U.S., the COVID-19 pandemic has closed schools and some of these school systems are not expected to re-open this school year. The experiences in Hong Kong, Taiwan and Singapore suggest that social distancing orders, if lifted after short periods, will have to be periodically re-instated to control COVID-19 flare ups. In short, we anticipate that the COVID-19 pandemic will likely double out-of-school time this year for many children in the U.S. and will exacerbate the risk factors for weight gain associated with summer recess.", "qid": 48, "docid": "x6x6a35w", "rank": 5, "score": 0.8072301745414734}, {"content": "Title: Infection prevention guidelines and considerations for paediatric risk groups when reopening primary schools during COVID-19 pandemic, Norway, April 2020 Content: In response to the coronavirus disease (COVID-19) pandemic, most countries implemented school closures. In Norway, schools closed on 13 March 2020. The evidence of effect on disease transmission was limited, while negative consequences were evident. Before reopening, risk-assessment for paediatric risk groups was performed, concluding that most children can attend school with few conditions requiring preventative homeschooling. We here present infection prevention and control guidelines for primary schools and recommendations for paediatric risk groups.", "qid": 48, "docid": "k36e2sob", "rank": 6, "score": 0.8059627413749695}, {"content": "Title: COVID-19 and the re-opening of schools: a policy maker\u2019s dilemma Content: The epidemic of coronavirus disease 2019 (COVID-19) broke out in Wuhan, China, in December 2019 and rapidly spread across the world. In order to counter this epidemic, several countries put in place different restrictive measures, such as the school\u2019s closure and a total lockdown. However, as the knowledge on the disease progresses, clinical evidence showed that children mainly have asymptomatic or mild disease and it has been suggested that they are also less likely to spread the virus. Moreover, the lockdown and the school closure could have negative consequences on children, affecting their social life, their education and their mental health. As many countries have already entered or are planning a phase of gradual lifting of the containment measures of social distancing, it seems plausible that the re-opening of nursery schools and primary schools could be considered a policy to be implemented at an early stage of recovery efforts, putting in place measures to do it safely, such as the maintenance of social distance, the reorganisation of classes into smaller groups, the provision of adequate sanitization of spaces, furniture and toys, the prompt identification of cases in the school environment and their tracing. Therefore, policy makers have the task of balancing pros and cons of the school re-opening strategy, taking into account psychological, educational and social consequences for children and their families. Another issue to be considered is represented by socio-economic disparities and inequalities which could be amplified by school\u2019s closure.", "qid": 48, "docid": "22y5ewq6", "rank": 7, "score": 0.8050732612609863}, {"content": "Title: COVID-19 and the re-opening of schools: a policy maker's dilemma Content: The epidemic of coronavirus disease 2019 (COVID-19) broke out in Wuhan, China, in December 2019 and rapidly spread across the world. In order to counter this epidemic, several countries put in place different restrictive measures, such as the school's closure and a total lockdown. However, as the knowledge on the disease progresses, clinical evidence showed that children mainly have asymptomatic or mild disease and it has been suggested that they are also less likely to spread the virus. Moreover, the lockdown and the school closure could have negative consequences on children, affecting their social life, their education and their mental health. As many countries have already entered or are planning a phase of gradual lifting of the containment measures of social distancing, it seems plausible that the re-opening of nursery schools and primary schools could be considered a policy to be implemented at an early stage of recovery efforts, putting in place measures to do it safely, such as the maintenance of social distance, the reorganisation of classes into smaller groups, the provision of adequate sanitization of spaces, furniture and toys, the prompt identification of cases in the school environment and their tracing. Therefore, policy makers have the task of balancing pros and cons of the school re-opening strategy, taking into account psychological, educational and social consequences for children and their families. Another issue to be considered is represented by socio-economic disparities and inequalities which could be amplified by school's closure.", "qid": 48, "docid": "5eg7hf6r", "rank": 8, "score": 0.804751992225647}, {"content": "Title: Shut and re-open: the role of schools in the spread of COVID-19 in Europe Content: We investigate the effect of school closure and subsequent reopening on the transmission of COVID-19, by considering Denmark, Norway, Sweden, and German states as case studies. By comparing the growth rates in daily hospitalisations or confirmed cases under different interventions, we provide evidence that the effect of school closure is visible as a reduction in the growth rate approximately 9 days after implementation. Limited school attendance, such as older students sitting exams or the partial return of younger year groups, does not appear to significantly affect community transmission. A large-scale reopening of schools while controlling or suppressing the epidemic appears feasible in countries such as Denmark or Norway, where community transmission is generally low. However, school reopening can contribute to significant increases in the growth rate in countries like Germany, where community transmission is relatively high. Our findings underscore the need for a cautious evaluation of reopening strategies that ensure low classroom occupancy and a solid infrastructure to quickly identify and isolate new infections.", "qid": 48, "docid": "r2x3awlw", "rank": 9, "score": 0.8014962077140808}, {"content": "Title: Little Risk of the COVID-19 Resurgence on Students in China (outside Hubei) Caused by School Reopening Content: Objective: School reopening has not yet started in China where the COVID-19 outbreak has reached ending stage, largely due to a great concern about COVID-19 infections on students. We attempted to quantitatively evaluate the risk of COVID-19 infections on students caused by school reopening. Study design: We collected the data of the numbers of teachers, population size and newly confirmed COVID-19 cases in the past 14 days in typical provinces/cities of China, and then analyzed the risk of COVID-19 infections in schools with respect to each province/city. Methods: A step-by-step procedure was explored to calculate the probability of COVID-19 infections on students as transmitted from infected teachers. Two critical assumptions for analysis were proposed: (i) only locally generated cases were counted while imported cases were omitted; (ii) the secondary attack rate of the COVID-19 virus in schools is similar to that in households in China, ranging from 3-10%. Results: The probability of COVID-19 resurgence within one week on students of primary, middle and high schools in China (outside Hubei) is extremely low (<0.2%) in each province/city, and such probability can be updated daily and weekly based on the newly confirmed cases in the past 14 days. In some areas without newly confirmed cases in the past 14 days, the risk is zero. Conclusions: Our work provides guidance for local governments to make risk level-based policies for school reopening. Currently, the risk of COVID-19 infections on students is extremely low in China (outside Hubei) and therefore school reopening can be initiated without the endanger of infections on students.", "qid": 48, "docid": "7en6cog7", "rank": 10, "score": 0.7906898856163025}, {"content": "Title: COVID-19 as a catalyst for educational change Content: The massive damages of COVID-19 may be incalculable. But in the spirit of never wasting a good crisis, COVID-19 represents an opportunity to rethink education. The rethinking should not be about improving schooling, but should focus on the what, how, and where of learning. This article highlights some of the questions that schools can ask as they reimagine post-COVID education.", "qid": 48, "docid": "w3ohzxn5", "rank": 11, "score": 0.7900761365890503}, {"content": "Title: Planning of School Teaching during COVID-19 Content: More than one billion students are out of school because of Covid-19, forced to a remote learning that has several drawbacks and has been hurriedly arranged; in addition, most countries are currently uncertain on how to plan school activities for the 2020-2021 school year; all of this makes learning and education some of the biggest world issues of the current pandemic. Unfortunately, due to the length of the incubation period of Covid-19, full opening of schools seems to be impractical till a vaccine is available. In order to support the possibility of some in-person learning, we study a mathematical model of the diffusion of the epidemic due to school opening, and evaluate plans aimed at containing the extra Covid-19 cases due to school activities while ensuring an adequate number of in-class learning periods. We consider a SEAIR model with an external source of infection and a suitable loss function; after a realistic parameter selection, we numerically determine optimal school opening strategies by simulated annealing. It turns out that blended models, with almost periodic alternations of in-class and remote teaching days or weeks, are generally optimal. Besides containing Covid-19 diffusion, these solutions could be pedagogically acceptable, and could also become a driving model for the society at large. In a prototypical example, the optimal strategy results in the school opening 90 days out of 200 with the number of Covid-19 cases among the individuals related to the school increasing by about 66%, instead of the about 250% increase that would have been a consequence of full opening.", "qid": 48, "docid": "rd8dqeot", "rank": 12, "score": 0.7882174253463745}, {"content": "Title: The impact of school reopening on the spread of COVID-19 in England Content: Background: In the UK, cases of COVID-19 have been declining since mid-April and there is good evidence to suggest that the effective reproduction number has dropped below 1, leading to a multi-phase relaxation plan for the country to emerge from lockdown. As part of this staggered process, primary schools are scheduled to partially reopen on 1st June. Evidence from a range of sources suggests that children are, in general, only mildly affected by the disease and have low mortality rates, though there is less certainty regarding children's role in transmission. Therefore, there is wide discussion on the impact of reopening schools. Methods: We compare eight strategies for reopening primary and secondary schools in England from 1st June, focusing on the return of particular year groups and the associated epidemic consequences. This is assessed through model simulation, modifying a previously developed dynamic transmission model for SARS-CoV-2. We quantify how the process of reopening schools affected contact patterns and anticipated secondary infections, the relative change in R according to the extent of school reopening, and determine the public health impact via estimated change in clinical cases and its sensitivity to decreases in adherence post strict lockdown. Findings: Whilst reopening schools, in any form, results in more mixing between children, an increase in R and hence transmission of the disease, the magnitude of that increase can be low dependent upon the age-groups that return to school and the behaviour of the remaining population. We predict that reopening schools in a way that allows half class sizes or that is focused on younger children is unlikely to push R above one, although there is noticeable variation between the regions of the country. Given that older children have a greater number of social contacts and hence a greater potential for transmission, our findings suggest reopening secondary schools results in larger increases in case burden than only reopening primary schools; reopening both generates the largest increase and could push R above one in some regions. The impact of less social-distancing in the rest of the population, generally has far larger effects than reopening schools and exacerbates the impacts of reopening. Discussion: Our work indicates that any reopening of schools will result in increased mixing and infection amongst children and the wider population, although the opening of schools alone is unlikely to push the value of R above one. However, impacts of other recent relaxations of lockdown measures are yet to be quantified, suggesting some regions may be closer to the critical threshold that would lead to a growth in cases. Given the uncertainties, in part due to limited data on COVID-19 in children, school reopening should be carefully monitored. Ultimately, the decision about reopening classrooms is a difficult trade-off between increased epidemiological consequences and the emotional, educational and developmental needs of children.", "qid": 48, "docid": "xhyqg5u2", "rank": 13, "score": 0.7860680222511292}, {"content": "Title: Education in the Context of the Pandemic: A Look at the Case of Portugal Content: The COVID-19 pandemic is causing structural and irreversible changes and transformations in individuals, families, companies, countries and in the world There will be a society before and after COVID-19 Education is a pillar of sustainability and of society's future which is also being damaged by this world crisis Professionals, students and family, the government, the educational system are looking for answers in record time This brief article aims to share Portugal's experience, a country marked by a series of successive reforms of the national education system", "qid": 48, "docid": "02zdg7ue", "rank": 14, "score": 0.7849493026733398}, {"content": "Title: Expected impact of reopening schools after lockdown on COVID-19 epidemic in Ile-de-France Content: As several countries around the world are planning exit strategies to progressively lift the rigid social restrictions implemented with lockdown, different options are being chosen regarding the closure or reopening of schools. We evaluate the expected impact of reopening schools in lIe-de-France region after the withdrawal of lockdown currently scheduled for May 11, 2020. We explore several scenarios of partial, progressive, or full school reopening, coupled with moderate social distancing interventions and large-scale tracing, testing, and isolation. Accounting for current uncertainty on the role of children in COVID-19 epidemic, we test different hypotheses on children's transmissibility distinguishing between younger children (pre-school and primary school age) and adolescents (middle and high school age). Reopening schools after lifting lockdown will likely lead to an increase in the number of COVID-19 cases in the following 2 months, even with lower transmissibility of children, yet protocols exist that would allow maintaining the epidemic under control without saturating the healthcare system. With pre-schools and primary schools in session starting May 11, ICU occupation would reach at most 72% [55,83]% (95% probability ranges) of a 1,500-bed capacity (here foreseen as the routine capacity restored in the region post-first wave) if no other school level reopens before summer or if middle and high schools reopen one month later through a progressive protocol (increasing attendance week by week). Full attendance of adolescents at school starting in June would overwhelm the ICU system (138% [118,159]% occupation). Reopening all schools on May 11 would likely lead to a second wave similar to the one recently experienced, except if maximum attendance is limited to 50% for both younger children and adolescents. Based on the estimated situation on May 11, no substantial difference in the epidemic risk is predicted between progressive and prompt reopening of pre-schools and primary schools, thus allowing full attendance of younger children mostly in need of resuming learning and development. Reopening would require however large-scale trace and testing to promptly isolate cases, in addition to moderate social distancing interventions. Full attendance in middle and high schools is instead not recommended. Findings are consistent across different assumptions on the relative transmissibility of younger children and for small increase of the reproductive number possibly due to decreasing compliance to lockdown.", "qid": 48, "docid": "qnlf5qfd", "rank": 15, "score": 0.7846155762672424}, {"content": "Title: School closure, COVID\u201019 and lunch programme: Unprecedented undernutrition crisis in low\u2010middle income countries Content: The coronavirus disease 2019 pandemic has affected nearly 70% of children and teenagers around the world due to school closure policies. School closure is implemented widely in order to prevent viral transmission and its impact on the broader community, based on preliminary recommendations and evidence from influenza. However, there is debate with regard to the effectiveness of school closures. Growing evidence suggests that a child's SARS\u2010CoV\u20102 infection is often mild or asymptomatic and that children may not be major SARS\u2010CoV\u20102 transmitters; thus, it is questionable if school closures prevent transmission significantly. This question is important as a majority of children in low\u2010 and middle\u2010income countries depend on free school meals; unexpected long\u2010term school closure may adversely impact nutrition and educational outcomes. Food insecurity is expected to be higher during the pandemic. In this viewpoint, we argue for a more thorough exploration of potential adverse impacts of school closures in low\u2010 and middle\u2010income countries and recommend actions to ensure that the health and learning needs of vulnerable populations are met in this time of crisis.", "qid": 48, "docid": "zc2u3hqv", "rank": 16, "score": 0.7838367223739624}, {"content": "Title: Initial Coronavirus Disease\u20132019 Closure Strategies Adopted by a Convenience Sample of US School Districts: Directions for Future Research Content: School closures are an important strategy to mitigate the impacts of a pandemic. But an optimal approach to transitioning from in-person to distance learning approaches is lacking. We analyzed a convenience sample of public K-12 schools in the early weeks of the COVID-19 pandemic in the United States. This initial snapshot provides some insights to inform future research into the variation of strategies across school districts, and would benefit from more rigorous methods to determine true correlations between demographic and geographic factors. Additionally, many of these strategies have evolved in response to ongoing and prolonged public health social distancing measures implemented after this analysis was conducted.", "qid": 48, "docid": "6n0ce55n", "rank": 17, "score": 0.7836792469024658}, {"content": "Title: Initial Coronavirus Disease-2019 Closure Strategies Adopted by a Convenience Sample of US School Districts: Directions for Future Research Content: School closures are an important strategy to mitigate the impacts of a pandemic. But an optimal approach to transitioning from in-person to distance learning approaches is lacking. We analyzed a convenience sample of public K-12 schools in the early weeks of the COVID-19 pandemic in the United States. This initial snapshot provides some insights to inform future research into the variation of strategies across school districts, and would benefit from more rigorous methods to determine true correlations between demographic and geographic factors. Additionally, many of these strategies have evolved in response to ongoing and prolonged public health social distancing measures implemented after this analysis was conducted.", "qid": 48, "docid": "xecvlxhg", "rank": 18, "score": 0.783679187297821}, {"content": "Title: Back to school: Safe for children with underlying medical conditions Content: As schools reopen as a result of low community transmission rates of COVID-19, parents and teachers will have understandable concerns about the risks to students and staff.", "qid": 48, "docid": "xu7bazzw", "rank": 19, "score": 0.7816046476364136}, {"content": "Title: Back to school: Safe for children with underlying medical conditions. Content: As schools reopen as a result of low community transmission rates of COVID-19, parents and teachers will have understandable concerns about the risks to students and staff.", "qid": 48, "docid": "6gn2seix", "rank": 20, "score": 0.7816046476364136}, {"content": "Title: Determining the optimal strategy for reopening schools, work and society in the UK: balancing earlier opening and the impact of test and trace strategies with the risk of occurrence of a secondary COVID-19 pandemic wave Content: Background In order to slow down the spread of SARS-CoV-2, the virus causing the COVID-19 pandemic, the UK government has imposed strict physical distancing (lockdown) measures including school 'dismissals' since 23 March 2020. As evidence is emerging that these measures may have slowed the spread of the pandemic, it is important to assess the impact of any changes in strategy, including scenarios for school reopening and broader relaxation of social distancing. This work uses an individual-based model to predict the impact of a suite of possible strategies to reopen schools in the UK, including that currently proposed by the UK government. Methods We use Covasim, a stochastic agent-based model for transmission of COVID-19, calibrated to the UK epidemic. The model describes individuals' contact networks stratified as household, school, work and community layers, and uses demographic and epidemiological data from the UK. We simulate a range of different school reopening strategies with a society-wide relaxation of lockdown measures and in the presence of different non-pharmaceutical interventions, to estimate the number of new infections, cumulative cases and deaths, as well as the effective reproduction number with different strategies. To account for uncertainties within the stochastic simulation, we also simulated different levels of infectiousness of children and young adults under 20 years old compared to older ages. Findings We found that with increased levels of testing of people (between 25% and 72% of symptomatic people tested at some point during an active COVID-19 infection depending on scenarios) and effective contact-tracing and isolation for infected individuals, an epidemic rebound may be prevented across all reopening scenarios, with the effective reproduction number (R) remaining below one and the cumulative number of new infections and deaths significantly lower than they would be if testing did not increase. If UK schools reopen in phases from June 2020, prevention of a second wave would require testing 51% of symptomatic infections, tracing of 40% of their contacts, and isolation of symptomatic and diagnosed cases. However, without such measures, reopening of schools together with gradual relaxing of the lockdown measures are likely to induce a secondary pandemic wave, as are other scenarios for reopening. When infectiousness of <20 year olds was varied from 100% to 50% of that of older ages, our findings remained unchanged. Interpretation To prevent a secondary COVID-19 wave, relaxation of social distancing including reopening schools in the UK must be implemented alongside an active large-scale population-wide testing of symptomatic individuals and effective tracing of their contacts, followed by isolation of symptomatic and diagnosed individuals. Such combined measures have a greater likelihood of controlling the transmission of SARS-CoV-2 and preventing a large number of COVID-19 deaths than reopening schools and society with the current level of implementation of testing and isolation of infected individuals.", "qid": 48, "docid": "4sxsyr6k", "rank": 21, "score": 0.7812381982803345}, {"content": "Title: School closure, COVID-19 and lunch programme: Unprecedented undernutrition crisis in low-middle income countries Content: The coronavirus disease 2019 pandemic has affected nearly 70% of children and teenagers around the world due to school closure policies. School closure is implemented widely in order to prevent viral transmission and its impact on the broader community, based on preliminary recommendations and evidence from influenza. However, there is debate with regard to the effectiveness of school closures. Growing evidence suggests that a child's SARS-CoV-2 infection is often mild or asymptomatic and that children may not be major SARS-CoV-2 transmitters; thus, it is questionable if school closures prevent transmission significantly. This question is important as a majority of children in low- and middle-income countries depend on free school meals; unexpected long-term school closure may adversely impact nutrition and educational outcomes. Food insecurity is expected to be higher during the pandemic. In this viewpoint, we argue for a more thorough exploration of potential adverse impacts of school closures in low- and middle-income countries and recommend actions to ensure that the health and learning needs of vulnerable populations are met in this time of crisis.", "qid": 48, "docid": "7ty971vj", "rank": 22, "score": 0.7811814546585083}, {"content": "Title: Dataset of Ex-pat Teachers in Southeast Asia's Intention to Leave due to the COVID-19 pandemic Content: The COVID-19 pandemic exerted an adverse influence on the global education system, especially since starting school lockdown. The growth of teacher unemployment figures climbed double-digit and spawned these unexpected sequels. For instance, while native teachers seemed indisposed to leave the profession with the aim of seeking another more profited and seasonal jobs, many ex-pat teachers presented themselves with moving or stayed dilemma in the way the government salvaged their situation. In preference with the ex-pat teacher's case, we elucidated further throughout an e-survey in the International Baccalaureate community on Facebook from 4 to 11 April 2020 for 18,000 ex-pat teachers, who are teaching at Southeast Asia. This dataset includes 307 responses of ex-pat teachers who are staying in Singapore, Thailand, Vietnam, the Philippines, and Indonesia during the pandemic. The dataset comprises (i) Survey partakers' Demographics; (ii) Ex-pat teachers' perceptions in the relation of national, regional and school plans were afoot to the pandemic; (iii) The degree of attachment of ex-pat teacher to their current society, the ex-pat community, friends, and families during the pandemic time; (iv) Ex-pat teachers' embryo intention to reconsider their current teaching location.", "qid": 48, "docid": "qb31rxnn", "rank": 23, "score": 0.78033447265625}, {"content": "Title: \u00dcberlegungen zur Lockerung des Lockdowns Content: The fight against the coronavirus pandemic has led to an insulation of social and economic life and will have considerable economic consequences. Important areas of the industry and service sectors were partially or completely shutdown. A resumption of activity should happen as soon as possible, once the medical pre-conditions have been established and are met. This requires a clear exit strategy and following several steps to return to previous welfare and growth data levels. After securing survival during this crisis via various liquidity lines and bridging loans, the economy\u2019s restart requires the relaunch of public infrastructure, especially of schools and kindergartens. To facilitate a coordinated and synchronised restart of complex industrial value chains, we need clear signals on a planned schedule. A tax policy driven departure signal and a demand side focused growth programme could make an important contribution to a new economic dynamic after the crisis.", "qid": 48, "docid": "zk0u366n", "rank": 24, "score": 0.7781424522399902}, {"content": "Title: Education and the COVID-19 pandemic Content: The COVID-19 pandemic is a huge challenge to education systems. This Viewpoint offers guidance to teachers, institutional heads, and officials on addressing the crisis. What preparations should institutions make in the short time available and how do they address students' needs by level and field of study? Reassuring students and parents is a vital element of institutional response. In ramping up capacity to teach remotely, schools and colleges should take advantage of asynchronous learning, which works best in digital formats. As well as the normal classroom subjects, teaching should include varied assignments and work that puts COVID-19 in a global and historical context. When constructing curricula, designing student assessment first helps teachers to focus. Finally, this Viewpoint suggests flexible ways to repair the damage to students' learning trajectories once the pandemic is over and gives a list of resources.", "qid": 48, "docid": "06mqd6vg", "rank": 25, "score": 0.769192099571228}, {"content": "Title: Education and the COVID-19 pandemic Content: The COVID-19 pandemic is a huge challenge to education systems. This Viewpoint offers guidance to teachers, institutional heads, and officials on addressing the crisis. What preparations should institutions make in the short time available and how do they address students\u2019 needs by level and field of study? Reassuring students and parents is a vital element of institutional response. In ramping up capacity to teach remotely, schools and colleges should take advantage of asynchronous learning, which works best in digital formats. As well as the normal classroom subjects, teaching should include varied assignments and work that puts COVID-19 in a global and historical context. When constructing curricula, designing student assessment first helps teachers to focus. Finally, this Viewpoint suggests flexible ways to repair the damage to students\u2019 learning trajectories once the pandemic is over and gives a list of resources.", "qid": 48, "docid": "744a3hga", "rank": 26, "score": 0.7686206102371216}, {"content": "Title: Dataset of Vietnamese teachers\u2019 perspectives and perceived support during the COVID-19 pandemic Content: The COVID-19 pandemic has caused unprecedented damage to the educational system worldwide. Besides the measurable economic impacts in the short-term and long-term, there is intangible destruction within educational institutions. In particular, teachers \u2013 the most critical intellectual resources of any schools \u2013 have to face various types of financial, physical, and mental struggles due to COVID-19. To capture the current context of more than one million Vietnamese teachers during COVID-19, we distributed an e-survey to more than 2,500 randomly selected teachers from two major teacher communities on Facebook from 6th to 11th April 2020. From over 373 responses, we excluded the observations which violated our cross-check questions and retained 294 observations for further analysis. This dataset includes: (i) Demographics of participants; (ii) Teachers' perspectives regarding the operation of teaching activities during the pandemic; (iii) Teachers' received support from their schools, government bodies, other stakeholders such as teacher unions, and parents' associations; and (iv) teachers' evaluation of school readiness toward digital transformation. Further, the dataset was supplemented with an additional question on the teachers' primary source of professional development activities during the pandemic.", "qid": 48, "docid": "lzv7p62f", "rank": 27, "score": 0.7684895992279053}, {"content": "Title: COVID-19 and schooling in South Africa: Who should go back to school first? Content: The COVID-19 pandemic is the largest social and economic shock of our lifetimes. As governments grapple with their responses to the virus, more than half the world\u2019s countries have closed their schools and severely limited almost all forms of public life. This will have a profound impact on children, both now and in the decade to come. As many countries start to send children back to school, a question arises: who should go back to school first? This Viewpoint addresses that question in the context of a middle-income country, South Africa. Based on a review of much of the evidence available at the time of publication, it concludes that the youngest children are least susceptible to harm from COVID-19, are less likely to spread the virus than adults, and also have the most to lose by being out of school. Hence, they should be the ones to return to school first.", "qid": 48, "docid": "rmefwih2", "rank": 28, "score": 0.7663279175758362}, {"content": "Title: The Coronavirus Pandemic and Lessons Learned in Preschools in Norway, Sweden and the United States: OMEP Policy Forum Content: The novel coronavirus, also known as COVID-19, has moved rapidly across the world in 2020. This article reports on the recent consequences of the pandemic for early childhood education in Sweden, Norway, and the United States. The authors illustrate the effects of the pandemic on preschools in their countries, against a backdrop of frequent changes in infection and mortality rates, epidemiological understandings, government strategies, and mitigation strategies regarding preschool closures. Teachers report their experiences and actions in specific early childhood education settings, across the three national contexts. These experiential snapshots identify program priorities, parents\u2019 and children\u2019s reactions, and the commitment and concerns of teachers. The conversations reveal culturally situated similarities of early childhood educational practices but also differences across contexts. Teachers report on the challenges of their experiences but also benefits for their practice and how they engage with children and their families. Ideas about future preparedness for such pandemics are also discussed.", "qid": 48, "docid": "cyfwm22e", "rank": 29, "score": 0.7654811143875122}, {"content": "Title: Helping children cope with the COVID-19 pandemic Content: Numerous societal changes in response to the COVID-19 pandemic, such as school closings and event cancellations, have caused anxiety and fear for children and young people. There are ways to help young people cope with the current situation including establishing an open dialogue, creating a structured daily routine with a schedule with assigned roles, and using social media and video conferencing to remain socially connected.", "qid": 48, "docid": "rfsituum", "rank": 30, "score": 0.7625817656517029}, {"content": "Title: Helping children cope with the COVID-19 pandemic. Content: Numerous societal changes in response to the COVID-19 pandemic, such as school closings and event cancellations, have caused anxiety and fear for children and young people. There are ways to help young people cope with the current situation including establishing an open dialogue, creating a structured daily routine with a schedule with assigned roles, and using social media and video conferencing to remain socially connected.", "qid": 48, "docid": "6d832az2", "rank": 31, "score": 0.7625817656517029}, {"content": "Title: School\u2019s Out for COVID-19: 50 Ways BCBA Trainees in Special Education Settings Can Accrue Independent Fieldwork Experience Hours During the Pandemic Content: Due to the COVID-19 pandemic and nationwide executive orders closing schools, many trainees completing their supervised independent fieldwork in educational settings lost the ability to accrue hours linked to restricted activities of a therapeutic and instructional nature with students (i.e., clients). Given the impact on trainees of the pandemic restrictions, we present 50 suggestions for trainees in school settings to continue to accrue hours for both restricted and unrestricted activities throughout the course of the COVID-19 pandemic.", "qid": 48, "docid": "yxec23lp", "rank": 32, "score": 0.7620294094085693}, {"content": "Title: COVID-19 , School Closings and Weight Gain. Content: We found the publication on \"COVID-19 Related School Closings and Risk of Weight Gain Among Children\" to be interesting.1 Rundle et al. noted that \"we anticipate that the COVID-19 pandemic will likely double out-of-school time this year for many children in the U.S. and will exacerbate the risk factors for weight gain associated with summer recess.\"1 In fact, there are several factors relating to nutritional status of the children. We would like to share observations from Thailand, the second country in the timeline of COVID-19.2 In Thailand, school aged children in rural areas where COVID-19 disease outbreak exists are usually underweight.3 Thus, school closing means the children have to live with poor parents adding to economic problems of the family.", "qid": 48, "docid": "qz6w094y", "rank": 33, "score": 0.7608441114425659}, {"content": "Title: How Much May COVID\u201019 School Closures Increase Childhood Obesity? Content: In a recent paper entitled, \u201cCOVID\u201019 Related School Closings and Risk of Weight Gain Among Children\u201d Rundle et al. (2020) proposed the COVID\u201019 pandemic may increase obesity among American children because the pandemic, \u201cwill likely double out\u2010of\u2010school time this year for many children in the United States and will exacerbate the risk factors for weight gain associated with summer recess\u201d (pg. 1). I add support to Rundle et al.\u2019s argument by demonstrating that doubling of out\u2010of\u2010school time alone may lead to a sizable increase in childhood obesity.", "qid": 48, "docid": "1rw80tde", "rank": 34, "score": 0.7606416940689087}, {"content": "Title: Education as the path to a sustainable recovery from COVID-19 Content: COVID-19 has disrupted education for millions of children across the globe. The education community is re-imagining and re-designing to build back better. This Viewpoint takes the principles behind UNESCO\u2019s Futures of Education initiative to highlight their importance in post-COVID-19 recovery. The pandemic has shown how communities can come together to educate children. The article argues that, post-COVID-19, education systems should recognize community-driven support systems, use technology to overcome the digital divide in learning, and focus more on SDG 4.7 and its links to climate crises.", "qid": 48, "docid": "gneuzgts", "rank": 35, "score": 0.7592007517814636}, {"content": "Title: How Much May COVID-19 School Closures Increase Childhood Obesity? Content: In a recent paper entitled, \"COVID-19 Related School Closings and Risk of Weight Gain Among Children\" Rundle et al. (2020) proposed the COVID-19 pandemic may increase obesity among American children because the pandemic, \"will likely double out-of-school time this year for many children in the United States and will exacerbate the risk factors for weight gain associated with summer recess\" (pg. 1). I add support to Rundle et al.'s argument by demonstrating that doubling of out-of-school time alone may lead to a sizable increase in childhood obesity.", "qid": 48, "docid": "8ew7rv5q", "rank": 36, "score": 0.7584485411643982}, {"content": "Title: How much leeway is there to relax COVID-19 control measures? Content: Following successful widespread non-pharmaceutical interventions aiming to control COVID-19, many jurisdictions are moving towards reopening economies and borders. Given that little immunity has developed in most populations, re-establishing higher contact rates within and between populations carries substantial risks. Using a Bayesian epidemiological model, we estimate the leeway to reopen in a range of national and regional jurisdictions that have experienced different COVID-19 epidemics. We estimate the risks associated with different levels of reopening and the likely burden of new cases due to introductions from other jurisdictions. We find widely varying leeway to reopen, high risks of exceeding past peak sizes, and high possible burdens per introduced case per week, up to hundreds in some jurisdictions. We recommend a cautious approach to reopening economies and borders, coupled with strong monitoring for changes in transmission.", "qid": 48, "docid": "4df5l01l", "rank": 37, "score": 0.7584168314933777}, {"content": "Title: Debate: COVID-19 and psychological well-being of children and adolescents in Italy Content: Italy was the first country in Europe to deal with COVID-19. Measures taken by the government to contain the spread of the virus were based mainly on quarantine and social distancing, with dramatic economic, social and psychological consequences. Since March, Italian children and adolescents are facing school closures, which have caused a disruption in the daily lives of millions of young people and their families. To date, despite the slow reopening, the government has decided to maintain school closures for the entire academic year, leaving the future of young people in uncertainty. There is already some evidence that quarantine and social isolation are having negative impact on children's and adolescents' psychological well-being. Moreover, this situation will mainly affect those children and adolescents with pre-existing vulnerabilities and those suffering of mental disorders. It is imperative to keep young people's needs at the core of reconstruction plans, allowing them to return to school safely, and providing them with some strategies to heal and dealing with this stressful and potentially traumatic situation.", "qid": 48, "docid": "8jvljcuh", "rank": 38, "score": 0.7579084634780884}, {"content": "Title: Debate: COVID-19 and psychological well-being of children and adolescents in Italy. Content: Italy was the first country in Europe to deal with COVID-19. Measures taken by the government to contain the spread of the virus were based mainly on quarantine and social distancing, with dramatic economic, social and psychological consequences. Since March, Italian children and adolescents are facing school closures, which have caused a disruption in the daily lives of millions of young people and their families. To date, despite the slow reopening, the government has decided to maintain school closures for the entire academic year, leaving the future of young people in uncertainty. There is already some evidence that quarantine and social isolation are having negative impact on children's and adolescents' psychological well-being. Moreover, this situation will mainly affect those children and adolescents with pre-existing vulnerabilities and those suffering of mental disorders. It is imperative to keep young people's needs at the core of reconstruction plans, allowing them to return to school safely, and providing them with some strategies to heal and dealing with this stressful and potentially traumatic situation.", "qid": 48, "docid": "lgf0nwgx", "rank": 39, "score": 0.7579084634780884}, {"content": "Title: No evidence of secondary transmission of COVID-19 from children attending school in Ireland, 2020 Content: As many countries begin to lift some of the restrictions to contain COVID-19 spread, lack of evidence of transmission in the school setting remains. We examined Irish notifications of SARS-CoV2 in the school setting before school closures on 12 March 2020 and identified no paediatric transmission. This adds to current evidence that children do not appear to be drivers of transmission, and we argue that reopening schools should be considered safe accompanied by certain measures.", "qid": 48, "docid": "i804iorq", "rank": 40, "score": 0.7578209638595581}, {"content": "Title: Returning to School: Separation Problems and Anxiety in the Age of Pandemics Content: The shift to the postpandemic school environment will cause dramatic changes and is likely to increase separation problems. In this article, we look at the anxiety problems that some parents and their children might experience when school reopens after the COVID-19 lockdown. Using a behavioral theory of development, we provide suggestions for how to handle the departure and separation problems that may emerge as parents drop their children off at school. Many parents are unsure about how to handle anxiety or fear as their children return to school or have to visit other environments outside their homes. Social distancing has caused families to develop stronger dependencies at home and to create new routines that vary, in many instances greatly, from their prepandemic routines. Families are adjusting to the new \u201cnormal.\u201d They are keeping their children busy with schoolwork as best they can. In particular, families have likely developed close attachment relationships. Families have been struggling with an unprecedented lockdown, and for many parents and their children, this extended period of family confinement and severe restrictions has been especially stressful, and the timing for returning to school is uncertain. We emphasize here that parents can be responsive to their children\u2019s needs, plan ahead, provide reassurance, and depart firmly without vacillating, and we provide other tips to avoid inadvertently shaping children\u2019s negative or anxiety behaviors as they go back to school. We offer some specific advice for parents and teachers to follow to prevent the departure and separation problems that typically develop during challenging behavioral interactions in school settings.", "qid": 48, "docid": "66c2qobr", "rank": 41, "score": 0.7574539184570312}, {"content": "Title: Letter to the Editor: Assessing the Long-Term Potential of Relaxing Regulations: Should We Go Back to Business as Usual? Content: The response to the COVID-19 pandemic resulted in reallocation of health care resources and removal of barriers to deliver expedited care to those in need. This might be a unique moment in history to reconsider the regulations within our health care system that significantly increase its cost.", "qid": 48, "docid": "bojiulk0", "rank": 42, "score": 0.7572537064552307}, {"content": "Title: Daily emotional well\u2010being during the COVID\u201019 pandemic Content: The COVID\u201019 outbreak has become one of the largest public health crises of our time. Governments have responded by implementing self\u2010isolation and physical distancing measures that have profoundly impacted daily life throughout the world. In this study, we aimed to investigate how people experience the activities, interactions, and settings of their lives during the pandemic. The sample (N = 604) was assessed in Ireland on the 25 March 2020, following the closure of schools and non\u2010essential businesses. We examined within\u2010person variance in emotional well\u2010being and how people spend their time. We found that while most time was spent in the home (74%), time spent outdoors (8%) was associated with markedly raised positive affect and reduced negative emotions. Exercising, going for walks, gardening, pursuing hobbies, and taking care of children were the activities associated with the greatest affective benefits. Home\u2010schooling children and obtaining information about COVID\u201019 were ranked lowest of all activities in terms of emotional experience. These findings highlight activities that may play a protective role in relation to well\u2010being during the pandemic, the importance of setting limits for exposure to COVID\u201019\u2010related media coverage, and the need for greater educational supports to facilitate home\u2010schooling during this challenging period.", "qid": 48, "docid": "n276aksa", "rank": 43, "score": 0.7570669651031494}, {"content": "Title: Challenges of COVID-19 in children in low- and middle-income countries Content: As the coronavirus pandemic extends to low and middle income countries (LMICs), there are growing concerns about the risk of coronavirus disease (COVID-19) in populations with high prevalence of comorbidities, the impact on health and economies more broadly and the capacity of existing health systems to manage the additional burden of COVID-19. The direct effects of COVID are less of a concern in children, who seem to be largely asymptomatic or to develop mild illness as occurs in high income countries; however children in LMICs constitute a high proportion of the population and may have a high prevalence of risk factors for severe lower respiratory infection such as HIV or malnutrition. Further diversion of resources from child health to address the pandemic among adults may further impact on care for children. Poor living conditions in LMICs including lack of sanitation, running water and overcrowding may facilitate transmission of SARS-CoV-2. The indirect effects of the pandemic on child health are of considerable concern, including increasing poverty levels, disrupted schooling, lack of access to school feeding schemes, reduced access to health facilities and interruptions in vaccination and other child health programs. Further challenges in LMICs include the inability to implement effective public health measures such as social distancing, hand hygiene, timely identification of infected people with self-isolation and universal use of masks. Lack of adequate personal protective equipment, especially N95 masks is a key concern for health care worker protection. While continued schooling is crucial for children in LMICs, provision of safe environments is especially challenging in overcrowded resource constrained schools. The current crisis is a harsh reminder of the global inequity in health in LMICs. The pandemic highlights key challenges to the provision of health in LMICs, but also provides opportunities to strengthen child health broadly in such settings.", "qid": 48, "docid": "kf68lraw", "rank": 44, "score": 0.7562280893325806}, {"content": "Title: Daily emotional well-being during the COVID-19 pandemic Content: The COVID-19 outbreak has become one of the largest public health crises of our time. Governments have responded by implementing self-isolation and physical distancing measures that have profoundly impacted daily life throughout the world. In this study, we aimed to investigate how people experience the activities, interactions, and settings of their lives during the pandemic. The sample (N = 604) was assessed in Ireland on the 25 March 2020, following the closure of schools and non-essential businesses. We examined within-person variance in emotional well-being and how people spend their time. We found that while most time was spent in the home (74%), time spent outdoors (8%) was associated with markedly raised positive affect and reduced negative emotions. Exercising, going for walks, gardening, pursuing hobbies, and taking care of children were the activities associated with the greatest affective benefits. Home-schooling children and obtaining information about COVID-19 were ranked lowest of all activities in terms of emotional experience. These findings highlight activities that may play a protective role in relation to well-being during the pandemic, the importance of setting limits for exposure to COVID-19-related media coverage, and the need for greater educational supports to facilitate home-schooling during this challenging period.", "qid": 48, "docid": "rhgfmqgu", "rank": 45, "score": 0.7558308243751526}, {"content": "Title: School Nurses on the Front Lines of Healthcare: The Approach to Maintaining Student Health and Wellness During COVID-19 School Closures Content: In response to the novel coronavirus disease 2019 (COVID-19) pandemic, most states in the United States enacted statewide school closures, ranging in duration from 1 month to the remainder of the academic year. The extended durations of these closures present unique challenges, as many families rely on the school as a source of physical activity, mental health services, psychosocial support, child care, and food security. While the school doors may be closed, the school nurse can still play a vital role in emergency management. This article discusses challenges and proposes solutions to maintaining student health and wellness during extended school closures due to the COVID-19 pandemic. Furthermore, it is inevitable that until a vaccine for coronavirus is developed and readily available, many schools will continue to see future closures, though likely for shorter periods of time, as they respond to local outbreaks.", "qid": 48, "docid": "xqmxyz7u", "rank": 46, "score": 0.7558122873306274}, {"content": "Title: Facing the University Environment with Covid-19 Pandemic: A Comparative Analysis between Romania and South Korea Content: The Covid-19 determined pandemic has affected all branches of socio-economic life, and the educational environment has not been bypassed The students' reaction to the measures of the total transfer of the teaching-learning process in the online environment, by universities closure, is proving to be one of the challenges determined by the current global pandemic manifestation The impact is highlighted by major changes with obvious patterns in the short time period The academic world is witnessing this changing from the position of forced adaptation, both teachers, administrative staff, and students being in the situation of reconsidering the entire system, in organization and functionality The on-line platforms have replaced the classrooms, the communication is made exclusively virtual, and the reactions caused by this form of reconfiguration are felt in multiple ways The present paper approaches the students' reaction to this necessity for adaptation, by comparison between the university environment from Romania and the one from South Korea The results indicate multiple similarities and minor differences between these two countries A main conclusion is that in technically, organizationally and emotionally-affective perspective, the situation is very similar, the differences being present only from a financial point of view and about the intention in student-teacher communication", "qid": 48, "docid": "tnbmn9m1", "rank": 47, "score": 0.7552280426025391}, {"content": "Title: How risk communication could have reduced controversy about school closures in Australia during the COVID-19 pandemic Content: Although there has been consistent evidence indicating that school closures have only limited efficacy in reducing community transmission of coronavirus disease 2019 (COVID-19), the question of whether children should be kept home from school has attracted extensive and often divisive public debate in Australia. In this article we analyse the factors that drove high levels of concern among parents, teachers and the public and led to both demands for school closures in late March 2020, and to many parents' reluctance to return their children to school in May 2020. We discuss how the use of well-established principles of risk communication might have reduced much of this community concern. Then we set out a range of practical suggestions for communication practices that build trust and hence diminish concerns in relation to managing schools over the long term of the COVID-19 pandemic.", "qid": 48, "docid": "pvus33s7", "rank": 48, "score": 0.7549450397491455}, {"content": "Title: How risk communication could have reduced controversy about school closures in Australia during the COVID-19 pandemic. Content: Although there has been consistent evidence indicating that school closures have only limited efficacy in reducing community transmission of coronavirus disease 2019 (COVID-19), the question of whether children should be kept home from school has attracted extensive and often divisive public debate in Australia. In this article we analyse the factors that drove high levels of concern among parents, teachers and the public and led to both demands for school closures in late March 2020, and to many parents' reluctance to return their children to school in May 2020. We discuss how the use of well-established principles of risk communication might have reduced much of this community concern. Then we set out a range of practical suggestions for communication practices that build trust and hence diminish concerns in relation to managing schools over the long term of the COVID-19 pandemic.", "qid": 48, "docid": "u3isdii7", "rank": 49, "score": 0.7549450397491455}, {"content": "Title: Planning phase-2 for the endoscopic units in Northern Italy after COVID-19 lockdown: an exit strategy with a lot of critical issues and a few opportunities. Content: Background and aims: Restarting activity in Endoscopic Departments (ED) after COVID-19 lockdown raises critical issues. This survey investigates strategies and uncertainties on resumption of elective activity. Methods: Directors of 55 EDs in Northern Italy received a questionnaire focusing on the impact of pandemic on activity and organization and on the resources available at re-opening. A section was devoted to gather forecasts and proposals on the return path to normality. Results: All centres had reduced their activities of at least 50% of the pre-COVID-19 period. A rate of endoscopists (13.6%), nurses (25.2%), and health assistants (14%) were not available since infected, or relocated to other departments. One third of endoscopic rooms were converted to COVID-19 care. Two third had the waiting or the recovery areas too small for distancing. A dedicated pathway for infected patients could not be guaranteed in 20% of EDs. Only one third of EDs judged realistic to completely restore a pre-crisis workload by the next months. Optimizing appropriateness of procedures, closer interaction with GPs and triaging patients with telemedicine were the proposals to re-open EDs. Conclusions: The critical issues while re-opening EDs calls for reducing the workload in the endoscopy units through appropriate rescheduling of procedures.", "qid": 48, "docid": "bmqr6l1r", "rank": 50, "score": 0.75445157289505}, {"content": "Title: Collective impacts on a global education emergency: The power of network response Content: The COVID-19 pandemic is an emergency of an exceptional scale, with major impacts on education globally and with significant new challenges for education in existing humanitarian contexts. This Viewpoint reflects on the immediate challenges of continuing education in humanitarian contexts and on the experience of the Inter-agency Network for Education in Emergencies (INEE) as a network supporting collective action of Education in Emergencies (EiE) practitioners globally. It also looks forward at INEE\u2019s plans to support quality distance education and issues to consider on the reopening of schools. It concludes with reflections on the needs and risks for EiE longer term.", "qid": 48, "docid": "5lntnce0", "rank": 51, "score": 0.7535396218299866}, {"content": "Title: Training disrupted: Practical tips for supporting competency-based medical education during the COVID-19 pandemic Content: The COVID-19 pandemic has disrupted healthcare systems around the world, impacting how we deliver medical education. The normal day-to-day routines have been altered for a number of reasons, including changes to scheduled training rotations, physical distancing requirements, trainee redeployment, and heightened level of concern. Medical educators will likely need to adapt their programs to maximize learning, maintain effective care delivery, and ensure competent graduates. Along with a continued focus on learner/faculty wellness, medical educators will have to optimize existing training experiences, adapt those that are no longer viable, employ new technologies, and be flexible when assessing competencies. These practical tips offer guidance on how to adapt medical education programs within the constraints of the pandemic landscape, stressing the need for communication, innovation, collaboration, flexibility, and planning within the era of competency-based medical education.", "qid": 48, "docid": "m0ndlduv", "rank": 52, "score": 0.7508033514022827}, {"content": "Title: Training disrupted: Practical tips for supporting competency-based medical education during the COVID-19 pandemic. Content: The COVID-19 pandemic has disrupted healthcare systems around the world, impacting how we deliver medical education. The normal day-to-day routines have been altered for a number of reasons, including changes to scheduled training rotations, physical distancing requirements, trainee redeployment, and heightened level of concern. Medical educators will likely need to adapt their programs to maximize learning, maintain effective care delivery, and ensure competent graduates. Along with a continued focus on learner/faculty wellness, medical educators will have to optimize existing training experiences, adapt those that are no longer viable, employ new technologies, and be flexible when assessing competencies. These practical tips offer guidance on how to adapt medical education programs within the constraints of the pandemic landscape, stressing the need for communication, innovation, collaboration, flexibility, and planning within the era of competency-based medical education.", "qid": 48, "docid": "7n1nyonb", "rank": 53, "score": 0.7508033514022827}, {"content": "Title: Children are unlikely to be the main drivers of the COVID\u201019 pandemic \u2013 a systematic review Content: AIM: Many countries have closed schools and kindergartens to minimise COVID\u201019, but the role that children play in disease transmission is unclear. METHODS: A systematic literature review of the MEDLINE and EMBASE databases and medRxiv/bioRxiv preprint servers to 11 May 2020 identified published and unpublished papers on COVID\u201019 transmission by children. RESULTS: We identified 700 scientific papers and letters and 47 full texts were studied in detail. Children accounted for a small fraction of COVID\u201019 cases and mostly had social contacts with peers or parents, rather than older people at risk of severe disease. Data on viral loads were scarce, but indicated that children may have lower levels than adults, partly because they often have fewer symptoms, and this should decrease the transmission risk. Household transmission studies showed that children were rarely the index case and case studies suggested that children with COVID\u201019 seldom caused outbreaks. However, it is highly likely that children can transmit the SARS\u2010COV\u20102 virus, which causes COVID\u201019, and even asymptomatic children can have viral loads. CONCLUSION: Children are unlikely to be the main drivers of the pandemic. Opening up schools and kindergartens is unlikely to impact COVID\u201019 mortality rates in older people.", "qid": 48, "docid": "5azti19e", "rank": 54, "score": 0.7503653168678284}, {"content": "Title: Pandemics and the Environmental Rebound Effect: Reflections from COVID-19 Content: The irruption of the COVID-19 pandemic has raised concerns on sustainability issues. The pandemic has accelerated the implementation of technologies such as ICT and shifts in mobility behaviour. Such changes have the potential to reduce environmental burdens, but also to trigger large environmental rebound effects. This perspective article reflects on some emerging concerns on the socio-economic effects of a pandemic on the environment from a rebound effect perspective. Although the pandemic offers potential to improve the environmental conditions, it brings also a high risk to produce Jevons\u2019 Paradox, i.e., increase environmental burdens rather than decrease them, as initially expected. Governments should be aware of these risks and assess the possibility to implement additional measures, like environmental taxation or limiting the use of resources, to help achieving sustainability targets.", "qid": 48, "docid": "k00sm084", "rank": 55, "score": 0.7497106790542603}, {"content": "Title: Impact of COVID-19 Second Wave on Healthcare Networks in the United States Content: The risk of overwhelming healthcare systems from a second wave of COVID-19 is yet to be quantified. Here, we investigate the impact of different reopening scenarios of states around the U.S. on COVID-19 hospitalized cases and the risk of overwhelming the healthcare system while considering resources at the county level. We show that the second wave might involve an unprecedented impact on the healthcare system if an increasing number of the population becomes susceptible and/or if the various protective measures are discontinued. Furthermore, we explore the ability of different mitigation strategies in providing considerable relief to the healthcare system. The results can aid healthcare planners, policymakers, and state officials in making decisions on additional resources required and on when to return to normalcy.", "qid": 48, "docid": "8kv7io05", "rank": 56, "score": 0.7496298551559448}, {"content": "Title: Children are unlikely to be the main drivers of the COVID-19 pandemic - A systematic review Content: AIM: Many countries have closed schools and kindergartens to minimise COVID-19, but the role that children play in disease transmission is unclear. METHODS: A systematic literature review of the MEDLINE and EMBASE databases and medRxiv/bioRxiv preprint servers to 11 May 2020 identified published and unpublished papers on COVID-19 transmission by children. RESULTS: We identified 700 scientific papers and letters and 47 full texts were studied in detail. Children accounted for a small fraction of COVID-19 cases and mostly had social contacts with peers or parents, rather than older people at risk of severe disease. Data on viral loads were scarce, but indicated that children may have lower levels than adults, partly because they often have fewer symptoms, and this should decrease the transmission risk. Household transmission studies showed that children were rarely the index case and case studies suggested that children with COVID-19 seldom caused outbreaks. However, it is highly likely that children can transmit the SARS-COV-2 virus, which causes COVID-19, and even asymptomatic children can have viral loads. CONCLUSION: Children are unlikely to be the main drivers of the pandemic. Opening up schools and kindergartens is unlikely to impact COVID-19 mortality rates in older people.", "qid": 48, "docid": "tm9uso6w", "rank": 57, "score": 0.7496041059494019}, {"content": "Title: Digital transformation of everyday life \u2013 How COVID-19 pandemic transformed the basic education of the young generation and why information management research should care? Content: Children of today have been surrounded by digital technology since their birth. However, children of today are not equally equipped for their technology rich future: various kinds of digital divides still prevail in the society and affect the young generation and their digital futures. Schools and education of children should undergo an extensive digital transformation to be able to meet the needs of the young generation and their digitalized future. The COVID-19 pandemic has suddenly and abruptly forced schools and education indeed to engage in such a transformation. In this study we examine the digital transformation initiated by the COVID-19 pandemic in the basic education of the young generation, the variety of digital divides emerging and reinforced, and the possible barriers reported along the way. We argue that information management research should better acknowledge children, their digitalized everyday life and their basic education as significant areas of concern. We should understand them as well as allow them to shape the education we offer in the context of higher education, but we should also aim at influencing the basic education of the young generation \u2013 for the purpose of equipping them with important skills and competencies for their digital futures but also for the purpose of arousing their interest in this important field, maybe even as a career option.", "qid": 48, "docid": "1sqseqbw", "rank": 58, "score": 0.7494333982467651}, {"content": "Title: Production networks and epidemic spreading: How to restart the UK economy? Content: We analyse the economics and epidemiology of different scenarios for a phased restart of the UK economy. Our economic model is designed to address the unique features of the COVID-19 pandemic. Social distancing measures affect both supply and demand, and input-output constraints play a key role in restricting economic output. Standard models for production functions are not adequate to model the short-term effects of lockdown. A survey of industry analysts conducted by IHS Markit allows us to evaluate which inputs for each industry are absolutely necessary for production over a two month period. Our model also includes inventory dynamics and feedback between unemployment and consumption. We demonstrate that economic outcomes are very sensitive to the choice of production function, show how supply constraints cause strong network effects, and find some counter-intuitive effects, such as that reopening only a few industries can actually lower aggregate output. Occupation-specific data and contact surveys allow us to estimate how different industries affect the transmission rate of the disease. We investigate six different re-opening scenarios, presenting our best estimates for the increase in R0 and the increase in GDP. Our results suggest that there is a reasonable compromise that yields a relatively small increase in R0 and delivers a substantial boost in economic output. This corresponds to a situation in which all non-consumer facing industries reopen, schools are open only for workers who need childcare, and everyone who can work from home continues to work from home.", "qid": 48, "docid": "uzdbibf5", "rank": 59, "score": 0.7489594221115112}, {"content": "Title: Education, the science of learning, and the COVID-19 crisis Content: In the COVID-19 crisis, the science of learning has two different responsibilities: first, to offer guidance about how best to deal with the impact of the current situation, including lockdown and home-schooling; and second, to consider bigger questions about what this large-scale educational experiment might mean for the future. The first part of this Viewpoint summarises advice for parents on mental health, and on becoming stand-in-teachers. The second part, taking the longer view, considers the potential negative impact of the COVID-19 crisis in increasing inequality in education; but also the potential positive impact of driving innovations in technology use for educating children.", "qid": 48, "docid": "v83dwt6k", "rank": 60, "score": 0.7484310269355774}, {"content": "Title: Preparing Students for a More Public Health-Aware Market in Response to COVID-19 Content: The COVID-19 pandemic has made the public more aware of public health and the role its professionals play in addressing the pandemic. Schools and programs in public health have a new opportunity to recruit, train, and sustain the public health workforce. Academic public health can further educate the public and prepare students for meaningful careers through interprofessional education and practice-based learning.", "qid": 48, "docid": "8ykrh75b", "rank": 61, "score": 0.7484172582626343}, {"content": "Title: Preparing Students for a More Public Health-Aware Market in Response to COVID-19. Content: The COVID-19 pandemic has made the public more aware of public health and the role its professionals play in addressing the pandemic. Schools and programs in public health have a new opportunity to recruit, train, and sustain the public health workforce. Academic public health can further educate the public and prepare students for meaningful careers through interprofessional education and practice-based learning.", "qid": 48, "docid": "6gwqo21j", "rank": 62, "score": 0.7484172582626343}, {"content": "Title: How to Safely Reopen Colleges and Universities During COVID-19: Experiences From Taiwan Content: Reopening colleges and universities during the coronavirus disease 2019 (COVID-19) pandemic poses a special challenge worldwide. Taiwan is one of the few countries where schools are functioning normally. To secure the safety of students and staff, the Ministry of Education in Taiwan established general guidelines for college campuses. The guidelines delineated creation of a task force at each university; school-based risk screening based on travel history, occupation, contacts, and clusters; measures on self-management of health and quarantine; general hygiene measures (including wearing masks indoors); principles on ventilation and sanitization; regulations on school assemblies; a process for reporting suspected cases; and policies on school closing and make-up classes. It also announced that a class should be suspended if 1 student or staff member in it tested positive and that a school should be closed for 14 days if it had 2 or more confirmed cases. As of 18 June 2020, there have been 7 confirmed cases in 6 Taiwanese universities since the start of the pandemic. One university was temporarily closed, adopted virtual classes, and quickly reopened after 14 days of contact tracing and quarantine of possible contacts. Taiwan's experience suggests that, under certain circumstances, safely reopening colleges and universities this fall may be feasible with a combination of strategies that include containment (access control with contact tracing and quarantine) and mitigation (hygiene, sanitation, ventilation, and social distancing) practices.", "qid": 48, "docid": "vgbhyzb9", "rank": 63, "score": 0.748321533203125}, {"content": "Title: The role of the orthopaedic surgeon in the COVID-19 era: cautions and perspectives Content: The current coronavirus disease 2019 (COVID-19) pandemic has revolutionized global healthcare in an unprecedented way and with unimaginable repercussions. Resource reallocation, socioeconomic confinement and reorganization of production activities are current challenges being faced both at the national and international levels, in a frame of uncertainty and fear. Hospitals have been restructured to provide the best care to COVID-19 patients while adopting preventive strategies not to spread the infection among healthcare providers and patients affected by other diseases. As a consequence, the concept of urgency and indications for elective treatments have been profoundly reshaped. In addition, several providers have been recruited in COVID-19 departments despite their original occupation, resulting in a profound rearrangement of both inpatient and outpatient care. Orthopaedic daily practice has been significantly affected by the pandemic. Surgical indications have been reformulated, with elective cases being promptly postponed and urgent interventions requiring exceptional attention, especially in suspected or COVID-19(+) patients. This has made a strong impact on inpatient management, with the need of a dedicated staff, patient isolation and restrictive visiting hour policies. On the other hand, outpatient visits have been limited to reduce contacts between patients and the hospital personnel, with considerable consequences on post-operative quality of care and the human side of medical practice. In this review, we aim to analyze the effect of the COVID-19 pandemic on the orthopaedic practice. Particular attention will be dedicated to opportune surgical indication, perioperative care and safe management of both inpatients and outpatients, also considering repercussions of the pandemic on resident education and ethical implications.", "qid": 48, "docid": "efwuy8p9", "rank": 64, "score": 0.7479457855224609}, {"content": "Title: A targeted e-learning approach to reduce student mixing during a pandemic Content: The COVID-19 pandemic has resulted in widespread closure of schools and universities. These institutions have turned to distance learning to provide educational continuity. Schools now face the challenge of how to reopen safely and resume in-class learning. However, there is little empirical evidence to guide decision-makers on how this can be achieved. Here, we show that selectively deploying e-learning for larger classes is highly effective at decreasing campus-wide opportunities for student-to-student contact, while allowing most in-class learning to continue uninterrupted. We conducted a natural experiment at a large university that implemented a series of e-learning interventions during the COVID-19 outbreak. Analyses of >24 million student connections to the university Wi-Fi network revealed that population size can be manipulated by e-learning in a targeted manner according to class size characteristics. Student mixing showed accelerated growth with population size according to a power law distribution. Therefore, a small e-learning dependent decrease in population size resulted in a large reduction in student clustering behaviour. Our results show that e-learning interventions can decrease potential for disease transmission while minimizing disruption to university operations. Universities should consider targeted e-learning a viable strategy for providing educational continuity during early or late stages of a disease outbreak.", "qid": 48, "docid": "f70a2twc", "rank": 65, "score": 0.7478615045547485}, {"content": "Title: How to manage the post pandemic opening? A Pontryagin Maximum Principle approach Content: The COVID-19 pandemic has completely disrupted the operation of our societies. Its elusive transmission process, characterized by an unusually long incubation period, as well as a high contagion capacity, has forced many countries to take quarantine and social isolation measures that conspire against the performance of national economies. This situation confronts decision makers in different countries with the alternative of reopening the economies, thus facing the unpredictable cost of a rebound of the infection. This work tries to offer an initial theoretical framework to handle this alternative.", "qid": 48, "docid": "dsmdqp2o", "rank": 66, "score": 0.7472547292709351}, {"content": "Title: Coronavirus Disease 2019, School Closures, and Children\u2019s Mental Health Content: Coronavirus disease 2019 (COVID-19), which was first identified in Wuhan, China, in late December of 2019 is rapidly spreading across the globe. The South Korean government has ordered the closure of all schools, as part of its attempts to use social distancing measures to prevent the spread of COVID-19. The effects of the school closures on reducing contagion are generally positive; however, the measure is controversial because of the socioeconomic ripple effect that accompanies it. The author briefly reviewed the existing literature on the mental health aspects of disasters and presents the issues related to school closures due to pandemics, from medical and socioeconomic perspectives and in terms of children\u2019s mental health. The results of this review suggest that research on children\u2019s mental health in relation to the adoption of school closures as a pandemic mitigation strategy is urgently needed.", "qid": 48, "docid": "y0ufxwhq", "rank": 67, "score": 0.7470849752426147}, {"content": "Title: Consequences of physical distancing emanating from the COVID-19 pandemic: An australian perspective Content: The sobering reality of the COVID-19 pandemic is that it has brought people together at home at a time when we want them apart in the community. This will bring both benefits and challenges. It will affect people differently based upon their age, health status, resilience, family support structures, and socio-economic background. This article will assess the impact in high income countries like Australia, where the initial wave of infection placed the elderly at the greatest risk of death whilst the protective measures of physical distancing, self-isolation, increased awareness of hygiene practices, and school closures with distance learning has had considerable impact on children and families acutely and may have ramifications for years to come.", "qid": 48, "docid": "9d7vxjys", "rank": 68, "score": 0.7466967701911926}, {"content": "Title: School closures during the 2009 influenza pandemic: national and local experiences Content: BACKGROUND: School closure is a non-pharmaceutical intervention that was considered in many national pandemic plans developed prior to the start of the influenza A(H1N1)pdm09 pandemic, and received considerable attention during the event. Here, we retrospectively review and compare national and local experiences with school closures in several countries during the A(H1N1)pdm09 pandemic. Our intention is not to make a systematic review of country experiences; rather, it is to present the diversity of school closure experiences and provide examples from national and local perspectives. METHODS: Data were gathered during and following a meeting, organized by the European Centres for Disease Control, on school closures held in October 2010 in Stockholm, Sweden. A standard data collection form was developed and sent to all participants. The twelve participating countries and administrative regions (Bulgaria, China, France, Hong Kong Special Administrative Region (SAR), Italy, Japan, New Zealand, Serbia, South Africa, Thailand, United Kingdom, and United States) provided data. RESULTS: Our review highlights the very diverse national and local experiences on school closures during the A(H1N1)pdm09 pandemic. The processes including who was in charge of making recommendations and who was in charge of making the decision to close, the school-based control strategies, the extent of school closures, the public health tradition of responses and expectations on school closure varied greatly between countries. Our review also discusses the many challenges associated with the implementation of this intervention and makes recommendations for further practical work in this area. CONCLUSIONS: The single most important factor to explain differences observed between countries may have been the different public health practises and public expectations concerning school closures and influenza in the selected countries.", "qid": 48, "docid": "3amxb7qr", "rank": 69, "score": 0.7463293671607971}, {"content": "Title: Student engagement in a public health initiative in response to COVID\u201019 Content: In face of the current pandemic, universities are closing worldwide. In Brazil, as elsewhere, academic activities have been suspended in response to the Ministry of Health's recommendations to socially distance. This created risk of suboptimally utilizing the great potential students have to contribute to the COVID-19 response.", "qid": 48, "docid": "m54tf1f6", "rank": 70, "score": 0.7459372282028198}, {"content": "Title: The global viralization of policies to contain the spreading of the COVID-19 pandemic: analyses of school closures and first reported cases. Content: Background With the exposure to the COVID-19 pandemic, countries swiftly implemented a variety of health policies. In this work we examine how rapid countries responded to this pandemic using two events: the day in which the first case of COVID-19 was reported, and first day in which countries used school closure as one of the measures to avoid outbreaks. Methods We compiled information from multiple sources, from December 31st 2019 to June 1st 2020, to trace when 172 countries reported their first COVID-19 case and implemented school closure to contain outbreaks. We applied cross-national Weibull survival analysis to evaluate the global speed of detection of first COVID-19 reported cases and school closure. We also assessed how health systems, globalization, economic development, political systems, and economic integration to China, Republic of Korea and Italy increased the speed of adoption. Results Ten days after the World Health Organization (WHO) declared COVID-19 to be an international emergency, countries were 28 (95% CI: 12,77) times more likely to report first COVID-19 cases and 42 (95% CI: 22,90) times more likely to close schools. One standard deviation increase in the epidemic security index rises the rate of report first cases by 37% (Hazard Ratio (HR) 1.37 (95% CI: 1.09,1.72) and delays the adoption for school closures by 36% (HR 0.64 (95% CI:0.50,0.82). One standard deviation increase in the globalization index augments the adoption for school closures by 74% (HR 1.74 (95% CI:1.34,2.24). Conclusion. After the WHO declared a global emergency, countries were unprecedently acting very rapidly. While countries more globally integrated were swifter in closing schools, countries with better designed health systems to tackle epidemics were slower in adopting it. More studies are needed to assess how the speed of school closures and other policies will affect the development of the pandemic.", "qid": 48, "docid": "5kbrsos9", "rank": 71, "score": 0.7459245920181274}, {"content": "Title: Hopelessness, helplessness and resilience: The importance of safeguarding our trainees' mental wellbeing during the COVID-19 pandemic Content: \u2022 The COVID-19 pandemic may put the mental wellbeing of trainees at risk. \u2022 Hopelessness, helplessness and burnout are important to be aware of. \u2022 We need to foster an open culture of trust and support. \u2022 We need to promote resilience in colleagues/trainees where possible.", "qid": 48, "docid": "c4dlym34", "rank": 72, "score": 0.7450423240661621}, {"content": "Title: Clinical nursing and midwifery education in the pandemic age Content: The COVID-19 pandemic has disrupted clinical nursing and midwifery education. This disruption has long-term implications for the nursing and midwifery workforce and for future healthcare responses to pandemics. Solutions may include enhanced partnerships between schools of nursing and midwifery and health service providers and including schools of nursing and midwifery in preparedness planning. These suggestions notwithstanding, we call upon national and international nursing and midwifery bodies to study how to further the clinical education of nurses and midwives during pandemics and other times of crisis.", "qid": 48, "docid": "2wwu9kh4", "rank": 73, "score": 0.7448508143424988}, {"content": "Title: Resuming elective surgical activity after the COVID-19 wave: what the patients need to know Content: As COVID-19 outbreak enters its second phase of lockdown ease, healthcare plans involve elective surgery re-establishment to provide essential life-saving care. Patients are increasingly requesting information about their facility's readiness for safely performing surgery. This information should be open and transparent including patient's education with objective data regarding the state of the pandemic in the country and the control measures undertaken by the facility.", "qid": 48, "docid": "uwrzpgrt", "rank": 74, "score": 0.7448257207870483}, {"content": "Title: Resuming elective surgical activity after the COVID-19 wave: what the patients need to know. Content: As COVID-19 outbreak enters its second phase of lockdown ease, healthcare plans involve elective surgery re-establishment to provide essential life-saving care. Patients are increasingly requesting information about their facility's readiness for safely performing surgery. This information should be open and transparent including patient's education with objective data regarding the state of the pandemic in the country and the control measures undertaken by the facility.", "qid": 48, "docid": "y7do987k", "rank": 75, "score": 0.7448256611824036}, {"content": "Title: U.S. faculty and administrators\u2019 experiences and approaches in the early weeks of the COVID-19 pandemic Content: The COVID-19 pandemic has had a profound and rapid impact on higher education institutions across the world. In this study, we report the findings of a survey investigating the rapid transition to emergency remote teaching in the early weeks of the pandemic at public and private post-secondary institutions in the United States. Participants consisted of 897 faculty and administrators at 672 U.S. institutions. Findings reveal that with few exceptions nearly all reporting institutions transitioned to emergency teaching and learning approaches. Administrators reported that faculty with and without online teaching experience pivoted to online teaching, and nearly all administrators indicated that those who did not have online teaching experience were in the process of learning how to teach online. Regardless of whether faculty had previous experience teaching online or not, many faculty reported that they were using new teaching methods. A majority of faculty reported making changes to their assignments or exams as a result of transitioning to a new mode of delivery. Nearly half reported lowering the expected volume of work for students (including dropping assignments or exams) and/or shifting to a pass/fail model for this semester. The primary areas where faculty and administrators identified a need for assistance related to student support, greater access to online digital materials, and guidance for working from home. This study provides an early snapshot of efforts towards teaching and learning continuity at a large scale and provides some insights for future research and practice.", "qid": 48, "docid": "zgaoxsps", "rank": 76, "score": 0.7438600063323975}, {"content": "Title: Art\u00edculo EspecialEl m\u00e9dico frente a la COVID-19: lecciones de una pandemia Content: Abstract Apart from its enormous health and economic impact, the COVID-19 pandemic has changed the way of practicing medicine and medical education. It is likely that this effect may accelerate the transformation that both activities are experiencing. The present article, written at the peak of the crisis, sets out some thoughts on four topics: 1) the publication of false and sensationalist news; 2) risks of taking medical decisions not based on the evidence; 3) the bioethical implications when there are sufficient resources available for everybody and; 4) the possible effects of the crisis on the teaching of medicine. This crisis should enable doctors, teachers and, students of medicine to draw conclusions and be better prepared for the future. Firstly, it is essential to maintain critical thinking that may protect against the \u201cinfodemic\u201d. Furthermore, the scientific and ethical standards learned in the faculty, should not be lowered, but remain intact. Lastly, it should be remembered that, in a devastating pandemic like the current one, apart from scientific medicine, which is practised with the brain, that other medicine that is practiced with the heart must also be practised.", "qid": 48, "docid": "lm1jcbyd", "rank": 77, "score": 0.7437169551849365}, {"content": "Title: Resumption of Respiratory Outpatient Services in the COVID-19 era: experience from Southern Italy Content: COVID-19 pandemic turned the entire health-care system organization upside-down, suspending elective activities and outpatient services. In Italy, we are entering a second phase of the pandemic and several strategies has been developed to \"re-open\" the country, some businesses, and also health-care outpatient activities. This manuscript describes the experience of a Southern Italy Respiratory Unit for safely resuming outpatient respiratory services and preventing COVID-19 transmission.", "qid": 48, "docid": "3vq5vq1t", "rank": 78, "score": 0.7432913780212402}, {"content": "Title: Resumption of Respiratory Outpatient Services in the COVID-19 era: experience from Southern Italy Content: COVID-19 pandemic turned the entire health-care system organization upside-down, suspending elective activities and outpatient services. In Italy, we are entering a second phase of the pandemic and several strategies has been developed to \u201cre-open\u201d the country, some businesses, and also health-care outpatient activities. This manuscript describes the experience of a Southern Italy Respiratory Unit for safely resuming outpatient respiratory services and preventing COVID-19 transmission.", "qid": 48, "docid": "6c7n0xir", "rank": 79, "score": 0.7432152032852173}, {"content": "Title: Can indoor sports centers be allowed to re-open during the COVID-19 pandemic based on a certificate of equivalence? Content: Within a time span of only a few months, the SARS-CoV-2 virus has managed to spread across the world. This virus can spread by close contact, which includes large droplet spray and inhalation of microscopic droplets, and by indirect contact via contaminated objects. While in most countries, supermarkets have remained open, due to the COVID-19 pandemic, authorities have ordered many other shops, restaurants, bars, music theaters and indoor sports centers to be closed. As part of COVID-19 (semi)lock-down exit strategies, many government authorities are now (May 2020) allowing a gradual re-opening, where sometimes indoor sport centers are last in line to be permitted to re-open. This technical note discusses the challenges in re-opening these facilities and the measures already suggested by some to tackle these challenges. It also elaborates three potential additional measures and based on these additional measures, it suggests the concept of a certificate of equivalence that could allow indoor sports centers with such a certificate to re-open more rapidly. It also attempts to stimulate increased preparedness of indoor sports centers for potential next waves of SARS-CoV-2 as well as future pandemics. It is concluded that fighting situations such as the COVID-19 pandemic and limiting economic damage requires increased collaboration and research by virologists, epidemiologists, microbiologists, aerosol scientists, building physicists, building services engineers and sports scientists.", "qid": 48, "docid": "kne820pv", "rank": 80, "score": 0.7430684566497803}, {"content": "Title: Resuming elective surgical services in times of COVID-19 infection Content: The consequences of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have been devastating to the healthcare system. As the positive effects of social distancing, mandatory masking, and societal lockdown on the spread of the disease and its incidence in the community were documented, societal and financial pressures mounted worldwide, prompting efforts to \u201cre-open\u201d countries, states, communities, businesses, and schools. The same happened with hospital, which had to start developing strategies to resume elective surgery activities. This manuscript describes the pre-requisites as well as the strategies for resuming surgical activity, be it in the outpatient or inpatient setting.", "qid": 48, "docid": "f0frlpwh", "rank": 81, "score": 0.7428568601608276}, {"content": "Title: Predicting the second wave of COVID-19 in Washtenaw County, MI Content: Marissa Renardy and Denise Kirschner University of Michigan Medical School The COVID-19 pandemic has highlighted the patchwork nature of disease epidemics, with infection spread dynamics varying wildly across countries and across states within the US. These heteroge- neous patterns are also observed within individual states, with patches of concentrated outbreaks. Data is being generated daily at all of these spatial scales, and answers to questions regarded re- opening strategies are desperately needed. Mathematical modeling is useful in exactly these cases, and using modeling at a county scale may be valuable to further predict disease dynamics for the purposes of public health interventions. To explore this issue, we study and predict the spread of COVID-19 in Washtenaw County, MI, the home to University of Michigan, Eastern Michigan University, and Google, as well as serving as a sister city to Detroit, MI where there has been a serious outbreak. Here, we apply a discrete and stochastic network-based modeling framework allowing us to track every individual in the county. In this framework, we construct contact net- works based on synthetic population datasets specific for Washtenaw County that are derived from US Census datasets. We assign individuals to households, workplaces, schools, and group quarters (such as prisons). In addition, we assign casual contacts to each individual at random. Using this framework, we explicitly simulate Michigan-specific government-mandated workplace and school closures as well as social distancing measures. We also perform sensitivity analyses to identify key model parameters and mechanisms contributing to the observed disease burden in the three months following the first observed cases on COVID-19 in Michigan. We then consider several scenarios for relaxing restrictions and reopening workplaces to predict what actions would be most prudent. In particular, we consider the effects of 1) different timings for reopening, and 2) different levels of workplace vs. casual contact re-engagement. Through simulations and sensitivity analyses, we explore mechanisms driving magnitude and timing of a second wave of infections upon re-opening. This model can be adapted to other US counties using synthetic population databases and data specific to those regions.", "qid": 48, "docid": "n1jmqx6m", "rank": 82, "score": 0.7425737977027893}, {"content": "Title: COVID-19 mathematical model reopening scenarios for Sao Paulo - Brazil Content: The objective of the current investigation was to produce a generalized computational model to predict consequences of various reopening scenarios on COVID-19 infections rates and available hospital resources in Sao Paulo - Brazil. We were able to use the Susceptible-Exposed-Infected-Recovered (SEIR) model to fit both accumulated death data and corrected accumulated cases data associated with COVID-19 for both Brazil and the state of Sao Paulo. In addition, we were able to simulate the consequences of reopening under different possible scenarios in Brazil, in special for the state of Sao Paulo. The model was able to provide a predicted scenario in which reopening could occur with minimal impact on human life considering people careful behavior in combination with continued social distancing measures.", "qid": 48, "docid": "e8744fcw", "rank": 83, "score": 0.7423266172409058}, {"content": "Title: Be aware of how COVID\u201019 could impact international students Content: The spread of COVID\u201019 has impacted every aspect of college and university operations \u2014 and life in general. As you look ahead, consider ways the pandemic could impact your current and potential international students so you can implement plans to address the challenges.", "qid": 48, "docid": "zxq502ym", "rank": 84, "score": 0.7423211932182312}, {"content": "Title: The Australian response to the COVID-19 pandemic and diabetes - Lessons learned Content: The COVID-19 pandemic has had a significant impact on the economy and health system of most countries in the world and this is also true of Australia. Australia has not seen the huge surge of COVID-19 positive cases and subsequent hospitalisations and deaths experienced in other parts of the world. However there have been important social and health strategies to \"flatten\" the curve, to reduce infections and to manage those infected. These have included closure of international and interstate borders, local lockdown measures, physical distancing, shift to work from home, closure of non-essential businesses and full or partial closure of all schools and tertiary education facilities. From the diabetes care perspective, there was a significant and concerted diversion of hospital resources and staff to COVID-19 specific activities. Reduced access to primary care, diagnostic and hospital services for diabetes, combined with fear of exposure to the virus in these settings, led to a significant drop in access to usual diabetes care. Provision of outpatient and private sector diabetes services via telehealth was encouraged and supported by expanded and new government subsidies. Importantly, for the first time, there was government funded subsidy for care delivered via the telephone and inclusion of credentialled diabetes educators in funded telephone/telehealth support. The Australian health professional and consumer organisations worked cooperatively producing guidelines, position statements and other educational resources specific for the COVID-19 setting. Once the COVID-19 pandemic is over, review of all the changes will be important, determining which should be permanently implemented. The learnings from COVID-19 should help prepare Australia for future pandemics or other major health crises.", "qid": 48, "docid": "w56ddzaw", "rank": 85, "score": 0.7416800260543823}, {"content": "Title: Health-education to prevent COVID-19 in schoolchildren: a call to action Content: BACKGROUND: There is currently considerable international debate around school closures/openings and the role of children in the transmission of coronavirus disease 2019 (COVID-19). Whilst evidence suggests that children are not impacted by COVID-19 as severely as adults, little is still known about their transmission potential, and with a lot of asymptomatic cases they may be silent transmitters (i.e. infectious without showing clinical signs of disease), albeit at a lower level than adults. In relation to this, it is somewhat concerning that in many countries children are cared for, or are often in close contact with, older individuals such as grandparents \u00e2\u0094\u0080 the age group most at risk of acquiring serious respiratory complications resulting in death. MAIN TEXT: We emphasise that in the absence of a vaccine or an effective therapeutic drug, preventive measures such as good hygiene practices \u00e2\u0094\u0080 hand washing, cough etiquette, disinfection of surfaces and social distancing represent the major (in fact only) weapons that we have against COVID-19. Accordingly, we stress that there is a pressing need to develop specific COVID-19 prevention messages for schoolchildren. CONCLUSION: An entertainment education intervention for schoolchildren systematically implemented in schools would be highly effective and fill this need. With such measures in place there would be greater confidence around the opening of schools.", "qid": 48, "docid": "ccx9klxa", "rank": 86, "score": 0.7414500713348389}, {"content": "Title: Medical students' preference for returning to the clinical setting during the COVID-19 pandemic Content: OBJECTIVES: The Covid-19 pandemic has led to widespread disruptions in the clinical education of medical students. In managing students' return to the clinical setting, medical schools face the challenge of balancing education, service, and risk considerations. To compound this challenge, medical students may prefer not to re-enter during a period of great uncertainty, leading to substantive downstream sequelae on individual, institutional, and national levels. Understanding students' views on resuming clinical experiences, therefore, is an important consideration. The purpose of this study was to assess medical students' preference for re-entering the clinical setting during a pandemic, and to explore personal and environmental characteristics associated with that preference. METHODS: We conducted an electronic survey of currently enrolled medical students of Duke-NUS Medical School in Singapore, less than a month into the pandemic. Survey items were aligned with a conceptual framework related to medical students' preference for returning to the clinical setting. The framework consisted of three domains: 1) non-modifiable demographic information, 2) factors thought to be modifiable through the course of medical education, including burnout, tolerance for ambiguity, motivation, and professionalism, and 3) students' perception of Covid-19 infection risk to self. RESULTS: Approximately one third of 179 students preferred not to return to the clinical setting. Results of a multivariable analysis indicated that compared to this group, the two-thirds of students favouring return showed evidence of greater autonomous (or internal) motivation, a greater sense of professional responsibility, and a lower self-perception of harbouring risk to patients. CONCLUSIONS: Students' preference regarding return to the clinical environment stems from the interplay of several key factors, and is substantively associated with perceptions of professional responsibility and their own potential risk to the healthcare system. Mindfully considering and addressing these issues may help medical schools in their preparation for returning students to the clinical setting.", "qid": 48, "docid": "jv3afofh", "rank": 87, "score": 0.7414369583129883}, {"content": "Title: Health-education to prevent COVID-19 in schoolchildren: a call to action Content: BACKGROUND: There is currently considerable international debate around school closures/openings and the role of children in the transmission of coronavirus disease 2019 (COVID-19). Whilst evidence suggests that children are not impacted by COVID-19 as severely as adults, little is still known about their transmission potential, and with a lot of asymptomatic cases they may be silent transmitters (i.e. infectious without showing clinical signs of disease), albeit at a lower level than adults. In relation to this, it is somewhat concerning that in many countries children are cared for, or are often in close contact with, older individuals such as grandparents \u2500 the age group most at risk of acquiring serious respiratory complications resulting in death. MAIN TEXT: We emphasise that in the absence of a vaccine or an effective therapeutic drug, preventive measures such as good hygiene practices \u2500 hand washing, cough etiquette, disinfection of surfaces and social distancing represent the major (in fact only) weapons that we have against COVID-19. Accordingly, we stress that there is a pressing need to develop specific COVID-19 prevention messages for schoolchildren. CONCLUSION: An entertainment education intervention for schoolchildren systematically implemented in schools would be highly effective and fill this need. With such measures in place there would be greater confidence around the opening of schools.", "qid": 48, "docid": "ynaum52m", "rank": 88, "score": 0.7412666082382202}, {"content": "Title: Flexible employment relationships and careers in times of the COVID-19 pandemic Content: The COVID-19 pandemic represents a crisis that affects several aspects of people's lives around the globe. Most of the affected countries took several measures, like lockdowns, business shutdowns, hygiene regulations, social distancing, school and university closings, or mobility tracking as a means of slowing down the distribution of COVID-19. These measures are expected to show short-term and long-term effects on people's working lives. However, most media reports focused on the effects of the COVID-19 pandemic on changes in work arrangements (e.g., short-time work, flexible location and hours) for workers in a regular employment relationship. We here focus on workers in flexible employment relationships (e.g. temporary agency work and other forms of subcontracted labor, as well as new forms of working, such as in the gig economy). Specifically, we will discuss (a) how the work and careers of individuals in flexible employment relationships might get affected by the COVID-19 pandemic; (b) outline ideas how to examine period effects of the COVID-19 pandemic on the work and careers of those individuals, and (c) outline how the pandemic can contribute to the ramification of flexible employment relationships.", "qid": 48, "docid": "9sbyha2v", "rank": 89, "score": 0.7409839034080505}, {"content": "Title: Service-learning in response to the coronavirus disease 2019 pandemic: Emerging lessons from the Department of Family Medicine and Public Health at the University of Botswana Content: The novel coronavirus disease 2019 (COVID-19) pandemic has disrupted many lives worldwide. Training programmes in academic institutions have also been affected by the pandemic. Teaching and learning family medicine and public health medicine in the COVID-19 era require adjustments to training activities. At the University of Botswana, the pandemic presented an opportunity to steer training programmes in the Department of Family Medicine and Public Health Medicine more towards service-learning. The department collaborated with the Ministry of Health and Wellness as well as the District Health Management teams in the national response to the pandemic as essential service providers. The increased demands for service provision were balanced with educational opportunities for trainees during the COVID-19 public health emergency. Including structured ongoing reflections for trainees involved in the COVID-19 response helps to connect service and the academic curriculum.", "qid": 48, "docid": "oslxnp2b", "rank": 90, "score": 0.7409828901290894}, {"content": "Title: Are we there yet? The transition from response to recovery for the COVID-19 pandemic Content: Abstract There is no corner of the planet that has not been impacted by the rapid spread of the novel coronavirus, COVID-19. While the COVID-19 pandemic has already had far-reaching socioeconomic consequences commonly associated with natural hazards (such as disruption to society, economic damage, and loss of lives), the response of governments around the world has been unparalleled and unlike anything seen before. Governments are faced with a myriad of multi-dimensional effects of the pandemic, including direct impacts on public health systems and population health and indirect socioeconomic effects including disruption to every single sector of the economy and mass unemployment. There is, additionally, the growing realisation that the timescale associated with this crisis may permanently change the very foundations of societies \u2018normal\u2019 day-to-day life. As the world transitions to recovering from COVID-19, those developing that recovery need support in adjusting and improving their policies and measures. The situation seems dire, the stakes are high. Literature about the transition between the response and recovery phase in relation to pandemics is scarce. Further complication is that the pandemic will not allow countries to simply transition to the full-scale recovery, instead, a rebound from recovery to response phase is expected for a certain period until the immunization is in place. Pandemics indeed force us to think beyond typical emergency management structures; the cycles of the disaster risk management in the case of biological and other natural hazards are not exactly the same and no one-size-fits-all approach may be used. Still, some parallels may be drawn with the efforts to combat natural hazards and some lessons may be used from previous and the current pandemic. Based on these experiences and reflections, this paper provides a set of policy directions to be considered during the transition towards, as well as throughout, this transition phase. It is suggested that meeting this global, multi-dimensional, and complex challenge will require considerable international collaboration (even convention) and macro-scale changes to global and national policies. The recovery issues are mainly going to be dominated by politics, economics and social science. Necessary for an effective recovery, the pandemic response needs to be a holistic response, combined with an improved data ecosystem between the public health system and the community. We should also view this outbreak and our response to it as an opportunity to learn lessons and reaffirm our universal commitment to sustainable development and enhancing wellbeing around the world.", "qid": 48, "docid": "3mu9rrql", "rank": 91, "score": 0.7406051754951477}, {"content": "Title: The Australian response to the COVID-19 pandemic and diabetes \u2013 lessons learned Content: The COVID-19 pandemic has had a significant impact on the economy and health system of most countries in the world and this is also true of Australia. Australia has not seen the huge surge of COVID-19 positive cases and subsequent hospitalisations and deaths experienced in other parts of the world. However there have been important social and health strategies to \u201cflatten\u201d the curve, to reduce infections and to manage those infected. These have included closure of international and interstate borders, local lockdown measures, physical distancing, shift to work from home, closure of non-essential businesses and full or partial closure of all schools and tertiary education facilities. From the diabetes care perspective, there was a significant and concerted diversion of hospital resources and staff to COVID-19 specific activities. Reduced access to primary care, diagnostic and hospital services for diabetes, combined with fear of exposure to the virus in these settings, led to a significant drop in access to usual diabetes care. Provision of outpatient and private sector diabetes services via telehealth was encouraged and supported by expanded and new government subsidies. Importantly, for the first time, there was government funded subsidy for care delivered via the telephone and inclusion of credentialled diabetes educators in funded telephone/telehealth support. The Australian health professional and consumer organisations worked cooperatively producing guidelines, position statements and other educational resources specific for the COVID-19 setting. Once the COVID-19 pandemic is over, review of all the changes will be important, determining which should be permanently implemented. The learnings from COVID-19 should help prepare Australia for future pandemics or other major health crises.", "qid": 48, "docid": "j2jvdpbg", "rank": 92, "score": 0.7405751943588257}, {"content": "Title: Financial implications of the CoviD-19 epidemic for hospitals: A case study Content: A concern about the COVID-19 pandemic is that U S hospitals may not have the capacity to serve all the patients seeking care With all these new patients, could the pandemic be financially beneficial for hospitals? We suggest the answer is likely no for three reasons First, many hospitals have experienced reductions in both surgical and clinic volumes resulting in substantial revenue losses Second, there are reports of increases in the cost of supplies Finally, the increase in intensive care services required to respond to the surge of COVID-19 patients will result in a shift of patient volume from acute to intensive care, and this shift will not likely improve profitability To estimate the possible magnitude of each of these effects, we analyze 2019 financial data from a profitable, well-run hospital in Washington State Our estimates suggest that the COVID-19 epidemic will cause dramatic financial losses for hospitals and that the bulk of those losses will result from lost revenue We suggest that these losses will be sufficiently large to create major changes in the hospital industry including changes in ownership, changes in access to credit, changes in care delivery and changes in choices of community benefit provision", "qid": 48, "docid": "g6m0a6xt", "rank": 93, "score": 0.7404054403305054}, {"content": "Title: Reopening Colleges and Universities During the COVID-19 Pandemic Content: In their article, Cheng and colleagues present the plan for reopening colleges and universities in Taiwan. There are important differences between Taiwan and other countries, but residential colleges and universities present similar challenges to pandemic control for all. Considering how well Taiwan has managed COVID-19 overall, the editorialists believe that the plan for safely reopening colleges and universities in Taiwan offers important principles.", "qid": 48, "docid": "hn4wg94k", "rank": 94, "score": 0.7400314807891846}, {"content": "Title: Clinical nursing and midwifery education in the pandemic age Content: The COVID\u201019 pandemic has disrupted clinical nursing and midwifery education. This disruption has long\u2010term implications for the nursing and midwifery workforce and for future healthcare responses to pandemics. Solutions may include enhanced partnerships between schools of nursing and midwifery and health service providers and including schools of nursing and midwifery in preparedness planning. These suggestions notwithstanding, we call upon national and international nursing and midwifery bodies to study how to further the clinical education of nurses and midwives during pandemics and other times of crisis.", "qid": 48, "docid": "t1birs9w", "rank": 95, "score": 0.7398864030838013}, {"content": "Title: Service-learning in response to the coronavirus disease 2019 pandemic: Emerging lessons from the Department of Family Medicine and Public Health at the University of Botswana Content: The novel coronavirus disease 2019 (COVID-19) pandemic has disrupted many lives worldwide. Training programmes in academic institutions have also been affected by the pandemic. Teaching and learning family medicine and public health medicine in the COVID-19 era require adjustments to training activities. At the University of Botswana, the pandemic presented an opportunity to steer training programmes in the Department of Family Medicine and Public Health Medicine more towards service-learning. The department collaborated with the Ministry of Health and Wellness as well as the District Health Management teams in the national response to the pandemic as essential service providers. The increased demands for service provision were balanced with educational opportunities for trainees during the COVID-19 public health emergency. Including structured ongoing reflections for trainees involved in the COVID-19 response helps to connect service and the academic curriculum. KEYWORDS: COVID-19; coronavirus; service-learning; pandemic; Botswana.", "qid": 48, "docid": "rakobuy1", "rank": 96, "score": 0.7392809391021729}, {"content": "Title: Economic interventions to ameliorate the impact of COVID-19 on the economy and health: an international comparison. Content: BACKGROUND The COVID-19 pandemic continues to challenge governments and policymakers worldwide. They have rightfully prioritised reducing the spread of the virus through social distancing interventions. However, shuttered business and widespread restrictions on travel and mobility have led to an economic collapse with increasing uncertainty of how quickly recovery will be achieved. METHODS The authors carried out a review of publicly available information on the economic intervention's countries have put in place to ameliorate the impact of COVID-19. RESULTS The strategies and scale of economic interventions have been broad, ranging from 2.5% to a reported 50% of Gross Domestic Product. CONCLUSIONS Numerous countries are beginning to ease lockdown restrictions and restart economies in different ways. There is therefore evolving, real-world data that should be used dynamically by governments and policymakers. The strategies on restarting the economy must be balanced against the uncertainty of a possible second wave of COVID-19. A nuanced approach to easing restrictions needs to take into account not only immediate risk to life but longer-term risks of widening inequalities and falling life expectancy.", "qid": 48, "docid": "lgbod553", "rank": 97, "score": 0.7391941547393799}, {"content": "Title: Flexible employment relationships and careers in times of the COVID-19 pandemic Content: Abstract The COVID-19 pandemic represents a crisis that affects several aspects of people's lives around the globe. Most of the affected countries took several measures, like lockdowns, business shutdowns, hygiene regulations, social distancing, school and university closings, or mobility tracking as a means of slowing down the distribution of COVID-19. These measures are expected to show short-term and long-term effects on people's working lives. However, most media reports focused on the effects of the COVID-19 pandemic on changes in work arrangements (e.g., short-time work, flexible location and hours) for workers in a regular employment relationship. We here focus on workers in flexible employment relationships (e.g. temporary agency work and other forms of subcontracted labor, as well as new forms of working, such as in the gig economy). Specifically, we will discuss (a) how the work and careers of individuals in flexible employment relationships might get affected by the COVID-19 pandemic; (b) outline ideas how to examine period effects of the COVID-19 pandemic on the work and careers of those individuals, and (c) outline how the pandemic can contribute to the ramification of flexible employment relationships.", "qid": 48, "docid": "jxzvyfwx", "rank": 98, "score": 0.7390492558479309}, {"content": "Title: Provide and Protect the Essential Components Content: This article takes a look at the current educational climate during the worldwide COVID-19 pandemic, specifically the place that physical education has during this time. It explores the importance of maintaining standards-based learning and the essential components of physical education.", "qid": 48, "docid": "v8bxdyon", "rank": 99, "score": 0.7386389374732971}, {"content": "Title: The Impact of the COVID-19 Pandemic on Fellowship Training: A National Survey of Pediatric Otolaryngology Fellowship Directors Content: OBJECTIVES: To gain a better understanding of the effects the COVID-19 pandemic has had on current and future pediatric otolaryngology fellowship training, as well as how the application process was impacted this past year. METHODS: An anonymous web-based survey consisting of 24 questions was sent to all fellowship directors. The survey questions were designed to gain a better understanding of the effects of the current COVID-19 pandemic on the surgical and clinical experience of current, to characterize the types of supplemental educational experiences that fellowship directors had incorporated into the curriculum to compensate for the decreased surgical and clinical workload, and highlight differences based on geographic location. RESULTS: Overall, 22 of 36 fellowship directors responded to our survey, for a total response rate of 61%. The Midwest had the highest response rate at 72.7%, followed by the Northeast (71.4%), the West (50%), and the South (50%). The vast majority of fellowship directors (77.2%) reported the COVID-19 pandemic had a \u201csignificant impact\u201d on overall pediatric otolaryngology fellowship training. 86.3% of fellowship directors reported that their programs were still performing some surgical operations, but with decreased overall volume. Interestingly, 13.6% of fellowship directors reported that their fellows had been pulled to medicine or ICU services to assist with the COVID-19 pandemic. Of these programs that had a fellow pulled to the ICU or medicine service, 2 out of 3 were located in the Northeast, with the remaining fellow being from a program in the South. CONCLUSION: Overall, pediatric otolaryngology fellowship directors reported the COVID-19 pandemic has had a significant impact on the overall fellowship experience within the field of pediatric otolaryngology, with the majority feeling that both their fellows surgical and clinical experience have been significantly impacted.", "qid": 48, "docid": "q29lgopf", "rank": 100, "score": 0.7378588914871216}]}
{"query": "do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection?", "hits": [{"content": "Title: Long-Term Persistence of Robust Antibody and Cytotoxic T Cell Responses in Recovered Patients Infected with SARS Coronavirus Content: Most of the individuals infected with SARS coronavirus (SARS-CoV) spontaneously recovered without clinical intervention. However, the immunological correlates associated with patients' recovery are currently unknown. In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL) responses. We have found persistence of robust antibody and CTL responses in all of the study subjects throughout the study period, with a moderate decline one year after the onset of symptoms. We have also identified two potential major CTL epitopes in N proteins based on ELISPOT analysis of pooled peptides. However, despite the potent immune responses and clinical recovery, peripheral lymphocyte counts in the recovered patients have not yet been restored to normal levels. In summary, our study has, for the first time, characterized the temporal and dynamic changes of humoral and CTL responses in the natural history of SARS-recovered individuals, and strongly supports the notion that high and sustainable levels of immune responses correlate strongly with the disease outcome. Our findings have direct implications for future design and development of effective therapeutic agents and vaccines against SARS-CoV infection.", "qid": 49, "docid": "itu39mln", "rank": 1, "score": 0.8312669396400452}, {"content": "Title: Breadth of concomitant immune responses underpinning viral clearance and patient recovery in a non-severe case of COVID-19 Content: We report the kinetics of the immune response in relation to clinical and virological features of a patient with mild-to-moderate coronavirus disease-19 (COVID-19) requiring hospitalisation. Increased antibody-secreting cells, follicular T-helper cells, activated CD4+ and CD8+ T-cells and IgM/IgG SARS-CoV-2-binding antibodies were detected in blood, prior to symptomatic recovery. These immunological changes persisted for at least 7 days following full resolution of symptoms, indicating substantial anti-viral immunity in this non-severe COVID-19.", "qid": 49, "docid": "kqanoog7", "rank": 2, "score": 0.8251227140426636}, {"content": "Title: Broad phenotypic alterations and potential dysfunctions of lymphocytes in COVID-19 recovered individuals Content: Background Lymphopenia is a typical symptom in the COVID-19 patients. While millions of patients are clinical recovered, little is known about the immune status of lymphocytes in these individuals. Methods A clinical recovered cohort (CR) of 55 COVID-19 individuals (discharged from hospital 4 to 11 weeks), and 55 age and sex matched healthy donors cohort (HD) were recruited. Detailed analysis on phenotype of the lymphocytes in peripheral blood mononuclear cells (PBMCs) was performed by flow cytometry. Findings Compared with cohort HD, the CD8+ T cells in cohort CR had higher Teff and Tem, but lower Tc1 (IFN-{gamma}+), Tc2 (IL-4+) and Tc17 (IL-17A+) frequencies. The CD4+ T cells of CR had decreased frequency, especially on the Tcm subset. Moreover, CD4+ T cells of CR expressed lower PD-1 and had lower frequencies of Th1 (IFN-{gamma}+), Th2 (IL-4+), Th17 (IL-17A+) as well as circulating Tfh (CXCR5+PD-1+). Accordingly, isotype-switched memory B cell (IgM-CD20hi) in CR had significantly lower proportion in B cells, though level of activation marker CD71 elevated. For CD3-HLA-DRlo lymphocytes of CR, besides levels of IFN-{gamma}, Granzyme B and T-bet were lower, the correlation between T-bet and IFN-{gamma} became irrelevant. In addition, taken into account of discharged days, all the lowered function associated phenotypes showed no recovery tendency within whole observation period. Interpretation The CR COVID-19 individuals still showed remarkable phenotypic alterations in lymphocytes after clinical recovery 4 to 11 weeks. This suggests SARS-CoV-2 infection imprints profoundly on lymphocytes and results in long-lasting potential dysfunctions.", "qid": 49, "docid": "avhxj8jk", "rank": 3, "score": 0.8190624713897705}, {"content": "Title: Relative COVID-19 viral persistence and antibody kinetics Content: Importance: The COVID-19 antibody response is a critical indicator for evaluating immunity and also serves as the knowledge base for vaccine development. The picture is still not clear because of many limitations including testing tools, time of sampling, and the unclear impact of varying clinical status. In addition to these problems, antibody levels may not be equivalent to protective capacity. Objective: To define the key factor for the different patterns of COVID-19 antibody response. Design: We elucidated the antibody response with time-series throat and serum samples for viral loads and antibody levels, then used a neutralization test to evaluate protectiveness. Setting: A medical center that typically cares for patients with moderate to severe diseases. Because of the low prevalence of COVID-19 in Taiwan and local government policy, however, we also admit COVID-19 patients with mild disease or even those without symptoms for inpatient care. Participants: RT-PCR-confirmed COVID-19 patients. Results: We found that only patients with relative persistence of virus at pharynx displayed strong antibody responses that were proportional to the pharyngeal viral load. They also had proportional neutralization titers per unit of serum. Although antibody levels decreased around 2 weeks after symptom onset, the neutralization efficacy per unit antibody remained steady and even continued to increase over time. The antibody response in patients with rapid virus clearance was weak, but the neutralization efficacy per unit antibody in these patients was comparable to those with persistent presence of virus. The deceased were with higher viral load, higher level of antibody, and higher neutralization titers in the serum, but the neutralization capacity per unit antibody is relatively low. Conclusions and Relevance: Strong antibody response depends on the relative persistence of the virus, instead of the absolute virus amount. The antibody response is still weak if large amount of virus is cleared quickly. The neutralization efficacy per unit antibody is comparable between high and low antibody patterns. Strong antibody response contains more inefficient and maybe even harmful antibodies. Low antibody response is also equipped with a capable B cell pool of efficient antibodies, which may expand with next virus encounter and confer protection.", "qid": 49, "docid": "nj5xe91b", "rank": 4, "score": 0.8131424188613892}, {"content": "Title: Reappearance of Effector T Cells Predicts Successful Recovery from COVID-19 Content: Background: Elucidating the role of T cell responses in COVID-19 is of utmost importance to understand the clearance of SARS-CoV-2 infection. Methods: 90 individuals were enrolled in this study, 30 hospitalized COVID-19 patients and 60 age- and gender-matched healthy controls (HC). Using two comprehensive 11-color flow cytometric panels conforming to Good Laboratory Practice (GLP) and approved for clinical diagnostics, we longitudinally examined cell count differences in lymphocyte populations and T cell activation in COVID-19 patients. Findings: Absolute numbers of lymphocyte subsets were differentially decreased in COVID-19 patients according to clinical severity. In severe disease (SD) patients, all lymphocyte subsets were reduced, whilst in mild disease (MD) NK, NKT and {gamma}{delta} T cells were at the level of HC. Additionally, we provide evidence of T cell activation in MD but not SD, when compared to HC. Interestingly, follow up samples revealed a marked increase in effector T cells and memory subsets in convalescing but not in non-convalescing patients. Interpretation: Our data suggest that activation and expansion of innate and adaptive lymphocytes play a major role in COVID-19. Additionally, recovery is associated with formation of T cell memory as suggested by the missing formation of effector and central memory T cells in SD but not in MD. Our data imply that the presence of SARS-CoV-2 responsive T cells contributes to convalescence in MD. Thus, understanding the T cell-response in the context of clinical severity might serve as foundation to overcome the lack of effective anti-viral immune response in severely affected COVID-19 patients and can offer prognostic value as biomarker for disease outcome and control.", "qid": 49, "docid": "5lhvix51", "rank": 5, "score": 0.8129111528396606}, {"content": "Title: Characterization of anti-viral immunity in recovered individuals infected by SARS-CoV-2 Content: The WHO has declared SARS-CoV-2 outbreak a public health emergency of international concern. However, to date, there was hardly any study in characterizing the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. In this study, we collected blood from COVID-19 patients who have recently become virus-free and therefore were discharged, and analyzed their SARS-CoV-2-specific antibody and T cell responses. We observed SARS-CoV-2-specific humoral and cellular immunity in the patients. Both were detected in newly discharged patients, suggesting both participate in immune-mediated protection to viral infection. However, follow-up patients (2 weeks post discharge) exhibited high titers of IgG antibodies, but with low levels of virus-specific T cells, suggesting that they may enter a quiescent state. Our work has thus provided a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It has also implications in designing an effective vaccine to protect and treat SARS-CoV-2 infection.", "qid": 49, "docid": "dptgg05n", "rank": 6, "score": 0.8122602105140686}, {"content": "Title: Serological surveys in Reunion Island of the first hospitalized patients revealed that long-lived immunoglobulin G antibodies specific against SARS-CoV2 virus are rapidly vanishing in severe cases Content: Both cellular and humoral immunities are critically important to control COVID19 infection but little is known about the kinetics of those responses and, in particular, in patients who will go on to develop a severe form of the disease over several weeks. We herein report the first set of data of our prospective cohort study of 90 hospitalized cases. Serological surveys were thoroughly performed over 2 month period by assessing IgG and IgM responses by immunofluorescence, immunoblot, Western blot and conventional ELISA using clinical RUN isolates of SARS-CoV-2 immobilized on 96 well plates. While the IgM and, unexpectedly, the IgG responses were readily detected early during the course of the disease (5-7 days post-first symptoms), our results (n=3-5 and over the full dilution set of the plasma 1/200 to 1/12800) demonstrated a significant decrease (over 2.5-fold) of IgG levels in severe (ICU) hospitalized patients (exemplified in patient 1) by WB and ELISA. In contrast, mild non-ICU patients had a steady and yet robust rise in their specific IgG levels against the virus. Interestingly, both responses (IgM and IgG) were initially against the nucleocapsid (50kDa band on the WB) and spreading to other major viral protein S and domains (S1 and S2. In conclusion, serological testing may be helpful for the diagnosis of patients with negative RT-PCR results and for the identification of asymptomatic cases. Moreover, medical care and protections should be maintained particularly for recovered patients (severe cases) who may remain at risk of relapsing or reinfection. Experiments to ascertain T cell responses but although their kinetics overtime are now highly warranted. All in all, these studies will help to delineate the best routes for vaccination.", "qid": 49, "docid": "4aawkp8p", "rank": 7, "score": 0.8110544681549072}, {"content": "Title: Reappearance of effector T cells is associated with recovery from COVID-19 Content: BACKGROUND: Elucidating the role of T cell responses in COVID-19 is of utmost importance to understand the clearance of SARS-CoV-2 infection. METHODS: 30 hospitalized COVID-19 patients and 60 age- and gender-matched healthy controls (HC) participated in this study. We used two comprehensive 11-colour flow cytometric panels conforming to Good Laboratory Practice and approved for clinical diagnostics. FINDINGS: Absolute numbers of lymphocyte subsets were differentially decreased in COVID-19 patients according to clinical severity. In severe disease (SD) patients, all lymphocyte subsets were reduced, whilst in mild disease (MD) NK, NKT and \u00ce\u00b3\u00ce\u00b4 T cells were at the level of HC. Additionally, we provide evidence of T cell activation in MD but not SD, when compared to HC. Follow up samples revealed a marked increase in effector T cells and memory subsets in convalescing but not in non-convalescing patients. INTERPRETATION: Our data suggest that activation and expansion of innate and adaptive lymphocytes play a major role in COVID-19. Additionally, recovery is associated with formation of T cell memory as suggested by the missing formation of effector and central memory T cells in SD but not in MD. Understanding T cell-responses in the context of clinical severity might serve as foundation to overcome the lack of effective anti-viral immune response in severely affected COVID-19 patients and can offer prognostic value as biomarker for disease outcome and control. FUNDING: Funded by State of Lower Saxony grant 14-76,103-184CORONA-11/20 and German Research Foundation, Excellence Strategy - EXC2155\"RESIST\"-Project ID39087428, and DFG-SFB900/3-Project ID158989968, grants SFB900-B3, SFB900-B8.", "qid": 49, "docid": "871812f7", "rank": 8, "score": 0.8047224283218384}, {"content": "Title: A case report of possible novel coronavirus 2019 reinfection Content: Since December 2019, COVID-19, the clinical syndrome associated with SARS-CoV-2 infection, has infected more than 6.2 million people and brought the function of the global community to a halt. As the number of patients recovered from COVID-19 rises and the world transitions toward reopening, the question of acquired immunity versus the possibility of reinfection are critical to anticipating future viral spread. Here, we present a case of a patient previously recovered from COVID-19 who re-presents with new respiratory, radiographical, laboratory, and RT-PCR findings concerning for re-infection. We review this case in the context of the evolving discussion and theories surrounding dynamic RT-PCR results, prolonged viral shedding, and the possibility of developed immunity.", "qid": 49, "docid": "aed6psww", "rank": 9, "score": 0.8045333027839661}, {"content": "Title: Reappearance of effector T cells is associated with recovery from COVID-19 Content: BACKGROUND: Elucidating the role of T cell responses in COVID-19 is of utmost importance to understand the clearance of SARS-CoV-2 infection. METHODS: 30 hospitalized COVID-19 patients and 60 age- and gender-matched healthy controls (HC) participated in this study. We used two comprehensive 11-colour flow cytometric panels conforming to Good Laboratory Practice and approved for clinical diagnostics. FINDINGS: Absolute numbers of lymphocyte subsets were differentially decreased in COVID-19 patients according to clinical severity. In severe disease (SD) patients, all lymphocyte subsets were reduced, whilst in mild disease (MD) NK, NKT and \u03b3\u03b4 T cells were at the level of HC. Additionally, we provide evidence of T cell activation in MD but not SD, when compared to HC. Follow up samples revealed a marked increase in effector T cells and memory subsets in convalescing but not in non-convalescing patients. INTERPRETATION: Our data suggest that activation and expansion of innate and adaptive lymphocytes play a major role in COVID-19. Additionally, recovery is associated with formation of T cell memory as suggested by the missing formation of effector and central memory T cells in SD but not in MD. Understanding T cell-responses in the context of clinical severity might serve as foundation to overcome the lack of effective anti-viral immune response in severely affected COVID-19 patients and can offer prognostic value as biomarker for disease outcome and control. FUNDING: Funded by State of Lower Saxony grant 14\u201376,103\u2013184CORONA-11/20 and German Research Foundation, Excellence Strategy \u2013 EXC2155\u201cRESIST\u201d\u2013Project ID39087428, and DFG-SFB900/3\u2013Project ID158989968, grants SFB900-B3, SFB900-B8.", "qid": 49, "docid": "9iuesnxo", "rank": 10, "score": 0.8042854070663452}, {"content": "Title: Deep immune profiling of COVID-19 patients reveals patient heterogeneity and distinct immunotypes with implications for therapeutic interventions Content: COVID-19 has become a global pandemic. Immune dysregulation has been implicated, but immune responses remain poorly understood. We analyzed 71 COVID-19 patients compared to recovered and healthy subjects using high dimensional cytometry. Integrated analysis of ~200 immune and >30 clinical features revealed activation of T cell and B cell subsets, but only in some patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses could reach >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable to uninfected subjects. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. These analyses identified three \u201cimmunotypes\u201d associated with poor clinical trajectories versus improving health. These immunotypes may have implications for therapeutics and vaccines.", "qid": 49, "docid": "wcmxmahq", "rank": 11, "score": 0.8013233542442322}, {"content": "Title: A possible role of immunopathogenesis in COVID-19 progression Content: Background: The efficacy of the humoral and cellular immunity determines the outcome of viral infections. An appropriate immune response mediates protection, whereas an overwhelming immune response has been associated with immune-mediated pathogenesis in viral infections. The current study explored the general and SARS-CoV-2 specific cellular and humoral immune status in patients with different COVID-19 severities. Methods: In this prospective study, we included 53 patients with moderate, severe, and critical COVID-19 manifestations comparing their quantitative, phenotypic, and functional characteristics of circulating immune cells, SARS-CoV-2 antigen specific T-cells, and humoral immunity. Results: Significantly diminished frequencies of CD8+T-cells, CD4+ and CD8+T-cell subsets with activated differentiated memory/effector phenotype and migratory capacity were found in circulation in patients with severe and/or critical COVID-19 as compared to patients with moderate disease. Importantly, the improvement of the clinical courses from severe to moderate was accompanied by an improvement in the T-cell subset alterations. Furthermore, we surprisingly observed a detectable SARS-CoV-2-reactive T-cell response in all three groups after stimulation with SARS-CoV-2 S-protein overlapping peptide pool already at the first visit. Of note, patients with a critical COVID-19 demonstrated a stronger response of SARS-CoV-2-reactive T-cells producing Th1 associated inflammatory cytokines. Furthermore, clear correlation between antibody titers and SARS-CoV-2-reactive CD4+ frequencies underscore the role of specific immunity in disease progression. Conclusion: Our data demonstrate that depletion of activated memory phenotype circulating T-cells and a strong SARS-CoV-2-specific cellular and humoral immunity are associated with COVID-19 disease severity. This counter-intuitive finding may have important implications for diagnostic, therapeutic and prophylactic COVID-19 management.", "qid": 49, "docid": "in91dr4g", "rank": 12, "score": 0.7978606820106506}, {"content": "Title: Reduction and Functional Exhaustion of T Cells in Patients with Coronavirus Disease 2019 (COVID-19) Content: BACKGROUND The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health, which has been declared a public health emergency of international concern (PHEIC) by the WHO. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. METHODS We retrospectively reviewed the counts of total T cells, CD4+, CD8+ T cell subsets, and serum cytokine concentration from inpatient data of 522 patients with laboratory-confirmed COVID-19, admitted into two hospitals in Wuhan from December 2019 to January 2020, and 40 healthy controls, who came to the hospitals for routine physical examination. In addition, the expression of T cell exhaustion markers PD-1 and Tim-3 were measured by flow cytometry in the peripheral blood of 14 COVID-19 cases. RESULTS The number of total T cells, CD4+ and CD8+ T cells were dramatically reduced in COVID-19 patients, especially among elderly patients (\u226560 years of age) and in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8+T cells or CD4+T cells lower than 800/\u03bcL, 300/\u03bcL, or 400/\u03bcL, respectively, are negatively correlated with patient survival. Statistical analysis demonstrated that T cell numbers are negatively correlated to serum IL-6, IL-10 and TNF-\u03b1 concentration, with patients in decline period showing reduced IL-6, IL-10 and TNF-\u03b1 concentrations and restored T cell counts. Finally, T cells from COVID-19 patients have significantly higher levels of the exhausted marker PD-1 as compared to health controls. Moreover, increasing PD-1 and Tim-3 expression on T cells could be seen as patients progressed from prodromal to overtly symptomatic stages, further indicative of T cell exhaustion. CONCLUSIONS T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients, with total T cells, CD8+T cells CD4+T cells counts lower than 800/\u03bcL, 300/\u03bcL, and 400/\u03bcL, respectively, may still require aggressive intervention even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.", "qid": 49, "docid": "yj25zkx6", "rank": 13, "score": 0.7976280450820923}, {"content": "Title: A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease Content: The duration and nature of immunity generated in response to SARS-CoV-2 infection is unknown. Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARSCoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The timescale of protection is a critical determinant of the future impact of the pathogen. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. The dynamics of immunity and nature of protection are relevant to discussions surrounding therapeutic use of convalescent sera as well as efforts to identify individuals with protective immunity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV-1, MERS-CoV and human endemic coronaviruses (HCoVs). We reviewed 1281 abstracts and identified 322 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While studies of SARS-CoV-2 are necessary to determine immune responses to it, evidence from other coronaviruses can provide clues and guide future research.", "qid": 49, "docid": "yzffm05r", "rank": 14, "score": 0.7975270748138428}, {"content": "Title: Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19) Content: Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. Methods: We retrospectively reviewed the counts of T cells and serum cytokine concentration from data of 522 patients with laboratory-confirmed COVID-19 and 40 healthy controls. In addition, the expression of T cell exhaustion markers were measured in 14 COVID-19 cases. Results: The number of total T cells, CD4+ and CD8+ T cells were dramatically reduced in COVID-19 patients, especially in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8+ T cells or CD4+ T cells lower than 800, 300, or 400/\u00b5L, respectively, were negatively correlated with patient survival. T cell numbers were negatively correlated to serum IL-6, IL-10, and TNF-&#945; concentration, with patients in the disease resolution period showing reduced IL-6, IL-10, and TNF-&#945; concentrations and restored T cell counts. T cells from COVID-19 patients had significantly higher levels of the exhausted marker PD-1. Increasing PD-1 and Tim-3 expression on T cells was seen as patients progressed from prodromal to overtly symptomatic stages. Conclusions: T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients with total T cells counts lower than 800/\u00b5L may still require urgent intervention, even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.", "qid": 49, "docid": "gqdyddtg", "rank": 15, "score": 0.796183705329895}, {"content": "Title: Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals Content: Summary The World Health Organization has declared SARS-CoV-2 virus outbreak a world-wide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in 8 newly discharged patients. Follow-up analysis on another cohort of 6 patients 2 weeks post discharge also revealed high titers of IgG antibodies. In all 14 patients tested, 13 displayed serum neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It has also implications in developing an effective vaccine to SARS-CoV-2 infection.", "qid": 49, "docid": "0tn06al2", "rank": 16, "score": 0.7954702377319336}, {"content": "Title: Clinical Characteristics on 25 Discharged Patients with COVID-19 Virus Returning Content: Here we report the clinical features of 25 discharged patients with COVID-19 recovery. Our analysis indicated that there was a significant inverse correlation existed between serum D-Dimer level and the duration of antiviral treatment, while lymphocyte concentration significantly positively correlated with the duration of virus reversal.", "qid": 49, "docid": "jarnavwl", "rank": 17, "score": 0.7944605350494385}, {"content": "Title: Clinical Characteristics of Re\u2010hospitalized Patients with COVID\u201019 in China Content: BACKGROUND: This study aims to observe the clinical characteristics of recovered patients from Coronavirus Disease 2019 (COVID 19) with positive in RT\u2010PCR or serum antibody. METHODS: The profile, clinical symptoms, laboratory outcomes and radiologic assessments were extracted on 11 patients, who tested positive for COVID\u201019 with RT\u2010PCR or serum antibody after discharged and was admitted to Hubei No. 3 People's Hospital of Jianghan University for a second treatment in March 2020. RESULTS: The average interval time between the first discharge and the second admission measured 16.00 \u00b1 7.14 days, ranging from 6 to 27 days. In the second hospitalization, 1 patient was positive for RT\u2010PCR and serum antibody IgM\u2010IgG, 5 patients were positive for both IgM and IgG but negative for RT\u2010PCR. 3 patients were positive for both RT\u2010PCR and IgG but negative for IgM. The main symptoms were cough (54.5%), fever (27.3%) and feeble (27.3%) in the second hospitalization. Compared with the first hospitalization, there were significant decreases in gastrointestinal symptoms (5 vs. 0, P=0.035), elevated levels of both white blood cell count(P=0.036) and lymphocyte count (P=0.002), remarkedly decreases in CRP and SAA (P<0.05) in the second hospitalization. Additionally, 6 patients' chest CT exhibited notable improvements in acute exudative lesions CONCLUSION: There could be the positive results for RT\u2010PCR analysis or serum IgM\u2010IgG in discharged patients, even with mild clinical symptoms, however, their laboratory outcomes and chest CT images would not indicate the on\u2010going development in those patients. This article is protected by copyright. All rights reserved.", "qid": 49, "docid": "f6xlfc7d", "rank": 18, "score": 0.794437050819397}, {"content": "Title: Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19) Content: Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. Methods: We retrospectively reviewed the counts of T cells and serum cytokine concentration from data of 522 patients with laboratory-confirmed COVID-19 and 40 healthy controls. In addition, the expression of T cell exhaustion markers were measured in 14 COVID-19 cases. Results: The number of total T cells, CD4(+) and CD8(+) T cells were dramatically reduced in COVID-19 patients, especially in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8(+) T cells or CD4(+) T cells lower than 800, 300, or 400/\u03bcL, respectively, were negatively correlated with patient survival. T cell numbers were negatively correlated to serum IL-6, IL-10, and TNF-\u03b1 concentration, with patients in the disease resolution period showing reduced IL-6, IL-10, and TNF-\u03b1 concentrations and restored T cell counts. T cells from COVID-19 patients had significantly higher levels of the exhausted marker PD-1. Increasing PD-1 and Tim-3 expression on T cells was seen as patients progressed from prodromal to overtly symptomatic stages. Conclusions: T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients with total T cells counts lower than 800/\u03bcL may still require urgent intervention, even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.", "qid": 49, "docid": "aqcllik0", "rank": 19, "score": 0.7941968441009521}, {"content": "Title: Protective immunity after COVID-19 has been questioned: what can we do without SARS-CoV-2-IgG detection? Content: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a severe acute respiratory syndrome that is called COVID-19. Clinical manifestations of COVID-19 include diarrhea, pneumonia, lymphopenia, exhausted lymphocytes, and pro-inflammatory cytokine production. Immunology is part of the process of clinical evolution, but there are some questions around immunity-based protection: (1) why some infected people have only mild symptoms of the disease or are asymptomatic; (2) why delayed and weak antibody responses are associated with severe outcomes; and (3) why positivity in molecular tests does not represent protective antibody IgG. Perhaps T cell responses may be the key to solving those questions. SARS-CoV-2-specific memory T cells persist in peripheral blood and may be capable of providing effective information about protective immunity. The T cells studies can be helpful in elucidating the pathways for development of vaccines, therapies, and diagnostics for COVID-19 and for filling these immunology knowledge gaps.", "qid": 49, "docid": "rsz7ch2a", "rank": 20, "score": 0.7930746078491211}, {"content": "Title: Longitudinal hematologic and immunologic variations associated with the progression of COVID-19 patients in China Content: Background Crucial roles of hematologic and immunologic responses in progression of COVID-19 remains largely unclear. Objective We sought to address the dynamic changes of hematologic and immunologic biomarkers and their associations with severity and outcomes of the disease. Methods A retrospective study including 548 COVID-19 patients with clarified outcome (discharged or deceased) from a national cohort in China was performed. Cross-sectional and longitudinal variations were compared and the associations with different severity and outcomes were analyzed. Results On admission, the counts of lymphocytes, T cell subsets, eosinophils and platelets decreased markedly, especially in severe/critical and fatal patients. Increased neutrophil count and neutrophils-to-lymphocytes ratio were predominant in severe/critical cases or non-survivors. During hospitalization, eosinophils, lymphocytes and platelets were shown an increasing trend in survivors, but maintained lower levels or dropped significantly afterwards in non-survivors. Non-survivors kept high level or showed an upward trend for neutrophils, IL-6, procalcitonin, D-dimer, amyloid A protein and C-reactive protein, which were kept stable or shown downward trend in survivors. Positive correlation between CD8+ T cell and lymphocytes count was found in survivors but not in non-survivors. A multivariate Cox regression model suggested that restored levels of lymphocytes, eosinophils and platelets could serve as the predictors for the recovery, while progressive increases in neutrophils, basophils and IL-6 were associated with fatal outcome. Conclusions Hematologic and immunologic impairment showed a significantly different profile between survivors and non-survivors in COVID-19 patients with different severity. The longitudinal variations of these biomarkers could serve to predict recovery or fatal outcome.", "qid": 49, "docid": "mfaza5rg", "rank": 21, "score": 0.7921484708786011}, {"content": "Title: Clinical characteristics of rehospitalized patients with COVID-19 in China Content: This study aims to observe the clinical characteristics of recovered patients from Coronavirus Disease 2019 (COVID-19) with positive in reverse transcription-polymerase chain reaction (RT-PCR) or serum antibody. The profile, clinical symptoms, laboratory outcomes, and radiologic assessments were extracted on 11 patients, who tested positive for COVID-19 with RT-PCR or serum antibody after discharged and was admitted to Hubei No. 3 People's Hospital of Jianghan University for a second treatment in March 2020. The average interval time between the first discharge and the second admission measured 16.00 \u00b1 7.14 days, ranging from 6 to 27 days. In the second hospitalization, one patient was positive for RT-PCR and serum antibody immunoglobulin M (IgM)-immunoglobulin G (IgG), five patients were positive for both IgM and IgG but negative for RT-PCR. Three patients were positive for both RT-PCR and IgG but negative for IgM. The main symptoms were cough (54.55%), fever (27.27%), and feeble (27.27%) in the second hospitalization. Compared with the first hospitalization, there were significant decreases in gastrointestinal symptoms (5 vs 0, P = .035), elevated levels of both white blood cell count (P = .036) and lymphocyte count (P = .002), remarkedly decreases in C-reactive protein and serum amyloid A (P < .05) in the second hospitalization. Additionally, six patients' chest computed tomography (CT) exhibited notable improvements in acute exudative lesions. There could be positive results for RT-PCR analysis or serum IgM-IgG in discharged patients, even with mild clinical symptoms, however, their laboratory outcomes and chest CT images would not indicate the on-going development in those patients.", "qid": 49, "docid": "evonlumf", "rank": 22, "score": 0.7920801639556885}, {"content": "Title: In-depth phenotyping of human peripheral blood mononuclear cells in convalescent COVID-19 patients following a mild versus severe disease course Content: Background: Covid-19, the disease caused by infection with SARS-CoV-2, has developed to a pandemic causing more than 239, 000 deaths worldwide as of 6th May according to the World Health Organization (WHO). It presents with a highly variable disease course ranging from a large proportion of asymptomatic cases to severe respiratory failure in 17-29% of cases even in the absence of apparent comorbidities 1, 2. This implies a diverse host immune response to SARS-CoV-2. The immunological characteristics underlying these divergent disease courses, however, still remain elusive. While insights into abrogations of innate immunity begin to emerge, adaptive immune responses towards SARS-CoV-2 are poorly investigated, although they serve as immune signatures of protection and vaccine responses. We therefore set out to characterize immune signatures of convalescent COVID-19 patients stratified according to their disease severity. Methods: We performed high-dimensional flow cytometric profiling of peripheral blood mononuclear cells of convalescent COVID-19 patients who we stratified according to their disease severity by a physician-assisted questionnaire based assessment of COVID-19 symptoms. Results: Surprisingly, we did not observe any difference in the relative proportions of any major immune cell type in convalescent patients presenting with different severity of COVID-19 disease except for a reduction in monocytes. The frequency of Tnaive T cells was significantly reduced in CD4+ and CD8+ T cells, whereas other T cell differentiations states (TCM, TEM, TEMRA) remained relatively unaffected by COVID-19 severity as assessed approximately two weeks after infection. Conclusions In our COVID-19 patient cohort, which is characterized by absence of comorbidities and therapeutic interventions other than symptomatic antipyretics, the immunophenotype is similar irrespective of a highly variable disease severity. Convalescence is therefore associated with a rather uniform immune signature. Abrogations, which were previously identified in the innate and adaptive immune compartment of COVID-19 patients should be scrutinized for direct associations with a preconditioned immune system shaped and made vulnerable for SARS-CoV-2 by preexisting comorbidities.", "qid": 49, "docid": "j008qh26", "rank": 23, "score": 0.7920682430267334}, {"content": "Title: Restoration of leukomonocyte counts is associated with viral clearance in COVID-19 hospitalized patients Content: Background: Viral clearance is one important indicator for the recovery of SARS-CoV-2 infected patients. Suboptimal T and B cell responses can delay viral clearance in MERS and SARS patients. The role of leukomonocytes in viral clearance of COVID-19 patients is not yet well defined.Methods: From January 26 to February 28, 2020, an observational study was launched at Zhongnan Hospital of Wuhan University, Wuhan, China. We enrolled 25 laboratory-confirmed COVID-19 patients, whose throat-swab specimens were tested positive for SARS-CoV-2 infection by qRT-PCR. We comprehensively analyzed clinical records, counts of lymphocyte subsets including CD3+, CD4+, CD8+ T cells, B cells and NK cells in the patients who successfully cleared SARS-CoV-2, and compared to those that failed to, after a standardized treatment of 8-14 days. Findings: In 25 enrolled COVID-19 patients, lymphopeniawas a common feature. After the treatment, 14 patients were tested negative for SARS-CoV-2. The patients that cleared the infection had restored the numbers of CD3+, CD4+, CD8+ T cellsand B cells as compared to the still viral RNA positive patients, while the recovered patients had a higher count of leukomonocytes. Conclusions: By comparison of leukomonocytes counts in COVID-19 patients at different stages of the disease, we found that CD3+, CD4+, CD8+ T cells and B cells appear to play important roles in viral clearance. The restoration of leukomonocytes counts from peripheral blood can be used as prognosis for the recovery of an COVID-19 infection. We propose that restoration of leukomonocytes counts can be added to the COVID-19 diagnostic guidanceas a criterion for releasing and discharging patients.", "qid": 49, "docid": "cv32u0ox", "rank": 24, "score": 0.7913807034492493}, {"content": "Title: The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic. Content: BACKGROUND: : SARS-CoV-2 viral infection causes COVID-19 that can result in severe acute respiratory distress syndrome (ARDS), which can cause significant mortality, leading to concern that immunosuppressive treatments for multiple sclerosis and other disorders have significant risks for both infection and ARDS. OBJECTIVE: : To examine the biology that potentially underpins immunity to the SARS-Cov-2 virus and the immunity-induced pathology related to COVID-19 and determine how this impinges on the use of current disease modifying treatments in multiple sclerosis. OBSERVATIONS: : Although information about the mechanisms of immunity are scant, it appears that monocyte/macrophages and then CD8 T cells are important in eliminating the SARS-CoV-2 virus. This may be facilitated via anti-viral antibody responses that may prevent re-infection. However, viral escape and infection of leucocytes to promote lymphopenia, apparent CD8 T cell exhaustion coupled with a cytokine storm appears to contribute to the damage in ARDS. IMPLICATIONS: : In contrast to ablative haematopoietic stem cell therapy, most multiple-sclerosis-related disease modifying therapies do not particularly target the innate immune system and few have any major long-term impact on CD8 T cells to limit protection against COVID-19. In addition, few block the formation of immature B cells within lymphoid tissue that will provide antibody-mediated protection from (re)infection. However, adjustments to dosing schedules may help de-risk the chance of infection further and reduce the concerns of people with MS being treated during the COVID-19 pandemic.", "qid": 49, "docid": "mpf6lxxr", "rank": 25, "score": 0.7900691628456116}, {"content": "Title: Detection of SARS-CoV-2-Specific Humoral and Cellular Immunity in COVID-19 Convalescent Individuals Content: The World Health Organization has declared SARS-CoV-2 virus outbreak a worldwide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free, and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in eight newly discharged patients. Follow-up analysis on another cohort of six patients 2 weeks post discharge also revealed high titers of immunoglobulin G (IgG) antibodies. In all 14 patients tested, 13 displayed serum-neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It also has implications in developing an effective vaccine to SARS-CoV-2 infection.", "qid": 49, "docid": "53j3ly3v", "rank": 26, "score": 0.7897263765335083}, {"content": "Title: Clinical features of COVID\u201019 convalescent patients with re\u2010positive nucleic acid detection Content: BACKGROUND: Coronavirus disease 2019 (COVID\u201019) is a pandemic that has rapidly spread worldwide. Increasingly, confirmed patients being discharged according to the current diagnosis and treatment protocols, follow\u2010up of convalescent patients is important to knowing about the outcome. METHODS: A retrospective study was performed among 98 convalescent patients with COVID\u201019 in a single medical center. The clinical features of patients during their hospitalization and 2\u2010week postdischarge quarantine were collected. RESULTS: Among the 98 COVID\u201019 convalescent patients, 17 (17.3%) were detected positive severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) nucleic acid during 2\u2010week postdischarge quarantine. The median time from discharge to SARS\u2010CoV\u20102 nucleic acid re\u2010positive was 4 days (IQR, 3\u20108.5).The median time from symptoms onset to final respiratory SARS\u2010CoV\u20102 detection of negative result was significantly longer in re\u2010positive group (34 days [IQR, 29.5\u201042.5]) than in non\u2010re\u2010positive group (19 days [IQR, 16\u201026]). On the other hand, the levels of CD3\u2010CD56 + NK cells during hospitalization and 2\u2010week postdischarge were higher in re\u2010positive group than in non\u2010re\u2010positive group (repeated measures ANOVA, P = .018). However, only one case in re\u2010positive group showed exudative lesion recurrence in pulmonary computed tomography (CT) with recurred symptoms. CONCLUSION: It is still possible for convalescent patients to show positive for SARS\u2010CoV\u20102 nucleic acid detection, but most of the re\u2010positive patients showed no deterioration in pulmonary CT findings. Continuous quarantine and close follow\u2010up for convalescent patients are necessary to prevent possible relapse and spread of the disease to some extent.", "qid": 49, "docid": "g5kbgymf", "rank": 27, "score": 0.7892336845397949}, {"content": "Title: SARS-CoV-2 epitopes are recognized by a public and diverse repertoire of human T-cell receptors Content: Understanding the determinants of adaptive immune response to SARS-CoV-2 is critical for fighting the ongoing COVID-19 pandemic. Here we assayed both antibody and T-cell reactivity to SARS-CoV-2 antigens in COVID-19 convalescent patients and healthy donors sampled before and during the pandemic. Our results show that while anti-SARS-CoV-2 antibodies can distinguish convalescent patients from healthy donors, the magnitude of T-cell response was more pronounced in healthy donors sampled during COVID-19 pandemic than in donors sampled before the outbreak. This hints at the possibility that some individuals have encountered the virus but were protected by T-cell cross-reactivity observed. A public and diverse T-cell response was observed for two A*02-restricted SARS-CoV-2 epitopes, revealing a set of T-cell receptor motifs displaying germline-encoded features. Bulk CD4+ and CD8+ T-cell response to SARS-CoV-2 glycoprotein S is characterized by multiple groups of homologous T-cell receptor sequences some of which are shared across multiple donors, indicating the existence of immunodominant epitopes. Overall, our findings indicate that T cells form an efficient response to SARS-CoV-2 and alongside the antibodies can serve as a useful biomarker for surveying SARS-CoV-2 exposure and immunity. We hope that data, including the set of specific T-cell receptors identified in this study can serve as a basis for future developments of SARS-CoV-2 vaccinations and monitoring.", "qid": 49, "docid": "ioihqf0r", "rank": 28, "score": 0.7890371084213257}, {"content": "Title: The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic Content: BACKGROUND: SARS-CoV-2 viral infection causes COVID-19 that can result in severe acute respiratory distress syndrome (ARDS), which can cause significant mortality, leading to concern that immunosuppressive treatments for multiple sclerosis and other disorders have significant risks for both infection and ARDS. OBJECTIVE: To examine the biology that potentially underpins immunity to the SARS-Cov-2 virus and the immunity-induced pathology related to COVID-19 and determine how this impinges on the use of current disease modifying treatments in multiple sclerosis. OBSERVATIONS: Although information about the mechanisms of immunity are scant, it appears that monocyte/macrophages and then CD8 T cells are important in eliminating the SARS-CoV-2 virus. This may be facilitated via anti-viral antibody responses that may prevent re-infection. However, viral escape and infection of leucocytes to promote lymphopenia, apparent CD8 T cell exhaustion coupled with a cytokine storm and vascular pathology appears to contribute to the damage in ARDS. IMPLICATIONS: In contrast to ablative haematopoietic stem cell therapy, most multiple-sclerosis-related disease modifying therapies do not particularly target the innate immune system and few have any major long-term impact on CD8 T cells to limit protection against COVID-19. In addition, few block the formation of immature B cells within lymphoid tissue that will provide antibody-mediated protection from (re)infection. However, adjustments to dosing schedules may help de-risk the chance of infection further and reduce the concerns of people with MS being treated during the COVID-19 pandemic.", "qid": 49, "docid": "j67b1leq", "rank": 29, "score": 0.7885260581970215}, {"content": "Title: Intrafamilial Exposure to SARS-CoV-2 Induces Cellular Immune Response without Seroconversion Content: Background. In the background of the current COVID-19 pandemic, serological tests are being used to assess past infection and immunity against SARS-CoV-2. This knowledge is paramount to determine the transmission dynamics of SARS-CoV-2 through the post pandemic period. Several individuals belonging to households with an index COVID-19 patient, reported symptoms of COVID-19 but discrepant serology results. Methods. Here we investigated the humoral and cellular immune responses against SARS-CoV-2 in seven families, including nine index patients and eight contacts, who had evidence of serological discordances within the households. Ten unexposed healthy donors were enrolled as controls. Results. All index patients recovered from a mild COVID-19. They all developed anti-SARS-CoV-2 antibodies and a significant T cell response detectable up to 69 days after symptom onset. Six of the eight contacts reported COVID-19 symptoms within 1 to 7 days after the index patients but all were SARS-CoV-2 seronegative. Six out of eight contacts developed a SARS-CoV-2-specific T cell response against structural and/or accessory proteins that lasts up to 80 days post symptom onset suggesting a past SARS-CoV-2 infection. Conclusion. Exposure to SARS-CoV-2 can induce virus-specific T cell responses without seroconversion. T cell responses may be more sensitive indicators of SARS-Co-V-2 exposure than antibodies. Our results indicate that epidemiological data relying only on the detection of SARS-CoV-2 antibodies may lead to a substantial underestimation of prior exposure to the virus", "qid": 49, "docid": "eml8uilb", "rank": 30, "score": 0.7879117727279663}, {"content": "Title: Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure Content: Summary Proper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7\u20138 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. All patients with SRF displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen D related (HLA-DR) expression accompanied by profound depletion of CD4 lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Tumor necrosis factor-\u03b1 (TNF-\u03b1) and interleukin-6 (IL-6) production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza. SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab; off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes. Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation.", "qid": 49, "docid": "e9mepqvn", "rank": 31, "score": 0.787516176700592}, {"content": "Title: Longitudinal immune profiling reveals distinct features of COVID-19 pathogenesis Content: Background The pathogenesis of COVID-19, caused by a novel strain of coronavirus (SARS-CoV-2), involves a complex host-virus interaction and is characterised by an exaggerated immune response, the specific components of which are poorly understood. Here we report the outcome of a longitudinal immune profiling study in hospitalised patients during the peak of the COVID-19 pandemic in the UK and show the relationship between immune responses and severity of the clinical presentation. Methods The Coronavirus Immune Response and Clinical Outcomes (CIRCO) study was conducted at four hospitals in Greater Manchester. Patients with SARS-CoV-2 infection, recruited as close to admission as possible, provided peripheral blood samples at enrolment and sequentially thereafter. Fresh samples were assessed for immune cells and proteins in whole blood and serum. Some samples were also stimulated for 3 hours with LPS and analysed for intracellular proteins. Results were stratified based on patient-level data including severity of symptoms and date of reported symptom onset. Findings Longitudinal analysis showed a very high neutrophil to T cell ratio and abnormal activation of monocytes in the blood, which displayed high levels of the cell cycle marker, Ki67 and low COX-2. These properties all reverted in patient with good outcome. Unexpectedly, multiple aspects of inflammation were diminished as patients progressed in severity and time, even in ITU patients not recovering. Interpretation This is the first detailed longitudinal analysis of COVID-19 patients of varying severity and outcome, revealing common features and aspects that track with severity. Patients destined for a severe outcome can be identified at admission when still displaying mild-moderate symptoms. We provide clues concerning pathogenesis that should influence clinical trials and therapeutics. Targeting pathways involved in neutrophil and monocyte release from the bone marrow should be tested in patients with COVID-19. Funding: The Kennedy Trust for Rheumatology Research, The Wellcome Trust, The Royal Society, The BBSRC, National Institute for Health Research (NIHR) Biomedical Research Centres (BRC).", "qid": 49, "docid": "p3st70u3", "rank": 32, "score": 0.7874457836151123}, {"content": "Title: Clinical features of COVID-19 convalescent patients with re-positive nucleic acid detection Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) is a pandemic that has rapidly spread worldwide. Increasingly, confirmed patients being discharged according to the current diagnosis and treatment protocols, follow-up of convalescent patients is important to knowing about the outcome. METHODS: A retrospective study was performed among 98 convalescent patients with COVID-19 in a single medical center. The clinical features of patients during their hospitalization and 2-week postdischarge quarantine were collected. RESULTS: Among the 98 COVID-19 convalescent patients, 17 (17.3%) were detected positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid during 2-week postdischarge quarantine. The median time from discharge to SARS-CoV-2 nucleic acid re-positive was 4 days (IQR, 3-8.5).The median time from symptoms onset to final respiratory SARS-CoV-2 detection of negative result was significantly longer in re-positive group (34 days [IQR, 29.5-42.5]) than in non-re-positive group (19 days [IQR, 16-26]). On the other hand, the levels of CD3-CD56 + NK cells during hospitalization and 2-week postdischarge were higher in re-positive group than in non-re-positive group (repeated measures ANOVA, P = .018). However, only one case in re-positive group showed exudative lesion recurrence in pulmonary computed tomography (CT) with recurred symptoms. CONCLUSION: It is still possible for convalescent patients to show positive for SARS-CoV-2 nucleic acid detection, but most of the re-positive patients showed no deterioration in pulmonary CT findings. Continuous quarantine and close follow-up for convalescent patients are necessary to prevent possible relapse and spread of the disease to some extent.", "qid": 49, "docid": "xybs5b24", "rank": 33, "score": 0.7871095538139343}, {"content": "Title: Recurrent pneumonia in a patient with new coronavirus infection after discharge from hospital for insufficient antibody production: a case report Content: BACKGROUND: The rapid spread of coronavirus disease 2019 (COVID-19) was declared as an emerging public health threat by the World Health Organization. As various measures have been taken successfully to combat the epidemic caused by SARS-CoV-2, a growing number of fully recovered patients have been discharged from hospitals. However, some of them have relapsed. Little is known about the causes that triggered the relapse. CASE PRESENTATION: We report a case of a 40 years old man who suffered from recurrent pulmonary infection with progression of lesions on chest computed tomography (CT), elevated levels of ferritin and IL2R, reduced lymphocyte count and positive oropharyngeal swab test for SARS-CoV-2 again after 5 days discharge from hospital. The anti-SARS-CoV-2 antibody level of this patient was very low at the time of relapse, suggesting a weak humoral immune response to the virus. Total exon sequencing revealed mutations in TRNT1 gene, which may be responsible for B cell immunodeficiency. Therefore, uncleared SARS-CoV-2 at his first discharge was likely to lead to his recurrence. However, viral superinfection and non-infectious organizing pneumonia could not be completely excluded. CONCLUSION: COVID-19 relapse may occur in a part of discharged patients with low titers of anti-SARS-CoV-2 antibodies. These patients should be maintained in isolation for longer time even after discharge. A more sensitive method to detect SARS-CoV-2 needs to be established and serological testing for specific antibodies may be used as a reference to determine the duration of isolation.", "qid": 49, "docid": "vsh9rdct", "rank": 34, "score": 0.786145806312561}, {"content": "Title: Industry call for covid-19 convalescent plasma collections Content: ABSTRACT Plasma of individuals recovered from COVID-19 is needed to address the immediate demand for treatment of SARS-CoV-2 infected patients in severe conditions This communication: highlights the need for COVID-19 convalescent plasma collections to manufacture hyperimmune immunoglobulin therapies, which take months to develop;advocates for the collection of convalescent plasma from asymptomatic donors who tested positive for SARS-CoV-2 virus but did not develop symptoms of the disease;and suggests to use convalescent plasma for transfusion as well as future hyperimmune immunoglobulins as pre- and post-exposure prophylactic treatments for individuals with high risks of exposure to the virus or contracting severe disease", "qid": 49, "docid": "zf4kwm1i", "rank": 35, "score": 0.7860252857208252}, {"content": "Title: The first, holistic immunological model of COVID-19: Implications for prevention, diagnosis, and public health measures Content: The natural history of COVID-19 caused by SARS-CoV-2 is extremely variable, ranging from asymptomatic or mild infection, mainly in children, to multi-organ failure, eventually fatal, mainly in the eldest. We propose here the first model explaining how the outcome of first, crucial 10-15 days after infection, depends on the balance between the cumulative dose of viral exposure and the efficacy of the local innate immune response (natural IgA and IgM antibodies, mannose-binding lectin). If SARS-CoV-2 runs the blockade of this innate immunity and spreads from the upper airways to the alveoli in the early phases of the infections, it can replicate with no local resistance, causing pneumonia and releasing high amounts of antigens. The delayed and strong adaptive immune response (high-affinity IgM and IgG antibodies) that follows, causes severe inflammation and triggers mediator cascades (complement, coagulation, and cytokine storm), leading to complications often requiring intensive therapy and being, in some patients, fatal. Low-moderate physical activity can still be recommended. However, extreme physical activity and oral breathing with hyperventilation during the incubation days and early stages of COVID-19 facilitates re-inhalation and early direct penetration of high numbers of own virus particles in the lower airways and the alveoli, without impacting on the airway's mucosae covered by neutralizing antibodies (\"viral auto-inhalation\" phenomenon). This allows the virus to bypass the efficient immune barrier of the upper airway mucosa in already infected, young, and otherwise healthy athletes. In conclusion, whether the virus or the adaptive immune response reaches the lungs first is a crucial factor deciding the fate of the patient. This \"quantitative and time-/sequence-dependent\" model has several implications for prevention, diagnosis, and therapy of COVID-19 at all ages.", "qid": 49, "docid": "ablxevct", "rank": 36, "score": 0.7859219312667847}, {"content": "Title: Complex Immune Dysregulation in Covid-19 Patients with Severe Respiratory Failure Content: Proper management of COVID-19 mandates better understanding of disease pathogenesis The sudden clinical deterioration 7-8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF All SRF patients displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen (HLA)-DR expression accompanied by profound depletion of CD4-lymphocytes, CD19- lymphocytes and natural killer cells TNF\u03b1 and IL-6 production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab;off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation", "qid": 49, "docid": "wunfrt1v", "rank": 37, "score": 0.7857454419136047}, {"content": "Title: Mesenchymal Stem Cells -Bridge Catalyst Between Innte And Adaptive Immunity In Covid 19 Content: Majority of patients infected with the COVID 19 virus display a mild to moderate course of disease and spontaneously recover at 14 - 20 days,. However, about 15 % of patients progress to severe stages and 2.5% of these patients succumb to this illness. Most patients with severe disease belong to the elderly age group (< 65 years of age) and have multiple associated co-morbidities. The immune responses induced by the COVID 19 virus, during the incubation and non-severe stages, requires the early initiation of a specific adaptive immune response to eliminate the virus and prevent the progress to severe stages. In patients with a dysfunctional bridge adaptive immunity, the innate immune response becomes exaggerated due to the lack of feedback from the adaptive immune cells. The resultant cytokine storm is responsible for the severe lung injury leading to acute respiratory distress syndrome seen in COVID 19 patients. Mesenchymal stem cells are known to suppress overactive immune responses as well as bring about tissue regeneration and repair. This immuno-modulatory effect of MSCs could hold potential to manage a patient with severe symptoms of COVID 19 infection due to a dysfunctional adaptive immune system.", "qid": 49, "docid": "4gfvbaj1", "rank": 38, "score": 0.7854827642440796}, {"content": "Title: PCR Assays Turned Positive in 25 Discharged COVID-19 Patients Content: We report the observation that 14.5% of COVID-19 patients had positive RT-PCR testing again after discharge. We describe correlations between laboratory parameters and treatment duration (r= -0.637; p=0.002) and time to virus recrudescence (r= 0.52; p=0.008) respectively, suggesting the need for additional measures to confirm illness resolution in COVID-19 patients.", "qid": 49, "docid": "6woq4p69", "rank": 39, "score": 0.7853952646255493}, {"content": "Title: Immune phenotyping based on neutrophil-to-lymphocyte ratio and IgG predicts disease severity and outcome for patients with COVID-19 Content: Background: A recently emerging respiratory disease named coronavirus disease 2019 (COVID-19) has quickly spread across the world. This disease is initiated by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and uncontrolled cytokine storm, but it remains unknown as to whether a robust antibody response is related to clinical deterioration and poor outcome in laboratory-confirmed COVID-19 patients. Methods: Anti-SARS-CoV-2 IgG and IgM antibodies were determined by chemiluminescence analysis (CLIA) in COVID-19 patients from a single center in Wuhan. Median IgG and IgM levels in acute and convalescent-phase sera (within 35 days) for all included patients were calculated and compared among severe and nonsevere patients. Immune response phenotyping based on late IgG levels and neutrophil-to-lymphocyte ratio (NLR) was characterized to stratify patients with different disease severities and outcome. Laboratory parameters in patients with different immune response phenotypes and disease severities were analyzed. Findings: A total of 222 patients were included in this study. IgG was first detected on day 4 of illness, and its peak levels occurred in the fourth week. Severe cases were more frequently found in patients with high IgG levels, compared to those who with low IgG levels (51.8% versus 32.3%; p=0.008). Severity rates for patients with NLRhiIgGhi, NLRhiIgGlo, NLRloIgGhi, and NLRloIgGlo phenotype was 72.3%, 48.5%, 33.3%, and 15.6%, respectively (p<0.0001). Furthermore, severe patients with NLRhiIgGhi, NLRhiIgGlo had higher proinflammatory cytokines levels including IL-2, IL-6 and IL-10, and decreased CD4+ T cell count compared to those with NLRloIgGlo phenotype (p<0.05). Recovery rate for severe patients with NLRhiIgGhi, NLRhiIgGlo, NLRloIgGhi, and NLRloIgGlo phenotype was 58.8% (20/34), 68.8% (11/16), 80.0% (4/5), and 100% (12/12), respectively (p=0.0592). Dead cases only occurred in NLRhiIgGhi and NLRhiIgGlo phenotypes. Interpretation: COVID-19 severity is associated with increased IgG response, and an immune response phenotyping based on late IgG response and NLR could act as a simple complementary tool to discriminate between severe and nonsevere COVID-19 patients, and further predict their clinical outcome.", "qid": 49, "docid": "68193u0a", "rank": 40, "score": 0.7851864099502563}, {"content": "Title: Biologikatherapie nach COVID-19-Infektion: Keine Reaktivierung einer COVID-19-Infektion bei positivem Antik\u00f6rperstatus SARS-CoV-2 unter Biologikatherapie Content: A case with rheumatoid arthritis and insufficient compensation under disease-modifying combined long-term therapy with methotrexate and leflunomide is reported. After recovery from a COVID-19 infection, a tumor necrosis factor (TNF) inhibitor therapy was initiated. Until now no reactivation of the COVID-19 infection with positive SARS-CoV\u20112 antibody status has occurred.", "qid": 49, "docid": "mjzsz7rz", "rank": 41, "score": 0.7849754095077515}, {"content": "Title: Immune Response, Inflammation, and the Clinical Spectrum of COVID-19 Content: The current COVID-19 pandemic began in December 2019 in Wuhan (China) and rapidly extended to become a global sanitary and economic emergency. Its etiological agent is the coronavirus SARS-CoV-2. COVID-19 presents a wide spectrum of clinical manifestations, which ranges from an asymptomatic infection to a severe pneumonia accompanied by multisystemic failure that can lead to a patient's death. The immune response to SARS-CoV-2 is known to involve all the components of the immune system that together appear responsible for viral elimination and recovery from the infection. Nonetheless, such immune responses are implicated in the disease's progression to a more severe and lethal process. This review describes the general aspects of both COVID-19 and its etiological agent SARS-CoV-2, stressing the similarities with other severe coronavirus infections, such as SARS and MERS, but more importantly, pointing toward the evidence supporting the hypothesis that the clinical spectrum of COVID-19 is a consequence of the corresponding variable spectrum of the immune responses to the virus. The critical point where progression of the disease ensues appears to center on loss of the immune regulation between protective and altered responses due to exacerbation of the inflammatory components. Finally, it appears possible to delineate certain major challenges deserving of exhaustive investigation to further understand COVID-19 immunopathogenesis, thus helping to design more effective diagnostic, therapeutic, and prophylactic strategies.", "qid": 49, "docid": "pjjrgn05", "rank": 42, "score": 0.7848004102706909}, {"content": "Title: Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent. Content: BACKGROUND Coronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Anti-viral immune response is crucial to achieve pathogen clearance, however in some patients an excessive and aberrant host immune response can lead to an acute respiratory distress syndrome. The comprehension of the mechanisms that regulate pathogen elimination, immunity, and pathology is essential to better characterize disease progression and widen the spectrum of therapeutic options. METHODS We performed a flow cytometric characterization of immune cells subsets from 30 COVID-19 patients and correlated these data with clinical outcomes. RESULTS COVID-19 patients showed decreased numbers of circulating T, B and NK cells, and exhibited a skewing of CD8+ T cells towards a terminally differentiated/senescent phenotype. In agreement, T CD4+, T CD8+ but also NK cells displayed reduced anti-viral cytokine production capability. Moreover, a reduced cytotoxic potential was identified in COVID-19 patients, particularly in those that required intensive care. The latter group of patients showed also increased serum IL-6 levels, that correlated to the frequency of granzyme-expressing NK cells. Off-label treatment with tocilizumab restored the cytotoxic potential of NK cells. CONCLUSION In conclusion, the association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore anti-viral mechanisms. FUNDING This study was supported by funds of Dept. of Experimental and Clinical Medicine of University of Florence (ex-60%) derived from Ministero dell'Istruzione, dell'Universit\u00e0 e della Ricerca (Italy).", "qid": 49, "docid": "z4uoyujr", "rank": 43, "score": 0.7839319705963135}, {"content": "Title: Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infection Content: Antibody (Ab) responses to SARS-CoV-2 can be detected in most infected individuals 10-15 days following the onset of COVID-19 symptoms. However, due to the recent emergence of this virus in the human population it is not yet known how long these Ab responses will be maintained or whether they will provide protection from re-infection. Using sequential serum samples collected up to 94 days post onset of symptoms (POS) from 65 RT-qPCR confirmed SARS-CoV-2-infected individuals, we show seroconversion in >95% of cases and neutralizing antibody (nAb) responses when sampled beyond 8 days POS. We demonstrate that the magnitude of the nAb response is dependent upon the disease severity, but this does not affect the kinetics of the nAb response. Declining nAb titres were observed during the follow up period. Whilst some individuals with high peak ID50 (>10,000) maintained titres >1,000 at >60 days POS, some with lower peak ID50 had titres approaching baseline within the follow up period. A similar decline in nAb titres was also observed in a cohort of seropositive healthcare workers from Guy's and St Thomas' Hospitals. We suggest that this transient nAb response is a feature shared by both a SARS-CoV-2 infection that causes low disease severity and the circulating seasonal coronaviruses that are associated with common colds. This study has important implications when considering widespread serological testing, Ab protection against re-infection with SARS-CoV-2 and the durability of vaccine protection.", "qid": 49, "docid": "7n6pva1l", "rank": 44, "score": 0.7838166952133179}, {"content": "Title: Immune modulation in COVID-19: Strategic considerations for personalized therapeutic intervention Content: We are learning that the host response to SARS-CoV-2 infection is complex and highly dynamic. Effective initial host defense in the lung is associated with mild symptoms and disease resolution. Viral evasion of the immune response can lead to refractory alveolar damage, ineffective lung repair mechanisms, and systemic inflammation with associated organ dysfunction. The immune response in these patients is highly variable and can include moderate to severe systemic inflammation and/or marked systemic immune suppression. There is unlikely to be a \"one size fits all\" approach to immunomodulation in patients with COVID-19. We believe that a personalized, immunophenotype-driven approach to immunomodulation that may include anti-cytokine therapy in carefully selected patients and immunostimulatory therapies in others is the shortest path to success in the study and treatment of patients with critical illness due to COVID-19.", "qid": 49, "docid": "8a351qol", "rank": 45, "score": 0.7833764553070068}, {"content": "Title: Magnitude and kinetics of anti-SARS-CoV-2 antibody responses and their relationship to disease severity Content: Background: SARS-CoV-2 infection can be detected indirectly by measuring the host immune response. Anti-viral antibody concentrations generally correlate with host protection and viral neutralization, but in rare cases, antibodies can promote disease progression. Elucidation of the kinetics and magnitude of the SARS-CoV-2 antibody response is essential to understand the pathogenesis of COVID-19 and identify potential therapeutic targets. Methods: Sera (n=533) from patients with RT-PCR confirmed COVID-19 (n=153) were tested using a high-throughput quantitative IgM and IgG assay that detects antibodies to the spike protein receptor binding domain and nucleocapsid protein. Individual and serial samples covered the time of initial diagnosis, during the disease course, and following recovery. We evaluated antibody kinetics and correlation between magnitude of the response and disease severity. Results: Patterns of SARS-CoV-2 antibody production varied considerably. Among 52 patients with 3 or more serial specimens, 44 (84.6%) and 42 (80.8%) had observed IgM and IgG seroconversion at a median of 8 and 10 days, respectively. Compared to those with milder disease, peak measurements were significantly higher for patients admitted to the intensive care unit for all time intervals between 6 and 20 days for IgM, and all intervals after 5 days for IgG. Conclusions: High sensitivity assays with a robust dynamic range provide a comprehensive picture of host antibody response to SARS-CoV-2. IgM and IgG responses were significantly higher in patients with severe than mild disease. These differences may affect strategies for seroprevalence studies, therapeutics and vaccine development.", "qid": 49, "docid": "by24cpyw", "rank": 46, "score": 0.7831318974494934}, {"content": "Title: Analysis of adaptive immune cell populations and phenotypes in the patients infected by SARS-CoV-2 Content: Coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, has rapidly spread to most of countries in the world, threatening the health and lives of many people. Unfortunately, information regarding the immunological characteristics in COVID-19 patients remains limited. Here we collected the blood samples from 18 healthy donors (HD) and 38 COVID-19 patients to analyze changes in the adaptive immune cell populations and phenotypes. In comparison to HD, the lymphocyte percentage was slightly decreased, the percentages of CD4 and CD8 T cells in lymphocytes are similar, whereas B cell percentage increased in COVID-19 patients. T cells, especially CD8 T cells, showed an enhanced expression of late activation marker CD25 and exhaustion marker PD-1. Importantly, SARS-CoV-2 induced an increased percentage of T follicular helpher (Tfh)- and germinal center B-like (GCB-like) cells in the blood. However, the parameters in COVD-19 patients remained unchanged across various age groups. Therefore, we demonstrated that the T and B cells can be activated normally and exhibit functional features. These data provide a clue that the adaptive immunity in most people could be primed to induce a significant immune response against SARS-CoV-2 infection upon receiving standard medical care.", "qid": 49, "docid": "zjgswsjj", "rank": 47, "score": 0.782843291759491}, {"content": "Title: Benign COVID-19 in an immunocompromised cancer patient - the case of a married couple Content: Respiratory failure in COVID-19 is a common feature in fatal cases and has been considered as a failure of the immune system to control the virus. Here we report the case of COVID-19 affecting an immunocompromised women and her presumably immunocompetent spouse. A married couple (age 60 years) was simultaneously admitted to the emergency department on 10 March 2020 because of dyspnoea and fever, consistent with COVID-19. The wife (patient 1) was partially immunocompromised as a consequence of a recently started chemotherapy with fulvestrant and abemaciclid for recurring breast cancer, her husband (patient 2) had been healthy except for a history of controlled arterial hypertension. Both patients were treated with darunavir/cobicistat and hydroxychloroquine. The clinical course of the immunocompromised partner was benign, without need of intensive care. She was able to leave the hospital on day 6 after admission. In contrast, her husband needed intensive care and his recovery was slow, although eventually successful too. These findings suggest that the course of COVID-19 is not necessarily ominous in the presence of a compromised immune response and tend to reinforce the emerging therapeutic concepts of a controlled mitigation of the immune cascade following SARS CoV-2 infection.", "qid": 49, "docid": "vnficfxz", "rank": 48, "score": 0.7823812961578369}, {"content": "Title: Benign COVID-19 in an immunocompromised cancer patient - the case of a married couple. Content: Respiratory failure in COVID-19 is a common feature in fatal cases and has been considered as a failure of the immune system to control the virus. Here we report the case of COVID-19 affecting an immunocompromised women and her presumably immunocompetent spouse. A married couple (age 60 years) was simultaneously admitted to the emergency department on 10 March 2020 because of dyspnoea and fever, consistent with COVID-19. The wife (patient 1) was partially immunocompromised as a consequence of a recently started chemotherapy with fulvestrant and abemaciclid for recurring breast cancer, her husband (patient 2) had been healthy except for a history of controlled arterial hypertension. Both patients were treated with darunavir/cobicistat and hydroxychloroquine. The clinical course of the immunocompromised partner was benign, without need of intensive care. She was able to leave the hospital on day 6 after admission. In contrast, her husband needed intensive care and his recovery was slow, although eventually successful too. These findings suggest that the course of COVID-19 is not necessarily ominous in the presence of a compromised immune response and tend to reinforce the emerging therapeutic concepts of a controlled mitigation of the immune cascade following SARS CoV-2 infection.", "qid": 49, "docid": "qz2pqtjo", "rank": 49, "score": 0.7823812961578369}, {"content": "Title: Understanding the T cell immune response in SARS coronavirus infection Content: The severe acute respiratory syndrome (SARS) epidemic started in late 2002 and swiftly spread across 5 continents with a mortality rate of around 10%. Although the epidemic was eventually controlled through the implementation of strict quarantine measures, there continues a need to investigate the SARS coronavirus (SARS-CoV) and develop interventions should it re-emerge. Numerous studies have shown that neutralizing antibodies against the virus can be found in patients infected with SARS-CoV within days upon the onset of illness and lasting up to several months. In contrast, there is little data on the kinetics of T cell responses during SARS-CoV infection and little is known about their role in the recovery process. However, recent studies in mice suggest the importance of T cells in viral clearance during SARS-CoV infection. Moreover, a growing number of studies have investigated the memory T cell responses in recovered SARS patients. This review covers the available literature on the emerging importance of T cell responses in SARS-CoV infection, particularly on the mapping of cytotoxic T lymphocyte (CTL) epitopes, longevity, polyfunctionality and human leukocyte antigen (HLA) association as well as their potential implications on treatment and vaccine development.", "qid": 49, "docid": "5uoepd0r", "rank": 50, "score": 0.7823788523674011}, {"content": "Title: Immune modulation in COVID-19: Strategic considerations for personalized therapeutic intervention Content: We are learning that the host response to SARS-CoV-2 infection is complex and highly dynamic. Effective initial host defense in the lung is associated with mild symptoms and disease resolution. Viral evasion of the immune response can lead to refractory alveolar damage, ineffective lung repair mechanisms, and systemic inflammation with associated organ dysfunction. The immune response in these patients is highly variable and can include moderate to severe systemic inflammation and/or marked systemic immune suppression. There is unlikely to be a \u201cone size fits all\u201d approach to immunomodulation in patients with COVID-19. We believe that a personalized, immunophenotype-driven approach to immunomodulation that may include anti-cytokine therapy in carefully selected patients and immunostimulatory therapies in others is the shortest path to success in the study and treatment of patients with critical illness due to COVID-19.", "qid": 49, "docid": "zlro6tel", "rank": 51, "score": 0.7822741866111755}, {"content": "Title: Antibody profiling of COVID-19 patients in an urban low-incidence region in Northern Germany Content: This explorative monocentric study shows IgA and IgG antibody profiles from 110 patients with self-reported mild to moderate, or no COVID-19 related symptoms after laboratory-confirmed infection with SARS-CoV-2. The study region is in an urban and well-defined environment in a low-incidence region in Northern Germany. We found that approx. 70 % of the patients developed sustainable antibodies 3 weeks or later after the infection. In about 30 % of the patients with mild to moderate symptoms, no significant antibodies could be detected in two consecutive analyses. Conversely, out of ten patients without symptoms, four were repeatedly positive. Expectedly, six had no specific antibodies. The data indicate that antibody-positivity is a useful indicator of a previous SARS-CoV-2 infection. Negative antibodies do not rule out SARS-CoV-2 infection. Future studies need to determine the functionality of the antibodies in terms of personal protection and ability to transmit the virus.", "qid": 49, "docid": "4888p05u", "rank": 52, "score": 0.7818892002105713}, {"content": "Title: Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent Content: BACKGROUND: Coronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Anti-viral immune response is crucial to achieve pathogen clearance, however in some patients an excessive and aberrant host immune response can lead to an acute respiratory distress syndrome. The comprehension of the mechanisms that regulate pathogen elimination, immunity, and pathology is essential to better characterize disease progression and widen the spectrum of therapeutic options. METHODS: We performed a flow cytometric characterization of immune cells subsets from 30 COVID-19 patients and correlated these data with clinical outcomes. RESULTS: COVID-19 patients showed decreased numbers of circulating T, B and NK cells, and exhibited a skewing of CD8+ T cells towards a terminally differentiated/senescent phenotype. In agreement, T CD4+, T CD8+ but also NK cells displayed reduced anti-viral cytokine production capability. Moreover, a reduced cytotoxic potential was identified in COVID-19 patients, particularly in those that required intensive care. The latter group of patients showed also increased serum IL-6 levels, that correlated to the frequency of granzyme-expressing NK cells. Off-label treatment with tocilizumab restored the cytotoxic potential of NK cells. CONCLUSION: In conclusion, the association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore anti-viral mechanisms. FUNDING: This study was supported by funds of Dept. of Experimental and Clinical Medicine of University of Florence (ex-60%) derived from Ministero dell'Istruzione, dell'Universit\u00e0 e della Ricerca (Italy).", "qid": 49, "docid": "gwrbvpz2", "rank": 53, "score": 0.7814645767211914}, {"content": "Title: Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients Content: COVID-19 is an ongoing global crisis in which the development of effective vaccines and therapeutics will depend critically on understanding the natural immunity to the virus, including the role of SARS-CoV-2-specific T cells. We have conducted a study of 42 patients following recovery from COVID-19, including 28 mild and 14 severe cases, comparing their T cell responses to those of 16 control donors. We assessed the immune memory of T cell responses using IFN\u03b3 based assays with overlapping peptides spanning SARS-CoV-2 apart from ORF1. We found the breadth, magnitude and frequency of memory T cell responses from COVID-19 were significantly higher in severe compared to mild COVID-19 cases, and this effect was most marked in response to spike, membrane, and ORF3a proteins. Total and spike-specific T cell responses correlated with the anti-Spike, anti-Receptor Binding Domain (RBD) as well as anti-Nucleoprotein (NP) endpoint antibody titre (p<0.001, <0.001 and =0.002). We identified 39 separate peptides containing CD4+ and/or CD8+ epitopes, which strikingly included six immunodominant epitope clusters targeted by T cells in many donors, including 3 clusters in spike (recognised by 29%, 24%, 18% donors), two in the membrane protein (M, 32%, 47%) and one in the nucleoprotein (Np, 35%). CD8+ responses were further defined for their HLA restriction, including B*4001-restricted T cells showing central memory and effector memory phenotype. In mild cases, higher frequencies of multi-cytokine producing M- and NP-specific CD8+ T cells than spike-specific CD8+ T cells were observed. They furthermore showed a higher ratio of SARS-CoV-2-specific CD8+ to CD4+ T cell responses. Immunodominant epitope clusters and peptides containing T cell epitopes identified in this study will provide critical tools to study the role of virus-specific T cells in control and resolution of SARS-CoV-2 infections. The identification of T cell specificity and functionality associated with milder disease, highlights the potential importance of including non-spike proteins within future COVID-19 vaccine design.", "qid": 49, "docid": "qo3cfytq", "rank": 54, "score": 0.78142249584198}, {"content": "Title: Human coronavirus reinfection dynamics: lessons for SARS-CoV-2 Content: In the current SARS-CoV-2 pandemic a key unsolved question is the quality and duration of acquired immunity in recovered individuals. This is crucial to solve, however SARS-CoV-2 has circulated for under five months, precluding a direct study. We therefore monitored 10 subjects over a time span of 35 years (1985-2020), providing a total of 2473 follow up person-months, and determined a) their antibody levels following infection by any of the four seasonal human coronaviruses, and b) the time period after which reinfections by the same virus can occur. An alarmingly short duration of protective immunity to coronaviruses was found by both analyses. We saw frequent reinfections at 12 months post-infection and a substantial reduction in antibody levels as soon as 6 months post-infection.", "qid": 49, "docid": "u5nxm9tu", "rank": 55, "score": 0.7813587188720703}, {"content": "Title: Expansion of SARS-CoV-2-specific Antibody-secreting Cells and Generation of Neutralizing Antibodies in Hospitalized COVID-19 Patients Content: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 and has since become a global pandemic. Pathogen-specific antibodies are typically a major predictor of protective immunity, yet B cell and antibody responses during COVID-19 are not fully understood. Here, we analyzed antibody-secreting cell (ASC) and antibody responses in twenty hospitalized COVID-19 patients. The patients exhibited typical symptoms of COVID-19, and presented with reduced lymphocyte numbers and increased T cell and B cell activation. Importantly, we detected an expansion of SARS-CoV-2 nucleocapsid protein-specific ASCs in all twenty COVID-19 patients using a multicolor FluoroSpot assay. Out of the 20 patients, 16 had developed SARS-CoV-2-neutralizing antibodies by the time of inclusion in the study. SARS-CoV-2-specific IgA, IgG and IgM antibody levels positively correlated with SARS-CoV-2-neutralizing antibody titers, suggesting that SARS-CoV-2-specific antibody levels may reflect the titers of neutralizing antibodies in COVID-19 patients during the acute phase of infection. Lastly, we showed that interleukin 6 (IL-6) and C-reactive protein (CRP) concentrations were higher in serum of patients who were hospitalized for longer, supporting the recent observations that IL-6 and CRP could be used to predict COVID-19 severity. Altogether, this study constitutes a detailed description of clinical and immunological parameters in twenty COVID-19 patients, with a focus on B cell and antibody responses, and provides tools to study immune responses to SARS-CoV-2 infection and vaccination.", "qid": 49, "docid": "um9lv53e", "rank": 56, "score": 0.781233012676239}, {"content": "Title: SARS-CoV-2 viral load and antibody responses: the case for convalescent plasma therapy. Content: Most patients with COVID-19 lack antibody to SARS-CoV-2 in the first 10 days of illness while the virus drives disease pathogenesis. SARS-CoV-2 antibody deficiency in the setting of a tissue viral burden suggests that using an antibody as a therapeutic agent would augment the antiviral immune response. In this issue of the JCI, Wang and collaborators describe the kinetics of viral load and antibody responses of 23 individuals with COVID-19 with mild and severe disease. The researchers found: 1) individuals with mild and severe disease produced neutralizing IgG to SARS-CoV-2 10 days after disease onset; 2) SARS-CoV-2 persisted longer in those with severe disease; and 3) there was cross-reactivity between antibodies to SARS-CoV-1 and SARS-CoV-2, but only antibodies from patients with COVID-19 neutralized SARS-CoV-2. These observations provide important information on the serological response to SARS-CoV-2 of hospitalized patients with COVID-19 that can inform the use of convalescent plasma therapy.", "qid": 49, "docid": "xp09u1tq", "rank": 57, "score": 0.7811846137046814}, {"content": "Title: SARS-CoV-2 viral load and antibody responses: the case for convalescent plasma therapy Content: Most patients with COVID-19 lack antibody to SARS-CoV-2 in the first 10 days of illness while the virus drives disease pathogenesis. SARS-CoV-2 antibody deficiency in the setting of a tissue viral burden suggests that using an antibody as a therapeutic agent would augment the antiviral immune response. In this issue of the JCI, Wang and collaborators describe the kinetics of viral load and antibody responses of 23 individuals with COVID-19 with mild and severe disease. The researchers found: 1) individuals with mild and severe disease produced neutralizing IgG to SARS-CoV-2 10 days after disease onset; 2) SARS-CoV-2 persisted longer in those with severe disease; and 3) there was cross-reactivity between antibodies to SARS-CoV-1 and SARS-CoV-2, but only antibodies from patients with COVID-19 neutralized SARS-CoV-2. These observations provide important information on the serological response to SARS-CoV-2 of hospitalized patients with COVID-19 that can inform the use of convalescent plasma therapy.", "qid": 49, "docid": "tckjc7os", "rank": 58, "score": 0.7811845541000366}, {"content": "Title: Clinical recurrences of COVID-19 symptoms after recovery: viral relapse, reinfection or inflammatory rebound? Content: For the first 3 months of COVID-19 pandemic, COVID-19 was expected to be an immunizing non-relapsing disease. We report a national case series of 11 virologically-confirmed COVID-19 patients having experienced a second clinically- and virologically-confirmed acute COVID-19 episode. According to the clinical history, we discuss either re-infection or reactivation hypothesis. Larger studies including further virological, immunological and epidemiologic data are needed to understand the mechanisms of these recurrences.", "qid": 49, "docid": "qg01p4bq", "rank": 59, "score": 0.7810048460960388}, {"content": "Title: Immune responses and pathogenesis of SARS-CoV-2 during an outbreak in Iran: Comparison with SARS and MERS Content: The beginning of 2020 has seen the emergence of COVID-19, an outbreak caused by a novel coronavirus, SARS-CoV-2, an important pathogen for humans. There is an urgent need to better understand this new virus and to develop ways to control its spread. In Iran, the first case of the COVID-19 was reported after spread from China and other countries. Fever, cough, and fatigue were the most common symptoms of this virus. In worldwide, the incubation period of COVID-19 was 3 to 7 days and approximately 80% of infections are mild or asymptomatic, 15% are severe, requiring oxygen, and 5% are critical infections, requiring ventilation. To mount an antiviral response, the innate immune system recognizes molecular structures that are produced by the invasion of the virus. COVID-19 infection induces IgG antibodies against N protein that can be detected by serum as early as day 4 after the onset of disease and with most patients seroconverting by day 14. Laboratory evidence of clinical patients showed that a specific T-cell response against SARS-CoV-2 is important for the recognition and killing of infected cells, particularly in the lungs of infected individuals. At present, there is no specific antiviral therapy for COVID-19 and the main treatments are supportive. In this review, we investigated the innate and acquired immune responses in patients who recovered from COVID-19, which could inform the design of prophylactic vaccines and immunotherapy for the future.", "qid": 49, "docid": "3nnlkbph", "rank": 60, "score": 0.7805593609809875}, {"content": "Title: Immunity after COVID-19: protection or sensitization ? Content: Motivated by historical and present clinical observations, we discuss the possible unfavorable evolution of the immunity (similar to documented antibody-dependent enhancement scenarios) after a first infection with COVID-19. More precisely we ask the question of how the epidemic outcomes are affected if the initial infection does not provide immunity but rather sensitization to future challenges. We first provide background comparison with the 2003 SARS epidemic. Then we use a compartmental epidemic model structured by immunity level (taken here as age classes) that we fit on available data; this allows to derive quantitative insights into the future number of severe cases and deaths.", "qid": 49, "docid": "g6g34uvh", "rank": 61, "score": 0.7798935174942017}, {"content": "Title: A systematic review of convalescent plasma treatment for COVID19 Content: Background. Transfusion of convalescent immune plasma (CP) is commonly used in epidemics. Several articles now describe clinical report data of CP for treatment of SARS-CoV-2-induced COVID-19 disease. Methods. A systematic literature review was conducted using the NCBI curated COVID-19 related open-resource literature database LitCovid to identify studies using CP as treatment for COVID-19 patients. We retrieved and curated all COVID-19 related patient and treatment characteristics from previously reported studies. A Poisson model was developed to evaluate the association between age of the patients, older age being the most common risk factor for COVID-19 mortality, and recovery time since CP treatment using data extracted from the literature. Results. From 18,293 identified COVID-19 related articles, we included ten studies reporting results of CP treatment for COVID-19 from a total of 61 patients. Decreased symptoms of severe COVID-19 and clearance of SARS-CoV-2 RNA were the most direct observations. We found that patients over the age of sixty who received CP treatment for COVID-19 had a significantly prolonged recovery estimated by viral clearance (from 10 to 29 days since first dose of CP) compared to younger patients, who recovered from the infection in less than a week after receiving CP treatment. Conclusions. Limited published results on plasma transfusion treatment for COVID-19 disease with concomitant treatments suggest that CP therapy for COVID-19 is well tolerated and effective. First randomized clinical trial results, however, reveal no improvements in recovery time for elderly patients with severe COVID-19 between standard treatment alone and added with convalescent plasma. Accordingly, we argue that older patients may need a significantly longer time for recovery. Further randomized clinical trial data for COVID-19 with rigorous ethical standards is urgently needed.", "qid": 49, "docid": "xnjpe1ss", "rank": 62, "score": 0.7796478867530823}, {"content": "Title: Increased expression of CD8 marker on T-cells in COVID-19 patients Content: BACKGROUND: Cell-mediated immunity including T-cells (T helper and cytotoxic) plays an essential role in efficient antiviral responses against coronavirus disease-2019 (COVID-19). Therefore, in this study, we evaluated the ratio and expression of CD4 and CD8 markers in COVID-19 patients to clarify the immune characterizations of CD4 and CD8 T-cells in COVID-19 patients. METHODS: Peripheral blood samples of 25 COVID-19 patients and 25 normal individuals with similar age and sex as the control group were collected. White blood cells, platelets, and lymphocytes were counted and CD4 and CD8 T lymphocytes were evaluated by flow cytometry. RESULTS: The number of white blood cells, lymphocytes, and platelets were reduced significantly in COVID-19 patients (P < 0.05). The difference in CD4:CD8 ratio, CD4 T-cell frequency, CD8 T-cell frequency, and CD4 mean fluorescence intensity (MFI) was not significant between COVID-19 patients and healthy individuals (P > 0.05); however, the CD8 MFI increased significantly in COVID-19 infected patients (P < 0.05). CONCLUSION: Although, there is no significant difference in the ratio of CD4 to CD8 between two groups, the expression level of CD8 in COVID-19 patients was significantly higher than the normal individuals. This result suggested that the cellular immune responses triggered by COVID-19 infection were developed through overexpression of CD8 and hyperactivation of cytotoxic T lymphocytes.", "qid": 49, "docid": "z6ytcze7", "rank": 63, "score": 0.7795721292495728}, {"content": "Title: COVID-19 in post-transplantation patients- report of two cases. Content: Coronavirus Disease 2019 (COVID-19) has become a pandemic since March 2020. We describe here, two cases of COVID-19 infection in a post-transplant setting. First one is a 59-year old renal transplant recipient; the second is a 51-year old allogeneic bone marrow transplant recipient. Both patients were on immunosuppressant therapy and had stable graft function before COVID-19 infection. After the diagnosis of COVID-19, immunosuppressive agents were discontinued and methylprednisolone with prophylactic antibiotics were initiated, however, the lung injury progressed. The T cells were extremely low in both patients after infection. Both patients died despite the maximal mechanical ventilatory support. Therefore, the prognosis of COVID-19 pneumonia following transplantation is not optimistic and remains guarded. Lower T cell count may be a surrogate for poor outcome.", "qid": 49, "docid": "x97yw3ip", "rank": 64, "score": 0.7794560194015503}, {"content": "Title: The unleashing of the immune system in COVID-19 and sepsis: the calm before the storm? Content: The novel coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sorely testing health care systems and economies around the world and is rightly considered as the major health emergency in a century. Despite the course of the disease appearing to be mild in many cases, a significant proportion of symptomatic patients develop pneumonia requiring hospitalisation or progress to manifest respiratory complications leading to intensive care treatment. Potential interventions for SARS-CoV2-associated pneumonia are being tested, some of which holding promise, but as of today none of these has yet demonstrated outstanding efficacy in treating COVID-19. In this article, we discuss fresh perspectives and insights into the potential role of immune dysregulation in COVID-19 as well as similarities with systemic inflammatory response in sepsis and the rationale for exploring novel treatment options affecting host immune response.", "qid": 49, "docid": "5ycxh1sq", "rank": 65, "score": 0.7794315814971924}, {"content": "Title: Aberrant hyperactivation of cytotoxic T-cell as a potential determinant of COVID-19 severity Content: OBJECTIVES: We hypothesized that immune response may contribute to progression of coronavirus disease-19 (COVID-19) at the second week of illness. Therefore, we compared cell-mediated immune (CMI) responses between severe and mild COVID-19 cases. METHODS: We examined peripheral blood mononuclear cells of laboratory-confirmed COVID-19 patients from their first and third weeks of illness. Severe pneumonia was defined as an oxygen saturation &#8804;93% at room air. Expressions of molecules related to T-cell activation and functions were analyzed by flow cytometry. RESULTS: The population dynamics of T cells at the first week were not different between the two groups. However, total numbers of CD4+ and CD8+ T cells tended to be lower in the severe group at the third week of illness. Expressions of Ki-67, PD-1, perforin, and granzyme B in CD4+ or CD8+ T cells were significantly higher in the severe group than in the mild group at the third week. In contrast to the mild group, the levels of their expression did not decrease in the severe group. CONCLUSIONS: Severe COVID-19 had a higher degree of proliferation, activation, and cytotoxicity of T-cells at the late phase of illness without cytotoxic T-cell contraction, which might contribute to the development of severe COVID-19.", "qid": 49, "docid": "32fho74f", "rank": 66, "score": 0.7791969776153564}, {"content": "Title: Aberrant hyperactivation of cytotoxic T-cell as a potential determinant of COVID-19 severity Content: Abstract Objectives We hypothesized that immune response may contribute to progression of coronavirus disease-19 (COVID-19) at the second week of illness. Therefore, we compared cell-mediated immune (CMI) responses between severe and mild COVID-19 cases. Methods We examined peripheral blood mononuclear cells of laboratory-confirmed COVID-19 patients from their first and third weeks of illness. Severe pneumonia was defined as an oxygen saturation \u2264 93% at room air. Expressions of molecules related to T-cell activation and functions were analyzed by flow cytometry. Results The population dynamics of T cells at the first week were not different between the two groups. However, total numbers of CD4+ and CD8 + T cells tended to be lower in the severe group at the third week of illness. Expressions of Ki-67, PD-1, perforin, and granzyme B in CD4+ or CD8+ T cells were significantly higher in the severe group than in the mild group at the third week. In contrast to the mild group, the levels of their expression did not decrease in severe group. Conclusions Severe COVID-19 had higher degree of proliferation, activation, and cytotoxicity of T-cells at the late phase of illness without cytotoxic T-cell contraction, which might contribute to the development of severe COVID-19.", "qid": 49, "docid": "m67acbzd", "rank": 67, "score": 0.7791798114776611}, {"content": "Title: Symptoms and immunoglobulin development in hospital staff exposed to a SARS-CoV-2 outbreak Content: BACKGROUND: Worldwide, the number of SARS-CoV-2 infections is increasing. Serological immunoglobulin tests may help to better understand the development of immune mechanisms against SARS-CoV-2 in COVID-19 cases and exposed but asymptomatic individuals. The aim of this study was to investigate exposure to SARS-CoV-2, symptoms, and antibody responses in a large sample of healthcare workers following a COVID-19 outbreak. METHODS: A COVID-19 outbreak among staff members of a major German children's and women's hospital was followed by massive RT-PCR SARS-CoV-2 tests and provided the opportunity to study symptoms, chains of infection, and SARS-CoV-2-specific antibody responses (IgG and IgA) by ELISA. Study participants were classified as COVID-19 cases, and persons with close, moderate, or no exposure to SARS-CoV-2 in the clinical setting, respectively. RESULTS: Out of 201 study participants, 31 were COVID-19 cases. While most study participants experienced many symptoms indicative for SARS-CoV-2 infection, anosmia and coughing were remarkably more frequent in COVID-19 cases. Approximately 80% of COVID-19 cases developed some specific antibody response (IgA and IgG) approximately 3 weeks after onset of symptoms. Subjects in the non-COVID-19 groups had also elevated IgG (1.8%) and IgA values (7.6%) irrespective of contact history with cases. CONCLUSION: We found that a significant number of diseased did not develop relevant antibody responses three weeks after symptom onset. Our data also suggest that exposure to COVID-19 positive co-workers in a hospital setting is not leading to the development of measurable immune responses in a significant proportion of asymptomatic contact persons.", "qid": 49, "docid": "gcil6lem", "rank": 68, "score": 0.7789899110794067}, {"content": "Title: Divergent SARS-CoV-2-specific T and B cell responses in severe but not mild COVID-19 Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. Understanding both the immunological processes providing specific immunity and potential immunopathology underlying the pathogenesis of this disease may provide valuable insights for potential therapeutic interventions. Here, we quantified SARS-CoV-2 specific immune responses in patients with different clinical courses. Compared to individuals with a mild clinical presentation, CD4+ T cell responses were qualitatively impaired in critically ill patients. Strikingly, however, in these patients the specific IgG antibody response was remarkably strong. The observed disparate T and B cell responses could be indicative of a deregulated immune response in critically ill COVID-19 patients.", "qid": 49, "docid": "hpbjdytv", "rank": 69, "score": 0.778969943523407}, {"content": "Title: Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery Content: BACKGROUND: The long-term pulmonary function and related physiological characteristics of COVID-19 survivors have not been studied in depth, thus many aspects are not understood. METHODS: COVID-19 survivors were recruited for high resolution computed tomography (HRCT) of the thorax, lung function and serum levels of SARS-CoV-2 IgG antibody tests 3 months after discharge. The relationship between the clinical characteristics and the pulmonary function or CT scores were investigated. FINDINGS: Fifty-five recovered patients participated in this study. SARS-CoV-2 infection related symptoms were detected in 35 of them and different degrees of radiological abnormalities were detected in 39 patients. Urea nitrogen concentration at admission was associated with the presence of CT abnormalities (P = 0.046, OR 7.149, 95% CI 1.038 to 49.216). Lung function abnormalities were detected in 14 patients and the measurement of D-dimer levels at admission may be useful for prediction of impaired diffusion defect (P = 0.031, OR 1.066, 95% CI 1.006 to 1.129). Of all the subjects, 47 of 55 patients tested positive for SARS-CoV-2 IgG in serum, among which the generation of Immunoglobulin G (IgG) antibody in female patients was stronger than male patients in infection rehabilitation phase. INTERPRETATION: Radiological and physiological abnormalities were still found in a considerable proportion of COVID-19 survivors without critical cases 3 months after discharge. Higher level of D-dimer on admission could effectively predict impaired DLCO after 3 months discharge. It is necessary to follow up the COVID-19 patients to appropriately manage any persistent or emerging long-term sequelae. FUNDING: Key Scientific Research Projects of Henan Higher Education Institutions", "qid": 49, "docid": "9cnuxusj", "rank": 70, "score": 0.7786502838134766}, {"content": "Title: Anti-SARS-CoV-2 virus antibody levels in convalescent plasma of six donors who have recovered from COVID-19 Content: Background: Anti-SARS-CoV-2 virus antibody levels in convalescent plasma (CP), which may be useful in severe Anti-SARS-CoV-2 virus infections, have been rarely reported. Results: A total of eight donors were considered for enrollment; two of them were excluded because of ineligible routine check. Of the six remaining participants, five samples were tested weakly positive by the IgM ELISA. Meanwhile, high titers of IgG were observed in five samples. The patient treated with CP did not require mechanical ventilation 11 days after plasma transfusion, and was then transferred to a general ward. Conclusions: Our serological findings in convalescent plasma from recovered patients may help facilitate understanding of the SARS-CoV-2 infection and establish CP donor screening protocol in COVID-19 outbreak. Methods: Anti-SARS-CoV-2 antibodies including IgM and IgG were measured by two enzyme-linked immunosorbent assays (ELISA) in convalescent plasma from six donors who have recovered from coronavirus disease 2019 (COVID-19) in Nanjing, China. CP was also utilized for the treatment of one severe COVID-19 patient.", "qid": 49, "docid": "5jdq6gk9", "rank": 71, "score": 0.7784298062324524}, {"content": "Title: Anti-SARS-CoV-2 virus antibody levels in convalescent plasma of six donors who have recovered from COVID-19 Content: BACKGROUND: Anti-SARS-CoV-2 virus antibody levels in convalescent plasma (CP), which may be useful in severe Anti-SARS-CoV-2 virus infections, have been rarely reported. RESULTS: A total of eight donors were considered for enrollment; two of them were excluded because of ineligible routine check. Of the six remaining participants, five samples were tested weakly positive by the IgM ELISA. Meanwhile, high titers of IgG were observed in five samples. The patient treated with CP did not require mechanical ventilation 11 days after plasma transfusion, and was then transferred to a general ward. CONCLUSIONS: Our serological findings in convalescent plasma from recovered patients may help facilitate understanding of the SARS-CoV-2 infection and establish CP donor screening protocol in COVID-19 outbreak. METHODS: Anti-SARS-CoV-2 antibodies including IgM and IgG were measured by two enzyme-linked immunosorbent assays (ELISA) in convalescent plasma from six donors who have recovered from coronavirus disease 2019 (COVID-19) in Nanjing, China. CP was also utilized for the treatment of one severe COVID-19 patient.", "qid": 49, "docid": "0sbmmv1g", "rank": 72, "score": 0.7784298062324524}, {"content": "Title: Perspectives of Immune Therapy in Coronavirus Disease 2019 Content: The global fight against coronavirus disease 2019 (COVID-19) is largely based on strategies to boost immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent its severe course and complications. The human defence may include antibodies which interact with SARS-CoV-2 and neutralize its aggressive actions on multiple organ systems. Protective cross-reactivity of antibodies against measles and other known viral infections has been postulated, primarily as a result of the initial observations of asymptomatic and mild COVID-19 in children. Uncontrolled case series have demonstrated virus-neutralizing effect of convalescent plasma, supporting its efficiency at early stages of contracting SARS-CoV-2. Given the variability of the virus structure, the utility of convalescent plasma is limited to the geographic area of its preparation, and for a short period of time. Intravenous immunoglobulin may also be protective in view of its nonspecific antiviral and immunomodulatory effects. Finally, human monoclonal antibodies may interact with some SARS-CoV-2 proteins, inhibiting the virus-receptor interaction and prevent tissue injury. The improved understanding of the host antiviral responses may help develop safe and effective immunotherapeutic strategies against COVID-19 in the foreseeable future.", "qid": 49, "docid": "0l86swz1", "rank": 73, "score": 0.7777881622314453}, {"content": "Title: The Dynamic Changes of Antibodies against SARS-CoV-2 during the Infection and Recovery of COVID-19 Content: Deciphering the dynamic changes of antibodies against SARS-CoV-2 is essential for understanding the immune response in COVID-19 patients. By comprehensively analyzing the laboratory findings of 1,850 patients, we describe the dynamic changes of the total antibody, spike protein (S)-, receptor-binding domain (RBD)-, and nucleoprotein (N)- specific IgM and IgG levels during SARS-CoV-2 infection and recovery. Our results indicate that the S-, RBD-, and N- specific IgG generation of severe/critical COVID-19 patients is one week later than mild/moderate cases, while the levels of these antibodies are 1.5-fold higher in severe/critical patients during hospitalization (P<0.01). The decrease of these IgG levels indicates the poor outcome of severe/critical patients. The RBD- and S-specific IgG levels are 2-fold higher in virus-free patients (P<0.05). Notably, we found that the patients who got re-infected had a low level of protective antibody on discharge. Therefore, our evidence proves that the dynamic changes of antibodies could provide an important reference for diagnosis, monitoring, and treatment, and shed new light on the precise management of COVID-19.", "qid": 49, "docid": "q5i8lpan", "rank": 74, "score": 0.7777582406997681}, {"content": "Title: Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID-19 Content: Background: SARS-CoV-2 infection causes an abrupt response by the host immune system, which is largely responsible for the pathogenesis and outcome of COVID-19. We aimed to investigate which specific responses from either cellular or humoral immunity associate to severity and progression of COVID-19. Methods: A cohort of 276 patients classified in mild, moderate and severe, was studied. Peripheral blood lymphocyte subpopulations were quantified by flow cytometry, and immunoglobulins and complement proteins by nephelometry. Results: At admission, dramatic lymphopenia of T, B and NK cells associated to severity. However, only the proportion of B cells increased, while T and NK cells appeared unaffected. Accordingly, the number of plasma cells and circulating follicular helper T cells (cTfh) increased, but levels of IgM, IgA and IgG were unaffected. When degrees of severity were considered, IgG was lower in severe patients, suggesting an IgG consumption by complement activation or antibody-dependent cellular cytotoxicity (ADCC). Activated CD56-CD16+ NK-cells, which mediate ADCC, were increased. Regarding complement, C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, compared to healthy donors. Moreover, IgG and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier. Conclusion: Our study provides important clues to understand the immune response observed in COVID-19 patients, which is probably related to viral clearance, but also underlies its pathogenesis and severity. This study associates for the first time COVID-19 severity with an imbalanced humoral immune response characterized by excessive consumption of IgG and C4, identifying new targets for therapeutic intervention.", "qid": 49, "docid": "7oaxtrul", "rank": 75, "score": 0.7769352197647095}, {"content": "Title: New IgM seroconversion and positive RT\u2010PCR test after exposure to the virus in recovered COVID\u201019 patient Content: To date, understanding whether acquired immunity and presence of anti SARS\u2010Cov2 antibodies protects against reinfection is one the most important focus of the scientific community [1\u20102]. Several studies suggest that acquired immunity may protect upon further exposure to SARS\u2010COV2 [3\u20106]. Contrary to this picture, we describe a case of a patient recovered from COVID\u201019 pneumonia with positive serology, followed up by 6 negative nasopharyngeal swab\u2010PCR tests performed along 1 month, who later on, after exposure to the virus, presented another positive RT\u2010PCR test and a second IgM seroconversion. This report opens up several possible interpretations. This article is protected by copyright. All rights reserved.", "qid": 49, "docid": "38mhmxvd", "rank": 76, "score": 0.7766457200050354}, {"content": "Title: Immune responses and pathogenesis of SARS\u2010CoV\u20102 during an outbreak in Iran: Comparison with SARS and MERS Content: The beginning of 2020 has seen the emergence of COVID\u201019, an outbreak caused by a novel coronavirus, SARS\u2010CoV\u20102, an important pathogen for humans. There is an urgent need to better understand this new virus and to develop ways to control its spread. In Iran, the first case of the COVID\u201019 was reported after spread from China and other countries. Fever, cough, and fatigue were the most common symptoms of this virus. In worldwide, the incubation period of COVID\u201019 was 3 to 7 days and approximately 80% of infections are mild or asymptomatic, 15% are severe, requiring oxygen, and 5% are critical infections, requiring ventilation. To mount an antiviral response, the innate immune system recognizes molecular structures that are produced by the invasion of the virus. COVID\u201019 infection induces IgG antibodies against N protein that can be detected by serum as early as day 4 after the onset of disease and with most patients seroconverting by day 14. Laboratory evidence of clinical patients showed that a specific T\u2010cell response against SARS\u2010CoV\u20102 is important for the recognition and killing of infected cells, particularly in the lungs of infected individuals. At present, there is no specific antiviral therapy for COVID\u201019 and the main treatments are supportive. In this review, we investigated the innate and acquired immune responses in patients who recovered from COVID\u201019, which could inform the design of prophylactic vaccines and immunotherapy for the future.", "qid": 49, "docid": "vpomgedg", "rank": 77, "score": 0.7766292691230774}, {"content": "Title: Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders Content: Background: To accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset. Results: Forty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P=0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset. Conclusions: Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys and for estimating the true infection prevalence in populations.", "qid": 49, "docid": "7l79ic0v", "rank": 78, "score": 0.7765838503837585}, {"content": "Title: Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections Content: The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described. We studied 37 asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization. Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy1. The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d). The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines. These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys.", "qid": 49, "docid": "gu3neito", "rank": 79, "score": 0.7765596508979797}, {"content": "Title: Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Content: The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described. We studied 37 asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization. Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy1. The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d). The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines. These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys.", "qid": 49, "docid": "lzgwxshi", "rank": 80, "score": 0.7765596508979797}, {"content": "Title: Immune Status of COVID-19 Patients with Reference to SARS and MERS Content: During this global pandemic of COVID-19 infection, it became well known that morbidity and mortality is especially high at the extreme of life especially in certain racial or ethnic groups like Americans and Africans This is presumed due to low immunity associated with other comorbid conditions like diabetes, hypertension, cardiovascular disease, obesity and metabolic syndrome But the information available on the immune status of COVID-19 patients is limited Attempts must be made to enhance our understanding of the immune status of COVID-19 patients by revisiting our knowledge on the immune mechanisms of already known coronaviruses such as SARS-CoV and MERS-CoV Early elevation of the serum levels of pro-inflammatory cytokines observed in SARS and MERS infection suggests a possible same type of cytokine storm-mediated lung damage in COVID-19 patients too Dysregulation of interferon-1 response and downstream cascade in initial innate immune response at virus entry point has been related to lethal pneumonia in COVID-19 patients Adaptive response of increased CD8+ levels in COVID-19 patients seems to be useful in mild cases where it causes deteriorating effects in progressed severe disease patients resulting in destruction of type 2 pneumocytes hence inability to regenerate the alveolar epithelium A phenomenon called cytokine storm activates violent immunological reactions in the lung tissue resulting in ARDS followed by multiple organ system damages in COVID-19 patients Several immune evading mechanisms are thought to be employed by severe respiratory syndrome virus-2 (SARS-CoV-2) that might have resulted in its extremely increased contagiousness probably related with its frequent RNA mutations Failure to develop adequate virus limiting immune reactions by some cured patients warrant monitoring of all recovered patients This rapid mini review is aimed to enhance our knowledge of the immune status of COVID-19 infected patients with reference to SARS-CoV and MERS-CoV", "qid": 49, "docid": "f37cp6j3", "rank": 81, "score": 0.7765588760375977}, {"content": "Title: How is immunosuppressive status affecting children and adults in SARS-CoV-2 infection? A systematic review Content: OBJECTIVES: SARS-CoV-2 infection has now a global resonance. Data on how COVID-19 is affecting immunocompromised patients are however few. With our study we aimed to systematically review the current knowledge on SARS-CoV-2 cases in children and adults with immunosuppression, to evaluate outcomes in this special population. METHODS: A systematic review of literature was carried out to identify relevant articles, searching the EMBASE, Medline, and Google Scholar databases. Studies reporting data on pre-defined outcomes and related to immunosuppressed adults and children with SARS-CoV-2 were included. RESULTS: Sixteen relevant articles were identified with 110 immunosuppressed patients, mostly presenting cancer, along with transplantation and immunodeficiency. Cancer was more often associated with a more severe course, but not necessarily with a bad prognosis. Our data show that both children and adults with immunosuppression seem to have a favorable disease course, as compared to the general population. CONCLUSION: Immunosuppressed patients with COVID-19 seem to be few in relation to the overall figures, and to present a favorable outcome as compared to other comorbidities. This might be explained by a hypothetical protective role of a weaker immune response, determining a milder disease presentation and thus underdiagnosis. Nevertheless, surveillance on this special population should be encouraged.", "qid": 49, "docid": "d8n3ydy5", "rank": 82, "score": 0.7765191793441772}, {"content": "Title: Evidence Supporting a Phased Immuno-physiological Approach to COVID-19 From Prevention Through Recovery. Content: This paper presents an evidence-based strategy for improving clinical outcomes in COVID-19. Recommendations are based on the phases of the disease, because optimal interventions for one phase may not be appropriate for a different phase. The four phases addressed are: Prevention, Infection, Inflammation and Recovery. Underlying this phased approach is recognition of emerging evidence for two different components of pathophysiology, early infection and late stage severe complications. These two aspects of the disease suggest two different patterns of clinical emphasis that seem on the surface to be not entirely concordant. We describe the application of therapeutic strategies and appropriate tactics that address four main stages of disease progression for COVID-19. Emerging evidence in COVID-19 suggests that the SARS-CoV-2 virus may both evade the innate immune response and kill macrophages. Delayed innate immune response and a depleted population of macrophages can theoretically result in a blunted antigen presentation, delaying and diminishing activation of the adaptive immune response. Thus, one clinical strategy involves supporting patient innate and adaptive immune responses early in the time course of illness, with the goal of improving the timeliness, readiness, and robustness of both the innate and adaptive immune responses. At the other end of the disease pathology spectrum, risk of fatality in COVID-19 is driven by excessive and persistent upregulation of inflammatory mechanisms associated with cytokine storm. Thus, the second clinical strategy is to prevent or mitigate excessive inflammatory response to prevent the cytokine storm associated with high mortality risk. Clinical support for immune system pathogen clearance mechanisms involves obligate activation of immune response components that are inherently inflammatory. This puts the goals of the first clinical strategy (immune activation) potentially at odds with the goals of the second strategy(mitigation of proinflammatory effects). This creates a need for discernment about the time course of the illness and with that, understanding of which components of an overall strategy to apply at each phase of the time course of the illness. We review evidence from early observational studies and the existing literature on both outcomes and mechanisms of disease, to inform a phased approach to support the patient at risk for infection, with infection, with escalating inflammation during infection, and at risk of negative sequelae as they move into recovery.", "qid": 49, "docid": "quweeq9e", "rank": 83, "score": 0.7764672040939331}, {"content": "Title: Retest positive for SARS-CoV-2 RNA of \"recovered\" patients with COVID-19: Persistence, sampling issues, or re-infection? Content: \"Retest Positive\" for severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) from \"recovered\" coronavirus disease-19 (COVID-19) has been reported and raised several important questions for this novel coronavirus and COVID-19 disease. In this commentary, we discussed several questions: (a) Can SARS-CoV-2 re-infect the individuals who recovered from COVID-19? This question is also associated with other questions: whether or not SARS-CoV-2 infection induces protective reaction or neutralized antibody? Will SARS-CoV-2 vaccines work? (b) Why could some recovered patients with COVID-19 be re-tested positive for SARS-CoV-2 RNA? (c) Are some recovered pwith atients COVID-19 with re-testing positive for SARS-CoV-2 RNA infectious? and (d) How should the COVID-19 patients with retest positive for SARS-CoV-2 be managed?", "qid": 49, "docid": "5x30jj1s", "rank": 84, "score": 0.7762743234634399}, {"content": "Title: Increased expression of CD8 marker on T-cells in COVID-19 patients Content: Abstract Background Cell-mediated immunity including T-cells (T helper and cytotoxic) plays an essential role in efficient antiviral responses against coronavirus disease-2019 (COVID-19). Therefore, in this study, we evaluated the ratio and expression of CD4 and CD8 markers in COVID-19 patients to clarify the immune characterizations of CD4 and CD8 T-cells in COVID-19 patients. Methods Peripheral blood samples of 25 COVID-19 patients and 25 normal individuals with similar age and sex as the control group were collected. White blood cells, platelets, and lymphocytes were counted and CD4 and CD8 T lymphocytes were evaluated by flow cytometry. Results The number of white blood cells, lymphocytes, and platelets were reduced significantly in COVID-19 patients (P < 0.05). The difference in CD4:CD8 ratio, CD4 T-cell frequency, CD8 T-cell frequency, and CD4 mean fluorescence intensity (MFI) was not significant between COVID-19 patients and healthy individuals (P > 0.05); however, the CD8 MFI increased significantly in COVID-19 infected patients (P < 0.05). Conclusion Although, there is no significant difference in the ratio of CD4 to CD8 between two groups, the expression level of CD8 in COVID-19 patients was significantly higher than the normal individuals. This result suggested that the cellular immune responses triggered by COVID-19 infection were developed through overexpression of CD8 and hyperactivation of cytotoxic T lymphocytes.", "qid": 49, "docid": "pjwgrejn", "rank": 85, "score": 0.7762507200241089}, {"content": "Title: Immune response to SARS\u2010CoV\u20102 and mechanisms of immunopathological changes in COVID\u201019 Content: As a zoonotic disease that has already spread globally to several million human beings and possibly to domestic and wild animals, eradication of coronavirus disease 2019 (COVID\u201019) appears practically impossible. There is a pressing need to improve our understanding of the immunology of this disease to contain the pandemic by developing vaccines and medicines for the prevention and treatment of patients. In this review, we aim to improve our understanding on the immune response and immunopathological changes in patients linked to detoriating clinical conditions such as, cytokine storm, acute respiratory distress syndrome, autopsy findings and changes in acute phase reactants and serum biochemistry in COVID\u201019. Similar to many other viral infections, asymptomatic disease is present in a significant but currently unknown fraction of the affected individuals.In the majority of the patients, a one\u2010week, self\u2010limiting viral respiratory disease typically occurs, which ends with the development of neutralizing anti\u2010viral T cell and antibody immunity. The IgM, IgA and IgG type virus\u2010specific antibodies levels are important measurements to predict population immunity against this disease and whether cross\u2010reactivity with other coronaviruses is taking place.High viral\u2010load during the first infection and repeated exposure to virus especially in healthcare workers can be an important factor for severity of disease. It should be noted that many aspects of severe patients are unique to COVID\u201019 and are rarely observed in other respiratory viral infections, such as severe lymphopenia and eosinopenia, extensive pneumonia and lung tissue damage, a cytokine storm leading to acute respiratory distress syndrome and multiorgan failure. Lymphopenia causes a defect in antiviral and immune regulatory immunity. At the same time, a cytokine storm starts with extensive activation of cytokine\u2010secreting cells with innate and adaptive immune mechanisms both of with contribute to a poor prognosis. Elevated levels of acute phase reactants and lymphopenia are early predictors of high disease severity. Prevention of development to severe disease, cytokine storm, acute respiratory distress syndrome and novel approachs to prevent their development will be main routes for future research areas. As we learn to live amidst the virus, understanding the immunology of the disease can assist in containing the pandemic and in developing vaccines and medicines to prevent and treat individual patients.", "qid": 49, "docid": "fczf3lzc", "rank": 86, "score": 0.776063084602356}, {"content": "Title: Immune alterations during SARS-CoV-2-related acute respiratory distress syndrome Content: We report a longitudinal analysis of the immune response associated with a fatal case of COVID-19. This patient exhibited a rapid evolution towards multiorgan failure. SARS-CoV-2 was detected in multiple nasopharyngeal, blood, and pleural samples, despite antiviral and immunomodulator treatment. Clinical evolution in the blood was marked by an increase (2-3 fold) in differentiated effector T cells expressing exhaustion (PD-1) and senescence (CD57) markers, an expansion of antibody-secreting cells, a 15-fold increase in {gamma}{delta} T-cell and proliferating NK-cell populations, and the total disappearance of monocytes, suggesting lung trafficking. In the serum, waves of a proinflammatory cytokine storm, Th1 and Th2 activation, and markers of T-cell exhaustion, apoptosis, cell cytotoxicity, and endothelial activation were observed until the fatal outcome. This case underscores the need for well-designed studies to investigate complementary approaches to control viral replication, the source of the hyperinflammatory status, and immunomodulation to target the pathophysiological response.", "qid": 49, "docid": "qfmvtkwb", "rank": 87, "score": 0.775765061378479}, {"content": "Title: Follow-up studies in COVID-19 recovered patients - is it mandatory? Content: The novel Coronavirus disease 2019 (COVID-19) is an illness caused due to Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The World Health Organization (WHO) has declared this outbreak a global health emergency and as on April 24, 2020, it has spread to 213 countries, with 25,91,015 confirmed cases and 742,855 cases have been recovered from COVID-19. In this dreadful situation our team has already published an article in the Science of the Total Environment, which elaborates the various aspects of the SARS-CoV-2 infection. In this situation, it is imperative to understand the possible outcome of COVID-19 recovered patients and determine if they have any other detrimental illnesses by longitudinal analysis to safeguard their life in future. It is necessary to follow-up these recovered patients and performs comprehensive assessments for detection and appropriate management towards their psychological, physical, and social realm. This urges us to suggest that it is highly important to provide counselling, moral support as well as a few recommended guidelines to the recovered patients and society to restore to normalcy. Epidemiological, clinical and immunological studies from COVID-19 recovered patients are particularly important to understand the disease and to prepare better for potential outbreaks in the future. Longitudinal studies on a larger cohort would help us to understand the in-depth prognosis as well as the pathogenesis of COVID-19. Also, follow-up studies will help us provide more information for the development of vaccines and drugs for these kinds of pandemics in the future. Hence, we recommend more studies are required to unravel the possible mechanism of COVID-19 infection and the after-effects of it to understand the characteristics of the virus and to develop the necessary precautionary measures to prevent it.", "qid": 49, "docid": "uqhaxqqh", "rank": 88, "score": 0.7754606008529663}, {"content": "Title: Lack of Reinfection in Rhesus Macaques Infected with SARS-CoV-2 Content: A global pandemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is ongoing spread. It remains unclear whether the convalescing patients have a risk of reinfection. Rhesus macaques were rechallenged with SARS-CoV-2 during an early recovery phase from initial infection characterized by weight loss, interstitial pneumonia and systemic viral dissemination mainly in respiratory and gastrointestinal tracts. The monkeys rechallenged with the identical SARS-CoV-2 strain have failed to produce detectable viral dissemination, clinical manifestations and histopathological changes. A notably enhanced neutralizing antibody response might contribute the protection of rhesus macaques from the reinfection by SARS-CoV-2. Our results indicated that primary SARS-CoV-2 infection protects from subsequent reinfection. One Sentence Summary Neutralizing antibodies against SARS-CoV-2 might protect rhesus macaques which have undergone an initial infection from reinfection during early recovery days.", "qid": 49, "docid": "q4m2uj6r", "rank": 89, "score": 0.7753955125808716}, {"content": "Title: Targeted Immunosuppression Distinguishes COVID-19 from Influenza in Moderate and Severe Disease Content: Coronavirus disease 2019 (COVID-19) is characterized by a high incidence of acute respiratory failure. The underlying immunopathology of that failure and how it compares to other causes of severe respiratory distress, such as influenza virus infection, are not fully understood. Here we addressed this by developing a prospective observational cohort of COVID-19 and influenza subjects with varying degrees of disease severity and assessing the quality and magnitude of their immune responses at the cellular and protein level. Additionally, we performed single-cell RNA transcriptional profiling of peripheral blood mononuclear cells from select subjects. The cohort consists of 79 COVID-19 subjects, 26 influenza subjects, and 15 control subjects, including 35 COVID-19 and 7 influenza subjects with acute respiratory failure. While COVID-19 subjects exhibited largely equivalent or greater activated lymphocyte counts compared to influenza subjects, they had fewer monocytes and lower surface HLA-class II expression on monocytes compared to influenza subjects and controls. At least two distinct immune profiles were observed by cytokine levels in severe COVID-19 patients: 3 of 71 patients were characterized by extreme inflammation, with greater than or equal to ~50% of the 35 cytokines measured greater than 2 standard deviations from the mean level of other severe patients (both influenza and COVID-19); the other immune profile, which characterized 68 of 71 subjects, had a mixed inflammatory signature, where 28 of 35 cytokines in COVID-19 patients had lower mean cytokine levels, though not all were statistically significant. Only 2 cytokines were higher in COVID-19 subjects compared to influenza subjects (IL-6 and IL-8). Influenza and COVID-19 patients could be distinguished statistically based on cytokine module expression, particularly after controlling for the significant effects of age on cytokine expression, but again with lower levels of most cytokines in COVID-19 subjects. Further, high circulating levels of IL-1RA and IL-6 were associated with increased odds of intubation in the combined influenza and COVID-19 cohort [OR = 3.93 and 4.30, respectively] as well as among only COVID-19 patients. Single cell transcriptional profiling of COVID-19 and influenza subjects with respiratory failure identified profound suppression in type I and type II interferon signaling in COVID-19 patients across multiple clusters. In contrast, COVID-19 cell clusters were enriched for alterations in metabolic, stress, and apoptotic pathways. These alterations were consistent with an increased glucocorticoid response in COVID-19 patients compared to influenza. When considered across the spectrum of innate and adaptive immune profiles, the immune pathologies underlying severe influenza and COVID-19 are substantially distinct. The majority of COVID-19 patients with acute respiratory failure do not have a cytokine storm phenotype but instead exhibit profound type I and type II IFN immunosuppression when compared to patients with acute influenza. Upregulation of a small number of inflammatory mediators, including IL-6, predicts acute respiratory failure in both COVID-19 and influenza patients.", "qid": 49, "docid": "z9uu4sj7", "rank": 90, "score": 0.775360107421875}, {"content": "Title: Convalescent donor SARS-COV-2-specific cytotoxic T lymphocyte infusion as a possible treatment option for COVID-19 patients with severe disease - has not received enough attention till date. Content: One of the hallmarks of COVID-19 is a reduction in lymphocyte counts, and the degree of reduction correlates with disease severity. Studies have shown a linear negative correlation between peripheral blood CD8+ T cells counts and viral copy numbers in nasopharynx and disease severity. In addition, CD8+ T cells are reported to be functionally 'exhausted'. Currently, there is no proven treatment for COVID-19. Cytotoxic T cells are key to fighting intracellular viruses. In the context of haematopoietic stem cell transplantation, a variety of viral infections have been successfully treated using off-the-shelf HLA-matched virus-specific cytotoxic T cells. A similar strategy using convalescent donor CD8+ T cells appears to be the need of the hour and has not received enough attention till date.", "qid": 49, "docid": "0rn439n7", "rank": 91, "score": 0.7752953767776489}, {"content": "Title: Symptoms and immunoglobulin development in hospital staff exposed to a SARS-CoV-2 outbreak. Content: BACKGROUND Worldwide, the number of SARS-CoV-2 infections is increasing. Serological immunoglobulin tests may help to better understand the development of immune mechanisms against SARS-CoV-2 in COVID-19 cases and exposed but asymptomatic individuals. The aim of this study was to investigate exposure to SARS-CoV-2, symptoms and antibody responses in a large sample of health care workers following a COVID-19 outbreak. METHODS A COVID-19 outbreak among staff members of a major German children's and women's hospital was followed by massive RT-PCR SARS-CoV-2 tests and provided the opportunity to study symptoms, chains of infection and SARS-CoV-2 specific antibody responses (IgG and IgA) by ELISA. Study participants were classified as COVID-19 cases, and persons with close, moderate or no exposure to SARS-CoV-2 in the clinical setting, respectively. RESULTS Out of 201 study participants, 31 were COVID-19 cases. While most study participants experienced many symptoms indicative for SARS-CoV-2 infection, anosmia and coughing were remarkably more frequent in COVID-19 cases. Approximately 80% of COVID-19 cases developed some specific antibody response (IgA and IgG) approximately 3 weeks after onset of symptoms. Subjects in the non COVID-19 groups had also elevated IgG (1.8%) and IgA values (7.6%) irrespective of contact history with cases. CONCLUSION We found that a significant number of diseased did not develop relevant antibody responses three weeks after symptom onset. Our data also suggests that exposure to COVID-19 positive co-workers in a hospital setting is not leading to the development of measurable immune responses in a significant proportion of asymptomatic contact-persons.", "qid": 49, "docid": "l11epnl4", "rank": 92, "score": 0.7752618789672852}, {"content": "Title: Longitudinal hematologic and immunologic variations associated with the progression of COVID-19 patients in China Content: BACKGROUND: Crucial roles of hematologic and immunologic responses in progression of coronavirus disease 2019 (COVID-19) remain largely unclear. OBJECTIVE: We sought to address the dynamic changes in hematologic and immunologic biomarkers and their associations with severity and outcomes of COVID-19. METHODS: A retrospective study including 548 patients with COVID-19 with clarified outcome (discharged or deceased) from a national cohort in China was performed. Cross-sectional and longitudinal variations were compared and the associations with different severity and outcomes were analyzed. RESULTS: On admission, the counts of lymphocytes, T-cell subsets, eosinophils, and platelets decreased markedly, especially in severe/critical and fatal patients. Increased neutrophil count and neutrophils-to-lymphocytes ratio were predominant in severe/critical cases or nonsurvivors. During hospitalization, eosinophils, lymphocytes, and platelets showed an increasing trend in survivors, but maintained lower levels or dropped significantly afterwards in nonsurvivors. Nonsurvivors kept a high level or showed an upward trend for neutrophils, IL-6, procalcitonin, D-dimer, amyloid A protein, and C-reactive protein, which were kept stable or showed a downward trend in survivors. Positive correlation between CD8+ T-cell and lymphocytes count was found in survivors but not in nonsurvivors. A multivariate Cox regression model suggested that restored levels of lymphocytes, eosinophils, and platelets could serve as predictors for recovery, whereas progressive increases in neutrophils, basophils, and IL-6 were associated with fatal outcome. CONCLUSIONS: Hematologic and immunologic impairment showed a significantly different profile between survivors and nonsurvivors in patients with COVID-19 with different severity. The longitudinal variations in these biomarkers could serve to predict recovery or fatal outcome.", "qid": 49, "docid": "u0j1atdh", "rank": 93, "score": 0.775117039680481}, {"content": "Title: Follow-up studies in COVID-19 recovered patients - is it mandatory? Content: Abstract The novel Coronavirus disease 2019 (COVID-19) is an illness caused due to Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The World Health Organization (WHO) has declared this outbreak a global health emergency and as on April 24, 2020, it has spread to 213 countries, with 25,91,015 confirmed cases and 742,855 cases have been recovered from COVID-19. In this dreadful situation our team has already published an article in the Science of the Total Environment, which elaborates the various aspects of the SARS-CoV-2 infection. In this situation, it is imperative to understand the possible outcome of COVID-19 recovered patients and determine if they have any other detrimental illnesses by longitudinal analysis to safeguard their life in future. It is necessary to follow-up these recovered patients and performs comprehensive assessments for detection and appropriate management towards their psychological, physical, and social realm. This urges us to suggest that it is highly important to provide counselling, moral support as well as a few recommended guidelines to the recovered patients and society to restore to normalcy. Epidemiological, clinical and immunological studies from COVID-19 recovered patients are particularly important to understand the disease and to prepare better for potential outbreaks in the future. Longitudinal studies on a larger cohort would help us to understand the in-depth prognosis as well as the pathogenesis of COVID-19. Also, follow-up studies will help us provide more information for the development of vaccines and drugs for these kinds of pandemics in the future. Hence, we recommend more studies are required to unravel the possible mechanism of COVID-19 infection and the after-effects of it to understand the characteristics of the virus and to develop the necessary precautionary measures to prevent it.", "qid": 49, "docid": "8p9d1c9k", "rank": 94, "score": 0.7749215364456177}, {"content": "Title: Protective immunity after COVID-19 has been questioned: What can we do without SARS-CoV-2-IgG detection? Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a severe acute respiratory syndrome that is called COVID-19. Clinical manifestations of COVID-19 include diarrhea, pneumonia, lymphopenia, exhausted lymphocytes, and pro-inflammatory cytokine production. Immunology is part of the process of clinical evolution, but there are some questions around immunity-based protection: (1) why some infected people have only mild symptoms of the disease or are asymptomatic; (2) why delayed and weak antibody responses are associated with severe outcomes; and (3) why positivity in molecular tests does not represent protective antibody IgG. Perhaps T cell responses may be the key to solving those questions. SARS-CoV-2-specific memory T cells persist in peripheral blood and may be capable of providing effective information about protective immunity. The T cells studies can be helpful in elucidating the pathways for development of vaccines, therapies, and diagnostics for COVID-19 and for filling these immunology knowledge gaps.", "qid": 49, "docid": "rs79r7kc", "rank": 95, "score": 0.7748807668685913}, {"content": "Title: Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19 Content: As a zoonotic disease that has already spread globally to several million human beings and possibly to domestic and wild animals, eradication of coronavirus disease 2019 (COVID-19) appears practically impossible. There is a pressing need to improve our understanding of the immunology of this disease to contain the pandemic by developing vaccines and medicines for the prevention and treatment of patients. In this review, we aim to improve our understanding on the immune response and immunopathological changes in patients linked to deteriorating clinical conditions such as cytokine storm, acute respiratory distress syndrome, autopsy findings and changes in acute-phase reactants, and serum biochemistry in COVID-19. Similar to many other viral infections, asymptomatic disease is present in a significant but currently unknown fraction of the affected individuals. In the majority of the patients, a 1-week, self-limiting viral respiratory disease typically occurs, which ends with the development of neutralizing antiviral T cell and antibody immunity. The IgM-, IgA-, and IgG-type virus-specific antibodies levels are important measurements to predict population immunity against this disease and whether cross-reactivity with other coronaviruses is taking place. High viral load during the first infection and repeated exposure to virus especially in healthcare workers can be an important factor for severity of disease. It should be noted that many aspects of severe patients are unique to COVID-19 and are rarely observed in other respiratory viral infections, such as severe lymphopenia and eosinopenia, extensive pneumonia and lung tissue damage, a cytokine storm leading to acute respiratory distress syndrome, and multiorgan failure. Lymphopenia causes a defect in antiviral and immune regulatory immunity. At the same time, a cytokine storm starts with extensive activation of cytokine-secreting cells with innate and adaptive immune mechanisms both of which contribute to a poor prognosis. Elevated levels of acute-phase reactants and lymphopenia are early predictors of high disease severity. Prevention of development to severe disease, cytokine storm, acute respiratory distress syndrome, and novel approaches to prevent their development will be main routes for future research areas. As we learn to live amidst the virus, understanding the immunology of the disease can assist in containing the pandemic and in developing vaccines and medicines to prevent and treat individual patients.", "qid": 49, "docid": "1w7g6dkq", "rank": 96, "score": 0.7748485803604126}, {"content": "Title: Position paper on the preparation of immune plasma to be used in the treatment of patients with COVID-19 Content: Passive immunotherapy with plasma derived from convalescent patients recovering from SARS-CoV-2 infection can be a promising approach in the treatment of COVID-19 patients. It is important that blood establishments are ready to satisfy requests for immune plasma by defining the requirements applicable to plasma donors and the standards for preparation, qualification, storage, distribution, and control of product use. This Position paper aims to give recommendations on the biological characteristics of a plasma preparation from convalescent donors and to support the evaluation of this therapeutic approach in more rigorous investigations.", "qid": 49, "docid": "82o0z8nn", "rank": 97, "score": 0.7748007774353027}, {"content": "Title: Position paper on the preparation of immune plasma to be used in the treatment of patients with COVID-19. Content: Passive immunotherapy with plasma derived from convalescent patients recovering from SARS-CoV-2 infection can be a promising approach in the treatment of COVID-19 patients. It is important that blood establishments are ready to satisfy requests for immune plasma by defining the requirements applicable to plasma donors and the standards for preparation, qualification, storage, distribution, and control of product use. This Position paper aims to give recommendations on the biological characteristics of a plasma preparation from convalescent donors and to support the evaluation of this therapeutic approach in more rigorous investigations.", "qid": 49, "docid": "woih3boo", "rank": 98, "score": 0.7748006582260132}, {"content": "Title: Immunopathology and immunotherapeutic strategies in severe acute respiratory syndrome coronavirus 2 infection Content: The outbreak of coronavirus disease 2019 (COVID-19) and pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a major concern globally. As of 14 April 2020, more than 1.9 million COVID-19 cases have been reported in 185 countries. Some patients with COVID-19 develop severe clinical manifestations, while others show mild symptoms, suggesting that dysregulation of the host immune response contributes to disease progression and severity. In this review, we have summarized and discussed recent immunological studies focusing on the response of the host immune system and the immunopathology of SARS-CoV-2 infection as well as immunotherapeutic strategies for COVID-19. Immune evasion by SARS-CoV-2, functional exhaustion of lymphocytes, and cytokine storm have been discussed as part of immunopathology mechanisms in SARS-CoV-2 infection. Some potential immunotherapeutic strategies to control the progression of COVID-19, such as passive antibody therapy and use of interferon &#945;\u00df and IL-6 receptor (IL-6R) inhibitor, have also been discussed. This may help us to understand the immune status of patients with COVID-19, particularly those with severe clinical presentation, and form a basis for further immunotherapeutic investigations.", "qid": 49, "docid": "2h8i4pyb", "rank": 99, "score": 0.7747251987457275}, {"content": "Title: Immunopathology and immunotherapeutic strategies in severe acute respiratory syndrome coronavirus 2 infection. Content: The outbreak of coronavirus disease 2019 (COVID-19) and pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a major concern globally. As of 14 April 2020, more than 1.9 million COVID-19 cases have been reported in 185 countries. Some patients with COVID-19 develop severe clinical manifestations, while others show mild symptoms, suggesting that dysregulation of the host immune response contributes to disease progression and severity. In this review, we have summarized and discussed recent immunological studies focusing on the response of the host immune system and the immunopathology of SARS-CoV-2 infection as well as immunotherapeutic strategies for COVID-19. Immune evasion by SARS-CoV-2, functional exhaustion of lymphocytes, and cytokine storm have been discussed as part of immunopathology mechanisms in SARS-CoV-2 infection. Some potential immunotherapeutic strategies to control the progression of COVID-19, such as passive antibody therapy and use of interferon \u03b1\u03b2 and IL-6 receptor (IL-6R) inhibitor, have also been discussed. This may help us to understand the immune status of patients with COVID-19, particularly those with severe clinical presentation, and form a basis for further immunotherapeutic investigations.", "qid": 49, "docid": "vlse2pzs", "rank": 100, "score": 0.7747217416763306}]}
{"query": "what is known about an mRNA vaccine for the SARS-CoV-2 virus?", "hits": [{"content": "Title: RNA to the rescue: RNA is one of the most promising targets for drug development given its wide variety of uses Content: The race for a vaccine against SARS-CoV-2 has accelerated research on RNA-based therapeutics. Beyond vaccines, RNA also shows great potential for cancer therapies.", "qid": 50, "docid": "avxexjl5", "rank": 1, "score": 0.7928109765052795}, {"content": "Title: RNA to the rescue: RNA is one of the most promising targets for drug development given its wide variety of uses Content: The race for a vaccine against SARS\u2010CoV\u20102 has accelerated research on RNA\u2010based therapeutics. Beyond vaccines, RNA also shows great potential for cancer therapies.[Image: see text]", "qid": 50, "docid": "xhm97wy2", "rank": 2, "score": 0.7799955010414124}, {"content": "Title: Leveraging mRNAs sequences to express SARS-CoV-2 antigens in vivo Content: SARS-CoV-2 has rapidly become a pandemic worldwide; therefore, an effective vaccine is urgently needed. Recently, messenger RNAs (mRNAs) have emerged as a promising platform for vaccination. Here, we systematically investigated the untranslated regions (UTRs) of mRNAs in order to enhance protein production. Through a comprehensive analysis of endogenous gene expression and de novo design of UTRs, we identified the optimal combination of 5\u2019 and 3\u2019 UTR, termed as NASAR, which was five to ten-fold more efficient than the tested endogenous UTRs. More importantly, NASAR mRNAs delivered by lipid-derived nanoparticles showed dramatic expression of potential SARS-CoV-2 antigens both in vitro and in vivo. These NASAR mRNAs merit further development as alternative SARS-CoV-2 vaccines.", "qid": 50, "docid": "aju2nr9x", "rank": 3, "score": 0.7790278792381287}, {"content": "Title: B-cell engineering: A promising approach towards vaccine development for COVID-19 Content: With the number of cases crossing six million (and more than three hundred and seventy thousand deaths) worldwide, there is a dire need of a vaccine (and repurposing of drugs) for SARS-CoV-2 disease (COVID-19). It can be argued that a vaccine may be the most efficient way to contain the spread of this disease and prevent its future onset. While many attempts are being made to design and develop a vaccine for SARS-CoV-2, pertinent technological hitches do exist. That is perhaps one of the reasons that we don't have vaccine for coronaviruses (including SARS-CoV-1 and MERS). Recently developed CRISPR-mediated genome editing approach can be repurposed into a cell-modification endeavor in addition to (and rather than) correcting defective parts of genome. With this premise, B-cells can be engineered into universal donor, antigen specific, perpetually viable, long lasting, non-oncogenic, relatively benign, antibody producing cells which may serve as an effective vaccine for SARS-CoV-2 and, by the same rationale, other viruses and pathogens.", "qid": 50, "docid": "4d13zapk", "rank": 4, "score": 0.7715137004852295}, {"content": "Title: SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness Content: A SARS-CoV-2 vaccine is needed to control the global COVID-19 public health crisis. Atomic-level structures directed the application of prefusion-stabilizing mutations that improved expression and immunogenicity of betacoronavirus spike proteins. Using this established immunogen design, the release of SARS-CoV-2 sequences triggered immediate rapid manufacturing of an mRNA vaccine expressing the prefusion-stabilized SARS-CoV-2 spike trimer (mRNA-1273). Here, we show that mRNA-1273 induces both potent neutralizing antibody and CD8 T cell responses and protects against SARS-CoV-2 infection in lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a Phase 2 clinical trial with a trajectory towards Phase 3 efficacy evaluation.", "qid": 50, "docid": "1v0f2dtx", "rank": 5, "score": 0.7707518339157104}, {"content": "Title: B-Cell Engineering: A promising approach towards vaccine development for COVID-19 Content: With the number of cases crossing three million (and more than two hundred and fifty thousand deaths) worldwide, there is a dire need of a vaccine (and repurposing of drugs) for SARS-CoV-2 disease (COVID-19). It can be argued that a vaccine may be the most efficient way to contain the spread of this disease and prevent its future onset. While many attempts are being made to design and develop a vaccine for SARS-CoV-2, pertinent technological hitches do exist. That is perhaps one of the reasons that we don\u2019t have vaccine for coronaviruses (including SARS-CoV-1 and MERS). Recently developed CRISPR-mediated genome editing approach can be repurposed into a cell modification endeavor rather than correcting defective parts of genome. With this premise, B-cells can be engineered into universal donor, antigen specific, perpetually viable, long lasting, non-oncogenic, relatively benign, antibody producing cells which may serve as an effective vaccine for SARS-CoV-2 and, by the same rationale, other viruses and pathogens.", "qid": 50, "docid": "fhhfyznj", "rank": 6, "score": 0.7697556018829346}, {"content": "Title: An Evidence Based Perspective on mRNA-SARS-CoV-2 Vaccine Development Content: The first outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in Wuhan, Hubei Province, China, in late 2019. The subsequent COVID-19 pandemic rapidly affected the health and economy of the world. The global approach to the pandemic was to isolate populations to reduce the spread of this deadly virus while vaccines began to be developed. In March 2020, the first phase I clinical trial of a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine, mRNA-1273, which encodes the spike protein (S protein) of SARS-CoV-2, began in the United States (US). The production of mRNA-based vaccines is a promising recent development in the production of vaccines. However, there remain significant challenges in the development and testing of vaccines as rapidly as possible to control COVID-19, which requires international collaboration. This review aims to describe the background to the rationale for the development of mRNA-based SARS-CoV-2 vaccines and the current status of the mRNA-1273 vaccine.", "qid": 50, "docid": "xbze5s3c", "rank": 7, "score": 0.7680726051330566}, {"content": "Title: Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice Content: The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle (LNP) as a vaccine. We observe remarkably high and dose-dependent SARS-CoV-2 specific antibody titers in mouse sera, as well as robust neutralization of both a pseudo-virus and wild-type virus. Upon further characterization we find that the neutralization is proportional to the quantity of specific IgG and of higher magnitude than recovered COVID-19 patients. saRNA LNP immunizations induce a Th1-biased response in mice, and there is no antibody-dependent enhancement (ADE) observed. Finally, we observe high cellular responses, as characterized by IFN-\u03b3 production, upon re-stimulation with SARS-CoV-2 peptides. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic.", "qid": 50, "docid": "1c15qxb8", "rank": 8, "score": 0.768018364906311}, {"content": "Title: Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice Content: The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle (LNP) as a vaccine. We observe remarkably high and dose-dependent SARS-CoV-2 specific antibody titers in mouse sera, as well as robust neutralization of both a pseudo-virus and wild-type virus. Upon further characterization we find that the neutralization is proportional to the quantity of specific IgG and of higher magnitude than recovered COVID-19 patients. saRNA LNP immunizations induce a Th1-biased response in mice, and there is no antibody-dependent enhancement (ADE) observed. Finally, we observe high cellular responses, as characterized by IFN-\u00ce\u00b3 production, upon re-stimulation with SARS-CoV-2 peptides. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic.", "qid": 50, "docid": "oiu80002", "rank": 9, "score": 0.7671791315078735}, {"content": "Title: SARS-CoV-2 will constantly sweep its tracks: a vaccine containing CpG motifs in 'lasso' for the multi-faced virus Content: During the current COVID-19 pandemic, the global ratio between the dead and the survivors is approximately 1 to 10, which has put humanity on high alert and provided strong motivation for the intensive search for vaccines and drugs. It is already clear that if we follow the most likely scenario, which is similar to that used to create seasonal influenza vaccines, then we will need to develop improved vaccine formulas every year to control the spread of the new, highly mutable coronavirus SARS-CoV-2. In this article, using well-known RNA viruses (HIV, influenza viruses, HCV) as examples, we consider the main successes and failures in creating primarily highly effective vaccines. The experience accumulated dealing with the biology of zoonotic RNA viruses suggests that the fight against COVID-19 will be difficult and lengthy. The most effective vaccines against SARS-CoV-2 will be those able to form highly effective memory cells for both humoral (memory B cells) and cellular (cross-reactive antiviral memory T cells) immunity. Unfortunately, RNA viruses constantly sweep their tracks and perhaps one of the most promising solutions in the fight against the COVID-19 pandemic is the creation of 'universal' vaccines based on conservative SARS-CoV-2 genome sequences (antigen-presenting) and unmethylated CpG dinucleotides (adjuvant) in the composition of the phosphorothioate backbone of single-stranded DNA oligonucleotides (ODN), which can be effective for long periods of use. Here, we propose a SARS-CoV-2 vaccine based on a lasso-like phosphorothioate oligonucleotide construction containing CpG motifs and the antigen-presenting unique ACG-containing genome sequence of SARS-CoV-2. We found that CpG dinucleotides are the least rare dinucleotides in the genomes of SARS-CoV-2 and other known human coronaviruses, and hypothesized that their higher frequency could be responsible for the unwanted increased lethality to the host, causing a 'cytokine storm' in people who overexpress cytokines through the activation of specific Toll-like receptors in a manner similar to TLR9-CpG ODN interactions. Interestingly, the virus strains sequenced in China (Wuhan) in February 2020 contained on average one CpG dinucleotide more in their genome than the later strains from the USA (New York) sequenced in May 2020. Obviously, during the first steps of the microevolution of SARS-CoV-2 in the human population, natural selection tends to select viral genomes containing fewer CpG motifs that do not trigger a strong innate immune response, so the infected person has moderate symptoms and spreads SARS-CoV-2 more readily. However, in our opinion, unmethylated CpG dinucleotides are also capable of preparing the host immune system for the coronavirus infection and should be present in SARS-CoV-2 vaccines as strong adjuvants.", "qid": 50, "docid": "mxcfkyui", "rank": 10, "score": 0.7623847723007202}, {"content": "Title: DNA vaccine protection against SARS-CoV-2 in rhesus macaques Content: The global COVID-19 pandemic caused by the SARS-CoV-2 virus has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 Spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. Following vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log(10) reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.", "qid": 50, "docid": "w9zyshzb", "rank": 11, "score": 0.761972188949585}, {"content": "Title: Designing a novel mRNA vaccine against SARS-CoV-2: An immunoinformatics approach Content: SARS-CoV-2 is the deadly virus behind COVID-19, the disease that went on to ravage the world and caused the biggest pandemic 21st century has witnessed so far. On the face of ongoing death and destruction, the urgent need for the discovery of a vaccine against the virus is paramount. This study resorted to the emerging discipline of immunoinformatics in order to design a multi-epitope mRNA vaccine against the spike glycoprotein of SARS-CoV-2. Various immunoinformatics tools were utilized to predict T and B lymphocyte epitopes. The epitopes were channeled through a filtering pipeline comprised of antigenicity, toxicity, allergenicity, and cytokine inducibility evaluation with the goal of selecting epitopes capable of generating both T and B cell-mediated immune responses. Molecular docking simulation between the epitopes and their corresponding MHC molecules was carried out. 13 epitopes, a highly immunogenic adjuvant, elements for proper sub-cellular trafficking, a secretion booster, and appropriate linkers were combined for constructing the vaccine. The vaccine was found to be antigenic, almost neutral at physiological pH, non-toxic, non-allergenic, capable of generating a robust immune response and had a decent worldwide population coverage. Based on these parameters, this design can be considered a promising choice for a vaccine against SARS-CoV-2.", "qid": 50, "docid": "q77da2y3", "rank": 12, "score": 0.7619322538375854}, {"content": "Title: Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design Content: As the SARS-CoV-2 pandemic is rapidly progressing, the need for the development of an effective vaccine is critical. A promising approach for vaccine development is to generate, through codon pair deoptimization, an attenuated virus. This approach carries the advantage that it only requires limited knowledge specific to the virus in question, other than its genome sequence. Therefore, it is well suited for emerging viruses for which we may not have extensive data. We performed comprehensive in silico analyses of several features of SARS-CoV-2 genomic sequence (e.g., codon usage, codon pair usage, dinucleotide/junction dinucleotide usage, RNA structure around the frameshift region) in comparison with other members of the coronaviridae family of viruses, the overall human genome, and the transcriptome of specific human tissues such as lung, which are primarily targeted by the virus. Our analysis identified the spike (S) and nucleocapsid (N) proteins as promising targets for deoptimization and suggests a roadmap for SARS-CoV-2 vaccine development, which can be generalizable to other viruses.", "qid": 50, "docid": "2fn25l6m", "rank": 13, "score": 0.7615591287612915}, {"content": "Title: SARS-CoV-2 will constantly sweep its tracks: a vaccine containing CpG motifs in \u2018lasso\u2019 for the multi-faced virus Content: During the current COVID-19 pandemic, the global ratio between the dead and the survivors is approximately 1 to 10, which has put humanity on high alert and provided strong motivation for the intensive search for vaccines and drugs. It is already clear that if we follow the most likely scenario, which is similar to that used to create seasonal influenza vaccines, then we will need to develop improved vaccine formulas every year to control the spread of the new, highly mutable coronavirus SARS-CoV-2. In this article, using well-known RNA viruses (HIV, influenza viruses, HCV) as examples, we consider the main successes and failures in creating primarily highly effective vaccines. The experience accumulated dealing with the biology of zoonotic RNA viruses suggests that the fight against COVID-19 will be difficult and lengthy. The most effective vaccines against SARS-CoV-2 will be those able to form highly effective memory cells for both humoral (memory B cells) and cellular (cross-reactive antiviral memory T cells) immunity. Unfortunately, RNA viruses constantly sweep their tracks and perhaps one of the most promising solutions in the fight against the COVID-19 pandemic is the creation of 'universal' vaccines based on conservative SARS-CoV-2 genome sequences (antigen-presenting) and unmethylated CpG dinucleotides (adjuvant) in the composition of the phosphorothioate backbone of single-stranded DNA oligonucleotides (ODN), which can be effective for long periods of use. Here, we propose a SARS-CoV-2 vaccine based on a lasso-like phosphorothioate oligonucleotide construction containing CpG motifs and the antigen-presenting unique ACG-containing genome sequence of SARS-CoV-2. We found that CpG dinucleotides are the least rare dinucleotides in the genomes of SARS-CoV-2 and other known human coronaviruses, and hypothesized that their higher frequency could be responsible for the unwanted increased lethality to the host, causing a \u2018cytokine storm\u2019 in people who overexpress cytokines through the activation of specific Toll-like receptors in a manner similar to TLR9-CpG ODN interactions. Interestingly, the virus strains sequenced in China (Wuhan) in February 2020 contained on average one CpG dinucleotide more in their genome than the later strains from the USA (New York) sequenced in May 2020. Obviously, during the first steps of the microevolution of SARS-CoV-2 in the human population, natural selection tends to select viral genomes containing fewer CpG motifs that do not trigger a strong innate immune response, so the infected person has moderate symptoms and spreads SARS-CoV-2 more readily. However, in our opinion, unmethylated CpG dinucleotides are also capable of preparing the host immune system for the coronavirus infection and should be present in SARS-CoV-2 vaccines as strong adjuvants.", "qid": 50, "docid": "xeq0dq6u", "rank": 14, "score": 0.7615573406219482}, {"content": "Title: DNA vaccine protection against SARS-CoV-2 in rhesus macaques Content: The global COVID-19 pandemic caused by the SARS-CoV-2 virus has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 Spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. Following vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.", "qid": 50, "docid": "pfjq2m42", "rank": 15, "score": 0.7613363265991211}, {"content": "Title: Vaccines against Coronaviruses: The State of the Art Content: The emerging epidemic caused by the new coronavirus SARS-CoV-2 represents the most important socio-health threat of the 21st century. The high contagiousness of the virus, the strong impact on the health system of the various countries and the absence to date of treatments able to improve the prognosis of the disease make the introduction of a vaccine indispensable, even though there are currently no approved human coronavirus vaccines. The aim of the study is to carry out a review of the medical literature concerning vaccine candidates for the main coronaviruses responsible for human epidemics, including recent advances in the development of a vaccine against COVID-19. This extensive review carried out on the vaccine candidates of the main epidemic coronaviruses of the past has shown that the studies in animal models suggest a high efficacy of potential vaccines in providing protection against viral challenges. Similar human studies have not yet been carried out, as the main trials are aimed at assessing mainly vaccine safety and immunogenicity. Whereas the severe acute respiratory syndrome (SARS-CoV) epidemic ended almost two decades ago and the Middle East respiratory syndrome (MERS-CoV) epidemic is now better controlled, as it is less contagious due to the high lethality of the virus, the current SARS-CoV-2 pandemic represents a problem that is certainly more compelling, which pushes us to accelerate the studies not only for the production of vaccines but also for innovative pharmacological treatments. SARS-CoV-2 vaccines might come too late to affect the first wave of this pandemic, but they might be useful if additional subsequent waves occur or in a post-pandemic perspective in which the virus continues to circulate as a seasonal virus.", "qid": 50, "docid": "x5zvwtj7", "rank": 16, "score": 0.7570139765739441}, {"content": "Title: Vaccines against Coronaviruses: The State of the Art. Content: The emerging epidemic caused by the new coronavirus SARS-CoV-2 represents the most important socio-health threat of the 21st century. The high contagiousness of the virus, the strong impact on the health system of the various countries and the absence to date of treatments able to improve the prognosis of the disease make the introduction of a vaccine indispensable, even though there are currently no approved human coronavirus vaccines. The aim of the study is to carry out a review of the medical literature concerning vaccine candidates for the main coronaviruses responsible for human epidemics, including recent advances in the development of a vaccine against COVID-19. This extensive review carried out on the vaccine candidates of the main epidemic coronaviruses of the past has shown that the studies in animal models suggest a high efficacy of potential vaccines in providing protection against viral challenges. Similar human studies have not yet been carried out, as the main trials are aimed at assessing mainly vaccine safety and immunogenicity. Whereas the severe acute respiratory syndrome (SARS-CoV) epidemic ended almost two decades ago and the Middle East respiratory syndrome (MERS-CoV) epidemic is now better controlled, as it is less contagious due to the high lethality of the virus, the current SARS-CoV-2 pandemic represents a problem that is certainly more compelling, which pushes us to accelerate the studies not only for the production of vaccines but also for innovative pharmacological treatments. SARS-CoV-2 vaccines might come too late to affect the first wave of this pandemic, but they might be useful if additional subsequent waves occur or in a post-pandemic perspective in which the virus continues to circulate as a seasonal virus.", "qid": 50, "docid": "zi1l5883", "rank": 17, "score": 0.7570139765739441}, {"content": "Title: A single dose SARS-CoV-2 simulating particle vaccine induces potent neutralizing activities Content: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for which a vaccine is urgently needed to control its spreading. To facilitate the representation of a native-like immunogen without being infectious, here, we reported a SARS-CoV-2 vaccine candidate (designated ShaCoVacc) by incorporating spike-encoding mRNA inside and decorating spike protein on the surface of the virus simulating particles (VSPs) derived from lentiviral particles. We characterized the mRNA copy number, glycosylation status, transduction efficiency, and innate immune property of the new vaccine platform. Importantly, we showed the ShaCoVacc induced strong spike-specific humoral immune responses and potent neutralizing activities by a single injection. Additionally, we disclosed the epitopes of spike-specific antibodies using peptide microarray and revealed epitopes susceptible to specific neutralizing antibodies. These results support further development of ShaCoVacc as a candidate vaccine for COVID-19 and VSP may serve as a new vaccine platform for emerging infectious diseases.", "qid": 50, "docid": "ptvsie6m", "rank": 18, "score": 0.7565893530845642}, {"content": "Title: Vaccination strategies to combat novel corona virus SARS-CoV-2 Content: The 2019-novel coronavirus disease (COVID-19) is caused by SARS-CoV-2 is transmitted from human to human has recently reported in China. Now COVID-19 has been spread all over the world and declared epidemics by WHO. It has caused a Public Health Emergency of International Concern. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Due to the rapid increase of SARS-CoV-2 infections and unavailability of antiviral therapeutic agents, developing an effective SAR-CoV-2 vaccine is urgently required. SARS-CoV-2 which is genetically similar to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) is an enveloped, single and positive-stranded RNA virus with a genome comprising 29,891 nucleotides, which encode the 12 putative open reading frames responsible for the synthesis of viral structural and nonstructural proteins which are very similar to SARS-CoV and MERS-CoV proteins. In this review we have summarized various vaccine candidates i.e., nucleotide, subunit and vector based as well as attenuated and inactivated forms, which have already been demonstrated their prophylactic efficacy against MERS-CoV and SARS-CoV, so these candidates could be used as a potential tool for the development of a safe and effective vaccine against SARS-CoV-2.", "qid": 50, "docid": "eq2ahtlc", "rank": 19, "score": 0.7558481693267822}, {"content": "Title: Potential adjuvants for the development of a SARS-CoV-2 vaccine based on experimental results from similar coronaviruses Content: The extensive efforts around the globe are being made to develop a suitable vaccine against COVID-19 (Coronavirus Disease-19) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2). An effective vaccine should be able to induce high titers of neutralizing antibodies to prevent the virus from attaching to the host cell receptors. However, to elicit the protective levels of antibodies, a vaccine may require multiple doses or assistance from other immunostimulatory molecules. Further, the vaccine should be able to induce protective levels of antibodies rapidly with the least amount of antigen used. This not only decreases the cost of a vaccine and make it affordable, but also reduces the quantity of the antigen used. As the pandemic has hit most countries across the globe, there will be an overwhelming demand for the vaccine in a quick time. Incorporating a suitable adjuvant in a SARS-CoV-2 vaccine may address these requirements. This review paper will discuss the experimental results of the adjuvanted vaccine studies with similar coronaviruses (CoVs) which might be useful to select an appropriate adjuvant for a vaccine against rapidly emerging SARS-CoV-2. We also discuss the current progress in the development of adjuvanted vaccines against the disease.", "qid": 50, "docid": "npc9qdex", "rank": 20, "score": 0.7528967261314392}, {"content": "Title: Recombinant Live Vaccines to Protect Against the Severe Acute Respiratory Syndrome Coronavirus Content: The severe acute respiratory syndrome (SARS) coronavirus (CoV) was identified as the etiological agent of an acute respiratory disease causing atypical pneumonia and diarrhea with high mortality. Different types of SARS-CoV vaccines, including nonreplicative and vectored vaccines, have been developed. Administration of these vaccines to animal model systems has shown promise for the generation of efficacious and safe vaccines. Nevertheless, the identification of side effects, preferentially in the elderly animal models, indicates the need to develop novel vaccines that should be tested in improved animal model systems. Live attenuated viruses have generally proven to be the most effective vaccines against viral infections. A limited number of SARS-CoV attenuating modifications have been described, including mutations, and partial or complete gene deletions affecting the replicase, like the nonstructural proteins (nsp1 or nsp2), or the structural genes, and drastic changes in the sequences that regulate the expression of viral subgenomic mRNAs. A promising vaccine candidate developed in our laboratory was based on deletion of the envelope E gene alone, or in combination with the removal of six additional genes nonessential for virus replication. Viruses lacking E protein were attenuated, grew in the lung, and provided homologous and heterologous protection. Improvements of this vaccine candidate have been directed toward increasing virus titers using the power of viruses with mutator phenotypes, while maintaining the attenuated phenotype. The safety of the live SARS-CoV vaccines is being increased by the insertion of complementary modifications in genes nsp1, nsp2, and 3a, by gene scrambling to prevent the rescue of a virulent phenotype by recombination or remodeling of vaccine genomes based on codon deoptimization using synthetic biology. The newly generated vaccine candidates are very promising, but need to be evaluated in animal model systems that include young and aged animals.", "qid": 50, "docid": "1ksz6nmx", "rank": 21, "score": 0.7528531551361084}, {"content": "Title: SARS-CoV-2 transcriptome analysis and molecular cataloguing of immunodominant epitopes for multi-epitope based vaccine design Content: SARS-CoV-2 is a single-stranded RNA virus that has caused more than 0.29 million deaths worldwide as of May 2020, and influence of COVID-19 pandemic is increasing continuously in the absence of approved vaccine and drug. Moreover, very limited information is available about SARS-CoV-2 expressed regions and immune responses. In this paper an effort has been made, to facilitate vaccine development by proposing multiple epitopes as potential vaccine candidates by utilising SARS-CoV-2 transcriptome data. Here, publicly available RNA-seq data of SARS-CoV-2 infection in NHBE and A549 human cell lines were used to construct SARS-CoV-2 transcriptome to understand disease pathogenesis and immune responses. In the first step, epitope prediction, MHC class I and II gene identification for epitopes, population coverage, antigenicity, immunogenicity, conservation and crossreactivity analysis with host antigens were performed by using SARS-CoV-2 transcriptome, and in the second step, structural compatibility of identified T-and B-cell epitopes were evaluated with MHC molecules and B-cell receptors through molecular docking studies. Quantification of MHC gene expression was also performed that indicated high variation in allele types and expression level of MHC genes with respect to cell lines. In A549 cell line, HLA-A*30:01:01:01 and HLA-B*44:03:01:01 were highly expressed, whereas 92 variants of HLA-A*24 genes such as HLA-A*24:02:01:01, HLA-A*24:286, HLA-A*24:479Q, HLA-A*24:02:134 and HLA-A*24:02:116 were highly expressed in NHBE cell lines. Prevalence of HLA-A*24 alleles was suggested as risk factors for H1N1 infection, and associated with type-1 diabetes. HLA-C*03:03, linked with male infertility factors was also highly expressed in SARS-CoV-2 infected NHBE cell lines. Finally, three potential T-cell and five B-cell epitopes were selected for molecular docking studies with twenty-two MHC molecules and two B-cell receptors respectively. The results of in silico analysis indicated that proposed epitopes have high potential to recognize immune response of SARS-CoV-2 infection. This study will facilitate in vitro and in vivo vaccine related research studies.", "qid": 50, "docid": "oiepgu0v", "rank": 22, "score": 0.7526585459709167}, {"content": "Title: Scrutinizing the SARS-CoV-2 protein information for the designing an effective vaccine encompassing both the T-cell and B-cell epitopes Content: Novel SARS coronavirus (SARS-CoV-2) has caused a pandemic condition world-wide and has been declared as public health emergency of International concern by WHO in a very short span of time. The community transmission of this highly infectious virus has severely affected various parts of China, Italy, Spain and USA among others. The prophylactic solution against SARS-CoV-2 infection is challenging due to the high mutation rate of its RNA genome. Herein, we exploited a next generation vaccinology approach to construct a multi-epitope vaccine candidate against SARS-CoV-2 with high antigenicity, safety and efficacy to combat this deadly infectious agent. The whole proteome was scrutinized for the screening of highly conserved, antigenic, non-allergen and non-toxic epitopes having high population coverage that can elicit both humoral and cellular mediated immune response against COVID-19 infection. These epitopes along with four different adjuvants were utilized to construct a multi-epitope vaccine candidate that can generate strong immunological memory response having high efficacy in humans. Various physiochemical analyses revealed the formation of a stable vaccine product having a high propensity to form a protective solution against the detrimental SARS-CoV-2 strain with high efficacy. The vaccine candidate interacted with immunological receptor TLR3 with high affinity depicting the generation of innate immunity. Further, the codon optimization and in silico expression show the plausibility of the high expression and easy purification of the vaccine product. Thus, this present study provides an initial platform of the rapid generation of an efficacious protective vaccine for combating COVID-19.", "qid": 50, "docid": "lmstdmyb", "rank": 23, "score": 0.7512911558151245}, {"content": "Title: Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine induces equivalent preclinical antibody titers and viral neutralization to recovered COVID-19 patients Content: The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle as a vaccine and demonstrate induction of robust neutralization of a pseudo-virus, proportional to quantity of specific IgG and of higher quantities than recovered COVID-19 patients. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic.", "qid": 50, "docid": "6ubk3rv7", "rank": 24, "score": 0.7507449388504028}, {"content": "Title: Design of a peptide-based subunit vaccine against novel coronavirus SARS-CoV-2 Content: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. In the absence of any antiviral or immunomodulatory therapies, the disease is spreading at an alarming rate. A possibility of a resurgence of COVID-19 in places where lockdowns have already worked is also developing. Thus, for controlling COVID-19, vaccines may be a better option than drugs. An mRNA-based anti-COVID-19 candidate vaccine has entered a phase 1 clinical trial. However, its efficacy and potency have to be evaluated and validated. Since vaccines have high failure rates, as an alternative, we are presenting a new, designed multi-peptide subunit-based epitope vaccine against COVID-19. The recombinant vaccine construct comprises an adjuvant, cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes joined by linkers. The computational data suggest that the vaccine is non-toxic, non-allergenic, thermostable, with the capability to elicit a humoral and cell-mediated immune response. The stabilization of the vaccine construct is validated with molecular dynamics simulation studies. This unique vaccine is made up of 33 highly antigenic epitopes from three proteins that have a prominent role in host-receptor recognition, viral entry, and pathogenicity. We advocate this vaccine must be synthesized and tested urgently as a public health priority.", "qid": 50, "docid": "8lktpcda", "rank": 25, "score": 0.7495647668838501}, {"content": "Title: Potential adjuvants for the development of a SARS-CoV-2 vaccine based on experimental results from similar coronaviruses Content: The extensive efforts around the globe are being made to develop a suitable vaccine against COVID-19 (Coronavirus Disease-19) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2). An effective vaccine should be able to induce high titers of neutralizing antibodies to prevent the virus from attaching to the host cell receptors. However, to elicit the protective levels of antibodies, a vaccine may require multiple doses or assistance from other immunostimulatory molecules. Further, the vaccine should be able to induce protective levels of antibodies rapidly with the least amount of antigen used. This decreases the cost of a vaccine and makes it affordable. As the pandemic has hit most countries across the globe, there will be an overwhelming demand for the vaccine in a quick time. Incorporating a suitable adjuvant in a SARS-CoV-2 vaccine may address these requirements. This review paper will discuss the experimental results of the adjuvanted vaccine studies with similar coronaviruses (CoVs) which might be useful to select an appropriate adjuvant for a vaccine against rapidly emergingSARS-CoV-2. We also discuss the current progress in the development of adjuvanted vaccines against the disease.", "qid": 50, "docid": "ttlyuj2e", "rank": 26, "score": 0.7493187189102173}, {"content": "Title: A SARS-CoV-2 vaccine candidate: In silico cloning and validation Content: SARS-CoV-2 is spreading globally at a rapid pace. To contain its spread and prevent further fatalities, the development of a vaccine against SARS-CoV-2 is an urgent prerequisite. Thus, in this article, by utilizing the in silico approach, a vaccine candidate for SARS-CoV-2 has been proposed. Moreover, the effectiveness and safety measures of our proposed epitopic vaccine candidate have been evaluated by in silico tools and servers (AllerTOP and AllergenFP servers). We observed that the vaccine candidate has no allergenicity and successfully combined with Toll-like receptor (TLR) protein to elicit an inflammatory immune response. Stable, functional mobility of the vaccine-TLR protein binding interface was confirmed by the Normal Mode Analysis. The in silico cloning model demonstrated the efficacy of the construct vaccine along with the identified epitopes against SARS-CoV-2. Taken together, our proposed in silico vaccine candidate has potent efficacy against COVID-19 infection, and successive research work might validate its effectiveness in in vitro and in vivo models.", "qid": 50, "docid": "du2zxq96", "rank": 27, "score": 0.7476104497909546}, {"content": "Title: In the search of potential epitopes for Wuhan seafood market pneumonia virus using high order nullomers Content: Alarms periodically emerge for viral pneumonia infections due to coronavirus. In all cases, these are zoonoses passing the barrier between species and infect humans. The legitimate concern of the international community is due to the fact that the new identified coronavirus, named SARS-CoV-2 (previously called 2019-nCoV), has a quite high mortality rate, around 2%, and a strong ability to spread, with an estimated reproduction number higher than 2. Even though all countries are doing their utmost to stop the pandemic, the only reliable solution to tackle the infection is the rapid development of a vaccine. For this purpose, the means of bioinformatics, applied in the context of reverse-vaccinology paradigm, can be of fundamental help to select the most promising peptides able to trigger an effective immune response. In this short report, using the concept of nullomer and introducing a distance from human self, we provide a list of peptides that could deserve experimental investigation in the view of a potential vaccine for SARS-CoV-2.", "qid": 50, "docid": "6uxxmts6", "rank": 28, "score": 0.7476051449775696}, {"content": "Title: Prospective vaccination of COVID-19 using shRNA-plasmid-LDH nanoconjugate Content: COVID-19 is the pandemic outbreak that is caused by SARS-CoV-2 virus from December, 2019. Human race do not know the curative measure of this devastating disease. In today\u2019s era of nanotechnology, it may use its knowledge to develop molecular vaccine to combat this disease. In this article we are intended to propose a hypothesis on the development of a vaccine that is molecular in nature to work against COVID-19. The nanoconjugate may comprise with the inorganic nanoparticle layered double hydroxide intercalated with shRNA-plasmid that have a sequence targeting towards the viral genome or viral mRNA. This nanoconjugate may be used as a nasal spray to deliver the shRNA-plasmid to the target site. The nanoconjugate will have several advantages such as they are biocompatible, they forms as stable knockdown to the target cells and they are stable in the nasal mucosa.", "qid": 50, "docid": "4nv059p1", "rank": 29, "score": 0.7468444108963013}, {"content": "Title: Fighting COVID-19: a quick review of diagnoses, therapies, and vaccines Content: The COVID-19 pandemic caused by a novel coronavirus, SARS-CoV-2, has infected more than 4.9 million individuals and resulted in over 300,000 deaths globally. The rapid spread of the virus and the precipitously increasing numbers of cases necessitate the urgent development of accurate diagnostic methods, effective treatments, and vaccines. Here, we review the progress of developing diagnostic methods, therapies, and vaccines for SARS-CoV-2 with a focus on current clinical trials and their challenges. For diagnosis, nucleic acid amplification tests remain the mainstay diagnostics for laboratory confirmation of SARS-CoV-2 infection, while serological antibody tests are used to aid contact tracing, epidemiological, and vaccine evaluation studies. Viral isolation is not recommended for routine diagnostic procedures due to safety concerns. Currently, no single effective drug or specific vaccine is available against SARS-CoV-2. Some candidate drugs targeting different levels and stages of human responses against COVID-19 such as cell membrane fusion, RNA-dependent RNA polymerase, viral protease inhibitor, interleukin 6 blocker, and convalescent plasma may improve the clinical outcomes of critical COVID-19 patients. Other supportive care measures for critical patients are still necessary. Advances in genetic sequencing and other technological developments have sped up the establishment of a variety of vaccine platforms. Accordingly, numerous vaccines are under development. Vaccine candidates against SARS-CoV-2 are mainly based upon the viral spike protein due to its vital role in viral infectivity, and most of these candidates have recently moved into clinical trials. Before the efficacy of such vaccines in humans is demonstrated, strong international coordination and collaboration among studies, pharmaceutical companies, regulators, and governments are needed to limit further damage due the emerging SARS-CoV-2 virus.", "qid": 50, "docid": "0g7a9s5z", "rank": 30, "score": 0.7459524869918823}, {"content": "Title: The potential danger of suboptimal antibody responses in COVID-19 Content: There is a desperate need for effective therapies and vaccines for SARS-CoV-2 to mitigate the growing economic crisis that has ensued from societal lockdown. Vaccines are being developed at an unprecedented speed and are already in clinical trials, without preclinical testing for safety and efficacy. Yet, safety evaluation of candidate vaccines must not be overlooked.", "qid": 50, "docid": "xee6npr3", "rank": 31, "score": 0.7459097504615784}, {"content": "Title: Prospects of Replication-Deficient Adenovirus Based Vaccine Development against SARS-CoV-2. Content: The current appearance of the new SARS coronavirus 2 (SARS-CoV-2) and it quickly spreading across the world poses a global health emergency. The serious outbreak position is affecting people worldwide and requires rapid measures to be taken by healthcare systems and governments. Vaccinations represent the most effective strategy to prevent the epidemic of the virus and to further reduce morbidity and mortality with long-lasting effects. Nevertheless, currently there are no licensed vaccines for the novel coronaviruses. Researchers and clinicians from all over the world are advancing the development of a vaccine against novel human SARS-CoV-2 using various approaches. Herein, we aim to present and discuss the progress and prospects in the field of vaccine research towards SARS-CoV-2 using adenovirus (AdV) replication deficient-based strategies, with a comprehension that may support research and combat this recent world health emergency.", "qid": 50, "docid": "gw6po8qg", "rank": 32, "score": 0.7456656694412231}, {"content": "Title: Prospects of Replication-Deficient Adenovirus Based Vaccine Development against SARS-CoV-2 Content: The current appearance of the new SARS coronavirus 2 (SARS-CoV-2) and it quickly spreading across the world poses a global health emergency. The serious outbreak position is affecting people worldwide and requires rapid measures to be taken by healthcare systems and governments. Vaccinations represent the most effective strategy to prevent the epidemic of the virus and to further reduce morbidity and mortality with long-lasting effects. Nevertheless, currently there are no licensed vaccines for the novel coronaviruses. Researchers and clinicians from all over the world are advancing the development of a vaccine against novel human SARS-CoV-2 using various approaches. Herein, we aim to present and discuss the progress and prospects in the field of vaccine research towards SARS-CoV-2 using adenovirus (AdV) replication deficient-based strategies, with a comprehension that may support research and combat this recent world health emergency.", "qid": 50, "docid": "cofi4cue", "rank": 33, "score": 0.7456656098365784}, {"content": "Title: Progress and Prospects on Vaccine Development against SARS-CoV-2 Content: In December 2019, the outbreak of pneumonia caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a serious pandemic in China and other countries worldwide. So far, more than 460,000 confirmed cases were diagnosed in nearly 190 countries, causing globally over 20,000 deaths. Currently, the epidemic is still spreading and there is no effective means to prevent the infection. Vaccines are proved to be the most effective and economical means to prevent and control infectious diseases. Several countries, companies, and institutions announced their programs and progress on vaccine development against the virus. While most of the vaccines are under design and preparation, there are some that have entered efficacy evaluation in animals and initial clinical trials. This review mainly focused on the progress and our prospects on field of vaccine development against SARS-CoV-2.", "qid": 50, "docid": "gl0wiyt2", "rank": 34, "score": 0.744691014289856}, {"content": "Title: Design of a peptide-based subunit vaccine against novel coronavirus SARS-CoV-2 Content: Abstract Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. In the absence of any antiviral or immunomodulatory therapies, the disease is spreading at an alarming rate. A possibility of a resurgence of COVID-19 in places where lockdowns have already worked is also developing. Thus, for controlling COVID-19, vaccines may be a better option than drugs. An mRNA-based anti-COVID-19 candidate vaccine has entered a phase 1 clinical trial. However, its efficacy and potency have to be evaluated and validated. Since vaccines have high failure rates, as an alternative, we are presenting a new, designed multi-peptide subunit-based epitope vaccine against COVID-19. The recombinant vaccine construct comprises an adjuvant, cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes joined by linkers. The computational data suggest that the vaccine is non-toxic, non-allergenic, thermostable, with the capability to elicit a humoral and cell-mediated immune response. The stabilization of the vaccine construct is validated with molecular dynamics simulation studies. This unique vaccine is made up of 33 highly antigenic epitopes from three proteins that have a prominent role in host-receptor recognition, viral entry, and pathogenicity. We advocate this vaccine must be synthesized and tested urgently as a public health priority.", "qid": 50, "docid": "d2j9wpqk", "rank": 35, "score": 0.7436564564704895}, {"content": "Title: [At least 68 vaccine candidates under development]. Content: The development of vaccines against SARS-CoV-2 is progressing at an unparalleled speed. As of the 29th of March, there were at least 68 vaccine candidates comprising several different vaccine designs, including whole killed virus, subunit, attenuated, viral vector, DNA and mRNA vaccines. Whilst it usually takes 10-15 years to develop a vaccine, it has only taken just over 9 weeks from the publication of the viral genetic sequence for the first vaccine candidate to reach clinical testing. Development has been expediated by using existing technological platforms and by performing preclinical and clinical testing simultaneously.", "qid": 50, "docid": "l9l6z1o0", "rank": 36, "score": 0.7425180673599243}, {"content": "Title: Replication-competent vesicular stomatitis virus vaccine vector protects against SARS-CoV-2-mediated pathogenesis Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of human infections and hundreds of thousands of deaths. Accordingly, an effective vaccine is of critical importance in mitigating coronavirus induced disease 2019 (COVID-19) and curtailing the pandemic. We developed a replication-competent vesicular stomatitis virus (VSV)-based vaccine by introducing a modified form of the SARS-CoV-2 spike gene in place of the native glycoprotein gene (VSV-eGFP-SARS-CoV-2). Immunization of mice with VSV-eGFP-SARS-CoV-2 elicits high titers of antibodies that neutralize SARS-CoV-2 infection and target the receptor binding domain that engages human angiotensin converting enzyme-2 (ACE2). Upon challenge with a human isolate of SARS-CoV-2, mice expressing human ACE2 and immunized with VSV-eGFP-SARS-CoV-2 show profoundly reduced viral infection and inflammation in the lung indicating protection against pneumonia. Finally, passive transfer of sera from VSV-eGFP-SARS-CoV-2-immunized animals protects na\u00efve mice from SARS-CoV-2 challenge. These data support development of VSV-eGFP-SARS-CoV-2 as an attenuated, replication-competent vaccine against SARS-CoV-2.", "qid": 50, "docid": "enli9n34", "rank": 37, "score": 0.7424861192703247}, {"content": "Title: Single-dose replicating RNA vaccine induces neutralizing antibodies against SARS-CoV-2 in nonhuman primates Content: The ongoing COVID-19 pandemic, caused by infection with SARS-CoV-2, is having a dramatic and deleterious impact on health services and the global economy. Grim public health statistics highlight the need for vaccines that can rapidly confer protection after a single dose and be manufactured using components suitable for scale-up and efficient distribution. In response, we have rapidly developed repRNA-CoV2S, a stable and highly immunogenic vaccine candidate comprised of an RNA replicon formulated with a novel Lipid InOrganic Nanoparticle (LION) designed to enhance vaccine stability, delivery and immunogenicity. We show that intramuscular injection of LION/repRNA-CoV2S elicits robust anti-SARS-CoV-2 spike protein IgG antibody isotypes indicative of a Type 1 T helper response as well as potent T cell responses in mice. Importantly, a single-dose administration in nonhuman primates elicited antibody responses that potently neutralized SARS-CoV-2. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection from SARS-CoV-2 infection.", "qid": 50, "docid": "wzv8n34v", "rank": 38, "score": 0.7418463230133057}, {"content": "Title: Fighting COVID-19: A quick review of diagnoses, therapies, and vaccines Content: The coronavirus disease 2019 (COVID-19) pandemic caused by a novel coronavirus, SARS-CoV-2, has infected more than 4.9 million individuals and resulted in over 300,000 deaths globally. The rapid spread of the virus and the precipitously increasing numbers of cases necessitate the urgent development of accurate diagnostic methods, effective treatments, and vaccines. Here, we review the progress of developing diagnostic methods, therapies, and vaccines for SARS-CoV-2 with a focus on current clinical trials and their challenges. For diagnosis, nucleic acid amplification tests remain the mainstay diagnostics for laboratory confirmation of SARS-CoV-2 infection, while serological antibody tests are used to aid contact tracing, epidemiological, and vaccine evaluation studies. Viral isolation is not recommended for routine diagnostic procedures due to safety concerns. Currently, no single effective drug or specific vaccine is available against SARS-CoV-2. Some candidate drugs targeting different levels and stages of human responses against COVID-19 such as cell membrane fusion, RNA-dependent RNA polymerase, viral protease inhibitor, interleukin 6 blocker, and convalescent plasma may improve the clinical outcomes of critical COVID-19 patients. Other supportive care measures for critical patients are still necessary. Advances in genetic sequencing and other technological developments have sped up the establishment of a variety of vaccine platforms. Accordingly, numerous vaccines are under development. Vaccine candidates against SARS-CoV-2 are mainly based upon the viral spike protein due to its vital role in viral infectivity, and most of these candidates have recently moved into clinical trials. Before the efficacy of such vaccines in humans is demonstrated, strong international coordination and collaboration among studies, pharmaceutical companies, regulators, and governments are needed to limit further damage due the emerging SARS-CoV-2 virus.", "qid": 50, "docid": "2vevp0fg", "rank": 39, "score": 0.7404932379722595}, {"content": "Title: An insight into the epitope-based peptide vaccine design strategy and studies against COVID-19 Content: SARS-CoV-2 is a new member of the coronavirus family and caused the pandemic of coronavirus disease 2019 (COVID-19) in 2020. It is crucial to design and produce an effective vaccine for the prevention of rapid transmission and possible deaths wcaused by the disease. Although intensive work and research are being carried out all over the world to develop a vaccine, an effective and approved formulation that can prevent the infection and limit the outbreak has not been announced yet. Among all types of vaccines, epitope-based peptide vaccines outshine with their low-cost production, easy modification in the structure, and safety. In this review, vaccine studies against COVID-19 have been summarized and detailed information about the epitope-based peptide vaccines against COVID-19 has been provided. We have not only compared the peptide vaccine with other types of vaccines but also presented comprehensive literature information about development steps for an effective and protective formulation to give an insight into on-going peptide vaccine studies against SARS-CoV-2.", "qid": 50, "docid": "j6gn8exx", "rank": 40, "score": 0.7403632402420044}, {"content": "Title: LinearDesign: Efficient Algorithms for Optimized mRNA Sequence Design Content: A messenger RNA (mRNA) vaccine has emerged as a promising direction to combat the current COVID-19 pandemic. This requires an mRNA sequence that is stable and highly productive in protein expression, features which have been shown to benefit from greater mRNA secondary structure folding stability and optimal codon usage. However, sequence design remains a hard problem due to the exponentially many synonymous mRNA sequences that encode the same protein. We show that this design problem can be reduced to a classical problem in formal language theory and computational linguistics that can be solved in O(n^3) time, where n is the mRNA sequence length. This algorithm could still be too slow for large n (e.g., n = 3, 822 nucleotides for the spike protein of SARS-CoV-2), so we further developed a linear-time approximate version, LinearDesign, inspired by our recent work, LinearFold. This algorithm, LinearDesign, can compute the approximate minimum free energy mRNA sequence for this spike protein in just 11 minutes using beam size b = 1, 000, with only 0.6% loss in free energy change compared to exact search (i.e., b = +infinity, which costs 1 hour). We also develop two algorithms for incorporating the codon optimality into the design, one based on k-best parsing to find alternative sequences and one directly incorporating codon optimality into the dynamic programming. Our work provides efficient computational tools to speed up and improve mRNA vaccine development.", "qid": 50, "docid": "v0m90h3n", "rank": 41, "score": 0.7403261661529541}, {"content": "Title: Phase 1/2 Study to Describe the Safety and Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: Interim Report Content: Abstract In March 2020, the WHO declared a pandemic of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With >8.8 million cases and >450,000 deaths reported globally, a vaccine is urgently needed. We report the available safety, tolerability, and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose escalation study among healthy adults, 18-55 years of age, randomized to receive 2 doses, separated by 21 days, of 10 g, 30 g, or 100 g of BNT162b1, a lipid nanoparticle-formulated, nucleoside-modified, mRNA vaccine that encodes trimerized SARS-CoV-2 spike glycoprotein RBD. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titers in sera increased with dose level and after a second dose. Geometric mean neutralizing titers reached 1.8- to 2.8-fold that of a panel of COVID-19 convalescent human sera. These results support further evaluation of this mRNA vaccine candidate.", "qid": 50, "docid": "akbq0ogs", "rank": 42, "score": 0.740266740322113}, {"content": "Title: Vaccines to prevent severe acute respiratory syndrome coronavirus-induced disease Content: An important effort has been performed after the emergence of severe acute respiratory syndrome (SARS) epidemic in 2003 to diagnose and prevent virus spreading. Several types of vaccines have been developed including inactivated viruses, subunit vaccines, virus-like particles (VLPs), DNA vaccines, heterologous expression systems, and vaccines derived from SARS-CoV genome by reverse genetics. This review describes several aspects essential to develop SARS-CoV vaccines, such as the correlates of protection, virus serotypes, vaccination side effects, and bio-safeguards that can be engineered into recombinant vaccine approaches based on the SARS-CoV genome. The production of effective and safe vaccines to prevent SARS has led to the development of promising vaccine candidates, in contrast to the design of vaccines for other coronaviruses, that in general has been less successful. After preclinical trials in animal models, efficacy and safety evaluation of the most promising vaccine candidates described has to be performed in humans.", "qid": 50, "docid": "gysf0vbv", "rank": 43, "score": 0.7393711805343628}, {"content": "Title: In the search of potential epitopes for Wuhan seafood market pneumonia virus using high order nullomers Content: Abstract Alarms periodically emerge for viral pneumonia infections due to coronavirus. In all cases, these are zoonoses passing the barrier between species and infect humans. The legitimate concern of the international community is due to the fact that the new identified coronavirus, named SARS-CoV-2 (previously called 2019-nCoV), has a quite high mortality rate, around 2%, and a strong ability to spread, with an estimated reproduction number higher than 2. Even though all countries are doing their utmost to stop the pandemic, the only reliable solution to tackle the infection is the rapid development of a vaccine. For this purpose, the means of bioinformatics, applied in the context of reverse-vaccinology paradigm, can be of fundamental help to select the most promising peptides able to trigger an effective immune response. In this short report, using the concept of nullomer and introducing a distance from human self, we provide a list of peptides that could deserve experimental investigation in the view of a potential vaccine for SARS-CoV-2.", "qid": 50, "docid": "stsvjqhu", "rank": 44, "score": 0.7382791042327881}, {"content": "Title: The vaccine journey for COVID-19: a comprehensive systematic review of current clinical trials in humans Content: INTRODUCTION: Since December 2019, there has been an outbreak of a novel beta-coronavirus (SARS-CoV-2) in Wuhan, China. On March the 11th the World Health Organization (WHO) declared COVID-19 as a pandemic, with over 118,000 cases in more than 110 countries around the world. In response to the global coronavirus disease 2019 (COVID-19) emergency, clinical trial research assessing the efficacy and safety of experimental vaccines to prevent COVID-19 are emerging at an unprecedented rate. The aim of this systematic review is to summarize the preliminary experiences and ongoing clinical trials of the major candidates and challenges of the vaccine strategies in humans. EVIDENCE ACQUISITION: After a priori protocol registration with PROSPERO (181483), a systematic research of the published literature was conducted on 24 April 2020 using Medline (via PubMed), Embase (via Ovid), and WHO databases. Moreover, to explore the more recent literature we also searched the preprint server medRxiv. Finally, we scrutinized the Cochrane COVID-19 study register and the COVID-19 section of ClinicalTrials.gov database for identifying relevant ongoing clinical trials. Thereafter we selected the articles according to the PRISMA guidelines. Animal or in-vitro experimental studies were excluded. Moreover editorials, commentaries, abstracts, reviews, book chapters, and articles not in English were not included. EVIDENCE SYNTHESIS: Our search identified 1359 published papers, 478 pre-print articles and 367 ongoing clinical trials. Finally, only ten ongoing clinical trials met the inclusion criteria. Specifically, seven developed vaccines for the S protein of SARS-CoV-2 and three clinical trials assessed the protective role of BCG vaccine against COVID-19. The first group included phase I/II trials with different types of molecules (DNA or mRNA vaccine, bacterial plasmid or viral vectors), the latter were phase III/IV trials designed on the basis of a heterologous lymphocyte activation by the BCG vaccine. CONCLUSIONS: This new disease is pushing the scientific community to develop swiftly a safe and effective vaccine. Notwithstanding the limitations of our analysis, given by the absence of available results, we try to provide a comprehensive view of the ongoing clinical trials in humans. Our analysis reveals a worldwide effort of both scientists and enterprises to achieve one of the most challenging goals of our century.", "qid": 50, "docid": "xt8tld2i", "rank": 45, "score": 0.7381184101104736}, {"content": "Title: A single-dose live-attenuated YF17D-vectored SARS-CoV2 vaccine candidate Content: The explosively expanding COVID-19 pandemic urges the development of safe, efficacious and fast-acting vaccines to quench the unrestrained spread of SARS-CoV-2. Several promising vaccine platforms, developed in recent years, are leveraged for a rapid emergency response to COVID-191. We employed the live-attenuated yellow fever 17D (YF17D) vaccine as a vector to express the prefusion form of the SARS-CoV-2 Spike antigen. In mice, the vaccine candidate, tentatively named YF-S0, induces high levels of SARS-CoV-2 neutralizing antibodies and a favorable Th1 cell-mediated immune response. In a stringent hamster SARS-CoV-2 challenge model2, vaccine candidate YF-S0 prevents infection with SARS-CoV-2. Moreover, a single dose confers protection from lung disease in most vaccinated animals even within 10 days. These results warrant further development of YF-S0 as a potent SARS-CoV-2 vaccine candidate.", "qid": 50, "docid": "zwsvlnwe", "rank": 46, "score": 0.7380884885787964}, {"content": "Title: In Silico design and characterization of multi-epitopes vaccine for SARS-CoV2 from its spike proteins Content: COVID 19 is disease caused by novel corona virus, SARS-CoV2 originated in China most probably of Bat origin. Till date, no specific vaccine or drug has been discovered to tackle the infections caused by SARS-CoV2. In response to this pandemic, we utilized bioinformatics knowledge to develop efficient vaccine candidate against SARS-CoV2. Designed vaccine was rich in effective BCR and TCR epitopes screened from the sequence of S-protein of SARS-CoV2. Predicted BCR and TCR epitopes were antigenic in nature non-toxic and probably non-allergen. Modelled and refined tertiary structure was predicted as valid for further use. Protein-Protein interaction prediction of TLR2/4 and designed vaccine indicates promising binding. Designed multiepitope vaccine has induced cell mediated and humoral immunity along with increased interferon gamma response. Macrophages and dendritic cells were also found increased over the vaccine exposure. In silico codon optimization and cloning in expression vector indicates that vaccine can be efficiently expressed in E. coli. In conclusion, predicted vaccine is a good antigen, probable no allergen and has potential to induce cellular and humoral immunity.", "qid": 50, "docid": "7dw32xby", "rank": 47, "score": 0.7380287647247314}, {"content": "Title: COVID\u201019 vaccines: knowing the unknown Content: Vaccine development against SARS\u2010CoV\u20102 has drawn attention around the globe due to the exploding pandemic. Although COVID\u201019 is caused by a new coronavirus, SARS\u2010CoV\u20102, previous research on other coronavirus vaccines, such as FIPV, SARS and MERS, has provided valuable information for the rapid development of COVID\u201019 vaccine. However, important knowledge gaps remain \u2013 some are specific to SARS\u2010CoV\u20102, others are fundamental to immunology and vaccinology. Here we discuss areas that need to be addressed for COVID\u201019 vaccine development, and what can be learned from examples of vaccine development in the past. Since the beginning of the outbreak, the research progress on COVID\u201019 has been remarkable. We are therefore optimistic about the rapid development of COVID\u201019 vaccine. This article is protected by copyright. All rights reserved", "qid": 50, "docid": "tdvb0fhv", "rank": 48, "score": 0.7353322505950928}, {"content": "Title: Towards effective COVID-19 vaccines: Updates, perspectives and challenges (Review) Content: In the current context of the pandemic triggered by SARS-COV-2, the immunization of the population through vaccination is recognized as a public health priority. In the case of SARS-COV-2, the genetic sequencing was done quickly, in one month. Since then, worldwide research has focused on obtaining a vaccine. This has a major economic impact because new technological platforms and advanced genetic engineering procedures are required to obtain a COVID-19 vaccine. The most difficult scientific challenge for this future vaccine obtained in the laboratory is the proof of clinical safety and efficacy. The biggest challenge of manufacturing is the construction and validation of production platforms capable of making the vaccine on a large scale.", "qid": 50, "docid": "0o05oskr", "rank": 49, "score": 0.7352584600448608}, {"content": "Title: Rapid development of an inactivated vaccine for SARS-CoV-2 Content: The COVID-19 pandemic caused by SARS-CoV-2 has brought about an unprecedented crisis, taking a heavy toll on human health, lives as well as the global economy. There are no SARS-CoV-2-specific treatments or vaccines available due to the novelty of this virus. Hence, rapid development of effective vaccines against SARS-CoV-2 is urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies potently neutralized 10 representative SARS-CoV-2 strains, indicative of a possible broader neutralizing ability against SARS-CoV-2 strains circulating worldwide. Immunization with two different doses (3\u03bcg or 6 \u03bcg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without any antibody-dependent enhancement of infection. Systematic evaluation of PiCoVacc via monitoring clinical signs, hematological and biochemical index, and histophathological analysis in macaques suggests that it is safe. These data support the rapid clinical development of SARS-CoV-2 vaccines for humans. One Sentence Summary A purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc) confers complete protection in non-human primates against SARS-CoV-2 strains circulating worldwide by eliciting potent humoral responses devoid of immunopathology", "qid": 50, "docid": "m1bvurwi", "rank": 50, "score": 0.7347445487976074}, {"content": "Title: Multi-epitope-based peptide vaccine design against SARS-CoV-2 using its spike protein Content: SARS CoV-2 has particularly been efficient in ensuring that many countries are brought to a standstill. With repercussions ranging from rampant mortality, fear, paranoia and economic recession, the virus has brought together countries in order to look at possible therapeutic countermeasures. With prophylactic interventions possibly months away from being particularly effective, a slew of measures and possibilities concerning the design of vaccines are being worked upon. We attempted a structure-based approach utilizing a combination of epitope prediction servers to develop a multi-epitope-based subunit vaccine that involves the two major domains of the spike glycoprotein of SARS CoV-2 (S1 and S2) coupled with a substantially effective chimeric adjuvant to create stable vaccine constructs through MD simulations. The designed constructs were evaluated based on their docking with Toll Like Receptor (TLR) 4. Our findings provide an epitope-based peptide fragment; which can be a potential candidate for the development of a vaccine against SARS-CoV-2. Recent experimental studies based on determining immunodominant regions across the spike glycoprotein of SARS-CoV-2 indicate the presence of the predicted epitopes included in this study.", "qid": 50, "docid": "i7oi7mfi", "rank": 51, "score": 0.7347245216369629}, {"content": "Title: [Recent developments in SARS vaccine studies]. Content: Severe acute respiratory syndrome (SARS) caused thousands of human infections worldwide and hundreds of deaths in just a few months. Evidence indicates that SARS coronavirus (SARS-CoV) has been circulating from animals to humans since before the 2002-2003 outbreak, suggesting that another pandemic may occur. This possibility has focused continuous action on SARS vaccine research. Inactivated vaccines, viral and bacterial vector vaccines, recombinant protein vaccines, subunit vaccines, DNA vaccines, and live-attenuated virus vaccines have been studied in different animal models. Although different animal models are used in vaccine studies, the most appropriate model for studying SARS is ferret since it develops the typical clinical signs, viral replication patterns and lung pathology compatible with that of SARS pathogenesis in humans. While there is much evidence that various vaccine strategies against SARS are safe and immunogenic, vaccinated animals still display significant disease upon challenge. Moreover, potential vaccine enhancement of SARS have also been shown in some studies. Data from the studies give an important information of the demand for further vaccine development research, especially focusing on mucosal immunization, T-cell immunity and combinations of heterologous vaccines in prime-boost regimens. In this review article developments on SARS vaccines have been discussed under the light of recent literature.", "qid": 50, "docid": "hx9sv1k1", "rank": 52, "score": 0.7344629168510437}, {"content": "Title: Vaccines for COVID-19: The current state of play Content: There is a strong consensus globally that a COVID-19 vaccine is likely the most effective approach to sustainably controlling the COVID-19 pandemic. An unprecedented research effort and global coordination has resulted in a rapid development of vaccine candidates and initiation of trials. Here, we review vaccine types, and progress with 10 vaccine candidates against SARS-CoV-2 - the virus that causes COVID-19 - currently undergoing early phase human trials. We also consider the many challenges of developing and deploying a new vaccine on a global scale, and recommend caution with respect to our expectations of the timeline that may be ahead.", "qid": 50, "docid": "o8bkorjn", "rank": 53, "score": 0.734359622001648}, {"content": "Title: COVID-19 vaccines: Knowing the unknown Content: Vaccine development against SARS-CoV-2 has drawn attention around the globe due to the exploding pandemic. Although COVID-19 is caused by a new coronavirus, SARS-CoV-2, previous research on other coronavirus vaccines, such as FIPV, SARS, and MERS, has provided valuable information for the rapid development of COVID-19 vaccine. However, important knowledge gaps remain - some are specific to SARS-CoV-2, others are fundamental to immunology and vaccinology. Here, we discuss areas that need to be addressed for COVID-19 vaccine development, and what can be learned from examples of vaccine development in the past. Since the beginning of the outbreak, the research progress on COVID-19 has been remarkable. We are therefore optimistic about the rapid development of COVID-19 vaccine.", "qid": 50, "docid": "hotn7qha", "rank": 54, "score": 0.7336450815200806}, {"content": "Title: Immunogenicity of a DNA vaccine candidate for COVID-19 Content: The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further dissemination of the disease. We have previously engineered a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein, the major surface antigen of coronaviruses, which is currently in clinical study. Here we build on this prior experience to generate a synthetic DNA-based vaccine candidate targeting SARS-CoV-2 S protein. The engineered construct, INO-4800, results in robust expression of the S protein in vitro. Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study.", "qid": 50, "docid": "f5xs0tv2", "rank": 55, "score": 0.7328634858131409}, {"content": "Title: Vaccine design for severe acute respiratory syndrome coronavirus. Content: Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a new coronavirus (SARS-CoV). Recent studies suggest that SARS-CoV is zoonotic and may have a broad host range besides humans. Although the global outbreak of SARS has been contained, there are serious concerns over its re-emergence and bioterrorism potential. As a part of preparedness, development of a safe and effective vaccine is one of the highest priorities in fighting SARS. A number of candidate vaccines, using a variety of approaches, are under development. The first vaccine tested in clinical trial is made from the inactivated form of SARS-CoV. Several live attenuated, genetically engineered or vector vaccines encoding the SARS-CoV spike (S) protein have been in pre-clinical studies. These vaccine candidates are effective in terms of eliciting protective immunity in the vaccinated animals. However, caution should be taken with the safety of whole virus or full-length S protein-based immunogens in humans because they may induce harmful immune or inflammatory responses. We propose to use the receptor-binding domain (RBD) of SARS-CoV S protein (residues 318--510) for developing a safe and effective subunit SARS vaccine, as it is not only a functional domain that mediates virus-receptor binding but also a major neutralization determinant of SARSCoV. It has been demonstrated that the RBD of SARS-CoV S protein contains multiple conformational epitopes capable of inducing highly potent neutralizing antibody responses and protective immunity.", "qid": 50, "docid": "t13zgiez", "rank": 56, "score": 0.7322073578834534}, {"content": "Title: SARS vaccines: where are we? Content: In this review, the current state of vaccine development against human severe acute respiratory syndrome (SARS) coronavirus, focusing on recently published data is assessed. We discuss which strategies have been assessed immunologically and which have been evaluated in SARS coronavirus challenge models. We discuss inactivated vaccines, virally and bacterially vectored vaccines, recombinant protein and DNA vaccines, as well as the use of attenuated vaccines. Data regarding the correlates of protection, animal models and the available evidence regarding potential vaccine enhancement of SARS disease are discussed. While there is much evidence that various vaccine strategies against SARS are safe and immunogenic, vaccinated animals still display significant disease upon challenge. Current data suggest that intranasal vaccination may be crucial and that new or combination strategies may be required for good protective efficacy against SARS in humans.", "qid": 50, "docid": "y4eyse0y", "rank": 57, "score": 0.7315108776092529}, {"content": "Title: Genome based Evolutionary study of SARS-CoV-2 towards the Prediction of Epitope Based Chimeric Vaccine Content: SARS-CoV-2 is known to infect the neurological, respiratory, enteric, and hepatic systems of human and has already become an unprecedented threat to global healthcare system. COVID-19, the most serious public condition caused by SARS-CoV-2 leads the world to an uncertainty alongside thousands of regular death scenes. Unavailability of specific therapeutics or approved vaccine has made the recovery of COVI-19 more troublesome and challenging. The present in silico study aimed to predict a novel chimeric vaccines by simultaneously targeting four major structural proteins via the establishment of ancestral relationship among different strains of coronaviruses. Conserved regions from the homologous protein sets of spike glycoprotein (S), membrane protein (M), envelope protein and nucleocapsid protein (N) were identified through multiple sequence alignment. The phylogeny analyses of whole genome stated that four proteins (S, E, M and N) reflected the close ancestral relation of SARS-CoV-2 to SARS-COV-1 and bat coronavirus. Numerous immunogenic epitopes (both T cell and B cell) were generated from the common fragments which were further ranked on the basis of antigenicity, transmembrane topology, conservancy level, toxicity and allergenicity pattern and population coverage analysis. Top putative epitopes were combined with appropriate adjuvants and linkers to construct a novel multiepitope subunit vaccine against COVID-19. The designed constructs were characterized based on physicochemical properties, allergenicity, antigenicity and solubility which revealed the superiority of construct V3 in terms safety and efficacy. Essential molecular dynamics and Normal Mode analysis confirmed minimal deformability of the refined model at molecular level. In addition, disulfide engineering was investigated to accelerate the stability of the protein. Molecular docking study ensured high binding affinity between construct V3 and HLA cells, as well as with different host receptors. Microbial expression and translational efficacy of the constructs were checked using pET28a(+) vector of E. coli strain K12. The development of preventive measures to combat COVID-19 infections might be aided the present study. However, the in vivo and in vitro validation might be ensured with wet lab trials using model animals for the implementation of the presented data.", "qid": 50, "docid": "t1xjy12y", "rank": 58, "score": 0.7313224077224731}, {"content": "Title: Global efforts on vaccines for COVID-19: Since, sooner or later, we all will catch the coronavirus Content: COVID-19 is an emerging infectious disease that has turned into a pandemic. It spreads through droplet transmission of the new coronavirus SARS-CoV-2. It is an RNA virus displaying a spike protein as the major surface protein with significant sequence similarity to SARS-CoV which causes severe acute respiratory syndrome. The receptor binding domain of the spike protein interacts with the human angiotensin converting enzyme 2 and is considered as the antigenic determinant for stimulating an immune response. While multiple candidate vaccines are currently under different stages of development, there are no known therapeutic interventions at the moment. This review describes the key genetic features that are being considered for generating vaccine candidates by employing innovative technologies. It also highlights the global efforts being undertaken to deliver vaccines for COVID-19 through unprecedented international cooperation and future challenges post development.", "qid": 50, "docid": "z5q82rmp", "rank": 59, "score": 0.7310556173324585}, {"content": "Title: Global efforts on vaccines for COVID-19: Since, sooner or later, we all will catch the coronavirus. Content: COVID-19 is an emerging infectious disease that has turned into a pandemic. It spreads through droplet transmission of the new coronavirus SARS-CoV-2. It is an RNA virus displaying a spike protein as the major surface protein with significant sequence similarity to SARS-CoV which causes severe acute respiratory syndrome. The receptor binding domain of the spike protein interacts with the human angiotensin converting enzyme 2 and is considered as the antigenic determinant for stimulating an immune response. While multiple candidate vaccines are currently under different stages of development, there are no known therapeutic interventions at the moment. This review describes the key genetic features that are being considered for generating vaccine candidates by employing innovative technologies. It also highlights the global efforts being undertaken to deliver vaccines for COVID-19 through unprecedented international cooperation and future challenges post development.", "qid": 50, "docid": "sdtiyrab", "rank": 60, "score": 0.7310556173324585}, {"content": "Title: From SARS-CoV to SARS-CoV-2: safety and broad-spectrum are important for coronavirus vaccine development Content: The global pandemic of COVID-19 caused by SARS-CoV-2 (also known as 2019-nCoV and HCoV-19) has posed serious threats to public health and economic stability worldwide, thus calling for development of vaccines against SARS-CoV-2 and other emerging and reemerging coronaviruses. Since SARS-CoV-2 and SARS-CoV have high similarity of their genomic sequences and share the same cellular receptor (ACE2), it is essential to learn the lessons and experiences from the development of SARS-CoV vaccines for the development of SARS-CoV-2 vaccines. In this review, we summarized the current knowledge on the advantages and disadvantages of the SARS-CoV vaccine candidates and prospected the strategies for the development of safe, effective and broad-spectrum coronavirus vaccines for prevention of infection by currently circulating SARS-CoV-2 and other emerging and reemerging coronaviruses that may cause future epidemics or pandemics.", "qid": 50, "docid": "8zzi6gu9", "rank": 61, "score": 0.7310101389884949}, {"content": "Title: Vaccines for COVID-19: the current state of play Content: There is a strong consensus globally that a COVID-19 vaccine is likely the most effective approach to sustainably controlling the COVID-19 pandemic. An unprecedented research effort and global coordination has resulted in a rapid development of vaccine candidates and initiation of trials. Here, we review vaccine types, and progress with 10 vaccine candidates against SARS-CoV-2 \u2013 the virus that causes COVID-19 - currently undergoing early phase human trials. We also consider the many challenges of developing and deploying a new vaccine on a global scale, and recommend caution with respect to our expectations of the timeline that may be ahead.", "qid": 50, "docid": "ievuxa6k", "rank": 62, "score": 0.7309322357177734}, {"content": "Title: Multi-epitope vaccine design using an immunoinformatics approach for 2019 novel coronavirus (SARS-CoV-2) Content: A new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. An in silico approach based on the available virus genome was applied to identify 19 high immunogenic B-cell epitopes and 499 human-leukocyte-antigen (HLA) restricted T-cell epitopes. Thirty multi-epitope peptide vaccines were designed by iNeo Suite, and manufactured by solid-phase synthesis. Docking analysis showed stable hydrogen bonds of epitopes with their corresponding HLA alleles. When four vaccine peptide candidates from the spike protein of SARS-CoV-2 were selected to immunize mice, a significantly larger amount of IgG in serum as well as an increase of CD19+ cells in ILNs was observed in peptide-immunized mice compared to the control mice. The ratio of IFN-\u03b3-secreting lymphocytes in CD4+ or CD8+ cells in the peptides-immunized mice were higher than that in the control mice. There were also a larger number of IFN-\u03b3-secreting T cells in spleen in the peptides-immunized mice. This study screened antigenic B-cell and T-cell epitopes in all encoded proteins of SARS-CoV-2, and further designed multi-epitope based peptide vaccine against viral structural proteins. The obtained vaccine peptides successfully elicited specific humoral and cellular immune responses in mice. Primate experiments and clinical trial are urgently required to validate the efficacy and safety of these vaccine peptides. Importance So far, a new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. Different from the development approaches for traditional vaccines, the development of our peptide vaccine is faster and simpler. In this study, we performed an in silico approach to identify the antigenic B-cell epitopes and human-leukocyte-antigen (HLA) restricted T-cell epitopes, and designed a panel of multi-epitope peptide vaccines. The resulting SARS-CoV-2 multi-epitope peptide vaccine could elicit specific humoral and cellular immune responses in mice efficiently, displaying its great potential in our fight of COVID-19.", "qid": 50, "docid": "qeo5dfxg", "rank": 63, "score": 0.7304314374923706}, {"content": "Title: The vaccine journey for COVID-19: a comprehensive systematic review of current clinical trials in humans. Content: INTRODUCTION Since December 2019, there has been an outbreak of a novel beta-coronavirus (SARS-CoV-2) in Wuhan, China. On March the 11th the World Health Organization (WHO) declared COVID-19 as a pandemic, with over 118,000 cases in more than 110 countries around the world. In response to the global coronavirus disease 2019 (COVID-19) emergency, clinical trial research assessing the efficacy and safety of experimental vaccines to prevent COVID-19 are emerging at an unprecedented rate. The aim of this systematic review is to summarize the preliminary experiences and ongoing clinical trials of the major candidates and challenges of the vaccine strategies in humans. EVIDENCE ACQUISITION After a priori protocol registration with PROSPERO (181483), a systematic research of the published literature was conducted on 24 April 2020 using Medline (via PubMed), Embase (via Ovid), and WHO databases. Moreover, to explore the more recent literature we also searched the preprint server medRxiv. Finally, we scrutinized the Cochrane COVID-19 study register and the COVID-19 section of ClinicalTrials.gov database for identifying relevant ongoing clinical trials. Thereafter we selected the articles according to the PRISMA guidelines. Animal or in-vitro experimental studies were excluded. Moreover editorials, commentaries, abstracts, reviews, book chapters, and articles not in English were not included. EVIDENCE SYNTHESIS Our search identified 1359 published papers, 478 pre-print articles and 367 ongoing clinical trials. Finally, only ten ongoing clinical trials met the inclusion criteria. Specifically, seven developed vaccines for the S protein of SARS-CoV-2 and three clinical trials assessed the protective role of BCG vaccine against COVID-19. The first group included phase I/II trials with different types of molecules (DNA or mRNA vaccine, bacterial plasmid or viral vectors), the latter were phase III/IV trials designed on the basis of a heterologous lymphocyte activation by the BCG vaccine. CONCLUSIONS This new disease is pushing the scientific community to develop swiftly a safe and effective vaccine. Notwithstanding the limitations of our analysis, given by the absence of available results, we try to provide a comprehensive view of the ongoing clinical trials in humans. Our analysis reveals a worldwide effort of both scientists and enterprises to achieve one of the most challenging goals of our century.", "qid": 50, "docid": "1yrcbm7e", "rank": 64, "score": 0.7301515936851501}, {"content": "Title: COVID-19 coronavirus vaccine design using reverse vaccinology and machine learning Content: To ultimately combat the emerging COVID-19 pandemic, it is desired to develop an effective and safe vaccine against this highly contagious disease caused by the SARS-CoV-2 coronavirus. Our literature and clinical trial survey showed that the whole virus, as well as the spike (S) protein, nucleocapsid (N) protein, and membrane protein, have been tested for vaccine development against SARS and MERS. We further used the Vaxign reverse vaccinology tool and the newly developed Vaxign-ML machine learning tool to predict COVID-19 vaccine candidates. The N protein was found to be conserved in the more pathogenic strains (SARS/MERS/COVID-19), but not in the other human coronaviruses that mostly cause mild symptoms. By investigating the entire proteome of SARS-CoV-2, six proteins, including the S protein and five non-structural proteins (nsp3, 3CL-pro, and nsp8\u201310) were predicted to be adhesins, which are crucial to the viral adhering and host invasion. The S, nsp3, and nsp8 proteins were also predicted by Vaxign-ML to induce high protective antigenicity. Besides the commonly used S protein, the nsp3 protein has not been tested in any coronavirus vaccine studies and was selected for further investigation. The nsp3 was found to be more conserved among SARS-CoV-2, SARS-CoV, and MERS-CoV than among 15 coronaviruses infecting human and other animals. The protein was also predicted to contain promiscuous MHC-I and MHC-II T-cell epitopes, and linear B-cell epitopes localized in specific locations and functional domains of the protein. Our predicted vaccine targets provide new strategies for effective and safe COVID-19 vaccine development.", "qid": 50, "docid": "ld0vo1rl", "rank": 65, "score": 0.7297757267951965}, {"content": "Title: Dose-dependent response to infection with SARS-CoV-2 in the ferret model: evidence of protection to re-challenge Content: In December 2019 an outbreak of coronavirus disease (COVID-19) emerged in Wuhan, China. The causative agent was subsequently identified and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which rapidly spread worldwide causing a pandemic. Currently there are no licensed vaccines or therapeutics available against SARS-CoV-2 but numerous candidate vaccines are in development and repurposed drugs are being tested in the clinic. There is a vital need for authentic COVID-19 animal models to further our understanding of pathogenesis and viral spread in addition to pre-clinical evaluation of candidate interventions. Here we report a dose titration study of SARS-CoV-2 to determine the most suitable infectious dose to use in the ferret model. We show that a high (5\u00d7106 pfu) and medium (5\u00d7104 pfu) dose of SARS-CoV-2 induces consistent upper respiratory tract (URT) viral RNA shedding in both groups of six challenged animals, whilst a low dose (5\u00d7102 pfu) resulted in only one of six displaying signs of URT viral RNA replication. The URT shedding lasted up to 21 days in the high dose animals with intermittent positive signal from day 14. Sequential culls revealed distinct pathological signs of mild multifocal bronchopneumonia in approximately 5-15% of the lung, observed on day 3 in high and medium dosed animals, with presence of mild broncho-interstitial pneumonia on day 7 onwards. No obvious elevated temperature or signs of coughing or dyspnoea were observed although animals did present with a consistent post-viral fatigue lasting from day 9-14 in the medium and high dose groups. After virus shedding ceased, re-challenged ferrets were shown to be fully protected from acute lung pathology. The endpoints of URT viral RNA replication in addition to distinct lung pathology and post viral fatigue were observed most consistently in the high dose group. This ferret model of SARS-CoV-2 infection presents a mild clinical disease (as displayed by 80% of patients infected with SARS-CoV-2). In addition, intermittent viral shedding on days 14-21 parallel observations reported in a minority of clinical cases.", "qid": 50, "docid": "08zf7161", "rank": 66, "score": 0.729325532913208}, {"content": "Title: Excavating SARS\u2010coronavirus 2 genome for epitope\u2010based subunit vaccine synthesis using immunoinformatics approach Content: Since the outbreak of severe acute respiratory syndrome\u2010coronavirus 2 (SARS\u2010CoV\u20102) in December 2019 in China, there has been an upsurge in the number of deaths and infected individuals throughout the world, thereby leading to the World Health Organization declaration of a pandemic. Since no specific therapy is currently available for the same, the present study was aimed to explore the SARS\u2010CoV\u20102 genome for the identification of immunogenic regions using immunoinformatics approach. A series of computational tools were applied in a systematic way to identify the epitopes that could be utilized in vaccine development. The screened\u2010out epitopes were passed through several immune filters, such as promiscuousity, conservancy, antigenicity, nonallergenicity, population coverage, nonhomologous to human proteins, and affinity with human leukocyte antigen alleles, to screen out the best possible ones. Further, a construct comprising 11 CD4, 12 CD8, 3 B cell, and 3 interferon\u2010\u03b3 epitopes, along with an adjuvant \u03b2\u2010defensin, was designed in silico, resulting in the formation of a multiepitope vaccine. The in silico immune simulation and population coverage analysis of the vaccine sequence showed its capacity to elicit cellular, humoral, and innate immune cells and to cover up a worldwide population of more than 97%. Further, the interaction analysis of the vaccine construct with Toll\u2010like receptor 3 (immune receptor) was carried out by docking and dynamics simulations, revealing high affinity, constancy, and pliability between the two. The overall findings suggest that the vaccine may be highly effective, and is therefore required to be tested in the lab settings to evaluate its efficacy.", "qid": 50, "docid": "q1ixys6v", "rank": 67, "score": 0.7291221022605896}, {"content": "Title: Induction of SARS-nucleoprotein-specific immune response by use of DNA vaccine Content: Abstract Induction of effective cytotoxic T lymphocyte (CTL) and/or a specific antibody against conserved viral proteins may be essential to the development of a safe and effective severe acute respiratory syndrome coronavirus (SARS-Cov) vaccine. DNA vaccination represents a new strategy for induction of humoral and cellular immune response. To determine the ability of SARS-Cov nucleoprotein (N protein) to induce antiviral immunity, in this report, we established a stable C2C12 line expressing SARS-Cov N protein, which was used as a target for specific CTL assay. We also expressed recombinant N proteins in Escherichia coli and prepared N protein-specific polyclonal antibodies. C3H/He mice were immunized with N protein-expressible pcDN-fn vector by intramuscular injections. We found that the DNA vaccination induced both N protein-specific antibody and specific CTL activity to the target. When C3H/He mice were immunized by three separate injections, high antibody titre (1:3200\u20131:6400, average titre is 1:4580) and high CTL activity (67.4\u00b18.4% (E:T=25:1), 69.6\u00b16.7% (E:T=50:1) and 71.8\u00b16.2% (E:T=100:1)) were observed. In the case of two vaccine injections, CTL activity was also high (56.6\u00b112.7% (E:T=25:1), 57.4\u00b111.7% (E:T=50:1) and 63.0\u00b16.3% (E:T=100:1)). However, antibody titres were much lower (1:200\u20131:3200, average titre is 1:980). Our results suggest that SARS-Cov nucleocapsid gene might be a candidate gene for SARS DNA vaccination.", "qid": 50, "docid": "pta94a8q", "rank": 68, "score": 0.7287691831588745}, {"content": "Title: Development of an inactivated vaccine candidate for SARS-CoV-2 Content: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome\u2013coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are currently no SARS-CoV-2-specific treatments or vaccines available due to the novelty of the virus. Hence, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against SARS-CoV-2 strains. Three immunizations using two different doses (3 \u03bcg or 6 \u03bcg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support clinical development of SARS-CoV-2 vaccines for humans.", "qid": 50, "docid": "f5s0ntps", "rank": 69, "score": 0.728116512298584}, {"content": "Title: On facing the SARS-cov-2 (COVID-19) with combination of nanomaterials and medicine: Possible strategies and first challenges Content: Global health is facing the most dangerous situation regarding the novel severe acute respiratory syndrome called coronavirus 2 (SARS-CoV-2), which is widely known as the abbreviated COVID-19 pandemic. This is due to the highly infectious nature of the disease and its possibility to cause pneumonia induced death in approximately 6.89% of infected individuals (data until 27 April 2020). The pathogen causing COVID-19 is called severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is believed to be originated from the Wuhan Province in China. Unfortunately, an effective and approved vaccine for SARS-CoV-2 virus is still not available, making the situation more dangerous and currently available medical care futile. This unmet medical need thus requires significant and very urgent research attention to develop an effective vaccine to address the SARS-CoV-2 virus. In this review, the state-of-the-art drug design strategies against the virus are critically summarized including exploitations of novel drugs and potentials of repurposed drugs. The applications of nanochemistry and general nanotechnology was also discussed to give the status of nanodiagnostic systems for COVID-19.", "qid": 50, "docid": "kx6asglb", "rank": 70, "score": 0.7276604175567627}, {"content": "Title: Coronavirus Vaccine: Light at the End of the Tunnel Content: The world is currently facing an unprecedented global pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Predicting the next source of the pandemic can be very challenging. As vaccination is the best way to prevent an infectious disease, the development of an effective vaccine against SARS-CoV-2 can not only reduce the morbidity and mortality associated with it, but can also lessen the economic impact. As the traditional method of vaccine development takes many years for a vaccine to be available to the society, the vaccine development for SARS-CoV-2 should be speeded up using a pandemic approach with fast-track approvals from the regulatory authorities. Various challenges associated with developing a vaccine during the pandemic such as technological hurdles, clinical development pathways, regulatory issues, and support from global funding agencies are expressed here.", "qid": 50, "docid": "e2g1iu39", "rank": 71, "score": 0.7276303172111511}, {"content": "Title: A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice Content: Public health measures have successfully identified and contained outbreaks of the severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV)(1,2,3,4,5), but concerns remain over the possibility of future recurrences. Finding a vaccine for this virus therefore remains a high priority. Here, we show that a DNA vaccine encoding the spike (S) glycoprotein of the SARS-CoV induces T cell and neutralizing antibody responses, as well as protective immunity, in a mouse model. Alternative forms of S were analysed by DNA immunization. These expression vectors induced robust immune responses mediated by CD4 and CD8 cells, as well as significant antibody titres, measured by enzyme-linked immunosorbent assay. Moreover, antibody responses in mice vaccinated with an expression vector encoding a form of S that includes its transmembrane domain elicited neutralizing antibodies. Viral replication was reduced by more than six orders of magnitude in the lungs of mice vaccinated with these S plasmid DNA expression vectors, and protection was mediated by a humoral but not a T-cell-dependent immune mechanism. Gene-based vaccination for the SARS-CoV elicits effective immune responses that generate protective immunity in an animal model. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature02463) contains supplementary material, which is available to authorized users.", "qid": 50, "docid": "7k088cqv", "rank": 72, "score": 0.7274419069290161}, {"content": "Title: Trained immunity: a tool for reducing susceptibility and severity of SARS-CoV-2 infection Content: Abstract SARS-CoV-2 infection is mild in the majority of individuals, but progresses into severe pneumonia in a small proportion of patients. The increased susceptibility to severe disease in the elderly and individuals with co-morbidities argues for an initial defect in anti-viral host defense mechanisms. Long-term boosting of innate immune responses, also termed \u2018trained immunity\u2019, by certain live vaccines (BCG, oral polio vaccine, measles) induces heterologous protection against infections, through epigenetic, transcriptional and functional reprogramming of innate immune cells. We propose that induction of trained immunity by whole microorganism vaccines may represent an important tool for reducing susceptibility and severity to SARS-CoV-2.", "qid": 50, "docid": "dqs21e0q", "rank": 73, "score": 0.7269451022148132}, {"content": "Title: A Highly Immunogenic Measles Virus-based Th1-biased COVID-19 Vaccine Content: The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has spread world-wide with millions of cases and hundreds of thousands of deaths to date. The gravity of the situation mandates accelerated efforts to identify safe and effective vaccines. Here, we generated measles virus (MeV)-based vaccine candidates expressing the SARS-CoV-2 spike glycoprotein (S). Insertion of the full-length S protein gene in two different MeV genomic positions resulted in modulated S protein expression. The variant with lower S protein expression levels was genetically stable and induced high levels of effective Th1-biased antibody and T cell responses in mice after two immunizations. In addition to neutralizing IgG antibody responses in a protective range, multifunctional CD8+ and CD4+ T cell responses with S protein-specific killing activity were detected. These results are highly encouraging and support further development of MeV-based COVID-19 vaccines. Author Contributions CH performed research, analyzed data, and wrote the paper; CS performed research and analyzed data; AA performed research and analyzed data; AE performed research and analyzed data; SM performed research, analyzed data, and wrote the paper; MH developed the bioinformatics pipeline and analyzed data; BS contributed new reagents and concepts; MDM designed and supervised research, analyzed data and wrote the paper; all authors read, corrected and approved the final manuscript. Significance Statement The COVID-19 pandemic has caused hundreds of thousands of deaths, yet. Therefore, effective vaccine concepts are urgently needed. In search for such a concept, we have analysed a measles virus-based vaccine candidate targeting SARS-CoV-2. Using this well known, safe vaccine backbone, we demonstrate here induction of functional immune responses in both arms of adaptive immunity with the desired immune bias. Therefore, occurrence of immunopathologies such as antibody-dependent enhancement or enhanced respiratory disease is rather unlikely. Moreover, the candidate still induces immunity against the measles, recognized as a looming second menace, when countries are entrapped to stop routine vaccination campaigns in the face of COVID-19. Thus, a bivalent measles-based COVID-19 vaccine could be the solution for two significant public health threats.", "qid": 50, "docid": "wc41epnv", "rank": 74, "score": 0.7269287705421448}, {"content": "Title: A SARS-CoV-2 Vaccination Strategy Focused on Population-Scale Immunity Content: Here we propose a vaccination strategy for SARS-CoV-2 based on identification of both highly conserved regions of the virus and newly acquired adaptations that are presented by MHC class I and II across the vast majority of the population, are highly dissimilar from the human proteome, and are predicted B cell epitopes. We present 65 peptide sequences that we expect to result in a safe and effective vaccine which can be rapidly tested in DNA, mRNA, or synthetic peptide constructs. These include epitopes that are contained within evolutionarily divergent regions of the spike protein reported to increase infectivity through increased binding to the ACE2 receptor, and within a novel furin cleavage site thought to increase membrane fusion. This vaccination strategy specifically targets unique vulnerabilities of SARS-CoV-2 and should engage a robust adaptive immune response in the vast majority of the human population.", "qid": 50, "docid": "qq22z25y", "rank": 75, "score": 0.726819634437561}, {"content": "Title: COVID-19 pandemic: an overview of epidemiology, parthenogenesis, diagnostics and potential vaccines and therapeutics Content: At the time of writing this review, severe acute respiratory coronavirus syndrome-2 (SARS-CoV-2) has infected more than 2,355,853 patients and resulted in more than 164,656 deaths worldwide (as of 20 April 2020). This review highlights the preventive measures, available clinical therapies and the potential of vaccine development against SARS-CoV-2 by taking into consideration the strong genetic similarities of the 2003 epidemic SARS-CoV. Recent studies are investigating the repurposing of US FDA-approved drugs as there is no available vaccine yet with many attempts under clinical evaluation. Several antivirals, antimalarials and immunomodulators that have shown activity against SARS-CoV and Middle East coronavirus respiratory syndromes are being evaluated. In particular, hydroxychloroquine, remdesivir, favipiravir, arbidol, tocilizumab and bevacizumab have shown promising results. The main aim of this review is to provide an overview of this pandemic and where we currently stand.", "qid": 50, "docid": "b0aaozmn", "rank": 76, "score": 0.7266018986701965}, {"content": "Title: COVID-19 pandemic: an overview of epidemiology, pathogenesis, diagnostics and potential vaccines and therapeutics Content: At the time of writing this review, severe acute respiratory coronavirus syndrome-2 (SARS-CoV-2) has infected more than 2,355,853 patients and resulted in more than 164,656 deaths worldwide (as of 20 April 2020). This review highlights the preventive measures, available clinical therapies and the potential of vaccine development against SARS-CoV-2 by taking into consideration the strong genetic similarities of the 2003 epidemic SARS-CoV. Recent studies are investigating the repurposing of US FDA-approved drugs as there is no available vaccine yet with many attempts under clinical evaluation. Several antivirals, antimalarials and immunomodulators that have shown activity against SARS-CoV and Middle East coronavirus respiratory syndromes are being evaluated. In particular, hydroxychloroquine, remdesivir, favipiravir, arbidol, tocilizumab and bevacizumab have shown promising results. The main aim of this review is to provide an overview of this pandemic and where we currently stand.", "qid": 50, "docid": "3framq60", "rank": 77, "score": 0.7266018986701965}, {"content": "Title: Development of vaccines and passive immunotherapy against SARS corona virus using SCID-PBL/hu mouse models Content: We have investigated novel vaccine strategies against severe acute respiratory syndrome (SARS) CoV using cDNA constructs encoding the structural antigens: (S), (M), (E), or (N) protein, derived from SARS CoV. PBL from healthy human volunteers were administered i.p. into IL-2 receptor \u03b3-chain disrupted SCID mice, and SCID-PBL/hu mice were constructed. These mice can be used to analyze the human immune response in vivo. SARS M DNA vaccine and N DNA vaccine induced human CTL specific for SARS CoV antigens. Alternatively, SARS M DNA vaccines inducing human neutralizing antibodies and human monoclonal antibodies against SARS CoV are now being developed. These results show that these vaccines can induce virus-specific immune responses and should provide a useful tool for development of protective and therapeutic vaccines.", "qid": 50, "docid": "bdse9o26", "rank": 78, "score": 0.7260379195213318}, {"content": "Title: Immunoinformatic identification of B cell and T cell epitopes in the SARS-CoV-2 proteome Content: A novel coronavirus (SARS-CoV-2) emerged from China in late 2019 and rapidly spread across the globe, infecting millions of people and generating societal disruption on a level not seen since the 1918 influenza pandemic. A safe and effective vaccine is desperately needed to prevent the continued spread of SARS-CoV-2; yet, rational vaccine design efforts are currently hampered by the lack of knowledge regarding viral epitopes targeted during an immune response, and the need for more in-depth knowledge on betacoronavirus immunology. To that end, we developed a computational workflow using a series of open-source algorithms and webtools to analyze the proteome of SARS-CoV-2 and identify putative T cell and B cell epitopes. Using increasingly stringent selection criteria to select peptides with significant HLA promiscuity and predicted antigenicity, we identified 41 potential T cell epitopes (5 HLA class I, 36 HLA class II) and 6 potential B cell epitopes, respectively. Docking analysis and binding predictions demonstrated enrichment for peptide binding to HLA-B (class I) and HLA-DRB1 (class II) molecules. Overlays of predicted B cell epitopes with the structure of the viral spike (S) glycoprotein revealed that 4 of 6 epitopes were located in the receptor-binding domain of the S protein. To our knowledge, this is the first study to comprehensively analyze all 10 (structural, non-structural and accessory) proteins from SARS-CoV-2 using predictive algorithms to identify potential targets for vaccine development. Significance Statement The novel coronavirus SARS-CoV-2 recently emerged from China, rapidly spreading and ushering in a global pandemic. Despite intensive research efforts, our knowledge of SARS-CoV-2 immunology and the proteins targeted by the immune response remains relatively limited, making it difficult to rationally design candidate vaccines. We employed a suite of bioinformatic tools, computational algorithms, and structural modeling to comprehensively analyze the entire SARS-CoV-2 proteome for potential T cell and B cell epitopes. Utilizing a set of stringent selection criteria to filter peptide epitopes, we identified 41 T cell epitopes (5 HLA class I, 36 HLA class II) and 6 B cell epitopes that could serve as promising targets for peptide-based vaccine development against this emerging global pathogen.", "qid": 50, "docid": "ymvrserl", "rank": 79, "score": 0.7258142828941345}, {"content": "Title: The SARS-CoV-2 Vaccine Pipeline: an Overview Content: Purpose of Review: The goal of this review is to provide a timely overview on efforts to develop a vaccine for the 2019 novel coronavirus SARS-CoV-2, the causative agent of coronavirus disease (COVID-19). Recent Findings: Previous research efforts to develop a severe acute respiratory syndrome coronavirus (SARS-CoV) vaccine in the years following the 2003 pandemic have opened the door for investigators to design vaccine concepts and approaches for the COVID-19 epidemic in China. Both SARS-CoV and SARS-CoV-2 exhibit a high degree of genetic similarity and bind to the same host cell ACE2 receptor. Based on previous experience with SARS-CoV vaccines, it is expected that all COVID-19 vaccines will require careful safety evaluations for immunopotentiation that could lead to increased infectivity or eosinophilic infiltration. Besides this, a COVID-19 vaccine target product profile must address vaccinating at-risk human populations including frontline healthcare workers, individuals over the age of 60, and those with underlying and debilitating chronic conditions. Among the vaccine technologies under evaluation are whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines. Summary: Each current vaccine strategy has distinct advantages and disadvantages. Therefore, it is paramount that multiple strategies be advanced quickly and then evaluated for safety and efficacy. Ultimately, the safety studies to minimize undesired immunopotentiation will become the most significant bottleneck in terms of time.", "qid": 50, "docid": "7jsponjx", "rank": 80, "score": 0.7257335186004639}, {"content": "Title: The SARS-CoV-2 Vaccine Pipeline: an Overview Content: PURPOSE OF REVIEW: The goal of this review is to provide a timely overview on efforts to develop a vaccine for the 2019 novel coronavirus SARS-CoV-2, the causative agent of coronavirus disease (COVID-19). RECENT FINDINGS: Previous research efforts to develop a severe acute respiratory syndrome coronavirus (SARS-CoV) vaccine in the years following the 2003 pandemic have opened the door for investigators to design vaccine concepts and approaches for the COVID-19 epidemic in China. Both SARS-CoV and SARS-CoV-2 exhibit a high degree of genetic similarity and bind to the same host cell ACE2 receptor. Based on previous experience with SARS-CoV vaccines, it is expected that all COVID-19 vaccines will require careful safety evaluations for immunopotentiation that could lead to increased infectivity or eosinophilic infiltration. Besides this, a COVID-19 vaccine target product profile must address vaccinating at-risk human populations including frontline healthcare workers, individuals over the age of 60, and those with underlying and debilitating chronic conditions. Among the vaccine technologies under evaluation are whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines. SUMMARY: Each current vaccine strategy has distinct advantages and disadvantages. Therefore, it is paramount that multiple strategies be advanced quickly and then evaluated for safety and efficacy. Ultimately, the safety studies to minimize undesired immunopotentiation will become the most significant bottleneck in terms of time.", "qid": 50, "docid": "rl2qxd03", "rank": 81, "score": 0.7257334589958191}, {"content": "Title: Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid translational development Content: BACKGROUND: Coronaviruses pose a serious threat to global health as evidenced by Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and COVID-19. SARS Coronavirus (SARS-CoV), MERS Coronavirus (MERS-CoV), and the novel coronavirus, previously dubbed 2019-nCoV, and now officially named SARS-CoV-2, are the causative agents of the SARS, MERS, and COVID-19 disease outbreaks, respectively. Safe vaccines that rapidly induce potent and long-lasting virus-specific immune responses against these infectious agents are urgently needed. The coronavirus spike (S) protein, a characteristic structural component of the viral envelope, is considered a key target for vaccines for the prevention of coronavirus infection. METHODS: We first generated codon optimized MERS-S1 subunit vaccines fused with a foldon trimerization domain to mimic the native viral structure. In variant constructs, we engineered immune stimulants (RS09 or flagellin, as TLR4 or TLR5 agonists, respectively) into this trimeric design. We comprehensively tested the pre-clinical immunogenicity of MERS-CoV vaccines in mice when delivered subcutaneously by traditional needle injection, or intracutaneously by dissolving microneedle arrays (MNAs) by evaluating virus specific IgG antibodies in the serum of vaccinated mice by ELISA and using virus neutralization assays. Driven by the urgent need for COVID-19 vaccines, we utilized this strategy to rapidly develop MNA SARS-CoV-2 subunit vaccines and tested their pre-clinical immunogenicity in vivo by exploiting our substantial experience with MNA MERS-CoV vaccines. FINDINGS: Here we describe the development of MNA delivered MERS-CoV vaccines and their pre-clinical immunogenicity. Specifically, MNA delivered MERS-S1 subunit vaccines elicited strong and long-lasting antigen-specific antibody responses. Building on our ongoing efforts to develop MERS-CoV vaccines, promising immunogenicity of MNA-delivered MERS-CoV vaccines, and our experience with MNA fabrication and delivery, including clinical trials, we rapidly designed and produced clinically-translatable MNA SARS-CoV-2 subunit vaccines within 4 weeks of the identification of the SARS-CoV-2 S1 sequence. Most importantly, these MNA delivered SARS-CoV-2 S1 subunit vaccines elicited potent antigen-specific antibody responses that were evident beginning 2 weeks after immunization. INTERPRETATION: MNA delivery of coronaviruses-S1 subunit vaccines is a promising immunization strategy against coronavirus infection. Progressive scientific and technological efforts enable quicker responses to emerging pandemics. Our ongoing efforts to develop MNA-MERS-S1 subunit vaccines enabled us to rapidly design and produce MNA SARS-CoV-2 subunit vaccines capable of inducing potent virus-specific antibody responses. Collectively, our results support the clinical development of MNA delivered recombinant protein subunit vaccines against SARS, MERS, COVID-19, and other emerging infectious diseases.", "qid": 50, "docid": "um3fa49r", "rank": 82, "score": 0.7254869937896729}, {"content": "Title: Development of Vaccines and Passive Immunotherapy Against Sars Coronavirus Using Mouse and Scid-PBL/hu Mouse Models Content: We have investigated novel vaccines strategies against severe acute respiratory syndrome (SARS) CoV infection using cDNA constructs encoding the structural antigens; spike (S), membrane (M), envelope (E), or nucleocapsid (N) protein, derived from SARS CoV (strain HKU39849, TW1, or FFM-1). As SARS-CoV is thought to infect the alveolar epithelial cell of the lung,in the present study, a type II alveolar epithelial cell clone, T7, was used to analyze the mechanism of CTL against SARS CoV membrane antigens. Mice vaccinated with SARS CoV (N) DNA or (M) DNA using pcDNA 3.1 (+) plasmid vector showed T-cell immune responses (CTL induction and proliferation) against type II alveolar epithelial cells (T7) transfected with SARS (N) or (M) DNA, respectively. To determine whether these DNA vaccines could induce T-cell immune responses in humans as well as in mice, SCID-PBL/hu mice were immunized with these DNA vaccines. PBL from healthy human volunteers were administered i.p. into IL-2 receptor gamma-chain-disrupted NOD-SCID mice [IL-2R(-/-) NOD-SCID]. SCID-PBL/hu mice thus constructed can be used to analyze the human immune response in vivo. The SCID-PBL/hu mice were immunized with SARS (N) DNA or (M) DNA and analyzed for a human T-cell immune response. The M DNA vaccine enhanced CTL activity and proliferation in the presence of M peptide in SCID-PBL/hu mice. Furthermore, the SARS N DNA vaccine induced CTL activity (IFN-gamma production by recombinant N protein or N protein-pulsed autologous B blast cells) and proliferation of spleen cells in SCID-PBL/hu mice. These results, demonstrate that SARS M and N DNA vaccines induced human CTL and human T-cell proliferative responses. On the other hand, we have developed SARS DNA vaccines that induce human neutralizing antibodies and human monoclonal antibodies against SARS CoV. Transgenic mice expressing SARS-CoV receptor (angiotensin converting enzyme 2) are also under development. These vaccines are expected to induce immune responses specific for SARS CoV in human and should provide useful tool for development of protective vaccines.", "qid": 50, "docid": "j4b88irz", "rank": 83, "score": 0.7253950834274292}, {"content": "Title: Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies Content: The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the available SARS-CoV-2 sequences (as of 9 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.", "qid": 50, "docid": "7i52vltp", "rank": 84, "score": 0.7251811027526855}, {"content": "Title: Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells Content: Current guidelines for COVID-19 management recommend the utilization of various repurposed drugs. Despite ongoing research toward the development of a vaccine against SARS-CoV-2, such a vaccine will not be available in time to contribute to the containment of the ongoing pandemic. Therefore, there is an urgent need to develop a framework for the rapid identification of novel targets for diagnostic and therapeutic interventions. We analyzed publicly available transcriptomic datasets of SARS-CoV infected humans and mammals to identify consistent differentially expressed genes then validated in SARS-CoV-2 infected epithelial cells transcriptomic datasets. Comprehensive toxicogenomic analysis of the identified genes to identify possible interactions with clinically proven drugs was carried out. We identified IFITM3 as an early upregulated gene, and valproic acid was found to enhance its mRNA expression as well as induce its antiviral action. These findings indicate that analysis of publicly available transcriptomic and toxicogenomic data represents a rapid approach for the identification of novel targets and molecules that can modify the action of such targets during the early phases of emerging infections like COVID-19.", "qid": 50, "docid": "cmfo60z0", "rank": 85, "score": 0.7250133156776428}, {"content": "Title: Optimization of a DNA vaccine against SARS. Content: Severe acute respiratory syndrome coronavirus (SARS-CoV) first appeared in Southern China in November 2002, and then quickly spread to 33 countries on five continents along international air travel routes. Although the SARS epidemic has been contained, there is a clear need for a safe and effective vaccine should an outbreak of a SARS-CoV infection reappear in human population. In this study, we tested four DNA-vaccine constructs: (1) pLL70, containing cDNA for the SARS-CoV spike (S) gene; (2) pcDNA-SS, containing codon-optimized S gene for SARS-CoV S protein (residues 12-1255) fused with a leader sequence derived from the human CD5 gene; (3) pcDNA-St, containing the gene encoding the N-portion of the codon-optimized S gene (residues 12-532) with the CD5 leader sequence; (4) pcDNA-St-VP22C, containing the gene encoding the N-portion of the codon-optimized S protein with the CD5 leader sequence fused with the C-terminal 138 amino acids of the bovine herpesvirus-1 (BHV-1) major tegument protein VP22. Each of these plasmids was intradermally administered to C57BL/6 mice in three separate immunizations. Analysis of humoral and cellular immune responses in immunized mice demonstrated that pcDNA-SS and pcDNA-St-VP22C are the most immunogenic SARS vaccine candidates.", "qid": 50, "docid": "6derrgno", "rank": 86, "score": 0.7244091033935547}, {"content": "Title: Age-related expression of SARS-CoV-2 priming protease TMPRSS2 in the developing lung Content: The emergence of the SARS-CoV-2 novel coronavirus has led to a global pandemic (COVID-19), with more than 5 million cases as of May 2020(1). Available data suggest that severe illness and death from COVID-19 are rare in the pediatric population(2). Integrating single-cell RNA sequencing of the developing mouse lung with temporally-resolved RNA-in-situ hybridization (ISH) in mouse and human lung tissue, we found expression of SARS-CoV-2 Spike protein primer TMPRSS2 was highest in ciliated cells and type I alveolar epithelial cells (AT1) and increased with aging in mice and humans. SARS-CoV-2 RNA colocalized with TMPRSS2 mRNA in lung cells from a patient who died of SARS-CoV-2. Together, these data suggest developmental regulation of TMPRSS2 may underlie the relative protection of infants and children from severe respiratory illness.", "qid": 50, "docid": "2syned3k", "rank": 87, "score": 0.7240158319473267}, {"content": "Title: Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies Content: The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the 120 available SARS-CoV-2 sequences (as of 21 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.", "qid": 50, "docid": "ojs5e7n9", "rank": 88, "score": 0.7238785028457642}, {"content": "Title: Physicochemical properties of SARS-CoV-2 for drug targeting, virus inactivation and attenuation, vaccine formulation and quality control Content: The material properties of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its proteins are discussed. We review the viral structure, size, rigidity, lipophilicity, isoelectric point, buoyant density and centrifugation conditions, stability against pH, temperature, UV light, gamma radiation, and susceptibility to various chemical agents including solvents and detergents. Possible inactivation, downstream, and formulation conditions are given including suitable buffers and some first ideas for quality-control methods. This information supports vaccine development and discussion with competent authorities during vaccine approval and is certainly related to drug-targeting strategies and hygienics. Several instructive tables are given, including the pI and grand average of hydropathicity (GRAVY) of SARS-CoV-1 and -2 proteins in comparison. SARS-CoV-1 and SARS-CoV-2 are similar in many regards, so information can often be derived. Both are unusually stable, but sensitive at their lipophilic membranes. However, since seemingly small differences can have strong effects, for example, on immunologically relevant epitope settings, unevaluated knowledge transfer from SARS-CoV-1 to SARS-CoV-2 cannot be advised. Published knowledge regarding downstream processes, formulations and quality assuring methods is, as yet, limited. However, standard approaches employed for other viruses and vaccines seem to be feasible including virus inactivation, centrifugation conditions, and the use of adjuvants.", "qid": 50, "docid": "zkavsvoh", "rank": 89, "score": 0.7237861156463623}, {"content": "Title: An infectious cDNA clone of SARS-CoV-2 Content: The ongoing pandemic of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), underscores the urgency to develop experimental systems for studying this virus and identifying countermeasures We report a reverse genetic system for SARS-CoV-2 Seven cDNA fragments spanning the SARS-CoV-2 genome were assembled into a full-genome cDNA RNA transcribed from the full-genome cDNA was highly infectious after electroporation into cells, producing 2 9\u00d7106 PFU/ml of virus Compared with a clinical isolate, the infectious clone-derived SARS-CoV-2 (icSARS-CoV-2) exhibited similar plaque morphology, viral RNA profile, and replication kinetics Additionally, icSARS-CoV-2 retained engineered molecular markers and did not acquire other mutations A stable mNeonGreen SARS-CoV-2 (icSARS-CoV2-mNG) was generated by introducing this reporter gene into OFR7 of the viral genome icSARSCoV-2-mNG was successfully used to evaluate the antiviral activities of interferon Collectively, the reverse genetic system and reporter virus provide key reagents to study SARS-CoV-2 and develop countermeasures", "qid": 50, "docid": "qiuf2okb", "rank": 90, "score": 0.7231488823890686}, {"content": "Title: Immunogenicity and protective efficacy in mice and hamsters of a \u03b2-propiolactone inactivated whole virus SARS-CoV vaccine. Content: The immunogenicity and efficacy of \u03b2-propiolactone (BPL) inactivated whole virion SARS-CoV (WI-SARS) vaccine was evaluated in BALB/c mice and golden Syrian hamsters. The vaccine preparation was tested with or without adjuvants. Adjuvant Systems AS01(B) and AS03(A) were selected and tested for their capacity to elicit high humoral and cellular immune responses to WI-SARS vaccine. We evaluated the effect of vaccine dose and each adjuvant on immunogenicity and efficacy in mice, and the effect of vaccine dose with or without the AS01(B) adjuvant on the immunogenicity and efficacy in hamsters. Efficacy was evaluated by challenge with wild-type virus at early and late time points (4 and 18 wk post-vaccination). A single dose of vaccine with or without adjuvant was poorly immunogenic in mice; a second dose resulted in a significant boost in antibody levels, even in the absence of adjuvant. The use of adjuvants resulted in higher antibody titers, with the AS01(B)-adjuvanted vaccine being slightly more immunogenic than the AS03(A)-adjuvanted vaccine. Two doses of WI-SARS with and without Adjuvant Systems were highly efficacious in mice. In hamsters, two doses of WI-SARS with and without AS01(B) were immunogenic, and two doses of 2 \u03bcg of WI-SARS with and without the adjuvant provided complete protection from early challenge. Although antibody titers had declined in all groups of vaccinated hamsters 18 wk after the second dose, the vaccinated hamsters were still partially protected from wild-type virus challenge. Vaccine with adjuvant provided better protection than non-adjuvanted WI-SARS vaccine at this later time point. Enhanced disease was not observed in the lungs or liver of hamsters following SARS-CoV challenge, regardless of the level of serum neutralizing antibodies.", "qid": 50, "docid": "2gsy750k", "rank": 91, "score": 0.7228987812995911}, {"content": "Title: Heterologous viral RNA export elements improve expression of severe acute respiratory syndrome (SARS) coronavirus spike protein and protective efficacy of DNA vaccines against SARS Content: Abstract The SARS-CoV spike glycoprotein (S) is the main target of the protective immune response in humans and animal models of SARS. Here, we demonstrated that efficient expression of S from the wild-type spike gene in cultured cells required the use of improved plasmid vectors containing donor and acceptor splice sites, as well as heterologous viral RNA export elements, such as the CTE of Mazon-Pfizer monkey virus or the PRE of Woodchuck hepatitis virus (WPRE). The presence of both splice sites and WPRE markedly improved the immunogenicity of S-based DNA vaccines against SARS. Upon immunization of mice with low doses (2 \u03bcg) of naked DNA, only intron and WPRE-containing vectors could induce neutralizing anti-S antibodies and provide protection against challenge with SARS-CoV. Our observations are likely to be useful for the construction of plasmid and viral vectors designed for optimal expression of intronless genes derived from cytoplasmic RNA viruses.", "qid": 50, "docid": "7del8d2p", "rank": 92, "score": 0.7228132486343384}, {"content": "Title: An Infectious cDNA Clone of SARS-CoV-2 Content: Summary The ongoing pandemic of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), underscores the urgency to develop experimental systems for studying this virus and identifying countermeasures. We report a reverse genetic system for SARS-CoV-2. Seven complimentary DNA (cDNA) fragments spanning the SARS-CoV-2 genome were assembled into a full-genome cDNA. RNA transcribed from the full-genome cDNA was highly infectious after electroporation into cells, producing 2.9 \u00d7 106 plaque-forming unit (PFU)/mL of virus. Compared with a clinical isolate, the infectious-clone-derived SARS-CoV-2 (icSARS-CoV-2) exhibited similar plaque morphology, viral RNA profile, and replication kinetics. Additionally, icSARS-CoV-2 retained engineered molecular markers and did not acquire other mutations. We generated a stable mNeonGreen SARS-CoV-2 (icSARS-CoV-2-mNG) by introducing this reporter gene into ORF7 of the viral genome. icSARS-CoV-2-mNG was successfully used to evaluate the antiviral activities of interferon (IFN). Collectively, the reverse genetic system and reporter virus provide key reagents to study SARS-CoV-2 and develop countermeasures.", "qid": 50, "docid": "06e3vxu9", "rank": 93, "score": 0.7226982712745667}, {"content": "Title: ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques Content: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the COVID-19 pandemic3. Vaccines are an essential countermeasure urgently needed to control the pandemic4. Here, we show that the adenovirus-vectored vaccine ChAdOx1 nCoV-19, encoding the spike protein of SARS-CoV-2, is immunogenic in mice, eliciting a robust humoral and cell-mediated response. This response was not Th2 dominated, as demonstrated by IgG subclass and cytokine expression profiling. A single vaccination with ChAdOx1 nCoV-19 induced a humoral and cellular immune response in rhesus macaques. We observed a significantly reduced viral load in bronchoalveolar lavage fluid and respiratory tract tissue of vaccinated animals challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated rhesus macaques. Importantly, no evidence of immune-enhanced disease following viral challenge in vaccinated animals was observed. ChAdOx1 nCoV-19 is currently under investigation in a phase I clinical trial. Safety, immunogenicity and efficacy against symptomatic PCR-positive COVID-19 disease will now be assessed in randomised controlled human clinical trials.", "qid": 50, "docid": "uexahhdr", "rank": 94, "score": 0.7223825454711914}, {"content": "Title: Medication for COVID-19\u2014an Overview of Approaches Currently Under Study Content: BACKGROUND: With the worldwide spread of SARS-CoV-2 infection, it is becoming increasingly urgent to develop a vaccine to prevent COVID-19, as well as effective drugs to treat it. METHODS: This article is based on a selective literature search in PubMed and ClinicalTrials.gov, followed by an assessment of the ongoing clinical trials that were revealed by the search. RESULTS: A number of substances have been found to prevent the reproduction of SARS-CoV-2 in vitro. These include virustatic agents that have already been approved for the treatment of other types of viral infection, as well as drugs that are currently used for entirely different purposes. High in vitro activity has been found for the nucleotide analogue remdesivir, for the antimalarial drug chloroquine, and for nitazoxanide, a drug used to treat protozoan infections. Because the virus enters human cells by way of the membrane-associated angiotensin converting enzyme 2 (ACE2), keeping the virus from docking to this receptor is a conceivable treatment approach. Transmembrane protease serine 2 (TMPRSS2) plays a role in the fusion of the virus with cells; inhibitors of this enzyme are known as well. The potential therapeutic efficacy and tolerability of these and other active substances remain to be investigated in clinical trials. At present, more than 80 trials on COVID-10 have already been registered with ClinicalTrials.gov. Some initial findings should already be available in late April 2020. CONCLUSION: Clinical trials are now indispensable in order to determine the true clinical benefits and risks of the substances that have been found to be active against SARS-CoV-2 in vitro. There is not yet any recommendation for the therapeutic use of any particular agent beyond standard supportive treatment.", "qid": 50, "docid": "vyeescn8", "rank": 95, "score": 0.7222209572792053}, {"content": "Title: Pharmacological and non-pharmacological efforts at prevention, mitigation, and treatment for COVID-19 Content: A global outbreak of the SARS-CoV-2 virus has infected millions of people over a short period of time. The communicability and increased mortality from the SARS-CoV-2 infection mandated the WHO to declare COVID-19 a worldwide pandemic. The virus outbreak has spread when there are no approved vaccines, treatments, or prophylactic therapies available. Researchers from all over the world have prioritized development of vaccines and antivirals. Several vaccine projects have seen successes in preclinical, phase I, and phase II clinical trials using recombinant DNA, mRNA, live attenuated virus, S-protein subunits, virus like particles, and viral vectors. Initial findings from antivirals such as remdesivir, favipiravir, danoprevir or lopinavir with ritonavir are presented. Immunomodulatory molecules such as sarilumab, tocilizumab, janus kinase inhibitors, and hyperimmune convalescent plasma have mixed outcomes from initial clinical findings; however, pending randomized controlled trials will assist national health institutions to make treatment recommendations for COVID-19. Where compassionate use of remdesivir has shown some benefits, therapies such as hydroxychloroquine have proven harmful due to their toxicities. This review discusses pharmacological interventions at play and evidence-based successes and limitations of non-pharmacological therapies such as social distancing, personal protective equipment, and ventilator support associated with the prevention and treatment of COVID-19.", "qid": 50, "docid": "np8jr9qk", "rank": 96, "score": 0.7220063209533691}, {"content": "Title: Pharmacological and non-pharmacological efforts at prevention, mitigation, and treatment for COVID-19. Content: A global outbreak of the SARS-CoV-2 virus has infected millions of people over a short period of time. The communicability and increased mortality from the SARS-CoV-2 infection mandated the WHO to declare COVID-19 a worldwide pandemic. The virus outbreak has spread when there are no approved vaccines, treatments, or prophylactic therapies available. Researchers from all over the world have prioritized development of vaccines and antivirals. Several vaccine projects have seen successes in preclinical, phase I, and phase II clinical trials using recombinant DNA, mRNA, live attenuated virus, S-protein subunits, virus like particles, and viral vectors. Initial findings from antivirals such as remdesivir, favipiravir, danoprevir or lopinavir with ritonavir are presented. Immunomodulatory molecules such as sarilumab, tocilizumab, janus kinase inhibitors, and hyperimmune convalescent plasma have mixed outcomes from initial clinical findings; however, pending randomized controlled trials will assist national health institutions to make treatment recommendations for COVID-19. Where compassionate use of remdesivir has shown some benefits, therapies such as hydroxychloroquine have proven harmful due to their toxicities. This review discusses pharmacological interventions at play and evidence-based successes and limitations of non-pharmacological therapies such as social distancing, personal protective equipment, and ventilator support associated with the prevention and treatment of COVID-19.", "qid": 50, "docid": "gxhztof5", "rank": 97, "score": 0.7220062613487244}, {"content": "Title: Shotgun proteomics of SARS-CoV-2 infected cells and its application to the optimisation of whole viral particle antigen production for vaccines Content: Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has resulted in a pandemic and continues to spread quickly around the globe. Currently, no effective vaccine is available to prevent COVID-19 and an intense global development activity is in progress. In this context, the different technology platforms face several challenges resulting from the involvement of a new virus still not fully characterised. Finding of the right conditions for virus amplification for the development of vaccines based on inactivated or attenuated whole viral particles is among them. Here, we describe the establishment of a workflow based on shotgun tandem mass spectrometry data to guide the optimisation of the conditions for viral amplification. In parallel, we analysed the dynamic of the host cell proteome following SARS-CoV-2 infection providing a global overview of biological processes modulated by the virus and that could be further explored to identify drug targets to address the pandemic.", "qid": 50, "docid": "kd02dehk", "rank": 98, "score": 0.7220054864883423}, {"content": "Title: Immune-mediated approaches against COVID-19 Content: The coronavirus disease-19 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The long incubation period of this new virus, which is mostly asymptomatic yet contagious, is a key reason for its rapid spread across the world. Currently, there is no worldwide-approved treatment for COVID-19. Therefore, the clinical and scientific communities have joint efforts to reduce the severe impact of the outbreak. Research on previous emerging infectious diseases have created valuable knowledge that is being exploited for drug repurposing and accelerated vaccine development. Nevertheless, it is important to generate knowledge on SARS-CoV-2 mechanisms of infection and its impact on host immunity, to guide the design of COVID-19 specific therapeutics and vaccines suitable for mass immunization. Nanoscale delivery systems are expected to play a paramount role in the success of these prophylactic and therapeutic approaches. This Review provides an overview of SARS-CoV-2 pathogenesis and examines immune-mediated approaches currently explored for COVID-19 treatments, with an emphasis on nanotechnological tools.", "qid": 50, "docid": "g1j8wk11", "rank": 99, "score": 0.7219696044921875}, {"content": "Title: Induction of Th1 type response by DNA vaccinations with N, M, and E genes against SARS-CoV in mice Content: Abstract Vaccination against the SARS-CoV infection is an attractive means to control the spread of viruses in public. In this study, we employed a DNA vaccine technology with the levamisole, our newly discovered chemical adjuvant, to generate Th1 type of response. To avoid the enhancement antibody issue, genes encoding the nucleocapsid, membrane, and envelope protein of SARS-CoV were cloned and their expressions in mammalian cells were determined. After the intramuscular introduction into animals, we observed that the constructs of the E, M, and N genes could induce high levels of specific antibodies, T cell proliferations, IFN-\u03b3, DTH responses, and in vivo cytotoxic T cells activities specifically against SARS-CoV antigens. The highest immune responses were generated by the construct encoding the nucleocapsid protein. The results suggest that the N, M, and E genes could be used as the targets to prevent SARS-CoV infection in the DNA vaccine development.", "qid": 50, "docid": "3fnwosst", "rank": 100, "score": 0.7219051122665405}]}
{"query": "has social distancing had an impact on slowing the spread of COVID-19?", "hits": [{"content": "Title: U.S. county level analysis to determine If social distancing slowed the spread of COVID-19 Content: OBJECTIVE. To analyze the effectiveness of social distancing in the United States (U.S.). METHODS. A novel cell-phone ping data was used to quantify the measures of social distancing by all U.S. counties. RESULTS. Using a difference-in-difference approach results show that social distancing has been effective in slowing the spread of COVID-19. CONCLUSIONS. As policymakers face the very difficult question of the necessity and effectiveness of social distancing across the U.S., counties where the policies have been imposed have effectively increased social distancing and have seen slowing the spread of COVID-19. These results might help policymakers to make the public understand the risks and benefits of the lockdown.", "qid": 10, "docid": "pn02p843", "rank": 1, "score": 0.8342075943946838}, {"content": "Title: On the benefits of flattening the curve: A perspective() Content: The many variations on a graphic illustrating the impact of non-pharmaceutical measures to mitigate pandemic influenza that have appeared in recent news reports about COVID-19 suggest a need to better explain the mechanism by which social distancing reduces the spread of infectious diseases. And some reports understate one benefit of reducing the frequency or proximity of interpersonal encounters, a reduction in the total number of infections. In hopes that understanding will increase compliance, we describe how social distancing a) reduces the peak incidence of infections, b) delays the occurrence of this peak, and c) reduces the total number of infections during epidemics. In view of the extraordinary efforts underway to identify existing medications that are active against SARS-CoV-2 and to develop new antiviral drugs, vaccines and antibody therapies, any of which may have community-level effects, we also describe how pharmaceutical interventions affect transmission.", "qid": 10, "docid": "zukjh1hr", "rank": 2, "score": 0.827835202217102}, {"content": "Title: Dynamics of COVID-19 under social distancing measures are driven by transmission network structure Content: In the absence of pharmaceutical interventions, social distancing is being used worldwide to curb the spread of COVID-19. The impact of these measures has been inconsistent, with some regions rapidly nearing disease elimination and others seeing delayed peaks or nearly flat epidemic curves. Here we build a stochastic epidemic model to examine the effects of COVID-19 clinical progression and transmission network structure on the outcomes of social distancing interventions. We find that the strength of within-household transmission is a critical determinant of success, governing the timing and size of the epidemic peak, the rate of decline, individual risks of infection, and the success of partial relaxation measures. The structure of residual external connections, driven by workforce participation and essential businesses, interacts to determine outcomes. These findings can improve future predictions of the timescale and efficacy of interventions needed to control similar outbreaks, and highlight the need for better quantification and control of household transmission.", "qid": 10, "docid": "v941u1t1", "rank": 3, "score": 0.8274010419845581}, {"content": "Title: On the benefits of flattening the curve: A perspective Content: The many variations on a graphic illustrating the impact of non-pharmaceutical measures to mitigate pandemic influenza that have appeared in recent news reports about COVID-19 suggest a need to better explain the mechanism by which social distancing reduces the spread of infectious diseases. And some reports understate one benefit of reducing the frequency or proximity of interpersonal encounters, a reduction in the total number of infections. In hopes that understanding will increase compliance, we describe how social distancing (a) reduces the peak incidence of infections, (b) delays the occurrence of this peak, and (c) reduces the total number of infections during epidemics. In view of the extraordinary efforts underway to identify existing medications that are active against SARS-CoV-2 and to develop new antiviral drugs, vaccines and antibody therapies, any of which may have community-level effects, we also describe how pharmaceutical interventions affect transmission.", "qid": 10, "docid": "883y61q5", "rank": 4, "score": 0.8264934420585632}, {"content": "Title: COVID-19 related social distancing measures and reduction in city mobility Content: In the absence of any pharmacological intervention, one approach to slowing the COVID-19 pandemic is reducing the contact rate in the population through social distancing. Governments the world over have instituted different measures to increase social distancing but information on their effectiveness in reducing mobility is lacking. We analyzed the mobility data from 41 cities to look at the effect of these interventions. The median mobility across cities on March 2, 2020 was 100% (IQR: 94%, 107%), which decreased to a median of 10% (IQR: 7%, 17%) on March 26, 2020. We found that the mobility decreased on average by 3.4% (95%CI: 3.3%, 3.6%) per day from March 2 through March 26. Social distancing measures decreased the mobility by an additional 23% (95%CI: 20%, 27%). Our study provides initial evidence for the reduction in mobility in cities instituting social distancing measures.", "qid": 10, "docid": "71b6ai77", "rank": 5, "score": 0.8255469799041748}, {"content": "Title: Social Distancing Has Merely Stabilized COVID-19 in the US Content: Social distancing measures, with varying degrees of restriction, have been imposed around the world in order to stem the spread of COVID-19. In this work we analyze the effect of current social distancing measures in the United States. We quantify the reduction in doubling rate, by state, that is associated with social distancing. We find that social distancing is associated with a statistically-significant reduction in the doubling rate for all but three states. At the same time, we do not find significant evidence that social distancing has resulted in a reduction in the number of daily confirmed cases. Instead, social distancing has merely stabilized the spread of the disease. We provide an illustration of our findings for each state, including point estimates of the effective reproduction number, R, both with and without social distancing. We also discuss the policy implications of our findings.", "qid": 10, "docid": "all7ocnd", "rank": 6, "score": 0.81978440284729}, {"content": "Title: Impact of non-pharmaceutical interventions against COVID-19 in Europe: a quasi-experimental study Content: The current epidemic of COVID-19 is unparalleled in recent history as are the social distancing interventions that have led to a significant halt on the economic and social life of so many countries. However, there is very little empirical evidence about which social distancing measures have the most impact. We report a quasi-experimental study of the impact of various interventions for control of the outbreak. Data on case numbers and deaths were taken from the daily published figures by the European Centre for Disease Control and dates of initiation of various control strategies from the Institute of Health Metrics and Evaluation website and published sources. Our primary analyses were modelled in R using Bayesian generalised additive mixed models (GAMM). We found that closure of education facilities, prohibiting mass gatherings and closure of some non-essential businesses were associated with reduced incidence whereas stay at home orders, closure of all non-businesses and requiring the wearing of facemasks or coverings in public was not associated with any independent additional impact. Our results could help inform strategies for coming out of lockdown.", "qid": 10, "docid": "3yi44xfe", "rank": 7, "score": 0.8149596452713013}, {"content": "Title: Fever and mobility data indicate social distancing has reduced incidence of communicable disease in the United States Content: In March of 2020, many U.S. state governments encouraged or mandated restrictions on social interactions to slow the spread of COVID-19, the disease caused by the novel coronavirus SARS-CoV-2 that has spread to nearly 180 countries. Estimating the effectiveness of these social-distancing strategies is challenging because surveillance of COVID-19 has been limited, with tests generally being prioritized for high-risk or hospitalized cases according to temporally and regionally varying criteria. Here we show that reductions in mobility across U.S. counties with at least 100 confirmed cases of COVID-19 led to reductions in fever incidences, as captured by smart thermometers, after a mean lag of 6.5 days ($90\\%$ within 3--10 days) that is consistent with the incubation period of COVID-19. Furthermore, counties with larger decreases in mobility subsequently achieved greater reductions in fevers ($p<0.01$), with the notable exception of New York City and its immediate vicinity. These results indicate that social distancing has reduced the transmission of influenza like illnesses, including COVID 19, and support social distancing as an effective strategy for slowing the spread of COVID-19.", "qid": 10, "docid": "cb5ebiiv", "rank": 8, "score": 0.8112828731536865}, {"content": "Title: Targeted adaptive isolation strategy for Covid-19 pandemic Content: We investigate the effects of social distancing in controlling the impact of the COVID-19 epidemic using a simple susceptible-infected-removed epidemic model. We show that an alternative or complementary approach based on targeted isolation of the vulnerable sub-population may provide a more efficient and robust strategy at a lower economic and social cost within a shorter timeframe resulting in a collectively immune population.", "qid": 10, "docid": "80d9p4j8", "rank": 9, "score": 0.807098388671875}, {"content": "Title: Targeted adaptive isolation strategy for COVID-19 pandemic Content: We investigate the effects of social distancing in controlling the impact of the COVID-19 epidemic using a simple susceptible-infected-removed epidemic model. We show that an alternative or complementary approach based on targeted isolation of the vulnerable sub-population may provide a more efficient and robust strategy at a lower economic and social cost within a shorter timeframe resulting in a collectively immune population.", "qid": 10, "docid": "qpufvt3o", "rank": 10, "score": 0.8070982694625854}, {"content": "Title: Enacting national social distancing policies corresponds with dramatic reduction in COVID19 infection rates Content: The outbreak the SARS-CoV-2 (CoV-2) virus has resulted in over 2.5 million cases of COVID19, greatly stressing global healthcare infrastructure. Lacking medical prophylactic measures to combat disease spread, many nations have adopted social distancing policies in order to mitigate transmission of CoV-2. While mathematical models have suggested the efficacy of social distancing to curb the spread of CoV-2, there is a lack of systematic studies to quantify the real-world efficacy of these approaches. Here, we quantify the spread rate of COVID19 before and after national social distancing measures were implemented in 26 nations and compare this to the changes in COVID19 spread rate over equivalent time periods in 27 nations that did not enact social distancing policies. We find that social distancing policies significantly reduced the COVID19 spread rate. Using mixed linear regression models we estimate that social distancing policies reduced the spread of COVID19 by 66%. These data suggest that social distancing policies may be a powerful tool to prevent spread of COVID19 in real-world scenarios.", "qid": 10, "docid": "vdrd74nz", "rank": 11, "score": 0.8070555925369263}, {"content": "Title: Effects of Government Mandated Social Distancing Measures on Cumulative Incidence of COVID-19 in the United States and its Most Populated Cities Content: COVID-19, caused by the SARS-CoV-2 virus, has quickly spread throughout the world, necessitating assessment of the most effective containment methods. Very little research exists on the effects of social distancing measures on this pandemic. The purpose of this study was to examine the effects of government implemented social distancing measures on the cumulative incidence rates of COVID-19 in the United States on a state level, and in the 25 most populated cities, while adjusting for socio-demographic risk factors. The social distancing variables assessed in this study were: days to closing of non-essential business; days to stay home orders; days to restrictions on gathering, days to restaurant closings and days to school closing. Using negative binomial regression, adjusted rate ratios and 95% confidence intervals were calculated comparing two levels of a binary variable: above median value, and median value and below for days to implementing a social distancing measure. For city level data, the effects of these social distancing variables were also assessed in high (above median value) vs low (median value and below) population density cities. For the state level analysis, days to school closing was associated with cumulative incidence, with an adjusted rate ratio of 1.59 (95% CI:1.03,2.44), p=0.04 at 35 days. Some results were counterintuitive, including inverse associations between cumulative incidence and days to closure of non-essential business and restrictions on gatherings. This finding is likely due to reverse causality, where locations with slower growth rates initially chose not to implement measures, and later implemented measures when they absolutely needed to respond to increasing rates of infection. Effects of social distancing measures seemed to vary by population density in cities. Our results suggest that the effect of social distancing measures may differ between states and cities and between locations with different population densities. States and cities need individual approaches to containment of an epidemic, with an awareness of their own structure in terms of crowding and socio-economic variables. In an effort to reduce infection rates, cities may want to implement social distancing in advance of state mandates.", "qid": 10, "docid": "in3pyyue", "rank": 12, "score": 0.8058815598487854}, {"content": "Title: Adoption and impact of non-pharmaceutical interventions for COVID-19 Content: Background: Several non-pharmaceutical interventions (NPIs) have been implemented across the world to control the coronavirus disease (COVID-19) pandemic. Social distancing (SD) interventions applied so far have included school closures, remote working and quarantine. These measures have been shown to have large impacts on pandemic influenza transmission. However, there has been comparatively little examination of such measures for COVID-19. Methods: We examined the existing literature, and collated data, on implementation of NPIs to examine their effects on the COVID-19 pandemic so far. Data on NPIs were collected from official government websites as well as from media sources. Results: Measures such as travel restrictions have been implemented in multiple countries and appears to have slowed the geographic spread of COVID-19 and reduced initial case numbers. We find that, due to the relatively sparse information on the differences with and without interventions, it is difficult to quantitatively assess the efficacy of many interventions. Similarly, whilst the comparison to other pandemic diseases such as influenza can be helpful, there are key differences that could affect the efficacy of similar NPIs. Conclusions: The timely implementation of control measures is key to their success and must strike a balance between early enough application to reduce the peak of the epidemic and ensuring that they can be feasibly maintained for an appropriate duration. Such measures can have large societal impacts and they need to be appropriately justified to the population. As the pandemic of COVID-19 progresses, quantifying the impact of interventions will be a vital consideration for the appropriate use of mitigation strategies.", "qid": 10, "docid": "hipujblu", "rank": 13, "score": 0.8054240942001343}, {"content": "Title: No Place Like Home: Cross-National Data Analysis of the Efficacy of Social Distancing During the COVID-19 Pandemic Content: BACKGROUND: In the absence of a cure in the time of a pandemic, social distancing measures seem to be the most effective intervention to slow the spread of disease. Various simulation-based studies have been conducted to investigate the effectiveness of these measures. While those studies unanimously confirm the mitigating effect of social distancing on disease spread, the reported effectiveness varies from 10% to more than 90% reduction in the number of infections. This level of uncertainty is mostly due to the complex dynamics of epidemics and their time-variant parameters. However, real transactional data can reduce uncertainty and provide a less noisy picture of the effectiveness of social distancing. OBJECTIVE: The aim of this paper was to integrate multiple transactional data sets (GPS mobility data from Google and Apple as well as disease statistics from the European Centre for Disease Prevention and Control) to study the role of social distancing policies in 26 countries and analyze the transmission rate of the coronavirus disease (COVID-19) pandemic over the course of 5 weeks. METHODS: Relying on the susceptible-infected-recovered (SIR) model and official COVID-19 reports, we first calculated the weekly transmission rate (\u00df) of COVID-19 in 26 countries for 5 consecutive weeks. Then, we integrated these data with the Google and Apple mobility data sets for the same time frame and used a machine learning approach to investigate the relationship between the mobility factors and \u00df values. RESULTS: Gradient boosted trees regression analysis showed that changes in mobility patterns resulting from social distancing policies explain approximately 47% of the variation in the disease transmission rates. CONCLUSIONS: Consistent with simulation-based studies, real cross-national transactional data confirms the effectiveness of social distancing interventions in slowing the spread of COVID-19. In addition to providing less noisy and more generalizable support for the idea of social distancing, we provide specific insights for public health policy makers regarding locations that should be given higher priority for enforcing social distancing measures.", "qid": 10, "docid": "qekxxsfy", "rank": 14, "score": 0.8028827905654907}, {"content": "Title: Diminishing Marginal Benefit of Social Distancing in Balancing COVID-19 Medical Demand-to-Supply Content: Social distancing has been adopted as a non-pharmaceutical intervention to prevent the COVID-19 pandemic from overwhelming the medical resources across the United States (US). The catastrophic socio-economic impacts of this intervention could outweigh its benefits if the timing and duration of implementation are left uncontrolled and ill-strategized. Here we investigate the dynamics of social distancing on age-stratified US population and benchmark its effectiveness in reducing the burden on hospital and ICU beds. Our findings highlight the diminishing marginal benefit of social distancing, characterized by a linear decrease in medical demands against an exponentially increasing social distancing duration. We determine an optimal intermittent social-to-no-distancing ratio of 5:1 corresponding to ~80% reduction in healthcare demands; beyond this ratio, benefit of social distancing diminishes to a negligible level. COVID-19 Medical Forecast: https://eece.wustl.edu/chakrabarty-group/covid/", "qid": 10, "docid": "rzh7ja6a", "rank": 15, "score": 0.8028208017349243}, {"content": "Title: Augmenting contact matrices with time-use data for fine-grained intervention modelling of disease dynamics: A modelling analysis Content: Background: Social distancing is an important public health intervention to reduce or interrupt the sustained community transmission of emerging infectious pathogens, such as SARS-CoV-2 during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to explore the impact on the epidemic curve of fewer contacts when individuals reduce the time they spend on selected daily activities. Methods: We combined the large-scale empirical data of a social contact survey and a time-use survey to estimate contact matrices by age group (0-15, 16-24, 25-44, 45-64, 65+) and daily activity (work, schooling, transportation, and four leisure activities: social visits, bar/cafe/restaurant visits, park visits, and non-essential shopping). We assumed that reductions in time are proportional to reductions in contacts. The derived matrices were then applied in an age-structured dynamic-transmission model of COVID-19 to explore the effects. Findings: The relative reductions in the derived contact matrices were highest when closing schools (in ages 0-14 years), workplaces (15-64 years), and stopping social visits (65+ years). For COVID-19, the closure of workplaces, schools, and stopping social visits had the largest impact on reducing the epidemic curve and delaying its peak, while the predicted impact of fewer contacts in parks, bars/cafes/restaurants, and non-essential shopping were minimal. Interpretation: We successfully augmented contact matrices with time-use data to predict the highest impact of social distancing measures from reduced contacts when spending less time at work, school, and on social visits. Although the predicted impact from other leisure activities with potential for close physical contact were minimal, changes in mixing patterns and time-use immediately after re-allowing social activities may pose increased short-term transmission risks, especially in potentially crowded environments indoors.", "qid": 10, "docid": "zkjiixuq", "rank": 16, "score": 0.8024471998214722}, {"content": "Title: Potential roles of social distancing in mitigating the spread of coronavirus disease 2019 (COVID-19) in South Korea Content: On January 20, 2020, the first COVID-19 case was confirmed in South Korea. After a rapid outbreak, the number of incident cases has been consistently decreasing since early March; this decrease has been widely attributed to its intensive testing. We report here on the likely role of social distancing in reducing transmission in South Korea. Our analysis suggests that transmission may still be persisting in some regions.", "qid": 10, "docid": "7t3ci8tl", "rank": 17, "score": 0.8022329807281494}, {"content": "Title: The differential impact of physical distancing strategies on social contacts relevant for the spread of COVID-19 Content: Physical distancing measures are intended to mitigate the spread of COVID-19. However, the impact these measures have on social contact and disease transmission patterns remains unclear. We ran the first comparative contact survey (N=53,708) across eight countries (Belgium, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States) for the period March 13 - April 13, 2020. Our results show that social contact numbers mainly decreased after governments issued physical distancing guidelines rather than after announcing national lockdown measures. Compared to pre-COVID levels, social contact numbers decreased by 48% - 85% across countries. Except in Italy, these reductions were smaller than those observed in Wuhan (China). However, they sufficed to bring the R0 below one in almost every context considered. Finally, in all countries studied, the numbers of contacts decreased more rapidly among older people than among younger people, indicating higher levels of protection for groups at greater risk.", "qid": 10, "docid": "u9fmokcf", "rank": 18, "score": 0.7986199855804443}, {"content": "Title: No Place Like Home: A Cross-National Assessment of the Efficacy of Social Distancing during the COVID-19 Pandemic. Content: BACKGROUND In the absence of a cure in the time of pandemics, social distancing measures seem to be the most effective intervention to slow down the spread of disease. Various simulation-based studies have been conducted in the past to investigate the effectiveness of such measures. While those studies unanimously confirm the mitigating effect of social distancing on the disease spread, the reported effectiveness varies from 10% to more than 90% reduction in the number of infections. This level of uncertainty is mostly due to the complex dynamics of epidemics and their time-variant parameters. A real transactional data, however, can reduce the uncertainty and provide a less noisy picture of social distancing effectiveness. OBJECTIVE In this paper, we integrate multiple transactional data sets (GPS mobility data from Google and Apple as well as disease statistics data from ECDC) to study the role of social distancing policies in 26 countries wherein the transmission rate of the COVID-19 pandemic is analyzed over the course of five weeks. METHODS Relying on the SIR model and official COVID-19 reports, we first calculated the weekly transmission rate (\u03b2) of the coronavirus disease in 26 countries for five consecutive weeks. Then we integrated that with the Google's and Apple's mobility data sets for the same time frame and used a machine learning approach to investigate the relationship between mobility factors and \u03b2 values. RESULTS Gradient Boosted Trees (GBT) regression analysis showed that changes in mobility patterns, resulted from social distancing policies, explain around 47% of the variation in the disease transmission rate. CONCLUSIONS Consistent with simulation-based studies, real cross-national transactional data confirms the effectiveness of social distancing interventions in slowing down the spread of the disease. Apart from providing less noisy and more generalizable support for the whole social distancing idea, we provide specific insights for public health policy-makers as to what locations should be given a higher priority for enforcing social distancing measures. CLINICALTRIAL", "qid": 10, "docid": "3nanf73b", "rank": 19, "score": 0.796649158000946}, {"content": "Title: Impacts of State-Level Policies on Social Distancing in the United States Using Aggregated Mobility Data during the COVID-19 Pandemic Content: Social distancing has emerged as the primary mitigation strategy to combat the COVID-19 pandemic in the United States. However, large-scale evaluation of the public's response to social distancing campaigns has been lacking. We used anonymized and aggregated mobility data from Google Location History users to estimate the impact of social distancing recommendations on bulk mobility among users who have opted into this service. We found that state-of-emergency declarations resulted in approximately a 10% reduction in time spent away from places of residence. Implementation of one or more social distancing policies resulted in an additional 25% reduction in mobility the following week. Subsequent shelter-in-place mandates provided an additional 29% reduction. Our findings provide evidence that state-wide mandates are effective in promoting social distancing within this study group.", "qid": 10, "docid": "f6rx4h3r", "rank": 20, "score": 0.7956744432449341}, {"content": "Title: The Benefits and Costs of Using Social Distancing to Flatten the Curve for COVID-19 Content: We examine the net benefits of social distancing to slow the spread of COVID-19 in USA. Social distancing saves lives but imposes large costs on society due to reduced economic activity. We use epidemiological and economic forecasting to perform a rapid benefit\u2013cost analysis of controlling the COVID-19 outbreak. Assuming that social distancing measures can substantially reduce contacts among individuals, we find net benefits of about $5.2 trillion in our benchmark case. We examine the magnitude of the critical parameters that might imply negative net benefits, including the value of statistical life and the discount rate. A key unknown factor is the speed of economic recovery with and without social distancing measures in place. A series of robustness checks also highlight the key role of the value of mortality risk reductions and discounting in the analysis and point to a need for effective economic stimulus when the outbreak has passed.", "qid": 10, "docid": "vfnpeuzr", "rank": 21, "score": 0.7933120131492615}, {"content": "Title: Modelling the potential impact of social distancing on the COVID-19 epidemic in South Africa Content: The novel coronavirus (COVID-19) pandemic continues to be a global health problem whose impact has been significantly felt in South Africa. Social distancing has been touted as the best form of response in managing a rapid increase in the number of infected cases. In this paper, we present a deterministic model to model the impact of social distancing on the transmission dynamics of COVID-19 in South Africa. The model is fitted to the currently available data on the cumulative number of infected cases and a scenario analysis on different levels of social distancing are presented. The results show a continued rise in the number of cases in the lock down period with the current levels of social distancing albeit at a lower rate. The model shows that the number of cases will rise to above 4000 cases by the end of the lockdown. The model also looks at the impact of relaxing the social distancing measures after the initial announcement of the lock down measures. A relaxation of the social distancing by 2% can result in a 23% rise in the number of cumulative cases while on the other hand increasing the levels of social distancing by 2% would reduce the number of cumulative cases by about 18%. These results have implications on the management and policy direction in the early phases of the epidemic.", "qid": 10, "docid": "q5xc4m3j", "rank": 22, "score": 0.7928694486618042}, {"content": "Title: Social network-based distancing strategies to flatten the COVID-19 curve in a post-lockdown world Content: Social distancing and isolation have been widely introduced to counter the COVID-19 pandemic. Adverse social, psychological and economic consequences of a complete or near-complete lockdown demand the development of more moderate contact-reduction policies. Adopting a social network approach, we evaluate the effectiveness of three distancing strategies designed to keep the curve flat and aid compliance in a post-lockdown world. These are: limiting interaction to a few repeated contacts akin to forming social bubbles; seeking similarity across contacts; and strengthening communities via triadic strategies. We simulate stochastic infection curves incorporating core elements from infection models, ideal-type social network models and statistical relational event models. We demonstrate that a strategic social network-based reduction of contact strongly enhances the effectiveness of social distancing measures while keeping risks lower. We provide scientific evidence for effective social distancing that can be applied in public health messaging and that can mitigate negative consequences of social isolation.", "qid": 10, "docid": "c5lankxq", "rank": 23, "score": 0.7927538156509399}, {"content": "Title: Social network-based distancing strategies to flatten the COVID-19 curve in a post-lockdown world. Content: Social distancing and isolation have been widely introduced to counter the COVID-19 pandemic. Adverse social, psychological and economic consequences of a complete or near-complete lockdown demand the development of more moderate contact-reduction policies. Adopting a social network approach, we evaluate the effectiveness of three distancing strategies designed to keep the curve flat and aid compliance in a post-lockdown world. These are: limiting interaction to a few repeated contacts akin to forming social bubbles; seeking similarity across contacts; and strengthening communities via triadic strategies. We simulate stochastic infection curves incorporating core elements from infection models, ideal-type social network models and statistical relational event models. We demonstrate that a strategic social network-based reduction of contact strongly enhances the effectiveness of social distancing measures while keeping risks lower. We provide scientific evidence for effective social distancing that can be applied in public health messaging and that can mitigate negative consequences of social isolation.", "qid": 10, "docid": "qpzg8lam", "rank": 24, "score": 0.7927538156509399}, {"content": "Title: Mobile phone location data reveal the effect and geographic variation of social distancing on the spread of the COVID-19 epidemic Content: The emergence of SARS-CoV-2 and the coronavirus infectious disease (COVID-19) has become a pandemic. Social (physical) distancing is a key non-pharmacologic control measure to reduce the transmission rate of SARS-COV-2, but high-level adherence is needed. Using daily travel distance and stay-at-home time derived from large-scale anonymous mobile phone location data provided by Descartes Labs and SafeGraph, we quantify the degree to which social distancing mandates have been followed in the U.S. and its effect on growth of COVID-19 cases. The correlation between the COVID-19 growth rate and travel distance decay rate and dwell time at home change rate was -0.586 (95% CI: -0.742 ~ -0.370) and 0.526 (95% CI: 0.293 ~ 0.700), respectively. Increases in state-specific doubling time of total cases ranged from 1.04 ~ 6.86 days to 3.66 ~ 30.29 days after social distancing orders were put in place, consistent with mechanistic epidemic prediction models. Social distancing mandates reduce the spread of COVID-19 when they are followed.", "qid": 10, "docid": "esa5700v", "rank": 25, "score": 0.7924398183822632}, {"content": "Title: Impact of Timing of and Adherence to Social Distancing Measures on COVID-19 Burden in the US: A Simulation Modeling Approach Content: BACKGROUND: Across the U.S., various social distancing measures were implemented to control COVID-19 pandemic. However, there is uncertainty in the effectiveness of such measures for specific regions with varying population demographics and different levels of adherence to social distancing. The objective of this paper is to determine the impact of social distancing measures in unique regions. METHODS: We developed COVid-19 Agent-based simulation Model (COVAM), an agent-based simulation model (ABM) that represents the social network and interactions among the people in a region considering population demographics, limited testing availability, imported infections from outside of the region, asymptomatic disease transmission, and adherence to social distancing measures. We adopted COVAM to represent COVID-19-associated events in Dane County, Wisconsin, Milwaukee metropolitan area, and New York City (NYC). We used COVAM to evaluate the impact of three different aspects of social distancing: 1) Adherence to social distancing measures; 2) timing of implementing social distancing; and 3) timing of easing social distancing. RESULTS: We found that the timing of social distancing and adherence level had a major effect on COVID-19 occurrence. For example, in NYC, implementing social distancing measures on March 5, 2020 instead of March 12, 2020 would have reduced the total number of confirmed cases from 191,984 to 43,968 as of May 30, whereas a 1-week delay in implementing such measures could have increased the number of confirmed cases to 1,299,420. Easing social distancing measures on June 1, 2020 instead of June 15, 2020 in NYC would increase the total number of confirmed cases from 275,587 to 379,858 as of July 31. CONCLUSION: The timing of implementing social distancing measures, adherence to the measures, and timing of their easing have major effects on the number of COVID-19 cases. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases Institute", "qid": 10, "docid": "aiah8kkn", "rank": 26, "score": 0.7919222712516785}, {"content": "Title: Flattening the curve and the effect of atypical events on mitigation measures in Mexico: a modeling perspective Content: On 23 and 30 March 2020 the Mexican Federal government implemented social distancing measures to mitigate the COVID-19 epidemic. We use a mathematical model to explore atypical transmission events within the confinement period, triggered by the timing and strength of short time perturbations of social distancing. We show that social distancing measures were successful in achieving a significant reduction of the effective contact rate in the early weeks of the intervention. However, \"flattening the curve\" had an undesirable effect, since the epidemic peak was delayed too far, almost to the government preset day for lifting restrictions (01 June 2020). If the peak indeed occurs in late May or early June, then the events of children's day and mother's day may either generate a later peak (worst case scenario), a long plateau with relatively constant but high incidence (middle case scenario) or the same peak date as in the original baseline epidemic curve, but with a post-peak interval of slower decay.", "qid": 10, "docid": "9azl5nl8", "rank": 27, "score": 0.791191816329956}, {"content": "Title: Quantifying what could have been \u2013 the impact of the Australian and New Zealand governments\u2019 response to COVID-19 Content: The Australian and New Zealand governments both initiated strict social distancing measures in response to the COVID-19 pandemic in late March. It remains difficult to quantify the impact this had in reducing the spread of the virus. Bayesian structural time series model provide a model to quantify the scenario in which these government-level interventions were not placed. Our models predict these strict social distancing measures caused a 79% and 61% reduction in the daily cases of COVID-19 across Australia and New Zealand respectively. This provides both evidence and impetus for governments considering similar measures in response to COVID-19 and other pandemics.", "qid": 10, "docid": "hzpbujye", "rank": 28, "score": 0.7909379005432129}, {"content": "Title: The effect of social distance measures on COVID-19 epidemics in Europe: an interrupted time series analysis Content: Following the introduction of unprecedented \u201cstay-at-home\u201d national policies, the COVID-19 pandemic recently started declining in Europe. Our research aims were to characterize the changepoint in the flow of the COVID-19 epidemic in each European country and to evaluate the association of the level of social distancing with the observed decline in the national epidemics. Interrupted time series analyses were conducted in 28 European countries. Social distance index was calculated based on Google Community Mobility Reports. Changepoints were estimated by threshold regression, national findings were analyzed by Poisson regression, and the effect of social distancing in mixed effects Poisson regression model. Our findings identified the most probable changepoints in 28 European countries. Before changepoint, incidence of new COVID-19 cases grew by 24% per day on average. From the changepoint, this growth rate was reduced to 0.9%, 0.3% increase, and to 0.7% and 1.7% decrease by increasing social distancing quartiles. The beneficial effect of higher social distance quartiles (i.e., turning the increase into decline) was statistically significant for the fourth quartile. Notably, many countries in lower quartiles also achieved a flat epidemic curve. In these countries, other plausible COVID-19 containment measures could contribute to controlling the first wave of the disease. The association of social distance quartiles with viral spread could also be hindered by local bottlenecks in infection control. Our results allow for moderate optimism related to the gradual lifting of social distance measures in the general population, and call for specific attention to the protection of focal micro-societies enriching high-risk elderly subjects, including nursing homes and chronic care facilities.", "qid": 10, "docid": "1abupl36", "rank": 29, "score": 0.7907949686050415}, {"content": "Title: How long does a lockdown need to be? Content: Social distancing, often in the form of lockdown, has been adopted by many countries as a way to contrast the spreading of COVID-19. We discuss the temporal aspects of social distancing in contrasting an epidemic diffusion. We argue that a strategy based uniquely on social distancing requires to maintain the relative measures for a very long time, while a more articulate strategy, which also uses early detection and prompt isolation, can be both more efficient on reducing the epidemic peak and allow to relax the social distancing measures after a much shorter time. We consider in more detail the situation in Italy, simulating the effect of different strategies through a recently introduced SIR-type epidemiological model. The short answer to the question in the title is:\"it depends on what else you do\".", "qid": 10, "docid": "gilpb3oy", "rank": 30, "score": 0.790392279624939}, {"content": "Title: The science of social distancing and total lock down: Does it work? whom does it benefit? Content: COVID-19 is spiralling like wild fire and has caused a global mayhem. Many lives have already been lost, and the global economy is at stake. In the absence of vaccine, social distancing and total lock down is the current mainstay in efforts to mitigate and flatten the epidemic curves. Several countries across the globe are currently implementing social distancing and total lock downs. However, what is social distancing and lock down? Does it work? Whom does it benefit? We expound on these questions and conclude that social distancing and lock down benefit the local and international community alike. Moreover, we hypothesis that evacuations may facilitate international spread of a highly contagious disease of pandemic potential.", "qid": 10, "docid": "45k6tp0b", "rank": 31, "score": 0.7899638414382935}, {"content": "Title: Quantifying what could have been - The impact of the Australian and New Zealand governments' response to COVID-19 Content: BACKGROUND: The Australian and New Zealand governments both initiated strict social distancing measures in response to the COVID-19 pandemic in late March. It remains difficult to quantify the impact this had in reducing the spread of the virus. METHODS: Bayesian structural time series model provide a model to quantify the scenario in which these government-level interventions were not placed. Our models predict these strict social distancing measures caused a 79% and 61% reduction in the daily cases of COVID-19 across Australia and New Zealand respectively. CONCLUSION: This provides both evidence and impetus for governments considering similar measures in response to COVID-19 and other pandemics.", "qid": 10, "docid": "xjr582j3", "rank": 32, "score": 0.7897694110870361}, {"content": "Title: Effects of the COVID-19 Pandemic on Population Mobility under Mild Policies: Causal Evidence from Sweden Content: Sweden has adopted far less restrictive social distancing policies than most countries following the COVID-19 pandemic. This paper uses data on all mobile phone users, from one major Swedish mobile phone network, to examine the impact of the Coronavirus outbreak under the Swedish mild recommendations and restrictions regime on individual mobility and if changes in geographical mobility vary over different socio-economic strata. Having access to data for January-March in both 2019 and 2020 enables the estimation of causal effects of the COVID-19 outbreak by adopting a Difference-in-Differences research design. The paper reaches four main conclusions: (i) The daytime population in residential areas increased significantly (64 percent average increase); (ii) The daytime presence in industrial and commercial areas decreased significantly (33 percent average decrease); (iii) The distance individuals move from their homes during a day was substantially reduced (38 percent decrease in the maximum distance moved and 36 percent increase in share of individuals who move less than one kilometer from home); (iv) Similar reductions in mobility were found for residents in areas with different socioeconomic and demographic characteristics. These results show that mild government policies can compel people to adopt social distancing behavior.", "qid": 10, "docid": "lb3j1buz", "rank": 33, "score": 0.7897207736968994}, {"content": "Title: Social Distancing is Effective at Mitigating COVID-19 Transmission in the United States Content: COVID-19 is present in every state and over 90 percent of all counties in the United States. Decentralized government efforts to reduce spread, combined with the complex dynamics of human mobility and the variable intensity of local outbreaks makes assessing the effect of large-scale social distancing on COVID-19 transmission in the U.S. is a challenge. We generate a novel metric to represent social distancing behavior derived from mobile phone data, and examine its relationship with COVID-19 case reports at the county level. Our analysis reveals that social distancing is strongly correlated with decreased COVID-19 case growth rates for the 25 most affected counties in the United States, with a lag period consistent with the incubation time of SARS-CoV-2. We also demonstrate evidence that social distancing was already under way in many U.S. counties before county and state-level policies were implemented. This study strongly supports social distancing as an effective way to mitigate COVID-19 transmission in the United States.", "qid": 10, "docid": "noyx53ej", "rank": 34, "score": 0.789645791053772}, {"content": "Title: The effect of social distance measures on COVID-19 epidemics in Europe: an interrupted time series analysis Content: Following the introduction of unprecedented \"stay-at-home\" national policies, the COVID-19 pandemic recently started declining in Europe. Our research aims were to characterize the changepoint in the flow of the COVID-19 epidemic in each European country and to evaluate the association of the level of social distancing with the observed decline in the national epidemics. Interrupted time series analyses were conducted in 28 European countries. Social distance index was calculated based on Google Community Mobility Reports. Changepoints were estimated by threshold regression, national findings were analyzed by Poisson regression, and the effect of social distancing in mixed effects Poisson regression model. Our findings identified the most probable changepoints in 28 European countries. Before changepoint, incidence of new COVID-19 cases grew by 24% per day on average. From the changepoint, this growth rate was reduced to 0.9%, 0.3% increase, and to 0.7% and 1.7% decrease by increasing social distancing quartiles. The beneficial effect of higher social distance quartiles (i.e., turning the increase into decline) was statistically significant for the fourth quartile. Notably, many countries in lower quartiles also achieved a flat epidemic curve. In these countries, other plausible COVID-19 containment measures could contribute to controlling the first wave of the disease. The association of social distance quartiles with viral spread could also be hindered by local bottlenecks in infection control. Our results allow for moderate optimism related to the gradual lifting of social distance measures in the general population, and call for specific attention to the protection of focal micro-societies enriching high-risk elderly subjects, including nursing homes and chronic care facilities.", "qid": 10, "docid": "4z3r8hoe", "rank": 35, "score": 0.7893128395080566}, {"content": "Title: Social Distancing Causally Impacts the Spread of SARS-CoV-2: A U.S. Nationwide Event Study Content: Background: To date, no study has examined the effectiveness of social distancing, while controlling for social mobility and social distancing restrictions in the United States. We utilize the quasi-experimental setting created by the nationwide protests precipitated by George Floyd's tragic death on May 25, 2020, to assess the causal impact of social distancing on the spread of SARS-CoV-2. Methods: Our sample period spans from January 22, 2020, to June 20, 2020, and consists of 474,422 county-days representing 3,142 counties from all 50 states and the District of Columbia. To assess the change in COVID-19 case counts following the protests, we employ a differences in differences estimation strategy in a multivariate setting, in which we control for social distancing restrictions and social mobility across counties. We also control for covariates that may influence COVID-19 transmission, and implement placebo tests using a Monte Carlo simulation. Findings: We document a country wide increase of over 3.06 cases per day, per 100,000 population, following the onset of the protests (95%CI: 2.47-3.65), and a further increase of 1.73 cases per day, per 100,000 population, in the counties in which the protests took place (95%CI: 0.59- 2.87). Relative to the week preceding the onset of the protests, this represents a 61.2% country wide increase in COVID-19 cases, and a further 34.6% increase in the protest counties. Interpretation: Our study documents a significant increase in COVID-19 case counts in counties that experienced a protest, and we conclude that social distancing practices causally impact the spread of SARS-CoV-2. The observed effect cannot be explained by changes in social distancing restrictions and social mobility, and placebo tests rule out the possibility that this finding is attributable to chance.", "qid": 10, "docid": "s74jgknw", "rank": 36, "score": 0.7879211902618408}, {"content": "Title: The effect of COVID-19 and subsequent social distancing on travel behavior Content: Abstract The spread of the COVID-19 virus has resulted in unprecedented measures restricting travel and activity participation in many countries. Social distancing, i.e., reducing interactions between individuals in order to slow down the spread of the virus, has become the new norm. In this viewpoint I will discuss the potential implications of social distancing on daily travel patterns. Avoiding social contact might completely change the number and types of out-of-home activities people perform, and how people reach these activities. It can be expected that the demand for travel will reduce and that people will travel less by public transport. Social distancing might negatively affect subjective well-being and health status, as it might result in social isolation and limited physical activity. As a result, walking and cycling, recreationally or utilitarian, can be important ways to maintain satisfactory levels of health and well-being. Policymakers and planners should consequently try to encourage active travel, while public transport operators should focus on creating ways to safely use public transport.", "qid": 10, "docid": "ocwetgv6", "rank": 37, "score": 0.7876284718513489}, {"content": "Title: Effectiveness and Compliance to Social Distancing During COVID-19 Content: In the absence of pharmaceutical interventions to curb the spread of COVID-19, countries relied on a number of nonpharmaceutical interventions to fight the first wave of the pandemic. The most prevalent one has been stay-at-home orders, whose the goal is to limit the physical contact between people, which consequently will reduce the number of secondary infections generated. In this work, we use a detailed set of mobility data to evaluate the impact that these interventions had on alleviating the spread of the virus in the US as measured through the COVID-19-related deaths. To establish this impact, we use the notion of Granger causality between two time-series. We show that there is a unidirectional Granger causality, from the median percentage of time spent daily at home to the daily number of COVID-19-related deaths with a lag of 2 weeks. We further analyze the mobility patterns at the census block level to identify which parts of the population might encounter difficulties in adhering and complying with social distancing measures. This information is important, since it can consequently drive interventions that aim at helping these parts of the population.", "qid": 10, "docid": "ibrrr546", "rank": 38, "score": 0.7876169681549072}, {"content": "Title: Social distancing: A non-pharmacological intervention for COVID-19 Content: Social distancing is one of the non-pharmacological measures to contain the infection of COVID-19. At this point in time, no vaccine is available to prevent the infection, no effective drugs are available to prevent and treat the disease, and none of the communities have acquired herd immunity. Various models have shown positive impact of social distancing, provided its implementation on vast majority of the population over a long period of time. Its effect is manifold. Besides flattening the curve, it impacts the political, fiscal, social, economic aspects of the society, along with socially vulnerable and economically underprivileged population. It becomes obsolete after the population develops herd immunity subsequent to widespread infection in the community, or after effective mass immunisation or specific drugs for its control, cure and prevention are available widely.", "qid": 10, "docid": "omygp8bu", "rank": 39, "score": 0.7873896360397339}, {"content": "Title: Social distancing: A non-pharmacological intervention for COVID-19. Content: Social distancing is one of the non-pharmacological measures to contain the infection of COVID-19. At this point in time, no vaccine is available to prevent the infection, no effective drugs are available to prevent and treat the disease, and none of the communities have acquired herd immunity. Various models have shown positive impact of social distancing, provided its implementation on vast majority of the population over a long period of time. Its effect is manifold. Besides flattening the curve, it impacts the political, fiscal, social, economic aspects of the society, along with socially vulnerable and economically underprivileged population. It becomes obsolete after the population develops herd immunity subsequent to widespread infection in the community, or after effective mass immunisation or specific drugs for its control, cure and prevention are available widely.", "qid": 10, "docid": "3cke9x69", "rank": 40, "score": 0.7873896360397339}, {"content": "Title: A novel COVID-19 epidemiological model with explicit susceptible and asymptomatic isolation compartments reveals unexpected consequences of timing social distancing Content: Motivated by the current COVID-19 epidemic, this work introduces an epidemiological model in which separate compartments are used for susceptible and asymptomatic \"socially distant\" populations. Distancing directives are represented by rates of flow into these compartments, as well as by a reduction in contacts that lessens disease transmission. The dynamical behavior of this system is analyzed, under various different rate control strategies, and the sensitivity of the basic reproduction number to various parameters is studied. One of the striking features of this model is the existence of a critical implementation delay in issuing separation mandates: while a delay of about four weeks does not have an appreciable effect, issuing mandates after this critical time results in a far greater incidence of infection. In other words, there is a nontrivial but tight \"window of opportunity\" for commencing social distancing. Different relaxation strategies are also simulated, with surprising results. Periodic relaxation policies suggest a schedule which may significantly inhibit peak infective load, but that this schedule is very sensitive to parameter values and the schedule's frequency. Further, we considered the impact of steadily reducing social distancing measures over time. We find that a too-sudden reopening of society may negate the progress achieved under initial distancing guidelines, if not carefully designed.", "qid": 10, "docid": "x9d7g5kb", "rank": 41, "score": 0.7861347794532776}, {"content": "Title: Evaluating the Effectiveness of Social Distancing Interventions to Delay or Flatten the Epidemic Curve of Coronavirus Disease Content: By April 2, 2020, >1 million persons worldwide were infected with severe acute respiratory syndrome coronavirus 2. We used a mathematical model to investigate the effectiveness of social distancing interventions in a mid-sized city. Interventions reduced contacts of adults >60 years of age, adults 20-59 years of age, and children <19 years of age for 6 weeks. Our results suggest interventions started earlier in the epidemic delay the epidemic curve and interventions started later flatten the epidemic curve. We noted that, while social distancing interventions were in place, 20% of new cases and most hospitalizations and deaths were averted, even with modest reductions in contact among adults. However, when interventions ended, the epidemic rebounded. Our models suggest that social distancing can provide crucial time to increase healthcare capacity but must occur in conjunction with testing and contact tracing of all suspected cases to mitigate virus transmission.", "qid": 10, "docid": "3mk5a5u6", "rank": 42, "score": 0.7860175967216492}, {"content": "Title: Evaluating the Effectiveness of Social Distancing Interventions to Delay or Flatten the Epidemic Curve of Coronavirus Disease. Content: By April 2, 2020, >1 million persons worldwide were infected with severe acute respiratory syndrome coronavirus 2. We used a mathematical model to investigate the effectiveness of social distancing interventions in a mid-sized city. Interventions reduced contacts of adults >60 years of age, adults 20-59 years of age, and children <19 years of age for 6 weeks. Our results suggest interventions started earlier in the epidemic delay the epidemic curve and interventions started later flatten the epidemic curve. We noted that, while social distancing interventions were in place, 20% of new cases and most hospitalizations and deaths were averted, even with modest reductions in contact among adults. However, when interventions ended, the epidemic rebounded. Our models suggest that social distancing can provide crucial time to increase healthcare capacity but must occur in conjunction with testing and contact tracing of all suspected cases to mitigate virus transmission.", "qid": 10, "docid": "x9zg7ulr", "rank": 43, "score": 0.7860175967216492}, {"content": "Title: Social network-based distancing strategies to flatten the COVID 19 curve in a post-lockdown world Content: Social distancing and isolation have been introduced widely to counter the COVID-19 pandemic. However, more moderate contact reduction policies become desirable owing to adverse social, psychological, and economic consequences of a complete or near-complete lockdown. Adopting a social network approach, we evaluate the effectiveness of three targeted distancing strategies designed to 'keep the curve flat' and aid compliance in a post-lockdown world. These are limiting interaction to a few repeated contacts, seeking similarity across contacts, and strengthening communities via triadic strategies. We simulate stochastic infection curves that incorporate core elements from infection models, ideal-type social network models, and statistical relational event models. We demonstrate that strategic reduction of contact can strongly increase the efficiency of social distancing measures, introducing the possibility of allowing some social contact while keeping risks low. This approach provides nuanced insights to policy makers for effective social distancing that can mitigate negative consequences of social isolation.", "qid": 10, "docid": "o8k66pes", "rank": 44, "score": 0.7844191789627075}, {"content": "Title: Voluntary Cyclical Distancing: A potential alternative to constant level mandatory social distancing, relying on an 'infection weather report' Content: COVID-19 has significantly changed our daily lives. Stay-at-home orders and forced closings of all non-essential businesses has had a significant impact on our economy. While it is important to ensure that the healthcare system is not overwhelmed, there are many questions that remain about the efficacy of extreme social distancing, and whether there are alternatives to mandatory lockdowns. This paper analyzes the utility of various levels of social distancing, and suggests an alternative approach using voluntary distancing informed by an infectious load index or 'infection weather report.'", "qid": 10, "docid": "xcfk4efo", "rank": 45, "score": 0.7843059301376343}, {"content": "Title: Strong Social Distancing Measures In The United States Reduced The COVID-19 Growth Rate Content: State and local governments imposed social distancing measures in March and April 2020 to contain the spread of the novel coronavirus disease (COVID-19). These measures included bans on large social gatherings; school closures; closures of entertainment venues, gyms, bars, and restaurant dining areas; and shelter-in-place orders. We evaluated the impact of these measures on the growth rate of confirmed COVID-19 cases across US counties between March 1, 2020, and April 27, 2020. An event study design allowed each policy's impact on COVID-19 case growth to evolve over time. Adoption of government-imposed social distancing measures reduced the daily growth rate of confirmed COVID-19 cases by 5.4 percentage points after one to five days, 6.8 percentage points after six to ten days, 8.2 percentage points after eleven to fifteen days, and 9.1 percentage points after sixteen to twenty days. Holding the amount of voluntary social distancing constant, these results imply that there would have been ten times greater spread of COVID-19 by April 27 without shelter-in-place orders (ten million cases) and more than thirty-five times greater spread without any of the four measures (thirty-five million cases). Our article illustrates the potential danger of exponential spread in the absence of interventions, providing information relevant to strategies for restarting economic activity.", "qid": 10, "docid": "h62xj47p", "rank": 46, "score": 0.7839601039886475}, {"content": "Title: Isolation and contact tracing can tip the scale to containment of COVID-19 in populations with social distancing Content: Background: Novel coronavirus (SARS-CoV-2) has extended its range of transmission in all parts of the world, with substantial variation in rates of transmission and severity of associated disease. Many countries have implemented social distancing as a measure to control further spread. Methods: We evaluate whether and under which conditions containment or slowing down COVID-19 epidemics are possible by isolation and contact tracing in settings with various levels of social distancing. We use a stochastic transmission model in which every person generates novel infections according to a probability distribution that is affected by the incubation period distribution (time from infection to symptoms), distribution of the latent period (time from infection to onset of infectiousness), and overall transmissibility. The model distinguishes between close contacts (e.g., within a household) and other contacts in the population. Social distancing affects the number of contacts outside but not within the household. Findings: The proportion of asymptomatic or unascertained cases has a strong impact on the controllability of the disease. If the proportion of asymptomatic infections is larger than 30%, contact tracing and isolation cannot achieve containment for an R0 of 2.5. Achieving containment by social distancing requires a reduction of numbers of non-household contacts by around 90%. Depending on the realized level of contact reduction, tracing and isolation of only household contacts, or of household and non-household contacts are necessary to reduce the effective reproduction number to below 1. A combination of social distancing with isolation and contact tracing leads to synergistic effects that increase the prospect of containment. Interpretation: Isolation and contact tracing can be an effective means to slow down epidemics, but only if the majority of cases are ascertained. In a situation with social distancing, contact tracing can act synergistically and tip the scale towards containment, and can therefore be a tool for controlling COVID-19 epidemics as part of an exit strategy from current lockdown measures.", "qid": 10, "docid": "6a6njt3u", "rank": 47, "score": 0.7839400768280029}, {"content": "Title: Act early, save lives: managing COVID-19 in Greece Content: Abstract Objectives: To assess the impact of the implemented social distancing interventions (SD) in Greece. Study Design: A dynamic, discrete time, stochastic individual-based model was developed to simulate COVID-19 transmission. Methods: We fit the transmission model to the observed trends in deaths and ICU beds use. Results: If Greece had not implemented the SD measures, the healthcare system would have been overwhelmed between 30 March and 4 of April. Additionally, the SD interventions averted 4360 deaths and prevent the healthcare system from overwhelmed. Conclusions: The fast reflexes of the Greek government limit the burden of the Covid-19 outbreak.", "qid": 10, "docid": "7mbvxx1n", "rank": 48, "score": 0.7837321758270264}, {"content": "Title: Forecasting the Spread of COVID-19 under Different Reopening Strategies Content: We combine COVID-19 case data with demographic and mobility data to estimate a modified susceptible-infected-recovered (SIR) model for the spread of this disease in the United States. We find that the incidence of infectious COVID-19 individuals has a concave effect on contagion, as would be expected if people have inter-related social networks. We also demonstrate that social distancing and population density have large effects on the rate of contagion. The social distancing in late March and April substantially reduced the number of COVID-19 cases. However, the concave contagion pattern means that when social distancing measures are lifted, the growth rate is considerable but will not be exponential as predicted by standard SIR models. Furthermore, counties with the lowest population density could likely avoid high levels of contagion even with no social distancing. We forecast rates of new cases for COVID-19 under different social distancing norms and find that if social distancing is eliminated there will be a massive increase in the cases of COVID-19, about double what would occur if the US only restored to 50% of the way to normalcy.", "qid": 10, "docid": "icituitn", "rank": 49, "score": 0.783338725566864}, {"content": "Title: Investigating duration and intensity of Covid-19 social-distancing strategies Content: The exponential character of the recent Covid-19 outbreak requires a change in strategy from containment to mitigation. Meanwhile, most countries apply social distancing with the objective to keep the number of critical cases below the capabilities of the health care system. Due to the novelty and rapid spread of the virus, an a priori assessment of this strategy was not possible. In this study, we present a model-based systems analysis to assess the effectiveness of social distancing measures in terms of intensity and duration of application. Results show a super-linear scaling between intensity (percent contact reduction) and required duration of application to have an added value (lower fatality rate). This holds true for an effective reproduction of R > 1 and is reverted for R < 1. If R is not reduced below 1, secondary effects of required long-term isolation are likely to unravel the added value of disease mitigation. We recommend an extinction strategy implemented by intense countermeasures.", "qid": 10, "docid": "b8f4a7o3", "rank": 50, "score": 0.7831357717514038}, {"content": "Title: Social distancing, population density, and spread of COVID-19 in England: a longitudinal study Content: BACKGROUND: The UK government introduced social distancing measures between 16-22 March 2020, aiming to slow down transmission of COVID-19. AIM: To explore the spreading of COVID-19 in relation to population density after the introduction of social distancing measures. DESIGN & SETTING: Longitudinal design with 5-weekly COVID-19 incidence rates per 100 000 people for 149 English Upper Tier Local Authorities (UTLAs), between 16 March and 19 April 2020. METHOD: Multivariable multilevel model to analyse weekly incidence rates per 100 000 people; time was level-1 unit and UTLA level-2 unit. Population density was divided into quartiles. The model included an interaction between week and population density. Potential confounders were percentage aged &#8805;65, percentage non-white British, and percentage in two highest classes of the National Statistics Socioeconomic Classification. Co-variates were male life expectancy at birth, and COVID-19 prevalence rate per 100 000 people on March 15. Confounders and co-variates were standardised around the mean. RESULTS: Incidence rates per 100 000 people peaked in the week of March 30-April 5, showing higher adjusted incidence rate per 100 000 people (46.2; 95% confidence interval [CI] = 40.6 to 51.8) in most densely populated ULTAs (quartile 4) than in less densely populated ULTAs (quartile 1: 33.3, 95% CI = 27.4 to 37.2; quartile 2: 35.9, 95% CI = 31.6 to 40.1). Thereafter, incidence rate dropped in the most densely populated ULTAs resulting in rate of 22.4 (95% CI = 16.9 to 28.0) in the week of April 13-19; this was lower than in quartiles 1, 2, and 3, respectively 31.4 (95% CI = 26.5 to 36.3), 34.2 (95% CI = 29.9 to 38.5), and 43.2 (95% CI = 39.0 to 47.4). CONCLUSION: After the introduction of social distancing measures, the incidence rates per 100 000 people dropped stronger in most densely populated ULTAs.", "qid": 10, "docid": "lezcbgx9", "rank": 51, "score": 0.7824653387069702}, {"content": "Title: The impact of early social distancing at COVID-19 Outbreak in the largest Metropolitan Area of Brazil. Content: We evaluated the impact of early social distancing on the COVID-19 transmission in the Sao Paulo metropolitan area. Using an age-stratified SEIR model, we determined the time-dependent reproductive number, and forecasted the ICU beds necessary to tackle this epidemic. Within 60 days, these measures might prevent 89,133 deaths.", "qid": 10, "docid": "9bi6pobg", "rank": 52, "score": 0.7819839715957642}, {"content": "Title: DOUBLE POWER LAW FOR COVID-19: PREDICTION OF NEW CASES AND DEATH RATES IN ITALY AND SPAIN Content: The novel corona virus SARS-CoV-2 appeared at the end of 2019, spreading rapidly and causing a severe respiratory syndrome (COVID-19) with high mortality (2-5%). Until a vaccine or therapy is found, the most effective method of prophylaxis has been to minimize transmission via rigorous social distancing and seclusion of all but essential workers. Such measures, implemented at different times and to varying degrees worldwide, have reduced the rate of transmission compared with early phases of the pandemic, resulting in flattening of the curve followed by a gradual reduction in mortality after >6 weeks of rigorous social distancing measures. The cost of rigorous social distancing has been seen in radically reduced economic activity, job losses, disruption of schooling and social institutions. A key question facing policy makers and individuals is when to resume normal economic and social activity in the face of persistent community transmission of SARS-CoV-2 . To help address this question, we have developed a model that accurately describes the entire transmission and mortality curves in Italy and Spain, two hard-hit countries that have maintained severe social distancing measures for over 2 months. Our model quantitatively describes the rapid rise and slow decay of new cases and deaths observed under stringent social distancing (the long tail effect). We predict that even when social distancing is rigorously maintained, the number of COVID-19 deaths after peak mortality may be 2-3 times larger than the total number of deaths up to the peak. Our model has important policy implications for countries currently debating how to ease social distancing measures.", "qid": 10, "docid": "zox6efyn", "rank": 53, "score": 0.7807207107543945}, {"content": "Title: Differential Effects of Intervention Timing on COVID-19 Spread in the United States Content: Assessing the effects of early non-pharmaceutical interventions(1\u20135) on COVID-19 spread in the United States is crucial for understanding and planning future control measures to combat the ongoing pandemic(6\u201310). Here we use county-level observations of reported infections and deaths(11), in conjunction with human mobility data(12) and a metapopulation transmission model(13,14), to quantify changes of disease transmission rates in US counties from March 15, 2020 to May 3, 2020. We find significant reductions of the basic reproductive numbers in major metropolitan areas in association with social distancing and other control measures. Counterfactual simulations indicate that, had these same control measures been implemented just 1\u20132 weeks earlier, a substantial number of cases and deaths could have been averted. Specifically, nationwide, 56.5% [95% Cl: 48.1%\u221265.9%] of reported infections and 54.0% [95% Cl: 43.6%\u221263.8%] of reported deaths as of May 3, 2020 could have been avoided if the same control measures had been implemented just one week earlier. We also examine the effects of delays in re-implementing social distancing following a relaxation of control measures. A longer response time results in a stronger rebound of infections and death. Our findings underscore the importance of early intervention and aggressive response in controlling the COVID-19 pandemic.", "qid": 10, "docid": "veeavho5", "rank": 54, "score": 0.7803382873535156}, {"content": "Title: Causal Impact of Masks, Policies, Behavior on Early Covid-19 Pandemic in the U.S. Content: This paper evaluates the dynamic impact of various policies, such as school, business, and restaurant closures, adopted by the US states on the growth rates of confirmed Covid-19 cases and social distancing behavior measured by Google Mobility Reports, where we take into consideration of people's voluntarily behavioral response to new information of transmission risks. Using the US state-level data, our analysis finds that both policies and information on transmission risks are important determinants of people's social distancing behavior, and shows that a change in policies explains a large fraction of observed changes in social distancing behavior. Our counterfactual experiments indicate that removing all policies on April 1st of 2020 would have lead to 30 to 200 times more additional cases by late May. Removing only the non-essential businesses closures (while maintaining restrictions on movie theaters and restaurants) would have increased the weekly growth rate of cases between -0.02 and 0.06 and would have lead to -10% to 40% more cases by late May. Finally, nationally mandating face masks for employees on April 1st would have reduced the case growth rate by 0.1-0.25. This leads to 30% to 57% fewer reported cases by late May, which translates into, roughly, 30-57 thousand saved lives.", "qid": 10, "docid": "2fokjcjr", "rank": 55, "score": 0.7801728844642639}, {"content": "Title: Impact of Social Distancing Measures on COVID-19 Healthcare Demand in Central Texas Content: A novel coronavirus (SARS-CoV-2) emerged in Wuhan, China in late 2019 and rapidly spread worldwide. In the absence of effective antiviral drugs and vaccines, well-targeted social distancing measures are essential for mitigating the COVID-19 pandemic, reducing strain on local health systems, and preventing mortality. Here, we provide a quantitative assessment of the efficacy of social distancing to slow COVID-19 transmission and reduce hospital surge, depending on the timing and extent of the measures imposed for a metropolitan region and its health care systems. We built a granular mathematical model of COVID-19 transmission that incorporated age-specific and risk-stratified heterogeneity, estimates for the transmission, and severity of COVID-19 using current best evidence. We performed thousands of stochastic simulations of COVID-19 transmission in the Austin-Round Rock Metropolitan Area to project the impact of school closures coupled with social distancing measures that were estimated to reduce non-household contacts by 0%, 25%, 50%, 75% or 90%. We compare early versus late implementation and estimate the number of COVID-19 hospitalizations, ICU patients, ventilator needs and deaths through mid-August, 2020. We queried local emergency services and hospital systems to estimate total hospital bed, ICU, and ventilator capacity for the region. We expected COVID-19 hospital beds and ICU requirements would surpass local capacity by mid-May if no intervention was taken. Assuming a four-day epidemic doubling time, school closures alone would be expected to reduce peak hospitalizations by only 18% and cumulative deaths by less than 3%. Immediate social distancing measures that reduced non-household contacts by over 75%, such as stay-at-home orders and closing of non-essential businesses, would be required to ensure that COVID-19 cases do not overwhelm local hospital surge capacity. Peak ICU bed demand prior to mid August 2020 would be expected to be reduced from 2,121 (95% CI: 2,018-2,208) with no intervention to 698 (95% CI: 204-1,100) with 75% social distancing and 136 (95% CI: 38-308) with 90% social distancing; current ICU bed capacity was estimated at 680. A two-week delay in implementation of such measures is projected to accelerate a local ICU bed shortage by four weeks. School closures alone hardly impact the epidemic curve. Immediate social distancing measures that reduce non-household contacts by over 75% were required to ensure that COVID-19 cases do not overwhelm local hospital surge capacity. These findings helped inform the Stay Home-Work Safe order enacted by the city of Austin, Texas on March 24, 2020 as a means of mitigating the emerging COVID-19 epidemic.", "qid": 10, "docid": "n0nch8he", "rank": 56, "score": 0.779770016670227}, {"content": "Title: Effects of social distancing on the spreading of COVID-19 inferred from mobile phone data Content: A better understanding of how the COVID-19 epidemic responds to social distancing efforts is required for the control of future outbreaks and to calibrate partial lock-downs. We present quantitative relationships between key parameters characterizing the COVID-19 epidemiology and social distancing efforts of nine selected European countries. Epidemiological parameters were extracted from the number of daily deaths data, while mitigation efforts are estimated from mobile phone tracking data. The decrease of the basic reproductive number (R0) as well as the duration of the initial exponential expansion phase of the epidemic strongly correlates with the magnitude of mobility reduction. Utilizing these relationships we decipher the relative impact of the timing and the extent of social distancing on the total death burden of the epidemic.", "qid": 10, "docid": "gz18sxzc", "rank": 57, "score": 0.7789323329925537}, {"content": "Title: Modeling the dynamics of COVID19 spread during and after social distancing Content: Non-pharmaceutical intervention measures, such as social distancing, have so far been the only means to slow the spread of COVID19. In the United States, strict social distancing has resulted in different types infection dynamics. In some states, such as New York, extensive infection spread was followed by a pronounced decline of infection levels. In other states, such as California, less infection spread occurred before strict social distancing, and a different pattern was observed. Instead of a pronounced infection decline, a long-lasting plateau is evident, characterized by similar daily new infection levels. While these plateau dynamics cannot be readily reproduced with standard SIR infection models, we show that network models, in which individuals and their social contacts are explicitly tracked, can reproduce the plateau if network connections are cut due to social distancing measures. The reason is that in networks characterized by a degree of 2D spatial structure, infection tends to spread quadratically with time, but as edges are randomly removed, the infection spreads along nearly one-dimensional infection \"corridors\", resulting in plateau dynamics. Interestingly, the plateau dynamics are predicted to eventually transition into an infection decline phase without any further increase in social distancing measures. Additionally, the models suggest that a potential second wave becomes significantly less pronounced if social distancing is only relaxed once the dynamics have transitioned to the decline phase. The network models analyzed here allow us to interpret and reconcile different infection dynamics during social distancing observed in various US states.", "qid": 10, "docid": "0b6dsdct", "rank": 58, "score": 0.7778511047363281}, {"content": "Title: A Modelling Analysis of Strategies for Relaxing COVID-19 Social Distancing Content: Abstract Background: The ability of countries to contain and control COVID-19 virus transmission via social distancing is critical in the absence of a vaccine. Early activation of robust measures has been shown to control the daily infection rate, and consequential pressure on the health care system. As countries begin to control COVID-19 spread an understanding of how to ease social distancing measures to prevent a rebound in cases and deaths is required. Methods: Using COVID-19 transmission data from the outbreak source in Hubei Province, China prior to activation of containment measures, we adapted an established individual-based simulation model of the city of Newcastle, Australia. Simulation of virus transmission in this model, with and without, social distancing measures activated permitted us to quantify social distancing effectiveness. Optimal strategies for relaxing social distancing were determined under two settings: with high numbers of daily cases, as in New York; and where early social distancing activation resulted in limited ongoing transmission, as in Perth, Australia. Findings: In countries where strong social distancing measures were activated after the COVID-19 virus had spread widely, our study found these measures are required to be maintained for significant periods before being eased, to return to a situation where daily case numbers become low. In countries where early responses to the COVID-19 pandemic have been highly successful, as in Australia, we show that a staged relaxation of social distancing prevents a rebound in cases. Interpretation: Modelling studies and direct observation have shown that robust and timely social distancing have the most effect in containing the spread of the COVID-19 virus. Questions arise as to the duration of strong social distancing measures, given they are highly disruptive to society and economic activity. This study demonstrates the necessity of holding robust social distancing in place until COVID-19 virus transmission has significantly decreased, and how they may then be safely eased.", "qid": 10, "docid": "t7p2j504", "rank": 59, "score": 0.7775429487228394}, {"content": "Title: Association of County-Level Socioeconomic and Political Characteristics with Engagement in Social Distancing for COVID-19 Content: The U.S. is the epicenter of the coronavirus disease 2019 (COVID-19) pandemic. In response, governments have implemented measures to slow transmission through \"social distancing.\" However, the practice of social distancing may depend on prevailing socioeconomic conditions and beliefs. Using 15-17 million anonymized cell phone records, we find that lower per capita income and greater Republican orientation were associated with significantly reduced social distancing among U.S. counties. These associations persisted after adjusting for county-level sociodemographic and labor market characteristics as well as state fixed effects. These results may help policymakers and health professionals identify communities that are most vulnerable to transmission and direct resources and communications accordingly.", "qid": 10, "docid": "lb0fd7ig", "rank": 60, "score": 0.7772412300109863}, {"content": "Title: Modeling the effects of intervention strategies on COVID-19 transmission dynamics Content: OBJECTIVES: To model the effects of continuous, intermittent, and stepping-down social distancing (SD) strategies and personal protection measures on COVID-19 transmission dynamics. METHODS: Constant, intermittent, and stepping-down SD strategies were modeled at 4 mean magnitudes (5%, 10 %, 15 % and 20 %), 2 time windows (40-days, 80-days), and 2 levels of personal caution (30 % and 50 %). RESULTS: The stepping-down strategy was the best long-term SD strategy to minimize the peak number of active COVID-19 cases and associated deaths. The stepping-down strategy also resulted in a reduction in total time required to SD over a two-year period by 6.5 % compared to an intermittent or constant SD strategy. An 80-day SD time-window was statistically more effective in maintaining control over the COVID-19 pandemic than a 40-day window. However, the results were dependent upon 50 % of people being cautious (engaging in personal protection measures). CONCLUSION: If people exercise caution while in public by protecting themselves (e.g., wearing a facemask, proper hand hygiene and avoid agglomeration) the magnitude and duration of SD necessary to maintain control over the pandemic can be reduced. Our models suggest that the most effective way to reduce SD over a two-year period is a stepping-down approach every 80 days. According to our model, this method would prevent a second peak and the number of intensive care units needed per day would be within the threshold of those currently available.", "qid": 10, "docid": "hy0ut8kf", "rank": 61, "score": 0.7764590978622437}, {"content": "Title: Modeling the effects of intervention strategies on COVID-19 transmission dynamics Content: OBJECTIVES: To model the effects of continuous, intermittent, and stepping-down social distancing (SD) strategies and personal protection measures on COVID-19 transmission dynamics. METHODS: Constant, intermittent, and stepping-down SD strategies were modeled at 4 mean magnitudes (5%, 10%, 15% and 20%), 2 time windows (40-days, 80-days), and 2 levels of personal caution (30% and 50%). RESULTS: The stepping-down strategy was the best long-term SD strategy to minimize the peak number of active COVID-19 cases and associated deaths. The stepping-down strategy also resulted in a reduction in total time required to SD over a two-year period by 6.5% compared to an intermittent or constant SD strategy. An 80-day SD time-window was statistically more effective in maintaining control over the COVID-19 pandemic than a 40-day window. However, the results were dependent upon 50% of people being cautious (engaging in personal protection measures). CONCLUSION: If people exercise caution while in public by protecting themselves (e.g., wearing a facemask, proper hand hygiene and avoid agglomeration) the magnitude and duration of SD necessary to maintain control over the pandemic can be reduced. Our models suggest that the most effective way to reduce SD over a two-year period is a stepping-down approach every 80 days. According to our model, this method would prevent a second peak and the number of intensive care units needed per day would be within the threshold of those currently available.", "qid": 10, "docid": "4dzkdgi8", "rank": 62, "score": 0.7764590978622437}, {"content": "Title: Social distancing, population density, and spread of COVID-19 in England: a longitudinal study. Content: BACKGROUND The UK government introduced social distancing measures between 16-22 March 2020, aiming to slow down transmission of COVID-19. AIM To explore the spreading of COVID-19 in relation to population density after the introduction of social distancing measures. DESIGN & SETTING Longitudinal design with 5-weekly COVID-19 incidence rates per 100 000 people for 149 English Upper Tier Local Authorities (UTLAs), between 16 March and 19 April 2020. METHOD Multivariable multilevel model to analyse weekly incidence rates per 100 000 people; time was level-1 unit and UTLA level-2 unit. Population density was divided into quartiles. The model included an interaction between week and population density. Potential confounders were percentage aged \u226565, percentage non-white British, and percentage in two highest classes of the National Statistics Socioeconomic Classification. Co-variates were male life expectancy at birth, and COVID-19 prevalence rate per 100 000 people on March 15. Confounders and co-variates were standardised around the mean. RESULTS Incidence rates per 100 000 people peaked in the week of March 30-April 5, showing higher adjusted incidence rate per 100 000 people (46.2; 95% confidence interval [CI] = 40.6 to 51.8) in most densely populated ULTAs (quartile 4) than in less densely populated ULTAs (quartile 1: 33.3, 95% CI = 27.4 to 37.2; quartile 2: 35.9, 95% CI = 31.6 to 40.1). Thereafter, incidence rate dropped in the most densely populated ULTAs resulting in rate of 22.4 (95% CI = 16.9 to 28.0) in the week of April 13-19; this was lower than in quartiles 1, 2, and 3, respectively 31.4 (95% CI = 26.5 to 36.3), 34.2 (95% CI = 29.9 to 38.5), and 43.2 (95% CI = 39.0 to 47.4). CONCLUSION After the introduction of social distancing measures, the incidence rates per 100 000 people dropped stronger in most densely populated ULTAs.", "qid": 10, "docid": "qrhzum9v", "rank": 63, "score": 0.7762033939361572}, {"content": "Title: Analyzing situational awareness through public opinion to predict adoption of social distancing amid pandemic COVID-19 Content: COVID-19 pandemic has affected over 100 countries in a matter of weeks. People's response toward social distancing in the emerging pandemic is uncertain. In this study, we evaluated the influence of information (formal and informal) sources on situational awareness of the public for adopting health-protective behaviors such as social distancing. For this purpose, a questionnaire-based survey was conducted. The hypothesis proposed suggests that adoption of social distancing practices is an outcome of situational awareness which is achieved by the information sources. Results suggest that information sources, formal (P = .001) and informal (P = 0.007) were found to be significantly related to perceived understanding. Findings also indicate that social distancing is significantly influenced by situational awareness, P = .000. It can, therefore, be concluded that an increase in situational awareness in times of public health crisis using formal information sources can significantly increase the adoption of protective health behavior and in turn contain the spread of infectious diseases.", "qid": 10, "docid": "e8gga4oh", "rank": 64, "score": 0.7758146524429321}, {"content": "Title: Observed mobility behavior data reveal social distancing inertia Content: The research team has utilized an integrated dataset, consisting of anonymized location data, COVID-19 case data, and census population information, to study the impact of COVID-19 on human mobility. The study revealed that statistics related to social distancing, namely trip rate, miles traveled per person, and percentage of population staying at home have all showed an unexpected trend, which we named social distancing inertia. The trends showed that as soon as COVID-19 cases were observed, the statistics started improving, regardless of government actions. This suggests that a portion of population who could and were willing to practice social distancing voluntarily and naturally reacted to the emergence of COVID-19 cases. However, after about two weeks, the statistics saturated and stopped improving, despite the continuous rise in COVID-19 cases. The study suggests that there is a natural behavior inertia toward social distancing, which puts a limit on the extent of improvement in the social-distancing-related statistics. The national data showed that the inertia phenomenon is universal, happening in all the U.S. states and for all the studied statistics. The U.S. states showed a synchronized trend, regardless of the timeline of their statewide COVID-19 case spreads or government orders.", "qid": 10, "docid": "hb1r2aw7", "rank": 65, "score": 0.7751904726028442}, {"content": "Title: Optimal control of the COVID-19 pandemic with non-pharmaceutical interventions Content: The COVID-19 pandemic has forced societies across the world to resort to social distancing to slow the spread of the SARS-CoV-2 virus. Due to the economic impacts of social distancing, there is growing desire to relax these measures. To characterize a range of possible strategies for control and to understand their consequences, we performed an optimal control analysis of a mathematical model of SARS-CoV-2 transmission. Given that the pandemic is already underway and controls have already been initiated, we calibrated our model to data from the US and focused our analysis on optimal controls from May 2020 through December 2021. We found that a major factor that differentiates strategies that prioritize lives saved versus reduced time under control is how quickly control is relaxed once social distancing restrictions expire in May 2020. Strategies that maintain control at a high level until summer 2020 allow for tapering of control thereafter and minimal deaths, whereas strategies that relax control in the short term lead to fewer options for control later and a higher likelihood of exceeding hospital capacity. Our results also highlight that the potential scope for controlling COVID-19 until a vaccine is available depends on epidemiological parameters about which there is still considerable uncertainty, including the basic reproduction number and the effectiveness of social distancing. In light of those uncertainties, our results do not constitute a quantitative forecast and instead provide a qualitative portrayal of possible outcomes from alternative approaches to control.", "qid": 10, "docid": "lnv8yi9l", "rank": 66, "score": 0.7749043703079224}, {"content": "Title: The Effect of Social Distancing on the Reach of an Epidemic in Social Networks Content: How does social distancing affect the reach of an epidemic in social networks? We present Monte Carlo simulation results of a Susceptible- Infected-Removed (SIR) model on a network, where individuals are limited in the number of other people they can interact with. While increased social distancing always reduces the spread of an infectious disease, the magnitude varies greatly depending on the topology of the social network. Our results also reveal the importance of coordination at the global level. In particular, the public health benefits from social distancing to a group (e.g., a country) may be completely undone if that group maintains connections with outside groups that are not social distancing.", "qid": 10, "docid": "k208rpth", "rank": 67, "score": 0.7748921513557434}, {"content": "Title: Analyzing situational awareness through public opinion to predict adoption of social distancing amid pandemic COVID\u201019 Content: COVID\u201019 pandemic has affected over 100 countries in a matter of weeks. People's response toward social distancing in the emerging pandemic is uncertain. In this study, we evaluated the influence of information (formal and informal) sources on situational awareness of the public for adopting health\u2010protective behaviors such as social distancing. For this purpose, a questionnaire\u2010based survey was conducted. The hypothesis proposed suggests that adoption of social distancing practices is an outcome of situational awareness which is achieved by the information sources. Results suggest that information sources, formal (P = .001) and informal (P = 0.007) were found to be significantly related to perceived understanding. Findings also indicate that social distancing is significantly influenced by situational awareness, P = .000. It can, therefore, be concluded that an increase in situational awareness in times of public health crisis using formal information sources can significantly increase the adoption of protective health behavior and in turn contain the spread of infectious diseases.", "qid": 10, "docid": "79m2t343", "rank": 68, "score": 0.7748405933380127}, {"content": "Title: The Effectiveness of Social Distancing in Mitigating COVID-19 Spread: a modelling analysis Content: Background The novel coronavirus COVID19 has been classified by the World Health Organisation as a pandemic due to its worldwide spread. The ability of countries to contain and control transmission is critical in the absence of a vaccine. We evaluated a range of social distancing measures to determine which strategies are most effective in reducing the peak daily infection rate, and consequential pressure on the health care system. Methods Using COVID19 transmission data from the outbreak source in Hubei Province, China, collected prior to activation of containment measures, we adapted an established individual based simulation model of the city of Newcastle, Australia, population 272,409. Simulation of virus transmission in this community model without interventions provided a baseline from which to compare alternative social distancing strategies. The infection history of each individual was determined, as was the time infected. From this model generated data, the rate of growth in cases, the magnitude of the epidemic peak, and the outbreak duration were obtained. Findings The application of all four social distancing interventions: school closure, workplace non-attendance, increased case isolation, and community contact reduction is highly effective in flattening the epidemic curve, reducing the maximum daily case numbers, and lengthening outbreak duration. These were also found to be effective even after 10 weeks delay from index case arrivals. The most effective single intervention was found to be increasing case isolation, to 100 percent of children and 90 percent of adults. Interpretation As strong social distancing intervention strategies had the most effect in reducing the epidemic peak, this strategy may be considered when weaker strategies are first tried and found to be less effective. Questions arise as to the duration of strong social distancing measures, given they are highly disruptive to society. Tradeoffs may need to be made between the effectiveness of social distancing strategies and population willingness to adhere to them.", "qid": 10, "docid": "qqsefagq", "rank": 69, "score": 0.7745099067687988}, {"content": "Title: COVID-19 pandemic-related lockdown: response time is more important than its strictness Content: The rapid spread of SARS-CoV-2 and its threat to health systems worldwide have led governments to take acute actions to enforce social distancing. Previous studies used complex epidemiological models to quantify the effect of lockdown policies on infection rates. However, these rely on prior assumptions or on official regulations. Here, we use country-specific reports of daily mobility from people cellular usage to model social distancing. Our data-driven model enabled the extraction of mobility characteristics which were crossed with observed mortality rates to show that: (1) the time at which social distancing was initiated is of utmost importance and explains 62% of the number of deaths, while the lockdown strictness or its duration are not as informative; (2) a delay of 7.49 days in initiating social distancing would double the number of deaths; and (3) the expected time from infection to fatality is 25.75 days and significantly varies among countries.", "qid": 10, "docid": "rjjc30lc", "rank": 70, "score": 0.7743731737136841}, {"content": "Title: Strong Social Distancing Measures In The United States Reduced The COVID-19 Growth Rate Content: State and local governments imposed social distancing measures in March and April of 2020 to contain the spread of novel coronavirus disease 2019 (COVID-19). These included large event bans, school closures, closures of entertainment venues, gyms, bars, and restaurant dining areas, and shelter-in-place orders (SIPOs). We evaluated the impact of these measures on the growth rate of confirmed COVID-19 cases across US counties between March 1, 2020 and April 27, 2020. An event-study design allowed each policy's impact on COVID-19 case growth to evolve over time. Adoption of government-imposed social distancing measures reduced the daily growth rate by 5.4 percentage points after 1-5 days, 6.8 after 6-10 days, 8.2 after 11-15 days, and 9.1 after 16-20 days. Holding the amount of voluntary social distancing constant, these results imply 10 times greater spread by April 27 without SIPOs (10 million cases) and more than 35 times greater spread without any of the four measures (35 million). Our paper illustrates the potential danger of exponential spread in the absence of interventions, providing relevant information to strategies for restarting economic activity. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].", "qid": 10, "docid": "h6ngg7ea", "rank": 71, "score": 0.7738132476806641}, {"content": "Title: Strong Social Distancing Measures In The United States Reduced The COVID-19 Growth Rate. Content: State and local governments imposed social distancing measures in March and April of 2020 to contain the spread of novel coronavirus disease 2019 (COVID-19). These included large event bans, school closures, closures of entertainment venues, gyms, bars, and restaurant dining areas, and shelter-in-place orders (SIPOs). We evaluated the impact of these measures on the growth rate of confirmed COVID-19 cases across US counties between March 1, 2020 and April 27, 2020. An event-study design allowed each policy's impact on COVID-19 case growth to evolve over time. Adoption of government-imposed social distancing measures reduced the daily growth rate by 5.4 percentage points after 1-5 days, 6.8 after 6-10 days, 8.2 after 11-15 days, and 9.1 after 16-20 days. Holding the amount of voluntary social distancing constant, these results imply 10 times greater spread by April 27 without SIPOs (10 million cases) and more than 35 times greater spread without any of the four measures (35 million). Our paper illustrates the potential danger of exponential spread in the absence of interventions, providing relevant information to strategies for restarting economic activity. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].", "qid": 10, "docid": "ereh4ub8", "rank": 72, "score": 0.7738132476806641}, {"content": "Title: Age-structured impact of social distancing on the COVID-19 epidemic in India Content: The outbreak of the novel coronavirus, COVID-19, has been declared a pandemic by the WHO. The structures of social contact critically determine the spread of the infection and, in the absence of vaccines, the control of these structures through large-scale social distancing measures appears to be the most effective means of mitigation. Here we use an age-structured SIR model with social contact matrices obtained from surveys and Bayesian imputation to study the progress of the COVID-19 epidemic in India. The basic reproductive ratio R0 and its time-dependent generalization are computed based on case data, age distribution and social contact structure. The impact of social distancing measures - workplace non-attendance, school closure, lockdown - and their efficacy with durations are then investigated. A three-week lockdown is found insufficient to prevent a resurgence and, instead, protocols of sustained lockdown with periodic relaxation are suggested. Forecasts are provided for the reduction in age-structured morbidity and mortality as a result of these measures. Our study underlines the importance of age and social contact structures in assessing the country-specific impact of mitigatory social distancing.", "qid": 10, "docid": "xbuypaf6", "rank": 73, "score": 0.7737714648246765}, {"content": "Title: The association between age, COVID-19 symptoms, and social distancing behavior in the United States Content: BACKGROUND: Public health authorities recommend that people practice social distancing, especially if they have symptoms of coronavirus disease (COVID-19), or are older and more at risk of serious illness if they become infected. We test the hypothesis that these groups are following these recommendations and are more likely to undertake social distancing. METHODS: We conducted an open online survey of 4,676 U.S. adults aged 18 and older between April 4 and April 7, 2020. We model the effects of age and common COVID-19 symptoms in the last two weeks on going out of the home for non-healthcare reasons the day before taking the survey, using a logistic model and the number of close contacts (within 6 feet) that respondents had with non-household members, using a Poisson count model. Our models control for several covariates, including other flu-like symptoms, sex, education, income, whether the respondent worked in February, household size, population density in the respondent\u2019s ZIP code, state fixed effects, and the day of completion of the survey. We also weight our analyses to make the sample representative of the U.S. adult population. FINDINGS: About 52 percent of the adult United States population went out of their home the previous day. On average, adults had close contact with 1.9 non-household members. We find that having at least one COVID-19 symptom (fever, dry cough, or shortness of breath) increased the likelihood of going out the previous day and having additional close contacts with non-household members; however, the estimates were not statistically significant. When disaggregating our analysis by COVID-19 symptoms, we find no strong evidence of greater social distancing by people with a fever or cough in the last two weeks, but we do find that those who experienced shortness of breath have fewer close contacts, with an incidence rate ratio (IRR) of 0.49 (95% CI: 0.30\u20130.78). Having other flu-like symptoms reduces the odds of going out by 0.32 (95% CI: 0.18\u20130.60) and the incidence rate of having close contacts by 42 percent (IRR = 0.58; 95% CI: 0.38\u20130.88). We find that older people are just as likely to leave their homes as younger people, but people over the age of 50 had less than half the predicted number of close contacts than those who were younger than 30. Our approach has the limitation that the survey sample is self-selected. Our findings may therefore be subject to selection bias that is not adequately controlled for by weighting. In addition, the possibility exists of confounding of the results due to omitted variable bias. CONCLUSIONS: We provide evidence that older people are having significantly fewer close contacts than younger people, which is in line with the public health authorities\u2019 recommendations. We also find that people experiencing shortness of breath are practicing more intense social distancing. However, we find that those with two other common COVID-19 symptoms, fever and dry cough, are not engaging in greater social distancing, suggesting that increased targeting on relevant symptoms, and messaging, may be required.", "qid": 10, "docid": "z49nb5ej", "rank": 74, "score": 0.7733904123306274}, {"content": "Title: Impact assessment of non-pharmaceutical interventions against COVID-19 and influenza in Hong Kong: an observational study Content: Background: A range of public health measures have been implemented to delay and reduce local transmission of COVID-19 in Hong Kong, and there have been major changes in behaviours of the general public. We examined the effect of these interventions and behavioral changes on the incidence of COVID-19 as well as on influenza virus infections which may share some aspects of transmission dynamics with COVID-19. Methods: We reviewed policy interventions and measured changes in population behaviours through two telephone surveys, on January 20-23 and February 11-14. We analysed data on laboratory-confirmed COVID-19 cases, influenza surveillance data in outpatients of all ages, and influenza hospitalisations in children. We estimated the daily effective reproduction number (R_t), for COVID-19 and influenza A(H1N1). Findings: COVID-19 transmissibility has remained at or below 1, indicating successful containment to date. Influenza transmission declined substantially after the implementation of social distancing measures and changes in population behaviours in late January, with a 44% (95% confidence interval, CI: 34% to 53%) reduction in transmissibility in the community, and a 33% (95% CI: 24% to 43%) reduction in transmissibility based on paediatric hospitalization rates. In the two surveys we estimated that 74.5% and 97.5% of the general adult population wore masks when going out, and 61.3% and 90.2% avoided going to crowded places, respectively. Implications: Containment measures, social distancing measures and changes in population behaviour have successfully prevented spread of COVID-19. The social distancing measures and behavioural changes led to a substantial reduction in influenza transmission in early February 2020. However, it may be challenging to avoid fatigue and sustain these measures and population behaviours as COVID-19 continues to spread globally. Funding: Health and Medical Research Fund, Hong Kong", "qid": 10, "docid": "ytsqfqvh", "rank": 75, "score": 0.7732445597648621}, {"content": "Title: Non-COVID-19 Deaths After Social Distancing in Norway Content: Lay persons and policy makers have speculated on how the imposition of social distancing to reduce SARS CoV-2 (severe acute respiratory syndrome coronavirus 2) infection has affected non-COVID-19 (coronavirus disease of 2019) deaths. No rigorous estimation of the effect appears in the scholarly literature. We use time-series methods to compare non-COVID-19 deaths observed in Norway before and during the epidemic to those expected from non-COVID-19 deaths in Sweden as well as from the history of Norwegian mortality trends. We find that in the first 8 weeks after the divergence between Swedish and Norwegian policies (the only period for which dependable data can be had) approximately 650 fewer Norwegians died than expected.", "qid": 10, "docid": "n4kke717", "rank": 76, "score": 0.7725517749786377}, {"content": "Title: Get the News Out Loudly and Quickly: The Influence of the Media on Limiting Emerging Infectious Disease Outbreaks Content: During outbreaks of infectious diseases with high morbidity and mortality, individuals closely follow media reports of the outbreak. Many will attempt to minimize contacts with other individuals in order to protect themselves from infection and possibly death. This process is called social distancing. Social distancing strategies include restricting socializing and travel, and using barrier protections. We use modeling to show that for short-term outbreaks, social distancing can have a large influence on reducing outbreak morbidity and mortality. In particular, public health agencies working together with the media can significantly reduce the severity of an outbreak by providing timely accounts of new infections and deaths. Our models show that the most effective strategy to reduce infections is to provide this information as early as possible, though providing it well into the course of the outbreak can still have a significant effect. However, our models for long-term outbreaks indicate that reporting historic infection data can result in more infections than with no reporting at all. We examine three types of media influence and we illustrate the media influence with a simulated outbreak of a generic emerging infectious disease in a small city. Social distancing can never be complete; however, for a spectrum of outbreaks, we show that leaving isolation (stopping applying social distancing measures) for up to 4 hours each day has modest effect on the overall morbidity and mortality.", "qid": 10, "docid": "6zployed", "rank": 77, "score": 0.7725437879562378}, {"content": "Title: Quantifying Projected Impact of Social Distancing Policies on COVID-19 Outcomes in the US Content: Current social distancing measures to impede COVID-19 (such as shelter-in-place) are economically unsustainable in the long term. Models are needed to understand the implications of possible relaxation options for these measures. We report such models, together with corresponding parameter estimation techniques and prediction outcomes, borrowing insights from another domain; namely, information cascades. Our models assume that the containment of the virus into isolated locales is no longer possible. Instead, we explore options that reduce the rate of spread. We predict COVID-19 contagion trends in different geographic regions under a\"what if\"scenario to understand the effects of potential policy decisions on regional trends. Our model allows experimentation with other policies that, we hope, can contribute to socially viable outcomes both in terms of health system capacity and economic impact. We apply our model to over 30 highly impacted states in the US and publish the results at https://covid19predictions.csl.illinois.edu/", "qid": 10, "docid": "5rz7gk3m", "rank": 78, "score": 0.7721002697944641}, {"content": "Title: Public perceptions and experiences of social distancing and social isolation during the COVID-19 pandemic: A UK-based focus group study Content: OBJECTIVE: Explore the perceptions and experiences of the UK public of social distancing and social isolation measures related to the COVID-19 pandemic. DESIGN: Qualitative study comprising five focus groups carried out online during the early stages of the UK's social distancing and isolation measures (5-12 days post lockdown). SETTING: Online video-conferencing PARTICIPANTS: 27 participants, all UK residents aged 18 years and older, representing a range of gender, ethnic, age and occupational backgrounds. RESULTS: The social distancing and isolation associated with COVID-19 policy has had having substantial negative impacts on the mental health and wellbeing of the UK public within a short time of policy implementation. It has disproportionately negatively affected those in low-paid or precarious employment. Practical social and economic losses - the loss of (in-person) social interaction, loss of income and loss of structure and routine - led to psychological and emotional 'losses' - the loss of motivation, loss of meaning, and loss of self-worth. Participants reported high adherence to distancing and isolation guidelines but reported seeing or hearing of non-adherence in others. A central concern for participants was the uncertainty duration of the measures, and their ability to cope longer-term. Some participants felt they would have lingering concerns over social contact while others were eager to return to high levels of social activity. CONCLUSIONS: A rapid response is necessary in terms of public health programming to mitigate the mental health impacts of COVID-19 social distancing and isolation. Initial high levels of support for, and adherence to, social distancing and isolation is likely to wane over time, particularly where end dates are uncertain. Social distancing and isolation 'exit strategies' must account for the fact that, although some individuals will voluntarily or habitually continue to socially distance, others will seek high levels of social engagement as soon as possible.", "qid": 10, "docid": "kweh1doo", "rank": 79, "score": 0.7717003226280212}, {"content": "Title: Predictions of COVID-19 dynamics in the UK: short-term forecasting and analysis of potential exit strategies Content: Background: Efforts to suppress transmission of SARS-CoV-2 in the UK have seen non-pharmaceutical interventions being invoked. The most severe measures to date include all restaurants, pubs and cafes being ordered to close on 20th March, followed by a \"stay at home\" order on the 23rd March and the closure of all non-essential retail outlets for an indefinite period. Government agencies are presently analysing how best to develop an exit strategy from these measures and to determine how the epidemic may progress once measures are lifted. Mathematical models are currently providing short and long term forecasts regarding the future course of the COVID-19 outbreak in the UK to support evidence-based policymaking. Methods: We present a deterministic, age-structured transmission model that uses real-time data on confirmed cases requiring hospital care and mortality to provide up-to-date predictions on epidemic spread in ten regions of the UK. We simulated a suite of scenarios to assess the impact of differing approaches to relaxing social distancing measures from 7th May 2020, on the estimated number of patients requiring inpatient and critical care treatment, and deaths. With regard to future epidemic outcomes, we investigated the impact of reducing compliance, ongoing shielding of elder age groups, reapplying stringent social distancing measures using region based triggers and the role of asymptomatic transmission. Findings: We find that significant relaxation of social distancing measures on 7th May can lead to a rapid resurgence of COVID-19 disease and the health system being quickly overwhelmed by a sizeable, second epidemic wave. In all considered age-shielding based strategies, we projected serious demand on critical care resources during the course of the pandemic. The reintroduction and release of strict measures on a regional basis, based on ICU bed occupancy, results in a long epidemic tail, until the second half of 2021, but ensures that the health service is protected by reintroducing social distancing measures for all individuals in a region when required. Conclusions: Our work supports the decision to apply stringent non-pharmaceutical measures in March 2020 to suppress the epidemic. We provide strong evidence to support the need for a cautious, measured approach to relaxation of lockdown measures, to protect the most vulnerable members of society and support the health service through subduing demand on hospital beds, in particular bed occupancy in intensive care units.", "qid": 10, "docid": "dwr0gwqu", "rank": 80, "score": 0.7716915607452393}, {"content": "Title: Quantifying the impact of physical distance measures on the transmission of COVID-19 in the UK Content: BACKGROUND: To mitigate and slow the spread of COVID-19, many countries have adopted unprecedented physical distancing policies, including the UK. We evaluate whether these measures might be sufficient to control the epidemic by estimating their impact on the reproduction number (R(0), the average number of secondary cases generated per case). METHODS: We asked a representative sample of UK adults about their contact patterns on the previous day. The questionnaire was conducted online via email recruitment and documents the age and location of contacts and a measure of their intimacy (whether physical contact was made or not). In addition, we asked about adherence to different physical distancing measures. The first surveys were sent on Tuesday, 24 March, 1 day after a \u201clockdown\u201d was implemented across the UK. We compared measured contact patterns during the \u201clockdown\u201d to patterns of social contact made during a non-epidemic period. By comparing these, we estimated the change in reproduction number as a consequence of the physical distancing measures imposed. We used a meta-analysis of published estimates to inform our estimates of the reproduction number before interventions were put in place. RESULTS: We found a 74% reduction in the average daily number of contacts observed per participant (from 10.8 to 2.8). This would be sufficient to reduce R(0) from 2.6 prior to lockdown to 0.62 (95% confidence interval [CI] 0.37\u20130.89) after the lockdown, based on all types of contact and 0.37 (95% CI = 0.22\u20130.53) for physical (skin to skin) contacts only. CONCLUSIONS: The physical distancing measures adopted by the UK public have substantially reduced contact levels and will likely lead to a substantial impact and a decline in cases in the coming weeks. However, this projected decline in incidence will not occur immediately as there are significant delays between infection, the onset of symptomatic disease, and hospitalisation, as well as further delays to these events being reported. Tracking behavioural change can give a more rapid assessment of the impact of physical distancing measures than routine epidemiological surveillance.", "qid": 10, "docid": "rqotfwm3", "rank": 81, "score": 0.7711299657821655}, {"content": "Title: Social distancing measures to control the COVID-19 pandemic: potential impacts and challenges in Brazil. Content: The COVID-19 pandemic has challenged researchers and policy makers to identify public safety measures forpreventing the collapse of healthcare systems and reducingdeaths. This narrative review summarizes the available evidence on the impact of social distancing measures on the epidemic and discusses the implementation of these measures in Brazil. Articles on the effect of social distancing on COVID-19 were selected from the PubMed, medRXiv and bioRvix databases. Federal and state legislation was analyzed to summarize the strategies implemented in Brazil. Social distancing measures adopted by the population appear effective, particularly when implemented in conjunction with the isolation of cases and quarantining of contacts. Therefore, social distancing measures, and social protection policies to guarantee the sustainability of these measures, should be implemented. To control COVID-19 in Brazil, it is also crucial that epidemiological monitoring is strengthened at all three levels of the Brazilian National Health System (SUS). This includes evaluating and usingsupplementary indicators to monitor the progression of the pandemic and the effect of the control measures, increasing testing capacity, and making disaggregated notificationsand testing resultstransparentand broadly available.", "qid": 10, "docid": "fex8sd1t", "rank": 82, "score": 0.7705708146095276}, {"content": "Title: Medidas de distanciamento social no controle da pandemia de COVID-19: potenciais impactos e desafios no Brasil./ Medidas de distanciamento social no controle da pandemia de COVID-19: potenciais impactos e desafios no Brasil./ Social distancing measures to control the COVID-19 pandemic: potential impacts and challenges in Brazil Content: The COVID-19 pandemic has challenged researchers and policy makers to identify public safety measures forpreventing the collapse of healthcare systems and reducingdeaths. This narrative review summarizes the available evidence on the impact of social distancing measures on the epidemic and discusses the implementation of these measures in Brazil. Articles on the effect of social distancing on COVID-19 were selected from the PubMed, medRXiv and bioRvix databases. Federal and state legislation was analyzed to summarize the strategies implemented in Brazil. Social distancing measures adopted by the population appear effective, particularly when implemented in conjunction with the isolation of cases and quarantining of contacts. Therefore, social distancing measures, and social protection policies to guarantee the sustainability of these measures, should be implemented. To control COVID-19 in Brazil, it is also crucial that epidemiological monitoring is strengthened at all three levels of the Brazilian National Health System (SUS). This includes evaluating and usingsupplementary indicators to monitor the progression of the pandemic and the effect of the control measures, increasing testing capacity, and making disaggregated notificationsand testing resultstransparentand broadly available.", "qid": 10, "docid": "gec6n7lb", "rank": 83, "score": 0.770570695400238}, {"content": "Title: Impact of social distancing measures for preventing coronavirus disease 2019 : A systematic review and meta-analysis protocol Content: Abstract Introduction: Social distancing measures (SDMs) protect public health from the outbreak of coronavirus disease 2019 (COVID-19). However, the impact of SDMs has been inconsistent and unclear. This study aims to assess the effects of SDMs (e.g. isolation, quarantine) for reducing the transmission of COVID-19. Methods and analysis: We will conduct a systematic review meta-analysis research of both randomised controlled trials and non-randomised controlled trials. We will search MEDLINE, EMBASE, Allied & Complementary Medicine, COVID-19 Research and WHO database on COVID-19 for primary studies assessing the enablers and barriers associated with SDMs, and will be reported in accordance with PRISMA statement. The PRISMA-P checklist will be used while preparing this protocol. We will use Joanna Briggs Institute guidelines (JBI Critical Appraisal Checklists) to assess the methodological qualities and synthesised performing thematic analysis. Two reviewers will independently screen the papers and extracted data. If sufficient data are available, the random-effects model for meta-analysis will be performed to measure the effect size of SDMs or the strengths of relationships. To assess the heterogeneity of effects, I2 together with the observed effects (Q-value, with degrees of freedom) will be used to provide the true effects in the analysis. Ethics and dissemination: Ethics approval and consent will not be required for this systematic review of the literature as it does not involve human participation. We will be able to disseminate the study findings using the following strategies: we will be publishing at least one paper in peer-reviewed journals, and an abstract will be presented at suitable national/international conferences or workshops. We will also share important information with public health authorities as well as with the World Health Organization.", "qid": 10, "docid": "3mwx9s5x", "rank": 84, "score": 0.7698749899864197}, {"content": "Title: Dynamic coupling between the COVID epidemic timeline and the behavioral response to PAUSE in New York State counties Content: By many expert opinions, the COVID 19 epidemic is still much in its developing stages. While awaiting for effective clinical answers for the outbreak, the best approach remains that of social distancing. This raises a few crucial questions related to the extent to which social distancing measures were (1) well timed, (2) necessary and (3) efficient. By investigating correlations between epidemic measures such as daily infection rate, and social mobility measures (as reported by Apple and Google), our study aims to establish whether data identifies social distancing measures as a primary player in controlling the outbreak in New York State.", "qid": 10, "docid": "k8eqzr6w", "rank": 85, "score": 0.7697516679763794}, {"content": "Title: Quantifying the impact of physical distance measures on the transmission of COVID-19 in the UK Content: Background: To mitigate and slow the spread of COVID-19, many countries have adopted unprecedented physical distancing policies, including the UK. We evaluate whether these measures might be sufficient to control the epidemic by estimating their impact on the reproduction number (R0, the average number of secondary cases generated per case). Methods: We asked a representative sample of UK adults about their contact patterns on the previous day. The questionnaire documents the age and location of contacts and as well as a measure of their intimacy (whether physical contact was made or not). In addition, we asked about adherence to different physical distancing measures. The first surveys were sent on Tuesday 24th March, one day after a \u201clockdown\u201d was implemented across the UK. We compared measured contact patterns during the lockdown to patterns of social contact made during a non-epidemic period. By comparing these, we estimated the change in reproduction number as a consequence of the physical distancing measures imposed. We used a meta-analysis of published estimates to inform our estimates of the reproduction number before interventions were put in place. Findings: We found a 73% reduction in the average daily number of contacts observed per participant (from 10.2 to 2.9). This would be sufficient to reduce R0 from 2.6 prior to lockdown to 0.62 (95% confidence interval [CI] 0.37 - 0.89) after the lockdown, based on all types of contact and 0.37 (95% CI = 0.22 - 0.53) for physical contacts only. Interpretation: The physical distancing measures adopted by the UK public have substantially reduced contact levels and will likely lead to a substantial impact and a decline in cases in the coming weeks. However, this projected decline in incidence will not occur immediately as there are significant delays between infection, the onset of symptomatic disease and hospitalisation, as well as further delays to these events being reported. Tracking behavioural change can give a more rapid assessment of the impact of physical distancing measures than routine epidemiological surveillance.", "qid": 10, "docid": "8do4tojk", "rank": 86, "score": 0.769665002822876}, {"content": "Title: Social Distancing as a Health Behavior: County-Level Movement in the United States During the COVID-19 Pandemic Is Associated with Conventional Health Behaviors Content: BACKGROUND: Social distancing-when people limit close contact with others outside their household-is a primary intervention available to combat the COVID-19 pandemic. The importance of social distancing is unlikely to change until effective treatments or vaccines become widely available. However, relatively little is known about how best to promote social distancing. Applying knowledge from social and behavioral research on conventional health behaviors (e.g., smoking, physical activity) to support public health efforts and research on social distancing is promising, but empirical evidence supporting this approach is needed. PURPOSE: We examined whether one type of social distancing behavior-reduced movement outside the home-was associated with conventional health behaviors. METHOD: We examined the association between GPS-derived movement behavior in 2,858 counties in USA from March 1 to April 7, 2020 and the prevalence of county-level indicators influenced by residents' conventional health behaviors. RESULTS: Changes in movement were associated with conventional health behaviors, and the magnitude of these associations were similar to the associations among the conventional health behaviors. Counties with healthier behaviors-particularly less obesity and greater physical activity-evidenced greater reduction in movement outside the home during the initial phases of the pandemic in the USA. CONCLUSIONS: Social distancing, in the form of reduced movement outside the home, is associated with conventional health behaviors. Existing scientific literature on health behavior and health behavior change can be more confidently used to promote social distancing behaviors during the COVID-19 pandemic.", "qid": 10, "docid": "cm41gpx1", "rank": 87, "score": 0.7691499590873718}, {"content": "Title: The Benefits and Costs of Social Distancing in Rich and Poor Countries Content: Social distancing is the primary policy prescription for combating the COVID-19 pandemic, and has been widely adopted in Europe and North America. We estimate the value of disease avoidance using an epidemiological model that projects the spread of COVID-19 across rich and poor countries. Social distancing measures that\"flatten the curve\"of the disease to bring demand within the capacity of healthcare systems are predicted to save many lives in high-income countries, such that practically any economic cost is worth bearing. These social distancing policies are estimated to be less effective in poor countries with younger populations less susceptible to COVID-19, and more limited healthcare systems, which were overwhelmed before the pandemic. Moreover, social distancing lowers disease risk by limiting people's economic opportunities. Poorer people are less willing to make those economic sacrifices. They place relatively greater value on their livelihood concerns compared to contracting COVID-19. Not only are the epidemiological and economic benefits of social distancing much smaller in poorer countries, such policies may exact a heavy toll on the poorest and most vulnerable. Workers in the informal sector lack the resources and social protections to isolate themselves and sacrifice economic opportunities until the virus passes. By limiting their ability to earn a living, social distancing can lead to an increase in hunger, deprivation, and related mortality and morbidity. Rather than a blanket adoption of social distancing measures, we advocate for the exploration of alternative harm-reduction strategies, including universal mask adoption and increased hygiene measures.", "qid": 10, "docid": "4u7qtoz7", "rank": 88, "score": 0.7689071893692017}, {"content": "Title: Causal Impact of Masks, Policies, Behavior on Early Covid-19 Pandemic in the U.S Content: This paper evaluates the dynamic impact of various policies adopted by US states on the growth rates of confirmed Covid-19 cases and deaths as well as social distancing behavior measured by Google Mobility Reports, where we take into consideration people's voluntarily behavioral response to new information of transmission risks. Our analysis finds that both policies and information on transmission risks are important determinants of Covid-19 cases and deaths and shows that a change in policies explains a large fraction of observed changes in social distancing behavior. Our counterfactual experiments suggest that nationally mandating face masks for employees on April 1st could have reduced the growth rate of cases and deaths by more than 10 percentage points in late April, and could have led to as much as 17 to 55 percent less deaths nationally by the end of May, which roughly translates into 17 to 55 thousand saved lives. Our estimates imply that removing non-essential business closures (while maintaining school closures, restrictions on movie theaters and restaurants) could have led to -20 to 60 percent more cases and deaths by the end of May. We also find that, without stay-at-home orders, cases would have been larger by 25 to 170 percent, which implies that 0.5 to 3.4 million more Americans could have been infected if stay-at-home orders had not been implemented. Finally, not having implemented any policies could have led to at least a 7 fold increase with an uninformative upper bound in cases (and deaths) by the end of May in the US, with considerable uncertainty over the effects of school closures, which had little cross-sectional variation.", "qid": 10, "docid": "2zkesall", "rank": 89, "score": 0.7685683965682983}, {"content": "Title: Optimal Control applied to a SEIR model of 2019-nCoV with social distancing Content: Does the implementation of social distancing measures have merit in controlling the spread of the novel coronavirus? In this study, we develop a mathematical model to explore the effect of social distancing on new disease infections. Mathematical analyses of our model indicate that successful eradication of the disease is strongly dependent on the chosen preventive measure. Numerical computations of the model solution demonstrate that the ability to flatten the curve becomes easier as social distancing is strictly enforced. Based on our model, we also formulate an optimal control problem and solve it using Pontryagin's Maximum Principle and an efficient numerical iterative method. Our numerical results of an optimal 2019-nCoV treatment protocol that yields a minimum disease burden from this disease indicates that social distancing is vitally important.", "qid": 10, "docid": "qm2qvcwk", "rank": 90, "score": 0.7683939337730408}, {"content": "Title: Early Mandated Social Distancing is a Strong Predictor of Reduction in Highest Number of New COVID-19 cases per Day within Various Geographic Regions Content: Mandated social distancing has been globally applied to limit the spread of corona virus disease 2019 (COVID-19) from highly pathogenic severe acute respiratory syndrome (SARS) -associated coronavirus 2 (SARS-CoV-2). The benefit of this community-based intervention in limiting COVID-19 has not been proven nor quantified. We examined the effect of timing of mandated social distancing on the rate of COVID-19 in 119 geographic regions derived from 41 states within United States and 78 countries. We found that highest number of new COVID-19 cases per day per million persons was significantly associated with total number of COVID-19 cases per million persons on the day before mandated social distancing (Beta;=0.66, p<0.0001). Our findings suggest that the initiation of mandated social distancing for each doubling in number of existing COVID-19 cases would result in eventual peak with 58% higher number of COVID-19 infections per day. Subgroup analysis on those regions where the highest number of new COVID-19 cases per day have peaked increased Beta to .85 (p<0.0001). We demonstrate that initiating mandated social distancing at a 10 times smaller number of COVID-19 cases will reduce the number of daily new COVID-19 cases at peak by 80% highlighting the importance of this community-based intervention.", "qid": 10, "docid": "xcxjc3po", "rank": 91, "score": 0.7681336402893066}, {"content": "Title: Quantifying the impact of physical distance measures on the transmission of COVID-19 in the UK Content: BACKGROUND: To mitigate and slow the spread of COVID-19, many countries have adopted unprecedented physical distancing policies, including the UK. We evaluate whether these measures might be sufficient to control the epidemic by estimating their impact on the reproduction number (R0, the average number of secondary cases generated per case). METHODS: We asked a representative sample of UK adults about their contact patterns on the previous day. The questionnaire was conducted online via email recruitment and documents the age and location of contacts and a measure of their intimacy (whether physical contact was made or not). In addition, we asked about adherence to different physical distancing measures. The first surveys were sent on Tuesday, 24 March, 1 day after a \"lockdown\" was implemented across the UK. We compared measured contact patterns during the \"lockdown\" to patterns of social contact made during a non-epidemic period. By comparing these, we estimated the change in reproduction number as a consequence of the physical distancing measures imposed. We used a meta-analysis of published estimates to inform our estimates of the reproduction number before interventions were put in place. RESULTS: We found a 74% reduction in the average daily number of contacts observed per participant (from 10.8 to 2.8). This would be sufficient to reduce R0 from 2.6 prior to lockdown to 0.62 (95% confidence interval [CI] 0.37-0.89) after the lockdown, based on all types of contact and 0.37 (95% CI = 0.22-0.53) for physical (skin to skin) contacts only. CONCLUSIONS: The physical distancing measures adopted by the UK public have substantially reduced contact levels and will likely lead to a substantial impact and a decline in cases in the coming weeks. However, this projected decline in incidence will not occur immediately as there are significant delays between infection, the onset of symptomatic disease, and hospitalisation, as well as further delays to these events being reported. Tracking behavioural change can give a more rapid assessment of the impact of physical distancing measures than routine epidemiological surveillance.", "qid": 10, "docid": "fac4ic30", "rank": 92, "score": 0.7676815986633301}, {"content": "Title: Mathematical modeling of COVID-19 containment strategies with considerations for limited medical resources Content: The outbreak of SARS-CoV-2 in China has spread around the world, infecting millions and causing governments to implement strict policies to counteract the spread of the disease. One of the most effective strategies in reducing the severity of the pandemic is social distancing, where members of the population systematically reduce their interactions with others to limit the transmission rate of the virus. However, the implementation of social distancing can be difficult and costly, making it imperative that both policy makers and the citizenry understand the potential benefits if done correctly and the risks if not. In this work, a mathematical model is developed to study the effects of social distancing on the spread of the SARS-CoV-2 virus in Canada. The model is based upon a standard epidemiological SEIRD model that has been stratified to directly incorporate the proportion of individuals who are following social distancing protocols. The model parameters characterizing the disease are estimated from current epidemiological data on COVID-19 using machine learning techniques. The results of the model show that social distancing policies in Canada have already saved thousands of lives and that the prolonged adherence to social distancing guidelines could save thousands more. Importantly, our model indicates that social distancing can significantly delay the onset of infection peaks, allowing more time for the production of a vaccine or additional medical resources. Furthermore, our results stress the importance of easing social distancing restrictions gradually, rather than all at once, in order to prevent a second wave of infections. Model results are compared to the current capacity of the Canadian healthcare system by examining the current and future number of ventilators available for use, emphasizing the need for the increased production of additional medical resources.", "qid": 10, "docid": "51g3vhcx", "rank": 93, "score": 0.7675004005432129}, {"content": "Title: An analysis of the ethics of lockdown in India Content: Over the past 6 months, coronavirus-induced disease (COVID-19) has spread across 212 countries, affecting millions of people. As it has no known cure, social distancing is highly recommended for prevention of spread of the disease. Here, we have described the impact of the social distancing measures implemented by the Government of India on various sections of the society, especially the vulnerable sections. Furthermore, we have presented an analysis of these measures, according to the World Health Organization\u00b4s Guidance for Managing Ethical Issues in Infectious Disease Outbreaks (2016); we have also applied principles, as applicable, from the Indian Council of Medical Research\u2019s National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (2017). Finally, we have presented several measures that should have been adopted before and in addition to implementing the lockdown to improve its effectiveness.", "qid": 10, "docid": "qipttim3", "rank": 94, "score": 0.7673720121383667}, {"content": "Title: Pandemic, Shutdown and Consumer Spending: Lessons from Scandinavian Policy Responses to COVID-19 Content: This paper uses transaction data from a large bank in Scandinavia to estimate the effect of social distancing laws on consumer spending in the COVID-19 pandemic. The analysis exploits a natural experiment to disentangle the effects of the virus and the laws aiming to contain it: Denmark and Sweden were similarly exposed to the pandemic but only Denmark imposed significant restrictions on social and economic activities. We estimate that aggregate spending dropped by around 25 percent in Sweden and, as a result of the shutdown, by 4 additional percentage points in Denmark. This implies that most of the economic contraction is caused by the virus itself and occurs regardless of social distancing laws. The age gradient in the estimates suggest that social distancing reinforces the virus-induced drop in spending for low health-risk individuals but attenuates it for high-risk individuals by lowering the overall prevalence of the virus in the society.", "qid": 10, "docid": "jb57e0w6", "rank": 95, "score": 0.7673709988594055}, {"content": "Title: A simplified model for expected development of the SARS-CoV-2 (Corona) spread in Germany and US after social distancing Content: Widespread opinions and discussion exist regarding the efficiency of social distancing after crucial spread of the SARS-CoV-2 virus during the actual Covid-19 pandemic. While Germany has released a federal law that prohibits any type of direct contact for more than 2 people other countries including the US released curfews. People are now wondering whether these measures are helpful to stop or hamper the Covid-19 pandemic and to limit the spread of the new corona virus. A quantitative statement on this question depends on many parameters that are difficult to grasp mathematically and cannot therefore be made conclusively (they include consistent adherence to the measures decided, the estimated number of unreported cases, the possible limitation by test capacities, possible mutations of the virus, etc ...). However, it turns out that a reduction in the actual daily new infection rate (actual daily growth rate of reported cases, in short: infection rate) from the current value of 30-35% in the US to 10% would be extremely effective in stopping the spread of the virus. The severe restrictions in Germany which closed any public events, schools and universities a week ago might already have contributed to a reduction of the growth rate of reported cases below 30%.", "qid": 10, "docid": "0o79m08j", "rank": 96, "score": 0.7672920823097229}, {"content": "Title: Social Distancing as a Health Behavior: County-Level Movement in the United States During the COVID-19 Pandemic Is Associated with Conventional Health Behaviors Content: BACKGROUND: Social distancing\u2014when people limit close contact with others outside their household\u2014is a primary intervention available to combat the COVID-19 pandemic. The importance of social distancing is unlikely to change until effective treatments or vaccines become widely available. However, relatively little is known about how best to promote social distancing. Applying knowledge from social and behavioral research on conventional health behaviors (e.g., smoking, physical activity) to support public health efforts and research on social distancing is promising, but empirical evidence supporting this approach is needed. PURPOSE: We examined whether one type of social distancing behavior\u2014reduced movement outside the home\u2014was associated with conventional health behaviors. METHOD: We examined the association between GPS-derived movement behavior in 2,858 counties in USA from March 1 to April 7, 2020 and the prevalence of county-level indicators influenced by residents\u2019 conventional health behaviors. RESULTS: Changes in movement were associated with conventional health behaviors, and the magnitude of these associations were similar to the associations among the conventional health behaviors. Counties with healthier behaviors\u2014particularly less obesity and greater physical activity\u2014evidenced greater reduction in movement outside the home during the initial phases of the pandemic in the USA. CONCLUSIONS: Social distancing, in the form of reduced movement outside the home, is associated with conventional health behaviors. Existing scientific literature on health behavior and health behavior change can be more confidently used to promote social distancing behaviors during the COVID-19 pandemic.", "qid": 10, "docid": "rziqtdp0", "rank": 97, "score": 0.7663657665252686}, {"content": "Title: A Decision Analytic Approach for Social Distancing Policies During the COVID-19 Pandemic Content: The COVID-19 pandemic has become a crucial public health issue in many countries including the United States. In the absence of the right vaccine strain and sufficient antiviral stockpiles on hand, nonpharmaceutical interventions have become valuable public health tools at the early stages of the pandemic and they are employed by many countries across the globe. These interventions are designed to increase social distancing between individuals to reduce the transmission of the virus and eventually dampen the burden on the healthcare system. The virus transmissibility is a function of the average number of contacts individuals have in their communities and it is highly dependent on population density and daily mobility patterns, along with other social factors. These show significant variation across the United States. In this article, we study the effectiveness of social distancing measures in communities with different population density. Specifically, first we show how the empirical estimation of reproduction number differs for two completely different states, thus the experience of the COVID-19 outbreak is drastically different, suggesting different outbreak growth rates in practice. Second, we develop an age-structured compartmental model for simulating the disease spread to demonstrate the variation in the observed outbreak characteristics. We find that early trigger and late trigger options present a trade-off between the peak magnitude and the overall death toll of the outbreak which may also vary across different populations.", "qid": 10, "docid": "baq47reg", "rank": 98, "score": 0.7661170363426208}, {"content": "Title: Dynamical model for social distancing in the U.S. during the COVID-19 epidemic Content: Background Social distancing has led to a flattening of the curve in many states across the U.S. This is part of a novel, massive, global social experiment which has served to mitigate the pandemic in the absence of a vaccine or effective anti-viral drugs. Hence it is important to be able to forecast hospitalizations reasonably accurately. Methods We propose on phenomenological grounds a generalized diffusion equation which in- corporates the effect of social distancing to forecast the temporal evolution of the probability of having a given number of hospitalizations. The probability density function is log-normal in the number of hospitalizations, which is useful in describing pandemics where the number of hospital- izations is very high. Findings We used this insight and data to make forecasts for states using Monte Carlo methods. Back testing validates our approach, which yields good results about a week into the future. States are beginning to reopen at the time of publication and our forecasts indicate possible precursors of increased hospitalizations. Additionally we studied the reproducibility Ro in New York (Italian strain) and California (Wuhan strain). We find that even if there is a difference in the transmission of the two strains, social distancing has been able to control the progression of COVID 19. Funding None.", "qid": 10, "docid": "gkkvu8d5", "rank": 99, "score": 0.7660435438156128}, {"content": "Title: Impact of social distancing during COVID-19 pandemic on crime in Los Angeles and Indianapolis Content: Governments have implemented social distancing measures to address the ongoing COVID-19 pandemic. The measures include instructions that individuals maintain social distance when in public, school closures, limitations on gatherings and business operations, and instructions to remain at home. Social distancing may have an impact on the volume and distribution of crime. Crimes such as residential burglary may decrease as a byproduct of increased guardianship over personal space and property. Crimes such as domestic violence may increase because of extended periods of contact between potential offenders and victims. Understanding the impact of social distancing on crime is critical for ensuring the safety of police and government capacity to deal with the evolving crisis. Understanding how social distancing policies impact crime may also provide insights into whether people are complying with public health measures. Examination of the most recently available data from both Los Angeles, CA, and Indianapolis, IN, shows that social distancing has had a statistically significant impact on a few specific crime types. However, the overall effect is notably less than might be expected given the scale of the disruption to social and economic life.", "qid": 10, "docid": "po2c65nb", "rank": 100, "score": 0.765953779220581}]}
{"query": "what are the guidelines for triaging patients infected with coronavirus?", "hits": [{"content": "Title: Simple, fast and affordable triaging pathway for COVID-19 Content: Coronavirus disease 2019 has caused a global pandemic. The majority of patients will experience mild disease, but others will develop a severe respiratory infection that requires hospitalisation. This is causing a significant strain on health services. Patients are presenting at emergency departments with symptoms of dyspnoea, dry cough and fever with varying severity. The appropriate triaging of patients will assist in preventing health services becoming overwhelmed during the pandemic. This is assisted through clinical assessment and various imaging and laboratory investigations, including chest X-ray, blood analysis and identification of viral infection with SARS-CoV-2. Here, a succinct triaging pathway that aims to be fast, reliable and affordable is presented. The hope is that such a pathway will assist health services in appropriately combating the pandemic.", "qid": 11, "docid": "h1z8rg9p", "rank": 1, "score": 0.7934631705284119}, {"content": "Title: Simple, fast and affordable triaging pathway for COVID-19. Content: Coronavirus disease 2019 has caused a global pandemic. The majority of patients will experience mild disease, but others will develop a severe respiratory infection that requires hospitalisation. This is causing a significant strain on health services. Patients are presenting at emergency departments with symptoms of dyspnoea, dry cough and fever with varying severity. The appropriate triaging of patients will assist in preventing health services becoming overwhelmed during the pandemic. This is assisted through clinical assessment and various imaging and laboratory investigations, including chest X-ray, blood analysis and identification of viral infection with SARS-CoV-2. Here, a succinct triaging pathway that aims to be fast, reliable and affordable is presented. The hope is that such a pathway will assist health services in appropriately combating the pandemic.", "qid": 11, "docid": "ba5x3ysq", "rank": 2, "score": 0.7934631705284119}, {"content": "Title: Radiotherapeutic management of brain tumours during the COVID-19 pandemic Content: AIM: The coronavirus disease (COVID-19) pandemic is bound to put tremendous pressure on the existing healthcare system. This aim of this technical note is to help in triaging patients with brain tumours who are sent for radiotherapy during this pandemic and to provide safe and evidence-based care. MATERIALS AND METHODS: Published data for this review were identified by systematically searching PubMed database from November 2007 onwards with the following Medical Subject Heading (Mesh) terms \u2018Brain tumours\u2019, \u2018COVID-19\u2019, \u2018coronavirus\u2019, \u2018SARS-nCoV-2\u2019, \u2018Radiotherapy\u2019, \u2018Guidelines\u2019 \u2018hypofractionation\u2019 using Boolean search algorithm. Articles in English language were reviewed. RESULTS: We tried to apply the as low as reasonable achievable (ALARA) principle in triaging and management of patients for radiotherapy. We identified protocols which have hypofractionated regimens (reducing patient visits to hospital, time spent in treatment console) with similar outcomes when compared to conventional fractionated regimens and not overburdening the healthcare facility. We also identified the tumours for which we could safely avoid or delay the initiation of radiotherapy. CONCLUSION: Treatment decisions made during the COVID-19 pandemic rely on the safety first/do no harm principle and evidence-based prioritisation of cases for triage. This article is a tool to aid in triaging and prioritising brain tumour patient management. This is for consideration during the pandemic only and certainly not as a strategy for permanent practice change.", "qid": 11, "docid": "v8mprtro", "rank": 3, "score": 0.7741515040397644}, {"content": "Title: Ethics in the Covid-19 emergency: Examining rationing decisions Content: Early last month, the Italian Society of Anaesthesia was forced to publish the above guideline (1) for the country's hospitals. Besides the rising cases of infection, the doctors realised that patients required up to 15-20 days of intensive care as the disease progressed (2). In the face of medical resource scarcities, the guideline established that everyone could not be saved from the coronavirus. And a massive death toll ensued.", "qid": 11, "docid": "toe6sl0l", "rank": 4, "score": 0.7714605331420898}, {"content": "Title: Ethics in the Covid-19 emergency: Examining rationing decisions. Content: Early last month, the Italian Society of Anaesthesia was forced to publish the above guideline (1) for the country's hospitals. Besides the rising cases of infection, the doctors realised that patients required up to 15-20 days of intensive care as the disease progressed (2). In the face of medical resource scarcities, the guideline established that everyone could not be saved from the coronavirus. And a massive death toll ensued.", "qid": 11, "docid": "mbtunaef", "rank": 5, "score": 0.7714605331420898}, {"content": "Title: Urologic oncology surgery during COVID-19: a rapid review of current triage guidance documents Content: The Coronavirus Disease 2019 pandemic placed urologic surgeons, and especially urologic oncologists, in an unprecedented situation. Providers and healthcare systems were forced to rapidly create triage schemas in order to preserve resources and reduce potential viral transmission while continuing to provide care for patients. We reviewed United States and international triage proposals from professional societies, peer-reviewed publications, and publicly available institutional guidelines to identify common themes and critical differences. To date, there are varying levels of agreement on the optimal triaging of urologic oncology cases. As the need to preserve resources and prevent viral transmission grows, prioritizing only high priority surgical cases is paramount. A similar approach to prioritization will also be needed as nonemergent cases are allowed to proceed in the coming weeks. While these decisions will often be made on a case-by-case basis, more nuanced surgeon-driven consensus guidelines are needed for the near future.", "qid": 11, "docid": "f7i85959", "rank": 6, "score": 0.769485354423523}, {"content": "Title: Management of Adult Inpatient Otolaryngologic Consultations During the COVID-19 Pandemic: A Proposed Tier-Based Triage System Content: The coronavirus disease 2019 (COVID-19) pandemic has placed tremendous strain on health care systems, leading to unprecedented challenges and obstacles in the delivery of patient care. Otolaryngologists are frequently called on for inpatient consultations for an array of pathologies, ranging from chronic benign conditions to acutely life-threatening processes. Professional otolaryngologic societies across the world have proposed limiting patient care to time-sensitive and urgent matters; however, limited literature is available to describe how this transient change in philosophy may translate to clinical practice. Here we present a structured algorithm that allows for rapid triage of otolaryngologic consults during the ongoing pandemic, in efforts to minimize infectious spread and protect clinicians while preserving high-quality patient care. Considerations for managing these consults are presented, with a commentary on practical and ethical considerations.", "qid": 11, "docid": "t8mxjwzo", "rank": 7, "score": 0.767578125}, {"content": "Title: Management of Adult Inpatient Otolaryngologic Consultations During the COVID-19 Pandemic: A Proposed Tier-Based Triage System. Content: The coronavirus disease 2019 (COVID-19) pandemic has placed tremendous strain on health care systems, leading to unprecedented challenges and obstacles in the delivery of patient care. Otolaryngologists are frequently called on for inpatient consultations for an array of pathologies, ranging from chronic benign conditions to acutely life-threatening processes. Professional otolaryngologic societies across the world have proposed limiting patient care to time-sensitive and urgent matters; however, limited literature is available to describe how this transient change in philosophy may translate to clinical practice. Here we present a structured algorithm that allows for rapid triage of otolaryngologic consults during the ongoing pandemic, in efforts to minimize infectious spread and protect clinicians while preserving high-quality patient care. Considerations for managing these consults are presented, with a commentary on practical and ethical considerations.", "qid": 11, "docid": "z0wkr2cb", "rank": 8, "score": 0.767578125}, {"content": "Title: Triaging algorithm for Head & Neck oncology follow-up patients in COVID-19 climate Content: Abstract The current climate is one of uncertainty and immeasurable tragedy for people afflicted by the pandemic of SARS-CoV-2 virus infection. As professionals, we have a duty of care towards all patients especially the vulnerable and those suffering with life-threatening illnesses such as oral cancer. We present a safe & objective triaging method for afflicted with this disease in the prevailing morbid situation.", "qid": 11, "docid": "qjd31m8l", "rank": 9, "score": 0.7652950882911682}, {"content": "Title: Adult ICU Triage During the Coronavirus Disease 2019 Pandemic: Who Will Live and Who Will Die? Recommendations to Improve Survival Content: OBJECTIVES: Coronavirus disease 2019 patients are currently overwhelming the world's healthcare systems. This article provides practical guidance to front-line physicians forced to make critical rationing decisions. DATA SOURCES: PubMed and Medline search for scientific literature, reviews, and guidance documents related to epidemic ICU triage including from professional bodies. STUDY SELECTION: Clinical studies, reviews, and guidelines were selected and reviewed by all authors and discussed by internet conference and email. DATA EXTRACTION: References and data were based on relevance and author consensus. DATA SYNTHESIS: We review key challenges of resource-driven triage and data from affected ICUs. We recommend that once available resources are maximally extended, triage is justified utilizing a strategy that provides the greatest good for the greatest number of patients. A triage algorithm based on clinical estimations of the incremental survival benefit (saving the most life-years) provided by ICU care is proposed. \"First come, first served\" is used to choose between individuals with equal priorities and benefits. The algorithm provides practical guidance, is easy to follow, rapidly implementable and flexible. It has four prioritization categories: performance score, ASA score, number of organ failures, and predicted survival. Individual units can readily adapt the algorithm to meet local requirements for the evolving pandemic. Although the algorithm improves consistency and provides practical and psychologic support to those performing triage, the final decision remains a clinical one. Depending on country and operational circumstances, triage decisions may be made by a triage team or individual doctors. However, an experienced critical care specialist physician should be ultimately responsible for the triage decision. Cautious discharge criteria are proposed acknowledging the difficulties to facilitate the admission of queuing patients. CONCLUSIONS: Individual institutions may use this guidance to develop prospective protocols that assist the implementation of triage decisions to ensure fairness, enhance consistency, and decrease provider moral distress.", "qid": 11, "docid": "mu0g857x", "rank": 10, "score": 0.7651240825653076}, {"content": "Title: Adult ICU Triage During the Coronavirus Disease 2019 Pandemic: Who Will Live and Who Will Die? Recommendations to Improve Survival Content: OBJECTIVES: Coronavirus disease 2019 patients are currently overwhelming the world\u2019s healthcare systems. This article provides practical guidance to front-line physicians forced to make critical rationing decisions. DATA SOURCES: PubMed and Medline search for scientific literature, reviews, and guidance documents related to epidemic ICU triage including from professional bodies. STUDY SELECTION: Clinical studies, reviews, and guidelines were selected and reviewed by all authors and discussed by internet conference and email. DATA EXTRACTION: References and data were based on relevance and author consensus. DATA SYNTHESIS: We review key challenges of resource-driven triage and data from affected ICUs. We recommend that once available resources are maximally extended, triage is justified utilizing a strategy that provides the greatest good for the greatest number of patients. A triage algorithm based on clinical estimations of the incremental survival benefit (saving the most life-years) provided by ICU care is proposed. \u201cFirst come, first served\u201d is used to choose between individuals with equal priorities and benefits. The algorithm provides practical guidance, is easy to follow, rapidly implementable and flexible. It has four prioritization categories: performance score, ASA score, number of organ failures, and predicted survival. Individual units can readily adapt the algorithm to meet local requirements for the evolving pandemic. Although the algorithm improves consistency and provides practical and psychologic support to those performing triage, the final decision remains a clinical one. Depending on country and operational circumstances, triage decisions may be made by a triage team or individual doctors. However, an experienced critical care specialist physician should be ultimately responsible for the triage decision. Cautious discharge criteria are proposed acknowledging the difficulties to facilitate the admission of queuing patients. CONCLUSIONS: Individual institutions may use this guidance to develop prospective protocols that assist the implementation of triage decisions to ensure fairness, enhance consistency, and decrease provider moral distress.", "qid": 11, "docid": "x0me00m0", "rank": 11, "score": 0.7644397020339966}, {"content": "Title: Ethical Framework for Nutrition Support Resource Allocation During Shortages: Lessons From COVID-19 Content: The coronavirus disease 2019 (COVID-19) pandemic has impacted all aspects of our population. The \"Troubling Trichotomy\" of what can be done technologically, what should be done ethically, and what must be done legally is a reality during these unusual circumstances. Recent ethical considerations regarding allocation of scarce resources, such as mechanical ventilators, have been proposed. These can apply to other disciplines such as nutrition support, although decisions regarding nutrition support have a diminished potential for devastating outcomes. The principal values and goals leading to an ethical framework for a uniform, fair, and objective approach are reviewed in this article, with a focus on nutrition support. Some historical aspects of shortages in nutrition supplies and products during normal circumstances, as well as others during national crises, are outlined. The development and implementation of protocols using a scoring system seems best addressed by multidisciplinary ethics and triage committees with synergistic but disparate functions. Triage committees should alleviate the burdens of unilateral decisions by the healthcare team caring for patients. The treating team should make every attempt to have patients and the public at large update or execute/develop advance directives. Legal considerations, as the third component of the Troubling Trichotomy, are of some concern when rationing care. The likelihood that criminal or civil charges could be brought against individual healthcare professionals or institutions can be minimized, if fair protocols are uniformly applied and deliberations well documented.", "qid": 11, "docid": "2onxj1oe", "rank": 12, "score": 0.7642425894737244}, {"content": "Title: Recommendations for the organization of electrophysiology and cardiac pacing services during the COVID-19 pandemic: Latin American Heart Rhythm Society (LAHRS) in collaboration with: Colombian College Of Electrophysiology, Argentinian Society of Cardiac Electrophysiology (SADEC), Brazilian Society Of Cardiac Arrhythmias (SOBRAC), Mexican Society Of Cardiac Electrophysiology (SOMEEC) Content: COVID-19 is a rapidly evolving public health emergency that has largely impacted the provision of healthcare services around the world. The challenge for electrophysiology teams is double; on one side preventing disease spread by limiting all nonessential face-to-face interactions, but at the same time ensuring continued care for patients who need it. These guidelines contain recommendations regarding triaging in order to define what procedures, device checks and clinic visits can be postponed during the pandemic. We also discuss best practices to protect patients and healthcare workers and provide guidance for the management of COVID-19 patients with arrhythmic conditions.", "qid": 11, "docid": "wydt1ykq", "rank": 13, "score": 0.7642219066619873}, {"content": "Title: Recommendations for the organization of electrophysiology and cardiac pacing services during the COVID-19 pandemic : Latin American Heart Rhythm Society (LAHRS) in collaboration with: Colombian College Of Electrophysiology, Argentinian Society of Cardiac Electrophysiology (SADEC), Brazilian Society Of Cardiac Arrhythmias (SOBRAC), Mexican Society Of Cardiac Electrophysiology (SOMEEC) Content: COVID-19 is a rapidly evolving public health emergency that has largely impacted the provision of healthcare services around the world. The challenge for electrophysiology teams is double; on one side preventing disease spread by limiting all nonessential face-to-face interactions, but at the same time ensuring continued care for patients who need it. These guidelines contain recommendations regarding triaging in order to define what procedures, device checks and clinic visits can be postponed during the pandemic. We also discuss best practices to protect patients and healthcare workers and provide guidance for the management of COVID-19 patients with arrhythmic conditions.", "qid": 11, "docid": "7jxwn2y6", "rank": 14, "score": 0.7642219066619873}, {"content": "Title: Ethical Framework for Nutrition Support Resource Allocation During Shortages: Lessons From COVID\u201019 Content: The coronavirus disease (COVID\u201019) pandemic has impacted all aspects of our population. The \u201cTroubling Trichotomy\u201d of what can be done technologically, what should be done ethically, and what must be done legally is a reality during these unusual circumstances. Recent ethical considerations regarding allocation of scarce resources, such as mechanical ventilators, have been proposed. These can apply to other disciplines such as nutrition support, although decisions regarding nutrition support have a diminished potential for devastating outcomes. The principal values and goals leading to an ethical framework for a uniform, fair, and objective approach are reviewed in this article, with a focus on nutrition support. Some historical aspects of shortages in nutrition supplies and products during normal circumstances, as well as others during national crises, are outlined. The development and implementation of protocols using a scoring system seems best addressed by multidisciplinary ethics and triage committees with synergistic but disparate functions. Triage committees should alleviate the burdens of unilateral decisions by the healthcare team caring for patients. The treating team should make every attempt to have patients and the public at large update or execute/develop advance directives. Legal considerations, as the third component of the Troubling Trichotomy, are of some concern when rationing care. The likelihood that criminal or civil charges could be brought against individual healthcare professionals or institutions can be minimized, if fair protocols are uniformly applied and deliberations well documented.", "qid": 11, "docid": "w10y5sf9", "rank": 15, "score": 0.7629119157791138}, {"content": "Title: Recommendations for Dental Care during COVID-19 Pandemic. Content: Dental clinics were suspected to be a hotspot for nosocomial transmission of coronavirus disease 19 (COVID-19), yet there has been no clear recommendation about emergency dental care and appropriate personal protective equipment during pandemics. In this paper, we aim to summarize recommendations for (i) patient risk assessment, (ii) patient triage, and (iii) measures to prevent infection of health professionals and nosocomial transmission in dental clinics. The available evidence was collected by performing searches on PubMed, Embase, and Cochrane databases. We reviewed papers on COVID-19, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza, and related respiratory viral diseases. Legal and ethical frameworks, as well as international (e.g., World Health Organization (WHO)) and national (e.g., public health institutes, dental associations) guidelines were screened to summarize recommendations related to dental emergency care. To assess the patient risk, a questionnaire was developed to classify patients at unknown, high, and very high risk. Patient triage recommendations were summarized in a flow chart that graded the emergency level of treatments (i.e., urgent, as soon as possible, and postpone). Measures to prevent disease transmission based on current evidence were grouped for dental health professionals, dental clinics, and patients. The present recommendations may support health professionals implement preventative measures during the pandemic.", "qid": 11, "docid": "qqqu1adu", "rank": 16, "score": 0.7628424763679504}, {"content": "Title: Triaging algorithm for head & neck oncology follow-up patients in COVID-19 climate Content: The current climate is one of uncertainty and immeasurable tragedy for people afflicted by the pandemic of SARS-CoV-2 virus infection. As professionals, we have a duty of care towards all patients especially the vulnerable and those suffering with life-threatening illnesses such as oral cancer. We present a safe & objective triaging method for afflicted with this disease in the prevailing morbid situation.", "qid": 11, "docid": "26jxvscc", "rank": 17, "score": 0.7623846530914307}, {"content": "Title: Israel Ad Hoc COVID\u201019 Committee: Guidelines for Care of Older Persons During a Pandemic Content: Early on, geriatricians in Israel viewed with increasing alarm the spread of coronavirus disease 2019 (COVID\u201019). It was clear that this viral disease exhibited a clear predilection for and danger to older persons. Informal contacts began with senior officials from the country's Ministry of Health, the Israel Medical Association, and the country's largest health fund; this was done to plan an approach to the possible coming storm. A group was formed, comprising three senior geriatricians, a former dean, a palliative care specialist, and a lawyer/ethicist. The members made every effort to ensure that their recommendations would be practical while at the same time taking into account the tenets of medical ethics. The committee's main task was to think through a workable approach because intensive care unit/ventilator resources may be far outstripped by those requiring such care. Recommendations included the approach to older persons both in the community and in long\u2010term care institutions, a triage instrument, and palliative care. Patient autonomy was emphasized, with a strong recommendation for people of all ages to update their advance directives or, if they did not have any, to quickly draw them up. Considering the value of distributive justice, with respect to triage, a \u201csoft utilitarian\u201d approach was advocated with the main criteria being function and comorbidity. Although chronological age was rejected as a sole criterion, in the case of an overwhelming crisis, \u201cbiological age\u201d would enter into the triage considerations, but only in the case of distinguishing between people with equal non\u2013age\u2010related deficits. The guideline emphasized that no matter what, in the spirit of beneficence, anyone who fell ill must receive active palliative care throughout the course of a COVD\u201019 infection but especially at the end of life. Furthermore, in the spirit of nonmaleficence, the frail, very old, and severely demented would be actively protected from dying on ventilation.", "qid": 11, "docid": "lb099dyt", "rank": 18, "score": 0.7599568963050842}, {"content": "Title: Organising a COVID-19 Triage Unit: a Swiss Perspective. Content: BACKGROUND With the rapid global spread of the acute respiratory syndrome coronavirus 2, urgent health-care measures have been implemented. We describe the organizational process in setting up a coronavirus disease 2019 triage unit in a Swiss tertiary care hospital. METHODS Our triage unit was set-up outside of the main hospital building and consists of three areas: 1. Pre-triage, 2. Triage, and 3. Triage plus. The Pre-triage check-points identify any potential COVID-19-infected patients and re-direct them to the main Triage area where trained medical staff screen which patients undergo diagnostic testing. If testing is indicated, nasopharyngeal swabs are performed. If patients require further investigations, they are referred to Triage plus. At this stage, patients are then discharged home after additional testing or admitted to the hospital for management. OBSERVATIONS A total of 1,265 patients were screened between March 10th 2020 and April 12th 2020 at our Triage unit. Of these, 112 (8.9%) tested positive. 73 (65%) of the positively-tested patients were female and 39 (35%) were male. The mean age for all patients was 43.8 years (SD 16.3 years). Distinguishing between genders, mean age for females was 41.1 (SD 16.5) and mean age for males was 48.6 (SD 14.9), with females being significantly younger than males (p<0.001). CONCLUSION Our triage unit was set-up as part of a large-scale restructuring process. Current challenges include low sensitivity for test results as well as limited staff and resources. We hope that our experience will help other health care institutions develop similar triage systems.", "qid": 11, "docid": "lom4jdcj", "rank": 19, "score": 0.7581647038459778}, {"content": "Title: Israel Ad Hoc COVID-19 Committee: Guidelines for Care of Older Persons During a Pandemic Content: Early on, geriatricians in Israel viewed with increasing alarm the spread of coronavirus disease 2019 (COVID-19). It was clear that this viral disease exhibited a clear predilection for and danger to older persons. Informal contacts began with senior officials from the country's Ministry of Health, the Israel Medical Association, and the country's largest health fund; this was done to plan an approach to the possible coming storm. A group was formed, comprising three senior geriatricians, a former dean, a palliative care specialist, and a lawyer/ethicist. The members made every effort to ensure that their recommendations would be practical while at the same time taking into account the tenets of medical ethics. The committee's main task was to think through a workable approach because intensive care unit/ventilator resources may be far outstripped by those requiring such care. Recommendations included the approach to older persons both in the community and in long-term care institutions, a triage instrument, and palliative care. Patient autonomy was emphasized, with a strong recommendation for people of all ages to update their advance directives or, if they did not have any, to quickly draw them up. Considering the value of distributive justice, with respect to triage, a \"soft utilitarian\" approach was advocated with the main criteria being function and comorbidity. Although chronological age was rejected as a sole criterion, in the case of an overwhelming crisis, \"biological age\" would enter into the triage considerations, but only in the case of distinguishing between people with equal non-age-related deficits. The guideline emphasized that no matter what, in the spirit of beneficence, anyone who fell ill must receive active palliative care throughout the course of a COVD-19 infection but especially at the end of life. Furthermore, in the spirit of nonmaleficence, the frail, very old, and severely demented would be actively protected from dying on ventilation. J Am Geriatr Soc 68:1370-1375, 2020.", "qid": 11, "docid": "ce4p827u", "rank": 20, "score": 0.7573568820953369}, {"content": "Title: Best practice statements and recommendations for caring for critically ill patients with COVID-19 Content: SOURCE CITATION: Alhazzani W, M\u00f8ller MH, Arabi YM, et al. Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Crit Care Med. 2020;48:e440-69. 32224769.", "qid": 11, "docid": "hgtelbmy", "rank": 21, "score": 0.7568753361701965}, {"content": "Title: Ethical surgical triage of patients with head and neck cancer during the COVID\u201019 pandemic Content: BACKGROUND: Coronavirus has serially overtaken our metropolitan hospitals. At peak, patients with acute respiratory distress syndrome may outnumber mechanical ventilators. In our Miami Hospital System, COVID\u201019 cases have multiplied for 4 weeks and elective surgery has been suspended. METHODS: An Otolaryngologic Triage Committee was created to appropriately allocate resources to patients. Hospital ethicists provided support. Our tumor conference screened patients for nonsurgical options. Patients were tested twice for coronavirus before performing urgent contaminated operations. N95 masks and protective equipment were conserved when possible. Patients with low\u2010grade cancers were advised to delay surgery, and other difficult decisions were made. RESULTS: Hundreds of surgeries were canceled. Sixty\u2010five cases screened over 3 weeks are tabulated. Physicians and patients expressed discomfort regarding perceived deviations from standards, but risk of COVID\u201019 exposure tempered these discussions. CONCLUSIONS: We describe the use of actively managed surgical triage to fairly balance our patient's health with public health concerns.", "qid": 11, "docid": "sicjrsl4", "rank": 22, "score": 0.7557039260864258}, {"content": "Title: Management of gynecology patients during the coronavirus disease 2019 pandemic: Chinese expert consensus Content: Since December 2019, the outbreak of novel coronavirus disease 2019 became a major epidemic threat in China and later spread worldwide. During the coronavirus disease 2019 outbreak in mainland China, the Chinese Obstetricians and Gynecologists Association distributed guidelines regarding the care of gynecologic patients. These guidelines were developed by the Department of Obstetrics and Gynecology at the Peking Union Medical College Hospital and represent an effort to integrate infection control strategy and promote professionalism in medical practice. The guidelines represent collaboration with experts from 31 provinces and autonomous regions of mainland China over 2 weeks' time. With the implementation of these guidelines, no nosocomial infections of coronavirus disease 2019 have been identified at the Peking Union Medical College Hospital. We think these guidelines might be helpful to departments of obstetrics and gynecology internationally during these unprecedented times. In our guidelines, we describe basic infection precaution principles, an epidemiologic screening tool, prioritization of surgical procedures, and operating room requirements. Using these principles, we then review the management of gynecologic patients during the coronavirus disease 2019 epidemic in the outpatient and operative and nonoperative inpatient settings and in clinical trials.", "qid": 11, "docid": "qe46tqwi", "rank": 23, "score": 0.7549029588699341}, {"content": "Title: Protective measures for COVID-19 for healthcare providers and laboratory personnel Content: In the COVID-19 pandemic, which affects the whole world, healthcare professionals (HCP) are at high risk of transmission due to their direct contact with patients with COVID-19. Therefore, how to ensure the triage of the patient with acute respiratory symptoms should be determined in advance, the contact distance should be arranged to be at least 2 m, COVID-19 suspect or diagnosed patient should be instructed to wear a surgical mask. During the care of these patients, HCP should wear their personal protective equipment (PPE) in accordance with the procedure and should not neglect hand hygiene. The samples of the patient with known or suspected COVID-19, patient should also be known to be risky in terms of contamination, and a risk assessment should be performed for the procedures to be performed in laboratories. The PPE should be used in accordance with the procedure to be performed. The protection of the HCP, who sacrifice at the risk of life, is possible only by complying with infection control and precautions.", "qid": 11, "docid": "5ozpmq39", "rank": 24, "score": 0.7548826336860657}, {"content": "Title: Ethical surgical triage of patients with head and neck cancer during the COVID-19 pandemic Content: BACKGROUND: Coronavirus has serially overtaken our metropolitan hospitals. At peak, patients with acute respiratory distress syndrome may outnumber mechanical ventilators. In our Miami Hospital System, COVID-19 cases have multiplied for 4 weeks and elective surgery has been suspended. METHODS: An Otolaryngologic Triage Committee was created to appropriately allocate resources to patients. Hospital ethicists provided support. Our tumor conference screened patients for nonsurgical options. Patients were tested twice for coronavirus before performing urgent contaminated operations. N95 masks and protective equipment were conserved when possible. Patients with low-grade cancers were advised to delay surgery, and other difficult decisions were made. RESULTS: Hundreds of surgeries were canceled. Sixty-five cases screened over 3 weeks are tabulated. Physicians and patients expressed discomfort regarding perceived deviations from standards, but risk of COVID-19 exposure tempered these discussions. CONCLUSIONS: We describe the use of actively managed surgical triage to fairly balance our patient's health with public health concerns.", "qid": 11, "docid": "3qk0lwh0", "rank": 25, "score": 0.753523051738739}, {"content": "Title: Bronchoscopy, laryngoscopy, and esophagoscopy during the COVID-19 pandemic Content: BACKGROUND: The United States now has the highest death toll due to COVID-19. Many otolaryngology procedures, including laryngoscopy, bronchoscopy, and esophagoscopy, place otolaryngologists at increased risk of coronavirus transmission due to close contact with respiratory droplets and aerosolization from the procedure. The aim of this study is to provide an overview of guidelines on how to perform these procedures during the coronavirus pandemic. METHODS: Literature review was performed. Articles citing laryngoscopy, bronchoscopy, esophagoscopy use with regard to COVID-19 were included. RESULTS: Laryngoscopy, bronchoscopy, and esophagoscopy are all used in both emergent and elective situations. Understanding the risk stratification of cases and the varied necessity of personal protective equipment is important in protecting patients and health care workers. CONCLUSIONS: Summary guidelines based on the literature available at this time are presented in order to decrease transmission of the virus and protect those involved.", "qid": 11, "docid": "ofr967il", "rank": 26, "score": 0.752783477306366}, {"content": "Title: Bronchoscopy, laryngoscopy, and esophagoscopy during the COVID\u201019 pandemic Content: BACKGROUND: The United States now has the highest death toll due to COVID\u201019. Many otolaryngology procedures, including laryngoscopy, bronchoscopy, and esophagoscopy, place otolaryngologists at increased risk of coronavirus transmission due to close contact with respiratory droplets and aerosolization from the procedure. The aim of this study is to provide an overview of guidelines on how to perform these procedures during the coronavirus pandemic. METHODS: Literature review was performed. Articles citing laryngoscopy, bronchoscopy, esophagoscopy use with regard to COVID\u201019 were included. RESULTS: Laryngoscopy, bronchoscopy, and esophagoscopy are all used in both emergent and elective situations. Understanding the risk stratification of cases and the varied necessity of personal protective equipment is important in protecting patients and health care workers. CONCLUSIONS: Summary guidelines based on the literature available at this time are presented in order to decrease transmission of the virus and protect those involved.", "qid": 11, "docid": "yv8sosen", "rank": 27, "score": 0.7514533996582031}, {"content": "Title: Clinical Management of Adult Coronavirus Infection Disease 2019 (COVID-19) Positive in the Setting of Low and Medium Intensity of Care: a Short Practical Review Content: Coronavirus disease 2019 (COVID-2019) is a viral infection which is rapidly spreading on a global scale and causing a severe acute respiratory syndrome that affects today about four and a half million registered cases of people around the world. The aim of this narrative review is to provide an urgent guidance for the doctors who take care of these patients. Recommendations contained in this protocol are based on limited, non-definitive, evidence and experience-based opinions about patients with low and medium intensity of care. A short guidance on the management of COVID-19 is provided for an extensive use in different hospital settings. The evidence-based knowledge of COVID-19 is rapidly evolving, and we hope that, in the near future, a definitive and most efficacious treatment will be available including a specific vaccine for SARS-CoV-2.", "qid": 11, "docid": "5c6lwhno", "rank": 28, "score": 0.7513017654418945}, {"content": "Title: Pathways for urology patients during the COVID-19 pandemic. Content: The public health emergency caused by the Coronavirus Disease 2019 (COVID-19) pandemic has resulted in a significant reallocation of health resources with a consequent reorganization of the clinical activities also in several urological centers. A panel of Italian urologists has agreed on a set of recommendations on pathways of pre-, intra- and post-operative care for urological patients undergoing urgent procedures or non-deferrable oncological interventions during the COVID-19 pandemic. Simplification of the diagnostic and staging pathway has to be prioritized in order to reduce hospital visits and consequently the risk of contagion. In absence of strict uniform regulations that impose the implementation of nasopharyngeal swabs, we recommend that an accurate triage for possible COVID-19 symptoms be performed both by telephone at home before hospitalization and at the time of hospitalization. We recommend that during hospital stay patients should be provided with as many instructions as possible to facilitate their return to, and stay at, home. Patients should be discharged under stable good conditions in order to minimize the risk of readmission. It is advisable to reduce or reschedule post-discharge controls and implement an adequate system of communication for telemonitoring discharged patients in order to reduce hospital visits.", "qid": 11, "docid": "5p53e2cx", "rank": 29, "score": 0.750985324382782}, {"content": "Title: Best practice statements and recommendations for caring for critically ill patients with COVID-19. Content: SOURCE CITATION Alhazzani W, M\u00f8ller MH, Arabi YM, et al. Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Crit Care Med. 2020;48:e440-69. 32224769.", "qid": 11, "docid": "ui6sjl5h", "rank": 30, "score": 0.7507356405258179}, {"content": "Title: Clinical pathways for urology patients during the COVID-19 pandemic Content: The public health emergency caused by the Coronavirus Disease 2019 (COVID-19) pandemic has resulted in a significant reallocation of health resources with a consequent reorganization of the clinical activities also in several urological centers. A panel of Italian urologists has agreed on a set of recommendations on pathways of pre-, intra- and post-operative care for urological patients undergoing urgent procedures or non-deferrable oncological interventions during the COVID-19 pandemic. Simplification of the diagnostic and staging pathway has to be prioritized in order to reduce hospital visits and consequently the risk of contagion. In absence of strict uniform regulations that impose the implementation of nasopharyngeal swabs, we recommend that an accurate triage for COVID-19 symptoms be performed both by telephone at home before hospitalization and at the time of hospitalization. We recommend that during hospital stay patients should be provided with as many instructions as possible to facilitate their return to, and stay at, home. Patients should be discharged under stable good conditions in order to minimize the risk of readmission. It is advisable to reduce or reschedule post-discharge controls and implement an adequate system of communication for telemonitoring discharged patients.", "qid": 11, "docid": "j7s6504d", "rank": 31, "score": 0.7506973743438721}, {"content": "Title: Triaging patients in the outbreak of the 2019 novel coronavirus Content: In the end of 2019, the epidemic of a new coronavirus (SARS-CoV-2) occurred in Wuhan and spread rapidly. Changsha, a city located south to the epicenter, was soon impacted. To control the transmission of the coronavirus and avoid nosocomial infection, triage procedures based on epidemiology were implemented in a local hospital of the city. This retrospective study analyzed the data collected during the triage period and found that COVID-19 patients were enriched seven folds into the Section A designated for rapid detection and quarantine. On the other side, roughly triple amounts of visits were received at the Section B for patients without obvious epidemiological history. Eight COVID-19 cases were spotted out of 247 suspected patients. More than 50% of the suspected patients were submitted to multiple rounds of nucleic acid analysis for SARS-CoV-2 infection. Of the 239 patients who were diagnosed as negative of the virus infection,188 were successfully revisited and none was reported as a COVID-19 case. Of the eight COVID-19 patients, three were confirmed only after multiple rounds of nucleic acid analysis. Besides comorbidities, delayed sharing of epidemiological history added another layer of complexity to the diagnosis in practice. While SARS-CoV-2 epidemic is being alerted in many countries, our report will be helpful to other colleagues in rapid identification of COVID-19 cases and controlling the transmission of the disease.", "qid": 11, "docid": "tof0so67", "rank": 32, "score": 0.7503983378410339}, {"content": "Title: Cardiac Surgery During the Coronavirus Disease 2019 Pandemic: Perioperative Considerations and Triage Recommendations Content: The coronavirus disease 2019 pandemic, caused by severe acute respiratory syndrome coronavirus-2, represents the third human affliction attributed to the highly pathogenic coronavirus in the current century. Because of its highly contagious nature and unprecedented global spread, its aggressive clinical presentation, and the lack of effective treatment, severe acute respiratory syndrome coronavirus-2 infection is causing the loss of thousands of lives and imparting unparalleled strain on healthcare systems around the world. In the current report, we discuss perioperative considerations for patients undergoing cardiac surgery and provide clinicians with recommendations to effectively triage and plan these procedures during the coronavirus disease 2019 outbreak. This will help reduce the risk of exposure to patients and healthcare workers and allocate resources appropriately to those in greatest need. We include an algorithm for preoperative testing for coronavirus disease 2019, personal protective equipment recommendations, and a classification system to categorize and prioritize common cardiac surgery procedures.", "qid": 11, "docid": "2n3cdspj", "rank": 33, "score": 0.7498883008956909}, {"content": "Title: [Az aneszteziol\u00f3giai \u00e9s intenz\u00edv ell\u00e1t\u00e1s kih\u00edv\u00e1sai a COVID\u00ad19-fertoz\u00e9ssel kapcsolatban. Gyakorlati aj\u00e1nl\u00e1s]/ Challenges of intensive care and anesthesiology related to COVID-19 pandemic. Practical considerations Content: Due to the coronavirus epidemic, healthcare systems face growing challenges all around the world nowadays. These challenges are the most critical in the field of intensive treatment and anesthesiology. One of the most important prerequisites of effective critical care treatment is preserving the involved healthcare workers from the infection, by providing them with detailed practical advices on the preventive measures and treatment strategies. The aim of the present review is to summarize the most important related knowledge available from previous experiences. Orv Hetil. 2020; 161(17): 652\u00ad659.", "qid": 11, "docid": "6opn3o7a", "rank": 34, "score": 0.7494484782218933}, {"content": "Title: Safe management of bodies of deceased persons with suspected or confirmed COVID-19: a rapid systematic review Content: INTRODUCTION: Proper strategies to minimise the risk of infection in individuals handling the bodies of deceased persons infected with 2019 novel coronavirus (2019-nCoV) are urgently needed. The objective of this study was to systematically review the literature to scope and assess the effects of specific strategies for the management of the bodies. METHODS: We searched five general, three Chinese and four coronavirus disease (COVID-19)\u2013specific electronic databases. We searched registries of clinical trials, websites of governmental and other relevant organisations, reference lists of the included papers and relevant systematic reviews, and Epistemonikos for relevant systematic reviews. We included guidance documents providing practical advice on the handling of bodies of deceased persons with suspected or confirmed COVID-19. Then, we sought primary evidence of any study design reporting on the efficacy and safety of the identified strategies in coronaviruses. We included evidence relevant to contextual factors (ie, acceptability). A single reviewer extracted data using a pilot-tested form and graded the certainty of the evidence using the GRADE approach. A second reviewer verified the data and assessments. RESULTS: We identified one study proposing an uncommon strategy for autopsies for patients with severe acute respiratory syndrome. The study provided very low-certainty evidence that it reduced the risk of transmission. We identified 23 guidance documents providing practical advice on the steps of handling the bodies: preparation, packing, and others and advice related to both the handling of the dead bodies and the use of personal protective equipment by individuals handling them. We did not identify COVID-19 evidence relevant to any of these steps. CONCLUSION: While a substantive number of guidance documents propose specific strategies, we identified no study providing direct evidence for the effects of any of those strategies. While this review highlights major research gaps, it allows interested entities to build their own guidance.", "qid": 11, "docid": "x5a9k1n5", "rank": 35, "score": 0.7491865754127502}, {"content": "Title: Clinical Guidance for the Management of Patients with Urothelial Cancers During the COVID-19 Pandemic - Rapid Review Content: The current COVID-19 pandemic presents a substantial obstacle to cancer patient care. Data from China as well as risk models suppose that cancer patients, particularly those on active, immunosuppressive therapies are at higher risks of severe infection from the illness. In addition, staff illness and restructuring of services to deal with the crisis will inevitably place treatment capacities under significant strain. These guidelines aim to expand on those provided by NHS England regarding cancer care during the coronavirus pandemic by examining the known literature and provide guidance in managing patients with urothelial and rarer urinary tract cancers. In particular, they address the estimated risk and benefits of standard treatments and consider the alternatives in the current situation. As a result, it is recommended that this guidance will help form a framework for shared decision making with patients. Moreover, they do not advise a one-size-fits-all approach but recommend continual assessment of the situation with discussion within and between centres.", "qid": 11, "docid": "8n35gazc", "rank": 36, "score": 0.7489351630210876}, {"content": "Title: Safe management of bodies of deceased persons with suspected or confirmed COVID-19: a rapid systematic review Content: INTRODUCTION: Proper strategies to minimise the risk of infection in individuals handling the bodies of deceased persons infected with 2019 novel coronavirus (2019-nCoV) are urgently needed. The objective of this study was to systematically review the literature to scope and assess the effects of specific strategies for the management of the bodies. METHODS: We searched five general, three Chinese and four coronavirus disease (COVID-19)-specific electronic databases. We searched registries of clinical trials, websites of governmental and other relevant organisations, reference lists of the included papers and relevant systematic reviews, and Epistemonikos for relevant systematic reviews. We included guidance documents providing practical advice on the handling of bodies of deceased persons with suspected or confirmed COVID-19. Then, we sought primary evidence of any study design reporting on the efficacy and safety of the identified strategies in coronaviruses. We included evidence relevant to contextual factors (ie, acceptability). A single reviewer extracted data using a pilot-tested form and graded the certainty of the evidence using the GRADE approach. A second reviewer verified the data and assessments. RESULTS: We identified one study proposing an uncommon strategy for autopsies for patients with severe acute respiratory syndrome. The study provided very low-certainty evidence that it reduced the risk of transmission. We identified 23 guidance documents providing practical advice on the steps of handling the bodies: preparation, packing, and others and advice related to both the handling of the dead bodies and the use of personal protective equipment by individuals handling them. We did not identify COVID-19 evidence relevant to any of these steps. CONCLUSION: While a substantive number of guidance documents propose specific strategies, we identified no study providing direct evidence for the effects of any of those strategies. While this review highlights major research gaps, it allows interested entities to build their own guidance.", "qid": 11, "docid": "awitkrbg", "rank": 37, "score": 0.7489068508148193}, {"content": "Title: Considerations for cardiac catheterization laboratory procedures during the COVID-19 pandemic perspectives from the Society for Cardiovascular Angiography and Interventions Emerging Leader Mentorship (SCAI ELM) Members and Graduates Content: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly infectious, carries significant morbidity and mortality, and has rapidly resulted in strained health care system and hospital resources. In addition to patient-related care concerns in infected individuals, focus must also relate to diminishing community spread, protection of staff, case selection, and concentration of resources. The current document based on available data and consensus opinion addresses appropriate catheterization laboratory preparedness for treating these patients, including procedure-room readiness to minimize external contamination, safe donning and doffing of personal protective equipment (PPE) to eliminate risk to staff, and staffing algorithms to minimize exposure and maximize team availability. Case selection and management of both emergent and urgent procedures are discussed in detail, including procedures that may be safely deferred or performed bedside.", "qid": 11, "docid": "5veg78oy", "rank": 38, "score": 0.748717725276947}, {"content": "Title: Peri-operative and critical care concerns in coronavirus pandemic Content: World Health Organization (WHO) declared novel coronavirus outbreak a \u201cpandemic\u201d on March 11(th), 2020. India has already reached Stage 2 (local transmission) and the Indian Government, in collaboration with the Indian Council of Medical Research (ICMR), is taking all necessary steps to halt the community transmission(Stage 3). Anaesthesiologists and intensivists around the globe are making untiring efforts akin to soldiers at the final frontier during war. All efforts pertaining to adequate staffing, Personal Protective Equipment (PPE) and strict adherence to hand hygiene measures are being stressed upon to prevent in-hospital transmission. In this article, all outbreak response measures including triaging, preparation of isolation rooms, decontamination and disinfection protocols as well as fundamental principles of critical care and anaesthetic management in Covid-19 cases is being discussed. All the recommendations have been derived from the past experiences of SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome) outbreak as well as upcoming guidelines from the international health fraternity and Indian Health Services.", "qid": 11, "docid": "909chgl0", "rank": 39, "score": 0.7486883401870728}, {"content": "Title: Organizing a COVID-19 triage unit: a Swiss perspective Content: Background: With the rapid global spread of the acute respiratory syndrome coronavirus 2, urgent health-care measures have been implemented. We describe the organizational process in setting up a coronavirus disease 2019 triage unit in a Swiss tertiary care hospital. Methods: Our triage unit was set-up outside of the main hospital building and consists of three areas: 1. Pre-triage, 2. Triage, and 3. Triage plus. The Pre-triage check-points identify any potential COVID-19-infected patients and re-direct them to the main Triage area where trained medical staff screen which patients undergo diagnostic testing. If testing is indicated, nasopharyngeal swabs are performed. If patients require further investigations, they are referred to Triage plus. At this stage, patients are then discharged home after additional testing or admitted to the hospital for management. Observations: A total of 1265 patients were screened between 10 March 2020 and 12 April 2020 at our Triage unit. Of these, 112 (8.9%) tested positive. 73 (65%) of the positively-tested patients were female and 39 (35%) were male. The mean age for all patients was 43.8 years (SD 16.3 years). Distinguishing between genders, mean age for females was 41.1 (SD 16.5) and mean age for males was 48.6 (SD 14.9), with females being significantly younger than males (p < 0.001). Conclusion: Our triage unit was set-up as part of a large-scale restructuring process. Current challenges include low sensitivity for test results as well as limited staff and resources. We hope that our experience will help other health care institutions develop similar triage systems.", "qid": 11, "docid": "holb6bk3", "rank": 40, "score": 0.7481143474578857}, {"content": "Title: Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19) Content: BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines.", "qid": 11, "docid": "6al503af", "rank": 41, "score": 0.7479037046432495}, {"content": "Title: Safety of psychotropic medications in people with COVID-19: evidence review and practical recommendations Content: BACKGROUND: The novel coronavirus pandemic calls for a rapid adaptation of conventional medical practices to meet the evolving needs of such vulnerable patients. People with coronavirus disease (COVID-19) may frequently require treatment with psychotropic medications, but are at the same time at higher risk for safety issues because of the complex underlying medical condition and the potential interaction with medical treatments. METHODS: In order to produce evidence-based practical recommendations on the optimal management of psychotropic medications in people with COVID-19, an international, multi-disciplinary working group was established. The methodology of the WHO Rapid Advice Guidelines in the context of a public health emergency and the principles of the AGREE statement were followed. Available evidence informing on the risk of respiratory, cardiovascular, infective, hemostatic, and consciousness alterations related to the use of psychotropic medications, and drug\u2013drug interactions between psychotropic and medical treatments used in people with COVID-19, was reviewed and discussed by the working group. RESULTS: All classes of psychotropic medications showed potentially relevant safety risks for people with COVID-19. A set of practical recommendations was drawn in order to inform frontline clinicians on the assessment of the anticipated risk of psychotropic-related unfavorable events, and the possible actions to take in order to effectively manage this risk, such as when it is appropriate to avoid, withdraw, switch, or adjust the dose of the medication. CONCLUSIONS: The present evidence-based recommendations will improve the quality of psychiatric care in people with COVID-19, allowing an appropriate management of the medical condition without worsening the psychiatric condition and vice versa.", "qid": 11, "docid": "kjxnanke", "rank": 42, "score": 0.7463173866271973}, {"content": "Title: Update for Anaesthetists on Clinical Features of COVID-19 Patients and Relevant Management Content: When preparing for the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the coronavirus infection disease (COVID-19) questions arose regarding various aspects concerning the anaesthetist. When reviewing the literature it became obvious that keeping up-to-date with all relevant publications is almost impossible. We searched for and summarised clinically relevant topics that could help making clinical decisions. This is a subjective analysis of literature concerning specific topics raised in our daily practice (e.g., clinical features of COVID-19 patients; ventilation of the critically ill COVID-19 patient; diagnostic of infection with SARS-CoV-2; stability of the virus; Covid-19 in specific patient populations, e.g., paediatrics, immunosuppressed patients, patients with hypertension, diabetes mellitus, kidney or liver disease; co-medication with non-steroidal anti-inflammatory drugs (NSAIDs); antiviral treatment) and we believe that these answers help colleagues in clinical decision-making. With ongoing treatment of severely ill COVID-19 patients other questions will come up. While respective guidelines on these topics will serve clinicians in clinical practice, regularly updating all guidelines concerning COVID-19 will be a necessary, although challenging task in the upcoming weeks and months. All recommendations during the current extremely rapid development of knowledge must be evaluated on a daily basis, as suggestions made today may be out-dated with the new evidence available tomorrow.", "qid": 11, "docid": "cfqfchk4", "rank": 43, "score": 0.7462863922119141}, {"content": "Title: Physiotherapy Care of Patients with Coronavirus Disease 2019 (COVID-19) - A Brazilian Experience Content: Some patients with coronavirus disease (COVID-19) present with severe acute respiratory syndrome, which causes multiple organ dysfunction, besides dysfunction of the respiratory system, that requires invasive procedures. On the basis of the opinions of front-line experts and a review of the relevant literature on several topics, we proposed clinical practice recommendations on the following aspects for physiotherapists facing challenges in treating patients and containing virus spread: 1. personal protective equipment, 2. conventional chest physiotherapy, 3. exercise and early mobilization, 4. oxygen therapy, 5. nebulizer treatment, 6. non-invasive ventilation and high-flow nasal oxygen, 7. endotracheal intubation, 8. protective mechanical ventilation, 9. management of mechanical ventilation in severe and refractory cases of hypoxemia, 10. prone positioning, 11. cuff pressure, 12. tube and nasotracheal suction, 13. humidifier use for ventilated patients, 14. methods of weaning ventilated patients and extubation, and 15. equipment and hand hygiene. These recommendations can serve as clinical practice guidelines for physiotherapists. This article details the development of guidelines on these aspects for physiotherapy of patients with COVID-19.", "qid": 11, "docid": "2tbowk4n", "rank": 44, "score": 0.7457236051559448}, {"content": "Title: Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19) Content: BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06022-5) contains supplementary material, which is available to authorized users.", "qid": 11, "docid": "11sxecb3", "rank": 45, "score": 0.7454476952552795}, {"content": "Title: [Ethical guides, criteria for admission in intensive care, palliative care. Multi-society recommendations for allocation of resources during the COVID-19 pandemic]. Content: Guidelines on resource allocation, ethics, triage processes with admission and discharge criteria from critical care and palliative care units during the pandemia are here presented. The interdisciplinary and multi-society panel that prepared these guidelines represented by bioethicists and specialists linked to the end of life: clinicians, geriatricians, emergentologists, intensivists, and experts in palliative care and cardiopulmonary resuscitation. The available information indicates that approximately 80% of people with COVID-19 will develop mild symptoms and will not require hospital care, while 15% will require intermediate or general room care, and the remaining 5% will require assistance in intensive care units. The need to think about justice and establish ethical criteria for allocation patients arise in conditions of exceeding available resources, such as outbreaks of diseases and pandemics, with transparency being the main criterion for allocation. These guides recommend general criteria for the allocation of resources relies on bioethical considerations, rooted in Human Rights and based on the value of the dignity of the human person and substantial principles such as solidarity, justice and equity. The guides are recommendations of general scope and their usefulness is to accompany and sustain the technical and scientific decisions made by the different specialists in the care of critically ill patients, but given the dynamic nature of the pandemic, a process of permanent revision and adaptation of recommendations must be ensured.", "qid": 11, "docid": "x06ujgin", "rank": 46, "score": 0.7452003359794617}, {"content": "Title: Critical Care Clinician Reports on Coronavirus Disease 2019: Results From a National Survey of 4,875 ICU Providers Content: IMPORTANCE: Global cases of coronavirus disease 2019 infection continue to increase, and significant numbers of patients are critically ill, placing an immense burden on ICU resources. Understanding baseline resource needs and surge capacity in the ICU will be essential to meet current and projected healthcare needs. Continued appraisal of the state of readiness for healthcare systems at individual, regional and national levels will be paramount to ensure we are poised to continue the fight against coronavirus disease 2019. OBJECTIVES: This study queried U.S. ICU clinician perspectives on ICU preparedness and concerns regarding delivering coronavirus disease 2019 patient care. DESIGN, SETTING, AND PARTICIPANTS: An anonymous web-based survey administered from March 18, 2020, to March 25, 2020 (email and newsletter) used survey methodology to query members of U.S. national critical care organizations. MAIN OUTCOMES AND MEASURES: Through a 12-item descriptive questionnaire, ICU clinicians were assessed regarding preparedness, techniques employed to augment critical care capacity, and concerns related to caring for coronavirus disease 2019 patients. RESULTS: A total of 4,875 ICU clinicians responded to the survey. Respondents included ICU nurses (n = 3,470, 71.3%), physicians (n = 664, 13.6%), advanced practice providers (nurse practitioners and physician assistants; n = 334, 6.9%), respiratory therapists (n = 236, 4.9%), and pharmacists (n = 79, 1.6%). Over half (n = 2,552, 52.5%) reported having cared for a presumed or confirmed coronavirus disease 2019 patient. The majority (n = 4,010, 82.9%) identified that their hospital was employing techniques to augment critical care capacity. However, 64.5% (n = 3,125) believed that their ICU facility and team were inadequately prepared to treat coronavirus disease 2019 patients. The majority (n = 4,547, 93.9%) anticipated ICU personal protective equipment shortages based upon their current use profile. The chief reported concerns include ICU resource shortages such as supplies, medications, beds, ICU staffing shortages, and patient surge leading to overcrowding. CONCLUSIONS AND RELEVANCE: This national ICU clinician survey indicates that hospitals are expanding ICU bed capacity to prepare for coronavirus disease 2019 patient surge. Importantly, amid this preparation, ICU clinicians harbor concerns regarding preparedness, staffing, and common use resources that merit specific education as well as resource allocation and utilization planning.", "qid": 11, "docid": "5au34a97", "rank": 47, "score": 0.7449028491973877}, {"content": "Title: Clinical Guidance for the Management of Patients with Urothelial Cancers During the COVID-19 Pandemic \u2013 Rapid Review Content: Abstract The current COVID-19 pandemic presents a substantial obstacle to cancer patient care. Data from China as well as risk models suppose that cancer patients, particularly those on active, immunosuppressive therapies are at higher risks of severe infection from the illness. In addition, staff illness and restructuring of services to deal with the crisis will inevitably place treatment capacities under significant strain. These guidelines aim to expand on those provided by NHS England regarding cancer care during the coronavirus pandemic by examining the known literature and provide guidance in managing patients with urothelial and rarer urinary tract cancers. In particular, they address the estimated risk and benefits of standard treatments and consider the alternatives in the current situation. As a result, it is recommended that this guidance will help form a framework for shared decision making with patients. Moreover, they do not advise a one-size-fits-all approach but recommend continual assessment of the situation with discussion within and between centres.", "qid": 11, "docid": "67pfen3n", "rank": 48, "score": 0.7446457147598267}, {"content": "Title: A Practical Approach to the Management of Cancer Patients During the Novel Coronavirus Disease 2019 (COVID\u201019) Pandemic: An International Collaborative Group Content: The outbreak of coronavirus disease 2019 (COVID\u201019) has rapidly spread globally since being identified as a public health emergency of major international concern and has now been declared a pandemic by the World Health Organization (WHO). In December 2019, an outbreak of atypical pneumonia, known as COVID\u201019, was identified in Wuhan, China. The newly identified zoonotic coronavirus, severe acute respiratory syndrome coronavirus\u20102 (SARS\u2010CoV\u20102), is characterized by rapid human\u2010to\u2010human transmission. Many cancer patients frequently visit the hospital for treatment and disease surveillance. They may be immunocompromised due to the underlying malignancy or anticancer therapy and are at higher risk of developing infections. Several factors increase the risk of infection, and cancer patients commonly have multiple risk factors. Cancer patients appear to have an estimated twofold increased risk of contracting SARS\u2010CoV\u20102 than the general population. With the WHO declaring the novel coronavirus outbreak a pandemic, there is an urgent need to address the impact of such a pandemic on cancer patients. This include changes to resource allocation, clinical care, and the consent process during a pandemic. Currently and due to limited data, there are no international guidelines to address the management of cancer patients in any infectious pandemic. In this review, the potential challenges associated with managing cancer patients during the COVID\u201019 infection pandemic will be addressed, with suggestions of some practical approaches. IMPLICATIONS FOR PRACTICE: The main management strategies for treating cancer patients during the COVID\u201019 epidemic include clear communication and education about hand hygiene, infection control measures, high\u2010risk exposure, and the signs and symptoms of COVID\u201019. Consideration of risk and benefit for active intervention in the cancer population must be individualized. Postponing elective surgery or adjuvant chemotherapy for cancer patients with low risk of progression should be considered on a case\u2010by\u2010case basis. Minimizing outpatient visits can help to mitigate exposure and possible further transmission. Telemedicine may be used to support patients to minimize number of visits and risk of exposure. More research is needed to better understand SARS\u2010CoV\u20102 virology and epidemiology.", "qid": 11, "docid": "d5tr12h9", "rank": 49, "score": 0.7443479299545288}, {"content": "Title: A protocol of infection control for mechanical thrombectomy in possible COVID-19 patients: Tokai university COVID-19 manual Content: The crisis of the coronavirus disease (COVID-19) is causing damage to the social and medical community. However, extreme emergency neuro-interventions such as mechanical thrombectomy still require the healthcare workers to offer the appropriate treatment while preventing further spread of the infection. This article outlines the necessary steps in managing a possible COVID-19 patient starting from patient screening to personnel infection and environmental contamination measures.", "qid": 11, "docid": "k7nwmldn", "rank": 50, "score": 0.7443015575408936}, {"content": "Title: A Practical Approach to the Management of Cancer Patients During the Novel Coronavirus Disease 2019 (COVID-19) Pandemic: An International Collaborative Group Content: The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread globally since being identified as a public health emergency of major international concern and has now been declared a pandemic by the World Health Organization (WHO). In December 2019, an outbreak of atypical pneumonia, known as COVID-19, was identified in Wuhan, China. The newly identified zoonotic coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is characterized by rapid human-to-human transmission. Many cancer patients frequently visit the hospital for treatment and disease surveillance. They may be immunocompromised due to the underlying malignancy or anticancer therapy and are at higher risk of developing infections. Several factors increase the risk of infection, and cancer patients commonly have multiple risk factors. Cancer patients appear to have an estimated twofold increased risk of contracting SARS-CoV-2 than the general population. With the WHO declaring the novel coronavirus outbreak a pandemic, there is an urgent need to address the impact of such a pandemic on cancer patients. This include changes to resource allocation, clinical care, and the consent process during a pandemic. Currently and due to limited data, there are no international guidelines to address the management of cancer patients in any infectious pandemic. In this review, the potential challenges associated with managing cancer patients during the COVID-19 infection pandemic will be addressed, with suggestions of some practical approaches. IMPLICATIONS FOR PRACTICE: The main management strategies for treating cancer patients during the COVID-19 epidemic include clear communication and education about hand hygiene, infection control measures, high-risk exposure, and the signs and symptoms of COVID-19. Consideration of risk and benefit for active intervention in the cancer population must be individualized. Postponing elective surgery or adjuvant chemotherapy for cancer patients with low risk of progression should be considered on a case-by-case basis. Minimizing outpatient visits can help to mitigate exposure and possible further transmission. Telemedicine may be used to support patients to minimize number of visits and risk of exposure. More research is needed to better understand SARS-CoV-2 virology and epidemiology.", "qid": 11, "docid": "zqzsgekj", "rank": 51, "score": 0.744202196598053}, {"content": "Title: Emergency management of 2019 novel coronavirus: implications for the dermatology department Content: Since cases first emerged in December 2019, COVID\u201019 (a type of coronavirus) has rapidly become pandemic. This fast\u2010tracked paper (published quickly) from China on COVID\u201019 is written by dermatologists at the epicentre of the outbreak in Wuhan. Dermatology clinic staff may be at risk because protective equipment is not routinely available, and skin lesions might possibly transmit the virus indirectly. These authors suggest preventive measures based on experience in this and previous coronavirus outbreaks. Online consultation for non\u2010urgent patients reduces the numbers of patients attending clinics. Nurse\u2010led triage, to identify patients with possible COVID\u201019, at the entrances of hospital and skin clinics directs patients with a cough or fever to a specific COVID\u201019 area and a dermatologist is consulted if the fever might be related to skin disease. Clinic staff wear N95 masks and observe hand hygiene during consultations. Patients are admitted to a ward only if routine blood tests and chest CT scans exclude COVID\u201019. Triage will not detect patients who are showing no symptoms but who are developing the disease, so the hospital should provide an on\u2010call expert team to discuss inpatients suspected or diagnosed with COVID\u201019 and refer them to radiology, respiratory or intensive care colleagues as required. Confirmed cases are managed following local policies. Skin disorders in COVID\u201019 inpatients can usually be managed remotely using photographs, email and teleconferencing. If necessary a multidisciplinary team (a team of medical staff from different specialties) can meet in the clean area of the isolation ward. If the dermatologist must see the patient, all records should be provided in advance to minimise exposure time. With these precautions, as of 20th February 2020 no infected patients were detected in the Wuhan Dermatology Department. This is a summary of the study: Emergency management for preventing and controlling nosocomial infection of 2019 novel coronavirus: implications for the dermatology department", "qid": 11, "docid": "amk3ll70", "rank": 52, "score": 0.7439489960670471}, {"content": "Title: Ethical aspects of the COVID-19 crisis: How to deal with an overwhelming shortage of acute beds Content: The current outbreak of SARS-CoV-2 has and continues to put huge pressure on intensive care units (ICUs) worldwide. Many patients with COVID-19 require some form of respiratory support and often have prolonged ICU stays, which results in a critical shortage of ICU beds. It is therefore not always physically possible to treat all the patients who require intensive care, raising major ethical dilemmas related to which patients should benefit from the limited resources and which should not. Here we consider some of the approaches to the acute shortages seen during this and other epidemics, including some guidelines for triaging ICU admissions and treatments.", "qid": 11, "docid": "bpnxkc7a", "rank": 53, "score": 0.7438366413116455}, {"content": "Title: A Systematic Review on Guidelines and Recommendations for Urology Standard of Care During the COVID-19 Pandemic Content: CONTEXT: The first case of the new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), was identified in Wuhan, China, in late 2019. Since then, the coronavirus disease 2019 (COVID-19) outbreak was reclassified as a pandemic, and health systems around the world have faced an unprecedented challenge. OBJECTIVE: To summarize guidelines and recommendations on the urology standard of care during the COVID-19 pandemic. EVIDENCE ACQUISITION: Guidelines and recommendations published between November 2019 and April 17, 2020 were retrieved using MEDLINE, EMBASE, and CINAHL. This was supplemented by searching the web pages of international urology societies. Our inclusion criteria were guidelines, recommendations, or best practice statements by international urology organizations and reference centers about urological care in different phases of the COVID-19 pandemic. Our systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Of 366 titles identified, 15 guidelines met our criteria. EVIDENCE SYNTHESIS: Of the 15 guidelines, 14 addressed emergency situations and 12 reported on assessment of elective uro-oncology procedures. There was consensus on postponing radical prostatectomy except for high-risk prostate cancer, and delaying treatment for low-grade bladder cancer, small renal masses up to T2, and stage I seminoma. According to nine guidelines that addressed endourology, obstructed or infected kidneys should be decompressed, whereas nonobstructing stones and stent removal should be rescheduled. Five guidelines/recommendations discussed laparoscopic and robotic surgery, while the remaining recommendations focused on outpatient procedures and consultations. All recommendations represented expert opinions, with three specifically endorsed by professional societies. Only the European Association of Urology guidelines provided evidence-based levels of evidence (mostly level 3 evidence). CONCLUSIONS: To make informed decisions during the COVID-19 pandemic, there are multiple national and international guidelines and recommendations for urologists to prioritize the provision of care. Differences among the guidelines were minimal. PATIENT SUMMARY: We performed a systematic review of published recommendations on urological practice during the coronavirus disease 2019 (COVID-19) pandemic, which provide guidance on prioritizing the timing for different types of urological care.", "qid": 11, "docid": "xml1vgwp", "rank": 54, "score": 0.7437161207199097}, {"content": "Title: Indian resuscitation council (IRC) suggested guidelines for comprehensive cardiopulmonary life support (CCLS) for suspected or confirmed coronavirus disease (COVID-19) patient Content: Management of the recent outbreak of the novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) remains challenging. The challenges are not only limited to its preventive strategies, but also extend to curative treatment, and are amplified during the management of critically ill patients with COVID-19. Older persons with comorbidities like diabetes mellitus, cardiac diseases, hepatic impairment, renal disorders and respiratory pathologies or immune impairing conditions are more vulnerable and have a higher mortality from COVID-19. Earlier, the Indian Resuscitation Council (IRC) had proposed the Comprehensive Cardiopulmonary Life Support (CCLS) for management of cardiac arrest victims in the hospital setting. However, in patients with COVID-19, the guidelines need to be modified,due to various concerns like differing etiology of cardiac arrest, virulence of the virus, risk of its transmission to rescuers, and the need to avoid or minimize aerosolization from the patient due to various interventions. There is limited evidence in these patients, as the SARS-CoV-2 is a novel infection and not much literature is available with high-level evidence related to CPR in patients of COVID-19. These suggested guidelines are a continuum of CCLS guidelines by IRC with an emphasis on the various challenges and concerns being faced during the resuscitative management of COVID-19 patients with cardiopulmonary arrest.", "qid": 11, "docid": "0j3qaxg0", "rank": 55, "score": 0.7436891198158264}, {"content": "Title: Triage of Scarce Critical Care Resources in COVID-19 An Implementation Guide for Regional Allocation: An Expert Panel Report of the Task Force for Mass Critical Care and the American College of Chest Physicians Content: Public health emergencies have the potential to place enormous strain on health systems. The current pandemic of the novel 2019 coronavirus disease has required hospitals in numerous countries to expand their surge capacity to meet the needs of patients with critical illness. When even surge capacity is exceeded, however, principles of critical care triage may be needed as a means to allocate scarce resources, such as mechanical ventilators or key medications. The goal of a triage system is to direct limited resources towards patients most likely to benefit from them. Implementing a triage system requires careful coordination between clinicians, health systems, local and regional governments, and the public, with a goal of transparency to maintain trust. We discuss the principles of tertiary triage and methods for implementing such a system, emphasizing that these systems should serve only as a last resort. Even under triage, we must uphold our obligation to care for all patients as best possible under difficult circumstances.", "qid": 11, "docid": "hlwcr2uh", "rank": 56, "score": 0.7435809373855591}, {"content": "Title: Urologie in der Corona-Virus-Pandemie \u00ad Leitfaden 4/20./ [Urology in the corona-virus pandemic-a guideline 4/20] Content: The coronavirus pandemic is a major challenge for healthcare systems worldwide. For urology, the expansion of the health-care structures for the treatment of patients suffering from COVID-19 should be supported as best as possible. At the same time, one should aim to ensure adequate care for urological emergencies and urgent urological treatments as far as possible, even during the pandemic. For this, patients must be prioritized individually, alternative therapy concepts must be considered and regional and supraregional cooperation must be used. Outpatient departments are of great importance in the care, examination and coordination of urological emergencies and urgent treatment. Urological clinics must prepare themselves to perform urgent operations and interventions on SARS-CoV\u00ad2-positive patients. Here, the creation of a separate, appropriately equipped emergency operating room to perform operations and interventions on SARS-CoV\u00ad2 patients should be considered. Furthermore strictly defined hygiene measures to protect employees in various clinical scenarios should be set up.", "qid": 11, "docid": "qqwu9cfd", "rank": 57, "score": 0.7433240413665771}, {"content": "Title: Screening and managing of suspected or confirmed novel coronavirus (COVID-19) patients: experiences from a tertiary hospital outside Hubei province Content: Objectives: To report our experiences screening and managing patients with suspected or confirmed novel coronavirus (COVID-19) disease using a hospital-specific protocol. Design: Longitudinal cohort study. Setting: A 1,200 bed tertiary care teaching hospital in Chengdu, Sichuan, China. Participants: 802 adults presenting to hospital with concerns of having COVID-19, 1,246 inpatients and 2,531 hospital visitors. Interventions: Screening and management of patients using a hospital-specific protocol, which included fever triage, monitoring visitors and patients, emergency response, personnel training for healthcare team members, health education for patients and family, medical materials management, disinfection and wastes disposal protocols. Results: Between 23 January and 28 February 2020, 73 people were identified as having fever plus respiratory signs with/without a history of exposure and were tested for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by our hospital lab using RT PCR. Forty-five of these 73 people were subsequently excluded based on one negative RT PCR result plus positive results to quick screening tests for flu or other respiratory viruses. The remaining 28 people received a second RT PCR test 24 h later. Three people were confirmed positive for COVID-19 based on two consecutive positive RT PCR tests whilst 25 people were excluded based on two consecutive negative tests. The three COVID-19 confirmed cases received non-critical care. There were no new infections of medical staff or new infections of other hospital inpatients. Conclusions: All three cases were detected as a result of vigilant monitoring of hospital visitors. Whilst screening out-patients presenting to a fever clinic remains important, monitoring visitors must not be overlooked.", "qid": 11, "docid": "nz02frdm", "rank": 58, "score": 0.7431924343109131}, {"content": "Title: Orthopaedic Guidelines for the COVID-19 Post-Outbreak Period: Experience from Wuhan, People's Republic of China Content: Currently, the coronavirus disease 2019 (COVID-19) crisis has rapidly spread worldwide. As the earliest outbreak area of the pandemic, Wuhan, People's Republic of China, is gradually recovering to its normal state under the effective control of government authorities. Outpatient services in major hospitals are now being restored. An accumulation of asymptomatic infections is a potential risk for medical personnel, especially when there is crowding in hospitals. As the biggest center for orthopaedic patients in Wuhan, our orthopaedic outpatient department admits >300 patients per day. Optimal guidelines on how to handle this huge number of patients during the post-outbreak stage of the COVID-19 pandemic, particularly with regard to potential asymptomatic infection, are urgently needed for orthopaedic surgeons. We have developed and proposed applicable guidelines to fill this knowledge gap, including the necessary protective strategies for medical personnel in orthopaedic outpatient and inpatient wards as well as during surgery. We also have provided mental health recommendations for health-care workers. To the best of our knowledge, these guidelines are the first of their kind for orthopaedic surgeons who are slowly reestablishing medical activity following the pandemic.", "qid": 11, "docid": "w3e6ul3v", "rank": 59, "score": 0.7430841326713562}, {"content": "Title: Orthopaedic Guidelines for the COVID-19 Post-Outbreak Period: Experience from Wuhan, People's Republic of China. Content: Currently, the coronavirus disease 2019 (COVID-19) crisis has rapidly spread worldwide. As the earliest outbreak area of the pandemic, Wuhan, People's Republic of China, is gradually recovering to its normal state under the effective control of government authorities. Outpatient services in major hospitals are now being restored. An accumulation of asymptomatic infections is a potential risk for medical personnel, especially when there is crowding in hospitals. As the biggest center for orthopaedic patients in Wuhan, our orthopaedic outpatient department admits >300 patients per day. Optimal guidelines on how to handle this huge number of patients during the post-outbreak stage of the COVID-19 pandemic, particularly with regard to potential asymptomatic infection, are urgently needed for orthopaedic surgeons. We have developed and proposed applicable guidelines to fill this knowledge gap, including the necessary protective strategies for medical personnel in orthopaedic outpatient and inpatient wards as well as during surgery. We also have provided mental health recommendations for health-care workers. To the best of our knowledge, these guidelines are the first of their kind for orthopaedic surgeons who are slowly reestablishing medical activity following the pandemic.", "qid": 11, "docid": "i1o9tbkm", "rank": 60, "score": 0.7430841326713562}, {"content": "Title: Breast Cancer Management Guidelines During COVID-19 Pandemic Content: The coronavirus disease (COVID-19) pandemic in 2020 has brought about complex challenges in healthcare delivery. With the new rules of lockdown and social distancing and with resources diverted to the management of COVID-19, there are difficulties in continuing usual cancer care. Patients are at risk of contracting COVID-19 with a high chance of patient to healthcare transmission and vice versa. Hospital visits, investigations and all modalities of treatment have potential complications that put patients at risk, some more than others. In this situation, there is a need to change our approach in the management of breast cancer to deliver it safely. We present modified guidelines based on the available consensus statements and evidence.", "qid": 11, "docid": "cgdrcjfq", "rank": 61, "score": 0.7421120405197144}, {"content": "Title: Optimal Management of Acute Lymphoblastic Leukemia (ALL) in Adult Patients During the Novel Coronavirus Disease 2019 (COVID-19) Pandemic Content: The outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency of major international concern. In December 2019, an outbreak of atypical pneumonia known as COVID-19 was identified in Wuhan, China. The newly identified zoonotic coronavirus, severe acute respiratory syndrome coronavirus-2 (SARSCoV-2), is characterized by rapid human-to-human transmission. Acute lymphoblastic leukemia (ALL) patients are often in need for intensive chemotherapy to induce remission that will be complicated with prolonged period of cytopenias. They are often recalled to the hospital for treatment and disease surveillance. These patients may be immunocompromised due to the underlying malignancy or anti-cancer therapy. ALL patients are at higher risk of developing life-threatening infections. Several factors increase the risk of infection and the presence of multiple risk factors in the same patient is common. Cancer patients had an estimated 2-fold increased risk of contracting SARS-CoV-2 than the general population. With the World Health Organization declaring the novel coronavirus outbreak a pandemic, there is an urgent need to address the impact of such pandemic on ALL patients. This include changes to resource allocation, clinical care, and the consent process during a pandemic. Currently and due to limited data, there are no international guidelines to address the optimal management of ALL patients in any infectious pandemic. In this review, we will address the potential challenges associated with managing ALL patients during the COVID-19 infection pandemic with suggestions of some practical approaches, focusing on screening asymptomatic ALL patients, diagnostic and response evaluation and choice of chemotherapy in different scenarios and setting and use of hematopoietic stem cell transplantation (HSCT).", "qid": 11, "docid": "snorvtez", "rank": 62, "score": 0.7420321702957153}, {"content": "Title: Optimal Management of Acute Lymphoblastic Leukemia (ALL) in Adult Patients During the Novel Coronavirus Disease 2019 (COVID-19) Pandemic. Content: The outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency of major international concern. In December 2019, an outbreak of atypical pneumonia known as COVID-19 was identified in Wuhan, China. The newly identified zoonotic coronavirus, severe acute respiratory syndrome coronavirus-2 (SARSCoV-2), is characterized by rapid human-to-human transmission. Acute lymphoblastic leukemia (ALL) patients are often in need for intensive chemotherapy to induce remission that will be complicated with prolonged period of cytopenias. They are often recalled to the hospital for treatment and disease surveillance. These patients may be immunocompromised due to the underlying malignancy or anti-cancer therapy. ALL patients are at higher risk of developing life-threatening infections. Several factors increase the risk of infection and the presence of multiple risk factors in the same patient is common. Cancer patients had an estimated 2-fold increased risk of contracting SARS-CoV-2 than the general population. With the World Health Organization declaring the novel coronavirus outbreak a pandemic, there is an urgent need to address the impact of such pandemic on ALL patients. This include changes to resource allocation, clinical care, and the consent process during a pandemic. Currently and due to limited data, there are no international guidelines to address the optimal management of ALL patients in any infectious pandemic. In this review, we will address the potential challenges associated with managing ALL patients during the COVID-19 infection pandemic with suggestions of some practical approaches, focusing on screening asymptomatic ALL patients, diagnostic and response evaluation and choice of chemotherapy in different scenarios and setting and use of hematopoietic stem cell transplantation (HSCT).", "qid": 11, "docid": "fayle15h", "rank": 63, "score": 0.7420320510864258}, {"content": "Title: Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19) Content: BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.", "qid": 11, "docid": "tj8fxw94", "rank": 64, "score": 0.7418251037597656}, {"content": "Title: Dead body management amidst global pandemic of Covid-19 Content: Covid-19 has reached almost all the nations in the world. More and more people are dying from it and in some countries, even the army has been called upon to help dispose of the dead as there is a shortage of coffins, and undertakers are overwhelmed. Therefore, it is essential to have measures in place to contain the spread of infection while handling dead bodies. In view of this, different guidelines and protocols have been proposed bearing in mind the limited information we have about the virus. This review article sets them out for better reference.", "qid": 11, "docid": "hom14b7d", "rank": 65, "score": 0.7417909502983093}, {"content": "Title: Dead body management amidst global pandemic of Covid-19. Content: Covid-19 has reached almost all the nations in the world. More and more people are dying from it and in some countries, even the army has been called upon to help dispose of the dead as there is a shortage of coffins, and undertakers are overwhelmed. Therefore, it is essential to have measures in place to contain the spread of infection while handling dead bodies. In view of this, different guidelines and protocols have been proposed bearing in mind the limited information we have about the virus. This review article sets them out for better reference.", "qid": 11, "docid": "i9budov6", "rank": 66, "score": 0.7417908310890198}, {"content": "Title: Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19) Content: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.", "qid": 11, "docid": "kqrkzvay", "rank": 67, "score": 0.7412924766540527}, {"content": "Title: Urologie in der Corona-Virus-Pandemie \u2013 Leitfaden 4/20 Content: The coronavirus pandemic is a major challenge for healthcare systems worldwide. For urology, the expansion of the health-care structures for the treatment of patients suffering from COVID-19 should be supported as best as possible. At the same time, one should aim to ensure adequate care for urological emergencies and urgent urological treatments as far as possible, even during the pandemic. For this, patients must be prioritized individually, alternative therapy concepts must be considered and regional and supraregional cooperation must be used. Outpatient departments are of great importance in the care, examination and coordination of urological emergencies and urgent treatment. Urological clinics must prepare themselves to perform urgent operations and interventions on SARS-CoV\u20112-positive patients. Here, the creation of a separate, appropriately equipped emergency operating room to perform operations and interventions on SARS-CoV\u20112 patients should be considered. Furthermore strictly defined hygiene measures to protect employees in various clinical scenarios should be set up.", "qid": 11, "docid": "nxcmf2l4", "rank": 68, "score": 0.7411887645721436}, {"content": "Title: A Novel Cohorting and Isolation Strategy for Suspected COVID-19 Cases during a Pandemic Content: INTRODUCTION: The COVID-19 pandemic presents a significant infection prevention and control challenge. The admission of large numbers of patients with suspected COVID-19 disease risks overwhelming the capacity to protect other patients from exposure. The delay between clinical suspicion and confirmatory testing adds to the complexity of the problem. METHODS: We implemented a triage tool aimed at minimising hospital acquired COVID-19 particularly to patients at risk of severe disease. Patients were allocated to triage categories defined by likelihood of COVID-19 and risk of a poor outcome. Category A (low-likelihood; high-risk), B (high-likelihood; high-risk), C (high-likelihood; low-risk) and D (low-likelihood; low-risk). This determined the order of priority for isolation in single-occupancy rooms with Category A the highest. Patients in other groups were cohorted when isolation capacity was limited with additional interventions to reduce transmission. RESULTS: 93 patients were evaluated with 79 (85%) receiving a COVID-19 diagnosis during their admission. Of those without a COVID-19 diagnosis: 10 were initially triaged to Category A; 0 to B; 1 to C and 4 to D. All high risk patients requiring isolation were, therefore, admitted to single-occupancy rooms and protected from exposure. 28 (30%) suspected COVID-19 patients were evaluated to be low risk (groups C & D) and eligible for cohorting. No symptomatic hospital acquired infections were detected in the cohorted patients. DISCUSSION: Application of a clinical triage tool to guide isolation and cohorting decisions may reduce the risk of hospital acquired transmission of COVID-19 especially to individuals at the greatest of risk of severe disease.", "qid": 11, "docid": "sglgo6hy", "rank": 69, "score": 0.7411206960678101}, {"content": "Title: Caring for Critically Ill Adults With Coronavirus Disease 2019 in a PICU: Recommendations by Dual Trained Intensivists Content: OBJECTIVE: In the midst of the severe acute respiratory syndrome coronavirus 2 pandemic, which causes coronavirus disease 2019, there is a recognized need to expand critical care services and beds beyond the traditional boundaries. There is considerable concern that widespread infection will result in a surge of critically ill patients that will overwhelm our present adult ICU capacity. In this setting, one proposal to add \"surge capacity\" has been the use of PICU beds and physicians to care for these critically ill adults. DESIGN: Narrative review/perspective. SETTING: Not applicable. PATIENTS: Not applicable. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The virus's high infectivity and prolonged asymptomatic shedding have resulted in an exponential growth in the number of cases in the United States within the past weeks with many (up to 6%) developing acute respiratory distress syndrome mandating critical care services. Coronavirus disease 2019 critical illness appears to be primarily occurring in adults. Although pediatric intensivists are well versed in the care of acute respiratory distress syndrome from viral pneumonia, the care of differing aged adult populations presents some unique challenges. In this statement, a team of adult and pediatric-trained critical care physicians provides guidance on common \"adult\" issues that may be encountered in the care of these patients and how they can best be managed in a PICU. CONCLUSIONS: This concise scientific statement includes references to the most recent and relevant guidelines and clinical trials that shape management decisions. The intention is to assist PICUs and intensivists in rapidly preparing for care of adult coronavirus disease 2019 patients should the need arise.", "qid": 11, "docid": "fije7qyo", "rank": 70, "score": 0.7408772706985474}, {"content": "Title: Managing Oncology Services During a Major Coronavirus Outbreak: Lessons From the Saudi Arabia Experience Content: Outbreaks of infectious etiology, particularly those caused by a novel virus that has no known treatment or vaccine, may result in the interruption of medical care provided to patients with cancer and put them at risk for undertreatment in addition to the risk of being exposed to infection, a life-threatening event among patients with cancer. This article describes the approach used to manage patients with cancer during a large-scale Middle East respiratory syndrome\u2013coronavirus hospital outbreak in Saudi Arabia to ensure continuity of care and minimize harm from treatment interruption or acquiring infection. The approach taken toward managing this high-risk situation (COVID-19) could be easily adopted by health care organizations and would be helpful to ensure readiness for the occurrence of future outbreaks of different infectious etiologies like those recent episodes of new coronavirus.", "qid": 11, "docid": "7e8dwcur", "rank": 71, "score": 0.740427553653717}, {"content": "Title: Managing Oncology Services During a Major Coronavirus Outbreak: Lessons From the Saudi Arabia Experience Content: Outbreaks of infectious etiology, particularly those caused by a novel virus that has no known treatment or vaccine, may result in the interruption of medical care provided to patients with cancer and put them at risk for undertreatment in addition to the risk of being exposed to infection, a life-threatening event among patients with cancer. This article describes the approach used to manage patients with cancer during a large-scale Middle East respiratory syndrome-coronavirus hospital outbreak in Saudi Arabia to ensure continuity of care and minimize harm from treatment interruption or acquiring infection. The approach taken toward managing this high-risk situation (COVID-19) could be easily adopted by health care organizations and would be helpful to ensure readiness for the occurrence of future outbreaks of different infectious etiologies like those recent episodes of new coronavirus.", "qid": 11, "docid": "tvslcuqq", "rank": 72, "score": 0.7400792241096497}, {"content": "Title: Point-of-Care Procedures in Physiatry: Practice Considerations During the Covid-19 Pandemic Content: Coronavirus disease 2019 is an active pandemic that has required rapid conversion of practice patterns to mitigate disease spread. Although recommendations have been released for physicians to postpone elective procedures, the utility of common physiatry procedures and their infectious risk profile have yet to be clearly delineated. In this article, we describe an update on existing national recommendations and outline considerations as practitioners and institutions strive to meet the needs of patients with disabilities.", "qid": 11, "docid": "uyw8t1fy", "rank": 73, "score": 0.7396748065948486}, {"content": "Title: Guidelines for the management of surgical departments in non-uniform hospitals during the COVID-19 pandemic Content: In the last several weeks we have been witnessing the exponentially progressing pandemic SARS-CoV-2 coronavirus. As the number of people infected with SARS-CoV2 escalates, the problem of surgical management of patients requiring urgent surgery is increasing. Patients infected with SARS-CoV2 virus but with negative test results will appear in general hospitals and may pose a risk to other patients and hospital staff. Health care workers constitutes nearly 17% of infected population in Poland, therefore early identification of infected people becomes a priority to protect human resources and to ensure continuity of the access to a surgical care. Both surgical operations, and endoscopic procedures are considered as interventions with an increased risk of infection. Therefore, determining the algorithm becomes crucial for qualifying patients for surgical treatment, but also to stratify the risk of personnel being infected during surgery and to adequately protect staff. Each hospital should be logistically prepared for the need to perform urgent surgery on a patient with suspected or confirmed infection, including personal protective equipment. Limited availability of the equipment, working under pressure and staff shortages in addition to a highly contagious pathogen necessitate a pragmatic management of human resources in health care. Instant synchronized action is needed, and clear uniform guidelines are essential for the healthcare system to provide citizens with the necessary surgical care while protecting both patients, and staff. This document presents current recommendations regarding surgery during the COVID-19 pandemic in Poland.", "qid": 11, "docid": "p5h752r6", "rank": 74, "score": 0.739313542842865}, {"content": "Title: Guidelines for the management of surgical departments in non-uniform hospitals during the COVID-19 pandemic. Content: In the last several weeks we have been witnessing the exponentially progressing pandemic SARS-CoV-2 coronavirus. As the number of people infected with SARS-CoV2 escalates, the problem of surgical management of patients requiring urgent surgery is increasing. Patients infected with SARS-CoV2 virus but with negative test results will appear in general hospitals and may pose a risk to other patients and hospital staff. Health care workers constitutes nearly 17% of infected population in Poland, therefore early identification of infected people becomes a priority to protect human resources and to ensure continuity of the access to a surgical care. Both surgical operations, and endoscopic procedures are considered as interventions with an increased risk of infection. Therefore, determining the algorithm becomes crucial for qualifying patients for surgical treatment, but also to stratify the risk of personnel being infected during surgery and to adequately protect staff. Each hospital should be logistically prepared for the need to perform urgent surgery on a patient with suspected or confirmed infection, including personal protective equipment. Limited availability of the equipment, working under pressure and staff shortages in addition to a highly contagious pathogen necessitate a pragmatic management of human resources in health care. Instant synchronized action is needed, and clear uniform guidelines are essential for the healthcare system to provide citizens with the necessary surgical care while protecting both patients, and staff. This document presents current recommendations regarding surgery during the COVID-19 pandemic in Poland.", "qid": 11, "docid": "kbyf6u49", "rank": 75, "score": 0.739313542842865}, {"content": "Title: Practical Considerations for Solid Organ Transplantation During the COVID-19 Global Outbreak: The Experience from Singapore Content: The current coronavirus disease 2019 (COVID-19) pandemic has not only caused global social disruptions but has also put tremendous strain on healthcare systems worldwide. With all attention and significant effort diverted to containing and managing the COVID-19 outbreak (and understandably so), essential medical services such as transplant services are likely to be affected. Closure of transplant programs in an outbreak caused by a highly transmissible novel pathogen may be inevitable owing to patient safety. Yet program closure is not without harm; patients on the transplant waitlist may die before the program reopens. By adopting a tiered approach based on outbreak disease alert levels, and having hospital guidelines based on the best available evidence, life-saving transplants can still be safely performed. We performed a lung transplant and a liver transplant successfully during the COVID-19 era. We present our guidelines and experience on managing the transplant service as well as the selection and management of donors and recipients. We also discuss clinical dilemmas in the management COVID-19 in the posttransplant recipient.", "qid": 11, "docid": "1ewe5upg", "rank": 76, "score": 0.7392884492874146}, {"content": "Title: Considerations for Management of Acute Coronary Syndromes During the SARS-CoV-2 (COVID-19) Pandemic Content: Accumulating evidence suggests that influenza and influenza-like illnesses can act as a trigger for acute myocardial infarction (AMI). Despite these unprecedented times providers should not overlook ACS guidelines, but may choose to modify the recommended approach in situations with confirmed or suspected COVID-19 disease. In this document, we suggest recommendations as to how to triage patients diagnosed with acute coronary syndromes (ACS) and provide with algorithms of how to manage the patients and decide the appropriate treatment options in the era of COVID-19 pandemic. We also address the inpatient logistics and discharge to follow-up considerations for the function of already established ACS network during the pandemic.", "qid": 11, "docid": "ro20ibaq", "rank": 77, "score": 0.7381887435913086}, {"content": "Title: Surgery in times of COVID-19\u2014recommendations for hospital and patient management Content: BACKGROUND: The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has escalated rapidly to a global pandemic stretching healthcare systems worldwide to their limits. Surgeons have had to immediately react to this unprecedented clinical challenge by systematically repurposing surgical wards. PURPOSE: To provide a detailed set of guidelines developed in a surgical ward at University Hospital Wuerzburg to safely accommodate the exponentially rising cases of SARS-CoV-2 infected patients without compromising the care of emergency surgery and oncological patients or jeopardizing the well-being of hospital staff. CONCLUSIONS: The dynamic prioritization of SARS-CoV-2 infected and surgical patient groups is key to preserving life while maintaining high surgical standards. Strictly segregating patient groups in emergency rooms, non-intensive care wards and operating areas prevents viral spread while adequately training and carefully selecting hospital staff allow them to confidently and successfully undertake their respective clinical duties.", "qid": 11, "docid": "547q3vf6", "rank": 78, "score": 0.7380286455154419}, {"content": "Title: Surgery in times of COVID-19-recommendations for hospital and patient management Content: BACKGROUND: The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has escalated rapidly to a global pandemic stretching healthcare systems worldwide to their limits. Surgeons have had to immediately react to this unprecedented clinical challenge by systematically repurposing surgical wards. PURPOSE: To provide a detailed set of guidelines developed in a surgical ward at University Hospital Wuerzburg to safely accommodate the exponentially rising cases of SARS-CoV-2 infected patients without compromising the care of emergency surgery and oncological patients or jeopardizing the well-being of hospital staff. CONCLUSIONS: The dynamic prioritization of SARS-CoV-2 infected and surgical patient groups is key to preserving life while maintaining high surgical standards. Strictly segregating patient groups in emergency rooms, non-intensive care wards and operating areas prevents viral spread while adequately training and carefully selecting hospital staff allow them to confidently and successfully undertake their respective clinical duties.", "qid": 11, "docid": "2rldos9q", "rank": 79, "score": 0.7380286455154419}, {"content": "Title: Medically Necessary, Time-Sensitive Procedures: Scoring System to Ethically and Efficiently Manage Resource Scarcity and Provider Risk During the COVID-19 Pandemic Content: Hospitals have severely curtailed the performance of nonurgent surgical procedures in anticipation of the need to redeploy healthcare resources to meet the projected massive medical needs of patients with coronavirus disease 2019 (COVID-19). Surgical treatment of non-COVID-19 related disease during this period, however, still remains necessary. The decision to proceed with medically necessary, time-sensitive (MeNTS) procedures in the setting of the COVID-19 pandemic requires incorporation of factors (resource limitations, COVID-19 transmission risk to providers and patients) heretofore not overtly considered by surgeons in the already complicated processes of clinical judgment and shared decision-making. We describe a scoring system that systematically integrates these factors to facilitate decision-making and triage for MeNTS procedures, and appropriately weighs individual patient risks with the ethical necessity of optimizing public health concerns. This approach is applicable across a broad range of hospital settings (academic and community, urban and rural) in the midst of the pandemic and may be able to inform case triage as operating room capacity resumes once the acute phase of the pandemic subsides.", "qid": 11, "docid": "u63upcz0", "rank": 80, "score": 0.7379018068313599}, {"content": "Title: Approach to Endoscopic Procedures: A Routine Protocol from a Quaternary University Referral Center Exclusively for Coronavirus Disease 2019 Patients Content: OBJECTIVES: The present coronavirus disease (COVID-19) pandemic has ushered in an unprecedented era of quality control that has necessitated advanced safety precautions and the need to ensure the adequate protection of healthcare professionals (HCPs). Endoscopy units, endoscopists, and other HCP may be at a significant risk for transmission of the virus. Given the immense burden on the healthcare system and surge in the number of patients with COVID-19, well-designed protocols and recommendations are needed. We aimed to systematically characterize our approach to endoscopic procedures in a quaternary university hospital setting and provide summary protocol recommendations. METHOD: This descriptive study details a COVID-19-specific protocol designed to minimize infection risks to patients and healthcare workers in the endoscopy unit. RESULTS: Our institution, located in S\u00e3o Paulo, Brazil, includes a 900-bed hospital, with a 200-bed-specific intensive care unit exclusively designed for patients with moderate and severe COVID-19. We highlighted recommendations for infection prevention and control during endoscopic procedures, including appropriate triage and screening, outpatient management and procedural recommendations, role and usage of personal protective equipment (PPE), and role and procedural logistics involving COVID-19-positive patients. We also detailed hospital protocols for reprocessing endoscopes and cleaning rooms and also provided recommendations to minimize severe acute respiratory syndrome coronavirus 2 transmission. CONCLUSION: This COVID-19-specific administrative and clinical protocol can be replicated or adapted in multiple institutions and endoscopy units worldwide. Furthermore, the recommendations and summary protocol may improve patient and HCP safety in these trying times.", "qid": 11, "docid": "8p8i4z18", "rank": 81, "score": 0.7378381490707397}, {"content": "Title: COVID-19 Pandemic: Consensus guidelines for preferred practices in an aesthetic clinic Content: Strict infection control measures in response to the current COVID-19 pandemic are expected to remain for an extended period. In aesthetic clinics, most procedures are provided on one to one basis by the physician or therapist. In such a scenario, guidelines detailing the infection control measures for aesthetic clinics are of particular importance. An online meeting of an international group of experts in the field of aesthetic medicine, with experience in administration of an aesthetic clinic, was convened. The meeting aimed to provide a set of consensus guidelines to protect clinic staff and patients from SARS-CoV-2 infection. Consensus guidelines for \"preferred practices\" were provided for scheduling of patients, patient evaluation and triaging, and for safety precautions about the different procedures. Procedures were categorized into low-risk, moderate risk, and high-risk based on the likelihood of transmission of SARS-CoV-2 virus from the patient to the treating physician or therapist. While not intended to be complete or exhaustive, these guidelines provide sound infection control measures for aesthetic practices. Since guidelines regarding safety measures and use of PPEs may vary from country to country, the local guidelines should also be followed to prevent COVID-19 infection in aesthetic clinics.", "qid": 11, "docid": "h822qpja", "rank": 82, "score": 0.7375280857086182}, {"content": "Title: COVID-19 Guidance for Triage of Operations for Thoracic Malignancies: A Consensus Statement from Thoracic Surgery Outcomes Research Network Content: Abstract The extraordinary demands of managing the COVID-19 pandemic has disrupted the world\u2019s ability to care for patients with thoracic malignancies. As a hospital\u2019s COVID-19 population increases and hospital resources are depleted, the ability to provide surgical care is progressively restricted - forcing surgeons to prioritize among their cancer populations. Representatives from multiple cancer, surgical and research organizations have come together to provide a guide for triaging patients with thoracic malignancies, as the impact of COVID-19 evolves as each hospital.", "qid": 11, "docid": "qyh1vkgi", "rank": 83, "score": 0.7373884916305542}, {"content": "Title: Multidisciplinary approach to COVID-19 and cancer: consensus from scientific societies in Argentina Content: INTRODUCTION: The world is living through an outbreak of an acute respiratory syndrome caused by a new betacoronavirus known as coronavirus 2 (SARS CoV-2), which has been declared an international public health emergency by the World Health Organisation. Cancer patients are a very special population in this setting since they are more susceptible to viral infections than the general population. Several recommendations have been made on this issue, most of them based on expert opinion and institutional experience. It is essential to gather the evidence available for decision making. OBJECTIVE: To review the evidence available in order to create a multi-institutional position from the perspective of scientific societies in Argentina involved in the management of cancer patients. METHODOLOGY: The review included two phases: 1) search and systematic revision of the medical literature; 2) consensus and revision of the document drafted by national scientific societies involved in the management and care of cancer patients using the modified Delphi method. The final results were presented at a videoconference with all the participants. Also, additional comment and recommendations were discussed. The final document was revised and approved for publication by the members of the panel. RESULTS: The consensus panel included 18 representatives from scientific societies from Argentina who assessed the evidence and then made recommendations for the management of cancer patients in our country. International guidelines (CDC; ASCO, NCCN and ESMO) were considered as a background for analysis, as well as institutional guidelines and an open ad hoc survey administered to 114 healthcare professionals from the scientific societies involved in this study. The recommendations are grouped as follows: 1) general care interventions\u2014training of the personnel, cleaning and disinfection of the hospital premises and patient scheduling; 2) treatment decisions\u2014patient care, surgeries, immunosuppressive therapy, radiotherapy and screening; 3) ethical considerations\u2014optimisation of resources, end-of-life care for critically-ill patients; 4) management of hospitalised patients; and 5) wellbeing of the healthcare team. The general recommendation arising from the study is that the management of cancer patients must adapt to the exceptional pandemic status quo without disregarding treatment or cure options. Moreover, healthcare professional accompaniment of all patients should not be neglected. All healthcare professionals must make a significant joint effort to create multidisciplinary teams to discuss the most appropriate measures for each particular situation. CONCLUSIONS: The scientific evidence available on this topic worldwide is in progress. This together with the epidemiologically shifting scenario poses unprecedented challenges in the management of cancer amidst this global pandemic. Furthermore, the key role of the healthcare structural organisation appears evident, such as the drafting of clear guidelines for all the stakeholders, adaptability to constant change and an interdisciplinary shared vision through consensus to provide adequate care to our cancer patients in the light of uncertainty and fast-paced change.", "qid": 11, "docid": "ddulfe06", "rank": 84, "score": 0.7366899251937866}, {"content": "Title: Atenci\u00f3n de pacientes oftalmol\u00f3gicos durante la pandemia COVID-19: revisi\u00f3n panor\u00e1mica r\u00e1pida./ Atenci\u00f3n de pacientes oftalmol\u00f3gicos durante la pandemia COVID-19: revisi\u00f3n panor\u00e1mica r\u00e1pida./ Care of ophthalmological patients during the COVID-19 pandemic: A rapid scoping review Content: Introduction: A new type of coronavirus (SARS-CoV-2) causes a respiratory distress syndrome that has been called COVID-19 and has generated an unprecedented pandemic. Serious complications include pneumonia, and mortality ranges from 2 to 5%. Until March 26, the World Health Organization reports 462 684 confirmed cases and 20 834 deaths worldwide. Dissemination occurs from aerosols or respiratory droplets. Different scientific societies have published clinical practice guidelines regarding ophthalmic care in the COVID-19 pandemic, but the information is presented inconsistently, which makes decision-making difficult. Methods: We conducted a sensitive bibliographic search in EMBASE and ophthalmic society webpages, of the clinical practice guidelines of ophthalmic care in pandemic COVID-19. We extracted the recommendations, organizing them into three categories: \"Which patients to attend\", \"How should the clinic work\", and \"What interventions should be avoided\". For each guideline, we assessed whether the search was systematic and whether the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was followed. Results: Fourteen relevant articles were found. Fifty-one recommendations were extracted and are shown in a summary table. None are based on a systematic search for evidence, nor do any use GRADE to develop the recommendations. Conclusions: The clinical practice guidelines that we reviewed all recommend rescheduling all non-urgent consultations and surgeries, reinforcing contact precautions, the use of personal protection elements, and the disinfection of surfaces and instruments. The guidelines should be improved by incorporating systematic searches for evidence, using GRADE for recommendations, and Appraisal of Guidelines for Research and Evaluation (AGREE II) for reporting.", "qid": 11, "docid": "of7nk5ox", "rank": 85, "score": 0.7366158962249756}, {"content": "Title: Management strategies for children with COVID-19: ESPR practical recommendations Content: During the outbreak of the COVID-19 pandemic, guidelines have been issued by international, national and local authorities to address management and the need for preparedness. Children with COVID-19 differ from adults in that they are less often and less severely affected. Additional precautions required in the management of children address their increased radiosensitivity, need for accompanying carers, and methods for dealing with children in a mixed adult-paediatric institution. In this guidance document, our aim is to define a pragmatic strategy for imaging children with an emphasis on proven or suspected COVID-19 cases. Children suspected of COVID-19 should not be imaged routinely. Imaging should be performed only when expected to alter patient management, depending on symptoms, preexisting conditions and clinical evolution. In order to prevent disease transmission, it is important to manage the inpatient caseload effectively by triaging children and carers outside the hospital, re-scheduling nonurgent elective procedures and managing symptomatic children and carers as COVID-19 positive until proven otherwise. Within the imaging department one should consider conducting portable examinations with COVID-19 machines or arranging dedicated COVID-19 paediatric imaging sessions and performing routine nasopharyngeal swab testing before imaging under general anaesthesia. Finally, regular personal hygiene, appropriate usage of personal protective equipment, awareness of which procedures are considered aerosol generating and information on how to best disinfect imaging machinery after examinations should be highlighted to all staff members. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00247-020-04749-3) contains supplementary material, which is available to authorized users.", "qid": 11, "docid": "dopm66uv", "rank": 86, "score": 0.7365704774856567}, {"content": "Title: Management strategies for children with COVID-19: ESPR practical recommendations Content: During the outbreak of the COVID-19 pandemic, guidelines have been issued by international, national and local authorities to address management and the need for preparedness. Children with COVID-19 differ from adults in that they are less often and less severely affected. Additional precautions required in the management of children address their increased radiosensitivity, need for accompanying carers, and methods for dealing with children in a mixed adult-paediatric institution. In this guidance document, our aim is to define a pragmatic strategy for imaging children with an emphasis on proven or suspected COVID-19 cases. Children suspected of COVID-19 should not be imaged routinely. Imaging should be performed only when expected to alter patient management, depending on symptoms, preexisting conditions and clinical evolution. In order to prevent disease transmission, it is important to manage the inpatient caseload effectively by triaging children and carers outside the hospital, re-scheduling nonurgent elective procedures and managing symptomatic children and carers as COVID-19 positive until proven otherwise. Within the imaging department one should consider conducting portable examinations with COVID-19 machines or arranging dedicated COVID-19 paediatric imaging sessions and performing routine nasopharyngeal swab testing before imaging under general anaesthesia. Finally, regular personal hygiene, appropriate usage of personal protective equipment, awareness of which procedures are considered aerosol generating and information on how to best disinfect imaging machinery after examinations should be highlighted to all staff members.", "qid": 11, "docid": "sen4w425", "rank": 87, "score": 0.7364058494567871}, {"content": "Title: Patients with Coronavirus 2019 (COVID-19) and Surgery: Guidelines and Checklist Proposal Content: The management of patients with novel coronavirus 2019 (COVID-19) represents a new challenge for medical and surgical teams. Each operating room in the world should be prepared thoughtfully, and the development of a protocol and patient route seems mandatory. An adequate degree of protection must be used. We propose recommendations to help different professionals in the establishment of protocols for the management of patients with COVID-19. We also offer a checklist that could be used in the operating room.", "qid": 11, "docid": "wa6cd7yt", "rank": 88, "score": 0.7363465428352356}, {"content": "Title: Eosinopenia and elevated C-reactive protein facilitate triage of COVID-19 patients in fever clinic: a retrospective case-control study Content: Background: Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a pandemic affecting over 200 countries. Many cities have established designated fever clinics to triage suspected COVID-19 patients from other patients with similar symptoms. However, given the limited availability of the nucleic acid test as well as long waiting time for both the test and radiographic examination, the quarantine or therapeutic decisions for a large number of mixed patients were often not made in time. We aimed to identify simple and quickly available laboratory biomarkers to facilitate effective triage at the fever clinics for sorting suspected COVID-19 patients from those with COVID-19-like symptoms. Methods: We collected clinical, etiological, and laboratory data of 989 patients who visited the Fever Clinic at Wuhan Union Hospital, Wuhan, China, from Jan 31 to Feb 21. Based on polymerase chain reaction (PCR) nucleic acid testing for SARS-CoV-2 infection, they were divided into two groups: SARS-CoV-2-positive patients as cases and SARS-CoV-2-negative patients as controls. We compared the clinical features and laboratory findings of the two groups, and analyzed the diagnostic performance of several laboratory parameters in predicting SARS-CoV-2 infection and made relevant comparisons to the China diagnosis guideline of having a normal or decreased number of leukocytes (&#8804;9\u00e2\u0080\u00a25 109/L) or lymphopenia (<1\u00e2\u0080\u00a21 109/L). Findings: Normal or decreased number of leukocytes (&#8804;9\u00e2\u0080\u00a25 109/L), lymphopenia (<1\u00e2\u0080\u00a21 109/L), eosinopenia (<0\u00e2\u0080\u00a202 109/L), and elevated hs-CRP (&#8805;4 mg/L) were presented in 95\u00e2\u0080\u00a20%, 52\u00e2\u0080\u00a22%, 74\u00e2\u0080\u00a27% and 86\u00e2\u0080\u00a27% of COVID-19 patients, much higher than 87\u00e2\u0080\u00a22%, 28\u00e2\u0080\u00a28%, 31\u00e2\u0080\u00a23% and 45\u00e2\u0080\u00a22% of the controls, respectively. The eosinopenia produced a sensitivity of 74\u00e2\u0080\u00a27% and specificity of 68\u00e2\u0080\u00a27% for separating the two groups with the area under the curve (AUC) of 0\u00e2\u0080\u00a2717. The combination of eosinopenia and elevated hs-CRP yielded a sensitivity of 67\u00e2\u0080\u00a29% and specificity of 78\u00e2\u0080\u00a22% (AUC=0\u00e2\u0080\u00a2730). The addition of eosinopenia alone or the combination of eosinopenia and elevated hs-CRP into the guideline-recommended diagnostic parameters for COVID-19 improved the predictive capacity with higher than zero of both net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Interpretation: The combination of eosinopenia and elevated hs-CRP can effectively triage suspected COVID-19 patients from other patients attending the fever clinic with COVID-19-like initial symptoms. This finding would be particularly useful for designing triage strategies in an epidemic region having a large number of patients with COVID-19 and other respiratory diseases while limited medical resources for nucleic acid tests and radiographic examination. Funding: This work was supported by the National Natural Science Foundation of China (NSFC) and the Major Scientific and Technological Innovation Projects of Hubei Province (MSTIP).", "qid": 11, "docid": "37dauvku", "rank": 89, "score": 0.7363133430480957}, {"content": "Title: Safeguarding the Maintenance Hemodialysis Patient Population during the Coronavirus Disease 19 Pandemic Content: The World Health Organization has recognized the pandemic nature of the coronavirus disease 19 (COVID-19) outbreak. A large proportion of positive patients require hospitalization, while 5-6% of them may need more aggressive therapies in intensive care. Most governments have recommended social separation and severe measures of prevention of further spreading of the epidemic. Because hemodialysis (HD) patients need to access hospital and dialysis center facilities 3 times a week, this category of patients requires special attention. In this editorial, we tried to summarize the experience of our centers that hopefully may contribute to help other centers and colleagues that are facing the coming wave of the epidemic. Special algorithms for COVID-19 spreading in the dialysis population, recommendations for isolation and preventive measures in positive HD patients, and finally directions to manage logistics and personnel are reported. These recommendations should be considered neither universal nor absolute. Instead, they require local adjustments based on geographic location, cultural and social environments, and level of available resources.", "qid": 11, "docid": "95d8nrs6", "rank": 90, "score": 0.7360513210296631}, {"content": "Title: Care of ophthalmological patients during the COVID-19 pandemic: A rapid scoping review. Content: Introduction A new type of coronavirus (SARS-CoV-2) causes a respiratory distress syndrome that has been called COVID-19 and has generated an unprecedented pandemic. Serious complications include pneumonia, and mortality ranges from 2 to 5%. Until March 26, the World Health Organization reports 462 684 confirmed cases and 20 834 deaths worldwide. Dissemination occurs from aerosols or respiratory droplets. Different scientific societies have published clinical practice guidelines regarding ophthalmic care in the COVID-19 pandemic, but the information is presented inconsistently, which makes decision-making difficult. Methods We conducted a sensitive bibliographic search in EMBASE and ophthalmic society webpages, of the clinical practice guidelines of ophthalmic care in pandemic COVID-19. We extracted the recommendations, organizing them into three categories: \"Which patients to attend\", \"How should the clinic work\", and \"What interventions should be avoided\". For each guideline, we assessed whether the search was systematic and whether the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was followed. Results Fourteen relevant articles were found. Fifty-one recommendations were extracted and are shown in a summary table. None are based on a systematic search for evidence, nor do any use GRADE to develop the recommendations. Conclusions The clinical practice guidelines that we reviewed all recommend rescheduling all non-urgent consultations and surgeries, reinforcing contact precautions, the use of personal protection elements, and the disinfection of surfaces and instruments. The guidelines should be improved by incorporating systematic searches for evidence, using GRADE for recommendations, and Appraisal of Guidelines for Research and Evaluation (AGREE II) for reporting.", "qid": 11, "docid": "8zqkel14", "rank": 91, "score": 0.7358569502830505}, {"content": "Title: Management of Gynecology Patients during COVID-19 Pandemic: Chinese Expert Consensus Content: Abstract: Since December 2019, the outbreak of novel coronavirus disease 2019 (COVID-19) became a major epidemic threat in China and later spread worldwide. During the COVID-19 outbreak in mainland China, the Chinese Obstetricians and Gynecologists Association (COGA) distributed guidelines regarding care of gynecologic patients. These guidelines were developed by the Obstetrics and Gynecology department at Peking Union Medical College Hospital (PUMCH) and represent an effort to integrate infection control strategy and promote professionalism in medical practice. The guidelines represent collaboration with experts from 31 provinces and autonomous regions of mainland China over 2 weeks' time. With the implementation of these guidelines no nosocomial infections of COVID-19 have been identified at PUMCH. We think these guidelines might be helpful to departments of obstetrics and gynecology internationally during these unprecedented times. In our guidelines, we describe basic infection precaution principles, an epidemiologic screening tool, prioritization of surgical procedures, and operating room requirements. Using these principles, we then review management of gynecologic patients during the COVID-19 epidemic in the outpatient and operative and non-operative inpatient settings, as well as in clinical trials.", "qid": 11, "docid": "eoho6ur0", "rank": 92, "score": 0.7356588840484619}, {"content": "Title: Inpatient Care of Patients with COVID-19: A Guide for Hospitalists Content: Abstract Since its emergence in December 2019, the virus known as severe acute respiratory syndrome coronavirus 2 has quickly caused a pandemic. This virus causes a disease now known as coronavirus disease 2019, or COVID-19. As an increasing proportion of the at-risk population becomes infected, and patients with severe illness are hospitalized, it is essential for hospitalists to remain current on how to best care for people with suspected or confirmed disease. Establishing a system for logistical planning, and accurate information sharing is strongly recommended. Infection control remains the ultimate goal. As such, healthcare workers should be educated on universal and isolation precautions, and the appropriate use of personal protective equipment. Social distancing should be encouraged to prevent the spread of infection, and creative and innovative ways to reduce contact may need to be considered. Moreover, it is imperative to prepare for contingencies as medical staff will inevitably get sick or become unavailable. Hospitalists have the difficult task of caring for patients, while also adapting to the many logistical and social elements of a pandemic.", "qid": 11, "docid": "kugr54if", "rank": 93, "score": 0.7354885339736938}, {"content": "Title: Review of Emerging Pharmacotherapy for the Treatment of Coronavirus Disease 2019 Content: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) has evolved into an emergent global pandemic. Coronavirus disease 2019 (COVID\u201019) can manifest on a spectrum of illness from mild disease to severe respiratory failure requiring intensive care unit admission. As the incidence continues to rise at a rapid pace, critical care teams are faced with challenging treatment decisions. There is currently no widely accepted standard of care in the pharmacologic management of patients with COVID\u201019. Urgent identification of potential treatment strategies is a priority. Therapies include novel agents available in clinical trials or through compassionate use, and other drugs, repurposed antiviral and immunomodulating therapies. Many have demonstrated in vitro or in vivo potential against other viruses that are similar to SARS\u2010CoV\u20102. Critically ill patients with COVID\u201019 have additional considerations related to adjustments for organ impairment and renal replacement therapies, complex lists of concurrent medications, limitations with drug administration and compatibility, and unique toxicities that should be evaluated when utilizing these therapies. The purpose of this review is to summarize practical considerations for pharmacotherapy in patients with COVID\u201019, with the intent of serving as a resource for health care providers at the forefront of clinical care during this pandemic.", "qid": 11, "docid": "bsdk64t1", "rank": 94, "score": 0.7353905439376831}, {"content": "Title: Triage Considerations for Patients Referred for Structural Heart Disease Intervention During the COVID-19 Pandemic: An ACC/SCAI Position Statement Content: The coronavirus disease-2019 (COVID-19) pandemic has strained health care resources around the world, causing many institutions to curtail or stop elective procedures. This has resulted in an inability to care for patients with valvular and structural heart disease in a timely fashion, potentially placing these patients at increased risk for adverse cardiovascular complications, including CHF and death. The effective triage of these patients has become challenging in the current environment as clinicians have had to weigh the risk of bringing susceptible patients into the hospital environment during the COVID-19 pandemic against the risk of delaying a needed procedure. In this document, the authors suggest guidelines for how to triage patients in need of structural heart disease interventions and provide a framework for how to decide when it may be appropriate to proceed with intervention despite the ongoing pandemic. In particular, the authors address the triage of patients in need of transcatheter aortic valve replacement and percutaneous mitral valve repair. The authors also address procedural issues and considerations for the function of structural heart disease teams during the COVID-19 pandemic.", "qid": 11, "docid": "hzi8zuyt", "rank": 95, "score": 0.7353122234344482}, {"content": "Title: Coronavirus Disease 2019 Pandemic Measures: Reports From a National Survey of 9,120 ICU Clinicians Content: Recent reports identify that among hospitalized coronavirus disease 2019 patients, 30% require ICU care. Understanding ICU resource needs remains an essential component of meeting current and projected needs of critically ill coronavirus disease 2019 patients. OBJECTIVES: This study queried U.S. ICU clinician perspectives on challenging aspects of care in managing coronavirus disease 2019 patients, current and anticipated resource demands, and personal stress. DESIGN, SETTING, AND PARTICIPANTS: Using a descriptive survey methodology, an anonymous web-based survey was administered from April 7, 2020, to April 22, 2020 (email and newsletter) to query members of U.S. national critical care organizations. MEASUREMENTS AND MAIN RESULTS: Through a 16-item descriptive questionnaire, ICU clinician perceptions were assessed regarding current and emerging critical ICU needs in managing the severe acute respiratory syndrome coronavirus 2 infected patients, resource levels, concerns about being exposed to severe acute respiratory syndrome coronavirus 2, and perceived level of personal stress. A total of 9,120 ICU clinicians responded to the survey, representing all 50 U.S. states, with 4,106 (56.9%) working in states with 20,000 or more coronavirus disease 2019 cases. The 7,317 respondents who indicated their profession included ICU nurses (n = 6,731, 91.3%), advanced practice providers (nurse practitioners and physician assistants; n = 334, 4.5%), physicians (n = 212, 2.9%), respiratory therapists (n = 31, 0.4%), and pharmacists (n = 30, 0.4%). A majority (n = 6,510, 88%) reported having cared for a patient with presumed or confirmed coronavirus disease 2019. The most critical ICU needs identified were personal protective equipment, specifically N95 respirator availability, and ICU staffing. Minimizing healthcare worker virus exposure during care was believed to be the most challenging aspect of coronavirus disease 2019 patient care (n = 2,323, 30.9%). Nurses report a high level of concern about exposing family members to severe acute respiratory syndrome coronavirus 2 (median score of 10 on 0\u201310 scale). Similarly, the level of concern reached the maximum score of 10 in ICU clinicians who had provided care to coronavirus disease 2019 patients. CONCLUSIONS: This national ICU clinician survey identifies continued concerns regarding personal protective equipment supplies with the chief issue being N95 respirator availability. As the pandemic continues, ICU clinicians anticipate a number of limited resources that may impact ICU care including personnel, capacity, and surge potential, as well as staff and subsequent family members exposure to severe acute respiratory syndrome coronavirus 2. These persistent concerns greatly magnify personal stress, offering a therapeutic target for professional organization and facility intervention efforts.", "qid": 11, "docid": "4asttsy2", "rank": 96, "score": 0.7351633310317993}, {"content": "Title: Challenges and Responses: A Tertiary Hospital in 2019-nCoV Epidemic Content: The recent outbreak of coronavirus in Wuhan, China, has imposed challenges on the Chinese medical system. Not only the dramatically increasing number of infected cases and insufficient medical resources, but also the peoples' panic throughout the whole country have made medical services extremely difficult. To respond to these challenges effectively, our hospital implemented an urgent response strategy, including human resources and medical resources preparation and re-allocation, immediate fever screening, strict patient-visiting flow management, and reasonable information communication. Our experience and response measures could provide a reference for other hospitals in the current situation.", "qid": 11, "docid": "10itpak2", "rank": 97, "score": 0.7349886894226074}, {"content": "Title: Triage during the COVID-19 epidemic in Spain: better and worse ethical arguments Content: The COVID-19 pandemic has generated an imbalance between the clinical needs of the population and the effective availability of advanced life support (ALS) resources. Triage protocols have thus become necessary. Triage decisions in situations of scarce resources were not extraordinary in the pre-COVID-19 era; these protocols abounded in the context of organ transplantation. However, this prior experience was not considered during the COVID-19 outbreak in Spain. Lacking national guidance or public coordination, each hospital has been forced to put forth independent and autonomous triage protocols, most of which were, nonetheless, based on common ethical principles and clinical criteria. However, controversial, non-clinical criteria have also been defended by Spanish scientific societies and public institutions, including setting an age cut-off value for unilaterally withholding ALS, using 'social utility' criteria, prioritising healthcare professionals or using 'first come, first served' policies. This paper describes the most common triage criteria used in the Spanish context during the COVID-19 epidemic. We will highlight our missed opportunities by comparing these criteria to those used in organ transplantation protocols. The problems posed by subjective, non-clinical criteria will also be discussed. We hope that this critical review might be of use to countries at earlier stages of the epidemic while we learn from our mistakes.", "qid": 11, "docid": "xtl8v5d1", "rank": 98, "score": 0.7349708080291748}, {"content": "Title: Point of care procedures in physiatry: Practice considerations during the Covid-19 pandemic Content: Coronavirus Disease 2019 (Covid-19) is an active pandemic that has required rapid conversion of practice patterns to mitigate disease spread. Although recommendations have been released for physicians to postpone elective procedures, the utility of common physiatry procedures and their infectious risk profile have yet to be clearly delineated. In this article, we describe an update on existing national recommendations and outline considerations as practitioners and institutions strive to meet the needs of patients with disabilities.", "qid": 11, "docid": "gr7oa9up", "rank": 99, "score": 0.7347143888473511}, {"content": "Title: Response of a comprehensive cancer center to the COVID-19 pandemic: the experience of the Fondazione IRCCS-Istituto Nazionale dei Tumori di Milano. Content: BACKGROUND The rapid spread of coronavirus disease (COVID-19) is affecting many countries. While healthcare systems need to cope with the need to treat a large number of people with different degrees of respiratory failure, actions to preserve aliquots of the healthcare system to guarantee treatment to patients are mandatory. METHODS In order to protect the Fondazione IRCCS-Istituto Nazionale dei Tumori di Milano from the spread of COVID-19, a number of to-hospital and within-hospital filters were applied. Among others, a triage process to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity in patients with cancer was developed consisting of high-resolution low-dose computed tomography (CT) scan followed by reverse transcription polymerase chain reaction (RT-PCR) detection of SARS-CoV-2 in nose-throat swabs whenever CT was suggestive of lung infection. To serve symptomatic patients who were already admitted to the hospital or in need of hospitalization while waiting for RT-PCR laboratory confirmation of infection, a COVID-19 surveillance zone was set up. RESULTS A total of 301 patients were screened between March 6 and April 3, 2020. Of these, 47 were hospitalized, 53 needed a differential diagnosis to continue with their cancer treatment, and 201 were about to undergo surgery. RT-PCR was positive in 13 of 40 hospitalized patients (32%), 14 of 52 day hospital patients (27%), and 6 of 201 surgical patients (3%). CONCLUSION Applying filters to protect our comprehensive cancer center from COVID-19 spread contributed to guaranteeing cancer care during the COVID-19 crisis in Milan. A surveillance area and surgical triage allowed us to protect the hospital from as many as 33 patients infected with SARS-CoV-2.", "qid": 11, "docid": "r4r1a6fd", "rank": 100, "score": 0.7345982789993286}]}
{"query": "what are best practices in hospitals and at home in maintaining quarantine?", "hits": [{"content": "Title: What does isolation mean in home healthcare? Content: In the event of an infectious disease outbreak, home health nurses are called upon to care for patients who have been placed on isolation precautions. To protect themselves, patients, and caregivers, nurses must be knowledgeable about infectious diseases and infection control procedures. A checklist is provided to assist the nurse and caregiver with guidance in performing the patient's care.", "qid": 12, "docid": "bdvcwaau", "rank": 1, "score": 0.7121639251708984}, {"content": "Title: Addressing the Gaps in Preparation for Quarantine Content: INTRODUCTION: In the event of an outbreak of a communicable respiratory illness, quarantine may become necessary. The New York Institute for All Hazard Preparedness (NYIAHP) of the State University of New York (SUNY) Downstate Medical Center, in cooperation with the New York City Department of Health and Mental Hygiene's Healthcare Emergency Preparedness Program, (NYC DOHMH-HEPP) quarantine working group, has developed a series of clinical protocols to help health care facilities respond to such an event. PROBLEM: Two full-scale exercises (FSEs) were designed and conducted a year apart in the quarantine unit at Kings County Hospital Center (KCHC) to test the efficacy and feasibility of these quarantine protocols. The goal of these exercises was to identify the gaps in preparedness for quarantine and increase hospital readiness for such an event. METHODS: Evaluators monitored for efficient management of critical physical plants, personnel and material resources. Players were expected to integrate and practice emergency response plans and protocols specific to quarantine. In developing the exercise objectives, five activities were selected for evaluation: Activation of the Unit, Staffing, Charting/Admission, Symptom Monitoring and Infection Control, and Client Management. RESULTS: The results of the initial FSE found that there were incomplete critical tasks within all five protocols: These deficiencies were detailed in an After Action Report and an Improvement Plan was presented to the KCHC Disaster Preparedness Committee a month after the initial FSE. In the second FSE a year later, all critical tasks for Activation of the unit, Staffing and Charting/Admission were achieved. Completion of critical tasks related to Symptom Monitoring and Infection Control and Client Management was improved in the second FSE, but some tasks were still not performed appropriately. CONCLUSION: In short, these exercises identified critical needs in disaster preparedness of the KCHC Quarantine Unit. The lessons learned from this logistical exercise enabled the planning group to have a better understanding of leadership needs, communication capabilities, and infection control procedures. Kings County Hospital Center performed well during these exercises. It was clear that performance in the second exercise was improved, and many problems noted in the first exercise were corrected. Staff also felt better prepared the second time. This supports the idea that frequent exercises are vital to maintain disaster readiness. R Nathawad, PM Roblin, D Pruitt, B Arquilla. Addressing the gaps in preparation for quarantine. Prehosp Disaster Med. 2013;28(2):1-7 23158909.", "qid": 12, "docid": "hdbbgee2", "rank": 2, "score": 0.711118221282959}, {"content": "Title: How long does Coronavirus survive on different surfaces? Content: Dental practices now need to be more vigilant than ever and pay extra attention to hygiene in the surgery Hospitals are currently operating an hourly total clean policy and it would be prudent for dental practices to look to operate something similar to reduce the possibility of viral transmission The Government is encouraging people to stay at home and maintain social distancing during the pandemic However, key workers must go to work, use public transport and mix with high risk people People also need to go to supermarkets to get their groceries The surfaces in these public places are likely to be contaminated;these germs can then be brought into homes or dental practices", "qid": 12, "docid": "7ftq02ev", "rank": 3, "score": 0.7101895809173584}, {"content": "Title: Healthcare personnel and nosocomial transmission of pandemic 2009 influenza. Content: Knowledge regarding the modes of transmission of pandemic 2009 H1N1 influenza continues to develop, as do recommendations for the prevention of spread within healthcare facilities. The adoption of the most prudent, multifaceted approaches is recommended until there is significant evidence to reduce protective measures. The greatest threat to healthcare personnel and patients appears to be exposure to patients, healthcare personnel, or visitors who have not been recognized as contagious. The processes used within healthcare facilities must hold this concept central to any infection control plan and act in a preventive manner. This article focuses on the development of an algorithm for intensive care unit intake precautions, based on the early identification of potential source patients, as well as appropriate selection and adequate use of personal protective equipment. Visitor management, hand and respiratory hygiene, and cough etiquette have been used as measures to decrease the spread of infection. Vaccination of healthcare personnel, combined with work furlough for ill workers, is also explored. Recommendations include the elimination of potential exposures, engineering and administrative controls, and utilization of personal protective equipment.", "qid": 12, "docid": "d2axm29e", "rank": 4, "score": 0.70876544713974}, {"content": "Title: Quarantine Stressing Voluntary Compliance Content: A 1-day table-top exercise in San Diego, California, in December 2004 emphasized voluntary compliance with home quarantine to control an emerging infectious disease outbreak. The exercise heightened local civilian-military collaboration in public health emergency management. Addressing concerns about lost income by residents in quarantine was particularly challenging.", "qid": 12, "docid": "bu617h9z", "rank": 5, "score": 0.7082948088645935}, {"content": "Title: ASID (HICSIG) position statement: infection control guidelines for patients with influenza-like illnesses, including pandemic (H1N1) influenza 2009, in Australian health care facilities. Content: Standard and Droplet Precautions are considered adequate to control the transmission of influenza in most health care situations. Vaccination of health care staff, carers and vulnerable patients against seasonal and, eventually, pandemic influenza strains is an essential protective strategy. Management principles include: performance of hand hygiene before and after every patient contact or contact with the patient environment, in accord with the national 5 Moments for Hand Hygiene Standard; disinfection of the patient environment; early identification and isolation of patients with suspected or proven influenza; adoption of a greater minimum distance of patient separation (2 metres) than previously recommended; use of a surgical mask and eye protection for personal protection on entry to infectious areas or within 2 metres of an infectious patient; contact tracing for patient and health care staff and restriction of prophylactic antivirals mainly to those at high risk of severe disease; in high aerosol-risk settings, use of particulate mask, eye protection, impervious long-sleeved gown, and gloves donned in that sequence and removed in reverse sequence, avoiding self-contamination; exclusion of symptomatic staff from the workplace until criteria for non-infectious status are met; reserving negative-pressure ventilation rooms (if available) for intensive care patients, especially those receiving non-invasive ventilation; ensuring that infectious postpartum women wear surgical masks when caring for their newborn infants and practise strict hand hygiene; and implementation of special arrangements for potentially infected newborns who require nursery or intensive care.", "qid": 12, "docid": "i6ygg9yh", "rank": 6, "score": 0.706356942653656}, {"content": "Title: Are Contact Precautions ethically justifiable in contemporary hospital care? Content: Hospital infection control practices known as Contact Precautions are recommended for the management of people with pathogens such as methicillin-resistant Staphylococcus aureus or vancomycin-resistant Enterococci. Background: The patient is isolated, and staff are required to wear gloves, and a gown or apron when providing care. A notice is displayed to remind staff of these requirements and an 'alert' message is placed in the patient's medical record. Objective: The aim of this article is to discuss and explore whether practices used in hospitals to reduce the transmission of endemic antibiotic-resistant organisms are ethically justified in today's healthcare environment in the developed world. In order to do this, the history of the development of these practices is summarised, and the evidence base for their effectiveness is reviewed. Key bioethics principles are then discussed and contextualised from the perspective of hospital infection prevention and control, and an ethically superior model for the prevention and control of healthcare associated infection is proposed.", "qid": 12, "docid": "ky79aheq", "rank": 7, "score": 0.6975700259208679}, {"content": "Title: The experience of quarantine for individuals affected by SARS in Toronto. Content: OBJECTIVE The purpose of this study was to explore the experience of home quarantine during the severe acute respiratory syndrome (SARS) outbreak in Toronto in 2003. DESIGN Qualitative descriptive design. SAMPLE Stratified random sampling techniques were used to generate a list of potential participants, who varied in terms of gender and closeness of exposure to someone with suspected SARS (contact level). Twenty-one individuals participated in the study. MEASUREMENTS All interviews were audiotaped and followed a semistructured interview guide. Participants were invited to describe their experience of quarantine in detail including their advice for Public Health. RESULTS The experience followed a trajectory of stages beginning before quarantine and ending after quarantine. Despite individual differences, common themes of uncertainty, isolation, and coping intersected the data. CONCLUSIONS Public Health has a dual role of monitoring compliance and providing support to people in quarantine. This study has implications for public health policy and practice in planning for future public health emergencies in terms of the information and the resources required to mount an effective response.", "qid": 12, "docid": "xdgd11k6", "rank": 8, "score": 0.6969035863876343}, {"content": "Title: Quarantine through History Content: Abstract This article reviews in a historical perspective and by means of documented examples the scientific principles relevant to the concept and effectiveness of quarantine, the logistic, economic, and political barriers to its correct implementation through time, and the health impact of local and large-scale quarantine. Quarantine is overall one of the oldest and most disseminated and, despite its limits, most effective health measures elaborated by mankind. The evidence-based history of medicine and evidence-based modern epidemiology indicate that the implementation of correct quarantine procedures is today still feasible and useful provided that a proactive collaboration is operative among those concerned and that the measures are tailored according to geographical, social, and health conditions.", "qid": 12, "docid": "d5p4chhg", "rank": 9, "score": 0.6938296556472778}, {"content": "Title: Infection in the critically ill\u2014questions we should be asking Content: Best practice in infection control and management in the critically ill continues to generate considerable debate. The wide variation in current practice is witness to this continuing uncertainty. In large part this is due to the lack of a decent evidence base and to an over-reliance on deep-set dogma. Data that go against the grain are often conveniently overlooked and political imperatives frequently supervene. This article highlights some of these discrepancies and argues for a more balanced, scientific approach. In this time of financial restraint, we need to identify true priorities from both health and economic perspectives, and to see what practices can safely and effectively be modified or abandoned.", "qid": 12, "docid": "urhviyme", "rank": 10, "score": 0.693450927734375}, {"content": "Title: Isolation Precautions in the Inpatient Setting Content: This article provides an overview of the use of standard and isolation precautions in the hospital setting, including droplet, airborne, and contact precautions. The article includes the indications for use, guidance for appropriate discontinuation of precautions, and the effect of precaution use on infection control measures, patient safety and experience, health care costs, and environmental outcomes.", "qid": 12, "docid": "nvpoz702", "rank": 11, "score": 0.6929619312286377}, {"content": "Title: Quarantine Through History Content: This article reviews in a historical perspective and by means of documented examples the scientific principles relevant to the concept and effectiveness of quarantine, the logistic, economic, and political barriers to its correct implementation through time, and the health impact of local and large-scale quarantine. Quarantine is overall one of the oldest and most disseminated and, despite its limits, most effective health measures elaborated by mankind. The evidence-based history of medicine and evidence-based modern epidemiology indicate that the implementation of correct quarantine procedures is today still feasible and useful provided that a proactive collaboration is operative among those concerned and that the measures are tailored according to geographical, social, and health conditions.", "qid": 12, "docid": "zcsqzz0v", "rank": 12, "score": 0.6927414536476135}, {"content": "Title: Implementing Basic Infection Control Practices in Disaster Situations Content: Infections, troublesome in even optimal health care environments, can be a source of serious and persistent concern for local populations and health care workers during a disaster, and in austere environments such as those found in Iraq and Afghanistan. For these scenarios, it is vital to have standard infection control practices in place and to have them used consistently. Only then will healthcare workers be able to contain the potential spread of disease and improve conditions for those affected.", "qid": 12, "docid": "ys0ndxun", "rank": 13, "score": 0.6916553974151611}, {"content": "Title: Promoting best practices for control of respiratory infections: collaboration between primary care and public health services. Content: OBJECTIVE To determine the effectiveness of a short-term intervention to promote best practices for control of respiratory infections in primary care physicians' offices. DESIGN Before-after observational study. SETTING Family physicians' offices in Ottawa, Ont. PARTICIPANTS General practitioners and office staff. INTERVENTIONS Four infection-control practices (use of masks, alcohol-based hand gel, and signs, and asking patients to sit at least 1 m apart in the waiting room) were observed, and 2 reported infection-control practices (disinfecting surfaces and use of hand-gel dispensers in examining rooms) were audited before the intervention and 6 weeks after the intervention. MAIN OUTCOME MEASURES Percentage of patients asked to use masks and alcohol-based hand gel, number of relevant signs, and percentage of patients asked to sit at least 1 m away from other patients. Percentage of surfaces disinfected and percentage of physicians using hand-gel dispensers in examining rooms. RESULTS Of 242 practices invited, 53 agreed to participate (22% response rate), and within those practices, 143/151 (95%) physicians participated. Signs regarding respiratory infection control measures increased from 15.4% to 81.1% following the intervention (P < .001). At least 1 patient with cough and fever was given a mask in 17% of practices before the intervention; during the observation period after the intervention, at least 1 patient was given a mask in 66.7% of practices (P < .001). Patients were instructed to use alcohol-based hand gel in 24.5% of practices before the intervention and in 79.2% of practices after it (P < .001). Instruction to sit at least 1 m from others in the waiting area was given in 39.6% of practices before the intervention and in 52.8% of practices following the intervention (P < .001). Before the intervention, the percentage of practices using all 4 audited primary prevention measures was 3.8%; after the intervention, 52.8% of practices were using them (P < .001), demonstrating a 49% increase in adoption of best practices. CONCLUSION A multifaceted intervention by public health nurses successfully promoted best practices for control of respiratory infections in primary care offices. Collaboration between public health services and primary care can promote best practices and warrants further study and development in areas of common interest.", "qid": 12, "docid": "0mcixa4c", "rank": 14, "score": 0.6910004615783691}, {"content": "Title: Application of the Updated CDC Isolation Guidelines for Health Care Facilities Content: THE CENTERS FOR DISEASE CONTROL and Prevention has published updated guidelines for isolation precautions that outline how health care workers can prevent the transmission of infectious agents to their patients and to themselves. THE GUIDELINES RE-EMPHASIZE standard precautions, which guide clinicians in the use of appropriate personal protective equipment (PPE), depending on the expected type of exposure. Respiratory hygiene/cough etiquette is incorporated into infection control practices as a new component of standard precautions. THE ARTICLE PROVIDES information on the new guidelines as well as information on newly emerging patho gens and methods to prevent disease transmission in health care settings.", "qid": 12, "docid": "q1rby2to", "rank": 15, "score": 0.690449059009552}, {"content": "Title: Effective infection prevention and control strategies in a large, accredited, psychiatric facility in Singapore Content: The Institute of Mental Health in Singapore continues to attempt to prevent the introduction of COVID-19, despite community transmission. Essential services are maintained and quarantine measures are currently unnecessary. To help similar organizations, strategies are listed along three themes: sustaining essential services, preventing infection, and managing human and consumable resources.", "qid": 12, "docid": "8rs3oep3", "rank": 16, "score": 0.689724862575531}, {"content": "Title: Quarantine and its legal dimension Content: Quarantine and isolation are public health measures used for centuries to prevent the spread of infectious diseases. Quarantine is separation of persons who have been exposed to an infection but asymptomatic, while isolation is separation of infected patients. Voluntary quarantine is preferred, but if necessary, it can be mandatory. These implementations can lead to restrictions on individual liberties, leading to ethical and legal problems. Isolation and quarantine enforcement are regulated by laws. Those who do not follow the quarantine rules could be punished. Isolation and quarantine practices in our country are described in General Hygiene Law. In this study the importance of quarantine, when and how it is applied, and its ethical and especially legal dimension are discussed.", "qid": 12, "docid": "ufbmmlmj", "rank": 17, "score": 0.6894892454147339}, {"content": "Title: Infection control practices among hospital health and support workers in Hong Kong Content: Summary A report by the Hong Kong government noted that hospital infection control standards were inadequate, requiring audit, development and implementation. In addition, hospital staff needed training in infection control measures. We investigated infection control practices among 162 hospital health workers (109 nurses, 45 doctors and 8 therapists) and 44 support workers in one acute hospital and two rehabilitation hospitals using a non-blinded, observational design. We examined compliance with isolation precautions and infection control guidelines, including proper wearing of a mask, goggles/face shield, or gown; handling patient care equipment, linen, and laundry; routine and terminal cleaning; and terminal cleaning of an isolation room. One major breakdown in compliance was use of sleeveless disposable plastic aprons instead of long-sleeved gowns during procedures likely to generate splashes or sprays of blood and body fluids. In more than half of the observed episodes, participants failed to disinfect medical devices, such as stethoscopes, before re-use. Thorough cleansing of commodes between patients was also lacking. Overall compliance with local and international infection control guidelines was satisfactory, but several aspects required improvement.", "qid": 12, "docid": "c0c4rjfa", "rank": 18, "score": 0.6858925819396973}, {"content": "Title: Are health care workers protected? An observational study of selection and removal of personal protective equipment in Canadian acute care hospitals Content: BACKGROUND: The proper use of personal protective equipment (PPE) by health care workers (HCWs) is vital in preventing the spread of infection and has implications for HCW safety. METHODS: An observational study was performed in 11 hospitals participating in the Canadian Nosocomial Infection Surveillance Program between January 7 and March 30, 2011. Using a standardized data collection tool, observers recorded HCWs selecting and removing PPE and performing hand hygiene on entry into the rooms of febrile respiratory illness patients. RESULTS: The majority of HCWs put on gloves (88%, n = 390), gown (83%, n = 368), and mask (88%, n = 386). Only 37% (n = 163) were observed to have put on eye protection. Working in a pediatric unit was significantly associated with not wearing eye protection (7%), gown (70%), gloves (77%), or mask (79%). Half of the observed HCWs (54%, n = 206) removed their PPE in the correct sequence. Twenty-six percent performed hand hygiene after removing their gloves, 46% after removing their gown, and 57% after removing their mask and/or eye protection. CONCLUSION: Overall adherence with appropriate PPE use in health care settings involving febrile respiratory illness patients was modest, particularly on pediatric units. Interventions to improve PPE use should be targeted toward the use of recommended precautions (eg, eye protection), HCWs working in pediatric units, the correct sequence of PPE removal, and performing hand hygiene.", "qid": 12, "docid": "18xf7a4f", "rank": 19, "score": 0.6841468811035156}, {"content": "Title: A home toolkit for primary prevention of influenza by individuals and families. Content: An influenza pandemic can overwhelm the capacities of hospitals, clinics, nursing facilities, and emergency services. The likelihood is that most of the individuals who are stricken will be cared for at home, and there is strong evidence that in-home caregivers bear a disproportionate risk of becoming infected. We reviewed the scientific literature after 2000 to identify steps that in-home caregivers can take to reduce the chances that they and other household members will become infected in the home. Personal hygiene, common masks, and technologies including air filters and UV light each offer incremental benefits, and in combination are expected to reduce a portion of the risk that household members face when caring for a member who has become infected. In pandemics and even seasonal epidemics, seemingly small steps can literally mean the difference between life and death, especially for in-home caregivers.", "qid": 12, "docid": "s4ahnmo8", "rank": 20, "score": 0.6829231977462769}, {"content": "Title: Raising the Yellow Flag: State Variation in Quarantine Laws. Content: Quarantine is an important but often misused tool of public health. An effective quarantine requires a process that inspires trust in government, only punishes noncompliance, and promotes a culture of social responsibility. Accomplishing successful quarantine requires incentives and enabling factors, payments, job security, and a tiered enforcement plan. In this article, we examine the variation in state-level quarantine laws and assess the effectiveness of these laws and regulations. We find that most states allow for an individual to have a hearing (63%) and to have a voice in burial and cremation procedures (71%), yet are weak on all other individual rights measures. Only 20% of states have provisions to protect employment when an individual is under quarantine, and less than half have plans for safe and humane quarantines. Decision makers at the state and local levels must make a concerted effort to revise and update quarantine laws and regulations. Ideally, these laws and regulations should be harmonized so as to avoid confusion and disruption between states, and public health officials should work with populations to identify and address the factors that will support successful quarantines if they are ever required.", "qid": 12, "docid": "ivznlkhp", "rank": 21, "score": 0.6823601722717285}, {"content": "Title: Is There a Case for Quarantine? Perspectives from SARS to Ebola. Content: Quarantine has been used for centuries in an effort to prevent the introduction, transmission, and spread of communicable diseases. While backed by legal authority, the public and even the health care worker community's understanding of the term is murky at best and scientific evidence to support the use of quarantine is frequently lacking. The multiple interpretations and references to quarantine, the inconsistent application of public health quarantine laws across jurisdictional boundaries, and reports of ineffectiveness are further complicated by associated infringement of civil liberties and human rights abuses. Given the need to balance public safety with human rights, we must be more precise about the meaning of quarantine and consider the efficacy and negative secondary effects resulting from its implementation. This article explains quarantine terminology and then uses a case study from Taiwan during the 2002-2003 severe acute respiratory syndrome (SARS) outbreak to illustrate the key principles associated with quarantine measures taken during the 2014 Ebola outbreak and the potential hazards that can arise from quarantines. Finally, we provide a quarantine and isolation decision tree to assist policy makers and public health officials in applying medically defensible, outcomes-based data and legal authorities to optimize management of emerging infectious diseases.", "qid": 12, "docid": "u4uvwpj0", "rank": 22, "score": 0.6823299527168274}, {"content": "Title: Perceptions of hand hygiene practices in China Content: Summary Hand hygiene is considered one of the most important infection control measures for preventing healthcare-associated infections. However, compliance rates with recommended hand hygiene practices in hospitals remain low. Previous literature on ways to improve hand hygiene practices has focused on the USA and Europe, whereas studies from developing countries are less common. In this study, we sought to identify common issues and potential strategies for improving hand hygiene practices in hospitals in China. We used a qualitative survey design based on in-depth interviews with 25 key hospital and public health staff in eight hospitals selected by the Chinese Ministry of Health. We found that hospital workers viewed hand hygiene as paramount to effective infection control and had adequate knowledge about proper hand hygiene practices. Despite these positive attitudes and adequate knowledge, critical challenges to improving rates of proper hand hygiene practices were identified. These included lack of needed resources, limited organisational authority of hospital infection control departments, and ineffective use of data monitoring and feedback to motivate improvements. Our study suggests that a pivotal issue for improving hand hygiene practice in China is providing infection control departments adequate attention, priority, and influence within the hospital, with a clear line of authority to senior management. Elevating the place of infection control on the hospital organisational chart and changing the paradigm of surveillance to continuous monitoring and effective data feedback are central to achieving improved hand hygiene practices and quality of care.", "qid": 12, "docid": "4g3x5dje", "rank": 23, "score": 0.6819963455200195}, {"content": "Title: Viral infections in children's wards\u2014how well do we manage them? Content: Abstract Children are frequently admitted to hospital wards with viral infections. Many are not life-threatening to the index case, but the spread to vulnerable patients who are already at higher risk should be avoided. To do so requires active awareness and availability of rapid diagnosis (i.e. the same day). Cohorting and handwashing have been found to be the best measures to prevent spread of respiratory syncytial virus (responsible for considerable morbidity every winter) in hospital wards.", "qid": 12, "docid": "tsvseiyw", "rank": 24, "score": 0.6819193363189697}, {"content": "Title: Strategy and technology to prevent hospital-acquired infections: Lessons from SARS, Ebola, and MERS in Asia and West Africa Content: Hospital-acquired infections (HAIs) are serious problems for healthcare systems, especially in developing countries where public health infrastructure and technology for infection preventions remain undeveloped. Here, we characterized how strategy and technology could be mobilized to improve the effectiveness of infection prevention and control in hospitals during the outbreaks of Ebola, Middle East respiratory syndrome (MERS), and severe acute respiratory syndrome (SARS) in Asia and West Africa. Published literature on the hospital-borne outbreaks of SARS, Ebola, and MERS in Asia and West Africa was comprehensively reviewed. The results showed that healthcare systems and hospital management in affected healthcare facilities had poor strategies and inadequate technologies and human resources for the prevention and control of HAIs, which led to increased morbidity, mortality, and unnecessary costs. We recommend that governments worldwide enforce disaster risk management, even when no outbreaks are imminent. Quarantine and ventilation functions should be taken into consideration in architectural design of hospitals and healthcare facilities. We also recommend that health authorities invest in training healthcare workers for disease outbreak response, as their preparedness is essential to reducing disaster risk.", "qid": 12, "docid": "hiw9unh3", "rank": 25, "score": 0.6810563802719116}, {"content": "Title: Knowledge and practices of isolation precautions among nurses in Jordan Content: BACKGROUND: Implementation of isolation precautions from the Centers for Disease Control and Prevention (CDC) has been justified through research and clinical evidence. However, nurses' understanding and compliance with these precautions is still unknown. The aim of this study was to assess nurses' knowledge and practices in relation to isolation precautions in Jordan. METHODS: A cross-sectional, descriptive design was used. The study took place in 8 hospitals in Jordan. A self-reported questionnaire and an observational checklist were developed based on the CDC (2007) isolation precautions guidelines. RESULTS: A total of 247 questionnaires were returned out of 400, for a response rate of 61.7%. The results show that most nurses (90%) have good knowledge of isolation precautions. However, only 65% of nurses reported good compliance with isolation precautions. The results of a t test revealed that nurses with Bachelor's degrees perform better in knowledge examinations than nurses with 2-year diplomas (P < .001). However, there was no significant difference in knowledge and self-report practices scores based on nurses' previous training and existence of isolation guidelines in their units or wards (P > .05). The results of the checklists confirm that there is a low compliance with standard isolation practice. In addition, the checklist shows that a high percentage of units and wards do not use isolation signs (46.4%) and posters (34.5%). CONCLUSIONS: This study revealed that educating nurses about isolation is not enough strategy to improve their compliance. It is important to adapt other strategies, such as supporting nurses by giving them a manageable workload, and providing more supplies and reminders of isolation precautions in the hospitals.", "qid": 12, "docid": "cq3foa1y", "rank": 26, "score": 0.6808910369873047}, {"content": "Title: Methods of Measuring Compliance with Transmission-Based Isolation Precautions: Comparison of Paper-Based and Electronic Data Collection Content: BACKGROUND: Decreasing transmission of resistant organisms in hospitals is a key goal of infection prevention plans. Studies have shown that health care worker (HCW) compliance with isolation precautions is inadequate. Direct observation of HCW behavior for measuring adherence is considered the \u201cgold standard\u201d but is labor intensive, requiring the collection and analysis of a large volume of observations. METHODS: Two methods of data collection were evaluated to asses HCW compliance: a manual method using a paper form (PF) with subsequent data entry into a database, and an electronic method using a web-based form (WBF) with real-time data recording. Observations were conducted at four hospitals (2,065 beds) to assess availability of gloves, gowns and masks, isolation sign postings, and HCW isolation practices. RESULTS: A total of 13,878 isolation rooms were observed in 2009. The median number of rooms observed/day for PF and WBF were 61 and 60 and the mean observation times/room were 149sec and 60sec, respectively. The WBF provided a time savings of 89 sec/room. CONCLUSIONS: Simple electronic forms can significantly decrease resources needed to monitor HCW adherence to hospital policies. The WBF decreased observation time by 60%, allowing for an increase in frequency and expansion of surveillance activities.", "qid": 12, "docid": "9s94o7i0", "rank": 27, "score": 0.6802907586097717}, {"content": "Title: COVID-19, Quarantines, Sheltering-in-Place, and Human Rights: The Developing Crisis Content: As COVID-19 has spread across the globe, quarantines and sheltering-in-place orders have become important public health tools but, as currently implemented, have eroded human rights, particularly for the marginalized, including essential workers, detainees, women, and children. Quarantines and sheltering-in-place orders must include explicit guarantees of human rights protections. We outline protections for the quarantined that communities and governments should strive to guarantee.", "qid": 12, "docid": "r8vug98w", "rank": 28, "score": 0.6800495386123657}, {"content": "Title: COVID-19, Quarantines, Sheltering-in-Place, and Human Rights: The Developing Crisis. Content: As COVID-19 has spread across the globe, quarantines and sheltering-in-place orders have become important public health tools but, as currently implemented, have eroded human rights, particularly for the marginalized, including essential workers, detainees, women, and children. Quarantines and sheltering-in-place orders must include explicit guarantees of human rights protections. We outline protections for the quarantined that communities and governments should strive to guarantee.", "qid": 12, "docid": "uys4etn0", "rank": 29, "score": 0.6800495386123657}, {"content": "Title: Evaluation of hospital mass screening and infection control practices in a pandemic influenza full-scale exercise. Content: OBJECTIVE Nonpharmacologic interventions such as limiting nosocomial spread have been suggested for mitigation of respiratory epidemics at health care facilities. This observational study tested the efficacy of a mass screening, isolation, and triage protocol in correctly identifying and placing in a cohort exercise subjects according to case status in the emergency departments at 3 acute care hospitals in Brooklyn, New York, during a simulated pandemic influenza outbreak. METHODS During a 1-day, full-scale exercise using 354 volunteer victims, variables assessing adherence to the mass screening protocol and infection control recommendations were evaluated using standardized forms. RESULTS While all hospitals were able to apply the suggested mass screening protocol for separation based on case status, significant differences were observed in several infection control variables among participating hospitals and different hospital areas. CONCLUSIONS Implementation of mass screening and other infection control interventions during a hospital full-scale exercise was feasible and resulted in measurable outcomes. Hospital drills may be an effective way of detecting and addressing variability in following infection control recommendations.", "qid": 12, "docid": "11aulpqb", "rank": 30, "score": 0.679352343082428}, {"content": "Title: How to improve adherence with quarantine: rapid review of the evidence Content: OBJECTIVES: The December 2019 outbreak of coronavirus has once again thrown the vexed issue of quarantine into the spotlight, with many countries asking their citizens to 'self-isolate' if they have potentially come into contact with the infection. However, adhering to quarantine is difficult. Decisions on how to apply quarantine should be based on the best available evidence to increase the likelihood of people adhering to protocols. We conducted a rapid review to identify factors associated with adherence to quarantine during infectious disease outbreaks. STUDY DESIGN: The study design is a rapid evidence review. METHODS: We searched Medline, PsycINFO and Web of Science for published literature on the reasons for and factors associated with adherence to quarantine during an infectious disease outbreak. RESULTS: We found 3163 articles and included 14 in the review. Adherence to quarantine ranged from as little as 0 up to 92.8%. The main factors which influenced or were associated with adherence decisions were the knowledge people had about the disease and quarantine procedure, social norms, perceived benefits of quarantine and perceived risk of the disease, as well as practical issues such as running out of supplies or the financial consequences of being out of work. CONCLUSIONS: People vary in their adherence to quarantine during infectious disease outbreaks. To improve this, public health officials should provide a timely, clear rationale for quarantine and information about protocols; emphasise social norms to encourage this altruistic behaviour; increase the perceived benefit that engaging in quarantine will have on public health; and ensure that sufficient supplies of food, medication and other essentials are provided.", "qid": 12, "docid": "kjnnh00e", "rank": 31, "score": 0.6792407035827637}, {"content": "Title: 15 Cleaning and decontamination of the healthcare environment Content: Abstract: Evidence is accumulating for the role of cleaning in controlling hospital infections. Hospital pathogens such as meticillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), norovirus, multi-resistant Gram-negative bacilli and Clostridium difficile persist in the healthcare environment for considerable lengths of time. Cleaning with both detergent and disinfectant-based regimens help control these pathogens in both routine and outbreak situations. The most important transmission risk comes from organisms on frequently handled items because hand contact with a contaminated site could deliver a pathogen to a patient. Cleaning practices should be tailored to clinical risk, near-patient areas and hand-touch-sites and scientifically evaluated for all surfaces and equipment in today\u2019s hospitals.", "qid": 12, "docid": "9rn8kzst", "rank": 32, "score": 0.6792258024215698}, {"content": "Title: How We Do It: Lessons on Outbreak Preparedness from the Cleveland Clinic Content: Disasters, including infectious disease outbreaks, are inevitable. Hospitals need to plan in advance to ensure that their systems can adapt to a rapidly changing environment if necessary. This review provides an overview of ten general principles that hospitals and healthcare systems should consider when developing disaster plans. The principles are consistent with an \"all-hazards\" approach to disaster mitigation. This approach is adapted to planning for a multiplicity of threats, but emphasizes highly relevant scenarios, such as the COVID-19 pandemic. We also describe specific ways these principles helped prepare our hospital for this pandemic. Key points include acting quickly, identifying and engaging key stakeholders early, providing accurate information, prioritizing employee safety and mental health, promoting a fully integrated clinical response, developing surge plans, preparing for ethical dilemmas, and having a cogent exit strategy for post disaster recovery.", "qid": 12, "docid": "2w99mje3", "rank": 33, "score": 0.6773508787155151}, {"content": "Title: A primer for pediatric radiologists on infection control in an era of COVID-19 Content: Pediatric radiology departments across the globe face unique challenges in the midst of the current COVID-19 pandemic that have not been addressed in professional guidelines. Providing a safe environment for personnel while continuing to deliver optimal care to patients is feasible when abiding by fundamental recommendations. In this article, we review current infection control practices across the multiple pediatric institutions represented on the Society for Pediatric Radiology (SPR) Quality and Safety committee. We discuss the routes of infectious transmission and appropriate transmission-based precautions, in addition to exploring strategies to optimize personal protective equipment (PPE) supplies. This work serves as a summary of current evidence-based recommendations for infection control, and current best practices specific to pediatric radiologists. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00247-020-04713-1) contains supplementary material, which is available to authorized users.", "qid": 12, "docid": "iy35298o", "rank": 34, "score": 0.6772075891494751}, {"content": "Title: Appraisal of recommended respiratory infection control practices in primary care and emergency department settings Content: BACKGROUND: The severe acute respiratory syndrome (SARS) epidemic and concern about pandemic influenza prompted the Centers for Disease Control and Prevention (CDC) to develop guidelines to prevent the transmission of all respiratory infections in health care settings during first contact with a potentially infected person. The extent to which health care workers and institutions use these CDC recommended practices is uncertain. METHODS: The study examined health care worker adherence to CDC recommended respiratory infection control practices in primary care clinics and emergency departments of 5 medical centers in King County, Washington, using a self-administered questionnaire. All clinical, allied, and administrative health care workers in study settings were invited to participate: 653 (53%) responded, and 630 were included. RESULTS: The survey revealed important shortcomings in overall personal and institutional use of CDC recommended practices, including deficiencies in posted alerts, patient masking and separation, hand hygiene, personal protective equipment, staff training, and written procedures. Use of recommended measures was generally higher among nursing staff than medical practitioners. CONCLUSION: This study found significant gaps in adherence to CDC recommendations for the control of respiratory infections in ambulatory care clinical settings. Practical strategies are needed to identify and reduce barriers to implementation of recommended practices for control of respiratory infections.", "qid": 12, "docid": "v6pqwgsy", "rank": 35, "score": 0.6760331392288208}, {"content": "Title: Factors influencing compliance with quarantine in Toronto during the 2003 SARS outbreak. Content: The purpose of this study was to cull lessons from Toronto's experiences with large-scale quarantine during the outbreak of Severe Acute Respiratory Syndrome in early 2003. We focused on issues that affected the population's willingness to comply with quarantine. Information was acquired from interviews, telephone polling, and focus groups. Issues of quarantine legitimacy, criteria for quarantine, and the need to allow some quarantined healthcare workers to leave their homes to go to work were identified. Also important was the need to answer questions from people entering quarantine about the continuation of their wages, salaries, and other forms of income while they were not working, and about the means by which they would be supplied with groceries and other services necessary for daily living. The threat of enforcement had less effect on compliance than did the credibility of compliance-monitoring. Fighting boredom and other psychological stresses of quarantine, muting the forces of stigma against those in quarantine, and crafting and delivering effective and believable communications to a population of mixed cultures and languages also were critical. The need for officials to develop consistent quarantine policies, procedures, and public messages across jurisdictional boundaries was paramount.", "qid": 12, "docid": "ehkht0mk", "rank": 36, "score": 0.6760101318359375}, {"content": "Title: COVID-19 and quarantine orders: A practical approach Content: Quarantine is a very effective method for containing the spread of highly infectious diseases in large populations during a pandemic, but it is only effective if properly implemented. The co-operation and compliance of people entering quarantine are critical to its success. However, owing to the isolating and social distancing nature of quarantine, it often leads to extreme economic hardship and shortages in basic needs such as food, medicine, water and communication- A nd to the curtailment of certain universal social norms such as attending a parent's funeral. To escape these hardships, people often refuse to enter voluntary quarantine, or breach quarantine rules. In these circumstances, health authorities are obliged to act in the best interests of the public and obtain court orders to force some people into quarantine. In further extreme circumstances, when a national lockdown is ordered, non-compliance with quarantine measures may result in arrests and penalties. The scope of this article is limited to the period prior to and following such a lockdown, during which quarantine may still be vital for the containment of COVID-19. Because a quarantine order will deprive an individual of his or her freedom, this must be carefully balanced with the public interest. This article explains the legal and ethical considerations of this balancing exercise and provides practical guidance for obtaining quarantine orders.", "qid": 12, "docid": "q49c71l1", "rank": 37, "score": 0.6758836507797241}, {"content": "Title: How to improve adherence with quarantine: Rapid review of the evidence Content: Objectives: The January 2020 outbreak of coronavirus has once again thrown the vexed issue of quarantine into the spotlight, with many countries asking their citizens to self-isolate if they have potentially come into contact with the infection. However, adhering to quarantine is difficult. Decisions on how to apply quarantine should be based on the best available evidence to increase the likelihood of people adhering to protocols. We conducted a rapid review to identify factors associated with adherence to quarantine during infectious disease outbreaks. Study design: Rapid evidence review. Methods: We searched Medline, PsycINFO and Web of Science for published literature on the reasons for and factors associated with adherence to quarantine during an infectious disease outbreak. Results: We found 3163 papers and included 14 in the review. Adherence to quarantine ranged from as little as 0 up to 92.8%. The main factors which influenced or were associated with adherence decisions were the knowledge people had about the disease and quarantine procedure, social norms, perceived benefits of quarantine and perceived risk of the disease, as well as practical issues such as running out of supplies or the financial consequences of being out of work. Conclusions: People vary in their adherence to quarantine during infectious disease outbreaks. To improve this, public health officials should provide a timely, clear rationale for quarantine and information about protocols; emphasise social norms to encourage this altruistic behaviour; increase the perceived benefit that engaging in quarantine will have on public health; and ensure that sufficient supplies of food, medication and other essentials are provided.", "qid": 12, "docid": "s0zdqd6d", "rank": 38, "score": 0.6753556728363037}, {"content": "Title: Infection control practices for SARS in Lao People's Democratic Republic, Taiwan, and Thailand: Experience from mobile SARS containment teams, 2003 Content: BACKGROUND: Despite available recommendations on infection control for severe acute respiratory syndrome (SARS), information is limited on actual practices in Asian hospitals during the epidemic. We describe practices observed by mobile SARS containment teams (mobile teams) during outbreak investigations. METHODS: We retrospectively summarized infection control practices observed in hospitals visited by mobile teams in the Lao People's Democratic Republic (PDR), Taiwan, and Thailand, during March and April 2003. RESULTS: Mobile teams investigated 22 reports of SARS in 20 hospitals (1, 5, and 14 hospitals in Lao PDR, Taiwan, and Thailand, respectively). Facilities ranged from urban hospitals with negative-pressure isolation rooms and high-efficiency particulate air filtration to rural hospitals with patient rooms open to outside air circulation and intermittent running water. At the time of mobile team visits, 5 (25%) hospitals implemented infection control practices consistent with World Health Organization recommendations on visitor policies, private negative-pressure rooms, and personal protective equipment. CONCLUSIONS: Early in the SARS epidemic, mobile teams found wide variations in infection control practices and resources among Asian hospitals evaluating patients for SARS, indicating the importance of ongoing assessment during SARS preparedness. Mobile teams are one mechanism to assess practices and promote implementation of recommended infection control measures.", "qid": 12, "docid": "d0ccqrmu", "rank": 39, "score": 0.6752399206161499}, {"content": "Title: Review of Hygiene and Disinfection Recommendations for Outpatient Glaucoma Care: A COVID Era Update Content: This review focuses on best practices and recommendations for hygiene and disinfection to limit exposure and transmission of infection in outpatient glaucoma clinics during the current COVID-19 pandemic.", "qid": 12, "docid": "welen5fl", "rank": 40, "score": 0.6751787066459656}, {"content": "Title: Barriers to at-home-preparedness in public health employees: implications for disaster preparedness training. Content: OBJECTIVES To assess \"at-home\" preparedness and barriers to preparedness in a cohort of public health employees. METHOD Conducted a cross-sectional survey involving 100 employees attending emergency preparedness training that emphasized incident command training and included a segment on \"at-home\" preparedness. RESULTS Fifteen percent of participants were rated as \"better prepared,\" and only 8% of participants would be considered \"most prepared.\" There was no relationship between the concern for bioterrorism and other disasters and preparedness. The principal barrier involved challenges in getting the task done versus lack of desire or knowledge. CONCLUSIONS There is great potential for distraction of public health workers during an emergent event if they are not prepared at home and have concern for family members. At-home preparedness training efforts that emphasize what should be done and why are likely to have limited impact on changing behavior. Strategies that ensure that small steps are taken are likely to be more successful.", "qid": 12, "docid": "6yhjuqxj", "rank": 41, "score": 0.6751324534416199}, {"content": "Title: Using effective hand hygiene practice to prevent and control infection Content: Decontamination using hand hygiene remains one of the most important and effective methods for reducing healthcare-associated infections and cross-infection between patients. In 1860, Florence Nightingale wrote that nurses should wash their hands frequently throughout the day, demonstrating an early awareness of the effectiveness of this simple procedure. The COVID-19 pandemic has demonstrated that effectively applied hand hygiene is a vital intervention that can be used to prevent the spread of disease. This article details the correct procedure required for effective hand hygiene and emphasises the need for nurses to keep up to date with evidence-based guidelines. The article also outlines the differences between hand decontamination using alcohol-based hand gels and soap and water, and the complex factors that can interfere with effective hand hygiene compliance.", "qid": 12, "docid": "k5lz7ql7", "rank": 42, "score": 0.6749927997589111}, {"content": "Title: Using effective hand hygiene practice to prevent and control infection. Content: Decontamination using hand hygiene remains one of the most important and effective methods for reducing healthcare-associated infections and cross-infection between patients. In 1860, Florence Nightingale wrote that nurses should wash their hands frequently throughout the day, demonstrating an early awareness of the effectiveness of this simple procedure. The COVID-19 pandemic has demonstrated that effectively applied hand hygiene is a vital intervention that can be used to prevent the spread of disease. This article details the correct procedure required for effective hand hygiene and emphasises the need for nurses to keep up to date with evidence-based guidelines. The article also outlines the differences between hand decontamination using alcohol-based hand gels and soap and water, and the complex factors that can interfere with effective hand hygiene compliance.", "qid": 12, "docid": "4jx0oq65", "rank": 43, "score": 0.6749927997589111}, {"content": "Title: Infection control practices in facilities for highly infectious diseases across Europe Content: Summary Background The management of patients with highly infectious diseases (HIDs) is a challenge for healthcare provision requiring a high level of care without compromising the safety of other patients and healthcare workers. Aim To study the infection control practice in isolation facilities participating in the European Network for Highly Infectious Diseases (EuroNHID) project. Methods A survey was conducted during 2009 of 48 isolation facilities caring for patients with HIDs in 16 European countries. Checklists and standard evaluation forms were used to collect and interpret data on hand hygiene, routine hygiene and disinfection, and waste management. Findings Forty percent of HIDs had no non-hand-operated sinks or alcohol-based antiseptic distributors, while 27% did not have procedures for routine hygiene, final disinfection, or safe discarding of non-disposable objects or equipment. There was considerable variation in the management of waste and in the training of housekeeping personnel. EuroNHID has developed recommendations for hand hygiene, disinfection, routine hygiene, and waste management. Conclusions Most aspects of hand hygiene, routine hygiene and disinfection, and waste management were considered at least partially adequate in the majority of European isolation facilities dedicated for the care of patients with HIDs. But considerable variability was observed, with management of waste and training of housekeeping personnel being generally less satisfactory.", "qid": 12, "docid": "098dcy4z", "rank": 44, "score": 0.6749226450920105}, {"content": "Title: How We Do It: Lessons on Outbreak Preparedness from the Cleveland Clinic Content: Abstract Disasters, including infectious disease outbreaks, are inevitable. Hospitals need to plan in advance to ensure that their systems can adapt to a rapidly changing environment if necessary. This review provides an overview of ten general principles that hospitals and healthcare systems should consider when developing disaster plans. The principles are consistent with an \u201call-hazards\u201d approach to disaster mitigation. This approach is adapted to planning for a multiplicity of threats, but emphasizes highly relevant scenarios, such as the COVID-19 pandemic. We also describe specific ways these principles helped prepare our hospital for this pandemic. Key points include acting quickly, identifying and engaging key stakeholders early, providing accurate information, prioritizing employee safety and mental health, promoting a fully integrated clinical response, developing surge plans, preparing for ethical dilemmas, and having a cogent exit strategy for post disaster recovery.", "qid": 12, "docid": "5lty18vs", "rank": 45, "score": 0.6748992800712585}, {"content": "Title: Methicillin-Resistant Staphylococcus aureus (MRSA) Contamination in Bedside Surfaces of a Hospital Ward and the Potential Effectiveness of Enhanced Disinfection with an Antimicrobial Polymer Surfactant Content: The aim in this study was to assess the effectiveness of a quaternary ammonium chloride (QAC) surfactant in reducing surface staphylococcal contamination in a routinely operating medical ward occupied by patients who had tested positive for methicillin-resistant Staphylococcus aureus (MRSA). The QAC being tested is an antibacterial film that is sprayed onto a surface and can remain active for up to 8 h. A field experimental study was designed with the QAC plus daily hypochlorite cleaning as the experimental group and hypochlorite cleaning alone as the control group. The method of swabbing on moistened surfaces was used for sampling. It was found that 83% and 77% of the bedside surfaces of MRSA-positive and MRSA-negative patients respectively were contaminated with staphylococci at 08:00 hours, and that the staphylococcal concentrations increased by 80% at 1200 h over a 4-hour period with routine ward and clinical activities. Irrespective of the MRSA status of the patients, high-touch surfaces around the bed-units within the studied medical ward were heavily contaminated (ranged 1 to 276 cfu/cm(2) amongst the sites with positive culture) with staphylococcal bacteria including MRSA, despite the implementation of daily hypochlorite wiping. However, the contamination rate dropped significantly from 78% to 11% after the application of the QAC polymer. In the experimental group, the mean staphylococcal concentration of bedside surfaces was significantly (p < 0.0001) reduced from 4.4 \u00b1 8.7 cfu/cm(2) at 08:00 hours to 0.07 \u00b1 0.26 cfu/cm(2) at 12:00 hours by the QAC polymer. The results of this study support the view that, in addition to hypochlorite wiping, the tested QAC surfactant is a potential environmental decontamination strategy for preventing the transmission of clinically important pathogens in medical wards.", "qid": 12, "docid": "xrf5sm6c", "rank": 46, "score": 0.6748877167701721}, {"content": "Title: The Role of the Home Environment in the Transmission of Infectious Diseases Content: The purpose of this paper is to examine current health care literature (1980\u20132000) regarding the microbiology of the home environment, to summarize evidence of transmission within the home, and to assess effectiveness of cleaning practices and products. The home environment, particularly the kitchen and bathroom, serves as a reservoir of large numbers of microorganisms, particularly Enterobacteriacae,and infectious disease transmission has been demonstrated to occur in 6\u201360% of households in which one member is ill. Current food preparation and cleaning practices provide multiple opportunities for intra-household member spread. Routine cleaning is often sufficient, but in cases of household infection, may not adequately reduce environmental contamination. The effectiveness of disinfectants varies considerably and depends on how they are used as well as their intrinsic efficacy. The behavioral aspects of infection prevention in the home (e.g., foodhandling and cleaning practices) warrant increased public attention and education.", "qid": 12, "docid": "jwpb7862", "rank": 47, "score": 0.6748160123825073}, {"content": "Title: Preventing healthcare\u2010associated infection: risks, healthcare systems and behaviour Content: More than 177 000 potentially preventable healthcare\u2010associated infections (HAIs) occur per annum in Australia with sizable attributable mortality. Organizational systems to protect against HAI in hospitals in Australia are relatively poorly developed. Awareness and practice of infection control by medical and other healthcare staff are often poor. These lapses in practice create significant risk for patients and staff from HAI. Excessive patient exposure to antimicrobials is another key factor in the emergence of antibiotic\u2010resistant bacteria and Clostridium difficile infection. Physicians must ensure that their interactions with patients are safe from the infection prevention standpoint. The critical preventative practice is hand hygiene in accord with the World Health Organization 5 moments model. Improving the use of antimicrobials, asepsis and immunization also has great importance. Hospitals should measure and feed back HAI rates to clinical teams. Physicians as leaders, role models and educators play an important part in promoting adherence to safe practices by other staff and students. They are also potentially effective system engineers who can embed safer practices in all elements of patient care and promote essential structural and organizational change. Patients and the public in general are becoming increasingly aware of the risk of infection when entering a hospital and expect their carers to adhere to safe practice. Poor infection control practice will be regarded in a negative light by patients and their families, regardless of any other manifest skills of the practitioner.", "qid": 12, "docid": "bc6sc2rc", "rank": 48, "score": 0.6744852662086487}, {"content": "Title: [Evaluating healthcare workers' infection control practice in a Lima metropolitan hospital during the influenza A(H1N1) epidemic]. Content: OBJECTIVE Determining healthcare workers' level of compliance with infection control practices in a Lima hospital during the influenza A(H1N1) epidemic. METHODS A cross-sectional observational study was made of 165 healthcare workers who provided inpatient care in risk areas like emergency services, emergency, intensive care and hospitalisation. The sample size was calculated using EpiInfo software (version 2000) and was based on simple systematic sampling. An ad hoc format validated by experts' judgement was used. RESULTS 23.6 % (39/165) of the respondents washed their hands before and after contact with patients, 72.7 % (96/132) wore gloves for healthcare when so indicated, 61.0 % (64/105) washed their hands after removing gloves, while 58.0 % (76/131) of those who had contact with contaminated material did so after such contact. Only 14.5 % (24/165) of workers engaged in good practice. CONCLUSIONS The percentage of healthcare workers' engaging in infection control practice in the study hospital during the 2009 influenza A(H1N1) epidemic was low.", "qid": 12, "docid": "ubp2otcf", "rank": 49, "score": 0.6744809746742249}, {"content": "Title: Family caregivers in public tertiary care hospitals in Bangladesh: Risks and opportunities for infection control Content: BACKGROUND: Family caregivers are integral to patient care in Bangladeshi public hospitals. This study explored family caregivers\u2019 activities and their perceptions and practices related to disease transmission and prevention in public hospitals. METHODS: Trained qualitative researchers conducted a total of 48 hours of observation in 3 public tertiary care hospitals and 12 in-depth interviews with family caregivers. RESULTS: Family caregivers provided care 24 hours a day, including bedside nursing, cleaning care, and psychologic support. During observations, family members provided 2,065 episodes of care giving, 75% (1,544) of which involved close contact with patients. We observed family caregivers washing their hands with soap on only 4 occasions. The majority of respondents said diseases are transmitted through physical contact with surfaces and objects that have been contaminated with patient secretions and excretions, and avoiding contact with these contaminated objects would help prevent disease. CONCLUSION: Family caregivers are at risk for hospital-acquired infection from their repeated exposure to infectious agents combined with their inadequate hand hygiene and knowledge about disease transmission. Future research should explore potential strategies to improve family caregivers\u2019 knowledge about disease transmission and reduce family caregiver exposures, which may be accomplished by improving care provided by health care workers.", "qid": 12, "docid": "3xtnztqm", "rank": 50, "score": 0.6740859746932983}, {"content": "Title: EMS Disease Exposure, Transmission, and Prevention: a Review Article Content: PURPOSE OF REVIEW: This article aims to review recent literature regarding the risks of disease exposure to pre-hospital providers and the patients they serve, as well as the challenges they face in minimizing transmission and exposure. RECENT FINDINGS: Many studies continue to show poor compliance with consistent universal precautions, as well as proper hand hygiene. Vaccination rates are suboptimal despite attempts to encourage compliance. With the spread of multi-drug resistant organisms, new techniques of decontamination need to be investigated. SUMMARY: There remains a general lack of information and studies regarding the risks of disease exposure and transmission to EMS providers despite the significance hazards their profession can pose. However, there remains a continued theme throughout the majority of EMS and pre-hospital studies, demonstrating that hand washing and consistent use of personal protective equipment remains a persistent, preventable means of disease exposure and transmission.", "qid": 12, "docid": "k4qwb7k8", "rank": 51, "score": 0.6740480661392212}, {"content": "Title: Barrier precautions, isolation protocols, and personal hygiene in veterinary hospitals Content: Because nosocomial and zoonotic diseases are inherent and ever-present risks in veterinary hospitals, proactive policies should be in place to reduce the risk of sporadic cases and outbreaks. Policies should ideally be put in place before disease issues arise, and policies should be effectively conveyed to all relevant personnel. Written policies are required for practical and liability reasons and should be reviewed regularly. Although no infection control program can eliminate disease concerns, proper implementation of barrier precautions and isolation can reduce the exposure of hospitalized animals and hospital personnel to infectious agents. Appropriate personal hygiene, particularly hand hygiene, can assist in the prevention of disease transmission when pathogens bypass barriers and are able to contact personnel. Veterinary hospitals have moral, professional, and legal requirements to provide a safe workplace and to reduce the risks to hospitalized patients. Based on experience in the human medical field and on the continual emergence of new infectious diseases, infection control challenges can only be expected to increase in the future. Regular reassessment of protocols based on ongoing research and clinical experiences is required.", "qid": 12, "docid": "2el9tx9v", "rank": 52, "score": 0.6738470792770386}, {"content": "Title: Economic analysis of healthcare-associated infection prevention and control interventions in medical and surgical units: Systematic review using a discounting approach Content: BACKGROUND: Nosocomial or healthcare-associated infections (HCAIs) are associated with a financial burden that affects both patients and healthcare institutions worldwide. The clinical best care practices (CBPs) of hand hygiene, hygiene and sanitation, screening, and basic and additional precautions aim to reduce this burden. The COVID-19 pandemic has confirmed these four CBPs are critically important prevention practices that limit the spread of HCAIs. AIM: This paper conducted a systematic review of economic evaluations related to these four CBPs using a discounting approach. METHODS: We searched for articles published between 2000 and 2019. We included economic evaluations of infection prevention and control of Clostridioides difficile-associated diarrhoea, meticillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and carbapenem-resistant Gram-negative bacilli. Results were analyzed with: cost-minimization, cost-effectiveness, cost-utility, cost-benefit and cost-consequence analyses. Articles were assessed for quality. RESULTS: A total of 11 898 articles were screened and seven were included. Most studies (4/7) were of overall moderate quality. All studies demonstrated cost effectiveness of CBPs. The average yearly net cost savings from the CBPs ranged from $252 847 (2019 $CAD) to $1 691 823 depending on the rate of discount (3% and 8%). The average incremental benefit cost ratio of CBPs varied from 2.48 to 7.66. CONCLUSION: In order to make efficient use of resources and maximize health benefits, ongoing research in the economic evaluation of infection control should be carried out to support evidence-based healthcare policy decisions.", "qid": 12, "docid": "u56zvty9", "rank": 53, "score": 0.673636794090271}, {"content": "Title: Infection prevention practices in the Netherlands: results from a National Survey Content: OBJECTIVE: To examine the extent to which acute care hospitals in the Netherlands have adopted recommended practices to prevent catheter-associated urinary tract infection (CAUTI), central line-associated bloodstream infection (CLABSI), ventilator-associated pneumonia (VAP), and Clostridioides difficile infection (CDI). METHODS: Between 18 July 2017 and 31 October 2017, we surveyed the infection prevention teams of all acute care hospitals in the Netherlands. The survey instrument was based on the \u2018Translating Healthcare-Associated Infection Prevention Research into Practice\u2019 (TRIP) questionnaire and adapted to the Dutch context. Descriptive statistics were used to examine the reported regular use of CAUTI, CLABSI, VAP, and CDI prevention practices as well as the hospital characteristics. RESULTS: Out of 72 eligible hospitals, 47 (65.3%) responded. Surveillance systems for monitoring CAUTI, CLABSI, VAP, and CDI were present in 17.8, 95.4, 26.2, and 77.3% of hospitals, respectively. Antimicrobial stewardship programs have been established in 91.5% of participating hospitals. For CAUTI, the majority of hospitals regularly used aseptic technique during catheter insertion (95%) and portable bladder ultrasound scanners (86.1%). Intermittent catheterization and catheter stop-orders were regularly used by 65.8 and 62.2% of hospitals. For CLABSI, all hospitals regularly used maximum sterile barrier precautions and chlorhexidine gluconate for insertion site antisepsis. Avoidance of the femoral site for central line insertions was regularly used by 65.9% of hospitals. Urinary catheters and central-lines impregnated with antibiotics or antiseptics were rarely used (\u2264 5%). Selective decontamination strategies for preventing VAP were used in 84% of hospitals. With the exception of disposable thermometers (31.8%), all prevention practices to prevent CDI were regularly used by more than 80% of hospitals. CONCLUSIONS: Most Dutch hospitals report regular use of recommended practices for preventing CLABSI and CDI. Several specific practices to prevent CAUTI and VAP were less frequently used, however, providing an opportunity for improvement.", "qid": 12, "docid": "xi59oxfo", "rank": 54, "score": 0.6735523343086243}, {"content": "Title: La surveillance des personnes contacts pour \u00c9bola : effets sociaux et enjeux \u00e9thiques au S\u00e9n\u00e9gal Content: Quarantine has been widely used during the Ebola outbreak in West Africa mainly to control transmission chains. This measure raises ethical issues that require documentation of the modalities of quarantine at the field level and its social effects for contact persons. In Senegal, 74 people were in contact with the Ebola case coming from Guinea in September 2014. Of these, 34 members of the case\u2019s household were contained together at home and monitored by officers. The remaining 40 health care workers from two facilities were dispersed in their family households and monitored by telephone or during doctors\u2019 visits. The study is based on in-depth interviews with 43 adult contacts about their experiences and perceptions, with additional observation for interpretation and contextualization. Containment at home was applied differently to contacts who lived with patient zero than to professional health care contacts. No coercion was used at first since all contacts adhered to surveillance, but some of them did not fully comply with movement restrictions. Contacts found biosafety precautions stigmatizing, especially during the first days when health workers and contacts were feeling an acute fear of contagion. The material support that was provided\u2014food and money\u2014was necessary since contacts could not work nor get resources, but it was too limited and delayed. The relational support they received was appreciated, as well as the protection from stigmatization by the police and follow-up workers. But the information delivered to contacts was insufficient, and some of them, including health workers, had little knowledge about EVD and Ebola transmission, which caused anxiety and emotional suffering. Some contacts experienced the loss of their jobs and loss of income; several could not easily or fully return to their previous living routines. Beyond its recommendations to enhance support measures, the study identifies the ethical stakes of quarantine in Senegal regarding informed consent and individual autonomy, non-maleficence and benevolence, and equity and adaptation to specific situations. Nevertheless, the balance between preventive benefits and individual inconveniences of quarantine should still be evaluated from a public health perspective.", "qid": 12, "docid": "19wkwldb", "rank": 55, "score": 0.6726456880569458}, {"content": "Title: Use of Unannounced \u201cMystery Patient Drills\u201d to Assess Hospital Emergency Department Preparedness for Communicable Diseases of Public Health Concern in New York City, 2016 Content: BACKGROUND: Recent infectious disease epidemics have highlighted the importance of rapid recognition and isolation of patients with severe infectious diseases. In response, the New York City Department of Health and Mental Hygiene carried out a series of unannounced \u201cMystery Patient Drills\u201d to assess Emergency Departments (ED) ability to identify and safely respond to patients with communicable diseases of public health concern. METHODS: All 911-receiving hospitals participating in the NYC Hospital Preparedness Program were recruited to participate. Scenarios utilized an actor presenting to an ED describing symptoms and history consistent with measles or MERS-CoV. An exercise evaluation guide captured performance measures to analyze 1) compliance with key infection control measures; 2) association between screening interventions (e.g., travel history) and implementation of infection control measures; 3) times from patient entry to triage, donning a mask, and placement into isolation. Post-drill report narratives were reviewed to identify additional strengths and challenges. RESULTS: Among 50 eligible hospitals, 49 participated in 2 drills (N = 98) during December 2015\u2013May 2016. Three pilot drills were excluded from the analysis. The patient was masked and isolated in 78% of drills; 61% of hospitals completed this process in both drills. Masking and isolation was observed in a higher proportion of drills when travel history was obtained, compared with drills when travel history was not obtained (88% vs. 21%; P < 0.0001). The median time from patient entry to masking was 1 minute and 9 minutes to placement into isolation. Overall, 36% of staff practiced hand hygiene and 77% entered the isolation room wearing Personal Protective Equipment. Identified best practices include the use of triage questionnaires to identify high-risk patients and algorithms to guide masking and isolation procedures. CONCLUSION: ED staff\u2019s ability to identify potentially infectious patients and implement recommended control measures varied. Drill findings were used to inform hospital improvement planning and will guide citywide efforts to improve healthcare system readiness for communicable diseases through addressing identified gaps and supporting implementation of best practice recommendations. DISCLOSURES: All authors: No reported disclosures.", "qid": 12, "docid": "y9ppd9c3", "rank": 56, "score": 0.6718093156814575}, {"content": "Title: Ethics and public health emergencies: restrictions on liberty. Content: Responses to public health emergencies can entail difficult decisions about restricting individual liberties to prevent the spread of disease. The quintessential example is quarantine. While isolating sick patients tends not to provoke much concern, quarantine of healthy people who only might be infected often is controversial. In fact, as the experience with severe acute respiratory syndrome (SARS) shows, the vast majority of those placed under quarantine typically don't become ill. Efforts to enforce involuntary quarantine through military or police powers also can backfire, stoking both panic and disease spread. Yet quarantine is part of a limited arsenal of options when effective treatment or prophylaxis is not available, and some evidence suggests it can be effective, especially when it is voluntary, home-based and accompanied by extensive outreach, communication and education efforts. Even assuming that quarantine is medically effective, however, it still must be ethically justified because it creates harms for many of those affected. Moreover, ethical principles of reciprocity, transparency, non-discrimination and accountability should guide any implementation of quarantine.", "qid": 12, "docid": "3rtx6fo3", "rank": 57, "score": 0.6715100407600403}, {"content": "Title: Infection control in residential care homes for the elderly in Hong Kong (2005-2014). Content: INTRODUCTION This serial cross-sectional survey study aimed to review the trend in various infection control practices in residential care homes for the elderly (RCHEs) in Hong Kong from 2005 to 2014. METHODS Annual cross-sectional surveys were conducted at all RCHEs in Hong Kong, including self-administered questionnaires, on-site interviews, inspections, and assessments conducted by trained nurses, from 2005 to 2014. In all, 98.5% to 100% of all RCHEs were surveyed each year based on the list of licensed RCHEs in Hong Kong. RESULTS There was a substantial increase in the proportion of RCHE residents aged \u226585 years, from 40.0% in 2005 to 50.2% in 2014 (P=0.002). The percentage of RCHE residents with special care needs also increased, from 22.3% in 2005 to 32.6% in 2014 for residents with dementia (P<0.001) and from 3.4% in 2005 to 5.0% in 2014 for residents with a long-term indwelling urinary catheter (P<0.001). The proportion of RCHEs with separate rooms for isolation areas ranged from 73.6% to 80% but did not show any significant trend over the study period. The proportion of RCHEs with alcohol hand rub available showed an increasing trend from 25.4% in 2006 to 99.2% in 2014 (P=0.008). The proportion of health or care workers (who were not the designated infection control officers) passing skills tests on hand washing techniques increased from 79.2% in 2006 to 91.5% in 2014 (P=0.02). An increasing trend was also observed for the proportion of infection control officers who were able to prepare properly diluted bleach solution, from 71.5% in 2005 to 92.2% in 2014 (P=0.002). CONCLUSIONS For infection control practice to continue improving, more effort should be made to enhance and maintain proper practice, and to mitigate the challenge posed by the high turnover rates of healthcare workers in RCHEs. Introduction of self-audits on infection control practices should be considered.", "qid": 12, "docid": "zp1ztg3c", "rank": 58, "score": 0.6705544590950012}, {"content": "Title: Lack of compliance with basic infection control measures during cardiopulmonary resuscitation\u2014Are we ready for another epidemic? Content: Summary Objective Healthcare workers in the emergency department are particularly vulnerable to communicable disease. This study aimed to evaluate compliance with standard precautions by analysis of the incidence and systems sources of such contaminations and by quantifying the use of personal protective equipment. Method A prospective observational study from 1 November 2005 to 30 April 2006, using analysis of video segments. Videotapes were recorded in two rooms designed for cardiopulmonary resuscitation of out-of-hospital cardiac arrests, and compliance with basic infection control measures by all emergency department crews was monitored. Results A total of 44 consecutive performances of cardiopulmonary resuscitation were recorded for time-motion analysis. The percentages of staff wearing personal protective equipment were 90%, 50%, 20% and 75% for masks, eye protection, gowns and gloves, respectively. Compliance ranking scored doctors as high, trainees as moderate and nursing staff as low. Overall contamination rate was 16.9\u00d710\u22122 events/person-min. The two leading systems sources for contamination were lack of specific task assignments among rescuers (44%) and inadequate preparation for procedures (42%). Conclusions Among healthcare workers in the emergency setting, the study disclosed suboptimal compliance with basic infection control measures, including use of personal protective equipment and avoiding contamination. By further time-motion analysis of resuscitation sessions, major systems sources and strategies for improvement could be identified.", "qid": 12, "docid": "64nix91j", "rank": 59, "score": 0.670421302318573}, {"content": "Title: Back to basics: hand hygiene and isolation Content: PURPOSE OF REVIEW: Hand hygiene and isolation are basic, but very effective, means of preventing the spread of pathogens in healthcare. Although the principle may be straightforward, this review highlights some of the controversies regarding the implementation and efficacy of these interventions. RECENT FINDINGS: Hand hygiene compliance is an accepted measure of quality and safety in many countries. The evidence for the efficacy of hand hygiene in directly reducing rates of hospital-acquired infections has strengthened in recent years, particularly in terms of reduced rates of staphylococcal sepsis. Defining the key components of effective implementation strategies and the ideal method(s) of assessing hand hygiene compliance are dependent on a range of factors associated with the healthcare system. Although patient isolation continues to be an important strategy, particularly in outbreaks, it also has some limitations and can be associated with negative effects. Recent detailed molecular epidemiology studies of key healthcare-acquired pathogens have questioned the true efficacy of isolation, alone as an effective method for the routine prevention of disease transmission. SUMMARY: Hand hygiene and isolation are key components of basic infection control. Recent insights into the benefits, limitations and even adverse effects of these interventions are important for their optimal implementation.", "qid": 12, "docid": "q4nzhbvt", "rank": 60, "score": 0.6695569753646851}, {"content": "Title: epic2: National Evidence-Based Guidelines for Preventing Healthcare-Associated Infections in NHS Hospitals in England Content: Executive Summary National evidence-based guidelines for preventing healthcare-associated infections (HCAI) in National Health Service (NHS) hospitals in England were commissioned by the Department of Health (DH) and developed during 1998-2000 by a nurse-led multi-professional team of researchers and specialist clinicians. Following extensive consultation, they were published in January 2001.1 These guidelines describe the precautions healthcare workers should take in three areas: standard principles for preventing HCAI, which include hospital environmental hygiene, hand hygiene, the use of personal protective equipment, and the safe use and disposal of sharps; preventing infections associated with the use of short-term indwelling urethral catheters; and preventing infections associated with central venous catheters. The evidence for these guidelines was identified by multiple systematic reviews of experimental and non-experimental research and expert opinion as reflected in systematically identified professional, national and international guidelines, which were formally assessed by a validated appraisal process. In 2003, we developed complementary national guidelines for preventing HCAI in primary and community care on behalf of the National Collaborating Centre for Nursing and Supportive Care (National Institute for Healthand Clinical Excellence).2 A cardinal feature of evidence-based guidelines is that they are subject to timely review in order that new research evidence and technological advances can be identified, appraised and, if shown to be effective in preventing HCAI, incorporated into amended guidelines. Periodically updating the evidence base and guideline recommendations is essential in order to maintain their validity and authority. Consequently, the DH commissioned a review of new evidence published following the last systematic reviews. We have now updated the evidence base for making infection prevention and control recommendations. A critical assessment of the updated evidence indicated that the original epic guidelines published in 2001 remain robust, relevant and appropriate but that adjustments need to be made to some guideline recommendations following a synopsis of the evidence underpinning the guidelines. These updated national guidelines (epic2) provide comprehensive recommendations for preventing HCAI in hospitals and other acute care settings based on the best currently available evidence. Because this is not always the best possible evidence, we have included a suggested agenda for further research in each section of the guidelines. National evidence-based guidelines are broad principles of best practice which need to be integrated into local practice guidelines. To monitor implementation, we have suggested key audit criteria for each section of recommendations. Clinically effective infection prevention and control practice is an essential feature of protecting patients. By incorporating these guidelines into routine daily clinical practice, patient safety can be enhanced and the risk of patients acquiring an infection during episodes of healthcare in NHS hospitals in England can be minimised.", "qid": 12, "docid": "757mh2mh", "rank": 61, "score": 0.6685495376586914}, {"content": "Title: Heating, ventilation and air conditioning (HVAC) in intensive care unit Content: The aim of this review is to describe variation in standards and guidelines on 'heating, ventilation and air-conditioning (HVAC)' system maintenance in the intensive care units, across the world, which is required to maintain good 'indoor air quality' as an important non-pharmacological strategy in preventing hospital-acquired infections. An online search and review of standards and guidelines published by various societies including American Institute of Architects (AIA), American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE), Centers for Disease Control and Prevention (CDC), Department of Health Estates and Facilities Division, Health Technical Memorandum 2025 (HTM) and Healthcare Infection Control Practices Advisory Committee (HICPAC) along with various national expert committee consensus statements, regional and hospital-based protocols available in a public domain were retrieved. Selected publications and textbooks describing HVAC structural aspects were also reviewed, and we described the basic structural details of HVAC system as well as variations in the practised standards of HVAC system in the ICU, worldwide. In summary, there is a need of universal standards for HVAC system with a specific mention on the type of ICU, which should be incorporated into existing infection control practice guidelines.", "qid": 12, "docid": "imlhz0nf", "rank": 62, "score": 0.6683865189552307}, {"content": "Title: Personal healthcare worker (HCW) and work-site characteristics that affect HCWs' use of respiratory-infection control measures in ambulatory healthcare settings. Content: OBJECTIVES To identify healthcare worker (HCW) and work-site characteristics associated with HCWs' reported use of recommended respiratory-infection control practices in primary and emergency care settings. DESIGN A cross-sectional study using a self-administered questionnaire for HCWs during the summer and fall of 2005. SETTING Primary and emergency care clinics at 5 medical centers in King County, Seattle, Washington. RESULTS Nurse professionals who reported receiving training (odds ratio [OR], 2.5 [confidence interval {CI}, 1.1-5.9]; P=.029), instructional feedback from supervisors (OR, 3.0 [CI, 1.5-5.9]; P=.002), and management support for implementing safe work practices had a higher odds of also reporting adherence to recommended respiratory precautions, compared with nurses who did not. Training was the only important determinant for adherence to respiratory precaution measures among medical practitioners (OR, 5.5 [CI, 1.2-25.8]; P=.031). The reported rate of adherence to hand hygiene practices was higher among nurse professionals who were male (OR, 2.2 [CI, 1.0-4.9]; P=.045), had infants, small children, or older adults living at home (OR, 2.2 [CI, 1.2-3.9]; P=.007), reported cleanliness and orderliness of the establishment where they worked (OR, 2.0 [CI, 1.1-3.5]; P=.019), had received respiratory-infection control training (OR, 3.2 [CI, 1.8-6.0]; P<.001), and reported fears about catching a dangerous respiratory infection at work (OR, 2.3 [CI, 1.2-4.5]; P=.011). CONCLUSION A number of HCW and work-site characteristics associated with HCWs' use of recommended respiratory-infection control measures have been identified. These potentially influential characteristics should be considered as targets or guides for further investigation, which should include the evaluation of intervention strategies.", "qid": 12, "docid": "3noawzpf", "rank": 63, "score": 0.6677793860435486}, {"content": "Title: What's the plan? The unique challenges facing the home and community care sector in preparing for a pandemic. Content: Recent experience with the outbreak of severe acute respiratory syndrome (SARS) in Canada and the global threat of the H5N1 virus (avian \"flu\") have increased the appetite for and urgency of pandemic planning as a policy issue. The healthcare setting is one of the most important areas to prepare for such an event, and it is crucial that discussions around doing so include all settings in which care is delivered. As the home and community care sector is increasingly utilized and likely to be relied upon even more during a pandemic, addressing the challenges to occupational health and safety uniquely faced by this sector will be vitally important to the entire health system. A pandemic plan that does not consider healthcare outside of the institutional setting is incomplete and will be likely to fail. This commentary outlines the challenges to providing care in the home and community that must be considered in any plan designed to deal with a pandemic on a system-wide level.", "qid": 12, "docid": "yifhgoal", "rank": 64, "score": 0.6677725315093994}, {"content": "Title: Recommendations in covid-19 times: a view for home care. Content: OBJECTIVE To suggest recommendations for the practice of Home Nursing in the context of COVID-19. METHOD Reflective study, originated from readings associated with the theme, available in current guidelines from the Pan American Health Organization, World Health Organization and the Ministry of Health. RESULTS Recommendations were developed from current scientific evidence for prevention of infections, control of epidemics and pandemics in the Brazilian home scenario. FINAL CONSIDERATIONS the reflections achieved contribute to guiding actions for better assistance to the patient, family caregivers and the community in the perspective of safe home care with COVID-19, and it is characterized as an introductory discussion on the theme, encouraging new studies to be carried out from the unfolding of the current scenario.", "qid": 12, "docid": "wi6hykvg", "rank": 65, "score": 0.66767418384552}, {"content": "Title: Do we need an ethical framework for hospital infection control? Content: Summary Strategies for the control of the spread of infection in hospitals may lead to constraints on individual autonomy, freedom of movement, or contact with others. Codes of (ethical) practice for healthcare professionals tend to emphasise responsibilities to individual patients. Ethical frameworks for public health focus on groups of individuals (populations), the majority of whom are relatively healthy and empowered. Hospital infection control professionals must take account of both of these perspectives, sensitive to the care of infected and potentially infectious individuals, while protecting the vulnerable and relatively dependent population of hospital patients from further compromise to their health. A number of frameworks for an ethics of public health have been proposed over the last few years but there are sufficient differences in ethical considerations between collective interventions that aim to protect and promote the health of the public and interventions taken in the context of hospital infection control to justify a distinctive ethics of hospital infection control. Professional bodies may be best placed to lead the development of such a framework.", "qid": 12, "docid": "woscjkii", "rank": 66, "score": 0.6674115657806396}, {"content": "Title: Current Practices for Infection Prevention in the Hospital Settings Content: The principles and practices aimed at prevention and control of hospital-acquired infections are directed at various links in the chain of transmission. They include the following: (1) to contain or eliminate the reservoirs of agents and/or to curtail the persistence of agents in a specific setting, (2) to protect the host against disease caused by microorganisms, and (3) to interrupt the transmission of infection. Interventions to modify environmental reservoirs are aimed at interrupting the transmission for these inanimate environmental sources. The barriers, e.g., masks, were used to keep the smells and \u201ccontagion\u201d away even before the germ theory of disease was conceived. The appropriate barriers now include gloves, gowns, and eye protection for blood/body fluid\u2013borne infections and high-filtration masks for infections transmitted by droplet nuclei. The most important and effective nosocomial infection control intervention remains the routine washing of hands before, between, and after patient contact in healthcare settings. This chapter focuses on the interruption of transmission of infectious agents in the hospital setting by Standard Precautions recommended for all patients and \u201cisolation\u201d of patients using precautions based on known methods of transmission.", "qid": 12, "docid": "mtpbzgr9", "rank": 67, "score": 0.6670759916305542}, {"content": "Title: Issues Relevant to the Adoption and Modification of Hospital Infection-Control Recommendations for Avian Influenza (H5N1 Infection) in Developing Countries Content: The reemergence of avian influenza (H5N1 infection) has heightened concern for a potential human influenza pandemic. Recommendations regarding preparation for a global avian influenza pandemic are available, and it is imperative that health care workers participate in preparedness planning and training. In developing countries, health care worker preparedness training should address the modes of avian influenza transmission and specify how to implement appropriate infection-control strategies to prevent and control the spread of avian influenza. We provide evidence for avian influenza transmission methods and identify prevention strategies relevant to infection control for hospitals in developing countries. Pandemic influenza preparedness plans must include health care administrative support, mechanisms to rapidly create temporary isolation facilities, systems to restrict access to exposed health care workers, and plans to involve specialists to screen and identify cases early, to provide for continuous monitoring to ensure adherence to optimal infection-control practices, and to provide regular feedback to health care workers", "qid": 12, "docid": "9zf2h0xr", "rank": 68, "score": 0.6668669581413269}, {"content": "Title: Infection prevention and control: Who is the judge, you or the guidelines? Content: Objectives The aim of this study was to explore the attitudes and behaviours of registered nurses and their colleagues around the adoption of standard precautions in order to determine strategies to promote adherence. Design A qualitative exploratory descriptive design used interviews and focus group to collect data. Setting Registered nurses and registered midwifes from a tertiary metropolitan hospital took part in the study. Participants A voluntary sample of 29 adults was recruited from the Australian nursing (n = 25) and midwifery (n = 4) workforce. There were six men (mean age = 36.83 years; SD = 8.93) and 23 women (mean age = 41.36 years; SD = 10.25). Participants were recruited through advertisement on notice boards and emails from unit managers. Results Thematic analysis revealed five themes but the focus here is on staff judgements which are against the guidelines. Participants indicated that where in their judgement the patient posed no risk and they judged themselves skilled in the procedure, they were justified in deviating from the guidelines. Some staff judgements appeared to be self-protecting, while others were irrational and inconsistent. Conclusions Despite use of standard precautions being mandated, staff often deviated from them based on their own assessment of the situation or the patient. Any deviance from the guidelines is of concern but especially so when staff take it upon themselves to apply their own criteria or judgements. These results also suggest there may be some organisational inadequacies with regards to training and supervision of staff.", "qid": 12, "docid": "v8fdik8a", "rank": 69, "score": 0.666582465171814}, {"content": "Title: Reducing antibiotic prescribing and addressing the global problem of antibiotic resistance by targeted hygiene in the home and everyday life settings: A Position Paper Content: Antimicrobial resistance (AMR) continues to threaten global health. Although global and national AMR action plans are in place, infection prevention and control is primarily discussed in the context of healthcare facilities with home and everyday life settings barely addressed. As seen with the recent global SARS-CoV-2 pandemic, everyday hygiene measures can play an important role in containing the threat from infectious microorganisms. This position paper has been developed following a meeting of global experts in London, 2019. It presents evidence that home and community settings are important for infection transmission and also the acquisition and spread of AMR. It also demonstrates that the targeted hygiene approach offers a framework for maximizing protection against colonization and infections, thereby reducing antibiotic prescribing and minimizing selection pressure for the development of antibiotic resistance. If combined with the provision of clean water and sanitation, targeted hygiene can reduce the circulation of resistant bacteria in homes and communities, regardless of a country's Human Development Index (overall social and economic development). Achieving a reduction of AMR strains in healthcare settings requires a mirrored reduction in the community. The authors call upon national and international policy makers, health agencies and healthcare professionals to further recognize the importance of targeted hygiene in the home and everyday life settings for preventing and controlling infection, in a unified quest to tackle AMR.", "qid": 12, "docid": "e0hd3iuu", "rank": 70, "score": 0.6665797829627991}, {"content": "Title: Survey of acute hospital infection control resources and services in the Republic of Ireland Content: Summary Following the development of national guidelines on the control of antimicrobial resistance in 2001, a survey was carried out in 2003 of all 68 acute hospitals in the Republic of Ireland on resources available and current practice to control and prevent nosocomial infection. Completed questionnaires were received from 66 hospitals (97%). The median number of acute inpatient beds per hospital was 156; this was 522 in regional/tertiary referral centres. Only 31 (47%) hospitals had on-site consultant microbiologist sessions, and there was an infection control nurse in 56 (85%) hospitals. Eighteen (29%) hospitals had an occupational health physician, and 48 (73%) hospitals had an infection control committee. There was a median of one isolation room for every 16 acute beds, and a median of five rooms with en-suite bathroom facilities per hospital in those hospitals that provided data. All hospitals had documented infection control policies, and these were available in electronic format in 25 (38%) hospitals. Fifty-five (83%) hospitals undertook surveillance of nosocomial infection, and alcohol-based hand hygiene facilities were available, either at a handwashing sink or at the entrance to a ward, in 57 (86%) hospitals. In the Republic of Ireland, there remains a significant shortage of microbiologists/infection control doctors, occupational health physicians and infection control nurses. Isolation facilities are also inadequate. Although there is much agreement internationally on the importance of nosocomial infection and the priorities for surveillance, there are no agreed basic minimum standards for the resources and facilities necessary to control and prevent nosocomial infection.", "qid": 12, "docid": "93whg9zx", "rank": 71, "score": 0.6665220260620117}, {"content": "Title: Reflection on SARS precautions in a severe intellectual disabilities hospital in Hong Kong Content: Background Hong Kong went through a battle with a new respiratory disease, severe acute respiratory syndrome (SARS), from March to June 2003. All clinical settings, including rehabilitative and infirmary setting, have actively involved in fighting against the infection. The intent of this paper was to reflect on the SARS precautionary measures that had been taken in a severe intellectual disabilities hospital in Hong Kong. Methods A review on six SARS precautionary measures were conducted. They were assessment of risk, formulation of operational guidelines, implementation of infection control measures, education and training of staff, conducting audits and carrying out environmental improvement work. Results Patients were at risk of getting infected from carers, visitors, volunteers, and staff and patients of general hospitals. A SARS Quarantine Unit, isolation ward, was opened to isolate patients who might have had close contact with SARS patients during a stay in a general hospital or when they returned from home leave. Undoubtedly, both staff and relatives participated in preventing the patients from being infected. No day leave and home leave was reported and the number of hospitalization in general hospital was decreased during the critical period. Three infection control audits were conducted and improvement work was carried out subsequently. Conclusion The practice of grouping within a standard isolation room is recommended to continue in the future. Moreover, intensive infection control training for all staff is of highest importance to safeguard the health of both staff and patient.", "qid": 12, "docid": "ax7tm4os", "rank": 72, "score": 0.6664328575134277}, {"content": "Title: Infection control in paediatric office settings Content: Transmission of infection in the paediatric office is of increasing concern. The present document discusses routes of transmission of infection and the principles of current infection control measures. Prevention includes appropriate office design and administrative policies, triage, routine practices for the care of all patients (eg, hand hygiene; use of gloves, masks, eye protection and gowns for specific procedures; adequate cleaning, disinfection and sterilization of surfaces and equipment including toys, and aseptic technique for invasive procedures), and additional precautions for specific infections. Personnel should be adequately immunized, and those infected should follow work-restriction policies.", "qid": 12, "docid": "29jiro0p", "rank": 73, "score": 0.6662899255752563}, {"content": "Title: Obstetricians on the Coronavirus Disease 2019 (COVID-19) Front Lines and the Confusing World of Personal Protective Equipment Content: As health care systems struggle to maintain adequate supplies of personal protective equipment, there is confusion and anxiety among obstetricians and others about how to best protect themselves, their coworkers, and their patients. Although use of personal protective equipment is a critical strategy to protect health care personnel from coronavirus disease 2019 (COVID-19), other strategies also need to be implemented on labor and delivery units to reduce the risk of health care\u2013associated transmission, including screening of all pregnant women who present for care (case identification), placing a mask on and rapidly isolating ill pregnant women, and minimizing the number of personnel who enter the room of an ill patient (physical distancing). Although the mechanism of transmission of COVID-19 is not known with certainty, current evidence suggests that COVID-19 is transmitted primarily through respiratory droplets. Therefore, strict adherence to hand hygiene and consistent use of recommended personal protective equipment are cornerstones for reducing transmission. In addition, it is critical that health care professionals receive training on and practice correct donning (putting on) and doffing (removing) of personal protective equipment and avoid touching their faces as well as their facial protection to minimize self-contamination.", "qid": 12, "docid": "9ae8qhcg", "rank": 74, "score": 0.6661734580993652}, {"content": "Title: Obstetricians on the Coronavirus Disease 2019 (COVID-19) Front Lines and the Confusing World of Personal Protective Equipment Content: As health care systems struggle to maintain adequate supplies of personal protective equipment, there is confusion and anxiety among obstetricians and others about how to best protect themselves, their coworkers, and their patients. Although use of personal protective equipment is a critical strategy to protect health care personnel from coronavirus disease 2019 (COVID-19), other strategies also need to be implemented on labor and delivery units to reduce the risk of health care-associated transmission, including screening of all pregnant women who present for care (case identification), placing a mask on and rapidly isolating ill pregnant women, and minimizing the number of personnel who enter the room of an ill patient (physical distancing). Although the mechanism of transmission of COVID-19 is not known with certainty, current evidence suggests that COVID-19 is transmitted primarily through respiratory droplets. Therefore, strict adherence to hand hygiene and consistent use of recommended personal protective equipment are cornerstones for reducing transmission. In addition, it is critical that health care professionals receive training on and practice correct donning (putting on) and doffing (removing) of personal protective equipment and avoid touching their faces as well as their facial protection to minimize self-contamination.", "qid": 12, "docid": "fw32babp", "rank": 75, "score": 0.6653956770896912}, {"content": "Title: Heating, ventilation and air conditioning (HVAC) in intensive care unit Content: The aim of this review is to describe variation in standards and guidelines on \u2018heating, ventilation and air-conditioning (HVAC)\u2019 system maintenance in the intensive care units, across the world, which is required to maintain good \u2018indoor air quality\u2019 as an important non-pharmacological strategy in preventing hospital-acquired infections. An online search and review of standards and guidelines published by various societies including American Institute of Architects (AIA), American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE), Centers for Disease Control and Prevention (CDC), Department of Health Estates and Facilities Division, Health Technical Memorandum 2025 (HTM) and Healthcare Infection Control Practices Advisory Committee (HICPAC) along with various national expert committee consensus statements, regional and hospital-based protocols available in a public domain were retrieved. Selected publications and textbooks describing HVAC structural aspects were also reviewed, and we described the basic structural details of HVAC system as well as variations in the practised standards of HVAC system in the ICU, worldwide. In summary, there is a need of universal standards for HVAC system with a specific mention on the type of ICU, which should be incorporated into existing infection control practice guidelines.", "qid": 12, "docid": "ydogpjyd", "rank": 76, "score": 0.6653620004653931}, {"content": "Title: Application of Biosafety Principles in Laboratory Analysis of Clinical Samples from Patients with COVID-19 Content: COVID-19 poses a great challenge to clinical and diagnostic services around the world. The need of biosafety practices can never be emphasised more than under current circumstances. The four pillars of biosafety namely, leadership, standard operating procedures, personal protective equipment (PPE) and engineering controls must be employed for effective and safe practices in the clinical setting in general and laboratory settings in particular. Risk assessment must be carried out before meeting up the diagnostic challenge for COVID-19 and essential biorisk management measures are required to be taken. In our resource-poor settings, we need to adapt safe but cost-effective and improvised solutions to ensure safe handling of clinical samples from COVID-19 patients in the laboratories. The correct use of PPE and their suitable alternatives are available for selection and use. Disinfection of the lab areas and safe disposal of the clinical samples from such patients is also of paramount importance.", "qid": 12, "docid": "8h4adfqi", "rank": 77, "score": 0.6649013757705688}, {"content": "Title: Application of Biosafety Principles in Laboratory Analysis of Clinical Samples from Patients with COVID-19. Content: COVID-19 poses a great challenge to clinical and diagnostic services around the world. The need of biosafety practices can never be emphasised more than under current circumstances. The four pillars of biosafety namely, leadership, standard operating procedures, personal protective equipment (PPE) and engineering controls must be employed for effective and safe practices in the clinical setting in general and laboratory settings in particular. Risk assessment must be carried out before meeting up the diagnostic challenge for COVID-19 and essential biorisk management measures are required to be taken. In our resource-poor settings, we need to adapt safe but cost-effective and improvised solutions to ensure safe handling of clinical samples from COVID-19 patients in the laboratories. The correct use of PPE and their suitable alternatives are available for selection and use. Disinfection of the lab areas and safe disposal of the clinical samples from such patients is also of paramount importance.", "qid": 12, "docid": "7z2cq8gq", "rank": 78, "score": 0.6649013757705688}, {"content": "Title: Fact-finding survey of nosocomial infection control in hospitals in Vietnam and application to training programs Content: Abstract Nosocomial infection control is crucial for improving the quality of medical care. It is also indispensable for implementing effective control measures for severe acute respiratory syndrome (SARS) and the possible occurrence of a human influenza pandemic. The present authors, in collaboration with Vietnamese hospital staff, performed a fact-finding survey of nosocomial infection control in hospitals in northern Vietnam and compared the results with those of a survey conducted 4 years previously. Remarkable improvement was recognized in this period, although there were considerable differences between the central hospitals in Hanoi and local hospitals. In the local hospitals, basic techniques and the systems for infection control were regarded as insufficient, and it is necessary to improve these techniques and systems under the guidance of hospitals in the central area. Based on the results of the survey, programs were prepared and training courses were organized in local hospitals. Evaluation conducted after the training courses showed a high degree of satisfaction among the trainees. The results of the survey and the training courses conducted during the study period are expected to contribute to the improvement of nosocomial infection control in remote areas of Vietnam", "qid": 12, "docid": "89ynxd0l", "rank": 79, "score": 0.6644010543823242}, {"content": "Title: How to improve adherence with quarantine: Rapid review of the evidence Content: Abstract Objectives The January 2020 outbreak of coronavirus has once again thrown the vexed issue of quarantine into the spotlight, with many countries asking their citizens to \u2018self-isolate\u2019 if they have potentially come into contact with the infection. However, adhering to quarantine is difficult. Decisions on how to apply quarantine should be based on the best available evidence to increase the likelihood of people adhering to protocols. We conducted a rapid review to identify factors associated with adherence to quarantine during infectious disease outbreaks. Study design Rapid evidence review. Methods We searched Medline, PsycINFO and Web of Science for published literature on the reasons for and factors associated with adherence to quarantine during an infectious disease outbreak. Results We found 3163 papers and included 14 in the review. Adherence to quarantine ranged from as little as 0 up to 92.8%. The main factors which influenced or were associated with adherence decisions were the knowledge people had about the disease and quarantine procedure, social norms, perceived benefits of quarantine and perceived risk of the disease, as well as practical issues such as running out of supplies or the financial consequences of being out of work. Conclusions People vary in their adherence to quarantine during infectious disease outbreaks. To improve this, public health officials should provide a timely, clear rationale for quarantine and information about protocols; emphasise social norms to encourage this altruistic behaviour; increase the perceived benefit that engaging in quarantine will have on public health; and ensure that sufficient supplies of food, medication and other essentials are provided.", "qid": 12, "docid": "9hrrkqgi", "rank": 80, "score": 0.6642078161239624}, {"content": "Title: An evaluation of SARS and droplet infection control practices in acute and rehabilitation hospitals in Hong Kong. Content: 1. This study has demonstrated that great efforts have been made by the Hospital Authority and the studied hospital cluster to contain and prevent infection, and that high levels of vigilance have been enforced in anticipation of future outbreaks of SARS and other droplet infections. 2. Most health care workers and support workers have good hospital infection control and isolation precaution knowledge levels. 3. Compliance with infection control guidelines is satisfactory and has increased compared with previous studies. 4. Most participants had positive perceptions of the guidelines and found the training programmes useful. 5. This study has identified several structures and infection control practice areas that need strengthening, including improving the clarity of some guidelines and minimising barriers to their implementation.", "qid": 12, "docid": "470hwio4", "rank": 81, "score": 0.6641578674316406}, {"content": "Title: Analysis of CDC social control measures using an agent-based simulation of an influenza epidemic in a city Content: BACKGROUND: The transmission of infectious disease amongst the human population is a complex process which requires advanced, often individual-based, models to capture the space-time details observed in reality. METHODS: An Individual Space-Time Activity-based Model (ISTAM) was applied to simulate the effectiveness of non-pharmaceutical control measures including: (1) refraining from social activities, (2) school closure and (3) household quarantine, for a hypothetical influenza outbreak in an urban area. RESULTS: Amongst the set of control measures tested, refraining from social activities with various compliance levels was relatively ineffective. Household quarantine was very effective, especially for the peak number of cases and total number of cases, with large differences between compliance levels. Household quarantine resulted in a decrease in the peak number of cases from more than 300 to around 158 for a 100% compliance level, a decrease of about 48.7%. The delay in the outbreak peak was about 3 to 17 days. The total number of cases decreased to a range of 3635-5403, that is, 63.7%-94.7% of the baseline value. When coupling control measures, household quarantine together with school closure was the most effective strategy. The resulting space-time distribution of infection in different classes of activity bundles (AB) suggests that the epidemic outbreak is strengthened amongst children and then spread to adults. By sensitivity analysis, this study demonstrated that earlier implementation of control measures leads to greater efficacy. Also, for infectious diseases with larger basic reproduction number, the effectiveness of non-pharmaceutical measures was shown to be limited. CONCLUSIONS: Simulated results showed that household quarantine was the most effective control measure, while school closure and household quarantine implemented together achieved the greatest benefit. Agent-based models should be applied in the future to evaluate the efficacy of control measures for a range of disease outbreaks in a range of settings given sufficient information about the given case and knowledge about the transmission processes at a fine scale.", "qid": 12, "docid": "grmef7ab", "rank": 82, "score": 0.6640691757202148}, {"content": "Title: Pro con debates in clinical medicine Infection prevention and control in cystic fibrosis: One size fits all? The argument in favour Content: This article advocates for a universal approach to infection control measures in cystic fibrosis. The central tenets of infection control include hand hygiene, contact precautions, regular microbiological surveillance and adopting inpatient, outpatient, domestic and social practices to minimise acquisition of common CF pathogens. Infection control measures should be proactive and prospective, assuming all patients harbour aggressive pathogens, and not relying on past culture results. The challenges of implementing these policies include cost, equipment, education, consistency, meticulousness all whilst balancing additional procedures to a busy clinical workload.", "qid": 12, "docid": "yiqra486", "rank": 83, "score": 0.6638827323913574}, {"content": "Title: A survey on infection control in emergency departments in Japan Content: AIM: Infection control in the emergency department is important for hospital risk management; however, few clinical guidelines have been established. This study aimed to determine whether hospitals in Japan have infection control manuals, and investigate the contents of manuals, consulting systems, and isolation facilities for emergency departments. METHODS: A total of 517 hospitals certified as educational institutions for board\u2010certified acute care physicians in Japan were requested between March and May 2015 to provide a written evaluation of the infection control in the emergency department. RESULTS: A total of 51 of 303 (16.8%) hospitals had no manuals regarding infection control in the emergency department. Among 250 hospitals having emergency department manuals, 115 (46.0%) did not include contents regarding disinfection and sterilization for imaging examination rooms, and only 44 (17.6%) had criteria for contacting the emergency medical service when patients are suspected of, or diagnosed with, communicable diseases. Of the 303 hospitals, 277 (91.4%) prepared specific manuals for the 2009 pandemic influenza. Of the 303 hospitals, 80 (26.4%) did not prepare manuals for the Ebola virus disease outbreak in West Africa in 2014. Furthermore, 92 (30.4%) of the 303 hospitals did not have any negative\u2010pressure isolation rooms. CONCLUSIONS: Practices and guidelines necessary for infection control in the emergency department were not sufficiently covered in the hospitals studied. Education, information sharing, and a checklist for preparing manuals are needed to establish better infection control systems in emergency departments.", "qid": 12, "docid": "95574k6h", "rank": 84, "score": 0.6638273000717163}, {"content": "Title: Infection prevention and control in paediatric office settings. Content: Transmission of infection in the paediatric office is an issue of increasing concern. This document discusses routes of transmission of infection and the principles of current infection control measures. Prevention includes appropriate office design and administrative policies, triage, routine practices for the care of all patients (e.g., hand hygiene; use of gloves, masks, eye protection, and gowns for specific procedures; adequate cleaning, disinfection, and sterilization of surfaces and equipment, including toys; and aseptic technique for invasive procedures), and additional precautions for specific infections. Personnel should be adequately immunized, and those infected should follow work-restriction policies.", "qid": 12, "docid": "77in6ocu", "rank": 85, "score": 0.6636140942573547}, {"content": "Title: Infection prevention and control in paediatric office settings Content: Transmission of infection in the paediatric office is an issue of increasing concern. This document discusses routes of transmission of infection and the principles of current infection control measures. Prevention includes appropriate office design and administrative policies, triage, routine practices for the care of all patients (e.g., hand hygiene; use of gloves, masks, eye protection, and gowns for specific procedures; adequate cleaning, disinfection, and sterilization of surfaces and equipment, including toys; and aseptic technique for invasive procedures), and additional precautions for specific infections. Personnel should be adequately immunized, and those infected should follow work-restriction policies.", "qid": 12, "docid": "fojzhlzx", "rank": 86, "score": 0.6636140942573547}, {"content": "Title: Perioperative COVID-19 Defense: An Evidence-Based Approach for Optimization of Infection Control and Operating Room Management Content: We describe an evidence-based approach for optimization of infection control and operating room management during the Coronavirus Disease 2019 (COVID-19) pandemic. Confirmed modes of viral transmission are primarily, but not exclusively, contact with contaminated environmental surfaces and aerosolization. Evidence-based improvement strategies for attenuation of residual environmental contamination involve a combination of deep cleaning with surface disinfectants and ultraviolet light (UV-C). (1) Place alcohol-based hand rubs on the intravenous (IV) pole to the left of the provider. Double glove during induction. (2) Place a wire basket lined with a zip closure plastic bag on the IV pole to the right of the provider. Place all contaminated instruments in the bag (eg, laryngoscope blades and handles) and close. Designate and maintain clean and dirty areas. After induction of anesthesia, wipe down all equipment and surfaces with disinfection wipes that contain a quaternary ammonium compound and alcohol. Use a top-down cleaning sequence adequate to reduce bioburden. Treat operating rooms using UV-C. (3) Decolonize patients using preprocedural chlorhexidine wipes, 2 doses of nasal povidone-iodine within 1 hour of incision, and chlorhexidine mouth rinse. (4) Create a closed lumen IV system and use hub disinfection. (5) Provide data feedback by surveillance of Enterococcus, Staphylococcusaureus, Klebsiella, Acinetobacter, Pseudomonas, and Enterobacter spp. (ESKAPE)transmission. (6) To reduce the use of surgical masks and to reduce potential COVID-19 exposure, use relatively long (eg, 12hours) staff shifts. If there are 8 essential cases to be done (each lasting 1\u20132 hours), the ideal solution is to have 2 teams complete the 8 cases, not 8 first case starts. (7) Do 1 case in each operating room daily, with terminal cleaning after each case including UV-C or equivalent. (8) Do not have patients go into a large, pooled phase I postanesthesia care unit because of the risk of contaminating facility at large along with many staff. Instead, have most patients recover in the room where they had surgery as is done routinely in Japan. These 8 programmatic recommendations stand on a substantial body of empirical evidence characterizing the epidemiology of perioperative transmission and infection development made possible by support from the Anesthesia Patient Safety Foundation (APSF).", "qid": 12, "docid": "7km43hig", "rank": 87, "score": 0.6635452508926392}, {"content": "Title: Recommendations in covid-19 times: a view for home care Content: OBJECTIVE: To suggest recommendations for the practice of Home Nursing in the context of COVID-19. METHOD: Reflective study, originated from readings associated with the theme, available in current guidelines from the Pan American Health Organization, World Health Organization and the Ministry of Health. RESULTS: Recommendations were developed from current scientific evidence for prevention of infections, control of epidemics and pandemics in the Brazilian home scenario. FINAL CONSIDERATIONS: the reflections achieved contribute to guiding actions for better assistance to the patient, family caregivers and the community in the perspective of safe home care with COVID-19, and it is characterized as an introductory discussion on the theme, encouraging new studies to be carried out from the unfolding of the current scenario.", "qid": 12, "docid": "856sbp1n", "rank": 88, "score": 0.6635023355484009}, {"content": "Title: How hospitals in mainland China responded to the outbreak of COVID-19 using IT-enabled services: an analysis of hospital news webpages Content: OBJECTIVE: Many countries have implemented quarantine rules during the global outbreak of COVID-19. Understanding how hospitals can continue providing services in an effective manner under these circumstances is thus important. In this study, we investigate how information technology (IT) helped hospitals in mainland China better respond to the outbreak of the pandemic. MATERIALS AND METHODS: We conducted a content analysis of pages published on the websites of the Top 50 hospitals in mainland China between January 22, 2020 and February 21, 2020. In total, we analyzed 368 pages that the hospitals published during the initial days of the COVID-19 pandemic. The purpose was to identify common themes related to the utilization of IT by these hospitals in response to the pandemic's outbreak. RESULTS: We identified five focal themes across the webpages published by the hospitals during our study period including (1) popular medical science education, (2) digitalized hospital processes, (3) knowledge management for medical professionals, (4) telemedicine, and (5) new IT initiatives for healthcare services. Our analysis revealed that Chinese hospitals spent greater effort in promoting popular medical science education in the initial stages of our study period and more on telemedicine in the latter stages. DISCUSSION: We propose a configurational approach for hospitals to design response strategies to pandemic outbreaks based on their available resources. CONCLUSION: Our study provides rich insights for hospitals to better utilize their IT resources and some recommendations for policy makers to better support hospitals in the future.", "qid": 12, "docid": "qkwgp18h", "rank": 89, "score": 0.6633895635604858}, {"content": "Title: Assessing the infection prevention components of home health emergency management plans Content: BACKGROUND: Home health emergency management plans are essential and must address infection prevention issues. Few home health planning documents exist, and many of those that have been developed do not address infection prevention issues, combine them with non\u2013infection prevention issues, or are disease/event-specific. An all-encompassing home health infection prevention emergency management planning guide is needed. METHODS: A literature review and Internet search were conducted in the summer of 2010, and data from relevant sources were extracted. A spreadsheet was created delineating home health emergency management plan components related to infection prevention. RESULTS: Of the sources screened, 41 were deemed relevant. Ten domains were identified: (1) having a plan; (2) assessing agency readiness; (3) having infection prevention policies and procedures; (4) having occupational health policies and procedures; (5) conducting surveillance and triage; (6) reporting incidents, having a communication plan, and managing information; (7) addressing surge capacity issues; (8) having anti-infective therapy and/or vaccines; (9) providing infection prevention education; and (10) managing water and waste management issues. CONCLUSION: Home health disaster planners or managers should use this article as an assessment tool for evaluating their agency\u2019s emergency management plan and for developing policies and procedures that will decrease the risk of infection transmission during a mass casualty event.", "qid": 12, "docid": "kzlmeqyr", "rank": 90, "score": 0.6632698178291321}, {"content": "Title: Lessons learned: protection of healthcare workers from infectious disease risks. Content: OBJECTIVE To summarize current concepts on preventing occupationally acquired infections in healthcare workers. DESIGN Review of the pertinent medical literature. SETTINGS Focus on healthcare workers practicing in acute care hospitals, especially intensive care units. SUBJECTS Healthcare workers. MEASUREMENTS AND MAIN RESULTS Key components of an effective infection control program include the following: 1) pre-exposure immunization with vaccines to prevent mumps, measles, rubella, varicella, pertussis, hepatitis B, and viral influenza; 2) adherence to standard precautions when providing patient care, especially the performance of hand hygiene before and after patient care; 3) rapid evaluation and initiation of appropriate isolation precautions for patients with potentially communicable diseases; 4) proper use of personal protective equipment such as masks, N95 respirators, eye protection, and gowns when caring for patients with potentially communicable diseases; and 5) evaluation of personnel with exposure to communicable diseases for receipt of postexposure prophylaxis. CONCLUSIONS Risks of acquisition of infectious diseases by healthcare workers can be minimized by adherence to current infection control guidelines.", "qid": 12, "docid": "i5funiin", "rank": 91, "score": 0.6631033420562744}, {"content": "Title: Quality of Respiratory Infection Disease Prevention in Outpatient and Emergency Departments in Hospitals in Inner Mongolia, China: An Exit Poll Survey Content: PURPOSE: Measures to prevent respiratory infection diseases (RIDs) in hospitals are important to protect both patients and physicians. In 2003, an outbreak of severe acute respiratory syndrome occurred in Inner Mongolia Autonomous Region (IMAR) of China. We aimed to evaluate competency in RID prevention procedures in terms of hospital performance and physician behavior. PATIENTS AND METHODS: We conducted a cross-sectional study in 10 tertiary general public hospitals in 3 cities of IMAR. In each hospital, we chose the respiratory and ear\u2013nose\u2013throat outpatient departments (OPDs) and the emergency department (ED) to invite patients with symptoms of cough to join the study before they consulted a physician. After their consultation, we asked the patients to complete a checklist to score the performance of the departments and the behavior of their physicians in terms of RID prevention practices according to international professional guidelines. RESULTS: From 711 respondents, in the domain of hospital performance, display of posters on directive to wash hands after coughing/sneezing had an average score of 0.452 (range 0\u20131), while other cough etiquette items had scores averaging between 0.33 and 0.39. The average score for air ventilation was 0.66. For physicians\u2019 performance, informing patients the location of handwashing facilities scored the highest (0.62), while low scores were seen for offering a mask to coughing patients (0.14) and encouraging coughing patients to distance themselves from others (0.17). Most RID prevention procedures received low scores in EDs in both hospital performance and physician behavior domains. CONCLUSION: Hospitals in IMAR should improve their performance in RID prevention procedures, especially in giving information to RID patients through the display of posters. The practice of physicians in preventing respiratory infection spread was suboptimum. ED staff and hospital administrators should improve their procedures to prevent the spread of respiratory infections, especially given the increasing occurrences of global pandemics such as COVID-19.", "qid": 12, "docid": "dsfkqagm", "rank": 92, "score": 0.6630743741989136}, {"content": "Title: Home monitoring for COVID-19 Content: Cleveland Clinic recognized the importance of mitigating community transmission of COVID-19 by keeping people at home. Patient-care activities quickly pivoted to remote touches, preserving continuity through a variety of digital and telephonic modalities. As the number of confirmed cases grew, standardizing home-based care became critical to managing high-risk patients, moderating the risk of exposure for healthcare workers, and reducing the amount of community spread through appropriate education on home-based care for exposed or infected individuals. This novel, team-based approach to caring for patients with COVID-19 incorporates a self-monitoring app for patient engagement, monitors symptoms for early intervention, and promotes a holistic view of care.", "qid": 12, "docid": "c3ehp7na", "rank": 93, "score": 0.6629316806793213}, {"content": "Title: Home monitoring for COVID-19. Content: Cleveland Clinic recognized the importance of mitigating community transmission of COVID-19 by keeping people at home. Patient-care activities quickly pivoted to remote touches, preserving continuity through a variety of digital and telephonic modalities. As the number of confirmed cases grew, standardizing home-based care became critical to managing high-risk patients, moderating the risk of exposure for healthcare workers, and reducing the amount of community spread through appropriate education on home-based care for exposed or infected individuals. This novel, team-based approach to caring for patients with COVID-19 incorporates a self-monitoring app for patient engagement, monitors symptoms for early intervention, and promotes a holistic view of care.", "qid": 12, "docid": "mz7nuskv", "rank": 94, "score": 0.6629316806793213}, {"content": "Title: How hospitals in mainland China responded to the outbreak of COVID-19 using IT-enabled services: an analysis of hospital news webpages Content: OBJECTIVE: Many countries have implemented quarantine rules during the global outbreak of COVID-19. Understanding how hospitals can continue providing services in an effective manner under these circumstances is thus important. In this study, we investigate how information technology (IT) helped hospitals in mainland China better respond to the outbreak of the pandemic. MATERIALS AND METHODS: We conducted a content analysis of pages published on the websites of the Top 50 hospitals in mainland China between January 22, 2020 and February 21, 2020. In total, we analyzed 368 pages that the hospitals published during the initial days of the COVID-19 pandemic. The purpose was to identify common themes related to the utilization of IT by these hospitals in response to the pandemic\u2019s outbreak. RESULTS: We identified five focal themes across the webpages published by the hospitals during our study period including (1) popular medical science education, (2) digitalized hospital processes, (3) knowledge management for medical professionals, (4) telemedicine, and (5) new IT initiatives for healthcare services. Our analysis revealed that Chinese hospitals spent greater effort in promoting popular medical science education in the initial stages of our study period and more on telemedicine in the latter stages. DISCUSSION: We propose a configurational approach for hospitals to design response strategies to pandemic outbreaks based on their available resources. CONCLUSION: Our study provides rich insights for hospitals to better utilize their IT resources and some recommendations for policy makers to better support hospitals in the future.", "qid": 12, "docid": "9baof9z8", "rank": 95, "score": 0.6627732515335083}, {"content": "Title: Infection control and pandemic influenza. Content: If an influenza pandemic occurs, the spread of the virus should be reduced for as long as possible while an effective vaccine is produced. Influenza spreads mainly by large respiratory droplets (> 5 microm) depositing onto the mucosal surfaces of the eye, mouth or respiratory tract. Hands are another major means for spread, and are frequently contaminated by droplets. The most effective way to reduce the spread of the virus is with good infection control practices and social distancing. Infection control practices include the use of personal protective equipment (PPE), hand hygiene, and respiratory hygiene and cough etiquette. Infected people should be isolated and spatial separation observed in common areas where infected people may be present. Any practices that create aerosols (eg, nebulisation) should be avoided, unless performed with appropriate precautions, especially with all people in the room wearing appropriate PPE. Now is the time to re-examine all our current practices so that we are better prepared, well practised and have good infection control practices in place for all transmissible respiratory infections.", "qid": 12, "docid": "z6upi7y2", "rank": 96, "score": 0.6627058982849121}, {"content": "Title: Guidelines for prevention of hospital acquired infections Content: These guidelines, written for clinicians, contains evidence-based recommendations for the prevention of hospital acquired infections Hospital acquired infections are a major cause of mortality and morbidity and provide challenge to clinicians. Measures of infection control include identifying patients at risk of nosocomial infections, observing hand hygiene, following standard precautions to reduce transmission and strategies to reduce VAP, CR-BSI, CAUTI. Environmental factors and architectural lay out also need to be emphasized upon. Infection prevention in special subsets of patients - burns patients, include identifying sources of organism, identification of organisms, isolation if required, antibiotic prophylaxis to be used selectively, early removal of necrotic tissue, prevention of tetanus, early nutrition and surveillance. Immunodeficient and Transplant recipients are at a higher risk of opportunistic infections. The post tranplant timetable is divided into three time periods for determining risk of infections. Room ventilation, cleaning and decontamination, protective clothing with care regarding food requires special consideration. Monitoring and Surveillance are prioritized depending upon the needs. Designated infection control teams should supervise the process and help in collection and compilation of data. Antibiotic Stewardship Recommendations include constituting a team, close coordination between teams, audit, formulary restriction, de-escalation, optimizing dosing, active use of information technology among other measure. The recommendations in these guidelines are intended to support, and not replace, good clinical judgment. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments.", "qid": 12, "docid": "4g9u7obr", "rank": 97, "score": 0.662689208984375}, {"content": "Title: Perioperative COVID-19 Defense: An Evidence-Based Approach for Optimization of Infection Control and Operating Room Management Content: We describe an evidence-based approach for optimization of infection control and operating room management during the coronavirus disease 2019 (COVID-19) pandemic. Confirmed modes of viral transmission are primarily, but not exclusively, contact with contaminated environmental surfaces and aerosolization. Evidence-based improvement strategies for attenuation of residual environmental contamination involve a combination of deep cleaning with surface disinfectants and ultraviolet light (UV-C). (1) Place alcohol-based hand rubs on the intravenous (IV) pole to the left of the provider. Double glove during induction. (2) Place a wire basket lined with a zip closure plastic bag on the IV pole to the right of the provider. Place all contaminated instruments in the bag (eg, laryngoscope blades and handles) and close. Designate and maintain clean and dirty areas. After induction of anesthesia, wipe down all equipment and surfaces with disinfection wipes that contain a quaternary ammonium compound and alcohol. Use a top-down cleaning sequence adequate to reduce bioburden. Treat operating rooms using UV-C. (3) Decolonize patients using preprocedural chlorhexidine wipes, 2 doses of nasal povidone-iodine within 1 hour of incision, and chlorhexidine mouth rinse. (4) Create a closed lumen IV system and use hub disinfection. (5) Provide data feedback by surveillance of Enterococcus, Staphylococcus aureus, Klebsiella, Acinetobacter, Pseudomonas, and Enterobacter spp. (ESKAPE) transmission. (6) To reduce the use of surgical masks and to reduce potential COVID-19 exposure, use relatively long (eg, 12 hours) staff shifts. If there are 8 essential cases to be done (each lasting 1-2 hours), the ideal solution is to have 2 teams complete the 8 cases, not 8 first case starts. (7) Do 1 case in each operating room daily, with terminal cleaning after each case including UV-C or equivalent. (8) Do not have patients go into a large, pooled phase I postanesthesia care unit because of the risk of contaminating facility at large along with many staff. Instead, have most patients recover in the room where they had surgery as is done routinely in Japan. These 8 programmatic recommendations stand on a substantial body of empirical evidence characterizing the epidemiology of perioperative transmission and infection development made possible by support from the Anesthesia Patient Safety Foundation (APSF).", "qid": 12, "docid": "wcqxqkqw", "rank": 98, "score": 0.6624784469604492}, {"content": "Title: If you ask them, will they come? Predictors of quarantine compliance during a hypothetical avian influenza pandemic: results from a statewide survey. Content: BACKGROUND An influenza pandemic, such as that of the H1N1 virus, raises questions about how to respond effectively to a lethal outbreak. Most plans have focused on minimizing impact by containing the virus through quarantine, but quarantine has not been used widely in the United States and little is known about what would be the public's response. The purpose of this study was to investigate factors that influence an individual's decision to comply with a hypothetical avian influenza quarantine order. METHODS A total of 1204 adult Pennsylvania residents participated in a random digit dial telephone sample. The residents were interviewed regarding their attitudes about and knowledge of avian influenza and about compliance with quarantine orders, including staying at home or traveling to a government-designated facility. RESULTS Analysis of variance showed differences among demographic groups in willingness to comply with quarantine orders, with women and individuals not presently employed more willing to stay at home or to travel to a government-designated facility if ordered. Those who did not regularly attend religious services were significantly less willing than those who did attend regularly to comply with any type of quarantine order. Regression analysis indicated that demographic variables, overall knowledge of avian influenza, attitudes about its severity, and the belief that the respondent and/or his or her significant other(s) may contract it were predictive. CONCLUSIONS The results of this study can provide health planners and policy makers with information for improving their efforts to conduct a quarantine successfully, including crafting messages and targeting information to certain groups of people to communicate risk about the epidemic.", "qid": 12, "docid": "5jjstgkl", "rank": 99, "score": 0.6623495817184448}, {"content": "Title: Environmental Cleaning and Disinfection Content: The guidelines in this article provide veterinarians, veterinary technicians, and veterinary health care workers with an overview of evidence-based recommendations for the best practices associated with environmental cleaning and disinfection of a veterinary clinic that deals with small animals. Hospital-associated infections and the control and prevention programs necessary to alleviate them are addressed from an environmental perspective. Measures of hospital cleaning and disinfection include understanding mechanisms and types of contamination in veterinary settings, recognizing areas of potential concern, addressing appropriate decontamination techniques and selection of disinfectants, the management of potentially contaminated equipment, laundry, and waste management, and environmental surveillance strategies.", "qid": 12, "docid": "kjjis7hu", "rank": 100, "score": 0.6623260974884033}]}
{"query": "what are the transmission routes of coronavirus?", "hits": [{"content": "Title: [Transmission routes of 2019-novel coronavirus (2019-nCoV)] Content: Since the outbreak of COVID-19 in Wuhan, China, at the end of 2019, it has demonstrated China's ability to identify unknown pathogens. At present, reports showed that the main transmission routes are respiratory droplets and indirect contact, other vertical transmission routes have yet to be confirmed. This review discusses the possible transmission routes of 2019-novel coronavirus (2019-nCoV), based on currently research, the main transmission routes are respiratory droplets and indirect contact, fecal-oral might bepossible, while aerosol, tear (conjunctival) and mother-to-fetus still have yet to be confirmed, providing a reference basis for 2019-nCoV prevention and control and public protection.", "qid": 13, "docid": "2yblpbwm", "rank": 1, "score": 0.790543258190155}, {"content": "Title: [Transmission routes of 2019-novel coronavirus (2019-nCoV)]. Content: Since the outbreak of COVID-19 in Wuhan, China, at the end of 2019, it has demonstrated China's ability to identify unknown pathogens. At present, reports showed that the main transmission routes are respiratory droplets and indirect contact, other vertical transmission routes have yet to be confirmed. This review discusses the possible transmission routes of 2019-novel coronavirus (2019-nCoV), based on currently research, the main transmission routes are respiratory droplets and indirect contact, fecal-oral might bepossible, while aerosol, tear (conjunctival) and mother-to-fetus still have yet to be confirmed, providing a reference basis for 2019-nCoV prevention and control and public protection.", "qid": 13, "docid": "85vnyr36", "rank": 2, "score": 0.790543258190155}, {"content": "Title: Transmission of SARS-CoV-2 via fecal-oral and aerosols-borne routes: Environmental dynamics and implications for wastewater management in underprivileged societies Content: The advent of novel human coronavirus (SARS-CoV-2) and its potential transmission via fecal-oral and aerosols-borne routes are upcoming challenges to understand the fate of the virus in the environment. In this short communication, we specifically looked at the possibilities of these transmission routes based on the available literature directly related to the SARS-CoV-2 as well as on the closer phylogenetic relatives such as SARS-CoV-1. The available data suggest that, in addition to human-to-human contact, the virus may spread via fecal-oral and aerosols-borne routes. Existing knowledge states that coronaviruses have low stability in the environment due to the natural action of oxidants that disrupt the viral envelope. Previous recommended dosage of chlorination has been found to be not sufficient to inactivate SARS-CoV-2 in places where viral load is high such as hospitals and airports. Although there is no current evidence showing that coronaviruses can be transmitted through contaminated drinking water, there is a growing concern on the impact of the current pandemic wave on underprivileged societies because of their poor wastewater treatment infrastructures, overpopulation, and outbreak management strategies. More research is encouraged to trace the actual fate of SARS-CoV-2 in the environment and to develop/revise the disinfection strategies accordingly.", "qid": 13, "docid": "9of9gijc", "rank": 3, "score": 0.7793906331062317}, {"content": "Title: A study of the probable transmission routes of MERS\u2010CoV during the first hospital outbreak in the Republic of Korea Content: Infections caused by the Middle East respiratory syndrome coronavirus (MERS\u2010CoV) are a serious health issue due to their prevalence and associated mortality. However, the transmission routes of the virus remain unclear, and thus, the current recommended control strategies are not evidence based. In this study, we investigated the transmission routes of MERS\u2010CoV during the first nosocomial outbreak in the Republic of Korea in May 2015 using a multi\u2010agent modeling framework. We identified seven hypothesized transmission modes based on the three main transmission routes (long\u2010range airborne, close contact, and fomite). The infection risks for each hypothesis were estimated using the multi\u2010agent modeling framework. Least\u2010squares fitting was conducted to compare the distribution of the predicted infection risk in the various scenarios with that of the reported attack rates and to identify the hypotheses with the best fit. In the scenarios in which the index patient was a super\u2010spreader, our model simulations suggested that MERS\u2010CoV probably spread via the long\u2010range airborne route. However, it is possible that the index patient shed an average viral load comparable to the loads reported in the literature, and that transmission occurred via a combined long\u2010range airborne and close contact route.", "qid": 13, "docid": "4nd5wzrm", "rank": 4, "score": 0.7781264781951904}, {"content": "Title: Potential fecal transmission of SARS-CoV-2: Current evidence and implications for public health Content: Coronavirus disease 2019 (COVID-19) emerged in Hubei Province, China in December 2019 and has since become a global pandemic, with hundreds of thousands of cases and over 165 countries affected. Primary routes of transmission of the causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are through respiratory droplets and close person-to-person contact. While information about other potential modes of transmission are relatively sparse, evidence supporting the possibility of a fecally mediated mode of transmission has been accumulating. Here, current knowledge on the potential for fecal transmission is briefly reviewed and the possible implications are discussed from a public health perspective.", "qid": 13, "docid": "12sbikmx", "rank": 5, "score": 0.7771272659301758}, {"content": "Title: Potential Fecal Transmission of SARS-CoV-2: Current Evidence and Implications for Public Health Content: Abstract Coronavirus disease 2019 (COVID-19) emerged in Hubei Province, China in December 2019 and has since become a global pandemic, with hundreds of thousands of cases and over 165 affected countries. Primary routes of transmission of the causative virus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are through respiratory droplets and close person-to-person contact. While information about other potential modes of transmission are relatively sparse, evidence supporting the possibility of a fecally-mediated mode of transmission has been accumulating. Here, current knowledge on the potential for fecal transmission is briefly reviewed and the possible implications are discussed from a public health perspective.", "qid": 13, "docid": "ruk46455", "rank": 6, "score": 0.7737268805503845}, {"content": "Title: Transmission of SARS-CoV-2 via fecal-oral and aerosols\u2013borne routes: Environmental dynamics and implications for wastewater management in underprivileged societies Content: Abstract The advent of novel human coronavirus (SARS-CoV-2) and its potential transmission via fecal-oral and aerosols-borne routes are upcoming challenges to understand the fate of the virus in the environment. In this short communication, we specifically looked at the possibilities of these transmission routes based on the available literature directly related to the SARS-CoV-2 as well as on the closer phylogenetic relatives such as SARS-CoV-1. The available data suggest that, in addition to human-to-human contact, the virus may spread via fecal-oral and aerosols-borne routes. Existing knowledge states that coronaviruses have low stability in the environment due to the natural action of oxidants that disrupt the viral envelope. Previous recommended dosage of chlorination has been found to be not sufficient to inactivate SARS-CoV-2 in places where viral load is high such as hospitals and airports. Although there is no current evidence showing that coronaviruses can be transmitted through contaminated drinking water, there is a growing concern on the impact of the current pandemic wave on underprivileged societies because of their poor wastewater treatment infrastructures, overpopulation, and outbreak management strategies. More research is encouraged to trace the actual fate of SARS-CoV-2 in the environment and to develop/revise the disinfection strategies accordingly.", "qid": 13, "docid": "ioo17gc3", "rank": 7, "score": 0.7671318650245667}, {"content": "Title: Emerging coronaviruses: first SARS, second MERS and third SARS-CoV-2: epidemiological updates of COVID-19. Content: Since December 2019, the emergence of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection has been reported unexpectedly in Wuhan, China, with staggering infection speed across China and around the world. To date, seven known strains of HCoVs belonging to four genera (i.e., \u03b1?, \u03b2?, \u03b3, and \u03b4-CoV) have been recognized; the latest one has been identified as the SARS-CoV-2. Although the common transmission routes of SARS-CoV-2 is the respiratory tract, it seems that other routes such as the gastrointestinal tract may be effective for the entry of the virus in the body. Although there are no biological markers to predict the susceptibility of humans to COVID-19, several risk factors have been identified to predict the susceptibility of patients to COVID-19. Initial data revealed that males, pregnant women, elderly, and underlying conditions predispose patients to higher morbidity or mortality and also might be at risk for a severe infection of COVID-19. There is a greater need to better understand the mechanisms and risk factors of transmission routes. To date, despite the whole world effort to review various aspects of SARS-CoV-2, including epidemiology, clinical manifestations, diagnosis, and treatment options, there are still gaps in the knowledge of this disease and many issues remain unclear. Therefore, there is an urgent need for update data on SARS-CoV-2. Here, this study provide the current epidemiological status (transmission routes and risk of transmission, possible origins and source, mortality and morbidity risk, and geographical distribution) of the SARS-CoV-2 in the world in 2020.", "qid": 13, "docid": "kkknzw2i", "rank": 8, "score": 0.7655313014984131}, {"content": "Title: Indirect Virus Transmission in Cluster of COVID-19 Cases, Wenzhou, China, 2020 Content: To determine possible modes of virus transmission, we investigated a cluster of coronavirus disease cases associated with a shopping mall in Wenzhou, China. Data indicated that indirect transmission of the causative virus occurred, perhaps resulting from virus contamination of common objects, virus aerosolization in a confined space, or spread from asymptomatic infected persons.", "qid": 13, "docid": "yp7bniwt", "rank": 9, "score": 0.7628383040428162}, {"content": "Title: Transmission of SARS-CoV-2: an update of current literature Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent for the 2019 coronavirus disease (COVID-19) pandemic, has caused a public health emergency. The need for additional research in viral pathogenesis is essential as the number of cases and deaths rise. Understanding the virus and its ability to cause disease has been the main focus of current literature; however, there is much unknown. Studies have revealed new findings related to the full transmission potential of SARS-CoV-2 and its subsequent ability to cause infection by different means. The virus is hypothesized to be of increased virulence compared with previous coronavirus that caused epidemics, in part due to its overall structural integrity and resilience to inactivation. To date, many studies have discussed that the rationale behind its transmission potential is that viral RNA has unexpectedly been detected in multiple bodily fluids, with some samples having remained positive for extended periods of time. Additionally, the receptor by which the virus gains cellular entry, ACE2, has been found to be expressed in different human body systems, thereby potentiating its infection in those locations. In this evidence-based comprehensive review, we discuss various potential routes of transmission of SARS-CoV-2\u2014respiratory/droplet, indirect, fecal-oral, vertical, sexual, and ocular. Understanding these different routes is important as they pertain to clinical practice, especially in taking preventative measures to mitigate the spread of SARS-CoV-2.", "qid": 13, "docid": "cfv0ta10", "rank": 10, "score": 0.7616898417472839}, {"content": "Title: Prevention and control of COVID-19 in nursing homes, orphanages, and prisons Content: As the number of Coronavirus Disease (2019) (COVID-19) cases increase globally, countries are taking more aggressive preventive measures against this pandemic. Transmission routes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) include droplet and contact transmissions. There are also evidence of transmission through aerosol generating procedures (AGP) in specific circumstances and settings. Institutionalized populations without mobility and living in close proximity with unavoidable contact are especially vulnerable to higher risks of COVID-19 infection, such as the elderly in nursing homes, children in orphanages, and inmates in prisons. In these places, higher prevention and control measures are needed. In this study, we proposed prevention and control strategies for these facilities and provided practical guidance for general measures, health management, personal protection measures, and prevention measures in nursing homes, orphanages, and prisons, respectively.", "qid": 13, "docid": "picxa3je", "rank": 11, "score": 0.7616254687309265}, {"content": "Title: The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned? Content: OBJECTIVES: To provide an overview of the three major deadly coronaviruses and identify areas for improvement of future preparedness plans, as well as provide a critical assessment of the risk factors and actionable items for stopping their spread, utilizing lessons learned from the first two deadly coronavirus outbreaks, as well as initial reports from the current novel coronavirus (COVID-19) epidemic in Wuhan, China. METHODS: Utilizing the Centers for Disease Control and Prevention (CDC, USA) website, and a comprehensive review of PubMed literature, we obtained information regarding clinical signs and symptoms, treatment and diagnosis, transmission methods, protection methods and risk factors for Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS) and COVID-19. Comparisons between the viruses were made. RESULTS: Inadequate risk assessment regarding the urgency of the situation, and limited reporting on the virus within China has, in part, led to the rapid spread of COVID-19 throughout mainland China and into proximal and distant countries. Compared with SARS and MERS, COVID-19 has spread more rapidly, due in part to increased globalization and the focus of the epidemic. Wuhan, China is a large hub connecting the North, South, East and West of China via railways and a major international airport. The availability of connecting flights, the timing of the outbreak during the Chinese (Lunar) New Year, and the massive rail transit hub located in Wuhan has enabled the virus to perforate throughout China, and eventually, globally. CONCLUSIONS: We conclude that we did not learn from the two prior epidemics of coronavirus and were ill-prepared to deal with the challenges the COVID-19 epidemic has posed. Future research should attempt to address the uses and implications of internet of things (IoT) technologies for mapping the spread of infection.", "qid": 13, "docid": "g7dhmyyo", "rank": 12, "score": 0.7613029479980469}, {"content": "Title: Is SARS-CoV-2 Also an Enteric Pathogen With Potential Fecal-Oral Transmission? A COVID-19 Virological and Clinical Review Content: In as few as 3 months, coronavirus disease 2019 (COVID-19) has spread and ravaged the world at an unprecedented speed in modern history, rivaling the 1918 flu pandemic. Severe acute respiratory syndrome coronavirus-2, the culprit virus, is highly contagious and stable in the environment and transmits predominantly among humans via the respiratory route. Accumulating evidence suggest that this virus, like many of its related viruses, may also be an enteric virus that can spread via the fecal-oral route. Such a hypothesis would also contribute to the rapidity and proliferation of this pandemic. Here we briefly summarize what is known about this family of viruses and literature basis of the hypothesis that severe acute respiratory syndrome coronavirus-2 is capable of infecting the gastrointestinal tract and shedding in the environment for potential human-to-human transmission.", "qid": 13, "docid": "yyfuu197", "rank": 13, "score": 0.7590116858482361}, {"content": "Title: Clusters of 2019 coronavirus disease (COVID-19) cases in Chinese tour groups Content: International travel may facilitate the spread of the novel coronavirus disease (COVID-19). The study describes clusters of COVID-19 cases within Chinese tour groups travelling in Europe January 16-28. We compared characteristics of cases and non-cases to determine transmission dynamics. The index case travelled from Wuhan, China, to Europe on January 16, 2020, and to Shanghai, China, on January 27, 2020, within a tour group (group A). Tour groups with the same outbound flight (group B) or the same tourism venue (group D), and all Chinese passengers on the inbound flight (group C) were investigated. The outbreak involved 11 confirmed cases, 10 suspected cases, and 6 tourists who remained healthy. Group A, involving 7 confirmed cases and 6 suspected cases, consisted of familial transmission followed by propagative transmission. There was less pathogenicity with propagative transmission than with familial transmission. Disease was transmitted in shared outbound flights, shopping venues within Europe, and inbound flight back to China. The novel coronavirus caused clustered cases of COVID-19 in tour groups. When tourism and travel opens up, governments will need to improve screening at airports and consider increased surveillance of tour groups - particularly those with older tour members.", "qid": 13, "docid": "0jlms3eo", "rank": 14, "score": 0.7575008273124695}, {"content": "Title: Clusters of 2019 coronavirus disease (COVID-19) cases in Chinese tour groups. Content: International travel may facilitate the spread of the novel coronavirus disease (COVID-19). The study describes clusters of COVID-19 cases within Chinese tour groups travelling in Europe January 16-28. We compared characteristics of cases and non-cases to determine transmission dynamics. The index case travelled from Wuhan, China, to Europe on January 16, 2020, and to Shanghai, China, on January 27, 2020, within a tour group (group A). Tour groups with the same outbound flight (group B) or the same tourism venue (group D), and all Chinese passengers on the inbound flight (group C) were investigated. The outbreak involved 11 confirmed cases, 10 suspected cases, and 6 tourists who remained healthy. Group A, involving 7 confirmed cases and 6 suspected cases, consisted of familial transmission followed by propagative transmission. There was less pathogenicity with propagative transmission than with familial transmission. Disease was transmitted in shared outbound flights, shopping venues within Europe, and inbound flight back to China. The novel coronavirus caused clustered cases of COVID-19 in tour groups. When tourism and travel opens up, governments will need to improve screening at airports and consider increased surveillance of tour groups - particularly those with older tour members.", "qid": 13, "docid": "t080mykk", "rank": 15, "score": 0.7575008273124695}, {"content": "Title: Transmission of SARS-CoV-2, Required Developments in Research and Associated Public Health Concerns Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading across the world to cause thousands of mortalities each day. Poor responses from the authorities to the spread of infection, lack of effective measures for prevention, unavailability of promising treatment options, and sufficient diagnostic options have created an alarming for the world. The transmission routes from human to human of SARS-CoV-2 can be the direct transmission, droplet inhalation transmission, contact transmission, transmission through saliva, and transmission via fecal\u2013oral routes. Due to the asymptomatic spread of SARS-CoV-2's, developing control and prevention measures is challenging. Implementing proper strategies addressing the infection control and clinical supplies, understanding the mechanism associated with pathogenesis, advancing in preventive measures and effective treatment and diagnostic options are necessary to control the ongoing pandemic. In this article, we briefly discuss the features, entry mechanism, infectiousness, and health consequences related to the COVID-19 outbreak.", "qid": 13, "docid": "2e4gz2bo", "rank": 16, "score": 0.7567635774612427}, {"content": "Title: Emerging coronaviruses: first SARS, second MERS and third SARS-CoV-2: epidemiological updates of COVID-19 Content: Since December 2019, the emergence of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection has been reported unexpectedly in Wuhan, China, with staggering infection speed across China and around the world To date, seven known strains of HCoVs belonging to four genera (i e , alpha?, beta?, gamma, and delta-CoV) have been recognized;the latest one has been identified as the SARS-CoV-2 Although the common transmission routes of SARS-CoV-2 is the respiratory tract, it seems that other routes such as the gastrointestinal tract may be effective for the entry of the virus in the body Although there are no biological markers to predict the susceptibility of humans to COVID-19, several risk factors have been identified to predict the susceptibility of patients to COVID-19 Initial data revealed that males, pregnant women, elderly, and underlying conditions predispose patients to higher morbidity or mortality and also might be at risk for a severe infection of COVID-19 There is a greater need to better understand the mechanisms and risk factors of transmission routes To date, despite the whole world effort to review various aspects of SARS-CoV-2, including epidemiology, clinical manifestations, diagnosis, and treatment options, there are still gaps in the knowledge of this disease and many issues remain unclear Therefore, there is an urgent need for update data on SARS-CoV-2 Here, this study provide the current epidemiological status (transmission routes and risk of transmission, possible origins and source, mortality and morbidity risk, and geographical distribution) of the SARS-CoV-2 in the world in 2020", "qid": 13, "docid": "o908k448", "rank": 17, "score": 0.7526541948318481}, {"content": "Title: SARS-CoV-2 and human milk: what is the evidence? Content: The novel coronavirus SARS-CoV-2 has emerged as one of the most compelling public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical, and public health communities have rapidly engaged to find answers and solutions. One area of active inquiry is understanding the mode(s) of SARS-CoV-2 transmission. While respiratory droplets are a known mechanism of transmission, other mechanisms are possible. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronavirus (including SARS-CoV-2) via human milk and/or breastfeeding. There is a single study providing some evidence of vertical transmission of human coronavirus 229E, a single study evaluating presence of SARS-CoV in human milk (it was negative), and no published data on MERS-CoV and human milk. There are 9 case studies of human milk tested for SARS-CoV-2; none detected the virus. Importantly, none of the published studies on coronaviruses and human milk report validation of their analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses (in particular, SARS-CoV-2) during breastfeeding are discussed.", "qid": 13, "docid": "nlq5755b", "rank": 18, "score": 0.7515991926193237}, {"content": "Title: Body fluids may contribute to human-to-human transmission of severe acute respiratory syndrome coronavirus 2: evidence and practical experience Content: BACKGROUND: In December 2019, an unbelievable outbreak of pneumonia associated with coronavirus was reported in the city of Wuhan, Hubei Province. This virus was called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although much effort has been spent on clarifying the transmission route of SARS-CoV-2, but, very little evidence is available regarding the relationship between human body fluids and transmission of SARS-CoV-2 virus. Considerable evidence from hospital in Wuhan indicates that strict rules to avoid occupational exposure to patients\u2019 body fluids in healthcare settings, particularly among every medical staff, limited person-to-person transmission of nosocomial infections by direct or indirect contact. CONCLUSION: We tried to provide important information for understanding the possible transmission routes of SARS-CoV-2 via body fluids including bronchoalveolar-lavage, saliva, blood, urine, feces, sputum, tears, and semen in order to control coronavirus disease 2019 (COVID-19) occurrences.", "qid": 13, "docid": "0a5fccio", "rank": 19, "score": 0.7513250112533569}, {"content": "Title: Mechanistic Transmission Modeling of COVID-19 on the Diamond Princess Cruise Ship Demonstrates the Importance of Aerosol Transmission Content: Background The current prevailing position is that coronavirus disease 2019 (COVID-19) is transmitted primarily through large respiratory droplets within close proximity (i.e., 1-2 m) of infected individuals. However, quantitative information on the relative importance of specific transmission pathways of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (i.e., droplets, aerosols, and fomites across short- and long-range distances) remains limited. Methods To evaluate the relative importance of multiple transmission routes for SARS-CoV-2, we leveraged detailed information available from the Diamond Princess Cruise Ship outbreak that occurred in early 2020. We developed a framework that combines stochastic Markov chain and negative exponential dose-response modeling with available empirical data on mechanisms of SARS-CoV-2 dynamics and human behaviors, which informs a modified version of the Reed-Frost epidemic model to predict daily and cumulative daily case counts on the ship. We modeled 21,600 scenarios to generate a matrix of solutions across a full range of assumptions for eight unknown or uncertain epidemic and mechanistic transmission factors, including the magnitude of droplet and aerosol emissions from infected individuals, the infectious dose for deposition of droplets and aerosols to the upper and lower respiratory tracts, and others. Findings A total of 132 model iterations met acceptability criteria (R2 > 0.95 for modeled vs. reported cumulative daily cases and R2 > 0 for daily cases). Analyzing only these successful model iterations yields insights into the likely values for uncertain parameters and quantifies the likely contributions of each defined mode of transmission. Mean estimates of the contributions of short-range, long-range, and fomite transmission modes to infected cases aboard the ship across the entire simulation time period were 35%, 35%, and 30%, respectively. Mean estimates of the contributions of large respiratory droplets and small respiratory aerosols were 41% and 59%. Short-range transmission was the dominant mode after passenger quarantine began, albeit due primarily to aerosol transmission, not droplets. Interpretation Our results demonstrate that aerosol inhalation was likely the dominant contributor to COVID-19 transmission among passengers aboard the Diamond Princess Cruise Ship. Moreover, close-range and long-range transmission likely contributed similarly to disease progression aboard the ship, with fomite transmission playing a smaller role. The passenger quarantine also affected the importance of each mode, demonstrating the impacts of the interventions. Although cruise ships represent unique built environments with high ventilation rates and no air recirculation, these findings underscore the importance of implementing public health measures that target the control of inhalation of aerosols in addition to ongoing measures targeting control of large droplet and fomite transmission, not only aboard cruise ships but in other indoor environments as well.", "qid": 13, "docid": "a2ktiude", "rank": 20, "score": 0.7510131001472473}, {"content": "Title: Emergence of COVID-19 Infection: What Is Known and What Is to Be Expected-Narrative Review Article Content: BACKGROUND: The discovery of the coronavirus disease 2019 (COVID-19) during a pneumonia outbreak in Wuhan city (China) has raised a global public health concern, as the city consists of around 11 million people and is considered a major transport and logistics hub. This deadly virus caused the world to be in high alert as the death toll and the number of confirmed cases is continuously rising since the first case was reported. The Chinese government warned that the transmission ability of the virus is increasing, and international efforts are needed to overcome this outbreak. The purpose of this review is to focus on the published articles about the new virus, which will give an insight into the current state of research and data available, as well as recommending future studies. METHODS: For this narrative review, more than 20 relevant scientific articles and reports were considered from various databases (e.g., Google Scholar, PubMed and Science Direct) using keywords such as Coronavirus Outbreak, COVID-19, Emerging Epidemics, Emerging Infections, and Novel Coronavirus. RESULTS: The results from this review show that the situation is rapidly evolving, as human-to-human transmission is occurring, and the number of new cases and mortalities is increasing by the day and on a global level. There is still ambiguity about mutation risks and how the virus spreads as the source was not yet identified. Major gaps in knowledge about the origin of the virus, epidemiology and transmission impose a great challenge, which emphasizes the need for further studies in the future.", "qid": 13, "docid": "fqs40ivc", "rank": 21, "score": 0.7509200572967529}, {"content": "Title: A comprehensive Chinese experience against SARS-CoV-2 in ophthalmology Content: The 2019 novel coronavirus disease (COVID-19) has now swept through the continents and poses a global threat to public health. Several investigations have been conducted to identify whether COVID-19 can be transmitted through the ocular route, and the conclusion is that it is a potential route but remains uncertain. Due to the face-to-face communication with patients, frequent exposure to tears and ocular discharge, and the unavoidable use of equipment which requires close proximity, ophthalmologists carry a high risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on 33 articles published by Chinese scholars, guidelines and clinical practice experience in domestic hospitals, we have summarized the Chinese experience through the lens of ophthalmology, hoping to make a contribution to protecting ophthalmologists and patients around the world.", "qid": 13, "docid": "3yxrqa22", "rank": 22, "score": 0.7508774995803833}, {"content": "Title: [Consideration and prevention for the aerosol transmission of 2019 novel coronavirus]. Content: Novel coronavirus pneumonia broke out from Wuhan, and spreading to the whole nation and world since Dec, 2019. It is now the critical stage to fight against the virus. Previous epidemiological investigations and animal experiments suggest aerosol could perform as virus transmitter. Based on the clinical observation, the possibility of aerosol transmission of 2019 novel coronavirus has aroused a lot of attention. This study focuses on the feature of aerosol transmission, and the pathogens involved in. We analyzed the possibility of aerosol transmission for the novel coronavirus. Relevant strategies to prevent novel coronavirus pneumonia are established, serving as references to the medical personnel and general public during their work or daily life. ( Chin J Ophthalmol, 2020, 56: ).", "qid": 13, "docid": "qz9rzie2", "rank": 23, "score": 0.7504212856292725}, {"content": "Title: [Consideration and prevention for the aerosol transmission of 2019 novel coronavirus] Content: Novel coronavirus pneumonia broke out from Wuhan, and spreading to the whole nation and world since Dec, 2019. It is now the critical stage to fight against the virus. Previous epidemiological investigations and animal experiments suggest aerosol could perform as virus transmitter. Based on the clinical observation, the possibility of aerosol transmission of 2019 novel coronavirus has aroused a lot of attention. This study focuses on the feature of aerosol transmission, and the pathogens involved in. We analyzed the possibility of aerosol transmission for the novel coronavirus. Relevant strategies to prevent novel coronavirus pneumonia are established, serving as references to the medical personnel and general public during their work or daily life. ( Chin J Ophthalmol, 2020, 56: ).", "qid": 13, "docid": "cfwtyud2", "rank": 24, "score": 0.7504212260246277}, {"content": "Title: The clinical dynamics of 18 cases of COVID-19 outside of Wuhan, China Content: The novel coronavirus can be transmitted from person to person with infection ranging from mild disease to severe pneumonia and radiological abnormalities on chest CT for most patients improved after RT-PCR conversion.", "qid": 13, "docid": "e3dh0huv", "rank": 25, "score": 0.7503643035888672}, {"content": "Title: Water matrices as potential source of SARS-CoV-2 transmission \u2013 An overview from environmental perspective Content: Abstract Evidently, the emergence of novel coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has rapidly blowout across the world. Since, the presence of coronaviruses, including SARS-CoV-2 in the fecal specimens and anal swabs of some infected patients, has raised emerging concern with the likelihood of fecal-based spread must be inspected and clarified. Therefore, herein, an effort has been made to spotlight the current scenarios and possible solutions to better understand the risks associated with the wastewater matrices as a potential source of SARS-CoV-2 transmission in the environment. The information reviewed here constitutes a paramount intellectual basis to sustenance ongoing research to tackle the SARS-CoV-2 issue. Thus, this overview indicates the most accessible frontiers related to the detection, quantification, and possible transmission of SARS-CoV-2 in the environment through water routes. The regulatory authorities and policymakers must assure the society via dissemination of evidence-based guidelines that the water matrices, including groundwater and drinking water resources are safe. Finally, we have identified and enlisted a number of pressing questions concerning the ongoing SARS-CoV-2 transmission or COVID-19 emergence issue that must be carefully answered to put further and deeper insight into SARS-CoV-2/COVID-19 in future studies.", "qid": 13, "docid": "96j45f1a", "rank": 26, "score": 0.7497257590293884}, {"content": "Title: Coronavirus testing indicates transmission risk increases along wildlife supply chains for human consumption in Viet Nam, 2013-2014 Content: Outbreaks of emerging coronaviruses in the past two decades and the current pandemic of a novel coronavirus (SARS-CoV-2) that emerged in China highlight the importance of this viral family as a zoonotic public health threat. To gain a better understanding of coronavirus presence and diversity in wildlife at wildlife-human interfaces in three southern provinces in Viet Nam 2013-2014, we used consensus Polymerase Chain Reactions to detect coronavirus sequences. In comparison to previous studies, we observed high proportions of positive samples among field rats (34.0%, 239/702) destined for human consumption and insectivorous bats in guano farms (74.8%, 234/313) adjacent to human dwellings. Most notably among field rats, the odds of coronavirus RNA detection significantly increased along the supply chain from field rats sold by traders (reference group; 20.7% positivity, 39/188) by a factor of 2.2 for field rats sold in large markets (32.0%, 116/363) and 10.0 for field rats sold and served in restaurants (55.6%, 84/151). Coronaviruses were detected in the majority of wildlife farms (60.7%, 17/28) and in the Malayan porcupines (6.0%, 20/331) and bamboo rats (6.3%, 6/96) that are farmed. We identified six known coronaviruses in bats and rodents, clustered in three Coronaviridae genera, including the Alpha-, Beta-, and Gammacoronaviruses. Our analysis also suggested either mixing of animal excreta in the environment or interspecies transmission of coronaviruses, as both bat and avian coronaviruses were detected in rodent feces in the trade. The mixing of multiple coronaviruses, and their apparent amplification along the wildlife supply chain into restaurants, suggests maximal risk for end consumers and likely underpins the mechanisms of zoonotic spillover to people.", "qid": 13, "docid": "3awtlpxw", "rank": 27, "score": 0.7487392425537109}, {"content": "Title: A mathematical model for the novel coronavirus epidemic in Wuhan, China Content: We propose a mathematical model to investigate the current outbreak of the coronavirus disease 2019 (COVID-19) in Wuhan, China. Our model describes the multiple transmission pathways in the infection dynamics, and emphasizes the role of the environmental reservoir in the transmission and spread of this disease. Our model also employs non-constant transmission rates which change with the epidemiological status and environmental conditions and which reflect the impact of the on-going disease control measures. We conduct a detailed analysis of this model, and demonstrate its application using publicly reported data. Among other findings, our analytical and numerical results indicate that the coronavirus infection would remain endemic, which necessitates long-term disease prevention and intervention programs.", "qid": 13, "docid": "5dpx5lez", "rank": 28, "score": 0.7481069564819336}, {"content": "Title: A mathematical model for the novel coronavirus epidemic in Wuhan, China. Content: We propose a mathematical model to investigate the current outbreak of the coronavirus disease 2019 (COVID-19) in Wuhan, China. Our model describes the multiple transmission pathways in the infection dynamics, and emphasizes the role of the environmental reservoir in the transmission and spread of this disease. Our model also employs non-constant transmission rates which change with the epidemiological status and environmental conditions and which reflect the impact of the on-going disease control measures. We conduct a detailed analysis of this model, and demonstrate its application using publicly reported data. Among other findings, our analytical and numerical results indicate that the coronavirus infection would remain endemic, which necessitates long-term disease prevention and intervention programs.", "qid": 13, "docid": "8mdnkegz", "rank": 29, "score": 0.7481069564819336}, {"content": "Title: Pattern of early human-to-human transmission of Wuhan 2019-nCoV Content: On December 31, 2019, the World Health Organization was notified about a cluster of pneumonia of unknown aetiology in the city of Wuhan, China. Chinese authorities later identified a new coronavirus (2019-nCoV) as the causative agent of the outbreak. As of January 23, 2020, 655 cases have been confirmed in China and several other countries. Understanding the transmission characteristics and the potential for sustained human-to-human transmission of 2019-nCoV is critically important for coordinating current screening and containment strategies, and determining whether the outbreak constitutes a public health emergency of international concern (PHEIC). We performed stochastic simulations of early outbreak trajectories that are consistent with the epidemiological findings to date. We found the basic reproduction number, R0, to be around 2.2 (90% high density interval 1.4\u20143.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of a similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and the 1918 pandemic influenza. These findings underline the importance of heightened screening, surveillance and control efforts, particularly at airports and other travel hubs, in order to prevent further international spread of 2019-nCoV.", "qid": 13, "docid": "jjkf5gg3", "rank": 30, "score": 0.7473690509796143}, {"content": "Title: Transmission routes of 2019-nCoV and controls in dental practice Content: A novel \u03b2-coronavirus (2019-nCoV) caused severe and even fetal pneumonia explored in a seafood market of Wuhan city, Hubei province, China, and rapidly spread to other provinces of China and other countries. The 2019-nCoV was different from SARS-CoV, but shared the same host receptor the human angiotensin-converting enzyme 2 (ACE2). The natural host of 2019-nCoV may be the bat Rhinolophus affinis as 2019-nCoV showed 96.2% of whole-genome identity to BatCoV RaTG13. The person-to-person transmission routes of 2019-nCoV included direct transmission, such as cough, sneeze, droplet inhalation transmission, and contact transmission, such as the contact with oral, nasal, and eye mucous membranes. 2019-nCoV can also be transmitted through the saliva, and the fetal\u2013oral routes may also be a potential person-to-person transmission route. The participants in dental practice expose to tremendous risk of 2019-nCoV infection due to the face-to-face communication and the exposure to saliva, blood, and other body fluids, and the handling of sharp instruments. Dental professionals play great roles in preventing the transmission of 2019-nCoV. Here we recommend the infection control measures during dental practice to block the person-to-person transmission routes in dental clinics and hospitals.", "qid": 13, "docid": "lasv4e6a", "rank": 31, "score": 0.746023416519165}, {"content": "Title: Effect of Nonpharmaceutical Interventions on Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, South Korea, 2020 Content: We analyzed transmission of coronavirus disease outside of the Daegu-Gyeongsangbuk provincial region in South Korea. We estimated that nonpharmaceutical measures reduced transmissibility by a maximum of 34% without resorting to a strict lockdown strategy. To optimize epidemic control, continuous efforts to monitor the transmissibility are needed.", "qid": 13, "docid": "12uca8kw", "rank": 32, "score": 0.7455365657806396}, {"content": "Title: Effect of Nonpharmaceutical Interventions on Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, South Korea, 2020. Content: We analyzed transmission of coronavirus disease outside of the Daegu-Gyeongsangbuk provincial region in South Korea. We estimated that nonpharmaceutical measures reduced transmissibility by a maximum of 34% without resorting to a strict lockdown strategy. To optimize epidemic control, continuous efforts to monitor the transmissibility are needed.", "qid": 13, "docid": "odmx6ng8", "rank": 33, "score": 0.7455365657806396}, {"content": "Title: A letter about the airborne transmission of sars-cov-2 based on the current evidence Content: World Health Organization has suggested that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted through person-to-person transmission and contact with contaminated surfaces. However, rapid spread of the coronavirus disease 2019 (COVID-19) suggests other routes such as airborne transmission may be involved. A few research studies have been conducted to evaluate the potential transmission of this virus through air. Although some studies have found no evidence of airborne transmission, other more recent work is proving the presence of SARS-CoV-2 even in public places. Also, the past experiences and knowledge about the mechanisms of similar viruses such as SARS-CoV support this hypothesis. It seems that the best decision at the moment is to follow a conservative approach, and accept the hypothesis that SARS-CoV-2 is able to be transmitted through air. By this, control measures could be employed to prevent further COVID-19 infection.", "qid": 13, "docid": "a1ha0hx4", "rank": 34, "score": 0.7451742887496948}, {"content": "Title: The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future Content: At the end of December 2019, a novel coronavirus, 2019-nCoV, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China, which has posed great threats to public health and attracted enormous attention around the world. To date, there are no clinically approved vaccines or antiviral drugs available for these human coronavirus infections. Intensive research on the novel emerging human infectious coronaviruses is urgently needed to elucidate their route of transmission and pathogenic mechanisms, and to identify potential drug targets, which would promote the development of effective preventive and therapeutic countermeasures. Herein, we describe the epidemic and etiological characteristics of 2019-nCoV, discuss its essential biological features, including tropism and receptor usage, summarize approaches for disease prevention and treatment, and speculate on the transmission route of 2019-nCoV.", "qid": 13, "docid": "co1mu99a", "rank": 35, "score": 0.7442501783370972}, {"content": "Title: SARS\u2010CoV\u20102 and human milk: What is the evidence? Content: The novel coronavirus SARS\u2010CoV\u20102 has emerged as one of the most compelling and concerning public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical and public health communities has rapidly engaged to collectively find answers and solutions. One area of active inquiry is understanding the mode(s) of SARS\u2010CoV\u20102 transmission. Although respiratory droplets are a known mechanism of transmission, other mechanisms are likely. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronaviruses (including SARS\u2010CoV\u20102) via human milk and/or breastfeeding. Results of the literature search reported here (finalized on 17 April 2020) revealed a single study providing some evidence of vertical transmission of human coronavirus 229E; a single study evaluating presence of SARS\u2010CoV in human milk (it was negative); and no published data on MERS\u2010CoV and human milk. We identified 13 studies reporting human milk tested for SARS\u2010CoV\u20102; one study (a non\u2010peer\u2010reviewed preprint) detected the virus in one milk sample, and another study detected SARS\u2010CoV\u20102 specific IgG in milk. Importantly, none of the studies on coronaviruses and human milk report validation of their collection and analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses (in particular, SARS\u2010CoV\u20102) during breastfeeding are discussed.", "qid": 13, "docid": "d0s028wl", "rank": 36, "score": 0.7439121007919312}, {"content": "Title: Ventilation in the Dental Clinic: An Effective Measure to Control Droplets and Aerosols during the Coronavirus Pandemic and Beyond. Content: Clinical and epidemiological studies suggest that human-to-human transmission of coronavirus disease 2019 (COVID-19) most frequently occurs through virus-laden respiratory droplets discharged from infected individuals while coughing and sneezing. Aerosols can act as another potential transmission route. The World Health Organisation (WHO) has advised medical personnel to consider taking 'airborne precautions'. It is important to protect dentists and patients and reduce the amount of spatter produced during dental procedures. In order to prevent airborne transmission, dental offices should be sufficiently ventilated, with great emphasis placed upon removing bioaerosols.", "qid": 13, "docid": "db97z3nl", "rank": 37, "score": 0.7435345649719238}, {"content": "Title: How does the outbreak of 2019-nCoV spread in mainland China? A retrospective analysis of the dynamic transmission routes Content: The fourth outbreak of the Coronaviruses, known as the 2019-nCoV, has occurred in Wuhan city of Hubei province in China in December 2019. We propose a time-varying sparse vector autoregressive (VAR) model to retrospectively analyze and visualize the dyamic transmission routes of this outbreak in mainland China over January 31 - February 19, 2020. Our results demonstrate that the influential inter-province routes from Hubei have become unidentifiable since February 4, whereas the self-transmission in each province was accelerating over February 4-15. From February 16, all routes became less detectable, and no influential transmissions could be identified on February 18 and 19. Such evidence supports the effectiveness of government interventions, including the travel restrictions in Hubei. Implications of our results suggest that in addition to the origin of the outbreak, virus preventions are of crucial importance in provinces with the largest migrant workers percentages (e.g., Jiangxi, Henan and Anhui) to controlling the spread of 2019-nCoV.", "qid": 13, "docid": "4k1i6y98", "rank": 38, "score": 0.7432463765144348}, {"content": "Title: Comparison of the COVID-19 infection risks by close contact and aerosol transmission Content: A comprehensive understanding of the transmission routes of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of great importance for the effective control of the spread of Corona Virus Disease 2019 (COVID-19). Human-to-human transmission by close contact where large respiratory droplets play a significant role has been established as the main transmission route. At the same time the transmission by small aerosol is getting increasing attention. There is no distinct boundary between droplets and aerosol in nature so it is natural to investigate the infection risk due to aerosol. Here, we utilized a newly developed dose-response relation, combined with a box model for the exposure estimation, to quantitatively evaluate the infection risk of SARS-CoV-2 through aerosol transmission and compared with the risk due to close contact. The results indicated that the median infection risk via aerosol transmission was about 3.7x10-5 (95% confidence interval: 3.5x10-6 to 4.4x10-4) for one hour of exposure in a room with the size of 10 m (width)x10 m (length)x3 m (height) with one infected individual in it. The risk was more than three orders of magnitude lower than the risk at short distance, about 12.8% within 1 m, based on a meta-analysis. A simple exponential regression model Risk=10-0.90xD+0.10 (D<=5 m) could be utilized to characterize the magnitude of infection risk in the considered scenario based on the distance D from the infected individual. With prolonged exposure duration and large exposed population, the infection caused by aerosol transmission could be considerable, thus it is necessary to be cautious for the potential aerosol transmission risk in such situations.", "qid": 13, "docid": "kt76tu24", "rank": 39, "score": 0.742748498916626}, {"content": "Title: HUMAN CORONAVIRUS DATA FROM FOUR CLINICAL TRIALS OF MASKS AND RESPIRATORS Content: There are few published data on the protection of masks or respirators against coronavirus infections. This is an important research question to inform the response to the COVID-19 epidemic. The transmission modes of human coronaviruses are similar, thought to be by droplet, contact and sometimes airborne routes. There are several randomised clinical trials of masks and respirators, but most used clinical endpoints or tested only for influenza. In four trials which we conducted, we tested for human coronaviruses, but only composite viral endpoints were reported in the trials. We reviewed and analysed the coronavirus data from four of our trials. Laboratory-confirmed coronavirus infections were identified in our community household trial (1 case), health worker trials (8 cases) and trial of mask use by sick patients (19 cases). No coronavirus infections were transmitted in households to parents who wore P2 or surgical masks, but one child with coronavirus infection transmitted infection to a parent in the control arm. No transmissions to close contacts occurred when worn by sick patients with coronavirus infections. There was a higher risk of coronavirus infection in HCWs who wore a mask compared to a respirator, but the difference was not statistically significant. These are the only available data on coronavirus infections associated with mask or respirator use. More clinical trials are needed to assess the efficacy of respiratory protection against coronavirus infections.", "qid": 13, "docid": "vjg2auh7", "rank": 40, "score": 0.742641031742096}, {"content": "Title: Human Coronavirus Data from Four Clinical Trials of Masks and Respirators Content: There are few published data on the protection of masks or respirators against coronavirus infections. This is an important research question to inform the response to the COVID-19 epidemic. The transmission modes of human coronaviruses are similar, thought to be by droplet, contact and sometimes airborne routes. There are several randomised clinical trials of masks and respirators, but most used clinical endpoints or tested only for influenza. In four trials which we conducted, we tested for human coronaviruses, but only composite viral endpoints were reported in the trials. We reviewed and analysed the coronavirus data from four of our trials. Laboratory-confirmed coronavirus infections were identified in our community household trial (1 case), health worker trials (8 cases) and trial of mask use by sick patients (19 cases). No coronavirus infections were transmitted in households to parents who wore P2 or surgical masks, but one child with coronavirus infection transmitted infection to a parent in the control arm. No transmissions to close contacts occurred when worn by sick patients with coronavirus infections. There was a higher risk of coronavirus infection in HCWs who wore a mask compared to a respirator, but the difference was not statistically significant. These are the only available data on coronavirus infections associated with mask or respirator use. More clinical trials are needed to assess the efficacy of respiratory protection against coronavirus infections.", "qid": 13, "docid": "gey0nidn", "rank": 41, "score": 0.742641031742096}, {"content": "Title: Global epidemiology, pathogenesis, immune response, diagnosis, treatment, economic and psychological impact, challenges, and future prevention of COVID-19: A scoping review Content: Background: Globally, the novel coronavirus, is a public health problem causing respiratory infections. Since the outbreak of severe acute and Middle East respiratory syndromes coronavirus was not reported to cause human infections. Now, it become an epidemic proportion with growing number of cases and deaths. Methods: A scoping review was conducted following the methodological framework. In this scoping review, 50 records published before 28 March, 2020 were included and discussed to better understand the current epidemiology, pathogenesis, immunological response, diagnosis, evasion mechanisms and suggested strategies to boost the immune system, challenges, treatment, and future preventions of the virus. PubMed, BioRxiv, MedRxiv, Global Health and google scholars were searched comprehensively for articles, preprints, grey literatures, reports, websites, conference proceedings and expert information. Studies conducted in human and published in the English language were included in the analysis. All the findings and statements of the review regarding the outbreak are based on published information as listed in citations. Results: We identified 360 records, of which 50 studies met the inclusion criteria. We synthesized the data from the included records and dig out the deep insights of them and pooled into this review. The burden of the outbreak is worsening due to overcrowding, presence of asymptomatic carriers, scarcity of test kits, the immune escaping ability of the virus and lack of awareness. Conclusions and recommendations: Due to the fast-spreading nature of COVID-19 the prevention and control strategies become challenging. It is imposing social, psychological, and socio-economic impacts. We recommended that following social distancing, isolation suspects, using personal protective equipment, health education and introducing handwashing practices, avoiding contact with animals, vaccine development and treatment for controlling and prevention.", "qid": 13, "docid": "prpooezh", "rank": 42, "score": 0.7421435117721558}, {"content": "Title: Cuidados enfermeros orientados a mitigar la transmisi\u00f3n del coronavirus en caso de positivos: una revisi\u00f3n narrativa./ [Nursing care for controlling coronavirus infections in positive cases: a narrative review.] Content: OBJECTIVE: This review aims to map scientific evidence in nursing care aimed at controlling coronavirus infections. METHODS: A bibliographic search was conducted in the Medline, CINAHL, Scopus and WOS main databases, with no date limit and using the keywords \"transmission\", \"infection\", \"contagious\", \"spreads\", \"coronavirinae\", \"coronavirus\", \"COVID 19\", \"sars cov 2\", \"nurses\" and \"nursing\". Initially, 154 studies were identified and, after selecting them according to eligibility criteria, 16 were included. RESULTS: Among the main recommendations according to the available evidence are air exchange in rooms as a measure to reduce the risk of infection among patients; reinforcement of measures in intensive care units; follow-up of positive case contacts; and adequate training of professionals. DISCUSSION AND CONCLUSIONS: The studies included in the review addressed infection prevention and control practices by analyzing risks associated with exposure and listing actions to avoid complications in critically ill patients. Patterns of case transmission, contacts and associated factors were identified. Professional knowledge and attitudes were also studied, showing the importance of good infection control training, and of sufficient equipment and adequate infrastructure.Nurses are important vectors of spread. Although there is little evidence available on the effectiveness of care to prevent the spread of SARS-CoV-2, published studies on the prevention and control of previous outbreaks of coronavirus are of considerable value.", "qid": 13, "docid": "fcpnweni", "rank": 43, "score": 0.7415598630905151}, {"content": "Title: 2019-nCoV (Wuhan virus), a novel Coronavirus: human-to-human transmission, travel-related cases, and vaccine readiness Content: On 31 December 2019 the Wuhan Health Commission reported a cluster of atypical pneumonia cases that was linked to a wet market in the city of Wuhan, China. The first patients began experiencing symptoms of illness in mid-December 2019. Clinical isolates were found to contain a novel coronavirus with similarity to bat coronaviruses. As of 28 January 2020, there are in excess of 4,500 laboratory-confirmed cases, with > 100 known deaths. As with the SARS-CoV, infections in children appear to be rare. Travel-related cases have been confirmed in multiple countries and regions outside mainland China including Germany, France, Thailand, Japan, South Korea, Vietnam, Canada, and the United States, as well as Hong Kong and Taiwan. Domestically in China, the virus has also been noted in several cities and provinces with cases in all but one provinence. While zoonotic transmission appears to be the original source of infections, the most alarming development is that human-to-human transmission is now prevelant. Of particular concern is that many healthcare workers have been infected in the current epidemic. There are several critical clinical questions that need to be resolved, including how efficient is human-to-human transmission? What is the animal reservoir? Is there an intermediate animal reservoir? Do the vaccines generated to the SARS-CoV or MERS-CoV or their proteins offer protection against 2019-nCoV? We offer a research perspective on the next steps for the generation of vaccines. We also present data on the use of in silico docking in gaining insight into 2019-nCoV Spike-receptor binding to aid in therapeutic development. Diagnostic PCR protocols can be found at https://www.who.int/health-topics/coronavirus/laboratory-diagnostics-for-novel-coronavirus.", "qid": 13, "docid": "bu1ib2ul", "rank": 44, "score": 0.7409984469413757}, {"content": "Title: 2019-nCoV (Wuhan virus), a novel Coronavirus: human-to-human transmission, travel-related cases, and vaccine readiness. Content: On 31 December 2019 the Wuhan Health Commission reported a cluster of atypical pneumonia cases that was linked to a wet market in the city of Wuhan, China. The first patients began experiencing symptoms of illness in mid-December 2019. Clinical isolates were found to contain a novel coronavirus with similarity to bat coronaviruses. As of 28 January 2020, there are in excess of 4,500 laboratory-confirmed cases, with > 100 known deaths. As with the SARS-CoV, infections in children appear to be rare. Travel-related cases have been confirmed in multiple countries and regions outside mainland China including Germany, France, Thailand, Japan, South Korea, Vietnam, Canada, and the United States, as well as Hong Kong and Taiwan. Domestically in China, the virus has also been noted in several cities and provinces with cases in all but one provinence. While zoonotic transmission appears to be the original source of infections, the most alarming development is that human-to-human transmission is now prevelant. Of particular concern is that many healthcare workers have been infected in the current epidemic. There are several critical clinical questions that need to be resolved, including how efficient is human-to-human transmission? What is the animal reservoir? Is there an intermediate animal reservoir? Do the vaccines generated to the SARS-CoV or MERS-CoV or their proteins offer protection against 2019-nCoV? We offer a research perspective on the next steps for the generation of vaccines. We also present data on the use of in silico docking in gaining insight into 2019-nCoV Spike-receptor binding to aid in therapeutic development. Diagnostic PCR protocols can be found at https://www.who.int/health-topics/coronavirus/laboratory-diagnostics-for-novel-coronavirus.", "qid": 13, "docid": "rxrlbw60", "rank": 45, "score": 0.7409984469413757}, {"content": "Title: Digestive system involvement of novel coronavirus infection: Prevention and control infection from a gastroenterology perspective Content: An epidemic of an acute respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) in Wuhan, China, now known as coronavirus disease 2019 (COVID\u201019), beginning in December 2019, has attracted an intense amount of attention worldwide. As the natural history and variety of clinical presentations of this disease unfolds, extrapulmonary symptoms of COVID\u201019 have emerged, especially in the digestive system. While the respiratory mode of transmission is well known and is probably the principal mode of transmission of this disease, a possibility of the fecal\u2010oral route of transmission has also emerged in various case series and clinical scenarios. In this review article, we summarize four different aspects in published studies to date: (a) gastrointestinal manifestations of COVID\u201019; (b) microbiological and virological investigations; (c) the role of fecal\u2010oral transmission; and (d) prevention and control of SARS\u2010CoV\u20102 infection in the digestive endoscopy room. A timely understanding of the relationship between the disease and the digestive system and implementing effective preventive measures are of great importance for a favorable outcome of the disease and can help climnicians to mitigate further transmission by taking appropriate measures.", "qid": 13, "docid": "xj9md751", "rank": 46, "score": 0.7409335374832153}, {"content": "Title: Coronavirus threat to Indian population: risk factors, transmission dynamics and preparedness to prevent the spread of the virus Content: Recent novel coronavirus outbreak in Wuhan City of Hubei province in China infected nearly 70,000 individuals and killed more than 1700 people within a short span of time leading to global pandemic. The disease is now spread to 26 countries in Asia, North America, Europe and Australasia. The virus is spreading rapidly to Asia-pacific and Southeast Asian countries. The disease is posing a serious threat to human population and has devastating impact on public health and economy. So far 3 Indians are infected and India is at risk of rapid spread of the disease because of its geographical location and other favorable conditions. With a poorer global health security index compared to China (India-57 and China-51), any such situation will have worse outcome. In near future there are also possibilities of similar kind of disease outbreak caused by new strains of coronaviruses due to factors like species jump of new viruses, high population density and inadequate medical facilities. In this short review we have highlighted the risk factors and transmission dynamics of coronaviruses that may pose a serious threat to India. We have also discussed about the possible preventive measure our country should take to control any such outbreak situation.", "qid": 13, "docid": "u4gc98g4", "rank": 47, "score": 0.7399587631225586}, {"content": "Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes Content: In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.", "qid": 13, "docid": "zztydksw", "rank": 48, "score": 0.7397027015686035}, {"content": "Title: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes Content: In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral\u2013fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral\u2013fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.", "qid": 13, "docid": "4aps0kvp", "rank": 49, "score": 0.7396050691604614}, {"content": "Title: A generalized overview of SARS-COV-2: Where does the current knowledge stand? Content: The novel coronavirus known to have brought the world to a standstill is responsible for many deaths throughout the globe as of now. The causative agent (SARS-CoV-2) for coronavirus disease 2019 (COVID-19) has been recognized as a zoonotic transfer. Although, the medium of animal-human transmission is still unknown, bats maybe a potential reservoir of this novel strain. Due to its high rate of transmission the most favorable way of limiting the outbreak\u2019s extent is by early diagnosis followed by isolation of the infected individuals. So far, the most widely used diagnosis methods are RT-qPCR which detects specific sequences of the viral RNA. Some other methods include serological tests and the recently introduced CRISPR-CAS-12 based assays. As of now, no specific therapeutic treatments are known for COVID-19 however the use of some broad-spectrum antiviral drugs and convalescent plasma therapy have demonstrated positive outcomes. Apart from these treatments, vaccine development for SARS-CoV-2 is also in progress by 17 known companies. This article provides a comprehensive insight on the recently emerged Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) including its origin, transmission mechanism, pathophysiology and updated treatment methods.", "qid": 13, "docid": "41rsi8ce", "rank": 50, "score": 0.7394232749938965}, {"content": "Title: Passengers' destinations from China: low risk of Novel Coronavirus (2019-nCoV) transmission into Africa and South America Content: Novel Coronavirus (2019-nCoV [SARS-COV-2]) was detected in humans during the last week of December 2019 at Wuhan city in China, and caused 24 554 cases in 27 countries and territories as of 5 February 2020. The objective of this study was to estimate the risk of transmission of 2019-nCoV through human passenger air flight from four major cities of China (Wuhan, Beijing, Shanghai and Guangzhou) to the passengers' destination countries. We extracted the weekly simulated passengers' end destination data for the period of 1\u201331 January 2020 from FLIRT, an online air travel dataset that uses information from 800 airlines to show the direct flight and passengers' end destination. We estimated a risk index of 2019-nCoV transmission based on the number of travellers to destination countries, weighted by the number of confirmed cases of the departed city reported by the World Health Organization (WHO). We ranked each country based on the risk index in four quantiles (4(th) quantile being the highest risk and 1(st) quantile being the lowest risk). During the period, 388 287 passengers were destined for 1297 airports in 168 countries or territories across the world. The risk index of 2019-nCoV among the countries had a very high correlation with the WHO-reported confirmed cases (0.97). According to our risk score classification, of the countries that reported at least one Coronavirus-infected pneumonia (COVID-19) case as of 5 February 2020, 24 countries were in the 4(th) quantile of the risk index, two in the 3(rd) quantile, one in the 2(nd) quantile and none in the 1(st) quantile. Outside China, countries with a higher risk of 2019-nCoV transmission are Thailand, Cambodia, Malaysia, Canada and the USA, all of which reported at least one case. In pan-Europe, UK, France, Russia, Germany and Italy; in North America, USA and Canada; in Oceania, Australia had high risk, all of them reported at least one case. In Africa and South America, the risk of transmission is very low with Ethiopia, South Africa, Egypt, Mauritius and Brazil showing a similar risk of transmission compared to the risk of any of the countries where at least one case is detected. The risk of transmission on 31 January 2020 was very high in neighbouring Asian countries, followed by Europe (UK, France, Russia and Germany), Oceania (Australia) and North America (USA and Canada). Increased public health response including early case recognition, isolation of identified case, contract tracing and targeted airport screening, public awareness and vigilance of health workers will help mitigate the force of further spread to na\u00efve countries.", "qid": 13, "docid": "32gw2ug3", "rank": 51, "score": 0.7389447689056396}, {"content": "Title: Digestive system involvement of novel coronavirus infection: Prevention and control infection from a gastroenterology perspective Content: An epidemic of an acute respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, now known as coronavirus disease 2019 (COVID-19), beginning in December 2019, has attracted an intense amount of attention worldwide. As the natural history and variety of clinical presentations of this disease unfolds, extrapulmonary symptoms of COVID-19 have emerged, especially in the digestive system. While the respiratory mode of transmission is well known and is probably the principal mode of transmission of this disease, a possibility of the fecal-oral route of transmission has also emerged in various case series and clinical scenarios. In this review article, we summarize four different aspects in published studies to date: (a) gastrointestinal manifestations of COVID-19; (b) microbiological and virological investigations; (c) the role of fecal-oral transmission; and (d) prevention and control of SARS-CoV-2 infection in the digestive endoscopy room. A timely understanding of the relationship between the disease and the digestive system and implementing effective preventive measures are of great importance for a favorable outcome of the disease and can help climnicians to mitigate further transmission by taking appropriate measures.", "qid": 13, "docid": "dz8blrzm", "rank": 52, "score": 0.7388677000999451}, {"content": "Title: [A special on epidemic prevention and control: precautions in ophthalmic practice in the prevention and control of the novel coronavirus pneumonia epidemic] Content: This article was published ahead of print on the official website of Chinese Journal of Ophthalmology on March 2, 2020. Prevention and control of novel coronavirus pneumonia is now the top priority, and the protection of the eyes in the fight against the epidemic has also been an issue of great concern. Based on the latest progress made in basic and clinical research and practical experience in epidemic prevention and control, this article delivers objective guidance on whether the eye is a route of transmission of novel coronavirus infection, the precautions that should be taken by ophthalmologists in clinical practice during the epidemic, the novel coronavirus infection in the eyes and its clinical manifestation, and the public health education on eye protection, so as to provide valuable evidence for the scientific prevention and control of the epidemic and developing targeted countermeasures. (Chin J Ophthalmol, 2020, 56: 330-332).", "qid": 13, "docid": "vorsh3m2", "rank": 53, "score": 0.7388577461242676}, {"content": "Title: Role of fomites in SARS transmission during the largest hospital outbreak in Hong Kong Content: The epidemic of severe acute respiratory syndrome (SARS) had a significant effect on global society in the early 2000s and the potential of its resurgence exists. Studies on the modes of transmission of SARS are limited though a number of outbreak studies have revealed the possible airborne route. To develop more specific and effective control strategies, we conducted a detailed mechanism-based investigation that explored the role of fomite transmission in the well-known Ward 8A outbreak. We considered three hypothetical transmission routes, i.e., the long-range airborne, fomite and combined routes, in 1,744 scenarios with combinations of some important parameters. A multi-agent model was used to predict the infection risk distributions of the three hypothetical routes. Model selection was carried out for different scenarios to compare the distributions of infection risk with that of the reported attack rates and select the hypotheses with the best fitness. Our results reveal that under the assumed conditions, the SARS coronavirus was most possible to have spread via the combined long-range airborne and fomite routes, and that the fomite route played a non-negligible role in the transmission.", "qid": 13, "docid": "8rfm0jxh", "rank": 54, "score": 0.7384899258613586}, {"content": "Title: Transmission routes of 2019-nCoV and controls in dental practice Content: A novel \u00df-coronavirus (2019-nCoV) caused severe and even fetal pneumonia explored in a seafood market of Wuhan city, Hubei province, China, and rapidly spread to other provinces of China and other countries. The 2019-nCoV was different from SARS-CoV, but shared the same host receptor the human angiotensin-converting enzyme 2 (ACE2). The natural host of 2019-nCoV may be the bat Rhinolophus affinis as 2019-nCoV showed 96.2% of whole-genome identity to BatCoV RaTG13. The person-to-person transmission routes of 2019-nCoV included direct transmission, such as cough, sneeze, droplet inhalation transmission, and contact transmission, such as the contact with oral, nasal, and eye mucous membranes. 2019-nCoV can also be transmitted through the saliva, and the fetal-oral routes may also be a potential person-to-person transmission route. The participants in dental practice expose to tremendous risk of 2019-nCoV infection due to the face-to-face communication and the exposure to saliva, blood, and other body fluids, and the handling of sharp instruments. Dental professionals play great roles in preventing the transmission of 2019-nCoV. Here we recommend the infection control measures during dental practice to block the person-to-person transmission routes in dental clinics and hospitals.", "qid": 13, "docid": "wywldhr0", "rank": 55, "score": 0.738334059715271}, {"content": "Title: What makes a foodborne virus: comparison between coronaviruses with human noroviruses Content: In order to answer the question whether coronaviruses (CoVs) can be transmitted via foods, this review made a comparison between CoVs with the most recognized foodborne virus, human noroviruses (NoVs). As a result, although CoVs indeed have shown the possibilities to remain infectious on foods and/or food packaging materials long enough (from several days to several weeks) to potentially cause transmission, they seem to be less persistent than NoVs towards common disinfection practices with alcohols, chlorine and ultraviolet (UV). More importantly, the chance of foodborne transmission of CoVs is considered low as CoVs mainly spread through the respiratory tract and there is no clear evidence showing CoVs can follow fecal-oral routes like human NoVs and other foodborne viruses.", "qid": 13, "docid": "zybdv7ic", "rank": 56, "score": 0.737838864326477}, {"content": "Title: Comprehensive update on current outbreak of novel coronavirus infection (2019-nCoV). Content: Recently, a new coronavirus disease (COVID-19) has emerged as a respiratory infection with significant concern for global public health hazards. With an initial suspicion of the animal to the human transmission for earlier cases, now the paradigm has shifted towards human to human transmission via droplets, contacts and/or through fomites. with each passing day, more and more confirmed cases are being reported worldwide which has alarmed the global authorities including World Health Organization (WHO), Centers for Disease Control and Prevention (CDC) and the National Health Commission of the People's Republic of China to take immediate action in order to reduce the transmission and subsequent mortalities associated with COVID-19 to as minimum as possible. Unfortunately, like the previous Coronavirus outbreaks, there is no definite antiviral therapy for the treatment of confirmed cases and hence preventing ourselves from contracting 2019-nCoV is the best way to prevent it from becoming pandemic. Herein, we aim to discuss the latest updates on the origin, genomic characteristics, diagnosis, treatment options and current efforts being made by international health organizations with regards to the 2019-nCoV outbreak.", "qid": 13, "docid": "yxizepar", "rank": 57, "score": 0.7376704812049866}, {"content": "Title: Passengers' destinations from China: low risk of Novel Coronavirus (2019-nCoV) transmission into Africa and South America Content: Novel Coronavirus (2019-nCoV [SARS-COV-2]) was detected in humans during the last week of December 2019 at Wuhan city in China, and caused 24 554 cases in 27 countries and territories as of 5 February 2020. The objective of this study was to estimate the risk of transmission of 2019-nCoV through human passenger air flight from four major cities of China (Wuhan, Beijing, Shanghai and Guangzhou) to the passengers' destination countries. We extracted the weekly simulated passengers' end destination data for the period of 1-31 January 2020 from FLIRT, an online air travel dataset that uses information from 800 airlines to show the direct flight and passengers' end destination. We estimated a risk index of 2019-nCoV transmission based on the number of travellers to destination countries, weighted by the number of confirmed cases of the departed city reported by the World Health Organization (WHO). We ranked each country based on the risk index in four quantiles (4th quantile being the highest risk and 1st quantile being the lowest risk). During the period, 388 287 passengers were destined for 1297 airports in 168 countries or territories across the world. The risk index of 2019-nCoV among the countries had a very high correlation with the WHO-reported confirmed cases (0.97). According to our risk score classification, of the countries that reported at least one Coronavirus-infected pneumonia (COVID-19) case as of 5 February 2020, 24 countries were in the 4th quantile of the risk index, two in the 3rd quantile, one in the 2nd quantile and none in the 1st quantile. Outside China, countries with a higher risk of 2019-nCoV transmission are Thailand, Cambodia, Malaysia, Canada and the USA, all of which reported at least one case. In pan-Europe, UK, France, Russia, Germany and Italy; in North America, USA and Canada; in Oceania, Australia had high risk, all of them reported at least one case. In Africa and South America, the risk of transmission is very low with Ethiopia, South Africa, Egypt, Mauritius and Brazil showing a similar risk of transmission compared to the risk of any of the countries where at least one case is detected. The risk of transmission on 31 January 2020 was very high in neighbouring Asian countries, followed by Europe (UK, France, Russia and Germany), Oceania (Australia) and North America (USA and Canada). Increased public health response including early case recognition, isolation of identified case, contract tracing and targeted airport screening, public awareness and vigilance of health workers will help mitigate the force of further spread to na\u00efve countries.", "qid": 13, "docid": "0mytklmf", "rank": 58, "score": 0.7375964522361755}, {"content": "Title: Work-related COVID-19 transmission in six Asian countries/areas: A follow-up study Content: OBJECTIVE: There is limited evidence of work-related transmission in the emerging coronaviral pandemic. We aimed to identify high-risk occupations for early coronavirus disease 2019 (COVID-19) local transmission. METHODS: In this observational study, we extracted confirmed COVID-19 cases from governmental investigation reports in Hong Kong, Japan, Singapore, Taiwan, Thailand, and Vietnam. We followed each country/area for 40 days after its first locally transmitted case, and excluded all imported cases. We defined a possible work-related case as a worker with evidence of close contact with another confirmed case due to work, or an unknown contact history but likely to be infected in the working environment (e.g. an airport taxi driver). We calculated the case number for each occupation, and illustrated the temporal distribution of all possible work-related cases and healthcare worker (HCW) cases. The temporal distribution was further defined as early outbreak (the earliest 10 days of the following period) and late outbreak (11(th) to 40(th) days of the following period). RESULTS: We identified 103 possible work-related cases (14.9%) among a total of 690 local transmissions. The five occupation groups with the most cases were healthcare workers (HCWs) (22%), drivers and transport workers (18%), services and sales workers (18%), cleaning and domestic workers (9%) and public safety workers (7%). Possible work-related transmission played a substantial role in early outbreak (47.7% of early cases). Occupations at risk varied from early outbreak (predominantly services and sales workers, drivers, construction laborers, and religious professionals) to late outbreak (predominantly HCWs, drivers, cleaning and domestic workers, police officers, and religious professionals). CONCLUSIONS: Work-related transmission is considerable in early COVID-19 outbreaks, and the elevated risk of infection was not limited to HCW. Implementing preventive/surveillance strategies for high-risk working populations is warranted.", "qid": 13, "docid": "lbd0mu7k", "rank": 59, "score": 0.7373920679092407}, {"content": "Title: Work-related COVID-19 transmission in six Asian countries/areas: A follow-up study Content: OBJECTIVE: There is limited evidence of work-related transmission in the emerging coronaviral pandemic. We aimed to identify high-risk occupations for early coronavirus disease 2019 (COVID-19) local transmission. METHODS: In this observational study, we extracted confirmed COVID-19 cases from governmental investigation reports in Hong Kong, Japan, Singapore, Taiwan, Thailand, and Vietnam. We followed each country/area for 40 days after its first locally transmitted case, and excluded all imported cases. We defined a possible work-related case as a worker with evidence of close contact with another confirmed case due to work, or an unknown contact history but likely to be infected in the working environment (e.g. an airport taxi driver). We calculated the case number for each occupation, and illustrated the temporal distribution of all possible work-related cases and healthcare worker (HCW) cases. The temporal distribution was further defined as early outbreak (the earliest 10 days of the following period) and late outbreak (11th to 40th days of the following period). RESULTS: We identified 103 possible work-related cases (14.9%) among a total of 690 local transmissions. The five occupation groups with the most cases were healthcare workers (HCWs) (22%), drivers and transport workers (18%), services and sales workers (18%), cleaning and domestic workers (9%) and public safety workers (7%). Possible work-related transmission played a substantial role in early outbreak (47.7% of early cases). Occupations at risk varied from early outbreak (predominantly services and sales workers, drivers, construction laborers, and religious professionals) to late outbreak (predominantly HCWs, drivers, cleaning and domestic workers, police officers, and religious professionals). CONCLUSIONS: Work-related transmission is considerable in early COVID-19 outbreaks, and the elevated risk of infection was not limited to HCW. Implementing preventive/surveillance strategies for high-risk working populations is warranted.", "qid": 13, "docid": "ruliehs0", "rank": 60, "score": 0.7372918128967285}, {"content": "Title: Narrative review of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: updates and implications for practice Content: Human coronaviruses (HCoVs) comprise six subtypes of coronavirus that are associated with a number of respiratory diseases such as common cold, pneumonia, and bronchitis. Middle East respiratory syndrome coronavirus (MERS-CoV) is one of these six HCoV subtypes. HCoVs can result in life-threatening respiratory diseases, such as pneumonia and bronchiolitis, and may cause enteric and neurologic diseases, especially in immunocompromised patients. This narrative review aimed to enrich the knowledge of health care professional regarding MERS-CoV infection epidemiology, control, and management. This review discusses MERS-CoV prevalence, clinical manifestation, modes of transmission, control measures, and management, which we identified in a search of various databases, related journals, and the published literature. It has been shown that MERS-CoV infection is likely to be transmitted among countries. Therefore, countries with a high rate of MERS-CoV infection are urged to develop and implement guidelines to minimize the spread of infection. Countries must give careful consideration to raising public awareness in regions that are affected by MERS-CoV infection and the importance of reporting any disease signs and symptoms, to receive proper care.", "qid": 13, "docid": "pfamlz3g", "rank": 61, "score": 0.7362933158874512}, {"content": "Title: Airborne transmission of severe acute respiratory syndrome coronavirus\u20102 to healthcare workers: a narrative review Content: Healthcare workers are at risk of infection during the severe acute respiratory syndrome coronavirus\u20102 pandemic. International guidance suggests direct droplet transmission is likely and airborne transmission occurs only with aerosol\u2010generating procedures. Recommendations determining infection control measures to ensure healthcare worker safety follow these presumptions. Three mechanisms have been described for the production of smaller sized respiratory particles (\u2018aerosols\u2019) that, if inhaled, can deposit in the distal airways. These include: laryngeal activity such as talking and coughing; high velocity gas flow; and cyclical opening and closure of terminal airways. Sneezing and coughing are effective aerosol generators, but all forms of expiration produce particles across a range of sizes. The 5\u2010\u03bcm diameter threshold used to differentiate droplet from airborne is an over\u2010simplification of multiple complex, poorly understood biological and physical variables. The evidence defining aerosol\u2010generating procedures comes largely from low\u2010quality case and cohort studies where the exact mode of transmission is unknown as aerosol production was never quantified. We propose that transmission is associated with time in proximity to severe acute respiratory syndrome coronavirus\u20101 patients with respiratory symptoms, rather than the procedures per se. There is no proven relation between any aerosol\u2010generating procedure with airborne viral content with the exception of bronchoscopy and suctioning. The mechanism for severe acute respiratory syndrome coronavirus\u20102 transmission is unknown but the evidence suggestive of airborne spread is growing. We speculate that infected patients who cough, have high work of breathing, increased closing capacity and altered respiratory tract lining fluid will be significant producers of pathogenic aerosols. We suggest several aerosol\u2010generating procedures may in fact result in less pathogen aerosolisation than a dyspnoeic and coughing patient. Healthcare workers should appraise the current evidence regarding transmission and apply this to the local infection prevalence. Measures to mitigate airborne transmission should be employed at times of risk. However, the mechanisms and risk factors for transmission are largely unconfirmed. Whilst awaiting robust evidence, a precautionary approach should be considered to assure healthcare worker safety.", "qid": 13, "docid": "0tm4im5i", "rank": 62, "score": 0.7357121706008911}, {"content": "Title: Coronaviruses in wastewater processes: source, fate and potential risks Content: Abstract The last 17 years have seen three major outbreaks caused by coronaviruses, with the latest outbreak, COVID-19, declared a pandemic by the World Health Organization. The frequency of these outbreaks, their mortality and associated disruption to normal life calls for concerted efforts to understand their occurrence and fate in different environments. There is an increased interest in the occurrence of coronaviruses in wastewater from the perspective of wastewater-based epidemiology. However, there is no comprehensive review of the knowledge on coronavirus occurrence, fate and potential transmission in wastewater. This paper, provides a review of the literature on the occurrence of coronaviruses in wastewater treatment processes. We discuss the presence of viral RNA in feces as a result of gastrointestinal infections resulting in diarrhoea. We also review the literature on their presence, survival and potential removal in common wastewater treatment processes. The detection of infectious viral particles in feces of patients raises questions on the potential risks of infection for people exposed to untreated sewage/wastewater. We, therefore, discuss the potential risk of infection with coronaviruses for workers in wastewater treatment plants and the public that may be exposed through faulty plumbing or burst sewer networks. The disruption of life and mortalities warrants a much more focused research on the role of environments, such as wastewater and surface water, in disease transmission. The current wealth of knowledge on coronaviruses in wastewater based on the reviewed literature is scant and therefore calls for further studies.", "qid": 13, "docid": "zwpgvn4y", "rank": 63, "score": 0.7356800436973572}, {"content": "Title: Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020 Content: Since December 2019, China has been experiencing a large outbreak of a novel coronavirus (2019-nCoV) which can cause respiratory disease and severe pneumonia. We estimated the basic reproduction number R0 of 2019-nCoV to be around 2.2 (90% high density interval: 1.4-3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and pandemic influenza, indicating a risk of global spread.", "qid": 13, "docid": "px5go7rc", "rank": 64, "score": 0.7354889512062073}, {"content": "Title: Airborne transmission of severe acute respiratory syndrome coronavirus-2 to healthcare workers: a narrative review Content: Healthcare workers are at risk of infection during the severe acute respiratory syndrome coronavirus-2 pandemic. International guidance suggests direct droplet transmission is likely and airborne transmission occurs only with aerosol-generating procedures. Recommendations determining infection control measures to ensure healthcare worker safety follow these presumptions. Three mechanisms have been described for the production of smaller sized respiratory particles ('aerosols') that, if inhaled, can deposit in the distal airways. These include: laryngeal activity such as talking and coughing; high velocity gas flow; and cyclical opening and closure of terminal airways. Sneezing and coughing are effective aerosol generators, but all forms of expiration produce particles across a range of sizes. The 5-\u00b5m diameter threshold used to differentiate droplet from airborne is an over-simplification of multiple complex, poorly understood biological and physical variables. The evidence defining aerosol-generating procedures comes largely from low-quality case and cohort studies where the exact mode of transmission is unknown as aerosol production was never quantified. We propose that transmission is associated with time in proximity to severe acute respiratory syndrome coronavirus-1 patients with respiratory symptoms, rather than the procedures per se. There is no proven relation between any aerosol-generating procedure with airborne viral content with the exception of bronchoscopy and suctioning. The mechanism for severe acute respiratory syndrome coronavirus-2 transmission is unknown but the evidence suggestive of airborne spread is growing. We speculate that infected patients who cough, have high work of breathing, increased closing capacity and altered respiratory tract lining fluid will be significant producers of pathogenic aerosols. We suggest several aerosol-generating procedures may in fact result in less pathogen aerosolisation than a dyspnoeic and coughing patient. Healthcare workers should appraise the current evidence regarding transmission and apply this to the local infection prevalence. Measures to mitigate airborne transmission should be employed at times of risk. However, the mechanisms and risk factors for transmission are largely unconfirmed. Whilst awaiting robust evidence, a precautionary approach should be considered to assure healthcare worker safety.", "qid": 13, "docid": "j4abgq88", "rank": 65, "score": 0.735363245010376}, {"content": "Title: COVID-19 pandemic: Impact of lockdown, contact and non-contact transmissions on infection dynamics Content: COVID-19 coronavirus pandemic has virtually locked down the entire world of human population, and through its rapid and unstoppable spread COVID-19 has essentially compartmentalised the population merely into susceptible, exposed, infected and recovered classes. Adapting the classical epidemic modelling framework, two distinct routes of COVID-19 transmission are incorporated into a model: (a) direct person-to-person contact transmission, and (b) indirect airborne and fomites-driven transmission. The indirect non-contact transmission route needs to explored in models of COVID-19 spread, because evidences show that this route of transmission is entirely viable with hugely uncertain level of relative contribution. This theoretical study based on model simulations demonstrates the following: (1) Not incorporating indirect transmission route in the model leads to underestimation of the basic reproduction number, and hence will impact on the COVID-19 mitigation decisions; (2) Lockdown measures can suppress the primary infection peak, but will lead to a secondary peak whose relative strength and time of occurrence depend on the success and duration of the lockdown measures; (3) To make lockdown effective, a considerable level of reduction in both contact and non-contact transmission rates over a long period is required; (4) To bring down the infection cases below any hypothetical health-care capacity, reduction of non-contact transmission rate is key, and hence active measures should be taken to reduce non-contact transmission (e.g., extensive uses of areal and aerosol disinfectant in public spaces to improve contaminated surfaces and air); (5) Any premature withdrawal of lockdown following the sign of a brief retracement in the infection cases can backfire, and can lead to a quicker, sharper and higher secondary peak, due to reactivation of the two transmission routes. Based on these results, this study recommends that any exit policy from lockdown, should take into account the level of transmission reduction in both routes, the absolute scale of which will vary among countries depending on their health-service capacity, but should be computed using accurate time-series data on infection cases and transmission rates.", "qid": 13, "docid": "61ta81iy", "rank": 66, "score": 0.7352775931358337}, {"content": "Title: Materno-fetal transmission of human coronaviruses: a prospective pilot study Content: This prospective pilot study investigates the possibility of materno-fetal transmission of human coronaviruses (HCoV) responsible for cases of neonatal infection. This vertical transmission was studied with 159 samples from mother-child couples: maternal vaginal (MV) and respiratory (MR) samples during labor; and newborn gastric sample (NG) with detection of HCoV (229E, OC-43, NL-63, HKU1) via real time RT PCR. HCoV was detected in 12 samples (229E: 11; HKU1: 1) from seven mother-child couples. For three couples, only MR tested positive (cases 1\u20133). For two other couples all three samples (MV, MR and NG) tested positive (cases 4 and 5). For case 6, only MV and NG tested positive. In case 7, only MV was positive. Possible vertical transmission of HCoV was hypothesized in this pilot study and requires further investigation on a larger scale.", "qid": 13, "docid": "f8dahf0a", "rank": 67, "score": 0.7351067066192627}, {"content": "Title: COVID-19: Transmission, prevention, and potential therapeutic opportunities Content: The novel coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global challenge. Despite intense research efforts worldwide, an effective vaccine and viable treatment options have eluded investigators. Therefore, infection prevention, early viral detection and identification of successful treatment protocols provide the best approach in controlling disease spread. In this review, current therapeutic options, preventive methods and transmission routes of COVID-19 are discussed.", "qid": 13, "docid": "6jsbh5or", "rank": 68, "score": 0.7346060872077942}, {"content": "Title: Pathways of the COVID-19 Pandemic with Human Mobility across Countries Content: This study develops a holistic view of the novel coronavirus (COVID-19) transmission worldwide through a spatial-temporal model with network dynamics. By using a unique human mobility dataset containing 547,166 flights with a total capacity of 101,455,913 passengers among 22 countries during the past three months, we analyze the associations between international travel movement in six continents and the new infections in these countries. Results show that policymakers should move away from the previous practices that focus only on restricting hotspot areas with high transmission rates. Instead, they should develop a new holistic view of global human mobility to adjust the international movement restriction. The study highlights that international human mobility is the key to understand the transmission pathways and the small world phenomenon in the global network of COVID-19 pandemic.", "qid": 13, "docid": "ff7ac0iy", "rank": 69, "score": 0.7342239618301392}, {"content": "Title: Community Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, Shenzhen, China, 2020 Content: Since early January 2020, after the outbreak of coronavirus infection in Wuhan, China, &#8776;365 confirmed cases have been reported in Shenzhen, China. The mode of community and intrafamily transmission is threatening residents in Shenzhen. Strategies to strengthen prevention and interruption of these transmissions should be urgently addressed.", "qid": 13, "docid": "caj12qby", "rank": 70, "score": 0.7341784238815308}, {"content": "Title: The early response to a novel coronavirus in the Middle East. Content: The detection of a novel coronavirus in patients from the Arabian Peninsula in late 2012 raised serious concerns of a possible international outbreak. Ministries of health of the three affected countries invited missions from the World Health Organization to participate in a review of data and capacity to detect and respond to further cases. Recommendations were made for investigations to answer critical questions about human-to-human transmission and the geographic extent of the virus. Additional recommendations were made to improve surveillance capacity by acquiring the capacity to test for the virus and enhance syndromic surveillance. Available evidence continues to suggest an unknown animal reservoir for the virus with sporadic zoonotic transmission the primary epidemiological pattern of transmission. Human-to-human transmission, while it can occur, does not appear to be sustained in the community.", "qid": 13, "docid": "wqfgk3vh", "rank": 71, "score": 0.7339916229248047}, {"content": "Title: Impacts of social and economic factors on the transmission of coronavirus disease 2019 (COVID-19) in China Content: This study models local and cross-city transmissions of the novel coronavirus in China between January 19 and February 29, 2020. We examine the role of various socioeconomic mediating factors, including public health measures that encourage social distancing in local communities. Weather characteristics 2 weeks prior are used as instrumental variables for causal inference. Stringent quarantines, city lockdowns, and local public health measures imposed in late January significantly decreased the virus transmission rate. The virus spread was contained by the middle of February. Population outflow from the outbreak source region posed a higher risk to the destination regions than other factors, including geographic proximity and similarity in economic conditions. We quantify the effects of different public health measures in reducing the number of infections through counterfactual analyses. Over 1.4 million infections and 56,000 deaths may have been avoided as a result of the national and provincial public health measures imposed in late January in China.", "qid": 13, "docid": "9lusan32", "rank": 72, "score": 0.7339104413986206}, {"content": "Title: A mathematical model for simulating the transmission of Wuhan novel Coronavirus Content: As reported by the World Health Organization, a novel coronavirus (2019-nCoV) was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January, 2020. In this study, we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source (probable be bats) to the human infection. Since the Bats-Hosts-Reservoir network was hard to explore clearly and public concerns were focusing on the transmission from a seafood market (reservoir) to people, we simplified the model as Reservoir-People transmission network model. The basic reproduction number (R0) was calculated from the RP model to assess the transmissibility of the 2019-nCoV.", "qid": 13, "docid": "v4mbry22", "rank": 73, "score": 0.7337231636047363}, {"content": "Title: Enhanced surveillance and investigation of coronavirus: what is required? Content: Following the discovery in September 2012 of 2 patients, both with links to the Eastern Mediterranean Region, with serious respiratory illness due to novel coronavirus, all countries have instigated surveillance and laboratory activities to detect further cases, with intensive case-contact investigations undertaken on laboratory confirmation of cases. A total of 30 cases, of whom 18 have died, and at least 3 clusters have been detected to date (1 cluster among health-care workers and another 2 clusters among family members). To date, transmission studies have shown a low risk of onward human transmission, with clinical presentation remaining severe for the majority. Many questions remain including the zoonotic source and geographical extent of infection. Surveillance has been extended to include clusters of cases or health-care workers with severe, undiagnosed respiratory illness regardless of travel history. Environmental studies, on-going surveillance and linked case-contact investigations will provide a critical role in answering some of these issues.", "qid": 13, "docid": "wgsjxck1", "rank": 74, "score": 0.7334499359130859}, {"content": "Title: Lutte contre la pand\u00e9mie de maladie \u00e0 coronavirus (Covid-19): tirer les le\u00e7ons de la r\u00e9ponse \u00e0 la maladie du virus Ebola Content: Abstract Coronavirus disease (COVID-19) is caused by a beta-coronavirus (SARS-CoV-2) that affects the lower respiratory tract and appears as pneumonia in humans. COVID-19 became apparent in December 2019 in Wuhan City of China, and has propagated profusely globally. Despite stringent global quarantine and containment drives, the incidence of COVID-19 keeps soaring high. Measures to minimize human-to-human transmission have been implemented to control the pandemic. However, special efforts to reduce transmission via efficient public health communications and dissemination of risks should be applied in susceptible populations including children, health care providers, and the elderly. In response to this global pandemic, this article summarizes proven strategies that could be employed to combat the COVID-19 disease outbreak, taking a cue from lessons learned from the Ebola virus disease response. R\u00e9sum\u00e9 La maladie \u00e0 coronavirus (COVID-19) est caus\u00e9e par un b\u00eata-coronavirus (SARS-CoV-2) qui affecte les voies respiratoires inf\u00e9rieures et se pr\u00e9sente sous forme de pneumonie chez l'homme. La COVID-19 est apparue en d\u00e9cembre 2019 dans la ville chinoise de Wuhan, et s'est propag\u00e9e \u00e0 grande \u00e9chelle dans le monde entier. Malgr\u00e9 des mesures de quarantaine et de confinement rigoureuses, l'incidence de COVID-19 continue de grimper en fl\u00e8che. Des mesures visant \u00e0 minimiser la transmission interhumaine ont \u00e9t\u00e9 mises en \u0153uvre pour contr\u00f4ler la pand\u00e9mie. Toutefois, des efforts particuliers pour r\u00e9duire la transmission par le biais de communications efficaces en mati\u00e8re de sant\u00e9 publique et de diffusion des risques doivent \u00eatre d\u00e9ploy\u00e9s dans les populations sensibles, notamment les enfants, les prestataires de soins de sant\u00e9 et les personnes \u00e2g\u00e9es. En r\u00e9ponse \u00e0 cette pand\u00e9mie mondiale, cet article r\u00e9sume les strat\u00e9gies \u00e9prouv\u00e9es qui pourraient \u00eatre employ\u00e9es pour combattre l'\u00e9pid\u00e9mie de maladie COVID-19, en s'inspirant des le\u00e7ons tir\u00e9es de la r\u00e9ponse \u00e0 la maladie du virus Ebola.", "qid": 13, "docid": "q66xifmu", "rank": 75, "score": 0.7333178520202637}, {"content": "Title: Phylogenetic analysis of the first four SARS\u2010CoV\u20102 cases in Chile Content: The current pandemic caused by the new coronavirus is a worldwide public health concern. To aboard this emergency, and like never before, scientific groups around the world have been working in a fast and coordinated way to get the maximum of information about this virus when it has been almost 3 months since the first cases were detected in Wuhan province in China. The complete genome sequences of around 450 isolates are available, and studies about similarities and differences among them and with the close related viruses that caused similar epidemics in this century. In this work, we studied the complete genome of the first four cases of the new coronavirus disease in Chile, from patients who traveled to Europe and Southeast Asia. Our findings reveal at least two different viral variants entries to Chilean territory, coming from Europe and Asia. We also sub\u2010classified the isolates into variants according to punctual mutations in the genome. Our work contributes to global information about transmission dynamics and the importance to take control measures to stop the spread of the infection.", "qid": 13, "docid": "i4xjk61t", "rank": 76, "score": 0.7330983281135559}, {"content": "Title: Novel coronavirus (COVID-19): Its implications for anesthesia Content: Once again in the same decade, global health delivery systems are facing with the daunting challenge of another variant of Coronavirus (COVID-19). Over the last 20 years at least six different variants of coronavirus have emerged. Infections caused by these viruses mainly cause life threatening respiratory implications. The recent outbreak of a novel Coronavirus in Wuhan, China has been labelled as public health emergency of international concern (PHEIC). Previous experiences of Coronavirus outbreaks have shown that health care workers are at a high risk of acquiring this infection. Anesthesiologists, are particularly vulnerable due to their frequent exposure to infected respiratory secretions. Therefore, to minimize the transmission of nCoV-2019 infection, proper infection control measures like correct workplace practices, appropriate usage of personal protective equipment, airborne and droplet precautions are mandatory while managing a suspected case of infected patient.", "qid": 13, "docid": "hbkikxx3", "rank": 77, "score": 0.7330698370933533}, {"content": "Title: 2019 Novel Coronavirus (COVID-19) Pandemic: Built Environment Considerations To Reduce Transmission Content: With the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in coronavirus disease 2019 (COVID-19), corporate entities, federal, state, county, and city governments, universities, school districts, places of worship, prisons, health care facilities, assisted living organizations, daycares, homeowners, and other building owners and occupants have an opportunity to reduce the potential for transmission through built environment (BE)-mediated pathways. Over the last decade, substantial research into the presence, abundance, diversity, function, and transmission of microbes in the BE has taken place and revealed common pathogen exchange pathways and mechanisms. In this paper, we synthesize this microbiology of the BE research and the known information about SARS-CoV-2 to provide actionable and achievable guidance to BE decision makers, building operators, and all indoor occupants attempting to minimize infectious disease transmission through environmentally mediated pathways. We believe this information is useful to corporate and public administrators and individuals responsible for building operations and environmental services in their decision-making process about the degree and duration of social-distancing measures during viral epidemics and pandemics. Author Video: An author video summary of this article is available.", "qid": 13, "docid": "89n52jny", "rank": 78, "score": 0.7329322099685669}, {"content": "Title: The Novel Coronavirus \u2013 A Snapshot of Current Knowledge Content: Another animal to human transmission of a coronavirus occurred in December 2019 on a live animal market in the Chinese city of Wuhan causing an epidemic in China, reaching now different continents. This minireview summarizes the research literature on the virological, clinical and epidemiological aspects of this epidemic published until end of February 2020.", "qid": 13, "docid": "t6zf5k99", "rank": 79, "score": 0.7326512336730957}, {"content": "Title: The Novel Coronavirus - A Snapshot of Current Knowledge Content: Another animal to human transmission of a coronavirus occurred in December 2019 on a live animal market in the Chinese city of Wuhan causing an epidemic in China, reaching now different continents. This minireview summarizes the research literature on the virological, clinical and epidemiological aspects of this epidemic published until end of February 2020.", "qid": 13, "docid": "itlz60rl", "rank": 80, "score": 0.7326512336730957}, {"content": "Title: Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020 Content: Since December 2019, China has been experiencing a large outbreak of a novel coronavirus (2019-nCoV) which can cause respiratory disease and severe pneumonia. We estimated the basic reproduction number R(0) of 2019-nCoV to be around 2.2 (90% high density interval: 1.4\u20133.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and pandemic influenza, indicating a risk of global spread.", "qid": 13, "docid": "zz4cczuj", "rank": 81, "score": 0.7326405644416809}, {"content": "Title: Coronavirus Disease 2019: Coronaviruses and Blood Safety Content: With the outbreak of unknown pneumonia in Wuhan, China, in December 2019, a new coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), aroused the attention of the entire world. The current outbreak of infections with SARS-CoV-2 is termed Coronavirus Disease 2019 (COVID-19). The World Health Organization declared COVID-19 in China as a Public Health Emergency of International Concern. Two other coronavirus infections-SARS in 2002-2003 and Middle East Respiratory Syndrome (MERS) in 2012-both caused severe respiratory syndrome in humans. All 3 of these emerging infectious diseases leading to a global spread are caused by \u00df-coronaviruses. Although coronaviruses usually infect the upper or lower respiratory tract, viral shedding in plasma or serum is common. Therefore, there is still a theoretical risk of transmission of coronaviruses through the transfusion of labile blood products. Because more and more asymptomatic infections are being found among COVID-19 cases, considerations of blood safety and coronaviruses have arisen especially in endemic areas. In this review, we detail current evidence and understanding of the transmission of SARS-CoV, MERS-CoV, and SARS-CoV-2 through blood products as of February 10, 2020, and also discuss pathogen inactivation methods on coronaviruses.", "qid": 13, "docid": "wpy3tt1x", "rank": 82, "score": 0.7325974702835083}, {"content": "Title: Evidence for gastrointestinal infection of SARS-CoV-2 Content: The new coronavirus (SARS-CoV-2) outbreak originating from Wuhan, China, poses a threat to global health. While it's evident that the virus invades respiratory tract and transmits from human to human through airway, other viral tropisms and transmission routes remain unknown. We tested viral RNA in stool from 73 SARS-CoV-2-infected hospitalized patients using rRT-PCR. 53.42% of the patients tested positive in stool. 23.29% of the patients remained positive in feces even after the viral RNA decreased to undetectable level in respiratory tract. The viral RNA was also detected in gastrointestinal tissues. Furthermore, gastric, duodenal and rectal epithelia showed positive immunofluorescent staining of viral host receptor ACE2 and viral nucleocapsid protein in a case of SARS-CoV-2 infection. Our results provide evidence for gastrointestinal infection of SARS-CoV-2, highlighting its potential fecal-oral transmission route.", "qid": 13, "docid": "7odpslba", "rank": 83, "score": 0.732580304145813}, {"content": "Title: Stability of bovine coronavirus on lettuce surfaces under household refrigeration conditions Content: Fecal suspensions with an aerosol route of transmission were responsible for a cluster of severe acute respiratory syndrome (SARS) cases in 2003 in Hong Kong. Based on that event, the World Health Organization recommended that research be implemented to define modes of transmission of SARS coronavirus through sewage, feces, food and water. Environmental studies have shown that animal coronaviruses remain infectious in water and sewage for up to a year depending on the temperature and humidity. In this study, we examined coronavirus stability on lettuce surfaces. A cell culture adapted bovine coronavirus, diluted in growth media or in bovine fecal suspensions to simulate fecal contamination was used to spike romaine lettuce. qRT-PCR detected viral RNA copy number ranging from 6.6 \u00d7 10(4) to 1.7 \u00d7 10(6) throughout the experimental period of 30 days. Whereas infectious viruses were detected for at least 14 days, the amount of infectious virus varied, depending upon the diluent used for spiking the lettuce. UV and confocal microscopic observation indicated attachment of residual labeled virions to the lettuce surface after the elution procedure, suggesting that rates of inactivation or detection of the virus may be underestimated. Thus, it is possible that contaminated vegetables may be potential vehicles for coronavirus zoonotic transmission to humans.", "qid": 13, "docid": "zmaw9lbz", "rank": 84, "score": 0.7324680089950562}, {"content": "Title: Transmission of respiratory viruses when using public ground transport: A rapid review to inform public health recommendations during the COVID-19 pandemic Content: In response to the COVID-19 pandemic, numerous countries worldwide declared national states of emergency and implemented interventions to minimise the risk of transmission among the public Evidence was needed to inform strategies for limiting COVID19 transmission on public transport On 20 March 2020, we searched MEDLINE, CENTRAL, Web of Science and the World Health Organization's database of `Global research on coronavirus disease (COVID-19)' to conduct a rapid review on interventions that reduce viral transmission on public ground transport After screening 74 records, we identified 4 eligible studies These studies suggest an increased risk of viral transmission with public transportation use that may be reduced with improved ventilation International and national guidelines suggest the following strategies: keep the public informed, stay at home when sick, and minimise public transport use Where use is unavoidable, environmental control, respiratory etiquette and hand hygiene are recommended, while a risk-based approach needs to guide the use of non-medical masks", "qid": 13, "docid": "443tznq3", "rank": 85, "score": 0.7324676513671875}, {"content": "Title: Work-related Covid-19 transmission Content: Importance: Our study helps fill the knowledge gap related to work-related transmission in the emerging coronaviral pandemic. Objective: To demonstrate high-risk occupations for early coronavirus disease 2019 (Covid-19) local transmission. Methods: In this observational study, we extracted confirmed Covid-19 cases from governmental investigation reports in Hong Kong, Japan, Singapore, Taiwan, Thailand, and Vietnam. We followed each country/area for 40 days after its first locally transmitted case, and excluded all imported cases. We defined a possible work-related case as a worker with evidence of close contact with another confirmed case due to work, or an unknown contact history but likely to be infected in the working environment (e.g. an airport taxi driver). We calculated the case number for each occupation, and illustrated the temporal distribution of all possible work-related cases and healthcare worker (HCW) cases. The temporal distribution was further defined as early outbreak (the earliest 10 days of the following period) and late outbreak (11th to 40th days of the following period). Results: We identified 103 possible work-related cases (14.9%) among a total of 690 local transmissions. The five occupation groups with the most cases were healthcare workers (HCWs) (22%), drivers and transport workers (18%), services and sales workers (18%), cleaning and domestic workers (9%) and public safety workers (7%). Possible work-related transmission played a substantial role in early outbreak (47.7% of early cases). Occupations at risk varied from early outbreak (predominantly services and sales workers, drivers, construction laborers, and religious professionals) to late outbreak (predominantly HCWs, drivers, cleaning and domestic workers, police officers, and religious professionals). Conclusions: Work-related transmission is considerable in early Covid-19 outbreaks, and the elevated risk of infection was not limited to HCW. Implementing preventive/surveillance strategies for high-risk working populations is warranted.", "qid": 13, "docid": "0ygaj2hm", "rank": 86, "score": 0.7324345707893372}, {"content": "Title: Severe Acute Respiratory Syndrome (SARS) and the GDP. Part I: Epidemiology, virology, pathology and general health issues Content: The health profession faces a new challenge with the emergence of a novel viral disease Severe Acute Respiratory Syndrome (SARS), a form of atypical pneumonia caused by a coronavirus termed SARS-CoV. This highly infectious disease has spread through 32 countries, infecting more than 8,400 patients with over 790 deaths in just over 6 months. Over one quarter of those infected were unsuspecting healthcare workers. The major transmission mode of SARS-coronavirus appears to be through droplet spread with other minor subsidiary modes of transmission such as close contact and fomites although air borne transmission has not been ruled out. There is as yet no definitive treatment protocol. Although the peak period of the outbreak is likely to have passed and the risk of SARS in the UK is therefore assessed to be low, the World Health Organisation has asked all countries to remain vigilant lest SARS re-emerges. Recent laboratory acquired cases of SARS reported from Taiwan and Beijing, China are a testimony to this risk. Until reliable diagnostic tests, vaccine and medications are available, control of SARS outbreaks depends on close surveillance, early identification of index cases, quick isolation of carriers and effective infection control and public health measures.", "qid": 13, "docid": "s9qvrkia", "rank": 87, "score": 0.7321547269821167}, {"content": "Title: Short Communication An epidemiological model for SARS-CoV-2 Content: Abstract The spread of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is here investigated from an epidemic model considering four pathways of person-to-person transmission. These pathways represent the propagation of this novel coronavirus by asymptomatic and symptomatic infected individuals. In this work, analytical expressions for the disease-free and endemic steady-states are derived. Also, the conditions for eradication of this contagious disease are determined. By taking into account realistic parameter values, the proposed model shows an oscillatory convergence to the endemic steady-state, which means the occurrence of a sequence of peaks in the number of sick individuals as time passes. These results are discussed from a public health standpoint.", "qid": 13, "docid": "0imdy5v4", "rank": 88, "score": 0.7319610118865967}, {"content": "Title: China\u2019s local governments are combating COVID-19 with unprecedented responses \u2014 from a Wenzhou governance perspective Content: The COVID-19 caused by a novel strain of Coronavirus has been spreading rapidly since its onset in Wuhan, the capital city of central China\u2019s Hubei Province, in December 2019. It is highly communicable through human-to-human transmission. China has been making unprecedented efforts in treating the confirmed cases, identifying and isolating their close contacts and suspected cases to control the source of infection and cut the route of transmission. China\u2019s devotion in handling this epidemic has effectively and efficiently curbed communication domestically and across the border. Representative measures adopted by Wenzhou, the worst hit city out of Hubei Province, are examined to elucidate those massive undertakings with the aim of enhancing international understanding and building global rapport in fighting this evolving epidemic situation.", "qid": 13, "docid": "ermbijfq", "rank": 89, "score": 0.7318037748336792}, {"content": "Title: Community Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, Shenzhen, China, 2020 Content: Since early January 2020, after the outbreak of coronavirus infection in Wuhan, China, \u2248365 confirmed cases have been reported in Shenzhen, China. The mode of community and intrafamily transmission is threatening residents in Shenzhen. Strategies to strengthen prevention and interruption of these transmissions should be urgently addressed.", "qid": 13, "docid": "sonxopa0", "rank": 90, "score": 0.7316373586654663}, {"content": "Title: Coronavirus in water environments: Occurrence, persistence and concentration methods - A scoping review Content: Coronaviruses (CoV) are a large family of viruses causing a spectrum of disease ranging from the common cold to more severe diseases as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). The recent outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency worldwide. SARS-CoV-2, the virus responsible for COVID-19, is spread by human-to-human transmission via droplets or direct contact. However, since SARS-CoV-2 (as well as other coronaviruses) has been found in the fecal samples and anal swabs of some patients, the possibility of fecal-oral (including waterborne) transmission need to be investigated and clarified. This scoping review was conducted to summarize research data on CoV in water environments. A literature survey was conducted using the electronic databases PubMed, EMBASE, and Web Science Core Collection. This comprehensive research yielded more than 3000 records, but only 12 met the criteria and were included and discussed in this review. In detail, the review captured relevant studies investigating three main areas: 1) CoV persistence/survival in waters; 2) CoV occurrence in water environments; 3) methods for recovery of CoV from waters. The data available suggest that: i) CoV seems to have a low stability in the environment and is very sensitive to oxidants, like chlorine; ii) CoV appears to be inactivated significantly faster in water than non-enveloped human enteric viruses with known waterborne transmission; iii) temperature is an important factor influencing viral survival (the titer of infectious virus declines more rapidly at 23\u00b0C-25 \u00b0C than at 4 \u00b0C); iv) there is no current evidence that human coronaviruses are present in surface or ground waters or are transmitted through contaminated drinking-water; v) further research is needed to adapt to enveloped viruses the methods commonly used for sampling and concentration of enteric, non enveloped viruses from water environments. The evidence-based knowledge reported in this paper is useful to support risk analysis processes within the drinking and wastewater chain (i.e., water and sanitation safety planning) to protect human health from exposure to coronavirus through water.", "qid": 13, "docid": "hn9fj8h8", "rank": 91, "score": 0.7314497232437134}, {"content": "Title: A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster Content: BACKGROUND: An ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date. METHODS: In this study, we report the epidemiological, clinical, laboratory, radiological, and microbiological findings of five patients in a family cluster who presented with unexplained pneumonia after returning to Shenzhen, Guangdong province, China, after a visit to Wuhan, and an additional family member who did not travel to Wuhan. Phylogenetic analysis of genetic sequences from these patients were done. FINDINGS: From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen between Dec 29, 2019 and Jan 4, 2020. Of six family members who travelled to Wuhan, five were identified as infected with the novel coronavirus. Additionally, one family member, who did not travel to Wuhan, became infected with the virus after several days of contact with four of the family members. None of the family members had contacts with Wuhan markets or animals, although two had visited a Wuhan hospital. Five family members (aged 36-66 years) presented with fever, upper or lower respiratory tract symptoms, or diarrhoea, or a combination of these 3-6 days after exposure. They presented to our hospital (The University of Hong Kong-Shenzhen Hospital, Shenzhen) 6-10 days after symptom onset. They and one asymptomatic child (aged 10 years) had radiological ground-glass lung opacities. Older patients (aged >60 years) had more systemic symptoms, extensive radiological ground-glass lung changes, lymphopenia, thrombocytopenia, and increased C-reactive protein and lactate dehydrogenase levels. The nasopharyngeal or throat swabs of these six patients were negative for known respiratory microbes by point-of-care multiplex RT-PCR, but five patients (four adults and the child) were RT-PCR positive for genes encoding the internal RNA-dependent RNA polymerase and surface Spike protein of this novel coronavirus, which were confirmed by Sanger sequencing. Phylogenetic analysis of these five patients' RT-PCR amplicons and two full genomes by next-generation sequencing showed that this is a novel coronavirus, which is closest to the bat severe acute respiatory syndrome (SARS)-related coronaviruses found in Chinese horseshoe bats. INTERPRETATION: Our findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travellers in other geographical regions. FUNDING: The Shaw Foundation Hong Kong, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, Sanming Project of Medicine (Shenzhen), and High Level-Hospital Program (Guangdong Health Commission).", "qid": 13, "docid": "gr0lzz6r", "rank": 92, "score": 0.7309445142745972}, {"content": "Title: Phylogenetic analysis of the first four SARS-CoV-2 cases in Chile Content: The current pandemic caused by the new coronavirus is a worldwide public health concern. To aboard this emergency, and like never before, scientific groups around the world have been working in a fast and coordinated way to get the maximum of information about this virus when it has been almost 3 months since the first cases were detected in Wuhan province in China. The complete genome sequences of around 450 isolates are available, and studies about similarities and differences among them and with the close related viruses that caused similar epidemics in this century. In this work, we studied the complete genome of the first four cases of the new coronavirus disease in Chile, from patients who traveled to Europe and Southeast Asia. Our findings reveal at least two different viral variants entries to Chilean territory, coming from Europe and Asia. We also sub-classified the isolates into variants according to punctual mutations in the genome. Our work contributes to global information about transmission dynamics and the importance to take control measures to stop the spread of the infection.", "qid": 13, "docid": "66j1icdo", "rank": 93, "score": 0.7308300733566284}, {"content": "Title: A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster Content: BACKGROUND: An ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date. METHODS: In this study, we report the epidemiological, clinical, laboratory, radiological, and microbiological findings of five patients in a family cluster who presented with unexplained pneumonia after returning to Shenzhen, Guangdong province, China, after a visit to Wuhan, and an additional family member who did not travel to Wuhan. Phylogenetic analysis of genetic sequences from these patients were done. FINDINGS: From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen between Dec 29, 2019 and Jan 4, 2020. Of six family members who travelled to Wuhan, five were identified as infected with the novel coronavirus. Additionally, one family member, who did not travel to Wuhan, became infected with the virus after several days of contact with four of the family members. None of the family members had contacts with Wuhan markets or animals, although two had visited a Wuhan hospital. Five family members (aged 36\u201366 years) presented with fever, upper or lower respiratory tract symptoms, or diarrhoea, or a combination of these 3\u20136 days after exposure. They presented to our hospital (The University of Hong Kong-Shenzhen Hospital, Shenzhen) 6\u201310 days after symptom onset. They and one asymptomatic child (aged 10 years) had radiological ground-glass lung opacities. Older patients (aged >60 years) had more systemic symptoms, extensive radiological ground-glass lung changes, lymphopenia, thrombocytopenia, and increased C-reactive protein and lactate dehydrogenase levels. The nasopharyngeal or throat swabs of these six patients were negative for known respiratory microbes by point-of-care multiplex RT-PCR, but five patients (four adults and the child) were RT-PCR positive for genes encoding the internal RNA-dependent RNA polymerase and surface Spike protein of this novel coronavirus, which were confirmed by Sanger sequencing. Phylogenetic analysis of these five patients' RT-PCR amplicons and two full genomes by next-generation sequencing showed that this is a novel coronavirus, which is closest to the bat severe acute respiatory syndrome (SARS)-related coronaviruses found in Chinese horseshoe bats. INTERPRETATION: Our findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travellers in other geographical regions. FUNDING: The Shaw Foundation Hong Kong, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, Sanming Project of Medicine (Shenzhen), and High Level-Hospital Program (Guangdong Health Commission).", "qid": 13, "docid": "j3avpu1y", "rank": 94, "score": 0.7307980060577393}, {"content": "Title: Coronavirus: Update Related to the Current Outbreak of COVID-19 Content: In December 2019, some cases of viral pneumonia were epidemiologically related to a new coronavirus in the province of Hubei, China. Subsequently, there has been an increase in infections attributable to this virus throughout China and worldwide. The World Health Organization (WHO) has officially named the infection coronavirus disease 2019 (COVID-19), and the virus has been classified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This appears to be a virus from Rhinolophus bats, but the intermediate host has not yet been identified. The mechanism of infection of SARS-CoV-2 is not yet known; it appears to have affinity for cells located in the lower airways, where it replicates. The interhuman transmission of coronaviruses mainly occurs through saliva droplets and direct and indirect contact via surfaces. As of March 10, 2020, the number of cases worldwide was 113,702. Along with severe acute respiratory syndrome (SARS) and Middle Eastern respiratory syndrome (MERS), COVID-19 appears to cause a severe clinical picture in humans, ranging from mild malaise to death by sepsis/acute respiratory distress syndrome. The prognosis is worse in elderly patients with comorbidities. To date, there is no specific therapy for COVID-19. Prevention of SARS-CoV-2 infection implies strategies that limit the spread of the virus. WHO and other international and national bodies have developed continuously updated strategic objectives and provisions to contain the spread of the virus and infection.", "qid": 13, "docid": "4u0appfs", "rank": 95, "score": 0.7307221293449402}, {"content": "Title: Coronavirus: Update Related to the Current Outbreak of COVID-19. Content: In December 2019, some cases of viral pneumonia were epidemiologically related to a new coronavirus in the province of Hubei, China. Subsequently, there has been an increase in infections attributable to this virus throughout China and worldwide. The World Health Organization (WHO) has officially named the infection coronavirus disease 2019 (COVID-19), and the virus has been classified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This appears to be a virus from Rhinolophus bats, but the intermediate host has not yet been identified. The mechanism of infection of SARS-CoV-2 is not yet known; it appears to have affinity for cells located in the lower airways, where it replicates. The interhuman transmission of coronaviruses mainly occurs through saliva droplets and direct and indirect contact via surfaces. As of March 10, 2020, the number of cases worldwide was 113,702. Along with severe acute respiratory syndrome (SARS) and Middle Eastern respiratory syndrome (MERS), COVID-19 appears to cause a severe clinical picture in humans, ranging from mild malaise to death by sepsis/acute respiratory distress syndrome. The prognosis is worse in elderly patients with comorbidities. To date, there is no specific therapy for COVID-19. Prevention of SARS-CoV-2 infection implies strategies that limit the spread of the virus. WHO and other international and national bodies have developed continuously updated strategic objectives and provisions to contain the spread of the virus and infection.", "qid": 13, "docid": "g1k3zlax", "rank": 96, "score": 0.7307221293449402}, {"content": "Title: Making waves: Coronavirus detection, presence and persistence in the water environment: State of the art and knowledge needs for public health Content: The main route of transmission of the human coronaviruses (HCoVs), and presumably also of the new pandemic SARS-CoV-2, is via droplets and close contacts, however their fecal elimination also suggests the possible spread via water. A scientific literature search was thus carried out to highlight the current state of the art and knowledge gaps regarding coronavirus in water. Since 1978 only 22 studies have met the inclusion criteria, and considered heterogeneous purposes, detection methods and types of water. In vitro experiments have addressed the recovery efficiency of analytical methods, survival in different types of water and the removal efficiency of water treatments. Field studies have monitored coronaviruses in surface waters, sewage, slurry, and biosolids. Overall, at the lab scale, HCoVs or surrogates can survive for several days at 4 \u00b0C, however their persistence is lower compared with non-enveloped viruses and is strongly influenced by temperature and organic or microbial pollution. HCoVs have rarely been detected in field investigations, however may be due to the low recovery efficiency of the analytical methods. The scarcity of information on HCoV in the environment suggests that research is needed to understand the fate of these viruses in the water cycle.", "qid": 13, "docid": "vuzf3dnr", "rank": 97, "score": 0.7306292057037354}, {"content": "Title: Making Waves: Coronavirus detection, presence and persistence in the water environment: State of the art and knowledge needs for public health Content: The main route of transmission of the human coronaviruses (HCoVs), and presumably also of the new pandemic SARS-CoV-2, is via droplets and close contacts, however their fecal elimination also suggests the possible spread via water. A scientific literature search was thus carried out to highlight the current state of the art and knowledge gaps regarding coronavirus in water. Since 1978 only 22 studies have met the inclusion criteria, and considered heterogeneous purposes, detection methods and types of water. In vitro experiments have addressed the recovery efficiency of analytical methods, survival in different types of water and the removal efficiency of water treatments. Field studies have monitored coronaviruses in surface waters, sewage, slurry, and biosolids. Overall, at the lab scale, HCoVs or surrogates can survive for several days at 4 \u00b0C, however their persistence is lower compared with non-enveloped viruses and is strongly influenced by temperature and organic or microbial pollution. HCoVs have rarely been detected in field investigations, however may be due to the low recovery efficiency of the analytical methods. The scarcity of information on HCoV in the environment suggests that research is needed to understand the fate of these viruses in the water cycle.", "qid": 13, "docid": "c17eijdt", "rank": 98, "score": 0.7306292057037354}, {"content": "Title: Global transmission network of SARS-CoV-2: from outbreak to pandemic Content: BACKGROUND. The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is straining health systems around the world. Although the Chinese government implemented a number of severe restrictions on people\u2019s movement in an attempt to contain its local and international spread, the virus had already reached many areas of the world in part due to its potent transmissibility and the fact that a substantial fraction of infected individuals develop little or no symptoms at all. Following its emergence, the virus started to generate sustained transmission in neighboring countries in Asia, Western Europe, Australia, Canada and the United States, and finally in South America and Africa. As the virus continues its global spread, a clear and evidence-based understanding of properties and dynamics of the global transmission network of SARS-CoV-2 is essential to design and put in place efficient and globally coordinated interventions. METHODS. We employ molecular surveillance data of SARS-CoV-2 epidemics for inference and comprehensive analysis of its global transmission network before the pandemic declaration. Our goal was to characterize the spatial-temporal transmission pathways that led to the establishment of the pandemic. We exploited a network-based approach specifically tailored to emerging outbreak settings. Specifically, it traces the accumulation of mutations in viral genomic variants via mutation trees, which are then used to infer transmission networks, revealing an up-to-date picture of the spread of SARS-CoV-2 between and within countries and geographic regions. RESULTS AND CONCLUSIONS. The analysis suggest multiple introductions of SARS-CoV-2 into the majority of world regions by means of heterogeneous transmission pathways. The transmission network is scale-free, with a few genomic variants responsible for the majority of possible transmissions. The network structure is in line with the available temporal information represented by sample collection times and suggest the expected sampling time difference of few days between potential transmission pairs. The inferred network structural properties, transmission clusters and pathways and virus introduction routes emphasize the extent of the global epidemiological linkage and demonstrate the importance of internationally coordinated public health measures.", "qid": 13, "docid": "ry9wpcxo", "rank": 99, "score": 0.7305068969726562}, {"content": "Title: A new threat from an old enemy: Re\u00ademergence of coronavirus (Review) Content: The new outbreak of coronavirus from December 2019 has brought attention to an old viral enemy and has raised concerns as to the ability of current protection measures and the healthcare system to handle such a threat. It has been known since the 1960s that coronaviruses can cause respiratory infections in humans; however, their epidemic potential was understood only during the past two decades. In the present review, we address current knowledge on coronaviruses from a short history to epidemiology, pathogenesis, clinical manifestation of the disease, as well as treatment and prevention strategies. Although a great amount of research and efforts have been made worldwide to prevent further outbreaks of coronavirus\u00adassociated disease, the spread and lethality of the 2019 outbreak (COVID\u00ad19) is proving to be higher than previous epidemics on account of international travel density and immune naivety of the population. Only strong, joint and coordinated efforts of worldwide healthcare systems, researchers, and pharmaceutical companies and receptive national leaders will succeed in suppressing an outbreak of this scale.", "qid": 13, "docid": "fw0d8807", "rank": 100, "score": 0.7298970222473145}]}
{"query": "what evidence is there related to COVID-19 super spreaders", "hits": [{"content": "Title: COVID-19 Super-spreaders: Definitional Quandaries and Implications Content: Uncertainty around the role 'super-spreaders' play in the transmission and escalation of infectious disease is compounded by its broad and vague definition. It is a term that has been much used in relation to COVID-19, particularly in social media. On its widest definition, it refers to a propensity to infect a larger than average number of people. Given the biological, behavioural and environmental variables relevant to infectivity, this might be pertinent to almost any infected individual who is not physically isolated from others. Nor is the term confined to individuals with a propensity to spread infectious disease: it can potentially be used to describe events, policies or settings. This article explores the use of the term and considers circumstances in which the wide definition can be problematic. One problem is that it can lead to undeserved apportionment of moral blame to alleged super-spreaders. Another is that it can detract from scientific investigation of the heterogeneity of COVID-19 transmission. The author calls for a clearer epidemiological definition.", "qid": 14, "docid": "v0vjkwy9", "rank": 1, "score": 0.7979121208190918}, {"content": "Title: Significance of super spreader events in COVID-19 Content: The number of secondary cases from each primary case determines how fast an epidemic grows. It is known that all cases do not spread the infection equally; super spreaders play an important role as they contribute disproportionately to a much larger number of cases including in the ongoing COVID-19 pandemic. Super spreaders have been reported for more than a century, but limited information is available in scientific literature. An epidemic containment strategy needs to include early identification of super spreaders to limit an explosive growth. Super spreaders tend to get stigmatized, resulting in late reporting and hiding of cases. It is important for program managers to be sensitive to the manner in which related information is shared with media and general public.", "qid": 14, "docid": "p48bw6s4", "rank": 2, "score": 0.7948942184448242}, {"content": "Title: Significance of super spreader events in COVID-19. Content: The number of secondary cases from each primary case determines how fast an epidemic grows. It is known that all cases do not spread the infection equally; super spreaders play an important role as they contribute disproportionately to a much larger number of cases including in the ongoing COVID-19 pandemic. Super spreaders have been reported for more than a century, but limited information is available in scientific literature. An epidemic containment strategy needs to include early identification of super spreaders to limit an explosive growth. Super spreaders tend to get stigmatized, resulting in late reporting and hiding of cases. It is important for program managers to be sensitive to the manner in which related information is shared with media and general public.", "qid": 14, "docid": "na3vrf5q", "rank": 3, "score": 0.7948942184448242}, {"content": "Title: Do superspreaders generate new superspreaders? A hypothesis to explain the propagation pattern of COVID-19 Content: The current global propagation of COVID-19 is heterogeneous, with slow transmission continuing in many countries and exponential propagation in others, where the time that it took for the explosive spread to begin varied greatly. It is proposed that this could be explained by cascading superspreading events, in which new infections caused by a superspreader are more likely to be highly infectious. The mechanism suggested for this is related to viral loads. Exposure to high viral loads may result in high-intensity infection, which exposes new cases to high viral loads. This notion is supported by experimental veterinary research.", "qid": 14, "docid": "oocco483", "rank": 4, "score": 0.7944893836975098}, {"content": "Title: Super-Spreader Businesses and Risk of COVID-19 Transmission Content: Purpose: The United States has the highest number of confirmed COVID-19 cases in the world to date, with over 94,000 COVID-19-related deaths. The true risk of a COVID-19 resurgence as states prepare to reopen businesses is unknown. This paper aims to classify businesses by their risk of transmission and quantify the relationship between the density of super-spreader businesses and COVID-19 cases. Methods: We constructed a COVID-19 Business Transmission Risk Index based upon the frequency and duration of visits and square footage of businesses pre-pandemic in 2019 in 8 states (Massachusetts, Rhode Island, Connecticut, New Hampshire, Vermont, Maine, New York, and California). We used this index to classify businesses as super-spreaders. Then, we analyzed the association between the density of super-spreader businesses in a county and the rate of COVID-19 cases. We performed significance testing using a negative binomial regression. The main outcome of interest is the cumulative number of COVID-19 cases each week. Results: We found a positive association between the density of super-spreader businesses and COVID-19 cases. A 1 percentage point increase in the density of super-spreader businesses is associated with 5% higher COVID-19 cases, all else equal. Conclusion: Higher densities of super-spreader businesses are associated with higher rates of COVID-19 cases. This may have important implications for how states reopen super-spreader businesses.", "qid": 14, "docid": "8ngri1x0", "rank": 5, "score": 0.7937666177749634}, {"content": "Title: Do superspreaders generate new superspreaders? a hypothesis to explain the propagation pattern of COVID-19 Content: Abstract The current global propagation of COVID-19 is heterogeneous, with slow transmission continuing in many countries, and exponential propagation in others, in which the time that took to begin this explosive spread varies greatly. It is proposed that this could be explained by cascading superspreading events, in which new infections caused by a superspreader are more likely to be highly infectious. The mechanism suggested for this is related to viral loads. Exposure to high viral loads may result in infections of high intensity, which exposes new cases to high viral loads, and so on. This notion is supported by experimental veterinary research.", "qid": 14, "docid": "5906wju4", "rank": 6, "score": 0.7932887077331543}, {"content": "Title: COVID-19 Super-spreaders: Definitional Quandaries and Implications Content: Uncertainty around the role \u2018super-spreaders\u2019 play in the transmission and escalation of infectious disease is compounded by its broad and vague definition. It is a term that has been much used in relation to COVID-19, particularly in social media. On its widest definition, it refers to a propensity to infect a larger than average number of people. Given the biological, behavioural and environmental variables relevant to infectivity, this might be pertinent to almost any infected individual who is not physically isolated from others. Nor is the term confined to individuals with a propensity to spread infectious disease: it can potentially be used to describe events, policies or settings. This article explores the use of the term and considers circumstances in which the wide definition can be problematic. One problem is that it can lead to undeserved apportionment of moral blame to alleged super-spreaders. Another is that it can detract from scientific investigation of the heterogeneity of COVID-19 transmission. The author calls for a clearer epidemiological definition.", "qid": 14, "docid": "s9dy7iyf", "rank": 7, "score": 0.7917364835739136}, {"content": "Title: Identification of a super-spreading chain of transmission associated with COVID-19 Content: Background: Super-spreading events were associated with the outbreaks of SARS and MERS, but their association with the outbreak of COVID-19 remains unknown. Here, we report a super-spreading transmission chain of SARS-CoV-2 involving an index patient, seven cancer patients, 40 health care workers and four family members. Methods: We conducted a retrospective study to identify the index patient and the exposed individuals linked to a chain of transmission associated with COVID-19. We collected and analyzed the data on demographic features, exposure history, clinical presentation, laboratory investigation, radiological examination, and disease outcome of these patients. Results: We identified the index patient and another presumptive super-spreader, who initiated and amplified a super-spreading transmission chain associated with COVID-19, respectively. There were 31 female and 21 male patients in this cohort, and the median age was 37 years (range: 22-79 years). Each of them had an exposure history with the index patient or his close contacts. Approximately 87% (45/52) of the patients had fever or other symptoms, 96% (50/52) had abnormal chest CT-scan findings, 86% of the tested patients (39/45) were positive for SARS-CoV-2 in the nasopharyngeal or throat swab specimen, 85% of the tested patients (29/34) were positive for SARS-CoV-2-specific IgM and/or IgG, 15% of the RT-PCR positive patients were tested negative for the specific IgM and/or IgG at the convalescent phase, and 15% of the RT-PCR negative patients were tested positive for the specific IgM and/or IgG. The severe patients experienced a significant decrease in oximetry saturation, lymphocyte, and platelet counts, along with a significant increase in C-reactive protein, D-dimer, and lactate dehydrogenase. All six fatal cases had comorbidities and five of the seven cancer patients (71%) died within 2-20 days of the disease onset. Conclusions: The super-spreading events were associated with the outbreak of COVID-19 in Wuhan and its impact on disease transmission warrants further investigation. Cancer patients appeared highly vulnerable to COVID-19. The finding that a significant portion of SARS-CoV-2 infected patients were tested negative for the serum specific IgM and IgG at the convalescent phase should be addressed by additional studies.", "qid": 14, "docid": "yp38t4yb", "rank": 8, "score": 0.7898159027099609}, {"content": "Title: Stochasticity and heterogeneity in the transmission dynamics of SARS-CoV-2 Content: SARS-CoV-2 causing COVID-19 disease has moved rapidly around the globe, infecting millions and killing hundreds of thousands. The basic reproduction number, which has been widely used and misused to characterize the transmissibility of the virus, hides the fact that transmission is stochastic, is dominated by a small number of individuals, and is driven by super-spreading events (SSEs). The distinct transmission features, such as high stochasticity under low prevalence, and the central role played by SSEs on transmission dynamics, should not be overlooked. Many explosive SSEs have occurred in indoor settings stoking the pandemic and shaping its spread, such as long-term care facilities, prisons, meat-packing plants, fish factories, cruise ships, family gatherings, parties and night clubs. These SSEs demonstrate the urgent need to understand routes of transmission, while posing an opportunity that outbreak can be effectively contained with targeted interventions to eliminate SSEs. Here, we describe the potential types of SSEs, how they influence transmission, and give recommendations for control of SARS-CoV-2.", "qid": 14, "docid": "en6fgilb", "rank": 9, "score": 0.7868723273277283}, {"content": "Title: Inferring super-spreading from transmission clusters of COVID-19 in Hong Kong, Japan and Singapore Content: Super-spreading events in an outbreak can change the nature of an epidemic. Therefore, it is useful for public health teams to determine if an ongoing outbreak has any contribution from such events, which may be amenable to interventions. We estimated the basic reproductive number (R(0)) and the dispersion factor (k) from empirical data on clusters of epidemiologically-linked COVID-19 cases in Hong Kong, Japan and Singapore. This allowed us to infer the presence or absence of super-spreading events during the early phase of these outbreaks. The relatively large values of k implied that large cluster sizes, compatible with super-spreading, were unlikely.", "qid": 14, "docid": "w4l2vpiy", "rank": 10, "score": 0.7806000709533691}, {"content": "Title: A super-spreader of COVID-19 in Ningbo city in China Content: An outbreak of Coronavirus Disease 2019 (COVID-19) has spread rapidly. It is imperative to control the epidemic by understanding the epidemiological feature, preventative quarantine, and effective hygiene measures. In the present study, we report a case of super-spreader who transmitted the disease to over twenty-eight persons in Ningbo, Zhejiang. Identifying and isolated super-spreaders, understanding the reasons behind the efficient transmission ability are important for the control and management of the ongoing COVID-19 pandemic.", "qid": 14, "docid": "37katpp3", "rank": 11, "score": 0.7803433537483215}, {"content": "Title: [The coronavirus COVID-19 pandemic. Past experience and scientific evidence at the end of March 2020]. Content: The COVID-19 epidemic has unexpectedly affected everyone, both professionals and lay people, although the possibility of a global pandemic has long been theoretically considered by epidemiologists, infectologists on the one hand, and sociologists, communication and even social behavioral behaviorists in theory. Yet, faced with \"real-time\" events, daily infection and mortality statistics, almost everyone feels ignorant or confusingly inexperienced. This summary is intended to provide an overview of scientific evidence. Compiled at the end of March 2020, the not-so-complete material, of course, contains quite a few elements that will be surpassed in a few weeks. The authors hope that in a forthcoming publication we can all report on a much better and more hopeful outlook. Orv Hetil. 2020; 161 (17): 644-651.", "qid": 14, "docid": "bwk5demo", "rank": 12, "score": 0.7759146690368652}, {"content": "Title: Relationship between perception and anxiety about COVID-19 infection and risk behaviors for spreading infection: A national survey in Japan Content: BACKGROUND: The novel corona virus infection (COVID-19) quickly became a pandemic state. Identifying characteristics of \u201cpossible super spreaders\u201d, suggested as a dominant cause of rapid spreading transmission, will help us to design proper prevention strategies. METHODS: We conducted a nation-wide online survey to investigate the relationship of perception and anxiety levels about COVID-19 to the possible risk behaviors for spread of the virus in Japan. We recruited a total of 4,000 citizens, who responded to the questionnaire including several questions regarding the level of fear and anxiety about COVID-19, infection preventive behaviors and access to media with trust level about the virus as well as some demographic and socioeconomic data during March 27th and 28th, 2020. FINDINGS: Thirteen-point-three percent of the participants rated \u201c1\u201d on a nine-point Likert with respect to the knowledge about COVID-19. Ten-point-one percent and 11.7% presented no anxiety of being infected and transmission to others. Ten-point-eight percent showed no worry about symptomatic aggravation. Eight-point-one percent had no serious concern about expanding infection. The distribution of these items was highly correlated with each other. Participants with the low level of knowledge about COVID-19 were likely to less frequently access any information sources and neither trust them. They were less anxious about their health status, and less likely to put precautionary behaviors such as washing hands and avoiding crowded spaces, suggested by statistical analyses. INTERPRETATION: The present study suggests that it is greatly important to enlighten those have no concerns about this crisis of COVID-19 and modify their risk behavior via various ways, in order to prevent and control this viral pandemic. FUNDING: This study was funded by the management grand provided to Chiba University Graduate School of Medicine and the Japan Society for the Promotion of Science KAKENHI grants.", "qid": 14, "docid": "5nkoybui", "rank": 13, "score": 0.7736408710479736}, {"content": "Title: Inferring super-spreading from transmission clusters of COVID-19 in Hong Kong, Japan and Singapore Content: Super-spreading events in an outbreak can change the nature of an epidemic. Therefore, it is useful for public health teams to determine if an ongoing outbreak has any contribution from such events, which may be amenable to interventions. We estimated the basic reproductive number (R0) and the dispersion factor (k) from empirical data on clusters of epidemiologically-linked COVID-19 cases in Hong Kong, Japan and Singapore. This allowed us to infer the presence or absence of super-spreading events during the early phase of these outbreaks. The relatively large values of k implied that large cluster sizes, compatible with super-spreading, were unlikely.", "qid": 14, "docid": "2t4fsfy9", "rank": 14, "score": 0.7735648155212402}, {"content": "Title: Reconstruction of Transmission Pairs for novel Coronavirus Disease 2019 (COVID-19) in mainland China: Estimation of Super-spreading Events, Serial Interval, and Hazard of Infection Content: BACKGROUND: Knowledge on the epidemiological features and transmission patterns of COVID-19 is accumulating. Detailed line-list data with household settings can advance the understanding of COVID-19 transmission dynamics. METHODS: A unique database with detailed demographic characteristics, travel history, social relationships, and epidemiological timelines for 1,407 transmission pairs that formed 643 transmission clusters in mainland China was reconstructed from 9,120 COVID-19 confirmed cases reported during January 15 - February 29, 2020. Statistical model fittings were used to identify the super-spreaders and estimate serial interval distributions. Age and gender-stratified hazard of infection were estimated for household versus non-household transmissions. RESULTS: There were 34 primary cases identified as super-spreaders, with 5 super-spreading events occurred within households. Mean and standard deviation of serial intervals were estimated as 5.0 (95% CrI: 4.4, 5.5) and 5.2 (95% CrI: 4.9, 5.7) days for household transmissions and 5.2 (95% CrI: 4.6, 5.8) and 5.3 (95% CrI: 4.9, 5.7) days for non-household transmissions, respectively. Hazard of being infected outside of households is higher for age between 18 and 64 years, whereas hazard of being infected within households is higher for young and old people. CONCLUSIONS: Non-negligible frequency of super-spreading events, short serial intervals, and a higher risk of being infected outside of households for male people of working age indicate a significant barrier to the identification and management of COVID-19 cases, which requires enhanced non-pharmaceutical interventions to mitigate this pandemic.", "qid": 14, "docid": "55f2cno3", "rank": 15, "score": 0.76948481798172}, {"content": "Title: [A koronav\u00edrus okozta COVID\u00ad19-pand\u00e9mia. Kor\u00e1bbi tapasztalatok \u00e9s tudom\u00e1nyos evidenci\u00e1k 2020. m\u00e1rcius v\u00e9g\u00e9n]/ The coronavirus-induced COVID-19 pandemic. Previous experiences and scientific evidences at the end of March, 2020 Content: The COVID-19 epidemic hit everyone, professionals and civilians alike. The possibility of a worldwide pandemic has long been theorized by epidemiologists, infectologists on the one hand, and sociologists and behavioral scientists dealing with communication and social habits on the other. Yet, faced with real-time events, daily infections and mortality statistics, almost everyone feels uninformed or disturbingly inexperienced. This summary aims to provide an overview of the latest scientific evidences. Of course, the incomplete material, compiled in late March 2020, will certainly contain a few elements that likely will be outdated in a few weeks. The authors hope that in the next publication we will all read much better and more hopeful prospects. Orv Hetil. 2020; 161(17): 644\u00ad651.", "qid": 14, "docid": "3v9w9jyc", "rank": 16, "score": 0.7691484689712524}, {"content": "Title: [Advances on presymptomatic or asymptomatic carrier transmission of COVID-19] Content: COVID-19 is rapidly spreading. Patients in incubation period and healthy carriers are possible sources for transmission. However, such sources of infection cannot be effectively identified due to the symptoms absent. The research evidence is very lacking so far, although there are a few studies suggesting that presymptomatic or asymptomatic carrier may cause COVID-19 transmission. Nearly half of the literature is in the state of preprint without peer review. The question of \"the degree to which presymptomatic or asymptomatic infections can transmit\" is not fully understood. There is an urgent need to screen infected carriers in larger close contacts or in the general population, and assess their risk for transmission.", "qid": 14, "docid": "3fd81ovn", "rank": 17, "score": 0.759760856628418}, {"content": "Title: [Advances on presymptomatic or asymptomatic carrier transmission of COVID-19]. Content: COVID-19 is rapidly spreading. Patients in incubation period and healthy carriers are possible sources for transmission. However, such sources of infection cannot be effectively identified due to the symptoms absent. The research evidence is very lacking so far, although there are a few studies suggesting that presymptomatic or asymptomatic carrier may cause COVID-19 transmission. Nearly half of the literature is in the state of preprint without peer review. The question of \"the degree to which presymptomatic or asymptomatic infections can transmit\" is not fully understood. There is an urgent need to screen infected carriers in larger close contacts or in the general population, and assess their risk for transmission.", "qid": 14, "docid": "xbv0b96w", "rank": 18, "score": 0.759760856628418}, {"content": "Title: Connecting the Dots of COVID-19 Transmissions in India Content: Witnessing its first case in late January 2020 India has seen a sharp rise in the number of positive cases of COVID-19. 34 States/UT (s) of the country have been found to be affected by the pandemic to date. We in this work, study the progress of COVID-19 pandemic in India. We aim to create transmission network visualization (s) of COVID-19 in India and perform analysis upon them. Using the transmission networks obtained we attempt to find the possible Super Spreader Individual (s) and Super Spreader Events (SSE) responsible for the outbreak in their respective regions. We discuss the potentials of network analysis in mitigating the further spread of the disease. This is one of the initial studies of the outbreak in India and the first attempt to study the pandemic in the country from a transmission network perspective.", "qid": 14, "docid": "d91t5o01", "rank": 19, "score": 0.7586956024169922}, {"content": "Title: Characterizing super-spreading events and age-specific infectivity of COVID-19 transmission in Georgia, USA Content: As the current COVID-19 pandemic continues to impact countries around the globe, refining our understanding of its transmission dynamics and the effectiveness of interventions is imperative. In particular, it is essential to obtain a firmer grasp on the effect of social distancing, potential individual-level heterogeneities in transmission such as age-specific infectivity, and impact of super-spreading. To this end, it is important to exploit multiple data streams that are becoming abundantly available during the pandemic. In this paper, we formulate an individual-level spatio-temporal mechanistic framework to statistically integrate case data with geo-location data and aggregate mobility data, enabling a more granular understanding of the transmission dynamics of COVID-19. We analyze reported cases from surveillance data, between March and early May 2020, in five (urban and rural) counties in the State of Georgia USA. We estimate natural history parameters of COVID-19 and infer unobserved quantities including infection times and transmission paths using Bayesian data-augmentation techniques. First, our results show that the overall median reproductive number was 2.88 (with 95% C.I. [1.85, 4.9]) before the state-wide shelter-in-place order issued in early April, and the effective reproductive number was reduced to below 1 about two weeks by the order. Super-spreading appears to be widespread across space and time, and it may have a particularly important role in driving the outbreak in the rural area and increasing importance towards later stages of outbreaks in both urban and rural settings. Overall, about 2% of cases may have directly infected 20% of all infections. We estimate that the infected children and younger adults (<60 years old) may be 2.38 [1.30, 3.51] times more transmissible than infected elderly (>=60), and the former may be the main driver of super-spreading. Through the synthesis of multiple data streams using our transmission modelling framework, our results enforce and improve our understanding of the natural history and transmission dynamics of COVID-19. More importantly, we reveal the roles of age-specific infectivity and characterize systematic variations and associated risk factors of super-spreading. These have important implications for the planning of relaxing social distancing and, more generally, designing optimal control measures.", "qid": 14, "docid": "2jy2hjwy", "rank": 20, "score": 0.7555906176567078}, {"content": "Title: Coronavirus disease (COVID-19): a scoping review Content: BackgroundIn December 2019, a pneumonia caused by a novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and has rapidly spread around the world since then.AimThis study aims to understand the research gaps related to COVID-19 and propose recommendations for future research.MethodsWe undertook a scoping review of COVID-19, comprehensively searching databases and other sources to identify literature on COVID-19 between 1 December 2019 and 6 February 2020. We analysed the sources, publication date, type and topic of the retrieved articles/studies.ResultsWe included 249 articles in this scoping review. More than half (59.0%) were conducted in China. Guidance/guidelines and consensuses statements (n\u00e2\u0080\u00af=\u00e2\u0080\u00af56; 22.5%) were the most common. Most (n\u00e2\u0080\u00af=\u00e2\u0080\u00af192; 77.1%) articles were published in peer-reviewed journals, 35 (14.1%) on preprint servers and 22 (8.8%) posted online. Ten genetic studies (4.0%) focused on the origin of SARS-CoV-2 while the topics of molecular studies varied. Nine of 22 epidemiological studies focused on estimating the basic reproduction number of COVID-19 infection (R0). Of all identified guidance/guidelines (n\u00e2\u0080\u00af=\u00e2\u0080\u00af35), only ten fulfilled the strict principles of evidence-based practice. The number of articles published per day increased rapidly until the end of January.ConclusionThe number of articles on COVID-19 steadily increased before 6 February 2020. However, they lack diversity and are almost non-existent in some study fields, such as clinical research. The findings suggest that evidence for the development of clinical practice guidelines and public health policies will be improved when more results from clinical research becomes available.", "qid": 14, "docid": "nk7w2ola", "rank": 21, "score": 0.7551802396774292}, {"content": "Title: COVID-19 in older people: a rapid clinical review Content: INTRODUCTION: the COVID-19 pandemic poses a high risk to older people. The aim of this article is to provide a rapid overview of the COVID-19 literature, with a specific focus on older adults. We frame our findings within an overview of the disease and have also evaluated the inclusion of older people within forthcoming clinical trials. METHODS: we searched PubMed and bioRxiv/medRxiv to identify English language papers describing the testing, treatment and prognosis of COVID-19. PubMed and bioRxiv/medRxiv searches took place on 20 and 24 March 2020, respectively. RESULTS: screening of over 1,100 peer-reviewed and pre-print papers yielded n = 22 on COVID-19 testing, n = 15 on treatment and n = 13 on prognosis. Viral polymerase chain reaction (PCR) and serology are the mainstays of testing, but a positive diagnosis may be increasingly supported by radiological findings. The current evidence for the effectiveness of antiviral, corticosteroid and immunotherapies is inconclusive, although trial data are largely based on younger people. In addition to age, male gender and comorbidities, specific laboratory and radiology findings are important prognostic factors. Evidence suggests that social distancing policies could have important negative consequences, particularly if in place for an extended period. CONCLUSION: given the established association between increasing age and poor prognosis in COVID-19, we anticipate that this rapid review of the current and emergent evidence might form a basis on which future work can be established. Exclusion of older people, particularly those with comorbidities, from clinical trials is well recognised and is potentially being perpetuated in the field of current COVID-19 research.", "qid": 14, "docid": "gj3xe6mf", "rank": 22, "score": 0.7546254396438599}, {"content": "Title: COVID-19 in Older People: A Rapid Clinical Review Content: INTRODUCTION: The COVID-19 pandemic poses a high risk to older people. The aim of this paper is to provide a rapid overview of the COVID-19 literature, with a specific focus on older adults. We frame our findings within an overview of the disease and have also evaluated the inclusion of older people within forthcoming clinical trials. METHODS: We searched PubMed and bioRxiv/medRxiv to identify English language papers describing the testing, treatment and prognosis of COVID-19. PubMed and bioRxiv/medRxiv searches took place on 20th and 24th March 2020, respectively. RESULTS: Screening of over 1100 peer-reviewed and pre-print papers yielded n = 22 on COVID-19 testing, n = 15 on treatment and n = 13 on prognosis. Viral-PCR and serology are the mainstays of testing but a positive diagnosis may be increasingly supported by radiological findings. The current evidence for the effectiveness of antiviral, corticosteroid and immunotherapies is inconclusive, although trial data are largely based on younger people. In addition to age, male gender and comorbidities, specific laboratory and radiology findings are important prognostic factors. Evidence suggests social distancing policies could have important negative consequences, particularly if in place for an extended period. CONCLUSION: Given the established association between increasing age and poor prognosis in COVID-19, we anticipate that this rapid review of the current and emergent evidence might form a basis on which future work can be established. Exclusion of older people, particularly those with comorbidities, from clinical trials is well recognised and is potentially being perpetuated in the field of current COVID-19 research.", "qid": 14, "docid": "kc3nb2pc", "rank": 23, "score": 0.752721905708313}, {"content": "Title: COVID-19 infodemic: More retweets for science-based information on coronavirus than for false information Content: The World Health Organization has not only signaled the health risks of COVID-19, but also labeled the situation as infodemic, due to the amount of information, true and false, circulating around this topic. Research shows that, in social media, falsehood is shared far more than evidence-based information. However, there is less research analyzing the circulation of false and evidence-based information during health emergencies. Thus, the present study aims at shedding new light on the type of tweets that circulated on Twitter around the COVID-19 outbreak for two days, in order to analyze how false and true information was shared. To that end, 1000 tweets have been analyzed. Results show that false information is tweeted more but retweeted less than science-based evidence or fact-checking tweets, while science-based evidence and fact-checking tweets capture more engagement than mere facts. These findings bring relevant insights to inform public health policies.", "qid": 14, "docid": "1asa4sej", "rank": 24, "score": 0.7527087926864624}, {"content": "Title: Is it super-spreading? Content: If the covid-19 virus is transmitted largely by superspreaders, it might not go pandemic, reports Debora MacKenzie", "qid": 14, "docid": "kb8dz8hd", "rank": 25, "score": 0.7510610818862915}, {"content": "Title: Effects of temperature and humidity on the spread of COVID-19: A systematic review. Content: Background: Faced with the global pandemic of COVID-19, declared by World Health Organization (WHO) on March 11th 2020, and the need to better understand the seasonal behavior of the virus, our team conducted this systematic review to describe current knowledge about the emergence and replicability of the virus and its correlation with different weather factors such as temperature and relative humidity. Methods: The review was registered with the PROSPERO database. The electronic databases PubMed, Scopus, Web of Science, Cochrane Library, LILACS, OpenGrey and Google Scholar were examined with the searches restricted to the years 2019 and 2020. Risk of bias assessment was performed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist tool. The GRADE tool was used to assess the quality of the evidence. Results: The initial screening identified 517 articles. After examination of the full texts, seventeen studies met the review's eligibility criteria. Great homogeneity was observed in the findings regarding the effect of temperature and humidity on the seasonal viability and transmissibility of COVID-19. Cold and dry conditions were potentiating factors on the spread of the virus. After quality assessment, four studies had a high risk of bias and thirteen studies were scored as moderate risk of bias. The certainty of evidence was graded as low for both outcomes evaluated. Conclusion: Considering the existing scientific evidence, warm and wet climates seem to reduce the spread of COVID-19. The certainty of the evidence generated was graded as low. However, these variables alone could not explain most of the variability in disease transmission.", "qid": 14, "docid": "w5tc6gmu", "rank": 26, "score": 0.7505925893783569}, {"content": "Title: Epidemiological and Clinical Aspects of COVID-19; a Narrative Review. Content: There are significant misconceptions and many obstacles in the way of illuminating the epidemiological and clinical aspects of COVID-19 as a new emerging epidemic. In addition, usefulness of some evidence published in the context of the recent epidemic for decision making in clinic as well as public health is questionable. However, misinterpreting or ignoring strong evidence in clinical practice and public health probably results in less effective and somehow more harmful decisions for individuals as well as subgroups in general populations of countries in the initial stages of this epidemic. Accordingly, our narrative review appraised epidemiological and clinical aspects of the disease including genetic diversity of coronavirus genus, mode of transmission, incubation period, infectivity, pathogenicity, virulence, immunogenicity, diagnosis, surveillance, clinical case management and also successful measures for preventing its spread in some communities.", "qid": 14, "docid": "lm1tiprk", "rank": 27, "score": 0.7503260374069214}, {"content": "Title: Epidemiological and Clinical Aspects of COVID-19; a Narrative Review Content: There are significant misconceptions and many obstacles in the way of illuminating the epidemiological and clinical aspects of COVID-19 as a new emerging epidemic. In addition, usefulness of some evidence published in the context of the recent epidemic for decision making in clinic as well as public health is questionable. However, misinterpreting or ignoring strong evidence in clinical practice and public health probably results in less effective and somehow more harmful decisions for individuals as well as subgroups in general populations of countries in the initial stages of this epidemic. Accordingly, our narrative review appraised epidemiological and clinical aspects of the disease including genetic diversity of coronavirus genus, mode of transmission, incubation period, infectivity, pathogenicity, virulence, immunogenicity, diagnosis, surveillance, clinical case management and also successful measures for preventing its spread in some communities.", "qid": 14, "docid": "vwf2djd4", "rank": 28, "score": 0.7503260374069214}, {"content": "Title: Review of published systematic reviews and meta-analyses on COVID-19 Content: Purpose: The rapid spread of the COVID-19 pandemic has prompted researchers from all over the world to share their experience. The results were numerous reports with variable quality. The latter has provided an impetus to examine all published meta-analyses and systematic reviews on COVID-19 to date to examine available evidence. Methods: Using predefined selection criteria, a literature search identified 43 eligible meta-analyses and/or systematic reviews. Results: Most (N=17) studies addressed clinical manifestations and associated comorbidity, 6 studies addressed clinical manifestations in pregnant women and younger individuals, 8 studies addressed diagnostic data, 9 studies addressed various interventions, and 9 studies addressed prevention and control. The number of studies included in the various systemic reviews and meta-analyses ranged from 2 to 89. While there were some similarities and consistency for some findings, e.g. the relation between comorbidities and disease severity, we also noted occasionally conflicting data. Conclusion: As more data are collected from patients infected with COVID-19 all over the world, more studies will undoubtedly be published and attention to scientific accuracy in the performance of trials must be exercised to inform clinical decision-making and treatment guidelines.", "qid": 14, "docid": "w170rm6q", "rank": 29, "score": 0.7500410079956055}, {"content": "Title: COVID-19 and cancer: do we really know what we think we know? Content: Early published data on COVID-19 in patients with cancer are being referenced in clinical guidelines, despite methodological flaws that limit the quality of much of this evidence. In the next phase of research in this area, we argue that the quality of observational evidence should be prioritized over speed of publication.", "qid": 14, "docid": "c2kecpoc", "rank": 30, "score": 0.7496718764305115}, {"content": "Title: MERS, SARS, and Ebola: The Role of Super-Spreaders in Infectious Disease Content: Super-spreading occurs when a single patient infects a disproportionate number of contacts. The 2015 MERS-CoV, 2003 SARS-CoV, and to a lesser extent 2014\u201315 Ebola virus outbreaks were driven by super-spreaders. We summarize documented super-spreading in these outbreaks, explore contributing factors, and suggest studies to better understand super-spreading.", "qid": 14, "docid": "414grqif", "rank": 31, "score": 0.7481719851493835}, {"content": "Title: SARS-CoV-2/COVID-19: Evolving Reality, Global Response, Knowledge Gaps and Opportunities. Content: Approximately 3 billion people around the world have gone into some form of social separation to mitigate the current SARS-CoV-2 pandemic. The uncontrolled influx of patients in need of emergency care has rapidly brought several national health systems to near-collapse with deadly consequences to those afflicted by COVID-19 and other critical diseases associated with COVID-19. Solid scientific evidence regarding SARS-CoV-2/COVID-19 remains scarce; there is an urgent need to expand our understanding of the SARS-CoV-2 pathophysiology to facilitate precise and targeted treatments. The capacity for rapid information dissemination has emerged as a double-edged sword; the existing gap of high-quality data is frequently filled by anecdotal reports, contradictory statements and misinformation. This review addresses several important aspects unique to the SARS-CoV-2/COVID-19 pandemic highlighting the most relevant knowledge gaps and existing windows-of-opportunity. Specifically, focus is given to SARS-CoV-2 immunopathogenesis in the context of experimental therapies and pre-clinical evidence and their applicability in supporting efficacious clinical trial planning. The review discusses the existing challenges of SARS-CoV-2 diagnostics and the potential application of translational technology for epidemiological predictions, patient monitoring and treatment decision-making in COVID-19. Furthermore, solutions for enhancing international strategies in translational research, cooperative networks and regulatory partnerships are contemplated.", "qid": 14, "docid": "848fswtv", "rank": 32, "score": 0.7474343180656433}, {"content": "Title: Discovering associations in COVID-19 related research papers Content: A COVID-19 pandemic has already proven itself to be a global challenge. It proves how vulnerable humanity can be. It has also mobilized researchers from different sciences and different countries in the search for a way to fight this potentially fatal disease. In line with this, our study analyses the abstracts of papers related to COVID-19 and coronavirus-related-research using association rule text mining in order to find the most interestingness words, on the one hand, and relationships between them on the other. Then, a method, called information cartography, was applied for extracting structured knowledge from a huge amount of association rules. On the basis of these methods, the purpose of our study was to show how researchers have responded in similar epidemic/pandemic situations throughout history.", "qid": 14, "docid": "zlg2fs0a", "rank": 33, "score": 0.746932864189148}, {"content": "Title: If COVID-19 Becomes Endemic will the Current Dental Guidelines Still Remain Valid? Content: In a recent paper, the authors Jamal et al reviewed various guidelines published by dental societies of the world for the prevention of transmission of COVID-19 virus in the dental care setting during the current pandemic(Jamal et al., 2020). While this review is very interesting, I have a genuine apprehension that these guidelines may not be valid for a long time and very soon new guidelines will be required in the unfortunate event of COVID-19 becoming endemic.", "qid": 14, "docid": "rvwjv8j2", "rank": 34, "score": 0.7460728883743286}, {"content": "Title: COVID-19: From pathogenesis models to the first drug trials Content: The number of people infected with SARS-CoV-2, and sadly dying from COVID-19, has exploded, and so the amount of literature on the novel coronavirus and the disease it causes has increased proportionately. The case numbers in some countries are beyond the epidemic peak, but the uncertainty about a second wave keeps politicians and societies under pressure. Appropriate decision-making and winning support from the population depends on precise scientific information rather than leaving the field to scaremongers of all proveniences. This mini-review is an update of earlier reports (Br\u00fcssow, Microb Biotechnol 2020a;13:607; Br\u00fcssow, Microb Biotechnol 2020b; https://doi.org/10.1111/1751-7915.13592).", "qid": 14, "docid": "ulth0px1", "rank": 35, "score": 0.7455728054046631}, {"content": "Title: Genetic cluster analysis of SARS-CoV-2 and the identification of those responsible for the major outbreaks in various countries Content: A newly emerged coronavirus, SARS-CoV-2, caused severe pneumonia outbreaks in China in December 2019 and has since spread to various countries around the world. To trace the evolution route and probe the transmission dynamics of this virus, we performed phylodynamic analysis of 247 high quality genomic sequences available in the GISAID platform as of 5 March 2020. Among them, four genetic clusters, defined as super-spreaders (SSs), could be identified and were found to be responsible for the major outbreaks that subsequently occurred in various countries. SS1 was widely disseminated in Asia and the US, and mainly responsible for outbreaks in the states of Washington and California as well as South Korea, whereas SS4 contributed to the pandemic in Europe. Using the signature mutations of each SS as markers, we further analysed 1539 genome sequences reported after 29 February 2020 and found that 90% of these genomes belonged to SSs, with SS4 being the most dominant. The relative degree of contribution of each SS to the pandemic in different continents was also depicted. Identification of these super-spreaders greatly facilitates development of new strategies to control the transmission of SARS-CoV-2.", "qid": 14, "docid": "3uzsx715", "rank": 36, "score": 0.7455501556396484}, {"content": "Title: Genetic cluster analysis of SARS-CoV-2 and the identification of those responsible for the major outbreaks in various countries. Content: A newly emerged coronavirus, SARS-CoV-2, caused severe pneumonia outbreaks in China in December 2019 and has since spread to various countries around the world. To trace the evolution route and probe the transmission dynamics of this virus, we performed phylodynamic analysis of 247 high quality genomic sequences available in the GISAID platform as of 5 March 2020. Among them, four genetic clusters, defined as super-spreaders (SSs), could be identified and were found to be responsible for the major outbreaks that subsequently occurred in various countries. SS1 was widely disseminated in Asia and the US, and mainly responsible for outbreaks in the states of Washington and California as well as South Korea, whereas SS4 contributed to the pandemic in Europe. Using the signature mutations of each SS as markers, we further analysed 1539 genome sequences reported after 29 February 2020 and found that 90% of these genomes belonged to SSs, with SS4 being the most dominant. The relative degree of contribution of each SS to the pandemic in different continents was also depicted. Identification of these super-spreaders greatly facilitates development of new strategies to control the transmission of SARS-CoV-2.", "qid": 14, "docid": "4zyfc0y4", "rank": 37, "score": 0.7455501556396484}, {"content": "Title: Epidemiological and Clinical Aspects of COVID-19;a Narrative Review Content: There are significant misconceptions and many obstacles in the way of illuminating the epidemiological and clinical aspects of COVID-19 as a new emerging epidemic In addition, usefulness of some evidence published in the context of the recent epidemic for decision making in clinic as well as public health is questionable However, misinterpreting or ignoring strong evidence in clinical practice and public health probably results in less effective and somehow more harmful decisions for individuals as well as subgroups in general populations of countries in the initial stages of this epidemic Accordingly, our narrative review appraised epidemiological and clinical aspects of the disease including genetic diversity of coronavirus genus, mode of transmission, incubation period, infectivity, pathogenicity, virulence, immunogenicity, diagnosis, surveillance, clinical case management and also successful measures for preventing its spread in some communities", "qid": 14, "docid": "lm90kdnb", "rank": 38, "score": 0.745517909526825}, {"content": "Title: COVID\u201019: From pathogenesis models to the first drug trials Content: The number of people infected with SARS\u2010CoV\u20102, and sadly dying from COVID\u201019, has exploded, and so the amount of literature on the novel coronavirus and the disease it causes has increased proportionately. The case numbers in some countries are beyond the epidemic peak, but the uncertainty about a second wave keeps politicians and societies under pressure. Appropriate decision\u2010making and winning support from the population depends on precise scientific information rather than leaving the field to scaremongers of all proveniences. This mini\u2010review is an update of earlier reports (Br\u00fcssow, Microb Biotechnol 2020a;13:607; Br\u00fcssow, Microb Biotechnol 2020b; https://doi.org/10.1111/1751-7915.13592).", "qid": 14, "docid": "raf5rlkq", "rank": 39, "score": 0.7451756596565247}, {"content": "Title: SARS-CoV-2/COVID-19: Evolving Reality, Global Response, Knowledge Gaps, and Opportunities Content: Approximately 3 billion people around the world have gone into some form of social separation to mitigate the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The uncontrolled influx of patients in need of emergency care has rapidly brought several national health systems to near-collapse with deadly consequences to those afflicted by Coronavirus Disease 2019 (COVID-19) and other critical diseases associated with COVID-19. Solid scientific evidence regarding SARS-CoV-2/COVID-19 remains scarce; there is an urgent need to expand our understanding of the SARS-CoV-2 pathophysiology to facilitate precise and targeted treatments. The capacity for rapid information dissemination has emerged as a double-edged sword; the existing gap of high-quality data is frequently filled by anecdotal reports, contradictory statements, and misinformation. This review addresses several important aspects unique to the SARS-CoV-2/COVID-19 pandemic highlighting the most relevant knowledge gaps and existing windows-of-opportunity. Specifically, focus is given on SARS-CoV-2 immunopathogenesis in the context of experimental therapies and preclinical evidence and their applicability in supporting efficacious clinical trial planning. The review discusses the existing challenges of SARS-CoV-2 diagnostics and the potential application of translational technology for epidemiological predictions, patient monitoring, and treatment decision-making in COVID-19. Furthermore, solutions for enhancing international strategies in translational research, cooperative networks, and regulatory partnerships are contemplated.", "qid": 14, "docid": "cujy4r31", "rank": 40, "score": 0.7449630498886108}, {"content": "Title: The COVID-19 pandemic: is our medicine still evidence-based? Content: There is no randomized controlled trial that demonstrated the efficacy of antiviral therapy against COVID-19 yet. However, physicians are prescribing different drugs to a large part of COVID-19 population in the hope they will cure them. This does not reflect the evidence-based medicine approach. What we need is more evidence-based knowledge about what routine care practices we should to apply to ameliorate symptoms of patients and fight COVID-19 pathology.", "qid": 14, "docid": "x82yaoxc", "rank": 41, "score": 0.7445439696311951}, {"content": "Title: What do we know about the SARS-CoV-2 coronavirus in the environment? Content: In view of the current situation regarding the Covid-19 disease, a discussion is proposed on the need for research focusing on the presence and evolution of the SARS-CoV-2 virus in water, soils and other environmental compartments, reached through wastewater and sewage sludge spreading. Also, the evaluation of current treatments for wastewater and sewage sludge, as well as the eventual development of new specific techniques, based on sorption, nanotechnology, etc., would be of great interest for controlling the environmental dissemination of these viruses in the current and eventual future outbreaks.", "qid": 14, "docid": "j37hmrum", "rank": 42, "score": 0.7443495988845825}, {"content": "Title: Coronavirus Disease 2019 Treatment: A Review of Early and Emerging Options Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has spread across the globe resulting in a pandemic. At the time of this review, COVID-19 has been diagnosed in more than 200 000 patients and associated with over 8000 deaths (Centers for Disease Control and Prevention, World Health Organization). On behalf of the Society of Infectious Diseases Pharmacists, we herein summarize the current evidence as of March 18, 2020 to provide guidance on potential COVID-19 treatment options. It is important to caution readers that new data emerges daily regarding clinical characteristics, treatment options, and outcomes for COVID-19. Optimized supportive care remains the mainstay of therapy, and the clinical efficacy for the subsequent agents is still under investigation. Antimicrobial stewardship programs, including infectious diseases pharmacists and physicians, are at the forefront of COVID-19 emergency preparedness. We encourage all readers to continue to assess clinical data as it emerges and share their experience within our community in a well-controlled, adequately powered fashion.", "qid": 14, "docid": "j0i9ozsz", "rank": 43, "score": 0.7443127632141113}, {"content": "Title: An exploration of how fake news is taking over social media and putting public health at risk. Content: Recent statistics show that almost 1/4 of a million people have died and four million people are affected either with mild or serious health problems caused by coronavirus (COVID-19). These numbers are rapidly increasing (World Health Organization, May 3, 2020c). There is much concern during this pandemic about the spread of misleading or inaccurate information. This article reports on a small study which attempted to identify the types and sources of COVID-19 misinformation. The authors identified and analysed 1225 pieces of COVID-19 fake news stories taken from fact-checkers, myth-busters and COVID-19 dashboards. The study is significant given the concern raised by the WHO Director-General that 'we are not just fighting the pandemic, we are also fighting infodemic'. The study concludes that the COVID-19 infodemic is full of false claims, half backed conspiracy theories and pseudoscientific therapies, regarding the diagnosis, treatment, prevention, origin and spread of the virus. Fake news is pervasive in social media, putting public health at risk. The scale of the crisis and ubiquity of the misleading information require that scientists, health information professionals and journalists exercise their professional responsibility to help the general public identify fake news stories. They should ensure that accurate information is published and disseminated.J.M.", "qid": 14, "docid": "518e2x3h", "rank": 44, "score": 0.7440682649612427}, {"content": "Title: If COVID\u201019 Becomes Endemic will the Current Dental Guidelines Still Remain Valid? Content: In a recent paper, the authors Jamal et al reviewed various guidelines published by dental societies of the world for the prevention of transmission of COVID\u201019 virus in the dental care setting during the current pandemic(Jamal et al., 2020). While this review is very interesting, I have a genuine apprehension that these guidelines may not be valid for a long time and very soon new guidelines will be required in the unfortunate event of COVID\u201019 becoming endemic.", "qid": 14, "docid": "hdswo6y8", "rank": 45, "score": 0.7439712285995483}, {"content": "Title: Super-factors associated with transmission of occupational COVID-2019 infection among healthcare staff in Wuhan , China. Content: BACKGROUND Globally, there have been many cases of COVID-2019 cases among medical staff, however, the main factors associated with the infection are not well understood. AIM To identify the super-factors causing COVID-19 infection in medical staff in China. METHODS A cross-sectional study was conducted between Jan. 1st, and Feb. 30th, 2020, where front line members of medical staff that took part in the care and treatment of patients with COVID-19 were enrolled. Epidemiological and demographic data between infected and uninfected groups were collected and compared. Social network analysis (SNA) was used to establish socio-metric social links between influencing factors. FINDINGS A total of 92 medical staff were enrolled. In all participant groups, the super-factor identified by the network was wearing a medical protective mask or surgical mask correctly (degree = 572; closeness =25; betweenness centrality = 3\u00b723). Touching the cheek, nose, and mouth while working was the super-factor in the infected group. This was the biggest node in the network and had the strongest influence (degree = 370; closeness = 29; betweenness centrality = 0\u00b737). Self-protection score was the super-factor in the uninfected group but was the isolated factor in the infected group (degree = 201; closeness = 28; betweenness centrality = 5\u00b764). For family members, the exposure history to Huanan Seafood Wholesale Market and the contact history to wild animals were two isolated nodes. CONCLUSION High self-protection score was the main factor that prevented medical staff from contracting COVID-19 infection. The main factor that contributed to COVID-19 infections among medical staff was touching the cheek, nose and mouth while working.", "qid": 14, "docid": "lmw1l7gz", "rank": 46, "score": 0.7438433766365051}, {"content": "Title: Aktu\u00e1ln\u00ed problematika COVID-19 z pohledu imunologa./ COVID-19 from the perspective of an immunologist Content: COVID-19 is an infectious disease caused by a coronavirus SARS-CoV-2. COVID-19 has a number of similarities to SARS and MERS diseases. Its highly contagious nature is particularly due to the rapid spread of the disease through asymptomatic individuals; however, the worlds most contagious infectious disease is still considered measles. Scientific data have revealed the interactions between COVID-19 and the immune system. These findings may contribute to the development of novel preventive and therapeutic approaches. Just as coronavirus itself the reports about the disease have massively spread through media and public contributing to overall public fear and stress. This promotion of non-scientific evidence and misinformation through social media might have also a devastating impact on the individuals immune system. Data regarding the mortality rates of COVID-19 have achieved unprecedented media and public engagements, however, the true facts about the disease prevention, immunomodulation and novel treatments are often left unsaid. We present the most recent facts about COVID-19 disease and its interactions with the immune system.", "qid": 14, "docid": "pfyqjrwk", "rank": 47, "score": 0.74326092004776}, {"content": "Title: COVID-19 from the perspective of an immunologist. Content: COVID-19 is an infectious disease caused by a coronavirus SARS-CoV-2. COVID-19 has a number of similarities to SARS and MERS diseases. Its highly contagious nature is particularly due to the rapid spread of the disease through asymptomatic individuals; however, the worlds most contagious infectious disease is still considered measles. Scientific data have revealed the interactions between COVID-19 and the immune system. These findings may contribute to the development of novel preventive and therapeutic approaches. Just as coronavirus itself the reports about the disease have massively spread through media and public contributing to overall public fear and stress. This promotion of non-scientific evidence and misinformation through social media might have also a devastating impact on the individuals immune system. Data regarding the mortality rates of COVID-19 have achieved unprecedented media and public engagements, however, the true facts about the disease prevention, immunomodulation and novel treatments are often left unsaid. We present the most recent facts about COVID-19 disease and its interactions with the immune system.", "qid": 14, "docid": "mwpbrbqu", "rank": 48, "score": 0.7432608604431152}, {"content": "Title: Logic in the time of coronavirus Content: Much has happened here since the local news media trumpeted the first Australian COVID-19 fatality, and stirred up a medieval fear of contagion. We now need to take a step back to examine the logic underlying the use of our limited COVID-19 countermeasures. Emerging infectious diseases by their nature, pose new challenges to the diagnostic-treatment-control nexus, and push our concepts of causality beyond the limits of the conventional Koch-Henle approach to aetiology. We need to use contemporary methods of assessing causality to ensure that clinical, laboratory and public health measures draw on a rational, evidence-based approach to argumentation. The purpose of any aetiological hypothesis is to derive actionable insights into this latest emerging infectious disease. This review is an introduction to a conversation with medical microbiologists, which will be supported by a moderated blog.", "qid": 14, "docid": "59rbolz3", "rank": 49, "score": 0.7431805729866028}, {"content": "Title: Logic in the time of coronavirus. Content: Much has happened here since the local news media trumpeted the first Australian COVID-19 fatality, and stirred up a medieval fear of contagion. We now need to take a step back to examine the logic underlying the use of our limited COVID-19 countermeasures. Emerging infectious diseases by their nature, pose new challenges to the diagnostic-treatment-control nexus, and push our concepts of causality beyond the limits of the conventional Koch-Henle approach to aetiology. We need to use contemporary methods of assessing causality to ensure that clinical, laboratory and public health measures draw on a rational, evidence-based approach to argumentation. The purpose of any aetiological hypothesis is to derive actionable insights into this latest emerging infectious disease. This review is an introduction to a conversation with medical microbiologists, which will be supported by a moderated blog.", "qid": 14, "docid": "cdxi5gkq", "rank": 50, "score": 0.7431805729866028}, {"content": "Title: Comparative Efficacy and Safety of Pharmacological Managements for Hospitalized COVID-19 Patients: Protocol for Systematic Review and Trade-Off Network Meta-Analysis. Content: Coronavirus-Disease 2019 (COVID-19) is the clinical disease caused by the SARS-CoV-2 virus, the infectious agent causing the ongoing pandemic that has impacted the lives of hundreds of millions of people in almost every nation worldwide. It is a potentially fatal disease to many vulnerable patients including the elderly and those with chronic illnesses; but because this virus is a novel one, there are no firmly established treatment protocols. Many treatment methods are being investigated worldwide, and scientific conclusions drawn from these endeavors are crucial for healthcare professionals in combating this disease. In this network meta-analysis, we focus specifically on the pharmacologic agents that have been investigated for the treatment of COVID-19 and aim to produce a comprehensive picture of the evidence from current data in order to produce relevant insights on the comparative efficacy and safety profiles of various pharmacologic agents against COVID-19.", "qid": 14, "docid": "30h09e1k", "rank": 51, "score": 0.7431771755218506}, {"content": "Title: No evidence for distinct types in the evolution of SARS-CoV-2 Content: A recent study by Tang et al. (2020) claimed that two major types of SARS-CoV-2 had evolved in the ongoing COVID-19 pandemic and that one of these types was more \u201caggressive\u201d than the other. Given the repercussions of these claims and the intense media coverage of these types of articles, we have examined in detail the data presented by Tang et al, and show that the major conclusions of that paper cannot be substantiated. Using examples from other viral outbreaks we discuss the difficulty in demonstrating the existence or nature of a functional effect of a viral mutation, and we advise against overinterpretation of genomic data during the pandemic.", "qid": 14, "docid": "m61qihyq", "rank": 52, "score": 0.7430827617645264}, {"content": "Title: COVID\u201019 suspicion and diagnosis: are we still chasing epidemiological criteria? Content: Italy was the second nation after China to be most involved into the COVID\u201019 outbreak. From the beginning, much attention has been attributed to the importance of epidemiological criteria (such as previous contact with confirmed COVID\u201019 cases, recent journey across China or the northern Italian regions) in order to assess a suspected patient for SARS\u2010CoV\u20102 infection. Despite this, by now evidences do exist about the possibly huge reservoir of asymptomatic patients and its underestimated ability to spread the infection. Thus, we do believe that when an infectious disease has a big ratio of asymptomatic cases, as for COVID\u201019, it is simply not safe to rely on epidemiological criteria and we briefly discuss this issue throughout the few new evidences there are about. This article is protected by copyright. All rights reserved.", "qid": 14, "docid": "p4ef9l3p", "rank": 53, "score": 0.7429984211921692}, {"content": "Title: Super-factors associated with transmission of occupational COVID-2019 infection among healthcare staff in Wuhan , China Content: BACKGROUND: Globally, there have been many cases of COVID-2019 cases among medical staff, however, the main factors associated with the infection are not well understood. AIM: To identify the super-factors causing COVID-19 infection in medical staff in China. METHODS: A cross-sectional study was conducted between Jan. 1st, and Feb. 30th, 2020, where front line members of medical staff that took part in the care and treatment of patients with COVID-19 were enrolled. Epidemiological and demographic data between infected and uninfected groups were collected and compared. Social network analysis (SNA) was used to establish socio-metric social links between influencing factors. FINDINGS: A total of 92 medical staff were enrolled. In all participant groups, the super-factor identified by the network was wearing a medical protective mask or surgical mask correctly (degree = 572; closeness =25; betweenness centrality = 3\u00b723). Touching the cheek, nose, and mouth while working was the super-factor in the infected group. This was the biggest node in the network and had the strongest influence (degree = 370; closeness = 29; betweenness centrality = 0\u00b737). Self-protection score was the super-factor in the uninfected group but was the isolated factor in the infected group (degree = 201; closeness = 28; betweenness centrality = 5\u00b764). For family members, the exposure history to Huanan Seafood Wholesale Market and the contact history to wild animals were two isolated nodes. CONCLUSION: High self-protection score was the main factor that prevented medical staff from contracting COVID-19 infection. The main factor that contributed to COVID-19 infections among medical staff was touching the cheek, nose and mouth while working.", "qid": 14, "docid": "x67wh2na", "rank": 54, "score": 0.742798388004303}, {"content": "Title: A comprehensive review on drug repositioning against coronavirus disease 2019 (COVID19) Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is the reason for this ongoing pandemic infection diseases termed coronavirus disease 2019 (COVID-19) that has emerged since early December 2019 in Wuhan City, Hubei Province, China. In this century, it is the worst threat to international health and the economy. After 4 months of COVID-19 outbreak, there is no certain and approved medicine against it. In this public health emergency, it makes sense to investigate the possible effects of old drugs and find drug repositioning that is efficient, economical, and riskless process. Old drugs that may be effective are from different pharmacological categories, antimalarials, anthelmintics, anti-protozoal, anti-HIVs, anti-influenza, anti-hepacivirus, antineoplastics, neutralizing antibodies, immunoglobulins, and interferons. In vitro, in vivo, or preliminary trials of these drugs in the treatment of COVID-19 have been encouraging, leading to new research projects and trials to find the best drug/s. In this review, we discuss the possible mechanisms of these drugs against COVID-19. Also, it should be mentioned that in this manuscript, we discuss preliminary rationales; however, clinical trial evidence is needed to prove them. COVID-19 therapy must be based on expert clinical experience and published literature and guidelines from major health organizations. Moreover, herein, we describe current evidence that may be changed in the future.", "qid": 14, "docid": "476uhzb6", "rank": 55, "score": 0.7424175143241882}, {"content": "Title: COVID-19 y el sistema renina, angiotensina, aldosterona. Una relaci\u00f3n compleja./ COVID-19 and the renin, angiotensin, aldosterone system. A complex relationship Content: The COVID-19 pandemic has had major negative health, psychological, social and economic repercussions for individuals, families, communities, countries and for humanity in general. The interrelation with age and the presence of chronic non-communicable diseases (hypertension, diabetes, obesity, smoking) seems to go further than what would be explained by the prevalence and distribution of both. The drugs that act on the renin-angiotensin-aldosterone system are in many cases the backbone for the management of these diseases, it has been known for a long time that these drugs significantly increase the expression of receptors for angiotensin conversion enzyme type 2 in the lung tissue. This fact, together with the knowledge that the route of entry of the virus into the cell is precisely the ACE-2 receptor, initiated a hypothesis, based on very low-quality evidence, which quickly became generalized in the media, that the use of these drugs could be negative and that they should be interrupted immediately. The response of practically all Scientific Societies was almost immediate, with the precise indication that treatment with these drugs should not be discontinued, since the evidence of their usefulness is based on very solid and high-quality evidence. Simultaneously, a different hypothesis also appeared, also based on very preliminary evidence, that these drugs are not only harmful but also beneficial, however these medicaments are not yet accepted as agents for the prevention or treatment of this disease or its complications. This review reports current knowledge on the relationship between COVID-19 and SRAA.", "qid": 14, "docid": "2vns1wdb", "rank": 56, "score": 0.7420742511749268}, {"content": "Title: COVID-19 and the renin, angiotensin, aldosterone system. A complex relationship. Content: The COVID-19 pandemic has had major negative health, psychological, social and economic repercussions for individuals, families, communities, countries and for humanity in general. The interrelation with age and the presence of chronic non-communicable diseases (hypertension, diabetes, obesity, smoking) seems to go further than what would be explained by the prevalence and distribution of both. The drugs that act on the renin-angiotensin-aldosterone system are in many cases the backbone for the management of these diseases, it has been known for a long time that these drugs significantly increase the expression of receptors for angiotensin conversion enzyme type 2 in the lung tissue. This fact, together with the knowledge that the route of entry of the virus into the cell is precisely the ACE-2 receptor, initiated a hypothesis, based on very low-quality evidence, which quickly became generalized in the media, that the use of these drugs could be negative and that they should be interrupted immediately. The response of practically all Scientific Societies was almost immediate, with the precise indication that treatment with these drugs should not be discontinued, since the evidence of their usefulness is based on very solid and high-quality evidence. Simultaneously, a different hypothesis also appeared, also based on very preliminary evidence, that these drugs are not only harmful but also beneficial, however these medicaments are not yet accepted as agents for the prevention or treatment of this disease or its complications. This review reports current knowledge on the relationship between COVID-19 and SRAA.", "qid": 14, "docid": "l8flafv4", "rank": 57, "score": 0.7420742511749268}, {"content": "Title: COVID-19 in cardiac arrest and infection risk to rescuers: A systematic review Content: BACKGROUND: There may be a risk of COVID-19 transmission to rescuers delivering treatment for cardiac arrest. The aim of this review was to identify the potential risk of transmission associated with key interventions (chest compressions, defibrillation, cardiopulmonary resuscitation) to inform international treatment recommendations. METHODS: We undertook a systematic review comprising three questions: (1) aerosol generation associated with key interventions; (2) risk of airborne infection transmission associated with key interventions; and (3) the effect of different personal protective equipment strategies. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and the World Health Organization COVID-19 database on 24th March 2020. Eligibility criteria were developed individually for each question. We assessed risk of bias for individual studies, and used the GRADE process to assess evidence certainty by outcome. RESULTS: We included eleven studies: two cohort studies, one case control study, five case reports, and three manikin randomised controlled trials. We did not find any direct evidence that chest compressions or defibrillation either are or are not associated with aerosol generation or transmission of infection. Data from manikin studies indicates that donning of personal protective equipment delays treatment delivery. Studies provided only indirect evidence, with no study describing patients with COVID-19. Evidence certainty was low or very low for all outcomes. CONCLUSION: It is uncertain whether chest compressions or defibrillation cause aerosol generation or transmission of COVID-19 to rescuers. There is very limited evidence and a rapid need for further studies. Review registration: PROSPERO CRD42020175594.", "qid": 14, "docid": "lg7gw58n", "rank": 58, "score": 0.7412912845611572}, {"content": "Title: Anti-RAS drugs and SARS-CoV-2 infection Content: \u00e2\u0080\u00a2There is no enough evidence to indicate that ACEIs and ARBs result in ACE2 upregulation.\u00e2\u0080\u00a2The level of ACE2 expression is not completely related with the risk of COVID-19 infection.\u00e2\u0080\u00a2There is currently no evidence that ACEI/ARB increase risk for COVID-19 infection from clinical trials.\u00e2\u0080\u00a2It is not recommended that COVID-19 patients with hypertension or normal hypertensive patients at risk for exposure to stop using ACEI/ARB or change to other antihypertensive drugs.", "qid": 14, "docid": "z3w87lsj", "rank": 59, "score": 0.7412233352661133}, {"content": "Title: A snapshot of the ongoing clinical research on COVID-19 Content: The pandemic of coronavirus disease 2019 (COVID-19) presents an unprecedented challenge to rapidly develop new diagnostic, preventive and therapeutic strategies. Currently, thousands of new COVID-19 patients are quickly enrolled in clinical studies. We aimed to investigate the characteristics of the COVID-19 studies registered in ClinicalTrials.gov and report the extent to which they have incorporated features that are desirable for generating high-quality evidence. On April 28, 2020, a total of 945 studies on COVID-19 have been registered in ClinicalTrials.gov; 586 studies are interventional (62.0%), the most frequent allocation scheme is the parallel group assignment (437; 74.6%), they are open-label and the most common primary purpose is the research on treatment. Too many of the ongoing interventional studies have a small expected sample size and may not generate credible evidence at completion. This might lead to a delayed recognition of effective therapies that are urgently needed, and a waste of time and resources. In the COVID-19 pandemic era, it is crucial that the adoption of new diagnostic, preventive and therapeutic strategies is based upon evidence coming from well-designed, adequately powered and carefully conducted clinical trials.", "qid": 14, "docid": "6vfrs6q9", "rank": 60, "score": 0.7411237359046936}, {"content": "Title: Coronavirus disease (COVID-19): a scoping review Content: BACKGROUND: In December 2019, a pneumonia caused by a novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and has rapidly spread around the world since then. AIM: This study aims to understand the research gaps related to COVID-19 and propose recommendations for future research. METHODS: We undertook a scoping review of COVID-19, comprehensively searching databases and other sources to identify literature on COVID-19 between 1 December 2019 and 6 February 2020. We analysed the sources, publication date, type and topic of the retrieved articles/studies. RESULTS: We included 249 articles in this scoping review. More than half (59.0%) were conducted in China. Guidance/guidelines and consensuses statements (n = 56; 22.5%) were the most common. Most (n = 192; 77.1%) articles were published in peer-reviewed journals, 35 (14.1%) on preprint servers and 22 (8.8%) posted online. Ten genetic studies (4.0%) focused on the origin of SARS-CoV-2 while the topics of molecular studies varied. Nine of 22 epidemiological studies focused on estimating the basic reproduction number of COVID-19 infection (R(0)). Of all identified guidance/guidelines (n = 35), only ten fulfilled the strict principles of evidence-based practice. The number of articles published per day increased rapidly until the end of January. CONCLUSION: The number of articles on COVID-19 steadily increased before 6 February 2020. However, they lack diversity and are almost non-existent in some study fields, such as clinical research. The findings suggest that evidence for the development of clinical practice guidelines and public health policies will be improved when more results from clinical research becomes available.", "qid": 14, "docid": "nzbopcxg", "rank": 61, "score": 0.7407761812210083}, {"content": "Title: Eat, Pray, Work: A meta-analysis of COVID-19 Transmission Risk in Common Activities of Work and Leisure Content: ABSTRACT. BACKGROUND. When the lockdowns are relaxed, the responsibility of mitigating the COVID-19 spread shifts from the governments to the individuals. To know how to conduct one-self, it is important for everyone to know the risks of transmission during the quotidian activities - meetings, meals, etc, from individuals who are known to them and looking healthy. METHODS. The detailed case-studies corresponding to 425 infections upon point-exposures over a specified duration are curated. The data from the case studies is summarized and reorganized to reflect different situations from the daily life. A meta-analysis of the attack rates of transmission and the number of infections per infected person are performed. RESULTS. The attack rates are very high in family dinners (66.7% (48.8-80.8%)) compared to sit-down dinners with lesser mixing among people eating at different tables (15.7% (12.1-20.1%)), both lasting a couple of hours. In an open workspace office floor organized in a two-half structure with shared elevators and restrooms and the employees speaking continuously, the average attack rate over the course of a few days was much higher in one half (78.7% (70.3-85.3%)) than the one for the entire floor (43.5% (37.0-50.1%)). Inferred data suggests that the transmission in elevators and trains may be lower under the conditions of using masks. In most of the instances we studied, the infected individuals spreading (35/44) and even super-spreading (3/6) were mostly without symptoms of coughing, sneezing or a fever. CONCLUSIONS. Although the basic reproduction number R0 is around 3.0, the number of infections caused, including the super-spreading events, seem to be limited by the number of personal interactions in a group and their proximity. By acknowledging the risks in daily life, from healthy-looking persons, one may be able to organize their interactions better to reduce the chances of spreading or super-spreading infections.", "qid": 14, "docid": "luhfvp8e", "rank": 62, "score": 0.7403842210769653}, {"content": "Title: COvid MEdicaTion (COMET) study: protocol for a cohort study Content: Various theories about drugs such as ACE inhibitors or angiotensin II receptor blockers (ARBs) in relation to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and clinical outcomes of COVID-19 are circulating in both mainstream media and medical literature. These are based on the fact that ACE2 facilitates SARS-CoV-2 cell invasion via binding of a viral spike protein to ACE2. However, the effect of ACE inhibitors, ARBs and other drugs on ACE2 is unclear and all theories are based on conflicting evidence mainly from animal studies. Therefore, clinical evidence is urgently needed. The aim of this study is to investigate the relationship between use of these drugs on clinical outcome of patients with COVID-19. Patients will be included from several hospitals in Europe. Data will be collected in a user-friendly database (Digitalis) on an external server. Analyses will be adjusted for sex, age and presence of cardiovascular disease, hypertension and diabetes. These results will enable more rational choices for randomised controlled trials for preventive and therapeutic strategies in COVID-19.", "qid": 14, "docid": "fb1zgn7e", "rank": 63, "score": 0.740044355392456}, {"content": "Title: An Exploratory Study of COVID-19 Misinformation on Twitter Content: Although a lot of correct and useful information is shared through channels such as Twitter, it has also become a home ground for misinformation on COVID-19. To tackle this still ongoing infodemic, scientific oversight as well as a better understanding by practitioners in crisis management is needed. We have conducted an exploratory study into the propagation, authors and content of misinformation on Twitter around the topic of COVID-19 in order to gain early insights into the COVID-19 infodemic. Our results enable us to not only give first indications but also to suggest gaps in the current scientific coverage of the topic. Moreover, we propose actions for authorities to counter misinformation and hints for social media users on how to help stop the spread of misinformation.", "qid": 14, "docid": "pe39ov47", "rank": 64, "score": 0.7399399280548096}, {"content": "Title: COVID-19 pandemic-a focused review for clinicians Content: BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 remains a significant issue for global health, economics and society. A wealth of data has been generated since its emergence in December 2019, and it is vital for clinicians to keep up with this data from across the world at a time of uncertainty and constantly evolving guidelines and clinical practice. OBJECTIVES: Here we provide an update for clinicians on the recent developments in the virology, diagnostics, clinical presentation, viral shedding, and treatment options for COVID-19 based on current literature. SOURCES: We considered published peer-reviewed papers and non-peer-reviewed pre-print manuscripts on COVID19 and related aspects with an emphasis on clinical management aspects. CONTENT: We describe the virological characteristics of SARS-CoV-2 and the clinical course of COVID-19 with an emphasis on diagnostic challenges, duration of viral shedding, severity markers and current treatment options. IMPLICATIONS: The key challenge in managing COVID-19 remains patient density. However, accurate diagnosis as well as early identification and management of high-risk severe cases are important for many clinicians. For improved management of cases, there is a need to understand test probability of serology, qRT-PCR and radiological testing, and the efficacy of available treatment options that could be used in severe cases with a high risk of mortality.", "qid": 14, "docid": "f33f0868", "rank": 65, "score": 0.7395969033241272}, {"content": "Title: Evaluating Transmission Heterogeneity and Super-Spreading Event of COVID-19 in a Metropolis of China Content: COVID-19 caused rapid mass infection worldwide. Understanding its transmission characteristics, including heterogeneity and the emergence of super spreading events (SSEs) where certain individuals infect large numbers of secondary cases, is of vital importance for prediction and intervention of future epidemics. Here, we collected information of all infected cases (135 cases) between 21 January and 26 February 2020 from official public sources in Tianjin, a metropolis of China, and grouped them into 43 transmission chains with the largest chain of 45 cases and the longest chain of four generations. Utilizing a heterogeneous transmission model based on branching process along with a negative binomial offspring distribution, we estimated the reproductive number R and the dispersion parameter k (lower value indicating higher heterogeneity) to be 0.67 (95% CI: 0.54-0.84) and 0.25 (95% CI: 0.13-0.88), respectively. A super-spreader causing six infections was identified in Tianjin. In addition, our simulation allowing for heterogeneity showed that the outbreak in Tianjin would have caused 165 infections and sustained for 7.56 generations on average if no control measures had been taken by local government since 28 January. Our results highlighted more efforts are needed to verify the transmission heterogeneity of COVID-19 in other populations and its contributing factors.", "qid": 14, "docid": "uo7ixk9r", "rank": 66, "score": 0.7395001649856567}, {"content": "Title: Clinical management of COVID-19 Content: The novel coronavirus disease 2019 (COVID-19) with its early origin from Wuhan city in China has evolved into a global pandemic. Maximal precautionary measures and resources have been put forward by most nations in war footing to mitigate transmission and decrease fatality rates. This article was aimed to review the evidence on clinical management and to deal with the identification of high-risk groups, warning signs, appropriate investigations, proper sample collection for confirmation, general and specific treatment measures, strategies as well as infection control in the healthcare settings. Advanced age, cardiovascular disease, diabetes, hypertension and cancer have been found to be the risk factors for severe disease. Fever lasting for >five days with tachypnoea, tachycardia or hypotension are indications for urgent attention and hospitalization in a patient with suspected COVID-19. At present, reverse transcription-polymerase chain reaction (RT-PCR) from the upper respiratory tract samples is the diagnostic test of choice. While many drugs have shown in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are insufficient clinical data to promote or dissuade their usage. Among the currently available drugs, hydroxychloroquine and lopinavir/ritonavir may be considered for patients with severe COVID-19 infection, awaiting further clinical trials. Stringent droplet and contact precautions will protect healthcare workers against most clinical exposures to COVID-19.", "qid": 14, "docid": "o8towjim", "rank": 67, "score": 0.7394847869873047}, {"content": "Title: Clinical management of COVID-19. Content: The novel coronavirus disease 2019 (COVID-19) with its early origin from Wuhan city in China has evolved into a global pandemic. Maximal precautionary measures and resources have been put forward by most nations in war footing to mitigate transmission and decrease fatality rates. This article was aimed to review the evidence on clinical management and to deal with the identification of high-risk groups, warning signs, appropriate investigations, proper sample collection for confirmation, general and specific treatment measures, strategies as well as infection control in the healthcare settings. Advanced age, cardiovascular disease, diabetes, hypertension and cancer have been found to be the risk factors for severe disease. Fever lasting for >five days with tachypnoea, tachycardia or hypotension are indications for urgent attention and hospitalization in a patient with suspected COVID-19. At present, reverse transcription-polymerase chain reaction (RT-PCR) from the upper respiratory tract samples is the diagnostic test of choice. While many drugs have shown in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are insufficient clinical data to promote or dissuade their usage. Among the currently available drugs, hydroxychloroquine and lopinavir/ritonavir may be considered for patients with severe COVID-19 infection, awaiting further clinical trials. Stringent droplet and contact precautions will protect healthcare workers against most clinical exposures to COVID-19.", "qid": 14, "docid": "syhgjmf8", "rank": 68, "score": 0.7394847869873047}, {"content": "Title: Consideration of the Aerosol Transmission for COVID-19 and Public Health Content: This article analyzes the available evidence to address airborne, aerosol transmission of the SARS-CoV-2. We review and present three lines of evidence: case reports of transmission for asymptomatic individuals in association with studies that show that normal breathing and talking produce predominantly small droplets of the size that are subject to aerosol transport; limited empirical data that have recorded aerosolized SARS-CoV-2 particles that remain suspended in the air for hours and are subject to transport over distances including outside of rooms and intrabuilding, and the broader literature that further supports the importance of aerosol transmission of infectious diseases. The weight of the available evidence warrants immediate attention to address the significance of aerosols and implications for public health protection.", "qid": 14, "docid": "zb3ok9b8", "rank": 69, "score": 0.7394602298736572}, {"content": "Title: Treatment and research lines for the patient with COVID-19. What do we have and where are we going? Content: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents the most significant global public health crisis of this generation. From the beginning of the pandemic, several publications and on-line resources about different treatment lines have been done, and development effort in response to the COVID-19 pandemic to investigate potential therapies is unprecedented. Unfortunately, until now, there is not enough evidence to recommend any specific anti-COVID19 treatment. Randomized clinical trials and high-quality evidence, even in the middle of a pandemic, are needed. We provide a review of the latest published literature on the therapeutic strategies and current investigational lines for SARS-CoV-2.", "qid": 14, "docid": "okrpa7k7", "rank": 70, "score": 0.739169180393219}, {"content": "Title: A Chronological and Geographical Analysis of Personal Reports of COVID-19 on Twitter Content: The rapidly evolving outbreak of COVID-19 presents challenges for actively monitoring its spread. In this study, we assessed a social media mining approach for automatically analyzing the chronological and geographical distribution of users in the United States reporting personal information related to COVID-19 on Twitter. The results suggest that our natural language processing and machine learning framework could help provide an early indication of the spread of COVID-19.", "qid": 14, "docid": "8f1arjw1", "rank": 71, "score": 0.7389235496520996}, {"content": "Title: Transmission of SARS-CoV-2 by inhalation of respiratory aerosol in the Skagit Valley Chorale superspreading event Content: During the 2020 COVID-19 pandemic, an outbreak occurred following attendance of a symptomatic index case at a regular weekly rehearsal on 10 March of the Skagit Valley Chorale (SVC). After that rehearsal, 53 members of the SVC among 61 in attendance were confirmed or strongly suspected to have contracted COVID-19 and two died. Transmission by the airborne route is likely. It is vital to identify features of cases such as this so as to better understand the factors that promote superspreading events. Based on a conditional assumption that transmission during this outbreak was by inhalation of respiratory aerosol, we use the available evidence to infer the emission rate of airborne infectious quanta from the primary source. We also explore how the risk of infection would vary with several influential factors: the rates of removal of respiratory aerosol by ventilation; deposition onto surfaces; and viral decay. The results indicate an emission rate of the order of a thousand quanta per hour (mean [interquartile range] for this event = 970 [680-1190] quanta per hour) and demonstrate that the risk of infection is modulated by ventilation conditions, occupant density, and duration of shared presence with an infectious individual.", "qid": 14, "docid": "mazqe344", "rank": 72, "score": 0.7387650012969971}, {"content": "Title: Evaluating Transmission Heterogeneity and Super-Spreading Event of COVID-19 in a Metropolis of China Content: COVID-19 caused rapid mass infection worldwide. Understanding its transmission characteristics, including heterogeneity and the emergence of super spreading events (SSEs) where certain individuals infect large numbers of secondary cases, is of vital importance for prediction and intervention of future epidemics. Here, we collected information of all infected cases (135 cases) between 21 January and 26 February 2020 from official public sources in Tianjin, a metropolis of China, and grouped them into 43 transmission chains with the largest chain of 45 cases and the longest chain of four generations. Utilizing a heterogeneous transmission model based on branching process along with a negative binomial offspring distribution, we estimated the reproductive number R and the dispersion parameter k (lower value indicating higher heterogeneity) to be 0.67 (95% CI: 0.54\u20130.84) and 0.25 (95% CI: 0.13\u20130.88), respectively. A super-spreader causing six infections was identified in Tianjin. In addition, our simulation allowing for heterogeneity showed that the outbreak in Tianjin would have caused 165 infections and sustained for 7.56 generations on average if no control measures had been taken by local government since 28 January. Our results highlighted more efforts are needed to verify the transmission heterogeneity of COVID-19 in other populations and its contributing factors.", "qid": 14, "docid": "3v4sedfo", "rank": 73, "score": 0.7383284568786621}, {"content": "Title: Nursing homes and the elderly regarding the COVID-19 pandemic: situation report from Hungary Content: The global impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is significant in terms of public health effects and its long-term socio-economic implications. Among all social groups, the elderly is by far the most affected age group regarding morbidity and mortality. In multiple countries spanning several continents, there are an increasing number of reports referencing the novel coronavirus disease-2019 (COVID-19) spread among nursing homes. These areas are now recognized as potent hotspots regarding the pandemic, which one considers with special regard. Herein, we present currently available data of fatal COVID-19 cases throughout Hungary, along with the analysis of the co-morbidity network. We also report on viral genomic data originating from a nursing home resident. The genomic data was used for viral haplotype network analysis. We emphasize the urgent need for public health authorities to focus on nursing homes and residential service units worldwide, especially in the care of the elderly and infirmed. Our results further emphasize the recent statement released by the World Health Organization (WHO) regarding the vulnerability among seniors and especially the high risk of COVID-19 emergence throughout nursing and social homes.", "qid": 14, "docid": "8wzrnwqh", "rank": 74, "score": 0.7379657626152039}, {"content": "Title: Nursing homes and the elderly regarding the COVID-19 pandemic: situation report from Hungary. Content: The global impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is significant in terms of public health effects and its long-term socio-economic implications. Among all social groups, the elderly is by far the most affected age group regarding morbidity and mortality. In multiple countries spanning several continents, there are an increasing number of reports referencing the novel coronavirus disease-2019 (COVID-19) spread among nursing homes. These areas are now recognized as potent hotspots regarding the pandemic, which one considers with special regard. Herein, we present currently available data of fatal COVID-19 cases throughout Hungary, along with the analysis of the co-morbidity network. We also report on viral genomic data originating from a nursing home resident. The genomic data was used for viral haplotype network analysis. We emphasize the urgent need for public health authorities to focus on nursing homes and residential service units worldwide, especially in the care of the elderly and infirmed. Our results further emphasize the recent statement released by the World Health Organization (WHO) regarding the vulnerability among seniors and especially the high risk of COVID-19 emergence throughout nursing and social homes.", "qid": 14, "docid": "kftsaksm", "rank": 75, "score": 0.7379657626152039}, {"content": "Title: Sustaining containment of COVID-19: global sharing for pandemic response Content: The coronavirus disease 2019 (COVID-19) outbreak, caused by SARS-CoV-2, has rapidly escalated into a global pandemic One of our significant concerns is that we have no data as to whether people, who acquired immunity against this deadly virus and recovered from COVID-19, are protected from further infections with the same virus Moreover, we have no data as to whether this pandemic will persist in our societies and continue vexing us for long periods of time Implementing science-based response strategy is essential to sustain containment of COVID-19 globally Rapidly sharing scientific information means providing real-time research data and relevant findings As an international academic journal, Global Health & Medicine publishes this special issue entitled \"GHM Special Topic: COVID-19\" It includes a range of articles describing COVID-19 based on frontline data from Japan, China, the United States, Italy, the United Kingdom, and other countries and areas worldwide Our hope is that the rapid publication and sharing of information contribute, in whichever possible way, to this global fight against COVID-19", "qid": 14, "docid": "6v1ydxwi", "rank": 76, "score": 0.7378773093223572}, {"content": "Title: COVID-19 y el sistema renina, angiotensina, aldosterona. Una relaci\u00f3n compleja Content: The COVID-19 pandemic has had major negative health, psychological, social and economic repercussions for individuals, families, communities, countries and for humanity in general The interrelation with age and the presence of chronic non-communicable diseases (hypertension, diabetes, obesity, smoking) seems to go further than what would be explained by the prevalence and distribution of both The drugs that act on the renin-angiotensin-aldosterone system are in many cases the backbone for the management of these diseases, it has been known for a long time that these drugs significantly increase the expression of receptors for angiotensin conversion enzyme type 2 in the lung tissue This fact, together with the knowledge that the route of entry of the virus into the cell is precisely the ACE-2 receptor, initiated a hypothesis, based on very low-quality evidence, which quickly became generalized in the media, that the use of these drugs could be negative and that they should be interrupted immediately The response of practically all Scientific Societies was almost immediate, with the precise indication that treatment with these drugs should not be discontinued, since the evidence of their usefulness is based on very solid and high-quality evidence Simultaneously, a different hypothesis also appeared, also based on very preliminary evidence, that these drugs are not only harmful but also beneficial, however these medicaments are not yet accepted as agents for the prevention or treatment of this disease or its complications This review reports current knowledge on the relationship between COVID-19 and SRAA", "qid": 14, "docid": "oweh98z2", "rank": 77, "score": 0.7376616597175598}, {"content": "Title: COVID-19 Transmission in Dental Practice: Brief Review of Preventive Measures in Italy. Content: The outbreak and diffusion of SARS-CoV-2, responsible for the coronavirus disease (COVID-19), has caused an emergency in the health system worldwide. After a first development in Wuhan, China, the virus spread in other countries, with Italy registering the second highest number of cases in Europe on the 7th of April 2020 (135,586 in total). The World Health Organization declared the pandemic diffusion of COVID-19, and restrictive measures to limit contagion have been taken in several countries. The virus has a predominantly respiratory transmission through aerosol and droplets. The importance of infection control is therefore crucial in limiting the effects of virus diffusion. We aim to discuss the risks related to dental practice and current recommendations for dental practitioners. A literature search was performed to retrieve articles on the management of COVID-19 diffusion in dental practice. The documented clinical experience, the measures of professional prevention, and the actual Italian situation were reported and described. Four articles were retrieved from the literature search. Among the eligible articles, 3 reported measures to contrast COVID-19 diffusion. The infection management protocols suggested were reviewed. Finally, recommendations based on the Italian experience in terms of patient triage, patients' entrance into the practice, dental treatment, and after-treatment management are reported and discussed. COVID-19 is a major emergency worldwide, which should not be underestimated. Due to the rapidly evolving situation, further assessment of the implications of COVID-19 outbreak in dental practice is needed.", "qid": 14, "docid": "211cg2i4", "rank": 78, "score": 0.7376397848129272}, {"content": "Title: COVID-19 Transmission in Dental Practice: Brief Review of Preventive Measures in Italy Content: The outbreak and diffusion of SARS-CoV-2, responsible for the coronavirus disease (COVID-19), has caused an emergency in the health system worldwide. After a first development in Wuhan, China, the virus spread in other countries, with Italy registering the second highest number of cases in Europe on the 7th of April 2020 (135,586 in total). The World Health Organization declared the pandemic diffusion of COVID-19, and restrictive measures to limit contagion have been taken in several countries. The virus has a predominantly respiratory transmission through aerosol and droplets. The importance of infection control is therefore crucial in limiting the effects of virus diffusion. We aim to discuss the risks related to dental practice and current recommendations for dental practitioners. A literature search was performed to retrieve articles on the management of COVID-19 diffusion in dental practice. The documented clinical experience, the measures of professional prevention, and the actual Italian situation were reported and described. Four articles were retrieved from the literature search. Among the eligible articles, 3 reported measures to contrast COVID-19 diffusion. The infection management protocols suggested were reviewed. Finally, recommendations based on the Italian experience in terms of patient triage, patients' entrance into the practice, dental treatment, and after-treatment management are reported and discussed. COVID-19 is a major emergency worldwide, which should not be underestimated. Due to the rapidly evolving situation, further assessment of the implications of COVID-19 outbreak in dental practice is needed.", "qid": 14, "docid": "csvrhimj", "rank": 79, "score": 0.7376396656036377}, {"content": "Title: Evidence synthesis relevant to COVID-19: a protocol for multiple systematic reviews and overviews of systematic reviews. Content: Introduction The evidence on COVID-19 is being produced at high speed, so it is challenging for decision-makers to keep up. It seems appropriate, then, to put into practice a novel approach able to provide the scientific community and other interested parties with quality evidence that is actionable, and rapidly and efficiently produced. Methods and analysis We designed a protocol for multiple parallel systematic reviews and overviews of systematic reviews in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). We will search for primary studies and systematic reviews that answer different questions related to COVID-19 using both a centralized repository (Epistemonikos database) and a manual search in MEDLINE/PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. We will also search for literature in several other sources. At least two researchers will independently undertake the selection of studies, data extraction, and assessment of the quality of the included studies. We will synthesize data for each question using meta-analysis, when possible, and we will prepare Summary of Findings tables according to the GRADE approach. All the evidence will be organized in an open platform (L\u00b7OVE - Living OVerview of Evidence) that will be continuously updated using artificial intelligence and a broad network of experts. Ethics and dissemination No ethics approval is considered necessary. The results of these articles will be widely disseminated via peer-reviewed publications, social networks, and traditional media, and will be sent to relevant international organizations discussing this topic.", "qid": 14, "docid": "niclwyzx", "rank": 80, "score": 0.7375881671905518}, {"content": "Title: Rich at risk: socio-economic drivers of COVID-19 pandemic spread Content: COVID-19, the novel coronavirus affecting the most part of worldwide countries since early 2020, is fast increasing its prevalence around the world, representing a significant emergency for the population and the health systems at large. While proper treatments are being developed, in-depth studies concerning its way of diffusion are necessary, in order to understand how the virus is actually spreading, through the investigation on some socio-economic indicators for the various countries in the world, retrieved through open-access data publicly available. The correlation analysis displayed significant relationships between COVID-19 incidence with several of such indicators, including the Gross Domestic Product per capita and the number of flights per capita, whereas mortality is mainly related to the main age of the population. All such data displayed an interesting mean to understand the way the virus has diffused worldwide, possibly representing the basis for future preventive measures to effectively challenge a new COVID-19 pandemic wave, but also other, similar pandemics.", "qid": 14, "docid": "arhpqgl6", "rank": 81, "score": 0.7375539541244507}, {"content": "Title: Psychology in the prevention and management of covid-19. Contributions from the initial evidence/ La psicolog\u00eda en la prevenci\u00f3n y manejo del covid-19. Aportes desde la evidencia inicial Content: In December 2019, highly lethal cases of pneumonia were reported in Wuhan, Hubei Province, China (COVID-19). This disease has spread rapidly around the world with thousands of confirmed cases and deaths, becoming a pandemic and challenging public health systems. There is no vaccine or scientifically proven treatment yet, but the exact behaviours that can prevent transmission and spread have been identified. This article systematizes initial available information on psychology and COVID-19. It is discussed that much of the problem of the disease can be avoided by changing people\u2019s behaviors and that psychology can help explain, prevent and intervene to solve it. Psychology has scientific evidence available that explains all these phenomena, evidence that should be highlighted by the same actors in the disciplines available to other areas of knowledge and especially for decision makers.", "qid": 14, "docid": "ye7klrrp", "rank": 82, "score": 0.7374980449676514}, {"content": "Title: S\u00edntesis de evidencia relevante para COVID-19: protocolo com\u00fan para m\u00faltiples revisiones sistem\u00e1ticas y revisiones panor\u00e1micas./ S\u00edntesis de evidencia relevante para COVID-19: protocolo com\u00fan para m\u00faltiples revisiones sistem\u00e1ticas y revisiones panor\u00e1micas./ Evidence synthesis relevant to COVID-19: a protocol for multiple systematic reviews and overviews of systematic reviews Content: Introduction: The evidence on COVID-19 is being produced at high speed, so it is challenging for decision-makers to keep up. It seems appropriate, then, to put into practice a novel approach able to provide the scientific community and other interested parties with quality evidence that is actionable, and rapidly and efficiently produced. Methods and analysis: We designed a protocol for multiple parallel systematic reviews and overviews of systematic reviews in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). We will search for primary studies and systematic reviews that answer different questions related to COVID-19 using both a centralized repository (Epistemonikos database) and a manual search in MEDLINE/PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. We will also search for literature in several other sources. At least two researchers will independently undertake the selection of studies, data extraction, and assessment of the quality of the included studies. We will synthesize data for each question using meta-analysis, when possible, and we will prepare Summary of Findings tables according to the GRADE approach. All the evidence will be organized in an open platform (L\u00b7OVE - Living OVerview of Evidence) that will be continuously updated using artificial intelligence and a broad network of experts. Ethics and dissemination: No ethics approval is considered necessary. The results of these articles will be widely disseminated via peer-reviewed publications, social networks, and traditional media, and will be sent to relevant international organizations discussing this topic.", "qid": 14, "docid": "iif60bfe", "rank": 83, "score": 0.7374297380447388}, {"content": "Title: Appropriate care for neonates born to mothers with COVID-19 disease Content: The global COVID-19 pandemic has been associated with high rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, morbidity and mortality in the general population. Evidence-based guidance on caring for babies born to mothers with COVID-19 is needed. There is currently insufficient evidence to suggest vertical transmission between mothers and their newborn infants. However, transmission can happen after birth from mothers or other carers. Based on the currently available data, prolonged skin-to-skin contact and early and exclusive breastfeeding remain the best strategies to reduce the risks of morbidity and mortality for both the mother with COVID-19 and her baby.", "qid": 14, "docid": "rfmhszlu", "rank": 84, "score": 0.73726886510849}, {"content": "Title: Attempting to understand the spread of SARS-CoV-2: Associations between the number of cases in regions and selected economic and geographic parameters Content: We present in this work some results from analysing the spread of Covid-19 in different countries and regions around the world and the potential relations with climate, geographical location, and GDP. While the situation remains dynamic, we believe this analysis has the potential to uncover certain underlying trends. We primarily intend the results to drive further, more detailed analysis of the relevant data by other researchers that would help us gather a better understanding of the situation, aiding our preparedness. Our observations show that countries in high latitudes, with temperate and/or continental climate, and with reasonably\"open\"economies are the most vulnerable to this outbreak.", "qid": 14, "docid": "7bg4tx9q", "rank": 85, "score": 0.7368104457855225}, {"content": "Title: The mystery of the COVID toes \u2013 turning evidence-based medicine on its head Content: The recent and rapid emergence of COVID-19 infection has led to a flood of publications describing all aspects of the disease and its presentation. The appearance of chilblain-like lesions, in children and young adults has particularly caught the attention of healthcare professionals with an interest in the foot. With such a novel infection, demand for information is high at a time when evidence is scarce. Consequently, there has been a renaissance in the publication of case studies. This type of research, previously relegated from many mainstream journals, as a low level source of evidence, has permitted the rapid reporting, publication and dissemination of much needed clinical data which can be used as a foundation to inform further research and investigations about a new global infection.", "qid": 14, "docid": "rh2h4kpg", "rank": 86, "score": 0.7368085384368896}, {"content": "Title: The mystery of the COVID toes - turning evidence-based medicine on its head Content: The recent and rapid emergence of COVID-19 infection has led to a flood of publications describing all aspects of the disease and its presentation. The appearance of chilblain-like lesions, in children and young adults has particularly caught the attention of healthcare professionals with an interest in the foot. With such a novel infection, demand for information is high at a time when evidence is scarce. Consequently, there has been a renaissance in the publication of case studies. This type of research, previously relegated from many mainstream journals, as a low level source of evidence, has permitted the rapid reporting, publication and dissemination of much needed clinical data which can be used as a foundation to inform further research and investigations about a new global infection.", "qid": 14, "docid": "9a6ikm6v", "rank": 87, "score": 0.7368085384368896}, {"content": "Title: COVID-19 in cardiac arrest and infection risk to rescuers: a systematic review Content: Abstract Background There may be a risk of COVID-19 transmission to rescuers delivering treatment for cardiac arrest. The aim of this review was to identify the potential risk of transmission associated with key interventions (chest compressions, defibrillation, cardiopulmonary resuscitation) to inform international treatment recommendations. Methods We undertook a systematic review comprising three questions: 1) aerosol generation associated with key interventions; 2) risk of airborne infection transmission associated with key interventions; and 3) the effect of different personal protective equipment strategies. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and the World Health Organisation COVID-19 database on 24th March 2020. Eligibility criteria were developed individually for each question. We assessed risk of bias for individual studies, and used the GRADE process to assess evidence certainty by outcome. Results We included eleven studies: two cohort studies, one case control study, five case reports, and three manikin randomised controlled trials. We did not find any direct evidence that chest compressions or defibrillation either are or are not associated with aerosol generation or transmission of infection. Data from manikin studies indicates that donning of personal protective equipment delays treatment delivery. Studies provided only indirect evidence, with no study describing patients with COVID-19. Evidence certainty was low or very low for all outcomes. Conclusion It is uncertain whether chest compressions or defibrillation cause aerosol generation or transmission of COVID-19 to rescuers. There is very limited evidence and a rapid need for further studies. Review registration: PROSPERO CRD42020175594", "qid": 14, "docid": "y18nru1d", "rank": 88, "score": 0.7366629838943481}, {"content": "Title: Emerging patterns of hypercoagulability associated with critical COVID-19: A review Content: Abstract While the COVID-19 pandemic sweeps the world, much evidence is being gathered regarding its novel pathological mechanisms. It is the authors\u2019 clinical experience that patients in the intensive care unit suffering from COVID-19 are extremely pro-coagulable, with venous and arterial thromboembolism frequently observed, and losses of vascular access lines and filtration circuits to thrombosis now commonplace. Here, we explore the evidence for hypercoagulability in this group, presenting evidence of both a localised pulmonary hypercoagulability, and a systemic hypercoagulability resulting in thrombosis distant to the pulmonary vasculature. Furthermore, we discuss the possible risk factors exacerbated by, or selected for in COVID-19. We review the available evidence for use of plasma D-dimer as a prognostic marker, exploring the possibility that it acts as a marker of a COVID-19-associated hypercoagulability. We review the evidence for a pro-coagulant subtype of disseminated intravascular coagulation, discussing its clinical significance. Finally, we discuss the current evidence surrounding treatment of COVID-19 hypercoagulability, including prophylactic and treatment-dose heparin, thrombolytic agents, antiplatelet agents, and direct thrombin inhibitors, among others. We suggest areas in which further investigation is urgently needed to reduce the startling incidence of thrombosis in this group, a complication no doubt contributing to morbidity and mortality.", "qid": 14, "docid": "9khivobg", "rank": 89, "score": 0.7365679144859314}, {"content": "Title: Doubling time tells how effective Covid-19 prevention works Content: Covid-19 (coronavirus disease 2019) is a rapidly spreading pandemic in many countries. The total confirmed cases of Covid-19 are exponentially increasing and many countries are fighting Covid-19 with all strategies. However, there is still lacking consensus for effective strategies. Here, I demonstrate the time dependence of the doubling time in the Covid-19 exponential growths. Tracking the time-dependent doubling time tells how well Covid-19 prevention works, giving an index for successful fighting.", "qid": 14, "docid": "d950qa2w", "rank": 90, "score": 0.7364709973335266}, {"content": "Title: Current Paradigms in COVID-19 Research: Proposed Treatment Strategies, Recent Trends and Future Directions. Content: BACKGROUND Recent pandemic of coronavirus disease caused by a novel coronavirus SARS-CoV-2 in humans is the third outbreak by this family of viruses leading to an acute respiratory infection which has been a major cause of morbidity and mortality worldwide.The virus belongs to the genus, Betacoronavirus which has been recently reported to have significant similarity (>89%) to a severe acute respiratory syndrome (SARS)-related member of the Sarbecoviruses. Current researches are not sufficient to understand the etiological and immunopathobiological parameters related to COVID-19 so as to have a therapeutic solution to the problem. METHODS A structured search of bibliographic databases for peer-reviewed research literature has been carried out using focused review questions and inclusion/exclusion criteria. Further Standard tools were implied in order to appraise the quality of retrieved papers. The characteristic outcomes of screened research and review articles along with analysis of the interventions and findings of included studies using a conceptual framework have been described employing a deductive qualitative content analysis methodology. RESULTS This review systematically summarizes the immune-pathobiological characteristics, diagnosis, potential therapeutic options for the treatment and prevention of COVID-19 based on the current published literature and evidence. The current review has covered 125 peer-reviewed articles, majority of which are from high-income technically developed countries providing the most recent updates about the current understanding of the COVID-19 bringing all the significant findings and related researches together at a single platform. In addition, possible therapeutic interventions, treatment strategies and vaccine development initiatives to manage COVID-19 have been proposed. CONCLUSIONS It is anticipated that this review would certainly assist the public in general and scientific community in particular to recognize and effectively deal with COVID-19, providing a reference guide for futuristic studies.", "qid": 14, "docid": "dze2wezc", "rank": 91, "score": 0.7362970113754272}, {"content": "Title: COVID-19 and dental practice: Overview and protocols during pandemic Content: In December 2019, in Wuhan (China), there were described the first cases of a Severe Acute Respiratory Syndrome caused by SARS-CoV-2 and named COVID-19 Since then the disease has spread in several countries and in March 2020 the WHO declared it pandemic COVID-19 is associated with a wide range of manifestations from no symptoms to temperature cough, dyspnea, need for artificial ventilation and eventually death Mortality has been reported to be around 3% Cases of spreading from asymptomatic infected individuals have been documented It has become clear that among healthcare professionals, dentists are the most exposed category to the risk of such infection as the routes of transmission are contact, droplets and aerosol, therefore the necessity of providing clear guidelines has suddenly arisen This article is aimed at analysing the available literature about \"SARS-CoV-2\" and \"COVID-19\", and comparing it with the guidelines for other coronavirus infections and dental practice with a view to providing clinical recommendations about prevention and infection control in the dental environment", "qid": 14, "docid": "gsq9ycn1", "rank": 92, "score": 0.7360925674438477}, {"content": "Title: SARS-CoV-2 infection, clinical features and outcome of COVID-19 in United Kingdom nursing homes Content: OBJECTIVES: To understand SARS-Co-V-2 infection and transmission in UK nursing homes in order to develop preventive strategies for protecting the frail elderly residents. METHODS: An outbreak investigation involving 394 residents and 70 staff, was carried out in 4 nursing homes affected by COVID-19 outbreaks in central London. Two point-prevalence surveys were performed one week apart where residents underwent SARS-CoV-2 testing and had relevant symptoms documented. Asymptomatic staff from three of the four homes were also offered SARS-CoV-2 testing. RESULTS: Overall, 26% (95% CI 22-31) of residents died over the two-month period. All-cause mortality increased by 203% (95% CI 70-336) compared with previous years. Systematic testing identified 40% (95% CI 35-46) of residents as positive for SARS-CoV-2, and of these 43% (95% CI 34-52) were asymptomatic and 18% (95% CI 11-24) had only atypical symptoms; 4% (95% CI -1 to 9) of asymptomatic staff also tested positive. CONCLUSIONS: The SARS-CoV-2 outbreak in four UK nursing homes was associated with very high infection and mortality rates. Many residents developed either atypical or had no discernible symptoms. A number of asymptomatic staff members also tested positive, suggesting a role for regular screening of both residents and staff in mitigating future outbreaks.", "qid": 14, "docid": "pep6fqzm", "rank": 93, "score": 0.7359963059425354}, {"content": "Title: Fatal Superimposed Bacterial Sepsis in a Healthy Coronavirus (COVID-19) Patient Content: Coronavirus disease 2019 (COVID-19) is a highly infectious disease caused by the newly discovered coronavirus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). The novel coronavirus first emerged in Wuhan, China, in December 2019 and has led to a global pandemic. The virus mainly spreads through respiratory droplets from an infected person, but environmental contamination can also act as a source of infection, making social distancing an important key in containing the spread of infection. Those with underlying health conditions are more susceptible to complications such as acute respiratory distress syndrome, which can be fatal. However, healthy individuals experience a mild flu-like illness or may be asymptomatic, recuperating from the infection even without any particular intervention. We present a case of a healthy COVID positive individual, with no underlying comorbidities, who rapidly deteriorated overnight on readmission to the hospital after initial discharge and succumbed to this disease due to a superimposed bacterial infection with COVID pneumonia. This case report highlights the importance of educating COVID-19 positive patients about the precautions, as well as signs and symptoms of a superimposed bacterial infection, when their plan of care is in a home setting. It also emphasizes the potential role of checking procalcitonin levels as a part of routine laboratory investigation at initial presentation in all suspected as well as confirmed COVID-19 cases to rule out an on-going bacterial infection that can prove fatal in the course of the disease.", "qid": 14, "docid": "e05ywn5e", "rank": 94, "score": 0.7359960079193115}, {"content": "Title: What do we know about the SARS-CoV-2 coronavirus in the environment? Content: Abstract In view of the current situation regarding the Covid-19 disease, a discussion is proposed on the need for research focusing on the presence and evolution of the SARS-CoV-2 virus in water, soils and other environmental compartments, reached through wastewater and sewage sludge spreading. Also, the evaluation of current treatments for wastewater and sewage sludge, as well as the eventual development of new specific techniques, based on sorption, nanotechnology, etc., would be of great interest for controlling the environmental dissemination of these viruses in the current and eventual future outbreaks.", "qid": 14, "docid": "vr3p7ri6", "rank": 95, "score": 0.7357089519500732}, {"content": "Title: Evaluating transmission heterogeneity and super-spreading event of COVID-19 in a metropolis of China Content: Background: COVID-19 caused rapid mass infection worldwide. Understanding its transmission characteristics including heterogeneity is of vital importance for prediction and intervention of future epidemics. In addition, transmission heterogeneity usually envokes super spreading events (SSEs) where certain individuals infect large numbers of secondary cases. Till now, studies of transmission heterogeneity of COVID-19 and its underlying reason are far from reaching an agreement. MethodsWe collected information of all infected cases between January 21 and February 26, 2020 from official public sources in Tianjin, a metropolis of China. Utilizing a heterogeneous transmission model based on branching process along with a negative binomial offspring distribution, we estimated the reproductive number R and the dispersion parameter k which characterized the transmission potential and heterogeneity, respectively. Furthermore, we studied the SSE in Tianjin outbreak and evaluated the effect of control measures undertaken by local government based on the heterogeneous model. Results: A total of 135 confirmed cases (including 34 imported cases and 101 local infections) in Tianjin by February 26th 2020 entered the study. We grouped them into 43 transmission chains with the largest chain of 45 cases and the longest chain of 4 generations. The estimated reproduction number R was at 0.67 (95%CI: 0.54[~]0.84), and the dispersion parameter k was at 0.25 (95% CI: 0.13[~]0.88). A super spreader causing six infections in Tianjin, was identified. In addition, our simulation results showed that the outbreak in Tianjin would have caused 165 infections and sustained for 7.56 generations on average if no control measures had been taken by local government since January 28th. Conclusions: Our analysis suggested that the transmission of COVID-19 was subcritical but with significant heterogeneity and may incur SSE. More efforts are needed to verify the transmission heterogeneity of COVID-19 in other populations and its contributing factors, which is important for developing targeted measures to curb the pandemic.", "qid": 14, "docid": "uicvudil", "rank": 96, "score": 0.735633134841919}, {"content": "Title: No evidence of secondary transmission of COVID-19 from children attending school in Ireland, 2020 Content: As many countries begin to lift some of the restrictions to contain COVID-19 spread, lack of evidence of transmission in the school setting remains. We examined Irish notifications of SARS-CoV2 in the school setting before school closures on 12 March 2020 and identified no paediatric transmission. This adds to current evidence that children do not appear to be drivers of transmission, and we argue that reopening schools should be considered safe accompanied by certain measures.", "qid": 14, "docid": "i804iorq", "rank": 97, "score": 0.7355716228485107}, {"content": "Title: We urgently need guidelines for managing COVID\u201019 in children with comorbidities Content: I read with great interest the systematic review by Ludvigsson on the coronavirus disease 2019 (COVID-19) (1). The author needs to be complimented for a well-timed, rigorous and rapid synthesis of the evidence from the rather scant data available on how the virus affects children. The review, which focused on all papers published up to 19 March, drew important conclusions that have significant practical implications for those involved in providing acute care for children suffering from this disease.", "qid": 14, "docid": "x257ssbn", "rank": 98, "score": 0.735429584980011}, {"content": "Title: Anti-RAS drugs and SARS-CoV-2 infection Content: \u2022 There is no enough evidence to indicate that ACEIs and ARBs result in ACE2 upregulation. \u2022 The level of ACE2 expression is not completely related with the risk of COVID-19 infection. \u2022 There is currently no evidence that ACEI/ARB increase risk for COVID-19 infection from clinical trials. \u2022 It is not recommended that COVID-19 patients with hypertension or normal hypertensive patients at risk for exposure to stop using ACEI/ARB or change to other antihypertensive drugs.", "qid": 14, "docid": "5y8cc5eb", "rank": 99, "score": 0.7353507280349731}, {"content": "Title: Using models to identify routes of nosocomial infection: a large hospital outbreak of SARS in Hong Kong. Content: Two factors dominated the epidemiology of severe acute respiratory syndrome (SARS) during the 2002-2003 global outbreak, namely super-spreading events (SSE) and hospital infections. Although both factors were important during the first and the largest hospital outbreak in Hong Kong, the relative importance of different routes of infection has not yet been quantified. We estimated the parameters of a novel mathematical model of hospital infection using SARS episode data. These estimates described levels of transmission between the index super-spreader, staff and patients, and were used to compare three plausible hypotheses. The broadest of the supported hypotheses ascribes the initial surge in cases to a single super-spreading individual and suggests that the per capita risk of infection to patients increased approximately one month after the start of the outbreak. Our estimate for the number of cases caused by the SSE is substantially lower than the previously reported values, which were mostly based on self-reported exposure information. This discrepancy suggests that the early identification of the index case as a super-spreader might have led to biased contact tracing, resulting in too few cases being attributed to staff-to-staff transmission. We propose that in future outbreaks of SARS or other directly transmissible respiratory pathogens, simple mathematical models could be used to validate preliminary conclusions concerning the relative importance of different routes of transmission with important implications for infection control.", "qid": 14, "docid": "9mhcr9h4", "rank": 100, "score": 0.7353469133377075}]}
{"query": "how long can the coronavirus live outside the body", "hits": [{"content": "Title: Viral survival Content: How long do viruses like cold, flu and coronavirus survive outside the body? What factors affect this?", "qid": 15, "docid": "959w9sln", "rank": 1, "score": 0.8442553281784058}, {"content": "Title: Viral survival Content: How long do viruses like cold, flu and coronavirus survive outside the body? What factors affect this? Douglas Fairchild, Two Harbors, Minnesota, US", "qid": 15, "docid": "hgau3922", "rank": 2, "score": 0.8233121037483215}, {"content": "Title: A pandemic in all but name Content: The spread of the coronavirus beyond China is entering a critical new phase", "qid": 15, "docid": "j472b35n", "rank": 3, "score": 0.767600417137146}, {"content": "Title: Persistence of SARS-CoV-2 in the environment and COVID-19 transmission risk from environmental matrices and surfaces Content: The Coronavirus disease 2019 (COVID-19) is spreading around the world, representing a global pandemic, counting, as of June 5th, 2020, over 6,600,000 confirmed cases and more than 390,000 deaths, with exponentially increasing numbers. In the first half of 2020, because of the widespread of the COVID-19, researches were focused on the monitoring of SARS-CoV-2 in water, wastewater, sludge, air, and on surfaces, in order to assess the risk of contracting the viral infection from contaminated environments. So far, the survival of the novel Coronavirus out of the human body has been reported for short time periods (from hours to few days, in optimized in vitro conditions), mainly because of the need of an host organism which could consent the viral attack, and due to the weak external membrane of the virus. SARS-CoV-2 viral shedding strategies in the environment, either through animate and unanimate matrices, or exploiting the organic matter in water, wastewater, and waste in general, have been discussed in the present article. We concluded that, besides the high infectuousness of the novel Coronavirus, the transmission of the pathogen may be efficiently contained applying the adequate preventive measures (e.g., personal protection equipments, and disinfecting agents), indicated by national and international health authories.", "qid": 15, "docid": "b5lcv77o", "rank": 4, "score": 0.7616903781890869}, {"content": "Title: Persistence of SARS-CoV-2 in the environment and COVID-19 transmission risk from environmental matrices and surfaces() Content: The Coronavirus disease 2019 (COVID-19) is spreading around the world, representing a global pandemic, counting, as of June 5th, 2020, over 6,600,000 confirmed cases and more than 390,000 deaths, with exponentially increasing numbers. In the first half of 2020, because of the widespread of the COVID-19, researches were focused on the monitoring of SARS-CoV-2 in water, wastewater, sludge, air, and on surfaces, in order to assess the risk of contracting the viral infection from contaminated environments. So far, the survival of the novel Coronavirus out of the human body has been reported for short time periods (from hours to few days, in optimized in vitro conditions), mainly because of the need of an host organism which could consent the viral attack, and due to the weak external membrane of the virus. SARS-CoV-2 viral shedding strategies in the environment, either through animate and unanimate matrices, or exploiting the organic matter in water, wastewater, and waste in general, have been discussed in the present article. We concluded that, besides the high infectuousness of the novel Coronavirus, the transmission of the pathogen may be efficiently contained applying the adequate preventive measures (e.g., personal protection equipments, and disinfecting agents), indicated by national and international health authories.", "qid": 15, "docid": "kxyd5uzp", "rank": 5, "score": 0.7616902589797974}, {"content": "Title: A new threat from an old enemy: Re-emergence of coronavirus (Review) Content: The new outbreak of coronavirus from December 2019 has brought attention to an old viral enemy and has raised concerns as to the ability of current protection measures and the healthcare system to handle such a threat. It has been known since the 1960s that coronaviruses can cause respiratory infections in humans; however, their epidemic potential was understood only during the past two decades. In the present review, we address current knowledge on coronaviruses from a short history to epidemiology, pathogenesis, clinical manifestation of the disease, as well as treatment and prevention strategies. Although a great amount of research and efforts have been made worldwide to prevent further outbreaks of coronavirus-associated disease, the spread and lethality of the 2019 outbreak (COVID-19) is proving to be higher than previous epidemics on account of international travel density and immune naivety of the population. Only strong, joint and coordinated efforts of worldwide healthcare systems, researchers, and pharmaceutical companies and receptive national leaders will succeed in suppressing an outbreak of this scale.", "qid": 15, "docid": "9jb3w0zu", "rank": 6, "score": 0.755050778388977}, {"content": "Title: A new threat from an old enemy: Re\u00ademergence of coronavirus (Review) Content: The new outbreak of coronavirus from December 2019 has brought attention to an old viral enemy and has raised concerns as to the ability of current protection measures and the healthcare system to handle such a threat. It has been known since the 1960s that coronaviruses can cause respiratory infections in humans; however, their epidemic potential was understood only during the past two decades. In the present review, we address current knowledge on coronaviruses from a short history to epidemiology, pathogenesis, clinical manifestation of the disease, as well as treatment and prevention strategies. Although a great amount of research and efforts have been made worldwide to prevent further outbreaks of coronavirus\u00adassociated disease, the spread and lethality of the 2019 outbreak (COVID\u00ad19) is proving to be higher than previous epidemics on account of international travel density and immune naivety of the population. Only strong, joint and coordinated efforts of worldwide healthcare systems, researchers, and pharmaceutical companies and receptive national leaders will succeed in suppressing an outbreak of this scale.", "qid": 15, "docid": "fw0d8807", "rank": 7, "score": 0.7537561655044556}, {"content": "Title: Stability of SARS-CoV-2 on environmental surfaces and in human excreta Content: At room temperature, SARS-CoV-2 was stable on environmental surfaces and remained viable up to 7 days on smooth surfaces. This virus could survive for several hours in feces and 3-4 days in urine.", "qid": 15, "docid": "ej93duxi", "rank": 8, "score": 0.7537329196929932}, {"content": "Title: Coronavirus in water environments: Occurrence, persistence and concentration methods - A scoping review Content: Coronaviruses (CoV) are a large family of viruses causing a spectrum of disease ranging from the common cold to more severe diseases as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). The recent outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency worldwide. SARS-CoV-2, the virus responsible for COVID-19, is spread by human-to-human transmission via droplets or direct contact. However, since SARS-CoV-2 (as well as other coronaviruses) has been found in the fecal samples and anal swabs of some patients, the possibility of fecal-oral (including waterborne) transmission need to be investigated and clarified. This scoping review was conducted to summarize research data on CoV in water environments. A literature survey was conducted using the electronic databases PubMed, EMBASE, and Web Science Core Collection. This comprehensive research yielded more than 3000 records, but only 12 met the criteria and were included and discussed in this review. In detail, the review captured relevant studies investigating three main areas: 1) CoV persistence/survival in waters; 2) CoV occurrence in water environments; 3) methods for recovery of CoV from waters. The data available suggest that: i) CoV seems to have a low stability in the environment and is very sensitive to oxidants, like chlorine; ii) CoV appears to be inactivated significantly faster in water than non-enveloped human enteric viruses with known waterborne transmission; iii) temperature is an important factor influencing viral survival (the titer of infectious virus declines more rapidly at 23\u00b0C-25 \u00b0C than at 4 \u00b0C); iv) there is no current evidence that human coronaviruses are present in surface or ground waters or are transmitted through contaminated drinking-water; v) further research is needed to adapt to enveloped viruses the methods commonly used for sampling and concentration of enteric, non enveloped viruses from water environments. The evidence-based knowledge reported in this paper is useful to support risk analysis processes within the drinking and wastewater chain (i.e., water and sanitation safety planning) to protect human health from exposure to coronavirus through water.", "qid": 15, "docid": "hn9fj8h8", "rank": 9, "score": 0.7531588077545166}, {"content": "Title: Phylogenetic analysis of the first four SARS\u2010CoV\u20102 cases in Chile Content: The current pandemic caused by the new coronavirus is a worldwide public health concern. To aboard this emergency, and like never before, scientific groups around the world have been working in a fast and coordinated way to get the maximum of information about this virus when it has been almost 3 months since the first cases were detected in Wuhan province in China. The complete genome sequences of around 450 isolates are available, and studies about similarities and differences among them and with the close related viruses that caused similar epidemics in this century. In this work, we studied the complete genome of the first four cases of the new coronavirus disease in Chile, from patients who traveled to Europe and Southeast Asia. Our findings reveal at least two different viral variants entries to Chilean territory, coming from Europe and Asia. We also sub\u2010classified the isolates into variants according to punctual mutations in the genome. Our work contributes to global information about transmission dynamics and the importance to take control measures to stop the spread of the infection.", "qid": 15, "docid": "i4xjk61t", "rank": 10, "score": 0.7528880834579468}, {"content": "Title: Phylogenetic analysis of the first four SARS-CoV-2 cases in Chile Content: The current pandemic caused by the new coronavirus is a worldwide public health concern. To aboard this emergency, and like never before, scientific groups around the world have been working in a fast and coordinated way to get the maximum of information about this virus when it has been almost 3 months since the first cases were detected in Wuhan province in China. The complete genome sequences of around 450 isolates are available, and studies about similarities and differences among them and with the close related viruses that caused similar epidemics in this century. In this work, we studied the complete genome of the first four cases of the new coronavirus disease in Chile, from patients who traveled to Europe and Southeast Asia. Our findings reveal at least two different viral variants entries to Chilean territory, coming from Europe and Asia. We also sub-classified the isolates into variants according to punctual mutations in the genome. Our work contributes to global information about transmission dynamics and the importance to take control measures to stop the spread of the infection.", "qid": 15, "docid": "66j1icdo", "rank": 11, "score": 0.7511464357376099}, {"content": "Title: Stability and infectivity of coronaviruses in inanimate environments Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious virus that can transmit through respiratory droplets, aerosols, or contacts. Frequent touching of contaminated surfaces in public areas is therefore a potential route of SARS-CoV-2 transmission. The inanimate surfaces have often been described as a source of nosocomial infections. However, summaries on the transmissibility of coronaviruses from contaminated surfaces to induce the coronavirus disease 2019 are rare at present. This review aims to summarize data on the persistence of different coronaviruses on inanimate surfaces. The literature was systematically searched on Medline without language restrictions. All reports with experimental evidence on the duration persistence of coronaviruses on any type of surface were included. Most viruses from the respiratory tract, such as coronaviruses, influenza, SARS-CoV, or rhinovirus, can persist on surfaces for a few days. Persistence time on inanimate surfaces varied from minutes to up to one month, depending on the environmental conditions. SARS-CoV-2 can be sustained in air in closed unventilated buses for at least 30 min without losing infectivity. The most common coronaviruses may well survive or persist on surfaces for up to one month. Viruses in respiratory or fecal specimens can maintain infectivity for quite a long time at room temperature. Absorbent materials like cotton are safer than unabsorbent materials for protection from virus infection. The risk of transmission via touching contaminated paper is low. Preventive strategies such as washing hands and wearing masks are critical to the control of coronavirus disease 2019.", "qid": 15, "docid": "ou7w3zkv", "rank": 12, "score": 0.7457147836685181}, {"content": "Title: Does SARS-CoV-2 has a longer incubation period than SARS and MERS? Content: The outbreak of a novel coronavirus (SARS-CoV-2) since December 2019 in Wuhan, the major transportation hub in central China, became an emergency of major international concern. While several etiological studies have begun to reveal the specific biological features of this virus, the epidemic characteristics need to be elucidated. Notably, a long incubation time was reported to be associated with SARS-CoV-2 infection, leading to adjustments in screening and control policies. To avoid the risk of virus spread, all potentially exposed subjects are required to be isolated for 14 days, which is the longest predicted incubation time. However, based on our analysis of a larger dataset available so far, we find there is no observable difference between the incubation time for SARS-CoV-2, severe acute respiratory syndrome coronavirus (SARS-CoV), and middle east respiratory syndrome coronavirus (MERS-CoV), highlighting the need for larger and well-annotated datasets.", "qid": 15, "docid": "mcf0zvaf", "rank": 13, "score": 0.7442855834960938}, {"content": "Title: Does SARS\u2010CoV\u20102 has a longer incubation period than SARS and MERS? Content: The outbreak of a novel coronavirus (SARS\u2010CoV\u20102) since December 2019 in Wuhan, the major transportation hub in central China, became an emergency of major international concern. While several etiological studies have begun to reveal the specific biological features of this virus, the epidemic characteristics need to be elucidated. Notably, a long incubation time was reported to be associated with SARS\u2010CoV\u20102 infection, leading to adjustments in screening and control policies. To avoid the risk of virus spread, all potentially exposed subjects are required to be isolated for 14 days, which is the longest predicted incubation time. However, based on our analysis of a larger dataset available so far, we find there is no observable difference between the incubation time for SARS\u2010CoV\u20102, severe acute respiratory syndrome coronavirus (SARS\u2010CoV), and middle east respiratory syndrome coronavirus (MERS\u2010CoV), highlighting the need for larger and well\u2010annotated datasets.", "qid": 15, "docid": "p7ifetgw", "rank": 14, "score": 0.7438861727714539}, {"content": "Title: COVID-19 Surface Persistence: A Recent Data Summary and Its Importance for Medical and Dental Settings Content: Recently, due to the coronavirus pandemic, many guidelines and anti-contagion strategies continue to report unclear information about the persistence of coronavirus disease 2019 (COVID-19) in the environment. This certainly generates insecurity and fear in people, with an important psychological component that is not to be underestimated at this stage of the pandemic. The purpose of this article is to highlight all the sources currently present in the literature concerning the persistence of the different coronaviruses in the environment as well as in medical and dental settings. As this was a current study, there are still not many sources in the literature, and scientific strategies are moving towards therapy and diagnosis, rather than knowing the characteristics of the virus. Such an article could be an aid to summarize virus features and formulate new guidelines and anti-spread strategies.", "qid": 15, "docid": "6fmuh2or", "rank": 15, "score": 0.7438400983810425}, {"content": "Title: Risk of SARS-CoV-2 infection from contaminated water systems Content: Following the outbreak of severe acute respiratory syndrome coronavirus (SARS-CoV-2) in China, airborne water droplets (aerosols) have been identified as the main transmission route, although other transmission routes are likely to exist. We quantify SARS-CoV-2 virus survivability within water and the risk of infection posed by faecal contaminated water within 39 countries. We identify that the virus can remain stable within water for up to 25 days, and country specific relative risk of infection posed by faecal contaminated water is related to the environment. Faecal contaminated rivers, waterways and water systems within countries with high infection rates can provide infectious doses >100 copies within 100 ml of water. The implications for freshwater systems, the coastal marine environment and virus resurgence are discussed.", "qid": 15, "docid": "ycdok8fc", "rank": 16, "score": 0.7438117861747742}, {"content": "Title: Emergence of COVID-19 Infection: What Is Known and What Is to Be Expected-Narrative Review Article Content: BACKGROUND: The discovery of the coronavirus disease 2019 (COVID-19) during a pneumonia outbreak in Wuhan city (China) has raised a global public health concern, as the city consists of around 11 million people and is considered a major transport and logistics hub. This deadly virus caused the world to be in high alert as the death toll and the number of confirmed cases is continuously rising since the first case was reported. The Chinese government warned that the transmission ability of the virus is increasing, and international efforts are needed to overcome this outbreak. The purpose of this review is to focus on the published articles about the new virus, which will give an insight into the current state of research and data available, as well as recommending future studies. METHODS: For this narrative review, more than 20 relevant scientific articles and reports were considered from various databases (e.g., Google Scholar, PubMed and Science Direct) using keywords such as Coronavirus Outbreak, COVID-19, Emerging Epidemics, Emerging Infections, and Novel Coronavirus. RESULTS: The results from this review show that the situation is rapidly evolving, as human-to-human transmission is occurring, and the number of new cases and mortalities is increasing by the day and on a global level. There is still ambiguity about mutation risks and how the virus spreads as the source was not yet identified. Major gaps in knowledge about the origin of the virus, epidemiology and transmission impose a great challenge, which emphasizes the need for further studies in the future.", "qid": 15, "docid": "fqs40ivc", "rank": 17, "score": 0.7435933947563171}, {"content": "Title: Is SARS-CoV-2 Also an Enteric Pathogen With Potential Fecal-Oral Transmission? A COVID-19 Virological and Clinical Review Content: In as few as 3 months, coronavirus disease 2019 (COVID-19) has spread and ravaged the world at an unprecedented speed in modern history, rivaling the 1918 flu pandemic. Severe acute respiratory syndrome coronavirus-2, the culprit virus, is highly contagious and stable in the environment and transmits predominantly among humans via the respiratory route. Accumulating evidence suggest that this virus, like many of its related viruses, may also be an enteric virus that can spread via the fecal-oral route. Such a hypothesis would also contribute to the rapidity and proliferation of this pandemic. Here we briefly summarize what is known about this family of viruses and literature basis of the hypothesis that severe acute respiratory syndrome coronavirus-2 is capable of infecting the gastrointestinal tract and shedding in the environment for potential human-to-human transmission.", "qid": 15, "docid": "yyfuu197", "rank": 18, "score": 0.7432690262794495}, {"content": "Title: Survival of Coronaviruses in Water and Wastewater Content: The advent of severe acute respiratory syndrome and its potential environmental transmission indicates the need for more information on the survival of coronavirus in water and wastewater. The survival of representative coronaviruses, feline infectious peritonitis virus, and human coronavirus 229E was determined in filtered and unfiltered tap water (4 and 23\u00b0C) and wastewater (23\u00b0C). This was compared to poliovirus 1 under the same test conditions. Inactivation of coronaviruses in the test water was highly dependent on temperature, level of organic matter, and presence of antagonistic bacteria. The time required for the virus titer to decrease 99.9% (T(99.9)) shows that in tap water, coronaviruses are inactivated faster in water at 23\u00b0C (10 days) than in water at 4\u00b0C (>100 days). Coronaviruses die off rapidly in wastewater, with T(99.9) values of between 2 and 4 days. Poliovirus survived longer than coronaviruses in all test waters, except the 4\u00b0C tap water.", "qid": 15, "docid": "0y8lfjkx", "rank": 19, "score": 0.7423220872879028}, {"content": "Title: Coronavirus in water environments: Occurrence, persistence and concentration methods - A scoping review Content: Abstract Coronaviruses (CoV) are a large family of viruses causing a spectrum of disease ranging from the common cold to more severe diseases as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). The recent outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency worldwide. SARS-CoV-2, the virus responsible for COVID-19, is spread by human-to-human transmission via droplets or direct contact. However, since SARS-CoV-2 (as well as other coronaviruses) has been found in the fecal samples and anal swabs of some patients, the possibility of fecal-oral (including waterborne) transmission need to be investigated and clarified. This scoping review was conducted to summarize research data on CoV in water environments. A literature survey was conducted using the electronic databases PubMed, EMBASE, and Web Science Core Collection. This comprehensive research yielded more than 3000 records, but only 12 met the criteria and were included and discussed in this review. In detail, the review captured relevant studies investigating three main areas: 1) CoV persistence/survival in waters; 2) CoV occurrence in water environments; 3) methods for recovery of CoV from waters. The data available suggest that: i) CoV seems to have a low stability in the environment and is very sensitive to oxidants, like chlorine; ii) CoV appears to be inactivated significantly faster in water than non-enveloped human enteric viruses with known waterborne transmission; iii) temperature is an important factor influencing viral survival (the titer of infectious virus declines more rapidly at 23\u00b0C\u201325 \u00b0C than at 4 \u00b0C); iv) there is no current evidence that human coronaviruses are present in surface or ground waters or are transmitted through contaminated drinking-water; v) further research is needed to adapt to enveloped viruses the methods commonly used for sampling and concentration of enteric, non enveloped viruses from water environments. The evidence-based knowledge reported in this paper is useful to support risk analysis processes within the drinking and wastewater chain (i.e., water and sanitation safety planning) to protect human health from exposure to coronavirus through water.", "qid": 15, "docid": "eyf2dogw", "rank": 20, "score": 0.7422229051589966}, {"content": "Title: Effect of Environmental Conditions on SARS-CoV-2 Stability in Human Nasal Mucus and Sputum Content: We found that environmental conditions affect the stability of severe acute respiratory syndrome coronavirus 2 in nasal mucus and sputum. The virus is more stable at low-temperature and low-humidity conditions, whereas warmer temperature and higher humidity shortened half-life. Although infectious virus was undetectable after 48 hours, viral RNA remained detectable for 7 days.", "qid": 15, "docid": "04awj06g", "rank": 21, "score": 0.7419930100440979}, {"content": "Title: Effect of Environmental Conditions on SARS-CoV-2 Stability in Human Nasal Mucus and Sputum. Content: We found that environmental conditions affect the stability of severe acute respiratory syndrome coronavirus 2 in nasal mucus and sputum. The virus is more stable at low-temperature and low-humidity conditions, whereas warmer temperature and higher humidity shortened half-life. Although infectious virus was undetectable after 48 hours, viral RNA remained detectable for 7 days.", "qid": 15, "docid": "4819g00y", "rank": 22, "score": 0.7419930100440979}, {"content": "Title: Novel coronavirus 2019 (COVID-19): Emergence and implications for emergency care Content: A novel coronavirus (COVID-19) causing acute illness with severe symptoms has been isolated in Wuhan, Hubei Province, China. Since its emergence, cases have been found worldwide, reminiscent of severe acute respiratory syndrome and Middle East respiratory syndrome outbreaks over the past 2 decades. Current understanding of this epidemic remains limited due to its rapid development and available data. While occurrence outside mainland China remains low, the likelihood of increasing cases globally continues to rise. Given this potential, it is imperative that emergency clinicians understand the preliminary data behind the dynamics of this disease, recognize possible presentations of patients, and understand proposed treatment modalities.", "qid": 15, "docid": "xncs76xv", "rank": 23, "score": 0.7415218353271484}, {"content": "Title: Survival of surrogate coronaviruses in water Content: Abstract The emergence of a previously unknown coronavirus infection, Severe Acute Respiratory Syndrome (SARS), demonstrated that fecally contaminated liquid droplets are a potential vehicle for the spread of a respiratory virus to large numbers of people. To assess potential risks from this pathway, there is a need for surrogates for SARS coronavirus to provide representative data on viral survival in contaminated water. This study evaluated survival of two surrogate coronaviruses, transmissible gastroenteritis (TGEV) and mouse hepatitis (MHV). These viruses remained infectious in water and sewage for days to weeks. At 25\u00b0C, time required for 99% reduction in reagent-grade water was 22 days for TGEV and 17 days for MHV. In pasteurized settled sewage, times for 99% reduction were 9 days for TGEV and 7 days for MHV. At 4\u00b0C, there was <1log10 infectivity decrease for both viruses after four weeks. Coronaviruses can remain infectious for long periods in water and pasteurized settled sewage, suggesting contaminated water is a potential vehicle for human exposure if aerosols are generated.", "qid": 15, "docid": "hky6isk2", "rank": 24, "score": 0.7406934499740601}, {"content": "Title: Stability of bovine coronavirus on lettuce surfaces under household refrigeration conditions Content: Fecal suspensions with an aerosol route of transmission were responsible for a cluster of severe acute respiratory syndrome (SARS) cases in 2003 in Hong Kong. Based on that event, the World Health Organization recommended that research be implemented to define modes of transmission of SARS coronavirus through sewage, feces, food and water. Environmental studies have shown that animal coronaviruses remain infectious in water and sewage for up to a year depending on the temperature and humidity. In this study, we examined coronavirus stability on lettuce surfaces. A cell culture adapted bovine coronavirus, diluted in growth media or in bovine fecal suspensions to simulate fecal contamination was used to spike romaine lettuce. qRT-PCR detected viral RNA copy number ranging from 6.6 \u00d7 10(4) to 1.7 \u00d7 10(6) throughout the experimental period of 30 days. Whereas infectious viruses were detected for at least 14 days, the amount of infectious virus varied, depending upon the diluent used for spiking the lettuce. UV and confocal microscopic observation indicated attachment of residual labeled virions to the lettuce surface after the elution procedure, suggesting that rates of inactivation or detection of the virus may be underestimated. Thus, it is possible that contaminated vegetables may be potential vehicles for coronavirus zoonotic transmission to humans.", "qid": 15, "docid": "zmaw9lbz", "rank": 25, "score": 0.7401955127716064}, {"content": "Title: Weathering the pandemic: How the Caribbean Basin can use viral and environmental patterns to predict, prepare, and respond to COVID-19 Content: The 2020 coronavirus pandemic is developing at different paces throughout the world. Some areas, like the Caribbean Basin, have yet to see the virus strike at full force. When it does, there is reasonable evidence to suggest the consequent COVID-19 outbreaks will overwhelm healthcare systems and economies. This is particularly concerning in the Caribbean as pandemics can have disproportionately higher mortality impacts on lower and middle-income countries. Preliminary observations from our team and others suggest that temperature and climatological factors could influence the spread of this novel coronavirus, making spatiotemporal predictions of its infectiousness possible. This review studies geographic and time-based distribution of known respiratory viruses in the Caribbean Basin in an attempt to foresee how the pandemic will develop in this region. This review is meant to aid in planning short- and long-term interventions to manage outbreaks at the international, national, and subnational levels in the region.", "qid": 15, "docid": "w5kjmw88", "rank": 26, "score": 0.7391147613525391}, {"content": "Title: COVID-19 Epidemic Outside China: 34 Founders and Exponential Growth Content: Background: In December 2019, pneumonia infected with a novel coronavirus burst in Wuhan, China. Now the situation is almost controlled in China but is worse outside China. We aimed to build a mathematical model to capture the global trend of epidemics outside China. Methods: In this retrospective, outside-China diagnosis number reported from Jan 21 to Feb 28, 2020 was downloaded from WHO website. We develop a simple regression model on these numbers: log10 (Nt+34)=0.0515*t+2.075 where Nt is the total diagnosed patient till the ith day, t=1 at Feb 1. Findings: Based on this model, we estimate that there have been about 34 unobserved founder patients at the beginning of spread outside China. The global trend is approximately exponential, with the rate of 10 folds every 19 days.", "qid": 15, "docid": "7reqkx3h", "rank": 27, "score": 0.7387043237686157}, {"content": "Title: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): a review Content: In recent years, the prevalence and spread of coronavirus has had a huge impact on global public health. Due to the incomplete understanding of the pathogenic mechanism of the virus, it is difficult for humans to fight against the virus quickly and effectively once the outbreak occurs. In early 2020, a novel coronavirus was discovered in Wuhan, China. Soon after, similar cases were found in other countries around the world, and the number of infected people increased rapidly. So far, the global cumulative number of infected people has exceeded 3 million, and more than 200,000 people have died, which has had a huge impact on global human health and economic development. Every outbreak of disease makes a deep impression on mankind. Herein, we summarize the virology, epidemiology, clinical manifestations, diagnosis, treatment and prevention of SARS-CoV-2, and hope that countries can control the outbreak as soon as possible to minimize the loss.", "qid": 15, "docid": "5l1bknw2", "rank": 28, "score": 0.7380067706108093}, {"content": "Title: Extra-pulmonary complications of COVID-19: a multi-system disease? Content: The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been recently declared a pandemic by the World Health Organization. In addition to its acute respiratory manifestations, SARS-CoV-2 may also adversely affect other organ systems. To date, however, there is very limited understanding of the extent and management of COVID-19-related conditions outside of the pulmonary system. This narrative review provides an overview of the current literature about the extra-pulmonary manifestations of COVID-19 that may affect the urinary, cardiovascular, gastrointestinal, hematological, hematopoietic, neurological, or reproductive systems. This review also describes current understanding of the extra-pulmonary complications caused by COVID-19 in order to improve the management and prognosis of patients with COVID-19. This article is protected by copyright. All rights reserved.", "qid": 15, "docid": "t9dpmh0h", "rank": 29, "score": 0.7375927567481995}, {"content": "Title: Effective Heat Inactivation of SARS-CoV-2 Content: The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) has quickly turned into a global pandemic. Infectious viruses had been isolated from oro- or naso-pharyngeal swabs, sputum and possibly stool samples of infected individuals. Handling these clinical specimens therefore poses a biosafety risk to both healthcare professionals and laboratory workers. In this study, we aimed to evaluate the stability of SARS-CoV-2 under different heat conditions and report that the virus is stable at 37 C for at least 24 hours. Heating at 56 C for 30 minutes, however, effectively inactivated the virus while preserved the stability of viral RNA in both human sera and sputum samples. These findings provide critical information regarding the biology of the virus as well as a practical way to inactivate infectious virus that is potentially found in clinical specimens.", "qid": 15, "docid": "og69izi3", "rank": 30, "score": 0.7369605302810669}, {"content": "Title: Novel Coronavirus Outbreak in Wuhan, China, 2020: Intense Surveillance Is Vital for Preventing Sustained Transmission in New Locations Content: The outbreak of pneumonia originating in Wuhan, China, has generated 24,500 confirmed cases, including 492 deaths, as of 5 February 2020. The virus (2019-nCoV) has spread elsewhere in China and to 24 countries, including South Korea, Thailand, Japan and USA. Fortunately, there has only been limited human-to-human transmission outside of China. Here, we assess the risk of sustained transmission whenever the coronavirus arrives in other countries. Data describing the times from symptom onset to hospitalisation for 47 patients infected early in the current outbreak are used to generate an estimate for the probability that an imported case is followed by sustained human-to-human transmission. Under the assumptions that the imported case is representative of the patients in China, and that the 2019-nCoV is similarly transmissible to the SARS coronavirus, the probability that an imported case is followed by sustained human-to-human transmission is 0.41 (credible interval [0.27, 0.55]). However, if the mean time from symptom onset to hospitalisation can be halved by intense surveillance, then the probability that an imported case leads to sustained transmission is only 0.012 (credible interval [0, 0.099]). This emphasises the importance of current surveillance efforts in countries around the world, to ensure that the ongoing outbreak will not become a global pandemic.", "qid": 15, "docid": "bim76jna", "rank": 31, "score": 0.7356922626495361}, {"content": "Title: Weathering the pandemic: How the Caribbean Basin can use viral and environmental patterns to predict, prepare and respond to COVID\u201019 Content: The 2020 coronavirus pandemic is developing at different paces throughout the world. Some areas, like the Caribbean Basin, have yet to see the virus strike at full force. When it does, there is reasonable evidence to suggest the consequent COVID\u201019 outbreaks will overwhelm healthcare systems and economies. This is particularly concerning in the Caribbean as pandemics can have disproportionately higher mortality impacts on lower and middle income countries. Preliminary observations from our team and others suggest that temperature and climatological factors could influence the spread of this novel coronavirus, making spatiotemporal predictions of its infectiousness possible. This review studies geographic and time\u2010based distribution of known respiratory viruses in the Caribbean Basin in an attempt to foresee how the pandemic will develop in this region. This review is meant to aid in planning short\u2010 and long\u2010term interventions to manage outbreaks at the international, national and sub\u2010national levels in the region. This article is protected by copyright. All rights reserved.", "qid": 15, "docid": "gan10za0", "rank": 32, "score": 0.7355200052261353}, {"content": "Title: A Simulation on Potential Secondary Spread of Novel Coronavirus in an Exported Country Using a Stochastic Epidemic SEIR Model Content: Ongoing outbreak of pneumonia caused by novel coronavirus (2019-nCoV) began in December 2019 in Wuhan, China, and the number of new patients continues to increase. Even though it began to spread to many other parts of the world, such as other Asian countries, the Americas, Europe, and the Middle East, the impact of secondary outbreaks caused by exported cases outside China remains unclear. We conducted simulations to estimate the impact of potential secondary outbreaks in a community outside China. Simulations using stochastic SEIR model were conducted, assuming one patient was imported to a community. Among 45 possible scenarios we prepared, the worst scenario resulted in the total number of persons recovered or removed to be 997 (95% CrI 990\u20131000) at day 100 and a maximum number of symptomatic infectious patients per day of 335 (95% CrI 232\u2013478). Calculated mean basic reproductive number (R(0)) was 6.5 (Interquartile range, IQR 5.6\u20137.2). However, better case scenarios with different parameters led to no secondary cases. Altering parameters, especially time to hospital visit. could change the impact of a secondary outbreak. With these multiple scenarios with different parameters, healthcare professionals might be able to better prepare for this viral infection.", "qid": 15, "docid": "rbwcm3hq", "rank": 33, "score": 0.7355017066001892}, {"content": "Title: Novel coronavirus 2019 (COVID\u201019): Emergence and implications for emergency care Content: A novel coronavirus (COVID\u201019) causing acute illness with severe symptoms has been isolated in Wuhan, Hubei Province, China. Since its emergence, cases have been found worldwide, reminiscent of severe acute respiratory syndrome and Middle East respiratory syndrome outbreaks over the past 2 decades. Current understanding of this epidemic remains limited due to its rapid development and available data. While occurrence outside mainland China remains low, the likelihood of increasing cases globally continues to rise. Given this potential, it is imperative that emergency clinicians understand the preliminary data behind the dynamics of this disease, recognize possible presentations of patients, and understand proposed treatment modalities.", "qid": 15, "docid": "w0mt034a", "rank": 34, "score": 0.7344825267791748}, {"content": "Title: Lessons from mainland China's epidemic experience about the growth rules of infected and recovered cases of COVID-19 worldwide Content: The novel coronavirus disease (COVID-19) that emerged at the end of 2019 has been controlled in mainland China so far, while it is still spreading globally. When the pandemic will end is a question of great concern. A logistic model depicting the growth rules of infected and recovered cases in mainland China may shed some light on this question. We extended this model to 31 countries outside China experiencing serious COVID-2019 outbreaks. The model well explained the data in our study (R2 >0.95). For infected cases, the semi-saturation period (SSP) ranges from 63 to 170 days (March 3 to June 18). The logistic growth rate of infected cases is positively correlated with that of recovered cases, and the same holds for the SSP. According to the linear connection between the growth rules for infected and recovered cases identified from the Chinese data, we predicted that the SSP of the recovered cases outside China ranges from 82 to 196 days (March 22 to July 8). More importantly, we found a strong positive correlation between the SSP of infected cases and the timing of the government's response, providing strong evidence for the effectiveness of rapid epidemic control measures in various countries.", "qid": 15, "docid": "yoe3eelz", "rank": 35, "score": 0.7344107627868652}, {"content": "Title: Transmission of SARS-CoV-2: an update of current literature Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent for the 2019 coronavirus disease (COVID-19) pandemic, has caused a public health emergency. The need for additional research in viral pathogenesis is essential as the number of cases and deaths rise. Understanding the virus and its ability to cause disease has been the main focus of current literature; however, there is much unknown. Studies have revealed new findings related to the full transmission potential of SARS-CoV-2 and its subsequent ability to cause infection by different means. The virus is hypothesized to be of increased virulence compared with previous coronavirus that caused epidemics, in part due to its overall structural integrity and resilience to inactivation. To date, many studies have discussed that the rationale behind its transmission potential is that viral RNA has unexpectedly been detected in multiple bodily fluids, with some samples having remained positive for extended periods of time. Additionally, the receptor by which the virus gains cellular entry, ACE2, has been found to be expressed in different human body systems, thereby potentiating its infection in those locations. In this evidence-based comprehensive review, we discuss various potential routes of transmission of SARS-CoV-2\u2014respiratory/droplet, indirect, fecal-oral, vertical, sexual, and ocular. Understanding these different routes is important as they pertain to clinical practice, especially in taking preventative measures to mitigate the spread of SARS-CoV-2.", "qid": 15, "docid": "cfv0ta10", "rank": 36, "score": 0.7341208457946777}, {"content": "Title: Distributions and risks of SARS-CoV-2 in hospital outdoor environment Content: The outbreak of coronavirus infectious disease-2019 (COVID-19) pneumonia since 2019 has rapidly spread throughout over 200 countries around the world. Till 14th May 2020, there are over 4 million confirmed cases and 300,000 deaths globally. To date, numerous studies focus on the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in indoor areas for its main transmission routes via human respiratory droplets and direct contact. It remains unclear about the distribution and transmission risks of SARS-CoV-2 in outdoor environment despite its threats to healthy people and communities. Here, we investigated the presence of SARS-CoV-2 virus in 73 specimens from outdoor environment of three hospitals in Wuhan. We found SARS-CoV-2 in soils (205-550 copies/g), wastewaters (255 to 1.9x104 copies/L) and aerosols (285-1130 copies/m3) in locations close to departments receiving COVID-19 patients or in wastewater treatment sectors, which revealed significant viral spill-over in hospital outdoor environment that was possibly via respiratory droplets from patients or airborne aerosols from wastewater containing SARS-CoV-2. In contrast, SARS-CoV-2 was not detected in other areas or on surfaces with regular disinfection. Soils eventually behave as viral receptors through deposition and potentially a secondary source spreading SARS-CoV-2 for a prolonged time. Our findings map the high-risk areas in hospital outdoor environment possessing spread risks of SARS-CoV-2, which require particular attention and complete sanitation for preventing SARS-CoV-2 outdoor transmission.", "qid": 15, "docid": "i9n71aw9", "rank": 37, "score": 0.7329518795013428}, {"content": "Title: 2019-20 Wuhan coronavirus outbreak: Intense surveillance is vital for preventing sustained transmission in new locations Content: The outbreak of pneumonia originating in Wuhan, China, has generated 830 confirmed cases, including 26 deaths, as of 24 January 2020. The virus (2019-nCoV) has spread elsewhere in China and to other countries, including South Korea, Thailand, Japan and USA. Fortunately, there has not yet been evidence of sustained human-to-human transmission outside of China. Here we assess the risk of sustained transmission whenever the coronavirus arrives in other countries. Data describing the times from symptom onset to hospitalisation for 47 patients infected in the current outbreak are used to generate an estimate for the probability that an imported case is followed by sustained human-to-human transmission. Under the assumptions that the imported case is representative of the patients in China, and that the 2019-nCoV is similarly transmissible to the SARS coronavirus, the probability that an imported case is followed by sustained human-to-human transmission is 0.37. However, if the mean time from symptom onset to hospitalisation can be halved by intense surveillance, then the probability that an imported case leads to sustained transmission is only 0.005. This emphasises the importance of current surveillance efforts in countries around the world, to ensure that the ongoing outbreak will not become a large global epidemic.", "qid": 15, "docid": "qpaig5tm", "rank": 38, "score": 0.7323048710823059}, {"content": "Title: SARS-CoV-2 Shedding from Asymptomatic Patients: Contribution of Potential Extrapulmonary Tissue Reservoirs Content: The ongoing pandemic COVID-19, caused by SARS-CoV-2, has already resulted in more than 3 million cases and more than 200,000 deaths globally. Significant clinical presentations of COVID-19 include respiratory symptoms and pneumonia. In a minority of patients, extrapulmonary organs (central nervous system, eyes, heart, and gut) are affected, with detection of viral RNA in bodily secretions (stool, tears, and saliva). Infection of such extrapulmonary organs may serve as a reservoir for SARS-CoV-2, representing a potential source of viral shedding after the cessation of respiratory symptoms in recovered patients or in asymptomatic individuals. It is extremely important to understand this phenomenon, as individuals with intermittent virus shedding could be falsely identified as reinfected and may benefit from ongoing antiviral treatment. The potential of SARS-CoV-2 infection to rapidly disseminate and infect extrapulmonary organs is likely mediated through the nonstructural and accessory proteins of SARS-CoV-2, which act as ligands for host cells, and through evasion of host immune responses. The focus of this perspective is the extrapulmonary tissues affected by SARS-CoV-2 and the potential implications of their involvement for disease pathogenesis and the development of medical countermeasures.", "qid": 15, "docid": "r5qyroo3", "rank": 39, "score": 0.7322512865066528}, {"content": "Title: SARS-CoV-2 Shedding from Asymptomatic Patients: Contribution of Potential Extrapulmonary Tissue Reservoirs. Content: The ongoing pandemic COVID-19, caused by SARS-CoV-2, has already resulted in more than 3 million cases and more than 200,000 deaths globally. Significant clinical presentations of COVID-19 include respiratory symptoms and pneumonia. In a minority of patients, extrapulmonary organs (central nervous system, eyes, heart, and gut) are affected, with detection of viral RNA in bodily secretions (stool, tears, and saliva). Infection of such extrapulmonary organs may serve as a reservoir for SARS-CoV-2, representing a potential source of viral shedding after the cessation of respiratory symptoms in recovered patients or in asymptomatic individuals. It is extremely important to understand this phenomenon, as individuals with intermittent virus shedding could be falsely identified as reinfected and may benefit from ongoing antiviral treatment. The potential of SARS-CoV-2 infection to rapidly disseminate and infect extrapulmonary organs is likely mediated through the nonstructural and accessory proteins of SARS-CoV-2, which act as ligands for host cells, and through evasion of host immune responses. The focus of this perspective is the extrapulmonary tissues affected by SARS-CoV-2 and the potential implications of their involvement for disease pathogenesis and the development of medical countermeasures.", "qid": 15, "docid": "g948h572", "rank": 40, "score": 0.7322512865066528}, {"content": "Title: Duration of viral detection in throat and rectum of a patient with COVID-19 Content: The rapid spread of coronavirus disease 2019 (COVID-19) raises concern about a global pandemic. Knowledge about the duration of viral shedding remains important for patient management and infection control. We report the duration of viral detection in throat and rectum of a COVID-19 patient treated at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. Despite clinical recovery, SARS-CoV-2 RNA remained detectable by real time RT-PCR in throat and rectal swabs until day 11 and 18 of hospitalization, respectively. Because live SARS-CoV-2 has been successfully isolated from a stool sample from a COVID-19 patient in China, the results demonstrate that COVID-19 patients may remain infectious for long periods, and fecal-oral transmission may be possible. Therefore, our finding has important implications for infection control.", "qid": 15, "docid": "q4i9kh65", "rank": 41, "score": 0.7321518659591675}, {"content": "Title: Use of Twitter social media activity as a proxy for human mobility to predict the spatiotemporal spread of COVID-19 at global scale Content: As of February 27, 2020, 82,294 confirmed cases of coronavirus disease (COVID-19) have been reported since December 2019, including 2,804 deaths, with cases reported throughout China, as well as in 45 international locations outside of mainland China. We predict the spatiotemporal spread of reported COVID- 19 cases at the global level during the first few weeks of the current outbreak by analyzing openly available geolocated Twitter social media data. Human mobility patterns were estimated by analyzing geolocated 2013-2015 Twitter data from users who had: i) tweeted at least twice on consecutive days from Wuhan, China, between November 1, 2013, and January 28, 2014, and November 1, 2014, and January 28, 2015; and ii) left Wuhan following their second tweet during the time period under investigation. Publicly available COVID-19 case data were used to investigate the correlation among cases reported during the current outbreak, locations visited by the study cohort of Twitter users, and airports with scheduled flights from Wuhan. Infectious Disease Vulnerability Index (IDVI) data were obtained to identify the capacity of countries receiving travellers from Wuhan to respond to COVID-19. Our study cohort comprised 161 users. Of these users, 133 (82.6%) posted tweets from 157 Chinese cities (1,344 tweets) during the 30 days after leaving Wuhan following their second tweet, with a median of 2 (IQR= 1-3) locations visited and a mean distance of 601 km (IQR= 295.2-834.7 km) traveled. Of our user cohort, 60 (37.2%) traveled abroad to 119 locations in 28 countries. Of the 82 COVID-19 cases reported outside China as of January 30, 2020, 54 cases had known geolocation coordinates and 74.1% (40 cases) were reported less than 15 km (median = 7.4 km, IQR= 2.9-285.5 km) from a location visited by at least one of our study cohort's users. Countries visited by the cohort's users and which have cases reported by January 30, 2020, had a median IDVI equal to 0.74. We show that social media data can be used to predict the spatiotemporal spread of infectious diseases such as COVID-19. Based on our analyses, we anticipate cases to be reported in Saudi Arabia and Indonesia; additionally, countries with a moderate to low IDVI (i.e. &#8804;0.7) such as Indonesia, Pakistan, and Turkey should be on high alert and develop COVID- 19 response plans as soon as permitting.", "qid": 15, "docid": "cmjefr4a", "rank": 42, "score": 0.7317919135093689}, {"content": "Title: Use of Twitter social media activity as a proxy for human mobility to predict the spatiotemporal spread of COVID-19 at global scale. Content: As of February 27, 2020, 82,294 confirmed cases of coronavirus disease (COVID-19) have been reported since December 2019, including 2,804 deaths, with cases reported throughout China, as well as in 45 international locations outside of mainland China. We predict the spatiotemporal spread of reported COVID- 19 cases at the global level during the first few weeks of the current outbreak by analyzing openly available geolocated Twitter social media data. Human mobility patterns were estimated by analyzing geolocated 2013-2015 Twitter data from users who had: i) tweeted at least twice on consecutive days from Wuhan, China, between November 1, 2013, and January 28, 2014, and November 1, 2014, and January 28, 2015; and ii) left Wuhan following their second tweet during the time period under investigation. Publicly available COVID-19 case data were used to investigate the correlation among cases reported during the current outbreak, locations visited by the study cohort of Twitter users, and airports with scheduled flights from Wuhan. Infectious Disease Vulnerability Index (IDVI) data were obtained to identify the capacity of countries receiving travellers from Wuhan to respond to COVID-19. Our study cohort comprised 161 users. Of these users, 133 (82.6%) posted tweets from 157 Chinese cities (1,344 tweets) during the 30 days after leaving Wuhan following their second tweet, with a median of 2 (IQR= 1-3) locations visited and a mean distance of 601 km (IQR= 295.2-834.7 km) traveled. Of our user cohort, 60 (37.2%) traveled abroad to 119 locations in 28 countries. Of the 82 COVID-19 cases reported outside China as of January 30, 2020, 54 cases had known geolocation coordinates and 74.1% (40 cases) were reported less than 15 km (median = 7.4 km, IQR= 2.9-285.5 km) from a location visited by at least one of our study cohort's users. Countries visited by the cohort's users and which have cases reported by January 30, 2020, had a median IDVI equal to 0.74. We show that social media data can be used to predict the spatiotemporal spread of infectious diseases such as COVID-19. Based on our analyses, we anticipate cases to be reported in Saudi Arabia and Indonesia; additionally, countries with a moderate to low IDVI (i.e. \u22640.7) such as Indonesia, Pakistan, and Turkey should be on high alert and develop COVID- 19 response plans as soon as permitting.", "qid": 15, "docid": "x38o0uzv", "rank": 43, "score": 0.7317919135093689}, {"content": "Title: Prolonged Persistence of SARS-CoV-2 RNA in Body Fluids Content: We prospectively assessed 49 coronavirus disease cases in Guangdong, China, to estimate the frequency and duration of detectable severe acute respiratory syndrome coronavirus 2 RNA in human body fluids. The prolonged persistence of virus RNA in various body fluids may guide the clinical diagnosis and prevention of onward virus transmission.", "qid": 15, "docid": "pubh7ovn", "rank": 44, "score": 0.7316778302192688}, {"content": "Title: Prolonged Persistence of SARS-CoV-2 RNA in Body Fluids. Content: We prospectively assessed 49 coronavirus disease cases in Guangdong, China, to estimate the frequency and duration of detectable severe acute respiratory syndrome coronavirus 2 RNA in human body fluids. The prolonged persistence of virus RNA in various body fluids may guide the clinical diagnosis and prevention of onward virus transmission.", "qid": 15, "docid": "4gj9d181", "rank": 45, "score": 0.7316778302192688}, {"content": "Title: Household transmissions of SARS-CoV-2 in the time of unprecedented travel lockdown in China Content: IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the city of Wuhan, China, in December 2019 and then spread globally. Limited information is available for characterizing epidemiological features and transmission patterns in the regions outside of Hubei Province. Detailed data on transmission at the individual level could be an asset to understand the transmission mechanisms and respective patterns in different settings. OBJECTIVE: To reconstruct infection events and transmission clusters of SARS-CoV-2 for estimating epidemiological characteristics at household and non-household settings, including super-spreading events, serial intervals, age- and gender-stratified risks of infection in China outside of Hubei Province. DESIGN, SETTING, AND PARTICIPANTS: 9,120 confirmed cases reported online by 264 Chinese urban Health Commissions in 27 provinces from January 20 to February 19, 2020. A line-list database is established with detailed information on demographic, social and epidemiological characteristics. The infection events are categorized into the household and non-household settings. EXPOSURES: Confirmed cases of SARS-CoV-2 infections. MAIN OUTCOMES AND MEASURES: Information about demographic characteristics, social relationships, travel history, timelines of potential exposure, symptom onset, confirmation, and hospitalization were extracted from online public reports. 1,407 infection events formed 643 transmission clusters were reconstructed. RESULTS: In total 34 primary cases were identified as super spreaders, and 5 household super-spreading events were observed. The mean serial interval is estimated to be 4.95 days (standard deviation: 5.24 days) and 5.19 days (standard deviation: 5.28 days) for households and non-household transmissions, respectively. The risk of being infected outside of households is higher for age groups between 18 and 64 years, whereas the hazard of being infected within households is higher for age groups of young (<18) and elderly (>65) people. CONCLUSIONS AND RELEVANCE: The identification of super-spreading events, short serial intervals, and a higher risk of being infected outside of households for male people of age between 18 and 64 indicate a significant barrier to the case identification and management, which calls for intensive non-pharmaceutical interventions (e.g. cancellation of public gathering, limited access of public services) as the potential mitigation strategies.", "qid": 15, "docid": "b10yokyu", "rank": 46, "score": 0.7316458225250244}, {"content": "Title: The effects of border control and quarantine measures on global spread of COVID-19 Content: The rapid expansion of coronavirus (COVID-19) has been observed in many parts of the world. Many newly reported cases of this new coronavirus during early outbreak phases have been associated with travel history from an epidemic region (identified as imported cases). For those cases without travel history, the risk of wider spreads through community contact is even higher. However, most population models assume a homogeneous infected population without considering that the imported and secondary cases contracted by the imported cases can pose a different risk to community spread. We have developed an \u201ceasy-to-use\u201d mathematical framework extending from a meta-population model embedding city-to-city connections to stratify the dynamics of transmission waves caused by imported, secondary, and others from an outbreak source region when control measures are considered. Using the dynamics of the secondary cases, we are able to determine the probability of community spread. Using the top 10 visiting cities from Wuhan in China as an example, we first demonstrated that the arrival time and the dynamics of the outbreaks at these cities can be successfully predicted under the reproductive number R0 = 2.92 and latent period \u03c4 = 5.2 days. Next, we showed that although control measures can gain extra 32.5 and 44.0 days in arrival time through a high intensive border control measure and a shorter time to quarantine under a low R0 (1.4), if the R0 is higher (2.92), only 10 extra days can be gained for each of the same measures. This suggests the importance of lowering the incidence at source regions together with infectious disease control measures in susceptible regions. The study allows us to assess the effects of border control and quarantine measures on the emergence and the global spread in a fully connected world using the dynamics of the secondary cases.", "qid": 15, "docid": "lwe7whmg", "rank": 47, "score": 0.7315995693206787}, {"content": "Title: Recreational waters \u2013 A potential transmission route for SARS-CoV-2 to humans? Content: Coronavirus disease 2019 (COVID-19), the respiratory illness caused by the novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has lead to high morbidity and mortality rates worldwide, has been causing major public health concerns since first detected in late 2019. Following identification of novel pathogens, questions in relation to dissemination of the pathogen and transmission routes begin to emerge. This rapidly spreading SARS-CoV-2 virus has been detected in both faecal and wastewater samples across the globe, highlighting the potential for faecal-oral transmission of the virus. As a result, concerns regarding the transmission of the virus in the environment and the risk associated with contracting the virus in recreational waters, particularly where inadequately treated wastewater is discharged, have been emerging in recent weeks. This paper highlights the need for further research to be carried out to investigate the presence, infectivity and viability of this newly identified SARS-CoV-2 virus in wastewater effluent and receiving recreational waters.", "qid": 15, "docid": "rfkcjpl1", "rank": 48, "score": 0.7308331727981567}, {"content": "Title: Recreational waters - A potential transmission route for SARS-CoV-2 to humans? Content: Coronavirus disease 2019 (COVID-19), the respiratory illness caused by the novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has lead to high morbidity and mortality rates worldwide, has been causing major public health concerns since first detected in late 2019. Following identification of novel pathogens, questions in relation to dissemination of the pathogen and transmission routes begin to emerge. This rapidly spreading SARS-CoV-2 virus has been detected in both faecal and wastewater samples across the globe, highlighting the potential for faecal-oral transmission of the virus. As a result, concerns regarding the transmission of the virus in the environment and the risk associated with contracting the virus in recreational waters, particularly where inadequately treated wastewater is discharged, have been emerging in recent weeks. This paper highlights the need for further research to be carried out to investigate the presence, infectivity and viability of this newly identified SARS-CoV-2 virus in wastewater effluent and receiving recreational waters.", "qid": 15, "docid": "nl8z6u5v", "rank": 49, "score": 0.7308331727981567}, {"content": "Title: Estimating the prevalence and risk of COVID-19 among international travelers and evacuees of Wuhan through modeling and case reports Content: Coronavirus disease 2019 (COVID-19) started in Wuhan, China and has spread through other provinces and countries through infected travelers. On January 23(rd), 2020, China issued a quarantine and travel ban on Wuhan because travelers from Wuhan were thought to account for the majority of exported COVID-19 cases to other countries. Additionally, countries evacuated their citizens from Wuhan after institution of the travel ban. Together, these two populations account for the vast majority of the \u201ctotal cases with travel history to China\u201d as designated by the World Health Organization (WHO). The current study aims to assess the prevalence and risk of COVID-19 among international travelers and evacuees of Wuhan. We first used case reports from Japan, Singapore, and Korea to investigate the date of flights of infected travelers. We then used airline traveler data and the number of infected exported cases to correlate the cases with the number of travelers for multiple countries. Our findings suggest that the risk of COVID-19 infection is highest among Wuhan travelers between January 19(th) and 22(nd), 2020, with an approximate infection rate of up to 1.3% among international travelers. We also observed that evacuee infection rates varied heavily between countries and propose that the timing of the evacuation and COVID-19 testing of asymptomatic evacuees played significant roles in the infection rates among evacuees. These findings suggest COVID-19 cases and infectivity are much higher than previous estimates, including numbers from the WHO and the literature, and that some estimates of the infectivity of COVID-19 may need re-assessment.", "qid": 15, "docid": "l88etofn", "rank": 50, "score": 0.7306597232818604}, {"content": "Title: Inanimate surfaces as potential source of 2019-nCoV spread and their disinfection with biocidal agents Content: The WHO has declared COVID-19 illness a global health concern which is caused by 2019-nCoV, causing severe respiratory tract infections in humans. Transmissibility among individual to individual have been reported through droplets and probably also via contaminated surfaces and hands. Human coronaviruses can persist on inanimate surfaces such as plastic, glass, fibers and metals up to nine days. 2019-nCoV remains infectious in air for 3 h and on inanimate surfaces such as cardboard, copper, plastic and steel up to 24, 4, 72 and 48 h respectively. Disinfectant activity of various biocidal agents against coronaviruses like ethanol (62\u201371%), sodium hypochlorite (0.1%) and hydrogen peroxide (0.5%) can be regarded effective against 2019-nCoV as well. As no vaccine and antiviral therapies have been discovered for 2019-nCoV, prevention of further spread will viable option to control the ongoing and future outbreaks.", "qid": 15, "docid": "esvutpel", "rank": 51, "score": 0.7306091785430908}, {"content": "Title: Making waves: Coronavirus detection, presence and persistence in the water environment: State of the art and knowledge needs for public health Content: The main route of transmission of the human coronaviruses (HCoVs), and presumably also of the new pandemic SARS-CoV-2, is via droplets and close contacts, however their fecal elimination also suggests the possible spread via water. A scientific literature search was thus carried out to highlight the current state of the art and knowledge gaps regarding coronavirus in water. Since 1978 only 22 studies have met the inclusion criteria, and considered heterogeneous purposes, detection methods and types of water. In vitro experiments have addressed the recovery efficiency of analytical methods, survival in different types of water and the removal efficiency of water treatments. Field studies have monitored coronaviruses in surface waters, sewage, slurry, and biosolids. Overall, at the lab scale, HCoVs or surrogates can survive for several days at 4 \u00b0C, however their persistence is lower compared with non-enveloped viruses and is strongly influenced by temperature and organic or microbial pollution. HCoVs have rarely been detected in field investigations, however may be due to the low recovery efficiency of the analytical methods. The scarcity of information on HCoV in the environment suggests that research is needed to understand the fate of these viruses in the water cycle.", "qid": 15, "docid": "vuzf3dnr", "rank": 52, "score": 0.7303116917610168}, {"content": "Title: Making Waves: Coronavirus detection, presence and persistence in the water environment: State of the art and knowledge needs for public health Content: The main route of transmission of the human coronaviruses (HCoVs), and presumably also of the new pandemic SARS-CoV-2, is via droplets and close contacts, however their fecal elimination also suggests the possible spread via water. A scientific literature search was thus carried out to highlight the current state of the art and knowledge gaps regarding coronavirus in water. Since 1978 only 22 studies have met the inclusion criteria, and considered heterogeneous purposes, detection methods and types of water. In vitro experiments have addressed the recovery efficiency of analytical methods, survival in different types of water and the removal efficiency of water treatments. Field studies have monitored coronaviruses in surface waters, sewage, slurry, and biosolids. Overall, at the lab scale, HCoVs or surrogates can survive for several days at 4 \u00b0C, however their persistence is lower compared with non-enveloped viruses and is strongly influenced by temperature and organic or microbial pollution. HCoVs have rarely been detected in field investigations, however may be due to the low recovery efficiency of the analytical methods. The scarcity of information on HCoV in the environment suggests that research is needed to understand the fate of these viruses in the water cycle.", "qid": 15, "docid": "c17eijdt", "rank": 53, "score": 0.7303116917610168}, {"content": "Title: The COVID\u201019 epidemic Content: The current outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; previously 2019-nCoV), epi-centered in Hubei Province of the People's Republic of China, has spread to many other countries. On January 30, 2020, the WHO Emergency Committee declared a global health emergency based on growing case notification rates at Chinese and international locations. The case detection rate is changing hourly and daily and can be tracked in almost real time on website provided by Johns Hopkins University [1] and other websites. As of early February 2020, China bears the large burden of morbidity and mortality, whereas the incidence in other Asian countries, in Europe and North America remains low so far.", "qid": 15, "docid": "e4hmo4yc", "rank": 54, "score": 0.7301009893417358}, {"content": "Title: Cirrhosis and COVID-19: a fatal case of viral peritonitis and disseminated infection Content: Pathogenesis and clinical presentation of Coronavirus Disease-19 outside the respiratory tract remain to be understood, especially in the immunocompromised. We report an unique case of cirrhosis decompensation with ascites and unprecedented evidence of SARS Coronavirus-2 peritonitis and disseminated infection, demonstrated by viral RNA detection in peritoneal fluid, as well as in blood serum, nasopharyngeal and stool specimens.", "qid": 15, "docid": "jrwdhmst", "rank": 55, "score": 0.7290342450141907}, {"content": "Title: Epidemiological and clinical characteristics of 671 COVID-19 patients in Henan Province, China Content: BACKGROUND: Despite many reports on the characteristics of coronavirus disease 2019 (COVID-19) in Wuhan, China, relatively little is known about the transmission features of COVID-19 outside Wuhan, especially at the provincial level. METHODS: We collected epidemiological, demographic, clinical, laboratory, radiological and occupation information, along with contact history, of 671 patients with laboratory-confirmed COVID-19 reported from January 23 to February 5, 2020, in Henan province, China. We described characteristics of these cases, compared the diagnostic accuracy and features of blood testing, computed tomography (CT) scans and X-rays, and analysed SARS-CoV-2 transmission sources and patients\u2019 occupations in Henan province. RESULTS: The mean age of patients in this case series was 43 years, 56.2% were male and 22.4% had coexisting medical disorders. The death rate was 0.3%. Fourteen patients did not show any symptoms. Lymphocyte percentage was associated with disease severity (\u03c7(2) = 6.71, P = 0.035) but had a large variation in each sample group. The mean time from illness onset to diagnosis was 5.6 days. A total of 330 patients had ever lived in or visited Wuhan, 150 had contact with confirmed cases, 323 had been to a hospital and 119 had been to a wet market. There were 33 patients who did not have a traceable transmission source, with 21.2% of these being farmers and 15.2% being workmen. CONCLUSIONS: Lymphocyte percentage was a sign of severe COVID-19 in general but was not a good diagnostic index. Longer time from illness onset to diagnosis was associated with higher COVID-19 severity, older age, higher likelihood of having coexisting cardiovascular diseases including hypertension, and being male. Farming was found to be a high-risk occupation in Henan province, China.", "qid": 15, "docid": "zbfomy4c", "rank": 56, "score": 0.7289013862609863}, {"content": "Title: A mathematical model for the novel coronavirus epidemic in Wuhan, China Content: We propose a mathematical model to investigate the current outbreak of the coronavirus disease 2019 (COVID-19) in Wuhan, China. Our model describes the multiple transmission pathways in the infection dynamics, and emphasizes the role of the environmental reservoir in the transmission and spread of this disease. Our model also employs non-constant transmission rates which change with the epidemiological status and environmental conditions and which reflect the impact of the on-going disease control measures. We conduct a detailed analysis of this model, and demonstrate its application using publicly reported data. Among other findings, our analytical and numerical results indicate that the coronavirus infection would remain endemic, which necessitates long-term disease prevention and intervention programs.", "qid": 15, "docid": "5dpx5lez", "rank": 57, "score": 0.7288193702697754}, {"content": "Title: A mathematical model for the novel coronavirus epidemic in Wuhan, China. Content: We propose a mathematical model to investigate the current outbreak of the coronavirus disease 2019 (COVID-19) in Wuhan, China. Our model describes the multiple transmission pathways in the infection dynamics, and emphasizes the role of the environmental reservoir in the transmission and spread of this disease. Our model also employs non-constant transmission rates which change with the epidemiological status and environmental conditions and which reflect the impact of the on-going disease control measures. We conduct a detailed analysis of this model, and demonstrate its application using publicly reported data. Among other findings, our analytical and numerical results indicate that the coronavirus infection would remain endemic, which necessitates long-term disease prevention and intervention programs.", "qid": 15, "docid": "8mdnkegz", "rank": 58, "score": 0.7288193702697754}, {"content": "Title: Infection Density and Epidemic Size of COVID-19 in China outside the Hubei province Content: The novel coronavirus (COVID-19) has spread to almost all countries in the world, claiming more than 160,000 lives and sickening more than 2,400,000 people by April 21, 2020. There has been research showing that on average, each infected person spreads the infection to more than two persons. Therefore the majority of the population is at risk of infection if no intervention measures were undertaken. The true size of the COVID-19 epidemic remains unknown, as a significant proportion of infected individuals only exhibit mild symptoms or are even asymptomatic. A timely assessment of the evolving epidemic size is crucial for resource allocation and triage decisions. In this article, we modify the back-calculation algorithm to obtain a lower bound estimate of the number of COVID-19 infected persons in China outside the Hubei province. We estimate the infection density among infected and show that the drastic control measures enforced throughout China following the lockdown of Wuhan City effectively slowed down the spread of the disease in two weeks. Our findings from China are expected to provide guidelines and enlightenment for surveillance and control activities of COVID-19 in other countries around the world.", "qid": 15, "docid": "sg66xcif", "rank": 59, "score": 0.7281628251075745}, {"content": "Title: Effect of Nonpharmaceutical Interventions on Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, South Korea, 2020 Content: We analyzed transmission of coronavirus disease outside of the Daegu-Gyeongsangbuk provincial region in South Korea. We estimated that nonpharmaceutical measures reduced transmissibility by a maximum of 34% without resorting to a strict lockdown strategy. To optimize epidemic control, continuous efforts to monitor the transmissibility are needed.", "qid": 15, "docid": "12uca8kw", "rank": 60, "score": 0.7270638942718506}, {"content": "Title: Effect of Nonpharmaceutical Interventions on Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, South Korea, 2020. Content: We analyzed transmission of coronavirus disease outside of the Daegu-Gyeongsangbuk provincial region in South Korea. We estimated that nonpharmaceutical measures reduced transmissibility by a maximum of 34% without resorting to a strict lockdown strategy. To optimize epidemic control, continuous efforts to monitor the transmissibility are needed.", "qid": 15, "docid": "odmx6ng8", "rank": 61, "score": 0.7270638942718506}, {"content": "Title: Novel coronavirus (Covid-19)-a critical review Content: No one has even imagined that infection in the respiratory system in the form of pneumonia because of novel coronavirus (SARS-CoV2) in small town of China, Wuhan during end of December in the year 2019 will come out as an extremely communicable infection. The World Health Organization (WHO) has acknowledged the current epidemic as a threat to whole population worldwide. At present, still we have not reached the advanced levels of research to treat and control this contagious disease. Due to lack of information about the pathogenesis and proliferation pathways of this novel corona virus, whole world is looking forward for its exact prophylaxis. On the basis of recent proofs provided by review and research articles from various gen-uine sources, we tried thoroughly to summarize the various factors regarding COVID-19 like its epidemiology, clinical characteristics, diagnosis, treatment and prevention. Through this review we have made an effort to present a com-mon conceptual literature on coronavirus to help community to fight against this dangerous virus, and will hope that this review will be a source of refer-ence to young researchers for advanced studies.", "qid": 15, "docid": "jfn1lh8b", "rank": 62, "score": 0.7270362377166748}, {"content": "Title: Estimating number of global importations of COVID-19 from Wuhan, risk of transmission outside mainland China and COVID-19 introduction index between countries outside mainland China Content: Background The emergence of a novel coronavirus (SARS-CoV-2) in Wuhan, China in early December 2019 has caused widespread transmission within the country, with over 1,000 deaths reported to date. Other countries have since reported coronavirus disease 2019 (COVID-19) importation from China, with some experiencing local transmission and even case importation from countries outside China. We aim to estimate the number of cases imported from Wuhan to each country or territory outside mainland China, and with these estimates assess the risk of onward local transmission and the relative potential of case importation between countries outside China. Methods We used the reported number of cases imported from Wuhan and flight data to generate an uncertainty distribution for the estimated number of imported cases from Wuhan to each location outside mainland China. This uncertainty was propagated to quantify the local outbreak risk using a branching process model. A COVID-19 introduction index was derived for each pair of donor and recipient countries, accounting for the local outbreak risk in the donor country and the between-country connectivity. Results We identified 13 countries or territories outside mainland China that may have under-detected COVID-19 importation from Wuhan, such as Thailand and Indonesia. In addition, 16 countries had a local outbreak risk estimate exceeding 50%, including four outside Asia. The COVID-19 introduction index highlights potential locations outside mainland China from which cases may be imported to each recipient country. Conclusions As SARS-CoV-2 continues to spread globally, more epicentres may emerge outside China. Hence, it is important for countries to remain alert for the possibilities of viral introduction from other countries outside China, even before local transmission in a source country becomes known.", "qid": 15, "docid": "2w3bx6p8", "rank": 63, "score": 0.726733922958374}, {"content": "Title: Discrete SIRIR modelling using empirical infection data shows that SARS-CoV-2 infection provides short-term immunity Content: The novel coronavirus SARS-CoV-2, which causes the COVID-19 disease, is now a global pandemic. Since December 2019, it has infected millions of people, caused the deaths of hundreds of thousands, and resulted in incalculable social and economic damage. Understanding the infectivity and transmission dynamics of the virus is essential for understanding how best to reduce mortality whilst ensuring minimal social restrictions to the lives of the general population. Anecdotal evidence is available, but detailed studies have not yet revealed whether infection with the virus results in immunity. In this work, we have extended the generic SIR framework to analyse empirical infection and fatality data from different regions to investigate the reinfection frequency of the disease. Our model predicts that cases of reinfection should have been observed by now if primary SARS-CoV-2 infection did not protect from subsequent exposure in the short term, however, no such cases have been documented. This work, therefore, provides a useful insight for serological testing strategies, lockdown easing and vaccine design.", "qid": 15, "docid": "el7mdliy", "rank": 64, "score": 0.726531982421875}, {"content": "Title: Modelling the thermal inactivation of viruses from the Coronaviridae family in suspensions or on surfaces with various relative humidities. Content: Temperature and relative humidity are major factors determining virus inactivation in the environment. This article reviews inactivation data of coronaviruses on surfaces and in liquids from published studies and develops secondary models to predict coronaviruses inactivation as a function of temperature and relative humidity. A total of 102 D-values (time to obtain a log10 reduction of virus infectivity), including values for SARS-CoV-2, were collected from 26 published studies. The values obtained from the different coronaviruses and studies were found to be generally consistent. Five different models were fitted to the global dataset of D-values. The most appropriate model considered temperature and relative humidity. A spreadsheet predicting the inactivation of coronaviruses and the associated uncertainty is presented and can be used to predict virus inactivation for untested temperatures, time points or new coronavirus strains.", "qid": 15, "docid": "4hbwg18z", "rank": 65, "score": 0.7261438369750977}, {"content": "Title: Scientometric Trends for Coronaviruses and Other Emerging Viral Infections Content: COVID-19 is the most rapidly expanding coronavirus outbreak in the past two decades. To provide a swift response to a novel outbreak, prior knowledge from similar outbreaks is essential. Here, we study the volume of research conducted on previous coronavirus outbreaks, specifically SARS and MERS, relative to other infectious diseases by analyzing over 35 million papers from the last 20 years. Our results demonstrate that previous coronavirus outbreaks have been understudied compared to other viruses. We also show that the research volume of emerging infectious diseases is very high after an outbreak and drops drastically upon the containment of the disease. This can yield inadequate research and limited investment in gaining a full understanding of novel coronavirus management and prevention. Independent of the outcome of the current COVID-19 outbreak, we believe that measures should be taken to encourage sustained research in the field.", "qid": 15, "docid": "kh9whqzd", "rank": 66, "score": 0.7259058952331543}, {"content": "Title: Factors associated with duration of viral shedding in adults with COVID-19 outside of Wuhan, China: A retrospective cohort study Content: Objectives: To investigate factors associated with the duration of viral shedding in patients with COVID-19 outside of Wuhan. Methods: In this retrospective cohort study, patients with laboratory-confirmed COVID-19 in Changsha, China were included. Clinical characteristics, laboratory findings, treatment and outcome were retrieved. Univariable and multivariable analysis were performed to explore potential factors. Results: Totally 147 patients with COVID-19 were included. The median duration of viral shedding (the number of days from symptoms onset till the successive negative detection of SARS-CoV-2 RNA) was 17 days (interquartile range [IQR], 12 to 21). Multivariable Logistic regression analysis indicated that the highest temperature at admission (odds ratio [OR], 5.200; 95% confidence interval [CI]: 1.190-22.726; p = 0.028) and time from symptom onset to admission (OR, 1.740; 95% CI: 1.296-2.337; p < 0.001) and hospital length of stay (OR, 1.604; 95% CI: 1.262-2.040; p < 0.001) were risk factors for prolonged duration of viral shedding. Conclusions: This is the study with relatively large sample size that mainly focused on the duration of viral shedding and relevant factors in patients with COVID-19 outside of Wuhan, China. Potential risk factors were identified and should be taken into consideration for the strategy of quarantine of infected patients.", "qid": 15, "docid": "02imjygp", "rank": 67, "score": 0.7257484197616577}, {"content": "Title: COVID-19: lessons to date from China Content: The pandemic due to a novel coronavirus has been sweeping across different regions of the globe since January 2020. Early reports of this infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) consisted of mostly adult patients. As the outbreak spreads rapidly beyond the epicentre of Wuhan, it becomes clear that infants and children of all ages are susceptible to this infection. In China, there have been more than 1200 paediatric cases. Most paediatric patients acquire the infection through household contact with infected adults. The disease in children is usually self-limiting and most infected children will recover uneventfully within 7-10 days. Other than symptoms of the respiratory tract, many children may present with gastrointestinal symptoms. Older children are more likely to have asymptomatic infection. Although deaths related to SARS-CoV-2 are rarely reported in the paediatric age group, young children and those with underlying medical conditions are more likely to develop severe illness. Only a small fraction of neonates born to infected mother would acquire the virus by vertical transmission. Because a large proportion of children and adolescents may have asymptomatic or mildly symptomatic infection, children are likely to play an important role in community transmission of this infection. Screening of children who have a definitive contact history will facilitate early diagnosis and isolation of all infected children. This review summarises the lessons learned in China with regard to the current understanding of SARS-CoV-2 infection in the paediatric population.", "qid": 15, "docid": "k4wbifxq", "rank": 68, "score": 0.7254570722579956}, {"content": "Title: COVID-19: lessons to date from China. Content: The pandemic due to a novel coronavirus has been sweeping across different regions of the globe since January 2020. Early reports of this infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) consisted of mostly adult patients. As the outbreak spreads rapidly beyond the epicentre of Wuhan, it becomes clear that infants and children of all ages are susceptible to this infection. In China, there have been more than 1200 paediatric cases. Most paediatric patients acquire the infection through household contact with infected adults. The disease in children is usually self-limiting and most infected children will recover uneventfully within 7-10 days. Other than symptoms of the respiratory tract, many children may present with gastrointestinal symptoms. Older children are more likely to have asymptomatic infection. Although deaths related to SARS-CoV-2 are rarely reported in the paediatric age group, young children and those with underlying medical conditions are more likely to develop severe illness. Only a small fraction of neonates born to infected mother would acquire the virus by vertical transmission. Because a large proportion of children and adolescents may have asymptomatic or mildly symptomatic infection, children are likely to play an important role in community transmission of this infection. Screening of children who have a definitive contact history will facilitate early diagnosis and isolation of all infected children. This review summarises the lessons learned in China with regard to the current understanding of SARS-CoV-2 infection in the paediatric population.", "qid": 15, "docid": "wz43k9z9", "rank": 69, "score": 0.7254570722579956}, {"content": "Title: Clinical and Epidemiological Features of a Family Cluster of Symptomatic and Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection Content: In a family experiencing coronavirus disease 2019, the parents and 2 children aged 2 and 5 years became infected but the youngest child was not infected. Both children initially shed infectious virus, but cleared the virus after 5 to 6 days in the nasopharynx. However, viral RNA was continuously detected in the children\u2019s stool for more than 4 weeks.", "qid": 15, "docid": "zz5bpas1", "rank": 70, "score": 0.7249969244003296}, {"content": "Title: Epidemiological and clinical characteristics of 671 COVID-19 patients in Henan Province, China Content: BACKGROUND: Despite many reports on the characteristics of coronavirus disease 2019 (COVID-19) in Wuhan, China, relatively little is known about the transmission features of COVID-19 outside Wuhan, especially at the provincial level. METHODS: We collected epidemiological, demographic, clinical, laboratory, radiological and occupation information, along with contact history, of 671 patients with laboratory-confirmed COVID-19 reported from January 23 to February 5, 2020, in Henan province, China. We described characteristics of these cases, compared the diagnostic accuracy and features of blood testing, computed tomography (CT) scans and X-rays, and analysed SARS-CoV-2 transmission sources and patients' occupations in Henan province. RESULTS: The mean age of patients in this case series was 43 years, 56.2% were male and 22.4% had coexisting medical disorders. The death rate was 0.3%. Fourteen patients did not show any symptoms. Lymphocyte percentage was associated with disease severity (&#967;2 = 6.71, P = 0.035) but had a large variation in each sample group. The mean time from illness onset to diagnosis was 5.6 days. A total of 330 patients had ever lived in or visited Wuhan, 150 had contact with confirmed cases, 323 had been to a hospital and 119 had been to a wet market. There were 33 patients who did not have a traceable transmission source, with 21.2% of these being farmers and 15.2% being workmen. CONCLUSIONS: Lymphocyte percentage was a sign of severe COVID-19 in general but was not a good diagnostic index. Longer time from illness onset to diagnosis was associated with higher COVID-19 severity, older age, higher likelihood of having coexisting cardiovascular diseases including hypertension, and being male. Farming was found to be a high-risk occupation in Henan province, China.", "qid": 15, "docid": "0hynq3pt", "rank": 71, "score": 0.7248613834381104}, {"content": "Title: Global epidemiology, pathogenesis, immune response, diagnosis, treatment, economic and psychological impact, challenges, and future prevention of COVID-19: A scoping review Content: Background: Globally, the novel coronavirus, is a public health problem causing respiratory infections. Since the outbreak of severe acute and Middle East respiratory syndromes coronavirus was not reported to cause human infections. Now, it become an epidemic proportion with growing number of cases and deaths. Methods: A scoping review was conducted following the methodological framework. In this scoping review, 50 records published before 28 March, 2020 were included and discussed to better understand the current epidemiology, pathogenesis, immunological response, diagnosis, evasion mechanisms and suggested strategies to boost the immune system, challenges, treatment, and future preventions of the virus. PubMed, BioRxiv, MedRxiv, Global Health and google scholars were searched comprehensively for articles, preprints, grey literatures, reports, websites, conference proceedings and expert information. Studies conducted in human and published in the English language were included in the analysis. All the findings and statements of the review regarding the outbreak are based on published information as listed in citations. Results: We identified 360 records, of which 50 studies met the inclusion criteria. We synthesized the data from the included records and dig out the deep insights of them and pooled into this review. The burden of the outbreak is worsening due to overcrowding, presence of asymptomatic carriers, scarcity of test kits, the immune escaping ability of the virus and lack of awareness. Conclusions and recommendations: Due to the fast-spreading nature of COVID-19 the prevention and control strategies become challenging. It is imposing social, psychological, and socio-economic impacts. We recommended that following social distancing, isolation suspects, using personal protective equipment, health education and introducing handwashing practices, avoiding contact with animals, vaccine development and treatment for controlling and prevention.", "qid": 15, "docid": "prpooezh", "rank": 72, "score": 0.7248457074165344}, {"content": "Title: Minimizing the risk of international spread of coronavirus disease 2019 (COVID-19) outbreak by targeting travelers Content: The Coronavirus Disease-2019 (COVID-19) outbreak has become a global health emergency owing to its magnitude, attributed deaths, and its propensity to spread across the world. In-fact, owing to its quick spread across international boundaries and the resulting caseload, the disease has been declared as a Public Health Emergency of International Concern on 30 January 2020. It is worth noting that out of the 395 cases detected in other nations, 165 (41.8%) have a positive history of travel to China. As of now, the World Health Organization has not recommended for any restrictions on the travel or trade aspects, but has clearly specified that implementation of International Health Regulations should be strictly done at the airports and seaports. In conclusion, the COVID- 19 outbreak has created an alarm across the globe as the causative virus is novel in nature. However, strengthening of standard infection control practices and adoption of preventive measures for travelers can significantly minimize the threat of further transmission of the disease.", "qid": 15, "docid": "9geqs2he", "rank": 73, "score": 0.7248384356498718}, {"content": "Title: The incubation period of 2019-nCoV infections among travellers from Wuhan, China Content: Currently, a novel coronavirus 2019-nCoV causes an outbreak of viral pneumonia in Wuhan, China. Little is known about its epidemiological characteristics. Using the travel history and symptom onset of 88 confirmed cases that were detected outside Wuhan, we estimate the mean incubation period to be 6.4 (5.6 - 7.7, 95% CI) days, ranging from 2.1 to 11.1 days (2.5th to 97.5th percentile). These values help to inform case definitions for 2019-nCoV and appropriate durations for quarantine.", "qid": 15, "docid": "u8goc7io", "rank": 74, "score": 0.7243887782096863}, {"content": "Title: Is the spread of COVID-19 across countries influenced by environmental, economic and social factors? Content: The SARS-CoV-2 virus, emerged from Wuhan, China is spreading all over the world in an unprecedented manner, causing millions of infections and thousands of deaths. However, the spread of the disease across countries and regions are not even. Why some countries and regions are more affected than some other countries and regions? We employ simple statistical methods to investigate any linkage between the severity of the disease and the environmental, economic and social factors of countries. The estimation results indicate that the number of confirmed cases of Coronavirus infection is higher in countries with lower yearly average temperatures, higher economic openness, and stronger political democracy. However, findings of this analysis should be interpreted carefully keeping in mind the fact that statistical relations do not necessarily imply causation. Only clinical experiments with medical expertise can confirm how the virus behaves in the environment.", "qid": 15, "docid": "na0dkca2", "rank": 75, "score": 0.7243162989616394}, {"content": "Title: SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes Content: SARS-CoV-2 virus, the causative agent of the coronavirus infectious disease-19 (COVID-19), is taking the globe by storm, approaching 500,000 confirmed cases and over 21,000 deaths as of March 25, 2020. While under control in some affected Asian countries (Taiwan, Singapore, Vietnam), the virus demonstrated an exponential phase of infectivity in several large countries (China in late January and February and many European countries and the USA in March), with cases exploding by 30-50,000/day in the third and fourth weeks of March, 2020. SARS-CoV-2 has proven to be particularly deadly to older adults and those with certain underlying medical conditions, many of whom are of advanced age. Here, we briefly review the virus, its structure and evolution, epidemiology and pathogenesis, immunogenicity and immune, and clinical response in older adults, using available knowledge on SARS-CoV-2 and its highly pathogenic relatives MERS-CoV and SARS-CoV-1. We conclude by discussing clinical and basic science approaches to protect older adults against this disease.", "qid": 15, "docid": "l9f7g2l4", "rank": 76, "score": 0.7238297462463379}, {"content": "Title: Clinical Characteristics and Reasons for Differences in Duration From Symptom Onset to Release From Quarantine Among Patients With COVID-19 in Liaocheng, China Content: Objective: This study aimed to identify additional characteristics and features of coronavirus disease (COVID-19) by assessing the clinical courses among COVID-19 patients in a region outside Hubei province. Methods: We analyzed retrospective data regarding general characteristics, epidemiologic history, underlying chronic diseases, clinical symptoms and complications, chest computed tomography findings, biochemical monitoring, disease severity, treatments, and outcomes among 37 adult patients with COVID-19. According to the duration from symptom onset to release from quarantine, the patients were divided into the \u226420 and >20-day groups, and the similarities and differences between them were compared. Results: Among the 37 patients, five had mild disease, 30 had moderate disease, one had severe disease, and one was critically ill. All of the patients were released from quarantine, and no mortality was observed. The average duration from symptom onset to release from quarantine was 20.2 \u00b1 6.6 days. The average duration from symptom onset to hospitalization was 4.1 \u00b1 3.7 days, and the patients were hospitalized for an average of 16.1 \u00b1 6.2 days. The average age was 44.3 \u00b1 1.67 years, and 78.4% of cases were caused by exposure to a patient with confirmed disease or the workplace of a patient with confirmed disease. The main symptoms were cough (67.6%), fever (62.2%), shortness of breath (32.4%), fatigue (24.3%), sore throat (21.6%), vomiting, and diarrhea (21.6%). White blood cell count was decreased in 27.0% of patients, and lymphocyte count was decreased in 62.2% of the patients, among whom 43.5% patients had counts of \u22640.6 \u00d7 10(9)/L. On admission, 86.5% of patients showed pneumonia in chest CT scans, including some asymptomatic patients, while 68.8% of patients showed bilateral infiltration. In the >20-day group, the average age was 49.9 \u00b1 1.38 years, and the average duration from symptom onset to hospitalization was 5.5 \u00b1 3.9 days. Compared with the \u226420-day group, patients in the >20-day group were older and the duration was longer (P < 0.05). All of the seven asymptomatic patients belonged to the \u226420-day group. When the 37 patients were released from quarantine, the white blood cell count of 16.2% of the patients was <4.0 \u00d7 10(9)/L, the lymphocyte count of 59.5% of the patients was <1.1 \u00d7 10(9)/L, and the absolute counts of white blood cells and lymphocytes were 5.02 \u00b1 1.34 \u00d7 10(9)/L and 1.03 \u00b1 0.34 \u00d7 10(9)/L, respectively, compared with those recorded on admission (P > 0.05). Conclusion: The majority of COVID-19 cases in the study area were mild and moderate, with good clinical outcomes. There were some special characteristics in the clinical course. The reasons for differences in the duration from symptom onset to release from quarantine were complex. There was no significant change in the number of granulocytes at the time of release from quarantine compared to that at the time of admission.", "qid": 15, "docid": "r9gq2oan", "rank": 77, "score": 0.7238280773162842}, {"content": "Title: Animal models for emerging coronavirus: progress and new insights Content: The emergences of coronaviruses have caused a serious global public health problem because their infection in humans caused the severe acute respiratory disease and deaths. The outbreaks of lethal coronaviruses have taken place for three times within recent two decades (SARS-CoV in 2002, MERS-CoV in 2012 and SARS-CoV-2 in 2019). Much more serious than SARS-CoV in 2002, the current SARS-CoV-2 infection has been spreading to more than 213 countries, areas or territories and causing more than two million cases up to date (17 April 2020). Unfortunately, no vaccine and specific anti-coronavirus drugs are available at present time. Current clinical treatment at hand is inadequate to suppress viral replication and inflammation, and reverse organ failure. Intensive research efforts have focused on increasing our understanding of viral biology of SARS-CoV-2, improving antiviral therapy and vaccination strategies. The animal models are important for both the fundamental research and drug discovery of coronavirus. This review aims to summarize the animal models currently available for SARS-CoV and MERS-CoV, and their potential use for the study of SARS-CoV-2. We will discuss the benefits and caveats of these animal models and present critical findings that might guide the fundamental studies and urgent treatment of SARS-CoV-2-caused diseases.", "qid": 15, "docid": "pld0clpd", "rank": 78, "score": 0.7238134145736694}, {"content": "Title: SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes Content: SARS-CoV-2 virus, the causative agent of the coronavirus infectious disease-19 (COVID-19), is taking the globe by storm, approaching 500,000 confirmed cases and over 21,000 deaths as of March 25, 2020. While under control in some affected Asian countries (Taiwan, Singapore, Vietnam), the virus demonstrated an exponential phase of infectivity in several large countries (China in late January and February and many European countries and the USA in March), with cases exploding by 30\u201350,000/day in the third and fourth weeks of March, 2020. SARS-CoV-2 has proven to be particularly deadly to older adults and those with certain underlying medical conditions, many of whom are of advanced age. Here, we briefly review the virus, its structure and evolution, epidemiology and pathogenesis, immunogenicity and immune, and clinical response in older adults, using available knowledge on SARS-CoV-2 and its highly pathogenic relatives MERS-CoV and SARS-CoV-1. We conclude by discussing clinical and basic science approaches to protect older adults against this disease.", "qid": 15, "docid": "f783oobv", "rank": 79, "score": 0.7238020896911621}, {"content": "Title: Coronavirus disease 2019: International public health considerations Content: On December 31, 2019, the Chinese government announced an outbreak of a novel coronavirus, recently named COVID\u201019. During the following weeks the international medical community has witnessed with unprecedented coverage the public health response both domestically by the Chinese government, and on an international scale as cases have spread to dozens of countries. While much regarding the virus and the Chinese public health response is still unknown, national and public health institutions globally are preparing for a pandemic. As cases and spread of the virus grow, emergency and other front\u2010line providers may become more anxious about the possibility of encountering a potential case. This review describes the tenets of a public health response to an infectious outbreak by using recent historical examples and also by characterizing what is known about the ongoing response to the COVID\u201019 outbreak. The intent of the review is to empower the practitioner to monitor and evaluate the local, national and global public health response to an emerging infectious disease.", "qid": 15, "docid": "rhfafy70", "rank": 80, "score": 0.7237929105758667}, {"content": "Title: Adaptation of coronavirus JHM to persistent infection of murine sac(-) cells. Content: Coronaviruses can establish persistent infections in the central nervous system of rodents, and these are associated with demyelinating encephalomyelitis. The effects of persistence on the virus are difficult to study in vivo but may have a crucial influence on the course of infection. We therefore produced a persistent infection in vitro using the neurotropic coronavirus JHM, in order to investigate the events underlying the establishment of such an infection and the adaptation of the virus to persistence. The persistent infection was maintained for over 115 passages and continued to release high levels of infectious virus. During the 18 months of culture the number of cells expressing virus antigen detected by indirect immune fluorescence decreased to 40%. Analysis showed that the carried virus contained a significant proportion of heterogeneous temperature-sensitive mutants. All virus clones isolated possessed the capacity to induce a more productive growth cycle, a less pronounced cytopathic effect and showed a much reduced neurovirulence when inoculated into newborn and weanling rats. Evidence for structural changes involving the surface peplomer protein (E2) was obtained using hybridoma antibodies, which neutralized the parental JHM virus but not the JHM-Pi virus. Defective interfering particles and interferon activities have been excluded as possible agents instrumental in the establishment and maintenance of the chronic infection, and we suggest that the emergence of virus variants of lowered virulence is central to these processes.", "qid": 15, "docid": "q9797wsr", "rank": 81, "score": 0.7235776782035828}, {"content": "Title: Chronic Living in a Communicable World Content: By April 2020, COVID-19 lockdowns had restricted the movements of over half the world's population. As health authorities advise people living with chronic conditions to self-isolate because they are at particular risk of serious complications and death, the epidemiological split between communicable and noncommunicable disease is tenuous. We argue that much more is at stake for people living with (multiple) medical conditions than being \"at risk\" of infection of coronavirus. We emphasize the need to attend to the long-term effects of COVID-19, but also the importance of the continued care of people living with other lifelong medical conditions.", "qid": 15, "docid": "gmcj27xz", "rank": 82, "score": 0.7235252857208252}, {"content": "Title: Chronic Living in a Communicable World. Content: By April 2020, COVID-19 lockdowns had restricted the movements of over half the world's population. As health authorities advise people living with chronic conditions to self-isolate because they are at particular risk of serious complications and death, the epidemiological split between communicable and noncommunicable disease is tenuous. We argue that much more is at stake for people living with (multiple) medical conditions than being \"at risk\" of infection of coronavirus. We emphasize the need to attend to the long-term effects of COVID-19, but also the importance of the continued care of people living with other lifelong medical conditions.", "qid": 15, "docid": "xui949ap", "rank": 83, "score": 0.7235252857208252}, {"content": "Title: Environmental concern regarding the effect of humidity and temperature on 2019-nCoV survival: fact or fiction Content: The new coronavirus, called 2019-nCoV, is a new type of virus that was first identified in Wuhan, China, in December 2019. Environmental conditions necessary for survival and spread of 2019-nCoV are somewhat transparent but unlike animal coronaviruses. We are poorly aware of their survival in environment and precise factors of their transmission. Countries located in east and west of globe did not have a significant impact on prevalence of disease among communities, and on the other hand, north and south have provided a model for relative prediction of disease outbreaks. The 2019-nCoV can survive for up to 9 days at 25 \u00b0C, and if this temperature rises to 30 \u00b0C, its lifespan will be shorter. The 2019-nCoV is sensitive to humidity, and lifespan of viruses in 50% humidity is longer than that of 30%. Also, temperature and humidity are important factors influencing the COVID-19 mortality rate and may facilitate 2019-nCoV transmission. Thus, considering the available and recent evidence, it seems that low temperatures, as well as dry and unventilated air, may affect stability and transmissibility of 2019-nCoV.", "qid": 15, "docid": "zqsfw75p", "rank": 84, "score": 0.7233415842056274}, {"content": "Title: High Contagiousness and Rapid Spread of Severe Acute Respiratory Syndrome Coronavirus 2 Content: Severe acute respiratory syndrome coronavirus 2 is the causative agent of the ongoing coronavirus disease pandemic. Initial estimates of the early dynamics of the outbreak in Wuhan, China, suggested a doubling time of the number of infected persons of 6\u20137 days and a basic reproductive number (R(0)) of 2.2\u20132.7. We collected extensive individual case reports across China and estimated key epidemiologic parameters, including the incubation period (4.2 days). We then designed 2 mathematical modeling approaches to infer the outbreak dynamics in Wuhan by using high-resolution domestic travel and infection data. Results show that the doubling time early in the epidemic in Wuhan was 2.3\u20133.3 days. Assuming a serial interval of 6\u20139 days, we calculated a median R(0) value of 5.7 (95% CI 3.8\u20138.9). We further show that active surveillance, contact tracing, quarantine, and early strong social distancing efforts are needed to stop transmission of the virus.", "qid": 15, "docid": "eo8rbcy2", "rank": 85, "score": 0.7233182191848755}, {"content": "Title: COVID\u201019 indirect contact transmission through the oral mucosa must not be ignored Content: BACKGROUND Coronavirus (CoV) is the single stranded sense RNA virus that has been known so far with the largest genomic capacity and plenty of natural hosts. In the past dozens of years, SARS-CoV under the branch of the new evolutionary tree has threatens greatly global public health and the severe acute respiratory syndrome new coronavirus (COVID-19) reported in China could cause fatal pathological lesions. Especially in areas with poor medical care, neglect of indirect transmission can cause more serious consequences. METHODS First of all, with reference to SARS-CoV and other relevant studies, the possibility of virus residues on the surface of multiple media is discussed. Further, it is found that the surface residue of this substance may be an important factor in iatrogenic infection. RESULTS This correspondence could point out the direction to study the pathomechanism of COVID-19 infecting human beings. CONCLUSIONS Mucosa exposure and inappropriate treatment of medical and non-medical articles used by the patients all could increase the risks of COVID-19 transmission.", "qid": 15, "docid": "adsgiizl", "rank": 86, "score": 0.7230334877967834}, {"content": "Title: Coronavirus threat to Indian population: risk factors, transmission dynamics and preparedness to prevent the spread of the virus Content: Recent novel coronavirus outbreak in Wuhan City of Hubei province in China infected nearly 70,000 individuals and killed more than 1700 people within a short span of time leading to global pandemic. The disease is now spread to 26 countries in Asia, North America, Europe and Australasia. The virus is spreading rapidly to Asia-pacific and Southeast Asian countries. The disease is posing a serious threat to human population and has devastating impact on public health and economy. So far 3 Indians are infected and India is at risk of rapid spread of the disease because of its geographical location and other favorable conditions. With a poorer global health security index compared to China (India-57 and China-51), any such situation will have worse outcome. In near future there are also possibilities of similar kind of disease outbreak caused by new strains of coronaviruses due to factors like species jump of new viruses, high population density and inadequate medical facilities. In this short review we have highlighted the risk factors and transmission dynamics of coronaviruses that may pose a serious threat to India. We have also discussed about the possible preventive measure our country should take to control any such outbreak situation.", "qid": 15, "docid": "u4gc98g4", "rank": 87, "score": 0.7230261564254761}, {"content": "Title: A novel coronavirus capable of lethal human infections: an emerging picture Content: SUMMARY: In September 2012, a novel coronavirus was isolated from a patient in Saudi Arabia who had died of an acute respiratory illness and renal failure. The clinical presentation was reminiscent of the outbreak caused by the SARS-coronavirus (SARS-CoV) exactly ten years ago that resulted in over 8000 cases. Sequence analysis of the new virus revealed that it was indeed a member of the same genus as SARS-CoV. By mid-February 2013, 12 laboratory-confirmed cases had been reported with 6 fatalities. The first 9 cases were in individuals resident in the Middle East, while the most recent 3 cases were in family members resident in the UK. The index case in the UK family cluster had travel history to Pakistan and Saudi Arabia. Although the current evidence suggests that this virus is not highly transmissible among humans, there is a real danger that it may spread to other parts of the world. Here, a brief review of the events is provided to summarize the rapidly emerging picture of this new virus.", "qid": 15, "docid": "covnpc8z", "rank": 88, "score": 0.7229803800582886}, {"content": "Title: Survival characteristics of airborne human coronavirus 229E. Content: The survival of airborne human coronavirus 229E (HCV/229E) was studied under different conditions of temperature (20 +/- 1 degree C and 6 +/- 1 degree C) and low (30 +/- 5%), medium (50 +/- 5%) or high (80 +/- 5%) relative humidities (RH). At 20 +/- 1 degree C, aerosolized HCV/229E was found to survive best at 50% RH with a half-life of 67.33 +/- 8.24 h while at 30% RH the virus half-life was 26.76 +/- 6.21 h. At 50% RH nearly 20% infectious virus was still detectable at 6 days. High RH at 20 +/- 1 degree C, on the other hand, was found to be the least favourable to the survival of aerosolized virus and under these conditions the virus half-life was only about 3 h; no virus could be detected after 24 h in aerosol. At 6 +/- 1 degree C, in either 50% or 30% RH conditions, the survival of HCV/229E was significantly enhanced, with the decay pattern essentially similar to that seen at 20 +/- 1 degree C. At low temperature and high RH (80%), however, the survival pattern was completely reversed, with the HCV/229E half-life increasing to 86.01 +/- 5.28 h, nearly 30 times that found at 20 +/- 1 degree C and high RH. Although optimal survival at 6 degree C still occurred at 50% RH, the pronounced stabilizing effect of low temperature on the survival of HCV/229E at high RH indicates that the role of the environment on the survival of viruses in air may be more complex and significant than previously thought.", "qid": 15, "docid": "oi7karvd", "rank": 89, "score": 0.7228773236274719}, {"content": "Title: The human enteric coronaviruses. Content: A coronarirus was seen in the faeces from 15 (4.2%) of 355 adults with diarrhoea and from 5 (5.2%) of 96 adults without diarrhoea. Similar particles were seen in the faeces from 5 (2.2%) of 227 children aged 1--14 years with gastroenteritis, but in none of those from 230 infants under one year of age with gastroenteritis. There was no evidence that the coronavirus was responsible for any of 34 outbreaks of gastroenteritis, although it possibly caused diarrhoea in patients admitted to a psycho-geriatric unit. Excretion of the virus often continued for many months. One strain was propagated in human embryo kidney monolayers and human embryo intestinal organ cultures, although serial passage could not be accomplished.", "qid": 15, "docid": "xmml8lxy", "rank": 90, "score": 0.7228264808654785}, {"content": "Title: Multiple drivers of the COVID-19 spread: role of climate, international mobility, and region-specific conditions Content: The novel Coronavirus Disease 2019 (COVID-19) has spread quickly across the globe. Here, we evaluated the role of climate (temperature and precipitation), region-specific susceptibility (BCG vaccination, malaria infection, and elderly population) and international traveller population (human mobility) in shaping the geographical patterns of COVID-19 cases across 1,055 countries/regions, and examined the sequential shift of multiple drivers of the accumulated cases from December, 2019 to April 12, 2020. The accumulated numbers of COVID-19 cases (per 1 million population) were well explained by a simple regression model. The explanatory power (R2) of the model increased up to > 70% in April 2020 as the COVID-19 spread progressed. Climate, host mobility, and host susceptibility largely explained the variance of the COVID-19 cases (per 1 million population), and their explanatory power improved as the pandemic progressed; the relative importance of host mobility and host susceptibility have been greater than that of climate. The number of days from outbreak onset showed greater explanatory power in the earlier stages of COVID-19 spread but rapidly lost its influence. Our findings demonstrate that the COVID-19 pandemic is deterministically driven by climate suitability, cross-border human mobility, and region-specific susceptibility. The present distribution of COVID-19 cases has not reached an equilibrium and is changing daily, especially in the Southern Hemisphere. Nevertheless, the present results, based on mapping the spread of COVID-19 and identifying multiple drivers of this outbreak trajectory, may contribute to a better understanding of the COVID-19 disease transmission risk and the measures against long-term epidemic.", "qid": 15, "docid": "d9zu9an6", "rank": 91, "score": 0.7227559089660645}, {"content": "Title: Experimental aerosol survival of SARS-CoV-2 in artificial saliva and tissue culture media at medium and high humidity Content: SARS-CoV-2, the causative agent of the COVID-19 pandemic, may be transmitted via airborne droplets or contact with surfaces onto which droplets have deposited. In this study, the ability of SARS-CoV-2 to survive in the dark, at two different relative humidity values and within artificial saliva, a clinically relevant matrix, was investigated. SARS-CoV-2 was found to be stable, in the dark, in a dynamic small particle aerosol under the four experimental conditions we tested and viable virus could still be detected after 90 minutes. The decay rate and half-life was determined and decay rates ranged from 0.4 to 2.27 % per minute and the half lives ranged from 30 to 177 minutes for the different conditions. This information can be used for advice and modelling and potential mitigation strategies.", "qid": 15, "docid": "txc0k2vb", "rank": 92, "score": 0.7226554751396179}, {"content": "Title: Risk estimation of the SARS-CoV-2 acute respiratory disease outbreak outside China Content: BACKGROUND: On December 31, 2019, the World Health Organization was alerted to the occurrence of cases of pneumonia in Wuhan, Hubei Province, China, that were caused by an unknown virus, which was later identified as a coronavirus and named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to estimate the reproductive number of SARS-CoV-2 in the Hubei Province and evaluate the risk of an acute respiratory coronavirus disease (COVID-19) outbreak outside China by using a mathematical model and stochastic simulations. RESULTS: We constructed a mathematical model of SARS-CoV-2 transmission dynamics, estimated the rate of transmission, and calculated the reproductive number in Hubei Province by using case-report data from January 11 to February 6, 2020. The possible number of secondary cases outside China was estimated by stochastic simulations in various scenarios of reductions in the duration to quarantine and rate of transmission. The rate of transmission was estimated as 0.8238 (95% confidence interval [CI] 0.8095\u20130.8382), and the basic reproductive number as 4.1192 (95% CI 4.0473\u20134.1912). Assuming the same rate of transmission as in Hubei Province, the possibility of no local transmission is 54.9% with a 24-h quarantine strategy, and the possibility of more than 20 local transmission cases is 7% outside of China. CONCLUSION: The reproductive number for SARS-CoV-2 transmission dynamics is significantly higher compared to that of the previous SARS epidemic in China. This implies that human-to-human transmission is a significant factor for contagion in Hubei Province. Results of the stochastic simulation emphasize the role of quarantine implementation, which is critical to prevent and control the SARS-CoV-2 outbreak outside China.", "qid": 15, "docid": "dz5nqpn5", "rank": 93, "score": 0.7225914001464844}, {"content": "Title: Risk estimation of the SARS-CoV-2 acute respiratory disease outbreak outside China Content: BACKGROUND: On December 31, 2019, the World Health Organization was alerted to the occurrence of cases of pneumonia in Wuhan, Hubei Province, China, that were caused by an unknown virus, which was later identified as a coronavirus and named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to estimate the reproductive number of SARS-CoV-2 in the Hubei Province and evaluate the risk of an acute respiratory coronavirus disease (COVID-19) outbreak outside China by using a mathematical model and stochastic simulations. RESULTS: We constructed a mathematical model of SARS-CoV-2 transmission dynamics, estimated the rate of transmission, and calculated the reproductive number in Hubei Province by using case-report data from January 11 to February 6, 2020. The possible number of secondary cases outside China was estimated by stochastic simulations in various scenarios of reductions in the duration to quarantine and rate of transmission. The rate of transmission was estimated as 0.8238 (95% confidence interval [CI] 0.8095-0.8382), and the basic reproductive number as 4.1192 (95% CI 4.0473-4.1912). Assuming the same rate of transmission as in Hubei Province, the possibility of no local transmission is 54.9% with a 24-h quarantine strategy, and the possibility of more than 20 local transmission cases is 7% outside of China. CONCLUSION: The reproductive number for SARS-CoV-2 transmission dynamics is significantly higher compared to that of the previous SARS epidemic in China. This implies that human-to-human transmission is a significant factor for contagion in Hubei Province. Results of the stochastic simulation emphasize the role of quarantine implementation, which is critical to prevent and control the SARS-CoV-2 outbreak outside China.", "qid": 15, "docid": "7b90iuzh", "rank": 94, "score": 0.7225441932678223}, {"content": "Title: Isolation and identification of human coronavirus 229E from frequently touched environmental surfaces of a university classroom that is cleaned daily Content: Frequently touched surfaces of a university classroom that is cleaned daily contained viable human coronavirus 229E (CoV-229E). Tests of a CoV-229E laboratory strain under conditions that simulated the ambient light, temperature, and relative humidity conditions of the classroom revealed that some of the virus remained viable on various surfaces for 7 days, suggesting CoV-229E is relatively stable in the environment. Our findings reinforce the notion that contact transmission may be possible for this virus.", "qid": 15, "docid": "khpc9f98", "rank": 95, "score": 0.7221918106079102}, {"content": "Title: Factors affecting stability and infectivity of SARS-CoV-2 Content: BACKGROUND: In late 2019, a novel human coronavirus, SARS-CoV-2, emerged in Wuhan, China. This virus has caused a global pandemic involving more than 200 countries. SARS-CoV-2 is highly adapted to humans and readily transmits from person-to-person. AIM: The aim of this study was to investigate the infectivity of SARS-CoV-2 under various environmental factors, disinfectants and different pH conditions. The efficacy of a variety of laboratory virus inactivation methods and home disinfectants against SARS-CoV-2 were investigated. METHODS: The residual virus in dried form or in solution was titrated on Vero E6 cell line at day 0, 1, 3, 5, and 7 after incubation at different temperatures. The viability of virus was determined after treatment with different disinfectants and pH solutions at room temperature (20\u00e2\u0088\u00bc25oC). FINDINGS: SARS-CoV-2 was able to retain viability for 3-5 days in dried form or 7 days in solution at room temperature. SARS-CoV-2 could be detected under a wide range of pH conditions from pH4 to pH11 for several days and 1 to 2 days in stool at room temperature but lost 5 logs of infectivity. A variety of commonly used disinfectants and laboratory inactivation procedures were found to reduce viral viability effectively. CONCLUSION: This study demonstrates the stability of SARS-CoV-2 on environmental surfaces and raises the possibility of faecal-oral transmission. Commonly used fixatives, nucleic acid extraction methods and heat inactivation were found to significantly reduce viral infectivity that could ensure hospital and laboratory safety during the COVID-19 pandemic.", "qid": 15, "docid": "eke4f5fn", "rank": 96, "score": 0.7221828699111938}, {"content": "Title: What does simple power law kinetics tell about our response to coronavirus pandemic? Content: Coronavirus pandemic of 2019-2020 has already affected over a million people and caused over 50,000 deaths worldwide (as on April 3, 2020). Roughly half of the world population has been asked to work from home and practice social distancing as the search for a vaccine continues. Though government interventions such as lockdown and social distancing are theoretically useful, its debatable whether such interventions are effective in flattening the curve, which is ceasing or reducing the growth of infection in control populations. In this article, I present a simple power law model that enables a comparison of countries in time windows of 14 days since first coronavirus related death is reported in that country. It therefore provides means to access the efficacy of above interventions.", "qid": 15, "docid": "y1727pi6", "rank": 97, "score": 0.7221540212631226}, {"content": "Title: Infection control in non\u2010clinical areas during the COVID\u201019 pandemic Content: Large numbers of healthcare workers have acquired coronavirus disease (COVID-19) in the workplace [1]. SARS-CoV-2 is easily transmissible as each person with COVID-19 infects approximately 2.2 close contacts, and asymptomatic transmission has been reported [2,3]. SARS-CoV-2 survives in aerosols and on surfaces from hours to days, respectively [4]. Therefore, we believe non-clinical areas are potentially high-risk for transmission between healthcare workers, and often neglected by infection prevention and control protocols. To alert others to this risk and how it may be reduced, we describe our non-clinical workplace infection prevention and control measures that have been modified from those originally developed during the 2003 severe acute respiratory syndrome epidemic [5].", "qid": 15, "docid": "w62mynqb", "rank": 98, "score": 0.721743643283844}, {"content": "Title: Effects of air temperature and relative humidity on coronavirus survival on surfaces. Content: Assessment of the risks posed by severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) on surfaces requires data on survival of this virus on environmental surfaces and on how survival is affected by environmental variables, such as air temperature (AT) and relative humidity (RH). The use of surrogate viruses has the potential to overcome the challenges of working with SARS-CoV and to increase the available data on coronavirus survival on surfaces. Two potential surrogates were evaluated in this study; transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) were used to determine effects of AT and RH on the survival of coronaviruses on stainless steel. At 4 degrees C, infectious virus persisted for as long as 28 days, and the lowest level of inactivation occurred at 20% RH. Inactivation was more rapid at 20 degrees C than at 4 degrees C at all humidity levels; the viruses persisted for 5 to 28 days, and the slowest inactivation occurred at low RH. Both viruses were inactivated more rapidly at 40 degrees C than at 20 degrees C. The relationship between inactivation and RH was not monotonic, and there was greater survival or a greater protective effect at low RH (20%) and high RH (80%) than at moderate RH (50%). There was also evidence of an interaction between AT and RH. The results show that when high numbers of viruses are deposited, TGEV and MHV may survive for days on surfaces at ATs and RHs typical of indoor environments. TGEV and MHV could serve as conservative surrogates for modeling exposure, the risk of transmission, and control measures for pathogenic enveloped viruses, such as SARS-CoV and influenza virus, on health care surfaces.", "qid": 15, "docid": "tjplc5j6", "rank": 99, "score": 0.7217428088188171}, {"content": "Title: Epidemiological Tools that Predict Partial Herd Immunity to SARS Coronavirus 2 Content: The outbreak of SARS coronavirus 2 (SARS-CoV-2), which occurred in Wuhan, China in December 2019, has caused a worldwide pandemic of coronavirus disease 2019 (COVID-19). However, there is a lack of epidemiological tools to guide effective public policy development. Here we present epidemiological evidence that SARS-CoV-2 S type exited Wuhan or other epicenters in China earlier than L type and conferred partial resistance to the virus on infected populations. Analysis of regional disparities in incidence has revealed that a sharp decline in influenza epidemics is a useful surrogate indicator for the undocumented spread of SARS-CoV-2. The biggest concern in the world is knowing when herd immunity has been achieved and scheduling a time to regain the living activities of each country. This study provides a useful tool to guide the development of local policies to contain the virus.", "qid": 15, "docid": "7onenxg7", "rank": 100, "score": 0.7213627696037292}]}
{"query": "how long does coronavirus remain stable  on surfaces?", "hits": [{"content": "Title: Isolation and identification of human coronavirus 229E from frequently touched environmental surfaces of a university classroom that is cleaned daily Content: Frequently touched surfaces of a university classroom that is cleaned daily contained viable human coronavirus 229E (CoV-229E). Tests of a CoV-229E laboratory strain under conditions that simulated the ambient light, temperature, and relative humidity conditions of the classroom revealed that some of the virus remained viable on various surfaces for 7 days, suggesting CoV-229E is relatively stable in the environment. Our findings reinforce the notion that contact transmission may be possible for this virus.", "qid": 16, "docid": "khpc9f98", "rank": 1, "score": 0.8383674621582031}, {"content": "Title: Stability and infectivity of coronaviruses in inanimate environments Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious virus that can transmit through respiratory droplets, aerosols, or contacts. Frequent touching of contaminated surfaces in public areas is therefore a potential route of SARS-CoV-2 transmission. The inanimate surfaces have often been described as a source of nosocomial infections. However, summaries on the transmissibility of coronaviruses from contaminated surfaces to induce the coronavirus disease 2019 are rare at present. This review aims to summarize data on the persistence of different coronaviruses on inanimate surfaces. The literature was systematically searched on Medline without language restrictions. All reports with experimental evidence on the duration persistence of coronaviruses on any type of surface were included. Most viruses from the respiratory tract, such as coronaviruses, influenza, SARS-CoV, or rhinovirus, can persist on surfaces for a few days. Persistence time on inanimate surfaces varied from minutes to up to one month, depending on the environmental conditions. SARS-CoV-2 can be sustained in air in closed unventilated buses for at least 30 min without losing infectivity. The most common coronaviruses may well survive or persist on surfaces for up to one month. Viruses in respiratory or fecal specimens can maintain infectivity for quite a long time at room temperature. Absorbent materials like cotton are safer than unabsorbent materials for protection from virus infection. The risk of transmission via touching contaminated paper is low. Preventive strategies such as washing hands and wearing masks are critical to the control of coronavirus disease 2019.", "qid": 16, "docid": "ou7w3zkv", "rank": 2, "score": 0.8288296461105347}, {"content": "Title: Stability of SARS-CoV-2 on environmental surfaces and in human excreta Content: At room temperature, SARS-CoV-2 was stable on environmental surfaces and remained viable up to 7 days on smooth surfaces. This virus could survive for several hours in feces and 3-4 days in urine.", "qid": 16, "docid": "ej93duxi", "rank": 3, "score": 0.8284991383552551}, {"content": "Title: Effect of Environmental Conditions on SARS-CoV-2 Stability in Human Nasal Mucus and Sputum Content: We found that environmental conditions affect the stability of severe acute respiratory syndrome coronavirus 2 in nasal mucus and sputum. The virus is more stable at low-temperature and low-humidity conditions, whereas warmer temperature and higher humidity shortened half-life. Although infectious virus was undetectable after 48 hours, viral RNA remained detectable for 7 days.", "qid": 16, "docid": "04awj06g", "rank": 4, "score": 0.8211350440979004}, {"content": "Title: Effect of Environmental Conditions on SARS-CoV-2 Stability in Human Nasal Mucus and Sputum. Content: We found that environmental conditions affect the stability of severe acute respiratory syndrome coronavirus 2 in nasal mucus and sputum. The virus is more stable at low-temperature and low-humidity conditions, whereas warmer temperature and higher humidity shortened half-life. Although infectious virus was undetectable after 48 hours, viral RNA remained detectable for 7 days.", "qid": 16, "docid": "4819g00y", "rank": 5, "score": 0.8211350440979004}, {"content": "Title: Inanimate surfaces as potential source of 2019-nCoV spread and their disinfection with biocidal agents Content: The WHO has declared COVID-19 illness a global health concern which is caused by 2019-nCoV, causing severe respiratory tract infections in humans. Transmissibility among individual to individual have been reported through droplets and probably also via contaminated surfaces and hands. Human coronaviruses can persist on inanimate surfaces such as plastic, glass, fibers and metals up to nine days. 2019-nCoV remains infectious in air for 3 h and on inanimate surfaces such as cardboard, copper, plastic and steel up to 24, 4, 72 and 48 h respectively. Disinfectant activity of various biocidal agents against coronaviruses like ethanol (62\u201371%), sodium hypochlorite (0.1%) and hydrogen peroxide (0.5%) can be regarded effective against 2019-nCoV as well. As no vaccine and antiviral therapies have been discovered for 2019-nCoV, prevention of further spread will viable option to control the ongoing and future outbreaks.", "qid": 16, "docid": "esvutpel", "rank": 6, "score": 0.8193621039390564}, {"content": "Title: Potential role of inanimate surfaces for the spread of coronaviruses and their inactivation with disinfectant agents Content: Summary The novel human coronavirus SARS-CoV-2 has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described, probably via droplets but possibly also via contaminated hands or surfaces. In a recent review on the persistence of human and veterinary coronaviruses on inanimate surfaces it was shown that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days. Some disinfectant agents effectively reduce coronavirus infectivity within 1 minute such 62%\u201371% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite. Other compounds such as 0.05%\u20130.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. An effective surface disinfection may help to ensure an early containment and prevention of further viral spread.", "qid": 16, "docid": "80dfqjql", "rank": 7, "score": 0.8006078004837036}, {"content": "Title: Modeling the Stability of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on Skin, Currency, and Clothing Content: A new coronavirus (SARS-CoV-2) emerged in the winter of 2019 in Wuhan, China, and rapidly spread around the world. The extent and efficiency of SARS-CoV-2 pandemic is far greater than previous coronaviruses that emerged in the 21st Century. Here, we modeled stability of SARS-CoV-2 on skin, paper currency, and clothing to determine if these surfaces may factor in the fomite transmission dynamics of SARS-CoV-2. Skin, currency, and clothing samples were exposed to SARS-CoV-2 under laboratory conditions and incubated at three different temperatures (4C, 22C, and 37C). Stability was evaluated at 0 hours (h), 4 h, 8 h, 24 h, 72 h, 96 h, 7 days, and 14 days post-exposure. SARS-CoV-2 was shown to be stable on skin through the duration of the experiment at 4C (14 days). Virus remained stable on skin for at least 96 h at 22C and for at least 8h at 37C. There were minimal differences between the tested currency samples. The virus remained stable on the $1 U.S.A. Bank Note for at least 96 h at 4C while viable virus was not detected on the $20 U.S.A. Bank Note samples beyond 72 h. The virus remained stable on both Bank Notes for at least 8 h at 22C and 4 h at 37C. Clothing samples were similar in stability to the currency with the virus being detected for at least 96 h at 4C and at least 4 h at 22C. No viable virus was detected on clothing samples at 37C after initial exposure. This study confirms the inverse relationship between virus stability and temperature. Furthermore, virus stability on skin demonstrates the need for continued hand hygiene practices to minimize fomite transmission both in the general population as well as workplaces where close contact is common.", "qid": 16, "docid": "ywusapij", "rank": 8, "score": 0.8001652359962463}, {"content": "Title: Stability of bovine coronavirus on lettuce surfaces under household refrigeration conditions Content: Fecal suspensions with an aerosol route of transmission were responsible for a cluster of severe acute respiratory syndrome (SARS) cases in 2003 in Hong Kong. Based on that event, the World Health Organization recommended that research be implemented to define modes of transmission of SARS coronavirus through sewage, feces, food and water. Environmental studies have shown that animal coronaviruses remain infectious in water and sewage for up to a year depending on the temperature and humidity. In this study, we examined coronavirus stability on lettuce surfaces. A cell culture adapted bovine coronavirus, diluted in growth media or in bovine fecal suspensions to simulate fecal contamination was used to spike romaine lettuce. qRT-PCR detected viral RNA copy number ranging from 6.6 \u00d7 10(4) to 1.7 \u00d7 10(6) throughout the experimental period of 30 days. Whereas infectious viruses were detected for at least 14 days, the amount of infectious virus varied, depending upon the diluent used for spiking the lettuce. UV and confocal microscopic observation indicated attachment of residual labeled virions to the lettuce surface after the elution procedure, suggesting that rates of inactivation or detection of the virus may be underestimated. Thus, it is possible that contaminated vegetables may be potential vehicles for coronavirus zoonotic transmission to humans.", "qid": 16, "docid": "zmaw9lbz", "rank": 9, "score": 0.7965445518493652}, {"content": "Title: Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents Content: Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62-71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05-0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.", "qid": 16, "docid": "ssq0dwmn", "rank": 10, "score": 0.7962636947631836}, {"content": "Title: Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents Content: Summary Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62\u201371% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05\u20130.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.", "qid": 16, "docid": "k9xhphpl", "rank": 11, "score": 0.7929157018661499}, {"content": "Title: Droplet evaporation residue indicating SARS-COV-2 survivability on surfaces Content: SARS-CoV-2 survives and remains viable on surfaces for several days under different environments as reported in recent studies. However, it is unclear how the viruses survive for such a long time and why their survivability varies across different surfaces. To address these questions, we conduct systematic experiments investigating the evaporation of droplets produced by a nebulizer and human-exhaled gas on surfaces. We found that these droplets do not disappear with evaporation, but instead shrink to a size of a few micrometers (referred to as residues), persist for more than 24 hours, and are highly durable against changes of environmental conditions. The characteristics of these residues change significantly across surface types. Specifically, surfaces with high thermal conductivity like copper do not leave any resolvable residues, while stainless steel, plastic, and glass surfaces form residues from a varying fraction of all deposited droplets at 40% relative humidity. Lowering humidity level suppresses the formation of residues while increasing humidity level enhances it. Our results suggest that these microscale residues can potentially insulate the virus against environmental changes, allowing them to survive inhospitable environments and remain infectious for prolonged durations after deposition. Our findings can also be extended to other viruses transmitted through respiratory droplets (e.g., SARS-CoV, flu viruses, etc.), and can thus lead to practical guidelines for disinfecting surfaces and other prevention measures (e.g., humidity control) for limiting viral transmission.", "qid": 16, "docid": "pdmfxssd", "rank": 12, "score": 0.7928886413574219}, {"content": "Title: Stability of SARS-CoV-2 on Critical Personal Protective Equipment Content: The spread of COVID-19 in healthcare settings is concerning, with healthcare workers representing a disproportionately high percentage of confirmed cases. Although SARS-CoV-2 virus has been found to persist on surfaces for a number of days, the extent and duration of fomites as a mode of transmission, particularly in healthcare settings, has not been fully characterized. To shed light on this critical matter, the present study provides the first comprehensive assessment of SARS-CoV-2 stability on experimentally contaminated personal protective equipment (PPE) widely used by healthcare workers and the general public. Persistence of viable virus was monitored over 21 days on eight different materials, including nitrile medical examination gloves, reinforced chemical resistant gloves, N-95 and N-100 particulate respirator masks, Tyvek, plastic, cotton, and stainless steel. Unlike previous reports, viable SARS-CoV-2 in the presence of a soil load persisted for up to 21 days on experimentally inoculated PPE, including materials from filtering facepiece respirators (N-95 and N-100 masks) and a plastic visor. Conversely, when applied to 100% cotton fabric, the virus underwent rapid degradation and became undetectable in less than 24 hours. These findings underline the importance of appropriate handling of contaminated PPE during and following use in high-risk settings and provide interesting insight into the potential utility of cotton, including cotton masks, in limiting COVID-19 transmission.", "qid": 16, "docid": "qpc4hyvl", "rank": 13, "score": 0.7913707494735718}, {"content": "Title: Increasing Temperature and Relative Humidity Accelerates Inactivation of SARS-CoV-2 on Surfaces Content: Coronavirus disease 2019 (COVID-19) was first identified in China in late 2019 and is caused by newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Previous studies had reported the stability of SARS-CoV-2 in cell culture media and deposited onto surfaces under a limited set of environmental conditions. Here, we broadly investigated the effects of relative humidity, temperature, and droplet size on the stability of SARS-CoV-2 in a simulated clinically relevant matrix dried on nonporous surfaces. The results show that SARS-CoV-2 decayed more rapidly when either humidity or temperature was increased but that droplet volume (1 to 50 \u03bcl) and surface type (stainless steel, plastic, or nitrile glove) did not significantly impact decay rate. At room temperature (24\u00b0C), virus half-life ranged from 6.3 to 18.6 h depending on the relative humidity but was reduced to 1.0 to 8.9 h when the temperature was increased to 35\u00b0C. These findings suggest that a potential for fomite transmission may persist for hours to days in indoor environments and have implications for assessment of the risk posed by surface contamination in indoor environments. IMPORTANCE Mitigating the transmission of SARS-CoV-2 in clinical settings and public spaces is critically important to reduce the number of COVID-19 cases while effective vaccines and therapeutics are under development. SARS-CoV-2 transmission is thought to primarily occur through direct person-to-person transfer of infectious respiratory droplets or through aerosol-generating medical procedures. However, contact with contaminated surfaces may also play a significant role. In this context, understanding the factors contributing to SARS-CoV-2 persistence on surfaces will enable a more accurate estimation of the risk of contact transmission and inform mitigation strategies. To this end, we have developed a simple mathematical model that can be used to estimate virus decay on nonporous surfaces under a range of conditions and which may be utilized operationally to identify indoor environments in which the virus is most persistent.", "qid": 16, "docid": "1vhprok9", "rank": 14, "score": 0.7879522442817688}, {"content": "Title: Increasing Temperature and Relative Humidity Accelerates Inactivation of SARS-CoV-2 on Surfaces Content: Coronavirus disease 2019 (COVID-19) was first identified in China in late 2019 and is caused by newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Previous studies had reported the stability of SARS-CoV-2 in cell culture media and deposited onto surfaces under a limited set of environmental conditions. Here, we broadly investigated the effects of relative humidity, temperature, and droplet size on the stability of SARS-CoV-2 in a simulated clinically relevant matrix dried on nonporous surfaces. The results show that SARS-CoV-2 decayed more rapidly when either humidity or temperature was increased but that droplet volume (1 to 50 \u00b5l) and surface type (stainless steel, plastic, or nitrile glove) did not significantly impact decay rate. At room temperature (24\u00b0C), virus half-life ranged from 6.3 to 18.6 h depending on the relative humidity but was reduced to 1.0 to 8.9 h when the temperature was increased to 35\u00b0C. These findings suggest that a potential for fomite transmission may persist for hours to days in indoor environments and have implications for assessment of the risk posed by surface contamination in indoor environments.IMPORTANCE Mitigating the transmission of SARS-CoV-2 in clinical settings and public spaces is critically important to reduce the number of COVID-19 cases while effective vaccines and therapeutics are under development. SARS-CoV-2 transmission is thought to primarily occur through direct person-to-person transfer of infectious respiratory droplets or through aerosol-generating medical procedures. However, contact with contaminated surfaces may also play a significant role. In this context, understanding the factors contributing to SARS-CoV-2 persistence on surfaces will enable a more accurate estimation of the risk of contact transmission and inform mitigation strategies. To this end, we have developed a simple mathematical model that can be used to estimate virus decay on nonporous surfaces under a range of conditions and which may be utilized operationally to identify indoor environments in which the virus is most persistent.", "qid": 16, "docid": "e2paoo2m", "rank": 15, "score": 0.7878236770629883}, {"content": "Title: The Effects of Temperature and Relative Humidity on the Viability of the SARS Coronavirus Content: The main route of transmission of SARS CoV infection is presumed to be respiratory droplets. However the virus is also detectable in other body fluids and excreta. The stability of the virus at different temperatures and relative humidity on smooth surfaces were studied. The dried virus on smooth surfaces retained its viability for over 5 days at temperatures of 22\u201325\u00b0C and relative humidity of 40\u201350%, that is, typical air-conditioned environments. However, virus viability was rapidly lost (>3 log(10)) at higher temperatures and higher relative humidity (e.g., 38\u00b0C, and relative humidity of >95%). The better stability of SARS coronavirus at low temperature and low humidity environment may facilitate its transmission in community in subtropical area (such as Hong Kong) during the spring and in air-conditioned environments. It may also explain why some Asian countries in tropical area (such as Malaysia, Indonesia or Thailand) with high temperature and high relative humidity environment did not have major community outbreaks of SARS.", "qid": 16, "docid": "x3b6j5d0", "rank": 16, "score": 0.7872440814971924}, {"content": "Title: Stability of SARS\u2010CoV\u20102 and other coronaviruses in the environment and on common touch surfaces and the influence of climatic conditions: A review Content: Although the unprecedented efforts the world has been taking to control the spread of the human coronavirus disease (COVID\u201019) and its causative aetiology [severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102)], the number of confirmed cases has been increasing drastically. Therefore, there is an urgent need for devising more efficient preventive measures, to limit the spread of the infection until an effective treatment or vaccine is available. The preventive measures depend mainly on the understanding of the transmission routes of this virus, its environmental stability, and its persistence on common touch surfaces. Due to the very limited knowledge about SARS\u2010CoV\u20102, we can speculate its stability in the light of previous studies conducted on other human and animal coronaviruses. In this review, we present the available data on the stability of coronaviruses (CoVs), including SARS\u2010CoV\u20102, from previous reports to help understand its environmental survival. According to available data, possible airborne transmission of SARS\u2010CoV\u20102 has been suggested. SARS\u2010CoV\u20102 and other human and animal CoVs have remarkably short persistence on copper, latex and surfaces with low porosity as compared to other surfaces like stainless steel, plastics, glass and highly porous fabrics. It has also been reported that SARS\u2010CoV\u20102 is associated with diarrhoea and that it is shed in the faeces of COVID\u201019 patients. Some CoVs show persistence in human excrement, sewage and waters for a few days. These findings suggest a possible risk of faecal\u2013oral, foodborne and waterborne transmission of SARS\u2010CoV\u20102 in developing countries that often use sewage\u2010polluted waters in irrigation and have poor water treatment systems. CoVs survive longer in the environment at lower temperatures and lower relative humidity. It has been suggested that large numbers of COVID\u201019 cases are associated with cold and dry climates in temperate regions of the world and that seasonality of the virus spread is suspected.", "qid": 16, "docid": "rhfwbyav", "rank": 17, "score": 0.7835994362831116}, {"content": "Title: Stability and inactivation of SARS coronavirus Content: The SARS-coronavirus (SARS-CoV) is a newly emerged, highly pathogenic agent that caused over 8,000 human infections with nearly 800 deaths between November 2002 and September 2003. While direct person-to-person transmission via respiratory droplets accounted for most cases, other modes have not been ruled out. Faecal shedding is common and prolonged and has caused an outbreak in Hong Kong. We studied the stability of SARS-CoV under different conditions, both in suspension and dried on surfaces, in comparison with other human-pathogenic viruses, including human coronavirus HCoV-229E. In suspension, HCoV-229E gradually lost its infectivity completely while SARS-CoV retained its infectivity for up to 9 days; in the dried state, survival times were 24 h versus 6 days. Thermal inactivation at 56\u00b0C was highly effective in the absence of protein, reducing the virus titre to below detectability; however, the addition of 20% protein exerted a protective effect resulting in residual infectivity. If protein-containing solutions are to be inactivated, heat treatment at 60\u00b0C for at least 30 min must be used. Different fixation procedures, e.g. for the preparation of immunofluorescence slides, as well as chemical means of virus inactivation commonly used in hospital and laboratory settings were generally found to be effective. Our investigations confirm that it is possible to care for SARS patients and to conduct laboratory scientific studies on SARS-CoV safely. Nevertheless, the agent\u2019s tenacity is considerably higher than that of HCoV-229E, and should SARS re-emerge, increased efforts need to be devoted to questions of environmental hygiene.", "qid": 16, "docid": "8s9671zf", "rank": 18, "score": 0.7818312644958496}, {"content": "Title: Effects of air temperature and relative humidity on coronavirus survival on surfaces. Content: Assessment of the risks posed by severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) on surfaces requires data on survival of this virus on environmental surfaces and on how survival is affected by environmental variables, such as air temperature (AT) and relative humidity (RH). The use of surrogate viruses has the potential to overcome the challenges of working with SARS-CoV and to increase the available data on coronavirus survival on surfaces. Two potential surrogates were evaluated in this study; transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) were used to determine effects of AT and RH on the survival of coronaviruses on stainless steel. At 4 degrees C, infectious virus persisted for as long as 28 days, and the lowest level of inactivation occurred at 20% RH. Inactivation was more rapid at 20 degrees C than at 4 degrees C at all humidity levels; the viruses persisted for 5 to 28 days, and the slowest inactivation occurred at low RH. Both viruses were inactivated more rapidly at 40 degrees C than at 20 degrees C. The relationship between inactivation and RH was not monotonic, and there was greater survival or a greater protective effect at low RH (20%) and high RH (80%) than at moderate RH (50%). There was also evidence of an interaction between AT and RH. The results show that when high numbers of viruses are deposited, TGEV and MHV may survive for days on surfaces at ATs and RHs typical of indoor environments. TGEV and MHV could serve as conservative surrogates for modeling exposure, the risk of transmission, and control measures for pathogenic enveloped viruses, such as SARS-CoV and influenza virus, on health care surfaces.", "qid": 16, "docid": "tjplc5j6", "rank": 19, "score": 0.7790642380714417}, {"content": "Title: Survival of Coronaviruses in Water and Wastewater Content: The advent of severe acute respiratory syndrome and its potential environmental transmission indicates the need for more information on the survival of coronavirus in water and wastewater. The survival of representative coronaviruses, feline infectious peritonitis virus, and human coronavirus 229E was determined in filtered and unfiltered tap water (4 and 23\u00b0C) and wastewater (23\u00b0C). This was compared to poliovirus 1 under the same test conditions. Inactivation of coronaviruses in the test water was highly dependent on temperature, level of organic matter, and presence of antagonistic bacteria. The time required for the virus titer to decrease 99.9% (T(99.9)) shows that in tap water, coronaviruses are inactivated faster in water at 23\u00b0C (10 days) than in water at 4\u00b0C (>100 days). Coronaviruses die off rapidly in wastewater, with T(99.9) values of between 2 and 4 days. Poliovirus survived longer than coronaviruses in all test waters, except the 4\u00b0C tap water.", "qid": 16, "docid": "0y8lfjkx", "rank": 20, "score": 0.7786436080932617}, {"content": "Title: Coronaviruses widespread on nonliving surfaces: important questions and promising answers Content: The world is facing, while writing this review, a global pandemic due to one of the types of the coronaviruses (i.e., COVID-19), which is a new virus. Among the most important reasons for the transmission of infection between humans is the presence of this virus active on the surfaces and materials. Here, we addressed important questions such as do coronaviruses remain active on the inanimate surfaces? Do the types of inanimate surfaces affect the activity of coronaviruses? What are the most suitable ingredients that used to inactivate viruses? This review article addressed many of the works that were done in the previous periods on the survival of many viruses from the coronaviruses family on various surfaces such as steel, glass, plastic, Teflon, ceramic tiles, silicon rubber and stainless steel copper alloys, Al surface, sterile sponges, surgical gloves and sterile latex. The impacts of environmental conditions such as temperature and humidity were presented and discussed. The most important active ingredients that can deactivate viruses on the surfaces were reported here. We hope that these active ingredients will have the same effect on COVID-19.", "qid": 16, "docid": "fxx5vrg0", "rank": 21, "score": 0.7785618305206299}, {"content": "Title: Coronaviruses widespread on nonliving surfaces: important questions and promising answers. Content: The world is facing, while writing this review, a global pandemic due to one of the types of the coronaviruses (i.e., COVID-19), which is a new virus. Among the most important reasons for the transmission of infection between humans is the presence of this virus active on the surfaces and materials. Here, we addressed important questions such as do coronaviruses remain active on the inanimate surfaces? Do the types of inanimate surfaces affect the activity of coronaviruses? What are the most suitable ingredients that used to inactivate viruses? This review article addressed many of the works that were done in the previous periods on the survival of many viruses from the coronaviruses family on various surfaces such as steel, glass, plastic, Teflon, ceramic tiles, silicon rubber and stainless steel copper alloys, Al surface, sterile sponges, surgical gloves and sterile latex. The impacts of environmental conditions such as temperature and humidity were presented and discussed. The most important active ingredients that can deactivate viruses on the surfaces were reported here. We hope that these active ingredients will have the same effect on COVID-19.", "qid": 16, "docid": "9xv9t5ba", "rank": 22, "score": 0.7785618305206299}, {"content": "Title: Stability of SARS-CoV-2 and other coronaviruses in the environment and on common touch surfaces and the influence of climatic conditions: a review Content: Although the unprecedented efforts the world has been taking to control the spread of the human coronavirus disease (COVID-19) and its causative etiology [Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2)], the number of confirmed cases has been increasing drastically. Therefore, there is an urgent need for devising more efficient preventive measures, to limit the spread of the infection until an effective treatment or vaccine is available. The preventive measures depend mainly on the understanding of the transmission routes of this virus, its environmental stability, and its persistence on common touch surfaces. Due to the very limited knowledge about SARS-CoV-2, we can speculate its stability in the light of previous studies conducted on other human and animal coronaviruses. In this review, we present the available data on the stability of coronaviruses (CoVs), including SARS-CoV-2, from previous reports to help understand its environmental survival. According to available data, possible airborne transmission of SARS-CoV-2 has been suggested. SARS-CoV-2 and other human and animal CoVs have remarkably short persistence on copper, latex, and surfaces with low porosity as compared to other surfaces like stainless steel, plastics, glass, and highly porous fabrics. It has also been reported that SARS-CoV-2 is associated with diarrhea and that it is shed in the feces of COVID-19 patients. Some CoVs show persistence in human excrement, sewage, and waters for a few days. These findings suggest a possible risk of fecal-oral, foodborne, and waterborne transmission of SARS-CoV-2 in developing countries that often use sewage-polluted waters in irrigation and have poor water treatment systems. CoVs survive longer in the environment at lower temperatures and lower relative humidity. It has been suggested that large numbers of COVID-19 cases are associated with cold and dry climates in temperate regions of the world and that seasonality of the virus spread is suspected.", "qid": 16, "docid": "z4vfjlbg", "rank": 23, "score": 0.7755279541015625}, {"content": "Title: Modelling the thermal inactivation of viruses from the Coronaviridae family in suspensions or on surfaces with various relative humidities. Content: Temperature and relative humidity are major factors determining virus inactivation in the environment. This article reviews inactivation data of coronaviruses on surfaces and in liquids from published studies and develops secondary models to predict coronaviruses inactivation as a function of temperature and relative humidity. A total of 102 D-values (time to obtain a log10 reduction of virus infectivity), including values for SARS-CoV-2, were collected from 26 published studies. The values obtained from the different coronaviruses and studies were found to be generally consistent. Five different models were fitted to the global dataset of D-values. The most appropriate model considered temperature and relative humidity. A spreadsheet predicting the inactivation of coronaviruses and the associated uncertainty is presented and can be used to predict virus inactivation for untested temperatures, time points or new coronavirus strains.", "qid": 16, "docid": "4hbwg18z", "rank": 24, "score": 0.775050163269043}, {"content": "Title: Stability of SARS coronavirus in human specimens and environment and its sensitivity to heating and UV irradiation. Content: OBJECTIVE The causal agent for SARS is considered as a novel coronavirus that has never been described both in human and animals previously. The stability of SARS coronavirus in human specimens and in environments was studied. METHODS Using a SARS coronavirus strain CoV-P9, which was isolated from pharyngeal swab of a probable SARS case in Beijing, its stability in mimic human specimens and in mimic environment including surfaces of commonly used materials or in household conditions, as well as its resistance to temperature and UV irradiation were analyzed. A total of 10(6) TCID50 viruses were placed in each tested condition, and changes of the viral infectivity in samples after treatments were measured by evaluating cytopathic effect (CPE) in cell line Vero-E6 at 48 h after infection. RESULTS The results showed that SARS coronavirus in the testing condition could survive in serum, 1:20 diluted sputum and feces for at least 96 h, whereas it could remain alive in urine for at least 72 h with a low level of infectivity. The survival abilities on the surfaces of eight different materials and in water were quite comparable, revealing reduction of infectivity after 72 to 96 h exposure. Viruses stayed stable at 4 degrees C, at room temperature (20 degrees C) and at 37 degrees C for at least 2 h without remarkable change in the infectious ability in cells, but were converted to be non-infectious after 90-, 60- and 30-min exposure at 56 degrees C, at 67 degrees C and at 75 degrees C, respectively. Irradiation of UV for 60 min on the virus in culture medium resulted in the destruction of viral infectivity at an undetectable level. CONCLUSION The survival ability of SARS coronavirus in human specimens and in environments seems to be relatively strong. Heating and UV irradiation can efficiently eliminate the viral infectivity.", "qid": 16, "docid": "gp3ib74q", "rank": 25, "score": 0.769473135471344}, {"content": "Title: Survival of human coronaviruses 229E and OC43 in suspension and after drying onsurfaces: a possible source ofhospital-acquired infections Content: Abstract Strains OC43 and 229E of human coronaviruses (HCoV) cause one-third of common colds and hospital-acquired upper respiratory tract HCoV infections have been reported in premature newborns. To evaluate possible sources of infection, virus survival was studied in aqueous suspensions and on absorptive and non-absorptive surfaces representative of a hospital environment. Virus susceptibility to chemical disinfection with standard products was also characterized. Virus survived in saline solution for as long as six days but less in culture medium, with or without added cells. After drying, HCoV-229E infectivity was still detectable after 3h on various surfaces (aluminum, sterile latex surgical gloves, sterile sponges) but HCoV-OC43 survived 1h or less. Of the various chemical disinfectants tested, Proviodine\u00ae reduced the virus infectious titre by at least 50%. This study suggests that surfaces and suspensions can be considered as possible sources of contamination that may lead to hospital-acquired infections with HCoV and should be appropriately disinfected.", "qid": 16, "docid": "5gayhkxx", "rank": 26, "score": 0.7683273553848267}, {"content": "Title: Prolonged Infectivity of SARS-CoV-2 in Fomites Content: We spotted severe acute respiratory syndrome coronavirus 2 on polystyrene plastic, aluminum, and glass for 96 hours with and without bovine serum albumin (3 g/L). We observed a steady infectivity (<1 log10 drop) on plastic, a 3.5 log10 decrease on glass, and a 6 log10 drop on aluminum. The presence of proteins noticeably prolonged infectivity.", "qid": 16, "docid": "3mcvp0h6", "rank": 27, "score": 0.7666350603103638}, {"content": "Title: Prolonged Infectivity of SARS-CoV-2 in Fomites. Content: We spotted severe acute respiratory syndrome coronavirus 2 on polystyrene plastic, aluminum, and glass for 96 hours with and without bovine serum albumin (3 g/L). We observed a steady infectivity (<1 log10 drop) on plastic, a 3.5 log10 decrease on glass, and a 6 log10 drop on aluminum. The presence of proteins noticeably prolonged infectivity.", "qid": 16, "docid": "vwmjf326", "rank": 28, "score": 0.7666350603103638}, {"content": "Title: Effective Heat Inactivation of SARS-CoV-2 Content: The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) has quickly turned into a global pandemic. Infectious viruses had been isolated from oro- or naso-pharyngeal swabs, sputum and possibly stool samples of infected individuals. Handling these clinical specimens therefore poses a biosafety risk to both healthcare professionals and laboratory workers. In this study, we aimed to evaluate the stability of SARS-CoV-2 under different heat conditions and report that the virus is stable at 37 C for at least 24 hours. Heating at 56 C for 30 minutes, however, effectively inactivated the virus while preserved the stability of viral RNA in both human sera and sputum samples. These findings provide critical information regarding the biology of the virus as well as a practical way to inactivate infectious virus that is potentially found in clinical specimens.", "qid": 16, "docid": "og69izi3", "rank": 29, "score": 0.7657110691070557}, {"content": "Title: Survival of surrogate coronaviruses in water Content: Abstract The emergence of a previously unknown coronavirus infection, Severe Acute Respiratory Syndrome (SARS), demonstrated that fecally contaminated liquid droplets are a potential vehicle for the spread of a respiratory virus to large numbers of people. To assess potential risks from this pathway, there is a need for surrogates for SARS coronavirus to provide representative data on viral survival in contaminated water. This study evaluated survival of two surrogate coronaviruses, transmissible gastroenteritis (TGEV) and mouse hepatitis (MHV). These viruses remained infectious in water and sewage for days to weeks. At 25\u00b0C, time required for 99% reduction in reagent-grade water was 22 days for TGEV and 17 days for MHV. In pasteurized settled sewage, times for 99% reduction were 9 days for TGEV and 7 days for MHV. At 4\u00b0C, there was <1log10 infectivity decrease for both viruses after four weeks. Coronaviruses can remain infectious for long periods in water and pasteurized settled sewage, suggesting contaminated water is a potential vehicle for human exposure if aerosols are generated.", "qid": 16, "docid": "hky6isk2", "rank": 30, "score": 0.7643101811408997}, {"content": "Title: Canine coronavirus inactivation with physical and chemical agents Content: Abstract Canine coronavirus (CCoV) is responsible for mild or moderate enteritis in puppies. The virus is highly contagious and avoiding contact with infected dogs and their excretions is the only way to ensure disease prevention. Since no studies have yet focused on the sensitivity of CCoV to chemical biocides the present investigation examined the efficiency of physical and chemical methods of viral inactivation. CCoV infectivity was stable at +56\u00b0C for up to 30min, but tended to decrease rapidly at +65\u00b0C and +75\u00b0C. Germicidal ultra-violet (UV\u2013C) light exposure demonstrated no significant effects on virus inactivation for up to 3 days. CCoV was observed to be more stable at pH 6.0\u20136.5 while extreme acidic conditions inactivated the virus. Two tested aldehydes inactivated the virus but their action was temperature- and time-dependent. The methods for CCoV inactivation could be applied as animal models to study human coronavirus infection, reducing the risk of accidental exposure of researchers to pathogens during routine laboratory procedures.", "qid": 16, "docid": "2j37561h", "rank": 31, "score": 0.7625640034675598}, {"content": "Title: Survival of Severe Acute Respiratory Syndrome Coronavirus Content: Background. The primary modes of transmission of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) appear to be direct mucus membrane contact with infectious droplets and through exposure to formites. Knowledge of the survival characteristics of the virus is essential for formulating appropriate infection-control measures. Methods. Survival of SARS-CoV strain GVU6109 was studied in stool and respiratory specimens. Survival of the virus on different environmental surfaces, including a laboratory request form, an impervious disposable gown, and a cotton nondisposable gown, was investigated. The virucidal effects of sodium hypochlorite, house detergent, and a peroxygen compound (Virkon S; Antec International) on the virus were also studied. Results. SARS-CoV GVU6109 can survive for 4 days in diarrheal stool samples with an alkaline pH, and it can remain infectious in respiratory specimens for >7 days at room temperature. Even at a relatively high concentration (10(4) tissue culture infective doses/mL), the virus could not be recovered after drying of a paper request form, and its infectivity was shown to last longer on the disposable gown than on the cotton gown. All disinfectants tested were shown to be able to reduce the virus load by >3 log within 5 min. Conclusions. Fecal and respiratory samples can remain infectious for a long period of time at room temperature. The risk of infection via contact with droplet-contaminated paper is small. Absorbent material, such as cotton, is preferred to nonabsorptive material for personal protective clothing for routine patient care where risk of large spillage is unlikely. The virus is easily inactivated by commonly used disinfectants.", "qid": 16, "docid": "h9gj814e", "rank": 32, "score": 0.7623823285102844}, {"content": "Title: Transmission of SARS and MERS coronaviruses and influenza virus in healthcare settings: the possible role of dry surface contamination Content: Summary Viruses with pandemic potential including H1N1, H5N1, and H5N7 influenza viruses, and severe acute respiratory syndrome (SARS)/Middle East respiratory syndrome (MERS) coronaviruses (CoV) have emerged in recent years. SARS-CoV, MERS-CoV, and influenza virus can survive on surfaces for extended periods, sometimes up to months. Factors influencing the survival of these viruses on surfaces include: strain variation, titre, surface type, suspending medium, mode of deposition, temperature and relative humidity, and the method used to determine the viability of the virus. Environmental sampling has identified contamination in field-settings with SARS-CoV and influenza virus, although the frequent use of molecular detection methods may not necessarily represent the presence of viable virus. The importance of indirect contact transmission (involving contamination of inanimate surfaces) is uncertain compared with other transmission routes, principally direct contact transmission (independent of surface contamination), droplet, and airborne routes. However, influenza virus and SARS-CoV may be shed into the environment and be transferred from environmental surfaces to hands of patients and healthcare providers. Emerging data suggest that MERS-CoV also shares these properties. Once contaminated from the environment, hands can then initiate self-inoculation of mucous membranes of the nose, eyes or mouth. Mathematical and animal models, and intervention studies suggest that contact transmission is the most important route in some scenarios. Infection prevention and control implications include the need for hand hygiene and personal protective equipment to minimize self-contamination and to protect against inoculation of mucosal surfaces and the respiratory tract, and enhanced surface cleaning and disinfection in healthcare settings.", "qid": 16, "docid": "pk8u9m7h", "rank": 33, "score": 0.761254072189331}, {"content": "Title: Aerosol and surface stability of HCoV-19 (SARS-CoV-2) compared to SARS-CoV-1 Content: A novel human coronavirus, now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, referred to as HCoV-19 here) that emerged in Wuhan, China in late 2019 is now causing a pandemic. Here, we analyze the aerosol and surface stability of HCoV-19 and compare it with SARS-CoV-1, the most closely related human coronavirus.2 We evaluated the stability of HCoV-19 and SARS-CoV-1 in aerosols and on different surfaces and estimated their decay rates using a Bayesian regression model", "qid": 16, "docid": "hiw576og", "rank": 34, "score": 0.7609660625457764}, {"content": "Title: Simulated Sunlight Rapidly Inactivates SARS-CoV-2 on Surfaces Content: Previous studies have demonstrated that SARS-CoV-2 is stable on surfaces for extended periods under indoor conditions. In the present study, simulated sunlight rapidly inactivated SARS-CoV-2 suspended in either simulated saliva or culture media and dried on stainless steel coupons. Ninety percent of infectious virus was inactivated every 6.8 minutes in simulated saliva and every 14.3 minutes in culture media when exposed to simulated sunlight representative of the summer solstice at 40\u00b0N latitude at sea level on a clear day. Significant inactivation also occurred, albeit at a slower rate, under lower simulated sunlight levels. The present study provides the first evidence that sunlight may rapidly inactivate SARS-CoV-2 on surfaces, suggesting that persistence, and subsequently exposure risk, may vary significantly between indoor and outdoor environments. Additionally, these data indicate that natural sunlight may be effective as a disinfectant for contaminated nonporous materials.", "qid": 16, "docid": "mixy6roy", "rank": 35, "score": 0.7570878267288208}, {"content": "Title: Effect of pH and temperature on the infectivity of human coronavirus 229E. Content: The stability of human coronavirus 229E infectivity was maximum at pH 6.0 when incubated at either 4 or 33 degrees C. However, the influence of pH was more pronounced at 33 degrees C. Viral infectivity was completely lost after a 14-day incubation period at 22, 33, or 37 degrees C but remained relatively constant at 4 degrees C for the same length of time. Finally, the infectious titer did not show any significant reduction when subjected to 25 cycles of thawing and freezing. These studies will contribute to optimize virus growth and storage conditions, which will facilitate the molecular characterization of this important pathogen.", "qid": 16, "docid": "jpw8f2op", "rank": 36, "score": 0.7538905739784241}, {"content": "Title: Human Coronavirus 229E Remains Infectious on Common Touch Surface Materials Content: The evolution of new and reemerging historic virulent strains of respiratory viruses from animal reservoirs is a significant threat to human health. Inefficient human-to-human transmission of zoonotic strains may initially limit the spread of transmission, but an infection may be contracted by touching contaminated surfaces. Enveloped viruses are often susceptible to environmental stresses, but the human coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) have recently caused increasing concern of contact transmission during outbreaks. We report here that pathogenic human coronavirus 229E remained infectious in a human lung cell culture model following at least 5 days of persistence on a range of common nonbiocidal surface materials, including polytetrafluoroethylene (Teflon; PTFE), polyvinyl chloride (PVC), ceramic tiles, glass, silicone rubber, and stainless steel. We have shown previously that noroviruses are destroyed on copper alloy surfaces. In this new study, human coronavirus 229E was rapidly inactivated on a range of copper alloys (within a few minutes for simulated fingertip contamination) and Cu/Zn brasses were very effective at lower copper concentration. Exposure to copper destroyed the viral genomes and irreversibly affected virus morphology, including disintegration of envelope and dispersal of surface spikes. Cu(I) and Cu(II) moieties were responsible for the inactivation, which was enhanced by reactive oxygen species generation on alloy surfaces, resulting in even faster inactivation than was seen with nonenveloped viruses on copper. Consequently, copper alloy surfaces could be employed in communal areas and at any mass gatherings to help reduce transmission of respiratory viruses from contaminated surfaces and protect the public health.", "qid": 16, "docid": "4d4l6mzl", "rank": 37, "score": 0.7536783218383789}, {"content": "Title: Stability of Middle East respiratory syndrome coronavirus (MERS-CoV) under different environmental conditions. Content: The stability of Middle East respiratory syndrome coronavirus (MERS-CoV) was determined at 20\u00b0C--40% relative humidity (RH); 30\u00b0C--30% RH and 30\u00b0C--80% RH. MERS-CoV was more stable at low temperature/low humidity conditions and could still be recovered after 48 hours. During aerosolisation of MERS-CoV, no decrease in stability was observed at 20\u00b0C--40% RH. These data suggest the potential of MERS-CoV to be transmitted via contact or fomite transmission due to prolonged environmental presence.", "qid": 16, "docid": "0wlapuuq", "rank": 38, "score": 0.753352165222168}, {"content": "Title: A Surface Coating that Rapidly Inactivates SARS-CoV-2. Content: SARS-CoV-2, the virus that causes the disease COVID-19, remains viable on solids for periods of up to one week, so one potential route for human infection is via exposure to an infectious dose from a solid. We have fabricated and tested a coating that is designed to reduce the longevity of SARS-CoV-2 on solids. The coating consists of cuprous oxide (Cu2O) particles bound with polyurethane. After one hour on coated glass or stainless steel, the viral titer was reduced by about 99.9% on average compared to the uncoated sample. An advantage of a polyurethane-based coating is that polyurethane is already used to coat a large number of everyday objects. Our coating adheres well to glass and stainless steel, as well as everyday items that people may fear to touch during a pandemic, such as a doorknob, a pen, and a credit card keypad button. The coating performs well in the cross-hatch durability test and remains intact and active after 13 days immersed in water, or after exposure to multiple cycles of exposure to virus and disinfection.", "qid": 16, "docid": "gxo13x70", "rank": 39, "score": 0.7528225183486938}, {"content": "Title: A Continuously Active Antimicrobial Coating effective against Human Coronavirus 229E Content: The disinfection of high-contact surfaces is seen as an infection control practice to prevent the spread of pathogens by fomites. Unfortunately, recontamination of these surfaces can occur any time after the use of common disinfectants. We recently reported on a novel continuously active antimicrobial coating which was shown to reduce the spread of healthcare acquired infections in hospitals. We evaluated a modified coating that demonstrated a residual efficacy against viruses. The coated surfaces were found to be effective against human coronavirus (HCoV) 229E, reducing the concentration of these viruses by greater than 90% in 10 minutes and by greater than 99.9% after two hours of contact. The coating formulation when tested in suspension yielded a greater than 99.99% reduction of HCoV 229E within ten minutes of contact. This outcome presents an opportunity for controlling the transmission of COVID-19 from contaminated fomites.", "qid": 16, "docid": "itm0bldp", "rank": 40, "score": 0.749688982963562}, {"content": "Title: Isothermal evaporation rate of deposited liquid aerosols and the SARS-CoV-2 coronavirus survival Content: It is shown that the evaporation rate of a liquid sample containing the culture of coronavirus affects its survival on a substrate. Possible mechanisms of such influence can be due to the appearance of large, about 140 bar, non comprehensive capillary pressures and the associated dynamic forces during the movement of the evaporation front in a sample with the virus. A simulation of isothermal evaporation of a thin liquid sample based on the Stefan problem was performed. The comparison of simulation data and recent experiments on the coronavirus survival on various surfaces showed that the rate of isothermal evaporation of aqueous samples, which is higher for heat-conducting materials, correlates well with the lifetime of the coronavirus on these surfaces.", "qid": 16, "docid": "80ev0j5a", "rank": 41, "score": 0.7492780685424805}, {"content": "Title: Study on the resistance of severe acute respiratory syndrome-associated coronavirus Content: Abstract In this study, the persistence of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) was observed in feces, urine and water. In addition, the inactivation of SARS-CoV in wastewater with sodium hypochlorite and chlorine dioxide was also studied. In vitro experiments demonstrated that the virus could only persist for 2 days in hospital wastewater, domestic sewage and dechlorinated tap water, while 3 days in feces, 14 days in PBS and 17 days in urine at 20\u00b0C. However, at 4\u00b0C, the SARS-CoV could persist for 14 days in wastewater and at least 17 days in feces or urine. SARS-CoV is more susceptible to disinfectants than Escherichia coli and f2 phage. Free chlorine was found to inactivate SARS-CoV better than chlorine dioxide. Free residue chlorine over 0.5mg/L for chlorine or 2.19mg/L for chlorine dioxide in wastewater ensures complete inactivation of SARS-CoV while it does not inactivate completely E. coli and f2 phage.", "qid": 16, "docid": "gwaqh4dd", "rank": 42, "score": 0.7466685771942139}, {"content": "Title: Sustainability of Coronavirus on different surfaces Content: Abstract COVID-19 is the name of the disease supposedly manifested in December 2019 from Wuhan, because of virus named as SARS-CoV-2. Now this disease has spread to almost all other parts of the world. COVID-19 pandemic has various reasons for its dramatic worldwide increase. Here, we have studied Coronavirus sustainability on various surfaces. Various disinfectants and their roles are discussed from the available literature. The infection capabilities of SARS-CoV-1 and SARS-CoV-2 for different materials are discussed and finally studies infection decay for SARS-CoV-1 and SARS-CoV-2.", "qid": 16, "docid": "f7gr98eb", "rank": 43, "score": 0.7431837916374207}, {"content": "Title: Risk of SARS-CoV-2 infection from contaminated water systems Content: Following the outbreak of severe acute respiratory syndrome coronavirus (SARS-CoV-2) in China, airborne water droplets (aerosols) have been identified as the main transmission route, although other transmission routes are likely to exist. We quantify SARS-CoV-2 virus survivability within water and the risk of infection posed by faecal contaminated water within 39 countries. We identify that the virus can remain stable within water for up to 25 days, and country specific relative risk of infection posed by faecal contaminated water is related to the environment. Faecal contaminated rivers, waterways and water systems within countries with high infection rates can provide infectious doses >100 copies within 100 ml of water. The implications for freshwater systems, the coastal marine environment and virus resurgence are discussed.", "qid": 16, "docid": "ycdok8fc", "rank": 44, "score": 0.74273282289505}, {"content": "Title: Factors affecting stability and infectivity of SARS-CoV-2 Content: BACKGROUND: In late 2019, a novel human coronavirus, SARS-CoV-2, emerged in Wuhan, China. This virus has caused a global pandemic involving more than 200 countries. SARS-CoV-2 is highly adapted to humans and readily transmits from person-to-person. AIM: The aim of this study was to investigate the infectivity of SARS-CoV-2 under various environmental factors, disinfectants and different pH conditions. The efficacy of a variety of laboratory virus inactivation methods and home disinfectants against SARS-CoV-2 were investigated. METHODS: The residual virus in dried form or in solution was titrated on Vero E6 cell line at day 0, 1, 3, 5, and 7 after incubation at different temperatures. The viability of virus was determined after treatment with different disinfectants and pH solutions at room temperature (20\u00e2\u0088\u00bc25oC). FINDINGS: SARS-CoV-2 was able to retain viability for 3-5 days in dried form or 7 days in solution at room temperature. SARS-CoV-2 could be detected under a wide range of pH conditions from pH4 to pH11 for several days and 1 to 2 days in stool at room temperature but lost 5 logs of infectivity. A variety of commonly used disinfectants and laboratory inactivation procedures were found to reduce viral viability effectively. CONCLUSION: This study demonstrates the stability of SARS-CoV-2 on environmental surfaces and raises the possibility of faecal-oral transmission. Commonly used fixatives, nucleic acid extraction methods and heat inactivation were found to significantly reduce viral infectivity that could ensure hospital and laboratory safety during the COVID-19 pandemic.", "qid": 16, "docid": "eke4f5fn", "rank": 45, "score": 0.7424675822257996}, {"content": "Title: Viral survival Content: How long do viruses like cold, flu and coronavirus survive outside the body? What factors affect this?", "qid": 16, "docid": "959w9sln", "rank": 46, "score": 0.7421075701713562}, {"content": "Title: Ozone Treatment for Elimination of Bacteria and SARS-CoV-2 for Medical Environments Content: Pathogenic bacteria and viruses in medical environments can lead to treatment complications and hospital-acquired infections (HAIs), and current cleaning protocols do not address hard-to-access areas or that may be beyond line-of-sight treatment such as with ultraviolet radiation. At the time of writing, the ongoing pandemic of the novel coronavirus known as novel coronavirus (2019-nCoV) has claimed over 4 million cases worldwide and is expected to have multiple peaks, with possible resurgences throughout 2020. It is therefore imperative that disinfection methods in the meantime be employed to keep up with the supply of personal protective equipment (PPE) and sterilize a wide array of surfaces as quarantine lockdowns begin to be lifted. Here, we tested the efficacy of Sani Sport ozone devices as a means to treat hospital equipment and surfaces for killing bacteria, degrading synthetic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, and RNA from non-replicative capsid enclosed SARS-CoV-2. We observed a rapid killing of medically-relevant and environmental bacteria (Escherichia coli, Enterococcus faecalis, Bacillus subtlis, and Deinococcus radiodurans) across four surfaces (blankets, catheter, remotes, and syringes) within 30 minutes, and up to a 99% reduction in viable bacteria at the end of 2-hour treatment cycles. Significant RNA degradation of synthetic SARS-CoV-2 RNA was seen an hour into the ozone treatment as compared to non-treated controls and a non-replicative form of the virus was shown to have significant RNA degradation at 30 minutes compared to a no treatment control and RNA degradation could be reliably detected at 10,000 and 1,000 copies of virus per sample. These results show the strong promise of ozone treatment for reducing risk of infection and HAIs.", "qid": 16, "docid": "k8hjo5yu", "rank": 47, "score": 0.7419191002845764}, {"content": "Title: Factors affecting stability and infectivity of SARS-CoV-2 Content: BACKGROUND: In late 2019, a novel human coronavirus, SARS-CoV-2, emerged in Wuhan, China. This virus has caused a global pandemic involving more than 200 countries. SARS-CoV-2 is highly adapted to humans and readily transmits from person-to-person. AIM: The aim of this study was to investigate the infectivity of SARS-CoV-2 under various environmental factors, disinfectants and different pH conditions. The efficacy of a variety of laboratory virus inactivation methods and home disinfectants against SARS-CoV-2 were investigated. METHODS: The residual virus in dried form or in solution was titrated on Vero E6 cell line at day 0, 1, 3, 5, and 7 after incubation at different temperatures. The viability of virus was determined after treatment with different disinfectants and pH solutions at room temperature (20\u223c25(o)C). FINDINGS: SARS-CoV-2 was able to retain viability for 3-5 days in dried form or 7 days in solution at room temperature. SARS-CoV-2 could be detected under a wide range of pH conditions from pH4 to pH11 for several days and 1 to 2 days in stool at room temperature but lost 5 logs of infectivity. A variety of commonly used disinfectants and laboratory inactivation procedures were found to reduce viral viability effectively. CONCLUSION: This study demonstrates the stability of SARS-CoV-2 on environmental surfaces and raises the possibility of faecal-oral transmission. Commonly used fixatives, nucleic acid extraction methods and heat inactivation were found to significantly reduce viral infectivity that could ensure hospital and laboratory safety during the COVID-19 pandemic.", "qid": 16, "docid": "kngf6qpe", "rank": 48, "score": 0.7418876886367798}, {"content": "Title: Using heat to kill SARS\u2010CoV\u20102 Content: The current coronavirus pandemic has reached global proportions and requires unparalleled collective and individual efforts to slow its spread. One critically important issue is the proper sterilization of physical objects that have been contaminated by the virus. Here, we review the currently existing literature on thermal inactivation of coronavirus (SARS\u2010CoV\u20102) and present preliminary guideless on temperatures and exposure durations required to sterilize. We also compare these temperatures/exposure durations with potential household appliances that may be thought capable of performing sterilization.", "qid": 16, "docid": "v7rlxiy1", "rank": 49, "score": 0.7416816353797913}, {"content": "Title: Virus survival in evaporated saliva microdroplets deposited on inanimate surfaces Content: The novel coronavirus respiratory syndrome (COVID-19) has now spread worldwide. The relative contribution of viral transmission via fomites is still unclear. SARS-CoV-2 has been shown to survive on inanimate surfaces for several days, yet the factors that determine its survival on surfaces are not well understood. Here we combine microscopy imaging with virus viability assays to study survival of three bacteriophages suggested as good models for human respiratory pathogens: the enveloped Phi6 (a surrogate for SARS-CoV-2), and the non-enveloped PhiX174 and MS2. We measured virus viability in human saliva microdroplets, SM buffer, and water following deposition on glass surfaces at various relative humidities (RH). Although saliva microdroplets dried out rapidly at all tested RH levels (unlike SM that remained hydrated at RH \u2265 57%), survival of all three viruses in dry saliva microdroplets was significantly higher than in water or SM. Thus, RH and hydration conditions are not sufficient to explain virus survival, indicating that the suspended medium, and association with saliva components in particular, likely affect physicochemical properties that determine virus survival. The observed high virus survival in dry saliva deposited on surfaces, under a wide range of RH levels, can have profound implications for human public health, specifically the COVID-19 pandemic.", "qid": 16, "docid": "atisrhas", "rank": 50, "score": 0.7413870692253113}, {"content": "Title: Making waves: Coronavirus detection, presence and persistence in the water environment: State of the art and knowledge needs for public health Content: The main route of transmission of the human coronaviruses (HCoVs), and presumably also of the new pandemic SARS-CoV-2, is via droplets and close contacts, however their fecal elimination also suggests the possible spread via water. A scientific literature search was thus carried out to highlight the current state of the art and knowledge gaps regarding coronavirus in water. Since 1978 only 22 studies have met the inclusion criteria, and considered heterogeneous purposes, detection methods and types of water. In vitro experiments have addressed the recovery efficiency of analytical methods, survival in different types of water and the removal efficiency of water treatments. Field studies have monitored coronaviruses in surface waters, sewage, slurry, and biosolids. Overall, at the lab scale, HCoVs or surrogates can survive for several days at 4 \u00b0C, however their persistence is lower compared with non-enveloped viruses and is strongly influenced by temperature and organic or microbial pollution. HCoVs have rarely been detected in field investigations, however may be due to the low recovery efficiency of the analytical methods. The scarcity of information on HCoV in the environment suggests that research is needed to understand the fate of these viruses in the water cycle.", "qid": 16, "docid": "vuzf3dnr", "rank": 51, "score": 0.7398954033851624}, {"content": "Title: Making Waves: Coronavirus detection, presence and persistence in the water environment: State of the art and knowledge needs for public health Content: The main route of transmission of the human coronaviruses (HCoVs), and presumably also of the new pandemic SARS-CoV-2, is via droplets and close contacts, however their fecal elimination also suggests the possible spread via water. A scientific literature search was thus carried out to highlight the current state of the art and knowledge gaps regarding coronavirus in water. Since 1978 only 22 studies have met the inclusion criteria, and considered heterogeneous purposes, detection methods and types of water. In vitro experiments have addressed the recovery efficiency of analytical methods, survival in different types of water and the removal efficiency of water treatments. Field studies have monitored coronaviruses in surface waters, sewage, slurry, and biosolids. Overall, at the lab scale, HCoVs or surrogates can survive for several days at 4 \u00b0C, however their persistence is lower compared with non-enveloped viruses and is strongly influenced by temperature and organic or microbial pollution. HCoVs have rarely been detected in field investigations, however may be due to the low recovery efficiency of the analytical methods. The scarcity of information on HCoV in the environment suggests that research is needed to understand the fate of these viruses in the water cycle.", "qid": 16, "docid": "c17eijdt", "rank": 52, "score": 0.7398954033851624}, {"content": "Title: Persistence of SARS-CoV-2 in the environment and COVID-19 transmission risk from environmental matrices and surfaces() Content: The Coronavirus disease 2019 (COVID-19) is spreading around the world, representing a global pandemic, counting, as of June 5th, 2020, over 6,600,000 confirmed cases and more than 390,000 deaths, with exponentially increasing numbers. In the first half of 2020, because of the widespread of the COVID-19, researches were focused on the monitoring of SARS-CoV-2 in water, wastewater, sludge, air, and on surfaces, in order to assess the risk of contracting the viral infection from contaminated environments. So far, the survival of the novel Coronavirus out of the human body has been reported for short time periods (from hours to few days, in optimized in vitro conditions), mainly because of the need of an host organism which could consent the viral attack, and due to the weak external membrane of the virus. SARS-CoV-2 viral shedding strategies in the environment, either through animate and unanimate matrices, or exploiting the organic matter in water, wastewater, and waste in general, have been discussed in the present article. We concluded that, besides the high infectuousness of the novel Coronavirus, the transmission of the pathogen may be efficiently contained applying the adequate preventive measures (e.g., personal protection equipments, and disinfecting agents), indicated by national and international health authories.", "qid": 16, "docid": "kxyd5uzp", "rank": 53, "score": 0.7385132908821106}, {"content": "Title: Persistence of SARS-CoV-2 in the environment and COVID-19 transmission risk from environmental matrices and surfaces Content: The Coronavirus disease 2019 (COVID-19) is spreading around the world, representing a global pandemic, counting, as of June 5th, 2020, over 6,600,000 confirmed cases and more than 390,000 deaths, with exponentially increasing numbers. In the first half of 2020, because of the widespread of the COVID-19, researches were focused on the monitoring of SARS-CoV-2 in water, wastewater, sludge, air, and on surfaces, in order to assess the risk of contracting the viral infection from contaminated environments. So far, the survival of the novel Coronavirus out of the human body has been reported for short time periods (from hours to few days, in optimized in vitro conditions), mainly because of the need of an host organism which could consent the viral attack, and due to the weak external membrane of the virus. SARS-CoV-2 viral shedding strategies in the environment, either through animate and unanimate matrices, or exploiting the organic matter in water, wastewater, and waste in general, have been discussed in the present article. We concluded that, besides the high infectuousness of the novel Coronavirus, the transmission of the pathogen may be efficiently contained applying the adequate preventive measures (e.g., personal protection equipments, and disinfecting agents), indicated by national and international health authories.", "qid": 16, "docid": "b5lcv77o", "rank": 54, "score": 0.7385132908821106}, {"content": "Title: Clinical and Epidemiological Features of a Family Cluster of Symptomatic and Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection Content: In a family experiencing coronavirus disease 2019, the parents and 2 children aged 2 and 5 years became infected but the youngest child was not infected. Both children initially shed infectious virus, but cleared the virus after 5 to 6 days in the nasopharynx. However, viral RNA was continuously detected in the children\u2019s stool for more than 4 weeks.", "qid": 16, "docid": "zz5bpas1", "rank": 55, "score": 0.7375766634941101}, {"content": "Title: Using heat to kill SARS-CoV-2 Content: The current coronavirus pandemic has reached global proportions and requires unparalleled collective and individual efforts to slow its spread. One critically important issue is the proper sterilization of physical objects that have been contaminated by the virus. Here, we review the currently existing literature on thermal inactivation of coronavirus (SARS-CoV-2) and present preliminary guideless on temperatures and exposure durations required to sterilize. We also compare these temperatures/exposure durations with potential household appliances that may be thought capable of performing sterilization.", "qid": 16, "docid": "0p0iyhc2", "rank": 56, "score": 0.7374753952026367}, {"content": "Title: The Seasonal End of Human Coronavirus Hospital Admissions with Implications for SARS-CoV-2 Content: The seasonality of influenza viruses and endemic human coronaviruses was tracked over an 8-year period to assess key epidemiologic reduction points in disease incidence for an urban area in the northeast United States. Patients admitted to a pediatric hospital with worsening respiratory symptoms were tested using a multiplex PCR assay from nasopharyngeal swabs. The additive seasonal effects of outdoor temperatures and indoor relative humidity (RH) were evaluated. The 8-year average peak activity of human coronaviruses occurred in the first week of January, when droplet and contact transmission was enabled by the low indoor RH of 20-30%. Previous studies have shown that an increase in RH to 50% has been associated with markedly reduced viability and transmission of influenza virus and animal coronaviruses. As disease incidence was reduced by 50% in early March, to 75% in early April, to greater than 99% at the end of April, a relationship was observed from colder temperatures in January with a low indoor RH to a gradual increase in outdoor temperatures in April with an indoor RH of 45-50%. As a lipid-bound, enveloped virus with similar size characteristics to endemic human coronaviruses, SARS-CoV-2 should be subject to the same dynamics of reduced viability and transmission with increased humidity. In addition to the major role of social distancing, the transition from lower to higher indoor RH with increasing outdoor temperatures could have an additive effect on the decrease in SARS-CoV-2 cases in May. Over the 8-year period of this study, human coronavirus activity was either zero or >99% reduction in the months of June through September, and the implication would be that SARS-Cov-2 may follow a similar pattern.", "qid": 16, "docid": "3xw4qjoy", "rank": 57, "score": 0.7355809211730957}, {"content": "Title: Viral Shedding and Environmental Cleaning in Middle East Respiratory Syndrome Coronavirus Infection Content: Viral shedding lasted 31 and 19 days from symptom onset in two patients with east respiratory syndrome coronavirus (MERS-CoV) pneumonia, respectively. Environmental real-time RT-PCR was weakly positive for bed guardrail and monitors. Even after cleaning the monitors with 70% alcohol-based disinfectant, RT-PCR was still weakly positive, and converted to negative only after wiping with diluted sodium chlorite. Further studies are required to clarify the appropriate methods to clean environments during and after treatment of patients with MERS-CoV infection.", "qid": 16, "docid": "x11dr866", "rank": 58, "score": 0.735051155090332}, {"content": "Title: Inactivation of surrogate coronaviruses on hard surfaces by health care germicides Content: BACKGROUND: In the 2003 severe acute respiratory syndrome outbreak, finding viral nucleic acids on hospital surfaces suggested surfaces could play a role in spread in health care environments. Surface disinfection may interrupt transmission, but few data exist on the effectiveness of health care germicides against coronaviruses on surfaces. METHODS: The efficacy of health care germicides against 2 surrogate coronaviruses, mouse hepatitis virus (MHV) and transmissible gastroenteritis virus (TGEV), was tested using the quantitative carrier method on stainless steel surfaces. Germicides were o-phenylphenol/p-tertiary amylphenol) (a phenolic), 70% ethanol, 1:100 sodium hypochlorite, ortho-phthalaldehyde (OPA), instant hand sanitizer (62% ethanol), and hand sanitizing spray (71% ethanol). RESULTS: After 1-minute contact time, for TGEV, there was a log(10) reduction factor of 3.2 for 70% ethanol, 2.0 for phenolic, 2.3 for OPA, 0.35 for 1:100 hypochlorite, 4.0 for 62% ethanol, and 3.5 for 71% ethanol. For MHV, log(10) reduction factors were 3.9 for 70% ethanol, 1.3 for phenolic, 1.7 for OPA, 0.62 for 1:100 hypochlorite, 2.7 for 62% ethanol, and 2.0 for 71% ethanol. CONCLUSION: Only ethanol reduced infectivity of the 2 coronaviruses by >3-log(10) after 1 minute. Germicides must be chosen carefully to ensure they are effective against viruses such as severe acute respiratory syndrome coronavirus.", "qid": 16, "docid": "yr1dq258", "rank": 59, "score": 0.7330542206764221}, {"content": "Title: Survival characteristics of airborne human coronavirus 229E. Content: The survival of airborne human coronavirus 229E (HCV/229E) was studied under different conditions of temperature (20 +/- 1 degree C and 6 +/- 1 degree C) and low (30 +/- 5%), medium (50 +/- 5%) or high (80 +/- 5%) relative humidities (RH). At 20 +/- 1 degree C, aerosolized HCV/229E was found to survive best at 50% RH with a half-life of 67.33 +/- 8.24 h while at 30% RH the virus half-life was 26.76 +/- 6.21 h. At 50% RH nearly 20% infectious virus was still detectable at 6 days. High RH at 20 +/- 1 degree C, on the other hand, was found to be the least favourable to the survival of aerosolized virus and under these conditions the virus half-life was only about 3 h; no virus could be detected after 24 h in aerosol. At 6 +/- 1 degree C, in either 50% or 30% RH conditions, the survival of HCV/229E was significantly enhanced, with the decay pattern essentially similar to that seen at 20 +/- 1 degree C. At low temperature and high RH (80%), however, the survival pattern was completely reversed, with the HCV/229E half-life increasing to 86.01 +/- 5.28 h, nearly 30 times that found at 20 +/- 1 degree C and high RH. Although optimal survival at 6 degree C still occurred at 50% RH, the pronounced stabilizing effect of low temperature on the survival of HCV/229E at high RH indicates that the role of the environment on the survival of viruses in air may be more complex and significant than previously thought.", "qid": 16, "docid": "oi7karvd", "rank": 60, "score": 0.7329002618789673}, {"content": "Title: Experimental aerosol survival of SARS-CoV-2 in artificial saliva and tissue culture media at medium and high humidity Content: SARS-CoV-2, the causative agent of the COVID-19 pandemic, may be transmitted via airborne droplets or contact with surfaces onto which droplets have deposited. In this study, the ability of SARS-CoV-2 to survive in the dark, at two different relative humidity values and within artificial saliva, a clinically relevant matrix, was investigated. SARS-CoV-2 was found to be stable, in the dark, in a dynamic small particle aerosol under the four experimental conditions we tested and viable virus could still be detected after 90 minutes. The decay rate and half-life was determined and decay rates ranged from 0.4 to 2.27 % per minute and the half lives ranged from 30 to 177 minutes for the different conditions. This information can be used for advice and modelling and potential mitigation strategies.", "qid": 16, "docid": "txc0k2vb", "rank": 61, "score": 0.7327049970626831}, {"content": "Title: Environmental contamination by SARS-CoV-2 of an imported case during incubation period Content: We collected environmental surface samples prior to and after disinfection of a quarantine room to evaluate the stability of SARS-CoV-2 during the incubation period of an imported case traveling to Qingdao, China. Overall, 11 of 23 (47.8%) of the first batch of environmental surface samples (within 4 h after case confirmation) were tested positive for SARS-CoV-2. Whereas only 2 of 23 (8.7%) of the second batch of environmental samples (after first disinfection) were tested positive for SARS-CoV-2. The majority of samples from the bedroom (70%) were positive for SARS-CoV-2, followed by 50% of samples from the bathroom and that of 33% from the corridor. The inner walls of toilet bowl and sewer inlet were the most contaminated sites with the highest viral loads. SARS-CoV-2 was widely distributed on object surfaces in a quarantine room of a later diagnosed COVID-19 case during the incubation period. Proper disinfection is crucial to minimize community transmission of this highly contagious virus.", "qid": 16, "docid": "sh3h6ggg", "rank": 62, "score": 0.7324045896530151}, {"content": "Title: Sustainability of Coronavirus on different surfaces Content: COVID-19 is the name of the disease supposedly manifested in December 2019 from Wuhan, because of virus named as SARS-CoV-2. Now this disease has spread to almost all other parts of the world. COVID-19 pandemic has various reasons for its dramatic worldwide increase. Here, we have studied Coronavirus sustainability on various surfaces. Various disinfectants and their roles are discussed from the available literature. The infection capabilities of SARS-CoV-1 and SARS-CoV-2 for different materials are discussed and finally studies infection decay for SARS-CoV-1 and SARS-CoV-2.", "qid": 16, "docid": "9fnpfncr", "rank": 63, "score": 0.732268214225769}, {"content": "Title: Stability of infectious human coronavirus NL63 Content: Abstract The human coronavirus NL63 was identified in 2004 and subsequent studies showed its worldwide distribution. Infection with this pathogen is associated with upper and lower respiratory tract diseases of mild to moderate severity. Furthermore, HCoV-NL63 is the main cause of croup in children. Within this study an optimal protocol for freeze-drying that allows safe and effective preservation of HCoV-NL63 infectious material was developed. Lyophilized virus preparations can be stored either at ambient temperature or at +4\u00b0C. In the latter case samples may be stored for at least two months. Surprisingly, conducted analysis showed that HCoV-NL63 virions are exquisitely stable in liquid media and can be stored also without preservatives at ambient temperature for up to 14 days.", "qid": 16, "docid": "qoi00ydx", "rank": 64, "score": 0.7316020131111145}, {"content": "Title: Persistence of Severe Acute Respiratory Syndrome Coronavirus 2 in Aerosol Suspensions Content: We aerosolized severe acute respiratory syndrome coronavirus 2 and determined that its dynamic aerosol efficiency surpassed those of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome. Although we performed experiment only once across several laboratories, our findings suggest retained infectivity and virion integrity for up to 16 hours in respirable-sized aerosols.", "qid": 16, "docid": "34ayx062", "rank": 65, "score": 0.7304703593254089}, {"content": "Title: Persistence of Severe Acute Respiratory Syndrome Coronavirus 2 in Aerosol Suspensions. Content: We aerosolized severe acute respiratory syndrome coronavirus 2 and determined that its dynamic aerosol efficiency surpassed those of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome. Although we performed experiment only once across several laboratories, our findings suggest retained infectivity and virion integrity for up to 16 hours in respirable-sized aerosols.", "qid": 16, "docid": "jincu9xx", "rank": 66, "score": 0.7304703593254089}, {"content": "Title: Physico-chemical properties of murine hepatitis virus, strain A59 Content: The infectivity of murine hepatitis virus (MHV-A59) was optimally stable at pH 6.0 and was unaffected by ionic strength or at least 15 cycles of freezing and thawing. It was completely inactivated within 25 minutes at 56\u00b0 C, but was protected by 1m magnesium chloride or magnesium sulphate. It was completely inactivated within 14 days at 37 and 22\u00b0C, but was relatively stable for as long as 72 days at 4\u00b0C and optimal pH.", "qid": 16, "docid": "ble8gn1l", "rank": 67, "score": 0.729965329170227}, {"content": "Title: An experimental study of the survival of turkey coronavirus at room temperature and +4\u00b0C Content: Turkey coronavirus (TCoV) is a gammacoronavirus (Coronaviridae, Nidovirales) responsible for digestive disorders in young turkeys. TCoV has been associated with poult enteritis complex, a syndrome that severely affects turkey production. No medical prophylaxis exists to control TCoV, therefore sanitary measures such as cleaning and disinfection are essential. It is thus important to evaluate temperatures that allow persistence of TCoV in the environment. Two series of aliquots of a suspension of a French isolate of TCoV (Fr TCoV) were stored at room temperature or +4\u00b0C for 0 to 40 days. As TCoV does not grow in cell culture, the presence of residual infectious TCoV in the stored samples was tested by inoculating embryonated specific pathogen free turkey eggs. As TCoV does not induce lesions in the embryo, virus replication in the jejunum and ileum of the embryos was detected 4 days post inoculation, using RNA extraction and a real-time reverse transcriptase-polymerase chain reaction based on the nucleocapsid gene. No surviving virus was detected after 10 days storage at +21.6\u00b11.4\u00b0C or after 40 days storage at +4.1\u00b11.6\u00b0C, these temperatures being representative of the mean summer and winter temperatures, respectively, in the major French poultry-producing region. The relatively short survival of the virus at room temperature should contribute to limited virus survival during summer months. However, infectious virus was still detected after 20 days storage at the cooler temperatures, a finding that suggests prolonged survival of Fr TCoV and easier transmission between poultry farms in a cool environment are possible.", "qid": 16, "docid": "ytx6sf3x", "rank": 68, "score": 0.7290802597999573}, {"content": "Title: In vitro studies on the use of clay, clay minerals and charcoal to adsorb bovine rotavirus and bovine coronavirus Content: Abstract Rotaviruses are the leading cause and coronaviruses are the major contributors of acute gastroenteritis in the young of various mammalian and avian species. Despite numerous trials and decades of research, vaccines have limited efficacy particularly for calves. As an alternative method of controlling infection, we have investigated broad spectrum antiviral agents that are not discriminatory among various viruses. This report involves testing a variety of adsorbent agents including charcoal, clay, and clay minerals to adsorb rotavirus and coronavirus in vitro. Results revealed that all the adsorbent agents had good to excellent capability of adsorbing rotavirus and excellent capability of adsorbing coronavirus. Percent adsorptions ranged from 78.74% to 99.89% for rotavirus and 99.99% for coronavirus; while sand (negative control) was <0.01%. A high affinity binding was present as determined by a low percent desorption (0.06\u20133.09%). However, the adsorbent bound virus complex retained, and may have actually enhanced, infectivity.", "qid": 16, "docid": "18bvwxci", "rank": 69, "score": 0.7289888262748718}, {"content": "Title: Viral survival Content: How long do viruses like cold, flu and coronavirus survive outside the body? What factors affect this? Douglas Fairchild, Two Harbors, Minnesota, US", "qid": 16, "docid": "hgau3922", "rank": 70, "score": 0.7286628484725952}, {"content": "Title: Environmental contamination by SARS-CoV-2 of an imported case during incubation period Content: Abstract We collected environmental surface samples prior to and after disinfection of a quarantine room to evaluate the stability of SARS-CoV-2 during the incubation period of an imported case traveling to Qingdao, China. Overall, 11 of 23 (47.8%) of the first batch of environmental surface samples (within 4 h after case confirmation) were tested positive for SARS-CoV-2. Whereas only 2 of 23 (8.7%) of the second batch of environmental samples (after first disinfection) were tested positive for SARS-CoV-2. The majority of samples from the bedroom (70%) were positive for SARS-CoV-2, followed by 50% of samples from the bathroom and that of 33% from the corridor. The inner walls of toilet bowl and sewer inlet were the most contaminated sites with the highest viral loads. SARS-CoV-2 was widely distributed on object surfaces in a quarantine room of a later diagnosed COVID-19 case during the incubation period. Proper disinfection is crucial to minimize community transmission of this highly contagious virus.", "qid": 16, "docid": "bfq7vvef", "rank": 71, "score": 0.7286500930786133}, {"content": "Title: Effects of temperature on COVID-19 transmission Content: Coronavirus disease 2019 (COVID19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV2), it was first identified in 2019 in Wuhan, China and has resulted in the 2019-20 coronavirus pandemic. As of March 1, 2020, 79,968 patients in China and 7169 outside of China had tested positive for COVID19 and a mortality rate of 3.6% has been observed amongst Chinese patients. Its primary mode of transmission is via respiratory droplets from coughs and sneezes. The virus can remain viable for up to three days on plastic and stainless steel or in aerosols for upto 3 hours and is relatively more stable than the known human coronaviruses. It is stable in faeces at room temperature for at least 1-2 days and can be stable in infected patients for up to 4 days. Heat at 56 degree Celsius kills the SARS coronavirus at around 10000 units per 15 minutes. Thus, temperature is an important factor in survival of COVID19 virus and this article focuses on understanding the relationship between temperature and COVID19 transmission from the data available between January-March 2020.", "qid": 16, "docid": "ycrrsr5c", "rank": 72, "score": 0.728153645992279}, {"content": "Title: Sentinel Coronavirus Environmental Monitoring Can Contribute to Detecting Asymptomatic SARS-CoV-2 Virus Spreaders and Can Verify Effectiveness of Workplace COVID-19 Controls Content: Detecting all workplace asymptomatic COVID-19 virus spreaders would require daily testing of employees, which is not practical. Over a two week period, nine workplace locations were chosen to test employees for SARS-CoV-2 infection (841 tests) and high-frequency-touch point environmental surfaces (5,500 tests) for Coronavirus using Eurofins COVID-19 SentinelTM RT-PCR methods. Of the 9 locations, 3 had one or employees infected with SARS-CoV-2, neither of whom had symptoms at the time of testing nor developed symptoms. Locations with Coronavirus contaminated surfaces were 10 times more likely to have clinically positive employees than locations with no or very few positive surfaces. Break room chairs, workbenches, and door handles were the most frequently contaminated surfaces. Coronavirus RNA was detected at very low concentrations (RT-PCR 34 to 38 Cq). Environmental monitoring can be used to validate intervention strategies and be useful to verify the effectiveness of such strategies on a regular basis.", "qid": 16, "docid": "aafb28xw", "rank": 73, "score": 0.7277412414550781}, {"content": "Title: Countermeasures against novel coronavirus in dental clinics Content: The cause of acute respiratory disease first reported in December 2019 in Wuhan City, Hubei Province, China, was a coronavirus called \"SARS-CoV-2\", which quickly spread throughout the world In Japan, 8,116 people, including cruise ship passengers and crew, have been infected (as of 10:30 a m , April 13), and the number of infected people is rapidly increasing (Table 1) Notably, the basal reproduction number (infectivity) of this infection is estimated R0 2 0-2 5 [Report of the WHO-China Joint Mission on CoronavirusDisease 2019 (February 16-24, 2020)], which is slightly higher than the usual influenza (measles: 12-18, rubella: 5-7, influenza/Spanish flu: 2-3) In addition to droplet and contact infections, aerosol infections have been pointed out as possible routes of infection Coronaviruses can survive on metal, glass, and plastic surfaces for up to 9 days at room temperature, and have been found to infect health care workers who are supposed to be on the defensive In particular, the risk of coronavirus exposure among dentists is the most serious in all industries What should the dental office do about this infection? In this issue, we introduce a special part of this series, \"Emergency Contribution: Countermeasures for novel Coronavirus Infection in Dental Clinics", "qid": 16, "docid": "91aug79x", "rank": 74, "score": 0.7274059057235718}, {"content": "Title: Fomite transmission and disinfection strategies for SARS-CoV-2 and related viruses Content: Contaminated objects or surfaces, referred to as fomites, play a critical role in the spread of viruses, including SARS-CoV-2, the virus responsible for the COVID-19 pandemic. The long persistence of viruses (hours to days) on surfaces calls for an urgent need for surface disinfection strategies to intercept virus transmission and the spread of the disease. Elucidating the physicochemical processes and surface science underlying the adsorption and transfer of virus between surfaces, as well as their inactivation, are important in understanding how the disease is transmitted, and in developing effective interception strategies. This review aims to summarize the current knowledge and underlying physicochemical processes of virus transmission, in particular via fomites, and common disinfection approaches. Gaps in knowledge and needs for further research are also identified. The review focuses on SARS-CoV-2, but will supplement the discussions with related viruses.", "qid": 16, "docid": "xbw72k4m", "rank": 75, "score": 0.7258089780807495}, {"content": "Title: Virucidal efficacy of physico-chemical treatments against coronaviruses and parvoviruses of laboratory animals. Content: Virucidal efficacy of chemical disinfectants, heating and ultraviolet radiation against mouse hepatitis virus (MHV), canine coronavirus (CCV), Kilham rat virus (KRV) and canine parvovirus (CPV) were examined. Coronaviruses (MHV and CCV) were inactivated by ethanol, isopropanol, benzalkonium chloride, iodophor, sodium hypochlorite, sodium chlorite, cresol soap and formaldehyde as well as by heating at 60 degrees C for 15 minutes, whereas parvoviruses (KRV and CPV) appeared to be inactivated by disinfectants such as formaldehyde, iodophor, sodium hypochlorite and sodium chlorite. Parvoviruses were stable under heating of up to 80 degrees C for 30 minutes. Ultraviolet radiation inactivated all viruses within 15 minutes. No significant differences in stability against physico-chemical treatments were seen between viruses in the same group.", "qid": 16, "docid": "9570px50", "rank": 76, "score": 0.7252730131149292}, {"content": "Title: Environmental and decontamination issues for human coronaviruses and their potential surrogates Content: Pandemic coronavirus disease-2019 (COVID-19) gives ample reason to generally review coronavirus (CoV) containment. For establishing some preliminary views on decontamination and disinfection, surrogate CoVs have commonly been assessed. This review serves to examine the existing science in regard to CoV containment generically and then to translate these findings into timely applications for COVID-19. There is widespread dissemination of CoVs in the immediate patient environment, and CoVs can potentially be spread via respiratory secretions, urine, and stool. Interpretations of the spread however must consider whether studies examine for viral RNA, virus viability by culture, or both. Presymptomatic, asymptomatic, and post-14 day virus excretion from patients may complicate the epidemiology. Whereas droplet spread is accepted, there continues to be controversy over the extent of possible airborne spread and especially now for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CoVs are stable in body secretions and sewage at reduced temperatures. In addition to temperature, dryness or relative humidity, initial viral burden, concomitant presence of bioburden, and the type of surface can all affect stability. Generalizing, CoVs can be susceptible to radiation, temperature extremes, pH extremes, peroxides, halogens, aldehydes, many solvents, and several alcohols. Whereas detergent surfactants can have some direct activity, these agents are better used as complements to a complex disinfectant solution. Disinfectants with multiple agents and adverse pH are more likely to be best active at higher water temperatures. Real-life assessments should be encouraged with working dilutions. The use of decontamination and disinfection should be balanced with considerations of patient and caregiver safety. Processes should also be balanced with considerations for other potential pathogens that must be targeted. Given some CoV differences and given that surrogate testing provides experimental correlates at best, direct assessments with SARS-CoV, Middle East respiratory syndrome-related coronavirus (MERS-CoV), and SARS-CoV-2 are required.", "qid": 16, "docid": "ou8lm4yl", "rank": 77, "score": 0.7247220277786255}, {"content": "Title: COVID-19 Surface Persistence: A Recent Data Summary and Its Importance for Medical and Dental Settings Content: Recently, due to the coronavirus pandemic, many guidelines and anti-contagion strategies continue to report unclear information about the persistence of coronavirus disease 2019 (COVID-19) in the environment. This certainly generates insecurity and fear in people, with an important psychological component that is not to be underestimated at this stage of the pandemic. The purpose of this article is to highlight all the sources currently present in the literature concerning the persistence of the different coronaviruses in the environment as well as in medical and dental settings. As this was a current study, there are still not many sources in the literature, and scientific strategies are moving towards therapy and diagnosis, rather than knowing the characteristics of the virus. Such an article could be an aid to summarize virus features and formulate new guidelines and anti-spread strategies.", "qid": 16, "docid": "6fmuh2or", "rank": 78, "score": 0.7234362363815308}, {"content": "Title: Quantitation, biological and physicochemical properties of cell culture-adapted porcine epidemic diarrhea coronavirus (PEDV) Content: Abstract The porcine epidemic coronavirus (PEDV), tentatively classified as a coronavirus, was adapted to Vero cells and a plaque test developed for infectivity titration, allowing us to test the biological and biophysical properties of the virus. Growth kinetics showed peak titers of 105.5 plaque-forming units ml\u22121 15 h after infection. Filtration experiments and electron microscopy revealed a particle diameter between 100 and 200 nm. The bouyant density of the virus was 1.18. The particle lost its infectivity on treatment with lipid solvents. Virus replication could not be inhibited by 5-iodo-2\u2032-deoxyuridine. PEDV was moderately stable at 50\u00b0C, but heat sensitivity was not altered by divalent cations. At 4\u00b0C, the virus was stable between pH 5.0 and 9.0, but at 37\u00b0C stability was restricted to the pH range 6.5\u20137.5. Viral infectivity was not impaired by ultrasonication or by multiple freezing and thawing. PEDV was not neutralized by transmissible gastroenteritis virus antiserum. On the basis of the tests carried out, PEDV is a pleomorphic, enveloped RNA virus with a particle diameter of \u223c 150 nm and a bouyant density of 1.18. Infectivity depends on the presence of trypsin, and infected cells show a tendency to fuse and to form syncytia. All of these properties, as well as its physicochemical characteristics, allow PEDV to be classified as a coronavirus.", "qid": 16, "docid": "j7bpccog", "rank": 79, "score": 0.723334789276123}, {"content": "Title: Coronavirus in water environments: Occurrence, persistence and concentration methods - A scoping review Content: Coronaviruses (CoV) are a large family of viruses causing a spectrum of disease ranging from the common cold to more severe diseases as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). The recent outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency worldwide. SARS-CoV-2, the virus responsible for COVID-19, is spread by human-to-human transmission via droplets or direct contact. However, since SARS-CoV-2 (as well as other coronaviruses) has been found in the fecal samples and anal swabs of some patients, the possibility of fecal-oral (including waterborne) transmission need to be investigated and clarified. This scoping review was conducted to summarize research data on CoV in water environments. A literature survey was conducted using the electronic databases PubMed, EMBASE, and Web Science Core Collection. This comprehensive research yielded more than 3000 records, but only 12 met the criteria and were included and discussed in this review. In detail, the review captured relevant studies investigating three main areas: 1) CoV persistence/survival in waters; 2) CoV occurrence in water environments; 3) methods for recovery of CoV from waters. The data available suggest that: i) CoV seems to have a low stability in the environment and is very sensitive to oxidants, like chlorine; ii) CoV appears to be inactivated significantly faster in water than non-enveloped human enteric viruses with known waterborne transmission; iii) temperature is an important factor influencing viral survival (the titer of infectious virus declines more rapidly at 23\u00b0C-25 \u00b0C than at 4 \u00b0C); iv) there is no current evidence that human coronaviruses are present in surface or ground waters or are transmitted through contaminated drinking-water; v) further research is needed to adapt to enveloped viruses the methods commonly used for sampling and concentration of enteric, non enveloped viruses from water environments. The evidence-based knowledge reported in this paper is useful to support risk analysis processes within the drinking and wastewater chain (i.e., water and sanitation safety planning) to protect human health from exposure to coronavirus through water.", "qid": 16, "docid": "hn9fj8h8", "rank": 80, "score": 0.7233016490936279}, {"content": "Title: Systematic Review and Meta-Analysis of the Persistence and Disinfection of Human Coronaviruses and Their Viral Surrogates in Water and Wastewater Content: [Image: see text] A systematic review and meta-analysis was conducted to identify decay rate constants (k) of human coronaviruses and their viral surrogates (i.e., animal coronaviruses and the enveloped bacteriophage Phi6) in water and wastewater and disinfection rates with exposure to free chlorine and germicidal ultraviolet light (UV(254)). Here, 73 k were identified, with only 12 for human coronaviruses, as opposed to animal coronaviruses or Phi6. In the absence of disinfectants, k increased with temperature. Between 22 and 25 \u00b0C, mean k for coronaviruses ranged from 0.19 \u00b1 0.06 d(\u20131) in laboratory buffer (n = 4) to 2.9 \u00b1 0.03 d(\u20131) in sterilized wastewater (n = 3), which are within the ranges observed for Phi6 and nonenveloped viruses. No free chlorine or UV(254) disinfection studies for coronaviruses were identified that met the systematic review inclusion criteria, although evidence from the literature suggests that coronaviruses would be inactivated if disinfectant doses recommended for nonenveloped viruses were applied. Three disinfection experiments were identified for Phi6. However, given different genome compositions and virion structures between coronaviruses and Phi6, it is not clear whether Phi6 should be used as a surrogate for evaluating free chlorine or UV(254)k. Therefore, there is a critical need for additional studies that specifically evaluate disinfection kinetics of coronaviruses in the aqueous environment.", "qid": 16, "docid": "5ufgrlnq", "rank": 81, "score": 0.7225584983825684}, {"content": "Title: Efficacy of a novel iodine complex solution, CupriDyne, in inactivating SARS-CoV-2 Content: The coronavirus known as SARS-CoV-2, which causes COVID-19 disease, is presently responsible for a global pandemic wherein more than 3.5 million people have been infected and more than 250,000 killed to-date. There is currently no vaccine for COVID-19, leaving governments and public health agencies with little defense against the virus aside from advising or enforcing best practices for virus transmission prevention, which include hand-washing, physical distancing, use of face covers, and use of effective disinfectants. In this study, a novel iodine complex called CupriDyne\u00ae was assessed for its ability to inactivate SARS-CoV-2. CupriDyne was shown to be effective in inactivating the virus in a time-dependent manner, reducing virus titers by 99% (2 logs) after 30 minutes, and reducing virus titers to below the detection limit after 60 minutes. The novel iodine complex tested herein offers a safe and gentle alternative to conventional disinfectants for use on indoor and outdoor surfaces.", "qid": 16, "docid": "d8xtacyj", "rank": 82, "score": 0.7216824293136597}, {"content": "Title: Extended Storage of SARS-CoV2 Nasopharyngeal Swabs Does Not Negatively Impact Results of Molecular-Based Testing Content: With the global outbreak of the novel coronavirus disease 2019, the demand for testing rapidly increased and quickly exceeded the testing capacities for many laboratories. Clinical tests which receive CE and FDA authorizations cannot always be tested thoroughly in a real-world environment. Here we demonstrate the long-term stability of nasopharyngeal swab specimens for SARS-CoV-2 molecular testing across three assays recently approved by the U.S. FDA under Emergency Use Authorization. This study demonstrates that nasopharyngeal swab specimens can be stored under refrigeration or even ambient conditions for 21 days without clinically impacting the results of the real-time RT-PCR testing.", "qid": 16, "docid": "hhk900c1", "rank": 83, "score": 0.7205857038497925}, {"content": "Title: Prolonged Persistence of SARS-CoV-2 RNA in Body Fluids Content: We prospectively assessed 49 coronavirus disease cases in Guangdong, China, to estimate the frequency and duration of detectable severe acute respiratory syndrome coronavirus 2 RNA in human body fluids. The prolonged persistence of virus RNA in various body fluids may guide the clinical diagnosis and prevention of onward virus transmission.", "qid": 16, "docid": "pubh7ovn", "rank": 84, "score": 0.720145583152771}, {"content": "Title: Prolonged Persistence of SARS-CoV-2 RNA in Body Fluids. Content: We prospectively assessed 49 coronavirus disease cases in Guangdong, China, to estimate the frequency and duration of detectable severe acute respiratory syndrome coronavirus 2 RNA in human body fluids. The prolonged persistence of virus RNA in various body fluids may guide the clinical diagnosis and prevention of onward virus transmission.", "qid": 16, "docid": "4gj9d181", "rank": 85, "score": 0.720145583152771}, {"content": "Title: Stability of SARS-CoV-2 in different environmental conditions Content: Stability of SARS-CoV-2 in different environmental conditions.", "qid": 16, "docid": "rbzl0txp", "rank": 86, "score": 0.7200444340705872}, {"content": "Title: Survival of Enveloped and Non-Enveloped Viruses on Inanimate Surfaces Content: In the present study, we evaluated the viability of non-enveloped viruses, minute virus of mice (MVM) and coxsackievirus B4 (CVB4), and enveloped-viruses, influenza A virus (H1N1) and herpes simplex virus type 1 (HSV-1), on surfaces. We also investigated the impact of the initial concentration of proteins and sodium chloride on the persistence of infectious CVB4 on surfaces. Viral suspensions (>10(4.5) TCID(50)) were applied to petri dish lids and dried under the air flow of a biosafety cabinet. The recovered viral preparations were titered on appropriate cell lines. Enveloped viruses persisted for less than 5 days while CVB4 and MVM persisted for weeks. However, repetitive cycles of drying and resuspension had a stronger virucidal effect on CVB4 than on H1N1 and HSV-1. These repetitive cycles had no effect on the infectious titer of MVM. When exposed to drying, the initial concentrations of bovine serum albumin (from 0 to 90 mg mL(\u22121)), fetal calf serum (from 0 to 100%), and sodium chloride (from 0 to 300 mg mL(\u22121)) affected the viability of CVB4. CVB4 was more likely to be inactivated by drying in a protein-rich medium, whereas the impact of drying was reduced in the presence of sodium chloride. The results of the present study demonstrated that the resistance of viruses to drying, as suggested by iterative drying, was not due to the heterogeneity of viral subpopulations, but was influenced by media compositions and component concentrations, as illustrated in the model of CVB4.", "qid": 16, "docid": "hrcffnpt", "rank": 87, "score": 0.7183423042297363}, {"content": "Title: [Diagnosis of bovine coronaviruses using mouse erythrocyte suspensions stabilized with formalin]. Content: Bovine coronavirus isolated from calf faeces diseased with gastroenteritis and passaged to colostrum-free calves agglutinated mouse and rat erythrocytes. The agglutination reaction depended on temperature and took place only at a temperature of 4 degrees C. At a temperature of 37 degrees C the agglutinate broke down within 15 minutes. The coronavirus could be detected by the haemagglutination test in the contents of the small and large intestines and in the faeces of experimentally and naturally infected calves. The agglutination capacity of mouse erythrocytes was not affected by careful fixation of these erythrocytes with formalin and subsequent lyophilization and remained unchanged for as long as 52 weeks of storage at a temperature of 4 degrees C. It was demonstrated by a comparative examination of 182 samples of the faeces of calves suffering from diarrhoea that haemagglutination test was as sensitive as electron microscopy.", "qid": 16, "docid": "3opcz6hb", "rank": 88, "score": 0.7180573344230652}, {"content": "Title: Coronavirus disinfection in histopathology Content: The 2019 Coronavirus epidemic, provisionally called 2019-nCoV, was first identified in Wuhan, China, in persons exposed to a seafood or wet market. There is an international push to contain the virus and prevent its spread. It is feasible that potentially infectious samples may be received in histopathology laboratories for diagnosis. This technical note presents disinfection procedures and histotechnology processes that should alleviate the risk of infection to laboratory staff. Using data obtained from similar coronaviruses, e.g. severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), experts are confident that 70% ethanol and 0.1% sodium hypochlorite should inactivate the virus. Formalin fixation and heating samples to 56oC, as used in routine tissue processing, were found to inactivate several coronaviruses and it is believed that 2019-nCoV would be similarly affected.", "qid": 16, "docid": "90j5ymmr", "rank": 89, "score": 0.7174104452133179}, {"content": "Title: Coronavirus disinfection in histopathology. Content: The 2019 Coronavirus epidemic, provisionally called 2019-nCoV, was first identified in Wuhan, China, in persons exposed to a seafood or wet market. There is an international push to contain the virus and prevent its spread. It is feasible that potentially infectious samples may be received in histopathology laboratories for diagnosis. This technical note presents disinfection procedures and histotechnology processes that should alleviate the risk of infection to laboratory staff. Using data obtained from similar coronaviruses, e.g. severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), experts are confident that 70% ethanol and 0.1% sodium hypochlorite should inactivate the virus. Formalin fixation and heating samples to 56oC, as used in routine tissue processing, were found to inactivate several coronaviruses and it is believed that 2019-nCoV would be similarly affected.", "qid": 16, "docid": "21stahui", "rank": 90, "score": 0.7174104452133179}, {"content": "Title: Persistence of Antibodies against Middle East Respiratory Syndrome Coronavirus Content: To determine how long antibodies against Middle East respiratory syndrome coronavirus persist, we measured long-term antibody responses among persons serologically positive or indeterminate after a 2012 outbreak in Jordan. Antibodies, including neutralizing antibodies, were detectable in 6 (86%) of 7 persons for at least 34 months after the outbreak.", "qid": 16, "docid": "8qauo907", "rank": 91, "score": 0.716781735420227}, {"content": "Title: Environmental Contamination and Viral Shedding in MERS Patients During MERS-CoV Outbreak in South Korea Content: Background. Although Middle East Respiratory Syndrome coronavirus (MERS-CoV) is characterized by a risk of nosocomial transmission, the detailed mode of transmission and period of virus shedding from infected patients are poorly understood. The aims of this study were to investigate the potential role of environmental contamination by MERS-CoV in healthcare settings and to define the period of viable virus shedding from MERS patients. Methods. We investigated environmental contamination from 4 patients in MERS-CoV units of 2 hospitals. MERS-CoV was detected by reverse transcription polymerase chain reaction (PCR) and viable virus was isolated by cultures. Results. Many environmental surfaces of MERS patient rooms, including points frequently touched by patients or healthcare workers, were contaminated by MERS-CoV. Viral RNA was detected up to five days from environmental surfaces following the last positive PCR from patients\u2019 respiratory specimens. MERS-CoV RNA was detected in samples from anterooms, medical devices, and air-ventilating equipment. In addition, MERS-CoV was isolated from environmental objects such as bed sheets, bedrails, IV fluid hangers, and X-ray devices. During the late clinical phase of MERS, viable virus could be isolated in 3 of the 4 enrolled patients on day 18 to day 25 after symptom onset. Conclusions. Most of touchable surfaces in MERS units were contaminated by patients and health care workers and the viable virus could shed through respiratory secretion from clinically fully recovered patients. These results emphasize the need for strict environmental surface hygiene practices, and sufficient isolation period based on laboratory results rather than solely on clinical symptoms.", "qid": 16, "docid": "wuv10bo9", "rank": 92, "score": 0.7166582345962524}, {"content": "Title: Regulation of viral persistence in human glioblastoma and rhabdomyosarcoma cells infected with coronavirus OC43 Content: Abstract Cultures of human rhabdomyosarcoma (RD) and human glioblastoma (U87-MG) were compared for their ability to sustain a persistent infection with coronavirus OC43. Within 28 days, infectious virus and hemagglutinin were being produced at high levels in both types of cells. Temperature sensitive plaque variants were recovered at 31 \u00b0C. In both cell types, the virus caused increased antigen synthesis and cell death, if the temperature was lowered to 31 \u00b0C. Infectious virus was lost if cells were treated with antiserum to whole virus or if the temperature was raised to 39.5 \u00b0C. Probing the cured cells with OC43-specific 32P-cDNA showed that cured cells contained no detectable viral RNA. The relative ease of establishment and cure of these persistent infectious makes them attractive as models to study coronavirus regulatory processes.", "qid": 16, "docid": "0fjgkot0", "rank": 93, "score": 0.7162454128265381}, {"content": "Title: Persistent viral RNA shedding after COVID\u201019 symptom resolution in older convalescent plasma donors Content: INTRODUCTION: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102), is responsible for a worldwide pandemic. While the medical community understands the mode of viral transmission, less is known about how long viral shedding occurs once viral symptoms have resolved. Our objective was to determine how long the SARS\u2010CoV\u20102 remains detectable following self\u2010reporting of viral symptom resolution. METHODS: This study was approved by the University of Wisconsin Institutional Review Board. A cohort of patients who were previously SARS\u2010CoV\u20102 positive less than 28 days after self\u2010reported symptom resolution were retested for proof of viral recovery by nasal swab reverse transcriptase polymerase chain reaction for SARS\u2010CoV\u20102 RNA. RESULTS: A total of 152 potential participants were screened, of which 5 declined, 54 were ineligible, and 93 were recruited; 86 of 93 completed testing. Eleven of 86 (13%) were still positive at a median of 19 days (range, 12\u201024 days) after symptom resolution. Positive participants were significantly older than negative participants (mean, 54 years; 95% confidence interval [CI], 44\u201063 vs 42 years; 95% CI, 38\u201046; P = .024). C (T) values were significantly, inversely associated with age (\u03b2 = \u2212.04; r (2) = 0.389; P = .04). The number of days since symptom recovery was not apparently different between positive and negative participants. CONCLUSION: We found evidence of persistent viral shedding in nasopharyngeal secretions more than 2 weeks after resolution of symptoms from confirmed COVID\u201019 infection. Persistent shedding was more common in older participants, and viral load was higher among older positive participants. These results underscore the necessity of testing COVID\u201019 convalescent plasma donors less than 28 days after symptom resolution.", "qid": 16, "docid": "kkzaq3jt", "rank": 94, "score": 0.7152034044265747}, {"content": "Title: Minimization of spreading of SARS-CoV-2 via household waste produced by subjects affected by COVID-19 or in quarantine Content: Currently available evidence supports that the predominant route of human-to-human transmission of the SARS-CoV-2 is through respiratory droplets. Indirect hands contact with surfaces contaminated by infectious droplets subsequently touching the mouth, nose or eyes seems to be another route of an indirect contact transmission. Persistence of the virus on different surfaces and other materials has been reported in recent studies: SARS-CoV-2 was more stable on plastic and stainless steel than on copper and cardboard. Viable virus was detected up to 72 h after application to different surfaces, although infectivity decay was also observed. This evidence suggests the likelihood that waste generated from patients affected by COVID-19 or subjects in quarantine treated in private houses or in areas different from hospitals and medical centres could be contaminated by SARS-CoV-2. Consequently, waste streams may represent a route for viral spreading being a potential risk also for the operators directly involved in the different phases of waste management. To address this concern, a specific multidisciplinary working group was settled by the Italian National Institute of Health (ISS) during the COVID-19 emergency, in order to establish guidelines related to solid waste collection, delivering, withdrawal, transport, treatment and disposal. Temporary stop of waste sorting, instructions for the population on how to package waste, instructions for Companies and operators for the adoption of adequate personal protection equipment (PPE), the use and sanitation of proper vehicles were among the main recommendations provided to the community by publications of freely downloadable reports and infographics in layman language. Incineration, sterilization and properly managed landfills were identified as the facilities to be preferentially adopted for the treatment of this kind of waste, considering the main inactivation strategies of SARS-CoV-2 (e.g. treatment length > 9 days and temperature > 70 \u00b0C for more than 5 min).", "qid": 16, "docid": "ts4hxku0", "rank": 95, "score": 0.715116024017334}, {"content": "Title: Adaptation of coronavirus JHM to persistent infection of murine sac(-) cells. Content: Coronaviruses can establish persistent infections in the central nervous system of rodents, and these are associated with demyelinating encephalomyelitis. The effects of persistence on the virus are difficult to study in vivo but may have a crucial influence on the course of infection. We therefore produced a persistent infection in vitro using the neurotropic coronavirus JHM, in order to investigate the events underlying the establishment of such an infection and the adaptation of the virus to persistence. The persistent infection was maintained for over 115 passages and continued to release high levels of infectious virus. During the 18 months of culture the number of cells expressing virus antigen detected by indirect immune fluorescence decreased to 40%. Analysis showed that the carried virus contained a significant proportion of heterogeneous temperature-sensitive mutants. All virus clones isolated possessed the capacity to induce a more productive growth cycle, a less pronounced cytopathic effect and showed a much reduced neurovirulence when inoculated into newborn and weanling rats. Evidence for structural changes involving the surface peplomer protein (E2) was obtained using hybridoma antibodies, which neutralized the parental JHM virus but not the JHM-Pi virus. Defective interfering particles and interferon activities have been excluded as possible agents instrumental in the establishment and maintenance of the chronic infection, and we suggest that the emergence of virus variants of lowered virulence is central to these processes.", "qid": 16, "docid": "q9797wsr", "rank": 96, "score": 0.7143324613571167}, {"content": "Title: Persistence of Bacteriophage Phi 6 on Porous and Non-Porous Surfaces; Potential for use as Ebola or Coronavirus Surrogate Content: The infection of healthcare workers during the 2013 -2016 Ebola outbreak raised concerns about fomite transmission. In the wake of the Coronavirus Disease 2019 (COVID-19) pandemic, investigations are ongoing to determine the role of fomites in coronavirus transmission as well. The bacteriophage Phi 6 has a phospholipid envelope and is commonly used in environmental studies as a surrogate for human enveloped viruses. The persistence of Phi 6 was evaluated as a surrogate for EBOV and coronaviruses on porous and nonporous hospital surfaces. Phi 6 was suspended in a body fluid simulant and inoculated onto 1 cm2 coupons of steel, plastic, and two fabric curtain types. The coupons were placed at two controlled absolute humidity (AH) levels; a low AH of 3.0 g/m3 and a high AH of 14.4 g/m3 Phi 6 declined at a slower rate on all materials under low AH conditions with a decay rate of 0.06 log10PFU/d to 0.11 log10PFU/d, as compared to the higher AH conditions with a decay rate of 0.65 log10PFU/h to 1.42 log10PFU/d. There was a significant difference in decay rates between porous and non-porous surfaces at both low AH (P < 0.0001) and high AH (P < 0.0001). Under these laboratory-simulated conditions, Phi 6 was found to be a conservative surrogate for EBOV under low AH conditions, in that it persisted longer than Ebola virus in similar AH conditions. Additionally, some coronaviruses persist longer than phi6 under similar conditions, therefore Phi6 may not be a suitable surrogate for coronaviruses.IMPORTANCE Understanding the persistence of enveloped viruses helps inform infection control practices and procedures in healthcare facilities and community settings. These data convey to public health investigators that enveloped viruses can persist and remain infective on surfaces, thus demonstrating a potential risk for transmission. Under these laboratory-simulated western indoor hospital conditions, Phi 6 was used to assess suitability as a surrogate for environmental persistence research related to enveloped viruses, including EBOV and coronaviruses.", "qid": 16, "docid": "a27luzwj", "rank": 97, "score": 0.7142143249511719}, {"content": "Title: Persistence of Bacteriophage Phi 6 on Porous and Non-Porous Surfaces; Potential for use as Ebola or Coronavirus Surrogate. Content: The infection of healthcare workers during the 2013 -2016 Ebola outbreak raised concerns about fomite transmission. In the wake of the Coronavirus Disease 2019 (COVID-19) pandemic, investigations are ongoing to determine the role of fomites in coronavirus transmission as well. The bacteriophage Phi 6 has a phospholipid envelope and is commonly used in environmental studies as a surrogate for human enveloped viruses. The persistence of Phi 6 was evaluated as a surrogate for EBOV and coronaviruses on porous and nonporous hospital surfaces. Phi 6 was suspended in a body fluid simulant and inoculated onto 1 cm2 coupons of steel, plastic, and two fabric curtain types. The coupons were placed at two controlled absolute humidity (AH) levels; a low AH of 3.0 g/m3 and a high AH of 14.4 g/m3 Phi 6 declined at a slower rate on all materials under low AH conditions with a decay rate of 0.06 log10PFU/d to 0.11 log10PFU/d, as compared to the higher AH conditions with a decay rate of 0.65 log10PFU/h to 1.42 log10PFU/d. There was a significant difference in decay rates between porous and non-porous surfaces at both low AH (P < 0.0001) and high AH (P < 0.0001). Under these laboratory-simulated conditions, Phi 6 was found to be a conservative surrogate for EBOV under low AH conditions, in that it persisted longer than Ebola virus in similar AH conditions. Additionally, some coronaviruses persist longer than phi6 under similar conditions, therefore Phi6 may not be a suitable surrogate for coronaviruses.IMPORTANCE Understanding the persistence of enveloped viruses helps inform infection control practices and procedures in healthcare facilities and community settings. These data convey to public health investigators that enveloped viruses can persist and remain infective on surfaces, thus demonstrating a potential risk for transmission. Under these laboratory-simulated western indoor hospital conditions, Phi 6 was used to assess suitability as a surrogate for environmental persistence research related to enveloped viruses, including EBOV and coronaviruses.", "qid": 16, "docid": "bgodmbru", "rank": 98, "score": 0.7142143249511719}, {"content": "Title: Human coronavirus reinfection dynamics: lessons for SARS-CoV-2 Content: In the current SARS-CoV-2 pandemic a key unsolved question is the quality and duration of acquired immunity in recovered individuals. This is crucial to solve, however SARS-CoV-2 has circulated for under five months, precluding a direct study. We therefore monitored 10 subjects over a time span of 35 years (1985-2020), providing a total of 2473 follow up person-months, and determined a) their antibody levels following infection by any of the four seasonal human coronaviruses, and b) the time period after which reinfections by the same virus can occur. An alarmingly short duration of protective immunity to coronaviruses was found by both analyses. We saw frequent reinfections at 12 months post-infection and a substantial reduction in antibody levels as soon as 6 months post-infection.", "qid": 16, "docid": "u5nxm9tu", "rank": 99, "score": 0.7141751050949097}, {"content": "Title: Stability of the COVID-19 virus under wet, dry and acidic conditions Content: COVID-19 has become a pandemic and is spreading fast worldwide. The COVID-19 virus is transmitted mainly through respiratory droplets and close contact. However, the fecal-oral transmission of the virus has not been ruled out and it is important to ascertain how acidic condition in the stomach affects the infectivity of the virus. Besides, it is unclear how stable the COVID-19 virus is under dry and wet conditions. In the present study, we have shown that the COVID-19 virus is extremely infectious as manifested by the infection of Vero-E6 cells by one PFU (Plaque Forming Unit) of the virus. We then investigated the stability of the COVID-19 virus in wet, dry and acidic (pH2.2) environments at room temperature. Results showed that the COVID-19 virus could survive for three days in wet and dry environments, but the dry condition is less favorable for the survival of the virus. Our study also demonstrated that the COVID-19 virus at a relative high titer (1.2 x 103 PFU) exhibits a certain degree of tolerance to acidic environment at least for 60 minutes. When the virus titer was \u22641.0 x 103 PFU, acid treatment (pH2.2) for 30 or 60 minute resulted in virus inactivation. It suggests that the virus at a high concentration may survive in the acidic environment of the stomach. The finding of the present study will contribute to the control of the spread of the COVID-19 virus.", "qid": 16, "docid": "3cm44rbz", "rank": 100, "score": 0.7141240835189819}]}
{"query": "are there any clinical trials available for the coronavirus", "hits": [{"content": "Title: A brief review of antiviral drugs evaluated in registered clinical trials for COVID-19 Content: Background: Although a number of antiviral agents have been evaluated for coronaviruses there are no approved drugs available. To provide an overview of the landscape of therapeutic research for COVID-19, we conducted a review of registered clinical trials. Methods: A review of currently registered clinical trials was performed on registries, including the Chinese (chictr.org.cn) and US (clinicaltrials.gov) databases to identify relevant studies up to March, 7th 2020. The search was conducted using the search terms \u201c2019-nCoV\u201d, \u201cCOVID-19\u201d, \u201cSARS-CoV-2\u201d, \u201cHcov-19\u201d, \u201cnew coronavirus\u201d, \u201cnovel coronavirus\u201d. We included interventional clinical trials focusing on patients with COVID-19 and assessing antiviral drugs or agents. Findings: Out of the 353 studies identified, 115 clinical trials were selected for data extraction. Phase IV trials were the most commonly reported study type (n=27, 23%). However, 62 trials (54%) did not describe the phase of the study. Eighty percent (n=92) of the trials were randomized with parallel assignment and the median number of planned inclusions was 63 (IQR, 36-120). Open-label studies were the most frequent (46%) followed by double-blind (13%) and single blind studies (10%). The most frequently assessed therapies were: stem cells therapy (n=23 trials), lopinavir/ritonavir (n=15), chloroquine (n=11), umifenovir (n=9), hydroxychloroquine (n=7), plasma treatment (n=7), favipiravir (n=7), methylprednisolone (n=5), and remdesivir (n=5). Remdesivir was tested in 5 trials with a median of 400 (IQR, 394-453) planned inclusions per trial, while stem cells therapy was tested in 23 trials, but had a median of 40 (IQR, 23-60) planned inclusions per trial. Lopinavir/ritonavir was associated with the highest total number of planned inclusions (2606) followed by remdesivir (2155). Only 52% of the clinical trials reported the treatment dose (n=60) and only 34% (n=39) the duration. The primary outcome was clinical in 76 studies (66%), virological in 27 (23%); radiological in 9 (8%) or immunological in three studies (3%). Interpretation: Numerous clinical trials have been registered since the beginning of the COVID-19 outbreak, however, a number of information regarding drugs or trial design were lacking. Funding: None", "qid": 17, "docid": "t1wpujpm", "rank": 1, "score": 0.8357535600662231}, {"content": "Title: An early assessment of the efficacy of medicines in the treatment of patients with COVID-19/ \u0420\u0410\u041d\u041d\u042f\u042f \u041e\u0426\u0415\u041d\u041a\u0410 \u042d\u0424\u0424\u0415\u041a\u0422\u0418\u0412\u041d\u041e\u0421\u0422\u0418 \u041b\u0415\u041a\u0410\u0420\u0421\u0422\u0412\u0415\u041d\u041d\u042b\u0425 \u0421\u0420\u0415\u0414\u0421\u0422\u0412 \u041f\u0420\u0418 \u041b\u0415\u0427\u0415\u041d\u0418\u0418 \u0411\u041e\u041b\u042c\u041d\u042b\u0425 \u0421 COVID-19 Content: Coronavirus infection 2019 is considered a modern challenge to the world community. In the absence of vaccines and antivirals, effective and safe medicines are an urgent request from the healthcare system. We have evaluated the medical technologies for COVID-19 which are being examined. The search was conducted on the \u0421linicalTrials.gov at the beginning of April 2020. As a result it was shown that the growth of new clinical trials in the world devoted to COVID-19 is growing by 65% per week. More often, interventional clinical trials of the II and III phases are carried out. Most studies are planned or conducted in Western Europe (n = 92), China (n = 79), and the United States (n = 51). Surrogate points are usually evaluated, such as: clinical recovery, symptom-based disease relief (fever, cough, diarrhea, myalgia, shortness of breath), lack of progression of shortness of breath, rate of artificial ventilation, rate of admission to the intensive care unit, etc. It is antimalarial drugs that are mainly studied. Currently, it is not possible to discuss the efficacy and safety of a drug in the treatment of COVID-19, as most studies have just begun. The therapeutic regimens proposed now in clinical recommendations have no evidence base, and the studies indicated in them are at best considered hypothesizing.", "qid": 17, "docid": "37ii08h8", "rank": 2, "score": 0.8196253776550293}, {"content": "Title: Review and methodological analysis of trials currently testing treatment and prevention options for the novel coronavirus disease (COVID-19) globally. Content: Background: As novel coronavirus disease (COVID-19) cases continue to steeply rise globally within an unprecedented short period of time, solid evidence from large randomised controlled trials is still lacking. Currently, numerous trials testing potential treatment and preventative options are undertaken globally. Objectives: We summarised all currently registered clinical trials examining treatment and prevention options for COVID-19 pneumonia. Additionally, we evaluated the quality of the retrieved interventional studies. Data sources: The ClinicalTrials.gov, the Chinese Clinical Trial Registry and the European Union Clinical Trials Register were systematically searched. Study eligibility criteria: Registered clinical trials examining treatment and/or prevention options for COVID-19 were included. No language, country or study design restrictions were applied. Withdrawn, cancelled studies and trials not reporting therapeutic or preventative strategies for COVID-19 were excluded. Participants and interventions: No restrictions in terms of participants' age and medical background or type of intervention were enforced. Methods: The registries were searched using the term \"coronavirus\" or \"COVID-19\" from their inception until 26th March 2020. Additional manual search of the registries was also performed. Eligible studies were summarised and tabulated. Interventional trials were methodologically analysed, excluding expanded access studies and trials testing Traditional Chinese Medicine. Results: In total, 309 trials evaluating therapeutic management options, 23 studies assessing preventive strategies and 3 studies examining both were retrieved. Interventional treatment studies were mostly randomised (n=150, 76%) and open-label (n=73, 37%) with a median number of planned inclusions of 90 (IQR 40-200). Major categories of interventions that are currently being investigated are discussed. Conclusion: Numerous clinical trials have been registered since the onset of the COVID-19 pandemic. Summarised data on these trials will assist physicians and researchers to promote patient care and guide future research efforts for COVID-19 pandemic containment. However, up to the end of March, 2020, significant information concerning reported trials was lacking.", "qid": 17, "docid": "di23na30", "rank": 3, "score": 0.8149027824401855}, {"content": "Title: Review of trials currently testing treatment and prevention of COVID-19 Content: BACKGROUND: As COVID-19 cases continue to rise globally, evidence from large randomized controlled trials is still lacking. Currently, numerous trials testing potential treatment and preventative options are being undertaken all over the world. OBJECTIVES: We summarized all registered clinical trials examining treatment and prevention options for COVID-19. Additionally, we evaluated the quality of the retrieved studies. DATA SOURCES: Clinicaltrials.gov, the Chinese Clinical Trial Registry and the European Union Clinical Trials Register were systematically searched. STUDY ELIGIBILITY CRITERIA: Registered clinical trials examining treatment and/or prevention options for COVID-19 were included. No language, country or study design restrictions were applied. We excluded withdrawn or cancelled studies and trials not reporting therapeutic or preventative strategies for COVID-19. PARTICIPANTS AND INTERVENTIONS: No restrictions in terms of participants' age and medical background or type of intervention were enforced. METHODS: The registries were searched using the term 'coronavirus' or 'COVID-19' from their inception until 26 March 2020. Additional manual search of the registries was also performed. Eligible studies were summarized and tabulated. Interventional trials were methodologically analysed, excluding expanded access studies and trials testing traditional Chinese medicine. RESULTS: In total, 309 trials evaluating therapeutic management options, 23 studies assessing preventive strategies and three studies examining both were retrieved. Finally, 214 studies were methodologically reviewed. Interventional treatment studies were mostly randomized (n = 150/198, 76%) and open label (n = 73/198, 37%) with a median number of planned inclusions of 90 (interquartile range 40-200). Major categories of interventions that are currently being investigated are discussed. CONCLUSIONS: Numerous clinical trials have been registered since the onset of the COVID-19 pandemic. Summarized data on these trials will assist physicians and researchers to promote patient care and guide future research efforts for COVID-19 pandemic containment.", "qid": 17, "docid": "0t974igx", "rank": 4, "score": 0.8144911527633667}, {"content": "Title: Major ongoing clinical trials for COVID-19 treatment and studies currently being conducted or scheduled in Japan Content: The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global public health and economies Currently, hundreds of clinical trials on a wide variety of treatments against COVID-19 are being conducted around the world Here, we conducted a search for ongoing clinical trials for the treatment of COVID-19 at the clinicaltrials gov database on April 2, 2020 In total, 48 clinical trials were identified, and of these, 41 trials adopted drug intervention and the other 7 trials utilized biological intervention The number of trials stratified by a chief country conducting the investigation were 18 in China, 5 in the United States, 4 in Canada, 3 in Italy, 2 in France and Brazil, and 4 trials are being performed multinationally The drugs utilized in more than one trials were remdesivir (6 trials), lopinavir/ritonavir (6 trials), hydroxychloroquine (6 trials), interferon (5 trials), methylprednisolone (3 trials), nitric oxide gas (3 trials), oseltamivir (2 trials), arbidol (2 trials), and vitamin C (2 trials) We also described the Japanese trials which are now being conducted or scheduled, utilizing lopinavir/ritonavir, remdesivir, favipiravir, ciclesonide and nafamostat", "qid": 17, "docid": "i4fz2c49", "rank": 5, "score": 0.8129560947418213}, {"content": "Title: Clinical Trials for COVID-19: Can we Better Use the Short Window of Opportunity? Content: The scientific community has risen to the coronavirus disease 2019 (COVID-19) challenge, coming up with an impressive list of candidate drugs and vaccines targeting an array of pharmacological and immunological mechanisms. Yet, generating clinical evidence of efficacy and safety of these candidate treatments may be frustrated by the absence of comprehensive trial coordination mechanisms. Many small stand-alone trials and observational studies of single-agent interventions are currently running or in planning; many of these will likely not deliver robust results that could support regulatory and patient-level treatment decisions. In this paper, we discuss actions that all stakeholders in the clinical trial ecosystem need to take to ensure that the window of opportunity during this pandemic will not shut, both for patients in need of treatment and for researchers to conduct decision-relevant clinical trials.", "qid": 17, "docid": "fz6eumik", "rank": 6, "score": 0.8112754225730896}, {"content": "Title: Review of trials currently testing treatment and prevention of COVID-19 Content: BACKGROUND: As COVID-19 cases continue to rise globally, evidence from large randomised controlled trials is still lacking. Currently, numerous trials testing potential treatment and preventative options are undertaken all over the world. OBJECTIVES: We summarised all registered clinical trials examining treatment and prevention options for COVID-19. Additionally, we evaluated the quality of the retrieved studies. DATA SOURCES: Clinicaltrials.gov, the Chinese Clinical Trial Registry and the European Union Clinical Trials Register were systematically searched. STUDY ELIGIBILITY CRITERIA: Registered clinical trials examining treatment and/or prevention options for COVID-19 were included. No language, country or study design restrictions were applied. We excluded withdrawn or cancelled studies and trials not reporting therapeutic or preventative strategies for COVID-19. PARTICIPANTS: and interventions: No restrictions in terms of participants\u2019 age and medical background or type of intervention were enforced. METHODS: The registries were searched using the term \u201ccoronavirus\u201d or \u201cCOVID-19\u201d from their inception until 26(th) March 2020.Additional manual search of the registries was also performed. Eligible studies were summarised and tabulated. Interventional trials were methodologically analysed, excluding expanded access studies and trials testing Traditional Chinese Medicine. RESULTS: In total, 309 trials evaluating therapeutic management options, 23 studies assessing preventive strategies and 3 studies examining both were retrieved. Finally, 214 studies were methodologically reviewed. Interventional treatment studies were mostly randomised (n=150, 76%) and open-label (n=73, 37%) with a median number of planned inclusions of 90 (IQR 40-200). Major categories of interventions that are currently being investigated are discussed. CONCLUSION: Numerous clinical trials have been registered since the onset of the COVID-19 pandemic. Summarised data on these trials will assist physicians and researchers to promote patient care and guide future research efforts for COVID-19 pandemic containment.", "qid": 17, "docid": "dsjq98ks", "rank": 7, "score": 0.8112553358078003}, {"content": "Title: Clinical trials on drug repositioning for COVID-19 treatment Content: The World Health Organization (WHO) was informed on December 2019 about a coronavirus pneumonia outbreak in Wuhan, Hubei province (China). Subsequently, on March 12, 2020, 125,048 cases and 4,614 deaths were reported. Coronavirus is an enveloped RNA virus, from the genus Betacoronavirus, that is distributed in birds, humans, and other mammals. WHO has named the novel coronavirus disease as COVID-19. More than 80 clinical trials have been launched to test coronavirus treatment, including some drug repurposing or repositioning for COVID-19. Hence, we performed a search in March 2020 of the clinicaltrials.gov database. The eligibility criteria for the retrieved studies were: contain a clinicaltrials.gov base identifier number; describe the number of participants and the period for the study; describe the participants\u2019 clinical conditions; and utilize interventions with medicines already studied or approved for any other disease in patients infected with the novel coronavirus SARS-CoV-2 (2019-nCoV). It is essential to emphasize that this article only captured trials listed in the clinicaltrials.gov database. We identified 24 clinical trials, involving more than 20 medicines, such as human immunoglobulin, interferons, chloroquine, hydroxychloroquine, arbidol, remdesivir, favipiravir, lopinavir, ritonavir, oseltamivir, methylprednisolone, bevacizumab, and traditional Chinese medicines (TCM). Although drug repurposing has some limitations, repositioning clinical trials may represent an attractive strategy because they facilitate the discovery of new classes of medicines; they have lower costs and take less time to reach the market; and there are existing pharmaceutical supply chains for formulation and distribution.", "qid": 17, "docid": "vxqdfiel", "rank": 8, "score": 0.8065111637115479}, {"content": "Title: The Rationale for Potential Pharmacotherapy of COVID-19 Content: On 11 March 2020, the coronavirus disease (COVID-19) was defined by the World Health Organization as a pandemic. Severe acute respiratory syndrome-2 (SARS-CoV-2) is the newly evolving human coronavirus infection that causes COVID-19, and it first appeared in Wuhan, China in December 2019 and spread rapidly all over the world. COVID-19 is being increasingly investigated through virology, epidemiology, and clinical management strategies. There is currently no established consensus on the standard of care in the pharmacological treatment of COVID-19 patients. However, certain medications suggested for other diseases have been shown to be potentially effective for treating this infection, though there has yet to be clear evidence. Therapies include new agents that are currently tested in several clinical trials, in addition to other medications that have been repurposed as antiviral and immune-modulating therapies. Previous high-morbidity human coronavirus epidemics such as the 2003 SARS-CoV and the 2012 Middle East respiratory syndrome coronavirus (MERS-CoV) prompted the identification of compounds that could theoretically be active against the emerging coronavirus SARS-CoV-2. Moreover, advances in molecular biology techniques and computational analysis have allowed for the better recognition of the virus structure and the quicker screening of chemical libraries to suggest potential therapies. This review aims to summarize rationalized pharmacotherapy considerations in COVID-19 patients in order to serve as a tool for health care professionals at the forefront of clinical care during this pandemic. All the reviewed therapies require either additional drug development or randomized large-scale clinical trials to be justified for clinical use.", "qid": 17, "docid": "ro1wrvf8", "rank": 9, "score": 0.8050280809402466}, {"content": "Title: Characteristics of registered clinical trials assessing treatments for COVID-19: a cross-sectional analysis Content: OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has prompted many initiatives to identify safe and efficacious treatments, yet little is known regarding where early efforts have focused. We aimed to characterise registered clinical trials assessing drugs or plasma treatments for COVID-19. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional analysis of clinical trials for the treatment of COVID-19 that were registered in the USA or in countries contributing to the WHO\u2019s International Clinical Trials Registry Platform. Relevant trial entries of drugs or plasma were downloaded on 26 March 2020, deduplicated, verified with reviews of major medical journals and WHO websites and independently analysed by two reviewers. MAIN OUTCOME(S): Trial intervention, sponsorship, critical design elements and specified outcomes RESULTS: Overall, 201 clinical trials were registered for testing the therapeutic benefits of 92 drugs or plasma, including 64 in monotherapy and 28 different combinations. Only eight (8.7%) products or combinations involved new molecular entities. The other test therapies had a wide range of prior medical uses, including as antivirals, antimalarials, immunosuppressants and oncology treatments. In 152 trials (75.7%), patients were randomised to treatment or comparator, including 55 trials with some form of blinding and 97 open-label studies. The 49 (24.4%) of trials without a randomised design included 29 single armed studies and 20 trials with some comparison group. Most trial designs featured multiple endpoints. Clinical endpoints were identified in 134 (66.7%) of trials and included COVID-19 symptoms, death, recovery, required intensive care and hospital discharge. Clinical scales were being used in 33 (16.4%) trials, most often measures of oxygenation and critical illness. Surrogate endpoints or biomarkers were studied in 88 (42.3%) of trials, primarily assays of viral load. Although the trials were initiated in more than 17 countries or regions, 100 (49.8%) were registered in China and 78 (37.8%) in the USA. Registered trials increased rapidly, with the number of registered trials doubling from 1 March to 26 March 2020. CONCLUSIONS: While accelerating morbidity and mortality from the COVID-19 pandemic has been paralleled by early and rapid clinical investigation, many trials lack features to optimise their scientific value. Global coordination and increased funding of high-quality research may help to maximise scientific progress in rapidly discovering safe and effective treatments.", "qid": 17, "docid": "uqsjl4re", "rank": 10, "score": 0.8032890558242798}, {"content": "Title: Characteristics of registered clinical trials assessing treatments for COVID-19: a cross-sectional analysis Content: OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has prompted many initiatives to identify safe and efficacious treatments, yet little is known regarding where early efforts have focused. We aimed to characterise registered clinical trials assessing drugs or plasma treatments for COVID-19. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional analysis of clinical trials for the treatment of COVID-19 that were registered in the USA or in countries contributing to the WHO's International Clinical Trials Registry Platform. Relevant trial entries of drugs or plasma were downloaded on 26 March 2020, deduplicated, verified with reviews of major medical journals and WHO websites and independently analysed by two reviewers. MAIN OUTCOMES: Trial intervention, sponsorship, critical design elements and specified outcomes RESULTS: Overall, 201 clinical trials were registered for testing the therapeutic benefits of 92 drugs or plasma, including 64 in monotherapy and 28 different combinations. Only eight (8.7%) products or combinations involved new molecular entities. The other test therapies had a wide range of prior medical uses, including as antivirals, antimalarials, immunosuppressants and oncology treatments. In 152 trials (75.7%), patients were randomised to treatment or comparator, including 55 trials with some form of blinding and 97 open-label studies. The 49 (24.4%) of trials without a randomised design included 29 single armed studies and 20 trials with some comparison group. Most trial designs featured multiple endpoints. Clinical endpoints were identified in 134 (66.7%) of trials and included COVID-19 symptoms, death, recovery, required intensive care and hospital discharge. Clinical scales were being used in 33 (16.4%) trials, most often measures of oxygenation and critical illness. Surrogate endpoints or biomarkers were studied in 88 (42.3%) of trials, primarily assays of viral load. Although the trials were initiated in more than 17 countries or regions, 100 (49.8%) were registered in China and 78 (37.8%) in the USA. Registered trials increased rapidly, with the number of registered trials doubling from 1 March to 26 March 2020. CONCLUSIONS: While accelerating morbidity and mortality from the COVID-19 pandemic has been paralleled by early and rapid clinical investigation, many trials lack features to optimise their scientific value. Global coordination and increased funding of high-quality research may help to maximise scientific progress in rapidly discovering safe and effective treatments.", "qid": 17, "docid": "k1eq4l3d", "rank": 11, "score": 0.8010857105255127}, {"content": "Title: Clinical trials for the prevention and treatment of COVID-19: current state of play Content: Since coronavirus disease 2019 (COVID-19) emerged in Wuhan, China in December 2019 and spread around the world, over 1100 clinical studies have been registered globally on clinical trials registries, including over 500 randomised controlled trials. Such rapid development and launch of clinical trials is impressive but presents challenges, including the potential for duplication and competition. There is currently no known effective treatment for COVID-19. In order to focus on those studies most likely to influence clinical practice, we summarise the 31 currently registered randomised trials with a target sample size of at least 1000 participants. We have grouped these trials into four categories: prophylaxis; treatment of outpatients with mild COVID-19; treatment of hospitalised patients with moderate COVID-19; and treatment of hospitalised patients with moderate or severe disease. The most common therapeutic agent being trialled currently is hydroxychloroquine (24 trials with potential sample size of over 25 000 participants), followed by lopinavir-ritonavir (seven trials) and remdesevir (five trials) There are many candidate drugs in pre-clinical and early phase development, and these form a pipeline for future large clinical trials if current candidate therapies prove ineffective or unsafe.", "qid": 17, "docid": "pftu5qea", "rank": 12, "score": 0.7968940734863281}, {"content": "Title: A snapshot of the ongoing clinical research on COVID-19 Content: The pandemic of coronavirus disease 2019 (COVID-19) presents an unprecedented challenge to rapidly develop new diagnostic, preventive and therapeutic strategies. Currently, thousands of new COVID-19 patients are quickly enrolled in clinical studies. We aimed to investigate the characteristics of the COVID-19 studies registered in ClinicalTrials.gov and report the extent to which they have incorporated features that are desirable for generating high-quality evidence. On April 28, 2020, a total of 945 studies on COVID-19 have been registered in ClinicalTrials.gov; 586 studies are interventional (62.0%), the most frequent allocation scheme is the parallel group assignment (437; 74.6%), they are open-label and the most common primary purpose is the research on treatment. Too many of the ongoing interventional studies have a small expected sample size and may not generate credible evidence at completion. This might lead to a delayed recognition of effective therapies that are urgently needed, and a waste of time and resources. In the COVID-19 pandemic era, it is crucial that the adoption of new diagnostic, preventive and therapeutic strategies is based upon evidence coming from well-designed, adequately powered and carefully conducted clinical trials.", "qid": 17, "docid": "6vfrs6q9", "rank": 13, "score": 0.7925574779510498}, {"content": "Title: [Comment] Treatment strategies to fight the new coronavirus SARS-CoV-2: A challenge for a Rubik's Cube solver Content: SARS-coronavirus-2 (SARS-CoV-2), the etiologic agent of the new lung disease COVID-19 is closely related to SARS-CoV, and together with MERS-CoV are three new human coronaviruses that emerged in the last 20 years. The COVID-19 outbreak is a rapidly evolving situation with higher transmissibility and infectivity compared with SARS and MERS. Clinical presentations range from asymptomatic or mild symptoms to severe illness. The prevalent cause of mortality is pneumonia that progresses to ARDS. The ongoing pandemic has already resulted in more than 135,000 deaths and an unprecedented burden on national health systems worldwide. Pending the availability of a vaccine, there is a critical need to identify effective treatments and a number of clinical trials have been implemented worldwide. Trials are based on repurposed drugs that are already approved for other infections, have acceptable safety profiles or have performed well in animal studies against the other two deadly coronaviruses. Supportive care remains the mainstay of therapy at present, as it is still unclear how well these data can be extrapolated to SARS-CoV-2. Most of those emerging re-introduced drugs are administered to patients in the context of clinical trials. In this review, we summarize the strategies currently employed in the treatment of COVID-19.", "qid": 17, "docid": "g8bu2ene", "rank": 14, "score": 0.7914227247238159}, {"content": "Title: Profiles of COVID-19 clinical trials in the Chinese Clinical Trial Registry Content: The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health crisis since its initial reports in China. Since no effective vaccine or drug has been developed to treat and combat the COVID-19, the current approaches for clinical management focus on supportive care. There is a pressing need for evidence-based interventions to address the devastating clinical and public health effects of the COVID-19 pandemic. The Chinese scientists supported by private and government resources have adopted extensive efforts to identify effective drugs against the virus. To date, a large number of clinical trials addressing various aspects of COVID-19 have been registered in the Chinese Clinical Trial Registry (ChiCTR), including more than 200 interventional studies. Under such an urgent circumstance, the scope and quality of these clinical studies vary significantly. Hence, this review aims to make a comprehensive analysis on the profiles of COVID-19 clinical trials registered in the ChiCTR, including a wide range of characteristics. Our findings will provide a useful summary on these clinical studies, since most of these studies will encounter major challenges from the design to completion. It will be a long road for the outcomes of these studies to be published and international collaboration will help the ultimate goals of developing new vaccines and antiviral drugs. Trial registration: ClinicalTrials.gov identifier: NCT04252664.. Trial registration: ClinicalTrials.gov identifier: NCT04257656..", "qid": 17, "docid": "pxzbkde0", "rank": 15, "score": 0.7911850214004517}, {"content": "Title: Profiles of COVID-19 clinical trials in the Chinese Clinical Trial Registry. Content: The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health crisis since its initial reports in China. Since no effective vaccine or drug has been developed to treat and combat the COVID-19, the current approaches for clinical management focus on supportive care. There is a pressing need for evidence-based interventions to address the devastating clinical and public health effects of the COVID-19 pandemic. The Chinese scientists supported by private and government resources have adopted extensive efforts to identify effective drugs against the virus. To date, a large number of clinical trials addressing various aspects of COVID-19 have been registered in the Chinese Clinical Trial Registry (ChiCTR), including more than 200 interventional studies. Under such an urgent circumstance, the scope and quality of these clinical studies vary significantly. Hence, this review aims to make a comprehensive analysis on the profiles of COVID-19 clinical trials registered in the ChiCTR, including a wide range of characteristics. Our findings will provide a useful summary on these clinical studies, since most of these studies will encounter major challenges from the design to completion. It will be a long road for the outcomes of these studies to be published and international collaboration will help the ultimate goals of developing new vaccines and antiviral drugs. Trial registration: ClinicalTrials.gov identifier: NCT04252664.. Trial registration: ClinicalTrials.gov identifier: NCT04257656..", "qid": 17, "docid": "hfo5221v", "rank": 16, "score": 0.7911850214004517}, {"content": "Title: Vaccines and Drug Therapeutics to Lock Down Novel Coronavirus Disease 2019 (COVID-19): A Systematic Review of Clinical Trials Content: The ongoing novel coronavirus disease 2019 (COVID-19) pandemic has been responsible for millions of infections and hundreds of thousands of deaths. To date, there is no approved targeted treatment, and many investigational therapeutic agents and vaccine candidates are being considered for the treatment of COVID-19. To extract and summarize information on potential vaccines and therapeutic agents against COVID-19 at different stages of clinical trials from January to March 2020, we reviewed major clinical trial databases such as ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP), and other primary registries between January and March 15, 2020. Interventional studies at different phases under the COVID-19 pipeline were included. A total of 249 clinical trials were identified between January to March 15, 2020. After filtering observational studies (194 studies), a total of 56 interventional trials were considered. The majority of clinical trials have been conducted on chloroquine (n=10) and traditional Chinese medications (TCMs; n=10), followed by antivirals (n=8), anti-inflammatory/immunosuppressants (n=9), cellular therapies (n=4), combinations of different antivirals therapies (n=3), antibacterial (n=1), and other therapies (n=5). Five vaccines are under phase I, and there are a couple of phase III trials on the Bacillus Calmette-Gu\u00e9rin (BCG) vaccine under investigation among healthcare workers. Many novel compounds and vaccines against COVID-19 are currently under investigation. Some candidates have been tested for other viral infections and are listed for clinical trials against the COVID-19 pipeline. Currently, there are no effective specific antivirals or drug combinations available for the treatment of COVID-19.", "qid": 17, "docid": "p36zubnf", "rank": 17, "score": 0.7901710271835327}, {"content": "Title: Clinical trials for the prevention and treatment of COVID\u201019: current state of play Content: Since coronavirus disease 2019 (COVID\u201019) emerged in Wuhan, China in December 2019 and spread around the world, over 1100 clinical studies have been registered globally on clinical trials registries, including over 500 randomised controlled trials. Such rapid development and launch of clinical trials is impressive but presents challenges, including the potential for duplication and competition. There is currently no known effective treatment for COVID\u201019. In order to focus on those studies most likely to influence clinical practice, we summarise the 31 currently registered randomised trials with a target sample size of at least 1000 participants. We have grouped these trials into four categories: prophylaxis; treatment of outpatients with mild COVID\u201019; treatment of hospitalised patients with moderate COVID\u201019; and treatment of hospitalised patients with moderate or severe disease. The most common therapeutic agent being trialled currently is hydroxychloroquine (24 trials with potential sample size of over 25 000 participants), followed by lopinavir\u2013ritonavir (seven trials) and remdesevir (five trials). There are many candidate drugs in pre\u2010clinical and early phase development, and these form a pipeline for future large clinical trials if current candidate therapies prove ineffective or unsafe.", "qid": 17, "docid": "6wszpqvx", "rank": 18, "score": 0.7892346382141113}, {"content": "Title: COVID-19 and toxicity from potential treatments: Panacea or poison Content: Since December 2019, coronavirus disease (COVID-19) has been increasingly spreading from its origin in Wuhan, China to many countries around the world eventuating in morbidity and mortality affecting millions of people. This pandemic has proven to be a challenge given that there is no immediate cure, no vaccine is currently available and medications or treatments being used are still undergoing clinical trials. There have already been examples of self-medication and overdose. Clearly, there is a need to further define the efficacy of treatments used in the management of COVID-19. This evidence needs to be backed by large randomised-controlled clinical trials. In the meantime, there will no doubt be further off-label use of these medications by patients and practitioners and possibly related toxicity.", "qid": 17, "docid": "kpnuuvz6", "rank": 19, "score": 0.7891182899475098}, {"content": "Title: Clinical trial analysis of 2019\u2010nCoV therapy registered in China Content: So far, there is a lack of effective drugs for the new coronavirus pneumonia. With more and more patients diagnosed, China has carried out more than 100 clinical studies of new coronavirus infection, including antiviral drugs, antimalarial drugs, glucocorticoids, plasma therapy, virus vaccine, and other Western drugs, while Chinese medicine research accounted for half of the studies. Most of the trials were initiated by investigators and the study period would last for 1 to 11 months. The primary endpoints included symptom improvement and virus nucleic acid turning negative, but the optimal endpoint has not been determined. Although the final results of studies will take a long time to complete, the interim research data may provide some help for the current urgent demand for drug treatment. Compared with that of during SARS period in 2003, China has the stronger capability to carry out clinical trials of new drugs in emergency period.", "qid": 17, "docid": "o8j17zzs", "rank": 20, "score": 0.787422239780426}, {"content": "Title: Clinical trial analysis of 2019-nCoV therapy registered in China Content: So far, there is a lack of effective drugs for the new coronavirus pneumonia. With more and more patients diagnosed, China has carried out more than 100 clinical studies of new coronavirus infection, including antiviral drugs, antimalarial drugs, glucocorticoids, plasma therapy, virus vaccine, and other Western drugs, while Chinese medicine research accounted for half of the studies. Most of the trials were initiated by investigators and the study period would last for 1 to 11 months. The primary endpoints included symptom improvement and virus nucleic acid turning negative, but the optimal endpoint has not been determined. Although the final results of studies will take a long time to complete, the interim research data may provide some help for the current urgent demand for drug treatment. Compared with that of during SARS period in 2003, China has the stronger capability to carry out clinical trials of new drugs in emergency period.", "qid": 17, "docid": "g7rjtlht", "rank": 21, "score": 0.787422239780426}, {"content": "Title: Systematic review of the registered clinical trials for coronavirus disease 2019 (COVID-19) Content: BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19), many researchers in China have performed related clinical research. However, systematic reviews of the registered clinical trials are still lacking. Therefore, we conducted a systematic review of clinical trials for COVID-19 to summarize their characteristics. METHODS: This study is based on the PRISMA recommendations in the Cochrane handbook. The Chinese Clinical Registration Center and the ClinicalTrials.gov databases were searched to identify registered clinical trials related to COVID-19. The retrieval inception date was February 9, 2020. Two researchers independently selected the literature based on the inclusion and exclusion criteria, extracted data, and evaluated the risk of bias. RESULTS: A total of 75 registered clinical trials (63 interventional studies and 12 observational studies) for COVID-19 were identified. The majority of clinical trials were sponsored by Chinese hospitals. Only 11 trials have begun to recruit patients, and none of the registered clinical trials have been completed; 34 trials were early clinical exploratory trials or in the pre-experiment stage, 13 trials were phase III, and four trials were phase IV. The intervention methods included traditional Chinese medicine in 26 trials, Western medicine in 30 trials, and integrated traditional Chinese medicine and Western medicine in 19 trials. The subjects were primarily non-critical adult patients (\u2265 18 years old). The median sample size of the trials was 100 (IQR: 60\u2013200), and the median length of the trial periods was 179 d (IQR: 94\u2013366 d). The main outcomes were clinical observation and examinations. Overall, the methodological quality of both the interventional trials and observational studies was low. CONCLUSIONS: Intensive clinical trials on the treatment of COVID-19 using traditional Chinese medicine and Western medicine are ongoing or will be performed in China. However, based on the uncertain methodological quality, small sample size, and long trial duration, we will not be able to obtain reliable, high-quality clinical evidence regarding the treatment of COVID-19 in the near future. Improving the quality of study design, prioritizing promising drugs, and using different designs and statistical methods are worth advocating and recommending for clinical trials of COVID-19 in the future.", "qid": 17, "docid": "pazjx1g5", "rank": 22, "score": 0.7862194776535034}, {"content": "Title: Rigorous Randomized Controlled Trial Implementation in the Era of COVID-19 Content: Rigorous Randomized Controlled Trial Implementation in the Era of Novel Coronavirus Disease (COVID-19).", "qid": 17, "docid": "nst527yx", "rank": 23, "score": 0.785557746887207}, {"content": "Title: Current status of potential therapeutic candidates for the COVID-19 crisis Content: As of April 15, 2020, the ongoing coronavirus disease 2019 (COVID-2019) pandemic has swept through 213 countries and infected more than 1,870,000 individuals, posing an unprecedented threat to international health and the economy. There is currently no specific treatment available for patients with COVID-19 infection. The lessons learned from past management of respiratory viral infections have provided insights into treating COVID-19. Numerous potential therapies, including supportive intervention, immunomodulatory agents, antiviral therapy, and convalescent plasma transfusion, have been tentatively applied in clinical settings. A number of these therapies have provided substantially curative benefits in treating patients with COVID-19 infection. Furthermore, intensive research and clinical trials are underway to assess the efficacy of existing drugs and identify potential therapeutic targets to develop new drugs for treating COVID-19. Herein, we summarize the current potential therapeutic approaches for diseases related to COVID-19 infection and introduce their mechanisms of action, safety, and effectiveness.", "qid": 17, "docid": "k9xqqcoc", "rank": 24, "score": 0.7853575944900513}, {"content": "Title: Ongoing Clinical Trials for the Management of the COVID-19 Pandemic Content: COVID-19 has rapidly developed into a worldwide pandemic with a significant health and economic burden. There are currently no approved treatments or preventative therapeutic strategies. Hundreds of clinical studies have been registered with the intention of discovering effective treatments. Here, we review currently registered interventional clinical trials for the treatment and prevention of COVID-19 to provide an overall summary and insight into the global response.", "qid": 17, "docid": "ibuqz948", "rank": 25, "score": 0.7853459715843201}, {"content": "Title: Treatment of SARS-CoV-2: How far have we reached? Content: The virus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is currently affecting more than 200 countries and territories worldwide. It has been declared as pandemic by World Health Organization (WHO) and the whole world is suffering from corona virus disease 2019 (COVID-19). Currently, no treatment for SARS-CoV-2 are approved because of lack of evidence, but a number of clinical trials are in process and we are expecting fruitful results very soon. This review focuses on various approaches of treatment and few of the most recent clinical trials carried out in this field.", "qid": 17, "docid": "lgzmwx3j", "rank": 26, "score": 0.7850844860076904}, {"content": "Title: Characteristics of COVID-19 Clinical Trials in China Based on the Registration Data on ChiCTR and ClinicalTrials.gov Content: Objective: This study aimed to evaluate the fundamental characteristics of coronavirus disease (COVID-19) clinical trials registered in China. Methods: COVID-19 clinical trials registered in China were analyzed from databases on ChiCTR and ClinicalTrials.gov. The study designs, samples, primary end points, and intervention measures were evaluated. Results: In total, 262 intervention clinical trials were retrieved on March 10, 2020. Overall, 181 (69.1%) trials involved two groups, 200 (76.3%) trials were randomized parallel trials, 24 (9.2%) trials were double blind, and 60.3% of trials included &#8804;100 participants. Sixty (22.9%) trials considered symptom improvement as the primary endpoint and 43 (16.4%) trials considered the rate or time at which the subjects became virus-free as the primary endpoint. Of 262 intervention studies, chemical drugs and biological products were studied in 105 (40.1%) intervention studies, of which antiviral drugs accounted for 15.3% and malaria drugs accounted for 8.4% of the studies. Among all trials, 27.9% of the studies used traditional Chinese medicine (TCM), 10.3% used cell therapy, and 5.0% used plasma therapy. Conclusion: This study is the first snapshot of the landscape of COVID-19 clinical trials registered in China and provided the basic features of clinical trial designs for the treatment and prevention of COVID-19 to offer useful information to guide future clinical trials on COVID-19 in other countries.", "qid": 17, "docid": "7izjhyyk", "rank": 27, "score": 0.7846070528030396}, {"content": "Title: Role of adjunctive treatment strategies in COVID-19 and a review of international and national clinical guidelines Content: The coronavirus disease (COVID-19) pandemic has led to a global struggle to cope with the sheer numbers of infected persons, many of whom require intensive care support or eventually succumb to the illness. The outbreak is managed by a combination of disease containment via public health measures and supportive care for those who are affected. To date, there is no specific anti-COVID-19 treatment. However, the urgency to identify treatments that could turn the tide has led to the emergence of several investigational drugs as potential candidates to improve outcome, especially in the severe to critically ill. While many of these adjunctive drugs are being investigated in clinical trials, professional bodies have attempted to clarify the setting where the use of these drugs may be considered as off-label or compassionate use. This review summarizes the clinical evidence of investigational adjunctive treatments used in COVID-19 patients as well as the recommendations of their use from guidelines issued by international and national organizations in healthcare.", "qid": 17, "docid": "4ea77hqx", "rank": 28, "score": 0.7845326662063599}, {"content": "Title: Current Status of Treatment Options, Clinical Trials, and Vaccine Development for SARS-CoV-2 Infection Content: The severe acute respiratory syndrome virus (SARS-CoV-2), a novel coronavirus first discovered in Wuhan, China in December 2019 causes the Coronavirus Disease 19 (COVID-19), which presents with a wide range of clinical symptoms from mild or moderate to severe and critical illnesses With the continuing transmission of the virus worldwide and the rapidly evolving situation globally, the World Health Organization (WHO) declared the COVID-19 outbreak a pandemic in March Currently, there is no proven specific treatment for this potentially deadly disease beyond supportive care However, a massive effort has been put globally into the investigation of medications and other interventional measures to fight COVID-19 Convalescent plasma therapy from recovered patients has recently drawn considerable interest Several alternative medical treatments, although evidence of their efficacy still lacking, have also gained popularity, especially in countries with such traditions such as India and China Rapid repurposing of drugs for COVID-19 has revealed a few promising candidate antiviral agents, but further research, especially high quality randomized controlled trials, will be needed to prove their efficacy and safety in the clinical use to treat COVID-19 Vaccine development has been the imperative task in the battle against SARS-CoV-2 While clinical trials have been launched for several candidate vaccines, research on COVID-19 vaccines is still at an early stage So far, optimized supportive care remains the best practice against COVID-19", "qid": 17, "docid": "0j5bg59c", "rank": 29, "score": 0.7837736010551453}, {"content": "Title: A large number of COVID-19 interventional clinical trials were registered soon after the pandemic onset: a descriptive analysis Content: BACKGROUND AND OBJECTIVE: There is a pressing need for evidence-based interventions to address the devastating clinical and public health effects of the coronavirus disease 2019 (COVID-19) pandemic. The number of registered trials related to COVID-19 is increasing by the day. The objective of this study was to describe the characteristics of the currently registered interventional clinical trials related to COVID-19. METHODS: We searched the World Health Organization's International Clinical Trials Registry Platform on May 15th, 2020. We included any entry that is related to COVID-19. We abstracted and then descriptively analyzed the following characteristics of the registered trials: study design, status, phase, primary endpoints, experimental interventions, and geographic location among other qualifiers. RESULTS: We identified 1,308 eligible registered trials. Most trials were registered with ClinicalTrials.gov (n = 703; 53.7%) and the Chinese Clinical Trial Registry (n = 291; 22.2%). The number of participants to be enrolled across these trials was 734,657, with a median of 110 participants per trial. The most commonly studied intervention category was pharmacologic (n = 763; 58.3%), with antiparasitic medications being the most common subcategory. Although over half of the trials were already recruiting, we identified published peer-reviewed results for only 8 of those trials. CONCLUSION: There is a relatively large number of registered trials but with very few results published so far. Although our findings suggest an appropriate initial response by the research community, the real challenge will be to get these trials completed, published, and translated into practice and policy.", "qid": 17, "docid": "81dmnya4", "rank": 30, "score": 0.7834907174110413}, {"content": "Title: Treatment and research lines for the patient with COVID-19. What do we have and where are we going? Content: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents the most significant global public health crisis of this generation. From the beginning of the pandemic, several publications and on-line resources about different treatment lines have been done, and development effort in response to the COVID-19 pandemic to investigate potential therapies is unprecedented. Unfortunately, until now, there is not enough evidence to recommend any specific anti-COVID19 treatment. Randomized clinical trials and high-quality evidence, even in the middle of a pandemic, are needed. We provide a review of the latest published literature on the therapeutic strategies and current investigational lines for SARS-CoV-2.", "qid": 17, "docid": "okrpa7k7", "rank": 31, "score": 0.7828368544578552}, {"content": "Title: Repurposing Existing Medications for Coronavirus Disease 2019: Protocol for a Rapid and Living Systematic Review Content: BACKGROUND: Coronavirus Disease 2019 (COVID-19) has no known specific treatments. However, there might be in vitro and early clinical data as well as evidence from Severe Acute Respiratory Syndrome and Middle Eastern Respiratory Syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19. METHODS: This systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and four groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence. DISCUSSION: The challenge posed by COVID-19 requires not just a rapid review of drugs that can be repurposed but also a sustained effort to integrate new evidence into a living systematic review. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2020 CRD42020175648", "qid": 17, "docid": "g2815zqn", "rank": 32, "score": 0.781655490398407}, {"content": "Title: Comprehensive analysis of drugs to treat SARS-CoV-2 infection: Mechanistic insights into current COVID-19 therapies (Review) Content: The major impact produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) focused many researchers attention to find treatments that can suppress transmission or ameliorate the disease. Despite the very fast and large flow of scientific data on possible treatment solutions, none have yet demonstrated unequivocal clinical utility against coronavirus disease 2019 (COVID-19). This work represents an exhaustive and critical review of all available data on potential treatments for COVID-19, highlighting their mechanistic characteristics and the strategy development rationale. Drug repurposing, also known as drug repositioning, and target based methods are the most used strategies to advance therapeutic solutions into clinical practice. Current in silico, in vitro and in vivo evidence regarding proposed treatments are summarized providing strong support for future research efforts.", "qid": 17, "docid": "de3mqy2d", "rank": 33, "score": 0.7812901139259338}, {"content": "Title: COVID\u201019 and toxicity from potential treatments: Panacea or poison Content: Since December 2019, coronavirus disease (COVID\u201019) has been increasingly spreading from its origin in Wuhan, China to many countries around the world eventuating in morbidity and mortality affecting millions of people. This pandemic has proven to be a challenge given that there is no immediate cure, no vaccine is currently available and medications or treatments being used are still undergoing clinical trials. There have already been examples of self\u2010medication and overdose. Clearly, there is a need to further define the efficacy of treatments used in the management of COVID\u201019. This evidence needs to be backed by large randomised\u2010controlled clinical trials. In the meantime, there will no doubt be further off\u2010label use of these medications by patients and practitioners and possibly related toxicity.", "qid": 17, "docid": "z7ajsf2r", "rank": 34, "score": 0.7811667919158936}, {"content": "Title: Comprehensive overview of COVID-19 clinical trials Content: Here, we present an overview of the clinical trials that are currently being conducted or have concluded to date on COVID-19 globally. A comprehensive search was conducted to present 16 trial registries from around the world. Collectively, there are 1,528 trials reported for COVID-19 to date. Out of them, 50 studies included paediatric age group from day 0 to less than or equal to 18 years of age. A few 18 studies involve only females and 20 only males. There are 2 trials currently underway in Bangladesh, 4 in Pakistan and 13 in India. Overall, 940 trials are related to medicines and/or interventions. They include standard of care for any viral illness, antivirals, anti-inflammatory and immune altering medications. Two out of 10 vaccine trials are novel vaccines. It is knowledgeable and resourceful to reach out to the concerned sponsor if a physician thinks his patient can benefit from the trials in the region.", "qid": 17, "docid": "7nm7s0l5", "rank": 35, "score": 0.7807226181030273}, {"content": "Title: Comprehensive overview of COVID-19 clinical trials. Content: Here, we present an overview of the clinical trials that are currently being conducted or have concluded to date on COVID-19 globally. A comprehensive search was conducted to present 16 trial registries from around the world. Collectively, there are 1,528 trials reported for COVID-19 to date. Out of them, 50 studies included paediatric age group from day 0 to less than or equal to 18 years of age. A few 18 studies involve only females and 20 only males. There are 2 trials currently underway in Bangladesh, 4 in Pakistan and 13 in India. Overall, 940 trials are related to medicines and/or interventions. They include standard of care for any viral illness, antivirals, anti-inflammatory and immune altering medications. Two out of 10 vaccine trials are novel vaccines. It is knowledgeable and resourceful to reach out to the concerned sponsor if a physician thinks his patient can benefit from the trials in the region.", "qid": 17, "docid": "fti60hts", "rank": 36, "score": 0.7807226181030273}, {"content": "Title: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review Content: Rapid diagnostics, vaccines and therapeutics are important interventions for the management of the 2019 novel coronavirus (2019-nCoV) outbreak. It is timely to systematically review the potential of these interventions, including those for Middle East respiratory syndrome-Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS)-CoV, to guide policymakers globally on their prioritization of resources for research and development. A systematic search was carried out in three major electronic databases (PubMed, Embase and Cochrane Library) to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Supplementary strategies through Google Search and personal communications were used. A total of 27 studies fulfilled the criteria for review. Several laboratory protocols for confirmation of suspected 2019-nCoV cases using real-time reverse transcription polymerase chain reaction (RT-PCR) have been published. A commercial RT-PCR kit developed by the Beijing Genomic Institute is currently widely used in China and likely in Asia. However, serological assays as well as point-of-care testing kits have not been developed but are likely in the near future. Several vaccine candidates are in the pipeline. The likely earliest Phase 1 vaccine trial is a synthetic DNA-based candidate. A number of novel compounds as well as therapeutics licensed for other conditions appear to have in vitro efficacy against the 2019-nCoV. Some are being tested in clinical trials against MERS-CoV and SARS-CoV, while others have been listed for clinical trials against 2019-nCoV. However, there are currently no effective specific antivirals or drug combinations supported by high-level evidence.", "qid": 17, "docid": "m95bmi9t", "rank": 37, "score": 0.7803969383239746}, {"content": "Title: Current evidence for directed and supportive investigational therapies against COVID-19 Content: Coronavirus disease 2019 (COVID-19) is a global health crisis. There is currently a great need for effective and safe therapies directed at the disease, but no drugs are presently registered for use in COVID-19. Several directed therapies have been proposed, and most are still in clinical trials. Currently available published, peer-reviewed results mostly involve small sample sizes with study limitations restricting the interpretation of the findings. Many trials currently published also do not have a control group, limiting the interpretation of the effect of the intervention. Investigational directed therapies as well as investigational supportive therapies against COVID-19 are reviewed here. Chloroquine and hydroxychloroquine show promise as directed therapies, but current trial results are conflicting. Lopinavir/ritonavir also shows potential, but was started late in the disease course in most trials. No randomised controlled evidence is currently available for remdesivir and favipiravir. Corticosteroid use is not recommended for directed therapy against COVID-19, and the role of tocilizumab is currently unclear, based on limited evidence. Early initiation of investigational directed therapies may provide benefit in selected patients. The results from larger randomised controlled trials will clarify the place of these therapies in COVID-19 treatment.", "qid": 17, "docid": "f33eb1nf", "rank": 38, "score": 0.7798726558685303}, {"content": "Title: Covid-19 and drug therapy, what we learned Content: COVID-19, the disease associated in December 2019 with the novel coronavirus SARS-CoV-2, was observed for the first time in China and then spread worldwide becoming pandemic. Currently, there is still no licensed specific antiviral treatment for the human coronavirus disease and a vaccine will not be ready soon. However, based on experience from the use of other antiviral agents to treat similar virusses, some treatment options have been tried with some efficacy. Clinical trials for future therapies are still ongoing. In the meantime, prevention, control, active communication and investment in research are the only ways to overcome this challenge.", "qid": 17, "docid": "538mkxfu", "rank": 39, "score": 0.7791880369186401}, {"content": "Title: The World of Clinical Trial Development Post COVID-19: Lessons Learned from a Global Pandemic Content: The novel coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a global health threat (1). Patients with cancer are one of the most vulnerable populations. During this pandemic, clinical trial accrual to NCI studies has fallen dramatically. Investigators quickly turned to regulatory bodies to simplify treatment schedules, facilitate telemedicine, and decrease required data collection. Going forward, the oncology research community must use the lessons learned to focus on redesigning studies to ensure that critical scientific questions are answered safely while expanding access and increasing partnerships with community physicians. These changes will accelerate clinical progress while protecting our patients.", "qid": 17, "docid": "e4gbxgk9", "rank": 40, "score": 0.7790607810020447}, {"content": "Title: Characteristics of COVID-19 Clinical Trials in China Based on the Registration Data on ChiCTR and ClinicalTrials.gov Content: OBJECTIVE: This study aimed to evaluate the fundamental characteristics of coronavirus disease (COVID-19) clinical trials registered in China. METHODS: COVID-19 clinical trials registered in China were analyzed from databases on ChiCTR and ClinicalTrials.gov. The study designs, samples, primary end points, and intervention measures were evaluated. RESULTS: In total, 262 intervention clinical trials were retrieved on March 10, 2020. Overall, 181 (69.1%) trials involved two groups, 200 (76.3%) trials were randomized parallel trials, 24 (9.2%) trials were double blind, and 60.3% of trials included \u2264100 participants. Sixty (22.9%) trials considered symptom improvement as the primary endpoint and 43 (16.4%) trials considered the rate or time at which the subjects became virus-free as the primary endpoint. Of 262 intervention studies, chemical drugs and biological products were studied in 105 (40.1%) intervention studies, of which antiviral drugs accounted for 15.3% and malaria drugs accounted for 8.4% of the studies. Among all trials, 27.9% of the studies used traditional Chinese medicine (TCM), 10.3% used cell therapy, and 5.0% used plasma therapy. CONCLUSION: This study is the first snapshot of the landscape of COVID-19 clinical trials registered in China and provided the basic features of clinical trial designs for the treatment and prevention of COVID-19 to offer useful information to guide future clinical trials on COVID-19 in other countries.", "qid": 17, "docid": "zed7d315", "rank": 41, "score": 0.7789571285247803}, {"content": "Title: Rapid Adaptation of a Surgical Research Unit to Conduct Clinical Trials during the Coronavirus-19 Pandemic. Content: The Coronavirus Disease 2019 (COVID-19) pandemic has brought most ongoing clinical trials to a standstill, while at the same time emphasizing the need for new therapeutic treatments and strategies to mitigate the morbidity and mortality related to COVID-19. Recent publication of several observational studies has generated much discussion surrounding efficacy of drugs including hydroxychloroquine, azithromycin, and remdesivir, stressing the need for high-quality prospective, randomized control trials in patients with COVID-19. Ongoing \u2018Stay at Home\u2019 orders and institutional policies mandating \u2018Work from Home\u2019 for non-essential employees, which includes most research personnel, have impacted the ability to implement and conduct clinical studies. This article discusses the approach of an experienced clinical trials unit to make adjustments for ongoing studies and ensure the safety of study participants. At the same time, plans were implemented to continue collection of data to achieve endpoints, safely enroll and follow participants in studies offering potential benefit, and quickly implement new COVID-19 clinical trials. The existence of a Division of Clinical Research with regulatory, budgeting, contracting, and coordinating expertise within a Department of Surgery can successfully accommodate a crisis situation and rapidly adapt to new requirements for the safe, efficient, and effective conversion to a remote work force without compromising the research process.", "qid": 17, "docid": "d3k26aar", "rank": 42, "score": 0.7788811326026917}, {"content": "Title: A Comprehensive Analysis of Clinical Trials in the COVID-19 Pandemic Era Content: Background and objective: Despite medical advances, we are facing the unprecedented disaster of the coronavirus disease 2019 (COVID-19) pandemic without available treatments and effective vaccines. As the COVID-19 pandemic has approached its culmination, desperate efforts have been made to seek proper treatments and response strategies, and the number of clinical trials has been rapidly increasing. In this time of the pandemic, it is believed that learning lessons from it would be meaningful in preparing for future pandemics. Thus, this study aims at providing a comprehensive landscape of COVID-19 related clinical trials based on the ClinicalTrials.gov database. Materials and methods: Up to 30 March 2020, we identified a total of 147 eligible clinical trials and reviewed the overview of the studies. Results: Until then, the most clinical trials were set up in China. Treatment approaches are the most frequent purpose of the registered studies. Chloroquine, interferon, and antiviral agents such as remdesivir, lopinavir, and ritonavir are agents under investigation in these trials. Conclusions: In this study, we introduced the promising therapeutic options that many researchers and clinicians are interested in, and to address the hidden issues behind clinical trials in this COVID-19 pandemic.", "qid": 17, "docid": "ykfm38tg", "rank": 43, "score": 0.778866171836853}, {"content": "Title: A Comprehensive Analysis of Clinical Trials in the COVID-19 Pandemic Era. Content: Background and objective: Despite medical advances, we are facing the unprecedented disaster of the coronavirus disease 2019 (COVID-19) pandemic without available treatments and effective vaccines. As the COVID-19 pandemic has approached its culmination, desperate efforts have been made to seek proper treatments and response strategies, and the number of clinical trials has been rapidly increasing. In this time of the pandemic, it is believed that learning lessons from it would be meaningful in preparing for future pandemics. Thus, this study aims at providing a comprehensive landscape of COVID-19 related clinical trials based on the ClinicalTrials.gov database. Materials and methods: Up to 30 March 2020, we identified a total of 147 eligible clinical trials and reviewed the overview of the studies. Results: Until then, the most clinical trials were set up in China. Treatment approaches are the most frequent purpose of the registered studies. Chloroquine, interferon, and antiviral agents such as remdesivir, lopinavir, and ritonavir are agents under investigation in these trials. Conclusions: In this study, we introduced the promising therapeutic options that many researchers and clinicians are interested in, and to address the hidden issues behind clinical trials in this COVID-19 pandemic.", "qid": 17, "docid": "bl4d808v", "rank": 44, "score": 0.7788661122322083}, {"content": "Title: Emergence of novel coronavirus and progress toward treatment and vaccine Content: In late December 2019, a group of patients was observed with pneumonia-like symptoms that were linked with a wet market in Wuhan, China. The patients were found to have a novel coronavirus genetically related to a bat coronavirus that was termed SARS-CoV-2. The virus gradually spread worldwide and was declared a pandemic by WHO. Scientists have started trials on potential preventive and treatment options. Currently, there is no specific approved treatment for SARS-CoV-2, and various clinical trials are underway to explore better treatments. Some previously approved antiviral and other drugs have shown some in vitro activity. Here we summarize the fight against this novel coronavirus with particular focus on the different treatment options and clinical trials exploring treatment as well as work done toward development of vaccines.", "qid": 17, "docid": "uw7qhwne", "rank": 45, "score": 0.7784407138824463}, {"content": "Title: Balancing evidence and frontline experience in the early phases of the COVID-19 pandemic: current position of the Italian Society of Anti-infective Therapy (SITA) and the Italian Society of Pulmonology (SIP) Content: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which has rapidly become epidemic in Italy and other European countries. The disease spectrum ranges from asymptomatic/mildly symptomatic presentations to acute respiratory failure. At the present time the absolute number of severe cases requiring ventilator support is reaching or even surpassing the intensive care unit bed capacity in the most affected regions and countries. OBJECTIVES: To narratively summarize the available literature on the management of COVID-19 in order to combine current evidence and frontline opinions and to provide balanced answers to pressing clinical questions. SOURCES: Inductive PubMed search for publications relevant to the topic. CONTENT: The available literature and the authors' frontline-based opinion are summarized in brief narrative answers to selected clinical questions, with a conclusive statement provided for each answer. IMPLICATIONS: Many off-label antiviral and anti-inflammatory drugs are currently being administered to patients with COVID-19. Physicians must be aware that, as they are not supported by high-level evidence, these treatments may often be ethically justifiable only in those worsening patients unlikely to improve only with supportive care, and who cannot be enrolled onto randomized clinical trials. Access to well-designed randomized controlled trials should be expanded as much as possible because it is the most secure way to change for the better our approach to COVID-19 patients.", "qid": 17, "docid": "w8yb5bfa", "rank": 46, "score": 0.7781870365142822}, {"content": "Title: Trials and tribulations: so many potential treatments, so few answers Content: PURPOSE: The purpose of this review is to quantify the landscape of current clinical trials ongoing for therapies in the treatment of COVID-19. A secondary purpose is to examine the relationship between public and scientific interests in potential therapies for COVID-19. METHODS: A systematic search of clinicaltrials.gov was undertaken on April 22, 2020, to identify all currently registered clinical trials investigating potential therapies for patients with COVID-19. Public interest in the various therapies was quantified utilizing Google Trends. Public interest in hydroxychloroquine and chloroquine was plotted against the cumulative number of active clinical trials evaluating antimalarials as potential COVID-19 therapies over time. RESULTS: There were 341 interventional studies and 208 different therapies actively registered on clinicaltrials.gov whose primary aim is the treatment of COVID-19. The median sample size was 120 patients (range 4-6000) with 154 (45%) trials reporting a planned sample size of 100 patients or less. There was a strong positive correlation (r = 0.76, p = 0.01) between the number of registered clinical trials and the public interest in the top ten proposed therapies. Following the spike in public interest, the average number of new trials increased tenfold with respect to antimalarial therapies. CONCLUSIONS: The relatively small sample sizes and the number of independent trials investigating similar therapies are concerning. Resources may not be being allocated based on scientific merit and may be driven by public consciousness and speculation. Moving forward, a concerted effort focused on implementing large, well-coordinated and carefully designed multi-armed clinical trials will help to ensure that the most promising therapeutic options are rigorously studied and clinically meaningful results produced.", "qid": 17, "docid": "yiyt11nn", "rank": 47, "score": 0.7778258323669434}, {"content": "Title: Trials and tribulations: so many potential treatments, so few answers Content: PURPOSE: The purpose of this review is to quantify the landscape of current clinical trials ongoing for therapies in the treatment of COVID-19. A secondary purpose is to examine the relationship between public and scientific interests in potential therapies for COVID-19. METHODS: A systematic search of clinicaltrials.gov was undertaken on April 22, 2020, to identify all currently registered clinical trials investigating potential therapies for patients with COVID-19. Public interest in the various therapies was quantified utilizing Google Trends. Public interest in hydroxychloroquine and chloroquine was plotted against the cumulative number of active clinical trials evaluating antimalarials as potential COVID-19 therapies over time. RESULTS: There were 341 interventional studies and 208 different therapies actively registered on clinicaltrials.gov whose primary aim is the treatment of COVID-19. The median sample size was 120 patients (range 4\u20136000) with 154 (45%) trials reporting a planned sample size of 100 patients or less. There was a strong positive correlation (r = 0.76, p = 0.01) between the number of registered clinical trials and the public interest in the top ten proposed therapies. Following the spike in public interest, the average number of new trials increased tenfold with respect to antimalarial therapies. CONCLUSIONS: The relatively small sample sizes and the number of independent trials investigating similar therapies are concerning. Resources may not be being allocated based on scientific merit and may be driven by public consciousness and speculation. Moving forward, a concerted effort focused on implementing large, well-coordinated and carefully designed multi-armed clinical trials will help to ensure that the most promising therapeutic options are rigorously studied and clinically meaningful results produced.", "qid": 17, "docid": "c4szyk26", "rank": 48, "score": 0.7776801586151123}, {"content": "Title: Comments on Zhang et al: Clinical trial analysis of 2019\u2010nCoV therapy registered in China Content: We have read the article by Zhang et al. published in the recent issue of the Journal of Medical Virology1 . Zhang and his colleagues have made a cross-sectional survey of currently registered clinical trials concerning 2019-nCoV, including the published literature. As such, they have given a preliminary assessment on the prospects of therapy for 2019-nCoV. This article is protected by copyright. All rights reserved.", "qid": 17, "docid": "rmpzsse9", "rank": 49, "score": 0.7773227691650391}, {"content": "Title: Available Evidence and Ongoing Clinical Trials of Remdesivir: Could It Be a Promising Therapeutic Option for COVID-19? Content: The novel coronavirus strain, severe acute respiratory syndrome coronavirus-2, the causative agent of COVID-19 emerged in Wuhan, China, in December 2019 and is skyrocketing throughout the globe and become a global public health emergency. Despite promising preventive measures being taken, there is no vaccine or drug therapy officially approved to prevent or treat the infection. Everybody is waiting the findings of ongoing clinical trials in various chemical and biological products. This review is specifically aimed to summarize the available evidence and ongoing clinical trials of remdesivir as a potential therapeutic option for COVID-19. Remdesivir is an investigational drug having broad spectrum antiviral activity with its target RNA dependent RNA polymerase. It has not yet been officially approved for Ebola and Coronaviruses. Several studies showed that remdesivir had promising in vitro and in vivo antiviral activities against SARS-CoV-1 and MERS-CoV strains. On the top of this, it exhibited a promising in vitro activity against SARS-CoV-2 strains though there are no published studies that substantiate its activity in vivo until the time of this review. There are few phase 3 randomized double-blind placebo controlled trials on the way to investigate the safety and efficacy of remdesivir. Of which, one completed double blind, placebo controlled trial showed that remdesivir showed faster time to clinical improvement in severe COVID-19 patients compared to placebo though not found statistically significant. In addition, two phase 3 randomized open label clinical trials coordinated by Gilead Sciences are being conducted. In addition, WHO Solidarity trial and INSERM DisCoVeRy trials (randomized open labels) were launched recently.", "qid": 17, "docid": "tasbdhs1", "rank": 50, "score": 0.7771780490875244}, {"content": "Title: An evidence-based framework for priority clinical research questions for COVID-19 Content: BACKGROUND: On 31 December, 2019, the World Health Organization China Country Office was informed of cases of pneumonia of unknown aetiology. Since then, there have been over 75 000 cases globally of the 2019 novel coronavirus (COVID-19), 2000 deaths, and over 14 000 cases recovered. Outbreaks of novel agents represent opportunities for clinical research to inform real-time public health action. In 2018, we conducted a systematic review to identify priority research questions for Severe Acute Respiratory Syndrome-related coronavirus (SARS-CoV) and Middle East Respiratory Syndrome-related coronavirus (MERS-CoV). Here, we review information available on COVID-19 and provide an evidenced-based framework for priority clinical research in the current outbreak. METHODS: Three bibliographic databases were searched to identify clinical studies published on SARS-CoV and MERS-CoV in the outbreak setting. Studies were grouped thematically according to clinical research questions addressed. In February 2020, available information on COVID19 was reviewed and compared to the results of the SARS-CoV and MERS-CoV systematic review. RESULTS: From the research objectives for SARS-CoV and MERS-CoV, ten themes in the literature were identified: Clinical characterisation, prognosis, diagnosis, clinical management, viral pathogenesis, epidemiological characterisation, infection prevention and control/transmission, susceptibility, psychosocial, and aetiology. For COVID19, some information on clinical presentation, diagnostic testing, and aetiology is available but many clinical research gaps have yet to be filled. CONCLUSIONS: Based on a systematic review of other severe coronaviruses, we summarise the state of clinical research for COVID-19, highlight the research gaps, and provide recommendations for the implementation of standardised protocols. Data based on internationally standardised protocols will inform clinical practice real-time.", "qid": 17, "docid": "i6pv90s9", "rank": 51, "score": 0.7771457433700562}, {"content": "Title: An evidence-based framework for priority clinical research questions for COVID-19 Content: Background: On 31 December, 2019, the World Health Organization China Country Office was informed of cases of pneumonia of unknown aetiology. Since then, there have been over 75 000 cases globally of the 2019 novel coronavirus (COVID-19), 2000 deaths, and over 14 000 cases recovered. Outbreaks of novel agents represent opportunities for clinical research to inform real-time public health action. In 2018, we conducted a systematic review to identify priority research questions for Severe Acute Respiratory Syndrome-related coronavirus (SARS-CoV) and Middle East Respiratory Syndrome-related coronavirus (MERS-CoV). Here, we review information available on COVID-19 and provide an evidenced-based framework for priority clinical research in the current outbreak. Methods: Three bibliographic databases were searched to identify clinical studies published on SARS-CoV and MERS-CoV in the outbreak setting. Studies were grouped thematically according to clinical research questions addressed. In February 2020, available information on COVID19 was reviewed and compared to the results of the SARS-CoV and MERS-CoV systematic review. Results: From the research objectives for SARS-CoV and MERS-CoV, ten themes in the literature were identified: Clinical characterisation, prognosis, diagnosis, clinical management, viral pathogenesis, epidemiological characterisation, infection prevention and control/transmission, susceptibility, psychosocial, and aetiology. For COVID19, some information on clinical presentation, diagnostic testing, and aetiology is available but many clinical research gaps have yet to be filled. Conclusions: Based on a systematic review of other severe coronaviruses, we summarise the state of clinical research for COVID-19, highlight the research gaps, and provide recommendations for the implementation of standardised protocols. Data based on internationally standardised protocols will inform clinical practice real-time.", "qid": 17, "docid": "1pgdofj6", "rank": 52, "score": 0.7771457433700562}, {"content": "Title: Review of Emerging Pharmacotherapy for the Treatment of Coronavirus Disease 2019 Content: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into an emergent global pandemic. Coronavirus disease 2019 (COVID-19) can manifest on a spectrum of illness from mild disease to severe respiratory failure requiring intensive care unit admission. As the incidence continues to rise at a rapid pace, critical care teams are faced with challenging treatment decisions. There is currently no widely accepted standard of care in the pharmacologic management of patients with COVID-19. Urgent identification of potential treatment strategies is a priority. Therapies include novel agents available in clinical trials or through compassionate use, and other drugs, repurposed antiviral and immunomodulating therapies. Many have demonstrated in vitro or in vivo potential against other viruses that are similar to SARS-CoV-2. Critically ill patients with COVID-19 have additional considerations related to adjustments for organ impairment and renal replacement therapies, complex lists of concurrent medications, limitations with drug administration and compatibility, and unique toxicities that should be evaluated when utilizing these therapies. The purpose of this review is to summarize practical considerations for pharmacotherapy in patients with COVID-19, with the intent of serving as a resource for health care providers at the forefront of clinical care during this pandemic.", "qid": 17, "docid": "2o4oagps", "rank": 53, "score": 0.7763403058052063}, {"content": "Title: Drug repurposing clinical trials in the search for life-saving COVID-19 therapies;research targets and methodological and ethical issues Content: Introduction: So far, there is no vaccine, nor are there effective drugs to treat COVID-19, an emerging viral respiratory infection deadlier than influenza Objective: To take a snapshot picture of planned and ongoing clinical research addressing drugs potentially useful for treating SAR-CoV-2 infections Method: A search was conducted (20 April 2020) in an international registry of clinical studies (https://ClinicalTrials gov, US NIH) After excluding observational studies and other interventions that fell outside the scope of this study, 294 research protocols (out of 516 retrieved protocols) were selected for analysis Results: Of 294 included trials, 249 were Randomized Controlled Trials (RCT), 118 of which were double-, triple- or quadruple-blinded studies The interventions (drug therapies) were compared with \"standard-of-care\" (SOC) or with the placebo plus SOC, or yet with presumed \"active\" comparators RCT focused on the primary treatment of the disease (inhibitors of viral replication) or on the therapy for resolution of hyperinflammation in pneumonia/Acute Respiratory Distress Syndrome (ARDS) and thromboembolism associated with SARS-CoV-2 The trials found in the database involve existing antiviral compounds and drugs with multiple modes of antiviral action Antiparasitic drugs, which inhibited viral replication in cell-culture assays, are being tested as well Regarding the adjunctive immunomodulatory, anti-inflammatory and antithrombotic therapies, a number of drugs with distinct pharmacological targets are under investigation in trials enrolling patients with severe COVID-19 Conclusions: Although many clinical studies of drugs for COVID-19 are planned or in progress, only a minority of them are sufficiently large, randomized and placebo-controlled trials with masking and concealment of allocation Owing to methodological limitations, only a few clinical trials found in the registry are likely to yield robust evidence of effectiveness and safety of drugs repurposable for COVID-19", "qid": 17, "docid": "a4oibkt9", "rank": 54, "score": 0.7762004137039185}, {"content": "Title: Pharmacologicaltreatment of COVID-19: lights and shadows Content: At the end of December 2019, a novel coronavirus, the severe acute respiratory syndrome coronavirus 2, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China and then the entire world, forcing the World Health Organization to make the assessment that the coronavirus disease (COVID-19) can be characterized as a pandemic, the first ever caused by a coronavirus. To date, clinical evidence and guidelines based on reliable data and randomized clinical trials for the treatment of COVID-19 are lacking. In the absence of definitive management protocols, many treatments for COVID-19 are currently being evaluated and tested worldwide. Some of these options were soon abandoned due to ineffectiveness, while others showed promising results. The basic treatments are mainly represented by antiviral drugs, even if the evidence is not satisfactory. Among the antivirals, the most promising appears to be remdesivir. Corticosteroids and tocilizumab seem to guarantee positive results in selected patients so far, although the timing of starting therapy and the most appropriate therapeutic schemes remain to be clarified. Efficacy of the other drugs is still uncertain, and they are currently used as a cocktail of treatments in the absence of definitive guidelines. What will represent the real solution to the enormous problem taking place worldwide is the identification of a safe and effective vaccine, for which enormous efforts and investments are underway.", "qid": 17, "docid": "o29773cz", "rank": 55, "score": 0.7761557102203369}, {"content": "Title: Characteristics of registered studies for Coronavirus disease 2019 (COVID-19): A systematic review Content: Abstract Background The World Health Organization characterized the Coronavirus disease 2019 (COVID-19) as a pandemic on March 11th. Many clinical trials on COVID-19 have been registered, and we aim to review the study characteristics and provide guidance for future trials to avoid duplicated effort. Methods Studies on COVID-19 registered before March 3rd, 2020 on eight registry platforms worldwide were searched and the data of design, participants, interventions, and outcomes were extracted and analyzed. Results Three hundred and ninety-three studies were identified and 380 (96.7%) were from mainland China, while 3 in Japan, 3 in France, 2 in the US, and 3 were international collaborative studies. Two hundred and sixty-six (67.7%) aimed at therapeutic effect, others were for prevention, diagnosis, prognosis, etc. Two hundred and two studies (51.4%) were randomized controlled trials. Two third of therapeutic studies tested Western medicines including antiviral drugs (17.7%), stem cell and cord blood therapy (10.2%), chloroquine and derivatives (8.3%), 16 (6.0%) on Chinese medicines, and 73 (27.4%) on integrated therapy of Western and Chinese medicines. Thirty-one studies among 266 therapeutic studies (11.7%) used mortality as primary outcome, while the most designed secondary outcomes were symptoms and signs (47.0%). Half of the studies (45.5%) had not started recruiting till March 3rd. Conclusions Inappropriate outcome setting, delayed recruitment and insufficient numbers of new cases in China implied many studies may fail to complete. Strategies and protocols of the studies with robust and rapid data sharing are warranted for emergency public health events, helping the timely evidence-based decision-making.", "qid": 17, "docid": "vhfu020h", "rank": 56, "score": 0.7755450010299683}, {"content": "Title: Implications of the lack of a unified research project framework: an investigation into the registration of clinical trials of COVID-19 Content: Objective: The aim of this study was to provide recommendations for improving the design of subsequent studies through analysis of the registered coronavirus disease 2019 (COVID-19) clinical trials.Methods: A retrospective analysis of 189 trial retrievals achieved on 20 February 2020.Results: A total of 189 trials are included in the study. There were 69.3% interventional studies, 21.7% observational studies, 5.3% diagnostic tests and 3.7% other studies. The following statistics are provided only for the interventional studies. Severity of disease: 5.3% light and common type, 17.6% severe and critically ill and 59.6% with no restricted classification. Medication use: 51.1% Western medicine, 32.1% Chinese medicine, 10.7% blood related product and 6.1% non-drug therapy. The median and inner quantile range of the sample sizes included in these studies: 104 (IQR: 60, 200). Primary outcome type most used: 45.8% with clinical characteristics and 21.4% with virological. Study design characteristics: 71% of all studies were randomized, 5% of all studies were blinded, 18% of all studies were multicenter and 76% of all studies were single center.Conclusion: Although many COVID-19 studies include randomization in their design, the lack of additional double-blind and placebo-controlled elements in their designs result in a less robust evaluation of intervention safety and efficacy. Furthermore, similar or repeated research and small sample studies that have less promise in gains of new information have possibly led to a shortage of recruitable patients and become a barrier to the completion of large multicenter clinical trial studies.", "qid": 17, "docid": "itpizzzh", "rank": 57, "score": 0.7753328084945679}, {"content": "Title: COVID\u201019 drug repurposing: Summary statistics on current clinical trials and promising untested candidates Content: Repurposing of existing antiviral drugs, immunological modulators, and supportive therapies represents a promising path toward rapidly developing new control strategies to mitigate the devastating public health consequences of the COVID\u201019 pandemic. A comprehensive text\u2010mining and manual curation approach was used to comb and summarize the most pertinent information from existing clinical trials and previous efforts to develop therapies against related betacoronaviruses, particularly SARS and MERS. In contrast to drugs in current trials, which have been derived overwhelmingly from studies on taxonomically unrelated RNA viruses, a number of untested small molecule antivirals had previously demonstrated remarkable in vitro specificity for SARS\u2010CoV or MERS\u2010CoV, with high selectivity indices, EC(50), and/or IC(50). Due to the rapid containment of the prior epidemics, however, these were generally not followed up with in vivo animal studies or clinical investigations, and thus largely overlooked as treatment prospects in the current COVID\u201019 trials. This brief review summarizes and tabulates core information on recent or ongoing drug repurposing\u2010focused clinical trials, while detailing the most promising untested candidates with prior documented success against the etiologic agents of SARS and/or MERS.", "qid": 17, "docid": "ra4uoosw", "rank": 58, "score": 0.7752372622489929}, {"content": "Title: Animal models for emerging coronavirus: progress and new insights Content: The emergences of coronaviruses have caused a serious global public health problem because their infection in humans caused the severe acute respiratory disease and deaths. The outbreaks of lethal coronaviruses have taken place for three times within recent two decades (SARS-CoV in 2002, MERS-CoV in 2012 and SARS-CoV-2 in 2019). Much more serious than SARS-CoV in 2002, the current SARS-CoV-2 infection has been spreading to more than 213 countries, areas or territories and causing more than two million cases up to date (17 April 2020). Unfortunately, no vaccine and specific anti-coronavirus drugs are available at present time. Current clinical treatment at hand is inadequate to suppress viral replication and inflammation, and reverse organ failure. Intensive research efforts have focused on increasing our understanding of viral biology of SARS-CoV-2, improving antiviral therapy and vaccination strategies. The animal models are important for both the fundamental research and drug discovery of coronavirus. This review aims to summarize the animal models currently available for SARS-CoV and MERS-CoV, and their potential use for the study of SARS-CoV-2. We will discuss the benefits and caveats of these animal models and present critical findings that might guide the fundamental studies and urgent treatment of SARS-CoV-2-caused diseases.", "qid": 17, "docid": "pld0clpd", "rank": 59, "score": 0.7750484943389893}, {"content": "Title: A comprehensive review on drug repositioning against coronavirus disease 2019 (COVID19) Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is the reason for this ongoing pandemic infection diseases termed coronavirus disease 2019 (COVID-19) that has emerged since early December 2019 in Wuhan City, Hubei Province, China. In this century, it is the worst threat to international health and the economy. After 4 months of COVID-19 outbreak, there is no certain and approved medicine against it. In this public health emergency, it makes sense to investigate the possible effects of old drugs and find drug repositioning that is efficient, economical, and riskless process. Old drugs that may be effective are from different pharmacological categories, antimalarials, anthelmintics, anti-protozoal, anti-HIVs, anti-influenza, anti-hepacivirus, antineoplastics, neutralizing antibodies, immunoglobulins, and interferons. In vitro, in vivo, or preliminary trials of these drugs in the treatment of COVID-19 have been encouraging, leading to new research projects and trials to find the best drug/s. In this review, we discuss the possible mechanisms of these drugs against COVID-19. Also, it should be mentioned that in this manuscript, we discuss preliminary rationales; however, clinical trial evidence is needed to prove them. COVID-19 therapy must be based on expert clinical experience and published literature and guidelines from major health organizations. Moreover, herein, we describe current evidence that may be changed in the future.", "qid": 17, "docid": "476uhzb6", "rank": 60, "score": 0.774696946144104}, {"content": "Title: Novel Stem Cells and Nucleic Acid-Based Vaccine Trials Against Viral Outbreak: A Systematic Evaluation During COVID-2019 Pandemic Content: The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak, the cause of coronavirus disease (COVID-19), has influenced health globally. So far, there are no established management options and prophylaxis for those who have been exposed to SARS-CoV-2, and those who develop COVID-19. Documented scientific evidences in similar viral outbreaks in past suggested few therapy regimens. These rather have not shown promising results in management of current pandemic. So, in the current review, we are exploring novel treatment strategies and therapies that are being explored and are in clinical and preclinical stages of research. To explore more about the same, we directed our search towards stem cell based, DNA based, or RNA based vaccines against COVID-19 under development by various universities, institutes or pharmaceutical companies. The current scientific literature and database search were performed by exploring various Trials registry (NIH: https://clinicaltrials.gov/ and https://www.coronavirus.gov) and Chinese clinical trial registry http://www.chictr.org.cn/) and for preclinical trials various University, Institutions, Pharmaceutical companies websites and news bulletins along with google search were checked routinely from 3rd March 2020 to 16 May 2020. The term \u201cStem Cell therapy and COVID-19\u201d, \u201cMesenchymal stem cell and corona 2019 virus\u201d, \u201cDNA Vaccines and COVID-19, RNA Vaccines and COVID-19\u201d and \u201cCell-based therapy with SARS-CoV-2, University/Institutions and COVID-19 research\u201d were used. The vaccine trials (Stem Cells/DNA/RNA) which were cancelled were not included in this review. Similarly, few others like repurposing of drugs, Nano Vaccines, other miscellaneous trials of Herbs, Music therapy etc., were also excluded. In the present review, we have included the various novel therapies like stem cell therapy, DNA or RNA vaccines which are under development and if proven successful may have a lasting impact on the health industry.", "qid": 17, "docid": "ajd9renr", "rank": 61, "score": 0.7746345400810242}, {"content": "Title: Combating devastating COVID-19 by drug repurposing Content: Despite advances in drug discovery, viral infections remain a major challenge for scientists across the globe. The recent pandemic of COVID-19 (coronavirus disease 2019), caused by a viral infection with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has created a disastrous situation all over the world. As no drugs are available to treat this life-threatening disease and the mortality rate due to COVID-19 is high, there is an utmost need to attempt to treat the infection using drug repurposing. Some countries are against the use of these drugs because of adverse effects associated with drug repurposing and lack of statistically significant clinical data, but they have been found to be effective in some countries to treat COVID-19 patients (off-label/investigational). This article emphasises possible drug candidates in the treatment of COVID-19. Most of these drugs were found to be effective in in vitro studies. There is a need to re-assess in vitro data and to carry out randomised clinical trials. Further investigations of these drugs are recommended on a priority basis.", "qid": 17, "docid": "qmlmiqtv", "rank": 62, "score": 0.7742516398429871}, {"content": "Title: Emergence of novel coronavirus and progress toward treatment and vaccine Content: In late December 2019, a group of patients was observed with pneumonia\u2010like symptoms that were linked with a wet market in Wuhan, China. The patients were found to have a novel coronavirus genetically related to a bat coronavirus that was termed SARS\u2010CoV\u20102. The virus gradually spread worldwide and was declared a pandemic by WHO. Scientists have started trials on potential preventive and treatment options. Currently, there is no specific approved treatment for SARS\u2010CoV\u20102, and various clinical trials are underway to explore better treatments. Some previously approved antiviral and other drugs have shown some in vitro activity. Here we summarize the fight against this novel coronavirus with particular focus on the different treatment options and clinical trials exploring treatment as well as work done toward development of vaccines.", "qid": 17, "docid": "3mpymd8a", "rank": 63, "score": 0.7735131978988647}, {"content": "Title: Chinese medicine for COVID-19: A protocol for systematic review and meta-analysis Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) is a respiratory illness that can spread from person to person. The virus that causes COVID-19 is a novel coronavirus that was first identified during an investigation into an outbreak in Wuhan, China. The clinical spectrum of SARS-CoV-2 infection appears to be wide, encompassing asymptomatic infection, mild upper respiratory tract illness, and severe viral pneumonia with respiratory failure and even death, with many patients being hospitalised with pneumonia. In China and East Asia, Chinese medicine has been widely used to treat diverse diseases for thousands of years. As an important means of treatment now, Chinese medicine plays a significant role in the treatment of respiratory diseases in China. The aim of this study is to assess the efficacy and safety of Chinese medicine for COVID-19. METHODS: We will search the following sources for the identification of trials: The Cochrane Library, PubMed, EMBASE, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure Database (CNKI), Chinese Science and Technique Journals Database (VIP), and the Wanfang Database. All the above databases will be searched from the available date of inception until the latest issue. No language or publication restriction will be used. Randomized controlled trials will be included if they recruited participants with COVID-19 for assessing the effect of Chinese medicine vs control (placebo, no treatment, and other therapeutic agents). Primary outcomes will include chest CT and nucleic acid detection of respiratory samples. Two authors will independently scan the articles searched, extract the data from articles included, and assess the risk of bias by Cochrane tool of risk of bias. Disagreements will be resolved by consensus or the involvement of a third party. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. Dichotomous variables will be reported as risk ratio or odds ratio with 95% confidence intervals (CIs) and continuous variables will be summarized as mean difference or standard mean difference with 95% CIs. RESULTS AND CONCLUSION: The available evidence of the treatment of COVID-19 with traditional Chinese medicine will be summarized, and evaluation of the efficacy and the adverse effects of these treatments will be made. This review will be disseminated in print by peer-review.", "qid": 17, "docid": "iqu4fu1t", "rank": 64, "score": 0.772986650466919}, {"content": "Title: COVID-19 drug repurposing: Summary statistics on current clinical trials and promising untested candidates Content: Repurposing of existing antiviral drugs, immunological modulators, and supportive therapies represents a promising path toward rapidly developing new control strategies to mitigate the devastating public health consequences of the COVID-19 pandemic. A comprehensive text-mining and manual curation approach was used to comb and summarize the most pertinent information from existing clinical trials and previous efforts to develop therapies against related betacoronaviruses, particularly SARS and MERS. In contrast to drugs in current trials, which have been derived overwhelmingly from studies on taxonomically unrelated RNA viruses, a number of untested small molecule antivirals had previously demonstrated remarkable in vitro specificity for SARS-CoV or MERS-CoV, with high selectivity indices, EC50 , and/or IC50 . Due to the rapid containment of the prior epidemics, however, these were generally not followed up with in vivo animal studies or clinical investigations, and thus largely overlooked as treatment prospects in the current COVID-19 trials. This brief review summarizes and tabulates core information on recent or ongoing drug repurposing-focused clinical trials, while detailing the most promising untested candidates with prior documented success against the etiologic agents of SARS and/or MERS.", "qid": 17, "docid": "f4xt36hf", "rank": 65, "score": 0.7727454304695129}, {"content": "Title: Ethical rationale for better coordination of clinical research on COVID-19 Content: Hundreds of clinical trials of potential treatments and vaccines for the \u201ccoronavirus 19 disease\u201d (COVID-19) have been set up in record time. This is a remarkable reaction to the global pandemic, but the absence of a global coordination of clinical research efforts raises serious ethical concerns. Some COVID-19 patients might carry the burden of clinical trial involvement even though their trial cannot be completed as researchers are competing for patients. A shortage of medicines can occur when existing drugs are diverted for clinical trials. Research ethics committees are overburdened with multiple applications. A multitude of trials can also overstretch medical staff and risk neglecting non-COVID-19 patients. And finally, conflicting conclusions from a multitude of heterogeneous trials might lead to delays in public health decisions about life-saving issues. These challenges are made worse by the unpredictable evolution of epidemics, the active involvement of political decision-makers in scientific issues and the pressure of social media globally. While freedom to conduct research must be safeguarded, global health emergency situations would greatly benefit from effective international coordination mechanisms for clinical research.", "qid": 17, "docid": "qf5x2hl6", "rank": 66, "score": 0.7721881866455078}, {"content": "Title: Review of Emerging Pharmacotherapy for the Treatment of Coronavirus Disease 2019 Content: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) has evolved into an emergent global pandemic. Coronavirus disease 2019 (COVID\u201019) can manifest on a spectrum of illness from mild disease to severe respiratory failure requiring intensive care unit admission. As the incidence continues to rise at a rapid pace, critical care teams are faced with challenging treatment decisions. There is currently no widely accepted standard of care in the pharmacologic management of patients with COVID\u201019. Urgent identification of potential treatment strategies is a priority. Therapies include novel agents available in clinical trials or through compassionate use, and other drugs, repurposed antiviral and immunomodulating therapies. Many have demonstrated in vitro or in vivo potential against other viruses that are similar to SARS\u2010CoV\u20102. Critically ill patients with COVID\u201019 have additional considerations related to adjustments for organ impairment and renal replacement therapies, complex lists of concurrent medications, limitations with drug administration and compatibility, and unique toxicities that should be evaluated when utilizing these therapies. The purpose of this review is to summarize practical considerations for pharmacotherapy in patients with COVID\u201019, with the intent of serving as a resource for health care providers at the forefront of clinical care during this pandemic.", "qid": 17, "docid": "bsdk64t1", "rank": 67, "score": 0.7721171975135803}, {"content": "Title: Safeguarding Non-COVID-19 Research: Looking Up from Ground Zero Content: The COVID-19 pandemic has kicked off a global race to launch clinical trials of experimental vaccines and treatments for the coronavirus. Worldwide, as resources are directed toward accelerating the research into unravelling the mechanism of COVID-19 pathophysiology, concerns have been raised regarding the future of clinical research in United Kingdom and elsewhere during the current pandemic. However, the real immediate impact of these restrictions due to lock-down is most acutely felt by scientists working on non-COVID-19 biomedical research bench and clinical researchers whose drug trials have to be delayed, suspended or ceased. Here, we highlight our views from \"ground zero\" as we represent those whose work are deeply affected by the restrictions. We draw attention to some of the practical realities and emotions experienced in the laboratory. In addition, we also highlight the difficulties for policy makers to maintain equanimity in prioritizing their decisions cross the different fields of science.", "qid": 17, "docid": "i3y5l2we", "rank": 68, "score": 0.7718009948730469}, {"content": "Title: Update on treatment of COVID-19: ongoing studies between promising and disappointing results Content: The COVID-19 pandemic represents the greatest global public health crisis since the pandemic influenza outbreak of 1918. We are facing a new virus, so several antiviral agents previously used to treat other coronavirus infections such as SARS and MERS are being considered as the first potential candidates to treat COVID-19. Thus, several agents have been used by the beginning of the current outbreak in China first and all over the word successively, as reported in several different guidelines and therapeutic recommendations. At the same time, a great number of clinical trials have been launched to investigate the potential efficacy therapies for COVID-19 highlighting the urgent need to get as quickly as possible high-quality evidence. Through PubMed, we explored the relevant articles published on treatment of COVID-19 and on trials ongoing up to April 15, 2020.", "qid": 17, "docid": "jtqyov26", "rank": 69, "score": 0.7714661955833435}, {"content": "Title: Update on treatment of COVID-19: ongoing studies between promising and disappointing results. Content: The COVID-19 pandemic represents the greatest global public health crisis since the pandemic influenza outbreak of 1918. We are facing a new virus, so several antiviral agents previously used to treat other coronavirus infections such as SARS and MERS are being considered as the first potential candidates to treat COVID-19. Thus, several agents have been used by the beginning of the current outbreak in China first and all over the word successively, as reported in several different guidelines and therapeutic recommendations. At the same time, a great number of clinical trials have been launched to investigate the potential efficacy therapies for COVID-19 highlighting the urgent need to get as quickly as possible high-quality evidence. Through PubMed, we explored the relevant articles published on treatment of COVID-19 and on trials ongoing up to April 15, 2020.", "qid": 17, "docid": "nmntjk0i", "rank": 70, "score": 0.7714661955833435}, {"content": "Title: COVID-19 Clinical trials: Quality matters more than quantity Content: Despite the ferment aroused in the scientific community by the COVID-19 outbreak and the over 11,000 papers listed in PubMed, published evidence on safe and effective drugs has not progressed yet at the same speed of the pandemic. However, clinical research is rapidly progressing, as shown by the hundreds of registered clinical trials on candidate drugs for COVID-19. Unfortunately, information on protocols of individual studies differs from registry to registry. Furthermore, study designs, criteria for stratification of patients and choice of outcomes are quite heterogeneous. All this makes data sharing and secondary analysis difficult. At last, small single centre studies and the use of drugs on a compassionate basis should be replaced by highly powered, multi-centre, multi-arm clinical trials, in order to provide the required evidence of safety and efficacy of novel or repurposed candidate drugs. Hopefully, the efforts of clinical researchers in the fight against the SARS Cov-2 will result into the identification of effective treatments. To make this possible, clinical research should be oriented by guidelines for more harmonized high-quality studies and by a united commitment of the scientific community to share personal knowledge and data. Allergists and clinical immunologists should have a leading role in this unprecedent challenge.", "qid": 17, "docid": "f590pp4j", "rank": 71, "score": 0.7712751030921936}, {"content": "Title: Cardiovascular Clinical Trials in a Pandemic: Immediate Implications of Coronavirus Disease 2019 Content: The coronavirus disease 2019 (COVID-19) pandemic started in Wuhan, Hubei Province, China, in December 2019, and by 24 April 2020, it had affected >2.73 million people in 185 countries and caused >192,000 deaths. Despite diverse societal measures to reduce transmission of the severe acute respiratory syndrome coronavirus 2, such as implementing social distancing, quarantine, curfews and total lockdowns, its control remains challenging. Healthcare practitioners are at the frontline of defence against the virus, with increasing institutional and governmental supports. Nevertheless, new or ongoing clinical trials, not related to the disease itself, remain important for the development of new therapies, and require interactions among patients, clinicians and research personnel, which is challenging, given isolation measures. In this article, the authors summarise the acute effects and consequences of the COVID-19 pandemic on current cardiovascular trials.", "qid": 17, "docid": "gduhterq", "rank": 72, "score": 0.7707571387290955}, {"content": "Title: Current status of potential therapeutic candidates for the COVID-19 crisis Content: Abstract As of April 15, 2020, the ongoing coronavirus disease 2019 (COVID-2019) pandemic has swept through 213 countries and infected more than 1,870,000 individuals, posing an unprecedented threat to international health and the economy. There is currently no specific treatment available for patients with COVID-19 infection. The lessons learned from past management of respiratory viral infections have provided insights into treating COVID-19. Numerous potential therapies, including supportive intervention, immunomodulatory agents, antiviral therapy, and convalescent plasma transfusion, have been tentatively applied in clinical settings. A number of these therapies have provided substantially curative benefits in treating patients with COVID-19 infection. Furthermore, intensive research and clinical trials are underway to assess the efficacy of existing drugs and identify potential therapeutic targets to develop new drugs for treating COVID-19. Herein, we summarize the current potential therapeutic approaches for diseases related to COVID-19 infection and introduce their mechanisms of action, safety, and effectiveness.", "qid": 17, "docid": "4zmqplz0", "rank": 73, "score": 0.7703976631164551}, {"content": "Title: Cardiovascular Disease Novel Coronavirus and the Search for Investigational Therapies Content: PURPOSE: The primary purpose of the current study was to investigate and summarize the registered trials that listed COVID-19 as the primary condition. METHODS: We performed a search on ClinicalTrials.gov using the independent search terms COVID-19, SARS, and SARS COV2, and then downloaded the data file on March 23, 2020. All trials were downloaded to a csv file and searched for appropriateness. RESULTS: Fifty-six of 124 (45.2%) registered trials were listed as recruiting. The majority (85, 68.5%) classified their study as interventional, 37 (29.8%) classified as observational and one (0.8%) each classified their study as either expanded access:individual patients | treatment IND/Protocol or expanded access:intermediate-size population | treatment IND/Protocol. There were 67 (54.0%) of the trials that listed drug as the type of study. Immunological and antiviral trials were the greatest, representing approximately 30% and 21%, respectively. When immunological and antiviral drugs were used alone or in combination, they represented 41.9% and 34.4%, respectively. Anti-malarial agents are represented in 7.5% of trials. Approximately 14% of trials involved Traditional Chinese Medicine. The aforementioned study agents used solely or in combination represented approximately 80% of therapeutic approaches to COVID19. CONCLUSION: There was a large and quick response on ClinicalTrials.gov to the COVID-19 outbreak. Many of the registered trials are currently recruiting new patients, while some will begin in the near future. Specific potential experimental therapies, including dosing and monitoring, might be found by reviewing content. Within clinicaltrials.gov, patients, family members, health care professionals and researchers can search and find ongoing and future trials for COVID-19.", "qid": 17, "docid": "4nci3fsi", "rank": 74, "score": 0.7703754901885986}, {"content": "Title: Importance of Pediatric Inclusion in COVID-19 Therapeutic Trials Content: Pediatric patients are excluded from most coronavirus disease 2019 (COVID-19) therapeutic trials. We outline a rationale for the inclusion of children in COVID-19 therapeutic trials, which enabled us to include children of all ages in a therapeutic COVID-19 trial at our institution.", "qid": 17, "docid": "omm04fg5", "rank": 75, "score": 0.7703483700752258}, {"content": "Title: Treatments for COVID-19: emerging drugs against the coronavirus Content: The Coronavirus disease 19 (COVID-19) outbreak has been recognized as a global threat to public health. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and no effective therapies currently exist against this novel viral agent. Along with extensive public health measures, an unprecedented global effort in identifying effective drugs for the treatment is being implemented. Potential drug targets are emerging as the result of a fast-evolving understanding of SARS-CoV-2 virology, host response to the infection, and clinical course of the disease. This brief review focuses on the latest and most promising pharmacological treatments against COVID-19 currently under investigation and discuss their potential use based on either documented efficacy in similar viral infections, or their activity against inflammatory syndromes. Ongoing clinical trials are also emphasized.", "qid": 17, "docid": "4ypv5bk5", "rank": 76, "score": 0.7701494693756104}, {"content": "Title: Treatments for COVID-19: emerging drugs against the coronavirus. Content: The Coronavirus disease 19 (COVID-19) outbreak has been recognized as a global threat to public health. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and no effective therapies currently exist against this novel viral agent. Along with extensive public health measures, an unprecedented global effort in identifying effective drugs for the treatment is being implemented. Potential drug targets are emerging as the result of a fast-evolving understanding of SARS-CoV-2 virology, host response to the infection, and clinical course of the disease. This brief review focuses on the latest and most promising pharmacological treatments against COVID-19 currently under investigation and discuss their potential use based on either documented efficacy in similar viral infections, or their activity against inflammatory syndromes. Ongoing clinical trials are also emphasized.", "qid": 17, "docid": "u3enawtb", "rank": 77, "score": 0.7701494693756104}, {"content": "Title: A living systematic review protocol for COVID-19 clinical trial registrations Content: Since the coronavirus disease 2019 (COVID-19) outbreak was identified in December 2019 in Wuhan, China, a strong response from the research community has been observed with the proliferation of independent clinical trials assessing diagnostic methods, therapeutic and prophylactic strategies. While there is no intervention for the prevention or treatment of COVID-19 with proven clinical efficacy to date, tools to distil the current research landscape by intervention, level of evidence and those studies likely powered to address future research questions is essential. This living systematic review aims to provide an open, accessible and frequently updated resource summarising the characteristics of COVID-19 clinical trial registrations. Weekly search updates of the WHO International Clinical Trials Registry Platform (ICTRP) and source registries will be conducted. Data extraction by two independent reviewers of trial characteristic variables including categorisation of trial design, geographic location, intervention type and targets, level of evidence and intervention adaptability to low resource settings will be completed. Descriptive and thematic synthesis will be conducted. A searchable and interactive visualisation of the results database will be created, and made openly available online. Weekly results from the continued search updates will be published and made available on the Infectious Diseases Data Observatory (IDDO) website ( COVID-19 website). This living systematic review will provide a useful resource of COVID-19 clinical trial registrations for researchers in a rapidly evolving context. In the future, this sustained review will allow prioritisation of research targets for individual patient data meta-analysis.", "qid": 17, "docid": "9lm0sz5p", "rank": 78, "score": 0.7700290083885193}, {"content": "Title: Implications of the lack of a unified research project framework: an investigation into the registration of clinical trials of COVID-19. Content: Objective: The aim of this study was to provide recommendations for improving the design of subsequent studies through analysis of the registered coronavirus disease 2019 (COVID-19) clinical trials.Methods: A retrospective analysis of 189 trials retrievals achieved on February 20, 2020.Results: A total of 189 trials are included in the study. There were 69.3% interventional studies, 21.7% observational studies, 5.3% diagnostic tests, and 3.7% other studies. The following statistics are provided only for the interventional studies. Severity of disease: 5.3% light and common type, 17.6% severe and critically ill, and 59.6% with no restricted classification. Medication use: 51.1% Western medicine, 32.1% Chinese medicine, 10.7% blood related product, and 6.1% non-drug therapy. The median and inner quantile range of the sample sizes included in these studies: 104 (IQR: 60, 200). Primary outcome type most used: 45.8% with clinical characteristics and 21.4% with virological. Study design characteristics: 71% of all studies were randomized, 5% of all studies were blinded, 18% of all studies were multicenter, and 76% of all studies were single-center.Conclusion: Although many COVID-19 studies include randomization in their design, the lack of additional double-blind and placebo-controlled elements in their designs result in a less robust evaluation of intervention safety and efficacy. Furthermore, similar or repeated research and small sample studies that have less promise in gains of new information have possibly led to a shortage of recruitable patients and become a barrier to the completion of large multicenter clinical trial studies.", "qid": 17, "docid": "yjx1rx3k", "rank": 79, "score": 0.7690229415893555}, {"content": "Title: Cardiovascular disease due to novel coronavirus and the search for investigational therapies Content: OBJECTIVE: The primary purpose of the study was to investigate and to summarize the registered trials that listed COVID-19 as the primary condition. METHODS: We performed a search on ClinicalTrials.gov using the independent search terms COVID-19, SARS, and SARS-CoV-2 and then downloaded the data file on March 23, 2020. All trials were downloaded to a csv file and searched for appropriateness. RESULTS: Of 124 registered trials, 56 (45.2%) were listed as recruiting. The majority (85 [68.5%]) were classified as interventional, 37 (29.8%) as observational, and one (0.8%) each as either expanded access: individual patients|treatment investigational new drug/protocol or expanded access: intermediate-size population|treatment investigational new drug/protocol. There were 67 (54.0%) trials that listed drug as the type of study. Immunologic and antiviral trials were the most common, representing approximately 30% and 21%, respectively. When immunologic and antiviral drugs were used alone or in combination, they represented 41.9% and 34.4%, respectively. Antimalarial agents are represented in 7.5% of trials. Approximately 14% of trials involved traditional Chinese medicine. The study agents used solely or in combination represented approximately 80% of therapeutic approaches to COVID-19. CONCLUSIONS: There was a large and quick response on ClinicalTrials.gov to the COVID-19 outbreak. Many of the registered trials are currently recruiting new patients, whereas some will begin in the near future. Specific potential experimental therapies, including dosing and monitoring, might be found by reviewing content. Within ClinicalTrials.gov, patients, family members, health care professionals, and researchers can search and find ongoing and future trials for COVID-19.", "qid": 17, "docid": "y6mpjjr2", "rank": 80, "score": 0.7689959406852722}, {"content": "Title: Molecular Aspects of Co-morbidities in COVID-19 Infection Content: Coronaviruses are a group of enveloped viruses with single-stranded non-segmented positive-sense RNA genomes In December 2019, SARS-CoV-2 appeared in China for the first time and quickly spread throughout the world Although certain medications suggested for other afflictions tend to be potentially effective for curing the infection, there is no approved vaccination or drug available for this virus yet Comprehension of the disease molecular pathogenesis could provide useful tools for COVID-19 patients in surveillance, prognosis, treatment, vaccine development and therapeutic targeting The present research aims to summarize the association in COVID-19 patients between molecular dimensions of comorbidities with clinical and preclinical information Developing an ACE2 inhibitor could be a possible therapeutic target Plasmin is another possible candidate both in diagnosis and treatment areas All predicted biomarkers must be validated either through randomized clinical trials or experimental assays before clinical application in patients", "qid": 17, "docid": "ymkv1yzw", "rank": 81, "score": 0.7688230872154236}, {"content": "Title: Battling COVID-19: using old weapons for a new enemy Content: Coronavirus disease-19 (COVID-19) has reached pandemic proportions. Most of the drugs that are being tried for the treatment have not been evaluated in any randomized controlled trials. The purpose of this review was to summarize the in-vitro and in-vivo efficacy of these drugs on Severe Acute Respiratory Syndrome (SARS-CoV-2) and related viruses (SARS and Middle East Respiratory Syndrome) and evaluate their potential for re-purposing them in the management of COVID-19.", "qid": 17, "docid": "yn7x9uit", "rank": 82, "score": 0.7684265375137329}, {"content": "Title: Review: Hydroxychloroquine and Chloroquine for Treatment of SARS-CoV-2 (COVID-19) Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging viral infection causing coronavirus disease 2019 (COVID-19). Hydroxychloroquine and chloroquine have garnered unprecedented attention as potential therapeutic agents against COVID-19 following several small clinical trials, uncontrolled case series, and public figure endorsements. While there is a growing body of scientific data, there is also concern for harm, particularly QTc prolongation and cardiac arrhythmias. Here, we perform a rapid narrative review and discuss the strengths and limitations of existing in vitro and clinical studies. We call for additional randomized controlled trial evidence prior to the widespread incorporation of hydroxychloroquine and chloroquine into national and international treatment guidelines.", "qid": 17, "docid": "wmpjfc02", "rank": 83, "score": 0.7682408094406128}, {"content": "Title: The vaccine journey for COVID-19: a comprehensive systematic review of current clinical trials in humans Content: INTRODUCTION: Since December 2019, there has been an outbreak of a novel beta-coronavirus (SARS-CoV-2) in Wuhan, China. On March the 11th the World Health Organization (WHO) declared COVID-19 as a pandemic, with over 118,000 cases in more than 110 countries around the world. In response to the global coronavirus disease 2019 (COVID-19) emergency, clinical trial research assessing the efficacy and safety of experimental vaccines to prevent COVID-19 are emerging at an unprecedented rate. The aim of this systematic review is to summarize the preliminary experiences and ongoing clinical trials of the major candidates and challenges of the vaccine strategies in humans. EVIDENCE ACQUISITION: After a priori protocol registration with PROSPERO (181483), a systematic research of the published literature was conducted on 24 April 2020 using Medline (via PubMed), Embase (via Ovid), and WHO databases. Moreover, to explore the more recent literature we also searched the preprint server medRxiv. Finally, we scrutinized the Cochrane COVID-19 study register and the COVID-19 section of ClinicalTrials.gov database for identifying relevant ongoing clinical trials. Thereafter we selected the articles according to the PRISMA guidelines. Animal or in-vitro experimental studies were excluded. Moreover editorials, commentaries, abstracts, reviews, book chapters, and articles not in English were not included. EVIDENCE SYNTHESIS: Our search identified 1359 published papers, 478 pre-print articles and 367 ongoing clinical trials. Finally, only ten ongoing clinical trials met the inclusion criteria. Specifically, seven developed vaccines for the S protein of SARS-CoV-2 and three clinical trials assessed the protective role of BCG vaccine against COVID-19. The first group included phase I/II trials with different types of molecules (DNA or mRNA vaccine, bacterial plasmid or viral vectors), the latter were phase III/IV trials designed on the basis of a heterologous lymphocyte activation by the BCG vaccine. CONCLUSIONS: This new disease is pushing the scientific community to develop swiftly a safe and effective vaccine. Notwithstanding the limitations of our analysis, given by the absence of available results, we try to provide a comprehensive view of the ongoing clinical trials in humans. Our analysis reveals a worldwide effort of both scientists and enterprises to achieve one of the most challenging goals of our century.", "qid": 17, "docid": "xt8tld2i", "rank": 84, "score": 0.7679734230041504}, {"content": "Title: Potential pharmacological agents for COVID-19 Content: A novel coronavirus disease 2019 (COVID-19) infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) first emerged in December 2019 in Wuhan, China, has become a global pandemic. Currently, the management of COVID-19 infection is mainly supportive. Several clinical trials worldwide are evaluating several drugs approved for other indications, as well as multiple investigational agents for the treatment and prevention of COVID-19. Here, we give a brief overview of pharmacological agents and other therapies which are under investigation as treatment options or adjunctive agents for patients infected with COVID-19 and for chemoprophylaxis for the prevention of COVID-19 infection. At the time of writing this commentary, there is no peer-reviewed published evidence from randomized clinical trials of any pharmacological agents improving outcomes in COVID-19 patients. However, it was reported that remdesivir an investigational antiviral agent hastens clinical recovery, but a study is yet to be published in peer-reviewed medical journal.", "qid": 17, "docid": "yoo3ic2c", "rank": 85, "score": 0.7679294943809509}, {"content": "Title: Potential pharmacological agents for COVID-19. Content: A novel coronavirus disease 2019 (COVID-19) infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) first emerged in December 2019 in Wuhan, China, has become a global pandemic. Currently, the management of COVID-19 infection is mainly supportive. Several clinical trials worldwide are evaluating several drugs approved for other indications, as well as multiple investigational agents for the treatment and prevention of COVID-19. Here, we give a brief overview of pharmacological agents and other therapies which are under investigation as treatment options or adjunctive agents for patients infected with COVID-19 and for chemoprophylaxis for the prevention of COVID-19 infection. At the time of writing this commentary, there is no peer-reviewed published evidence from randomized clinical trials of any pharmacological agents improving outcomes in COVID-19 patients. However, it was reported that remdesivir an investigational antiviral agent hastens clinical recovery, but a study is yet to be published in peer-reviewed medical journal.", "qid": 17, "docid": "6cm1vp7h", "rank": 86, "score": 0.7679294943809509}, {"content": "Title: Global research trend in the treatment of the new Coronavirus diseases (COVID-19) : bibliometric analysis. Content: The Coronavirus 2019 (COVID-19) pandemic has caused worldwide concern and has become a major medical problem. Vaccines and therapeutics are important interventions for the management of this outbreak. This study aims to used bibliometric methods to identify research trends in the domain of therapeutics and vaccines to cure patients with COVID-19 since the beginning of the pandemic. The Web of Science Core Collection database was retrieved for articles on therapeutic approaches to coronavirus disease management published between January 1, 2020 and May 20, 2020. Identified and analyzed the data included title, corresponding author, language, publication time, publication type, research focus. A total of 1569 articles on coronavirus therapeutic means from 84 countries were published in 620 journals. We note the remarkable progressive increase in the number of publications related to research on therapies and vaccines for COVID-19. The United States provided the largest number of articles (405), followed by China (364). Journal of Medical Virology published most of them (n=40). 1005 (64.05%) were articles, 286 (18.23%) were letters, 230 (14.66%) were reviews. The terms \"COVID- 19\" or \"SARS-CoV-2\" or \"Coronavirus\" or \"hydroxychloroquine\" or \"chloroquine\" or \"2019-nCOV\" or \"ACE2\" or \"treatment\" or \"remdesivir\" or \"pneumonia\" were most frequently used, as shown in the density visualization map. A network analysis based on keyword co-occurrence revealed five distinct types of studies: clinical, biological, epidemiological, pandemic management, and therapeutics (vaccines and treatments). COVID-19 is a major disease that has had an impact on international public health at the global level. Several avenues for treatment and vaccines have been explored. Most of them focus on older drugs used to treat other diseases that have been effective for other types of coronaviruses. There is a discrepancy in the results obtained from the studies of the drugs included in this study. Randomized clinical trials are needed to evaluate older drugs and develop new treatment options.", "qid": 17, "docid": "s4pyk264", "rank": 87, "score": 0.7677000761032104}, {"content": "Title: SARS, MERS and SARS-CoV-2 (COVID-19) treatment: a patent review. Content: Introduction: Coronavirus has been responsible for several virus outbreaks since 2003, caused by SARS-CoV-1, MERS-CoV, and currently SARS-CoV-2 (COVID-19), the causative agent of coronavirus disease in 2019. COVID-19 has become a global public health emergency because of its high virulence and mortality capacity. This patent review aims to provide an overview of the patents that present possible treatments for SARS-CoV-1, SARS-CoV-2 and MERS-CoV.Areas covered: To treat SARS, MERS and SARS-CoV-2, researchers have filed patents for a number of therapeutic agents. Most of the treatments found were protease inhibitors aimed at proteases such as PLpro, 3CLpro, RNA helicase, and Spike protein, or used monoclonal antibodies and interferons. In addition, the use of Chinese folk medicine and its multitude of medicinal plants with strong antiviral properties was reinforced. Thus, these therapies used in previous epidemics can serve as an aid in the new pandemic by SARS-CoV-2 and be a starting point for new treatments.Expert opinion: The various antiviral alternatives presented in this review offer therapeutic options to fight coronavirus infections. If shown to be effective, these drugs may be extremely important in the current pandemic.", "qid": 17, "docid": "muvdjras", "rank": 88, "score": 0.7676112651824951}, {"content": "Title: SARS, MERS and SARS-CoV-2 (COVID-19) treatment: a patent review Content: INTRODUCTION: Coronavirus has been responsible for several virus outbreaks since 2003, caused by SARS-CoV-1, MERS-CoV, and currently SARS-CoV-2 (COVID-19), the causative agent of coronavirus disease in 2019. COVID-19 has become a global public health emergency because of its high virulence and mortality capacity. This patent review aims to provide an overview of the patents that present possible treatments for SARS-CoV-1, SARS-CoV-2 and MERS-CoV. AREAS COVERED: To treat SARS, MERS and SARS-CoV-2, researchers have filed patents for a number of therapeutic agents. Most of the treatments found were protease inhibitors aimed at proteases such as PLpro, 3 CLpro, RNA helicase, and Spike protein, or used monoclonal antibodies and interferons. In addition, the use of Chinese folk medicine and its multitude of medicinal plants with strong antiviral properties was reinforced. Thus, these therapies used in previous epidemics can serve as an aid in the new pandemic by SARS-CoV-2 and be a starting point for new treatments. EXPERT OPINION: The various antiviral alternatives presented in this review offer therapeutic options to fight coronavirus infections. If shown to be effective, these drugs may be extremely important in the current pandemic.", "qid": 17, "docid": "o30tdbgy", "rank": 89, "score": 0.7675021886825562}, {"content": "Title: COVID\u201019Clinical trials: quality matters more than quantity Content: Despite the ferment aroused in the scientific community by the COVID\u201019 outbreak and the over 11,000 papers listed in PubMed, published evidence on safe and effective drugs has not progressed yet at the same speed of the pandemic. However, clinical research is rapidly progressing, as shown by the hundreds of registered clinical trials on candidate drugs for COVID\u201019. Unfortunately, information on protocols of individual studies differs from registry to registry. Furthermore, study designs, criteria for stratification of patients and choice of outcomes are quite heterogeneous. All this makes data sharing and secondary analysis difficult.At last, small single centre studies and the use of drugs on a compassionate basis should be replaced by highly powered, multi\u2010centre, multi\u2010arm clinical trials, in orderto provide the required evidence of safety and efficacy of novel or repurposed candidate drugs. Hopefully, the efforts of clinical researchers in the fight against the SARS Cov\u20102 will result into the identification of effective treatments. To make this possible, clinical research should be oriented by guidelines for more harmonized high\u2010quality studies and by a united commitment of the scientific community to share personal knowledge and data. Allergists and clinical immunologists should have a leading role in this unprecedent challenge.", "qid": 17, "docid": "5wsfr0oz", "rank": 90, "score": 0.7672688961029053}, {"content": "Title: Medical treatment options for COVID-19 Content: Therapeutic options for coronavirus disease 2019 are desperately needed to respond to the ongoing severe acute respiratory syndrome coronavirus 2 pandemic. Both antiviral drugs and immunomodulators might have their place in the management of coronavirus disease 2019. Unfortunately, no drugs have been approved yet to treat infections with human coronaviruses. As it will take years to develop new therapies for severe acute respiratory syndrome coronavirus 2, the current focus is on the repurposing of drugs that have been approved or are in development for other conditions. Several clinical trials have already been conducted or are currently ongoing to evaluate the efficacy of such drugs. Here, we discuss the potential of these therapies for the treatment of coronavirus disease 2019.", "qid": 17, "docid": "7y87ktmi", "rank": 91, "score": 0.7670525312423706}, {"content": "Title: Cardiovascular Safety of Potential Drugs for the Treatment of Coronavirus Disease 2019 Content: Coronavirus disease 2019 (COVID-19) has become a global pandemic. It is still uncontrolled in most countries and no therapies are currently available. Various drugs are under investigation for its treatment. The disease is known to have worse outcomes in patients who have underlying cardiovascular disease. Chloroquine/hydroxychloroquine, azithromycin, remdesivir and lopinavir/ritonavir are currently being studied in trials and show some promise. Conduction disorders, heart failure, and mortality have been reported with the use of these drugs. It is important to have knowledge of potential cardiotoxic effects of these drugs before using them for COVID-19 patients for better allocation of healthcare resources and improvement in clinical outcomes.", "qid": 17, "docid": "23bvmeym", "rank": 92, "score": 0.766952633857727}, {"content": "Title: COVID-19 trials in Italy: A call for simplicity, top standards and global pooling Content: The novel coronavirus disease, affecting ~9 million people in the past five months and causing >460,000 deaths worldwide, is completely new to mankind. More than 2,000 research projects registered at ClinTrials.gov are aiming at finding effective treatments for rapid transfer to clinical practice. Unfortunately, just few studies have a sufficiently valid design to provide reliable information for clinical practice.", "qid": 17, "docid": "edy3mvur", "rank": 93, "score": 0.7669304013252258}, {"content": "Title: COVID-19 Drug Treatment in China Content: PURPOSE OF REVIEW: An unprecedented outbreak of the novel coronavirus in China (COVID-19) occurred in December 2019, and then engulfed the entire world, presenting a significant and urgent threat to global health. Many research institutes have been involved in the development of drugs and vaccines against COVID-19. RECENT FINDINGS: At present, the strategy of new use of old drugs is mainly used to screen candidate drugs against the novel coronavirus (later termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) and inhibit excessive immune response. Related research has made great progress. SUMMARY: In this review, we summarize the drugs used for COVID-19 treatment in China based on the emerging basic and clinical data. It is hoped that this review will be useful to provide guidance for the prevention, treatment, and control of COVID-19.", "qid": 17, "docid": "m5oq6ygu", "rank": 94, "score": 0.766331672668457}, {"content": "Title: Potential therapeutic agents against COVID-19: What we know so far Content: The emerging outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 continues to spread all over the world. Agents or vaccines of proven efficacy to treat or prevent human coronavirus infection are in urgent need and are being investigated vigorously worldwide. This review summarizes the current evidence of potential therapeutic agents, such as lopinavir/ritonavir, remdesivir, favipiravir, chloroquine, hydroxychloroquine, interferon, ribavirin, tocilizumab, and sarilumab. More clinical trials are being conducted for further confirmation of the efficacy and safety of these agents in treating COVID-19.", "qid": 17, "docid": "eitnkdi9", "rank": 95, "score": 0.766266942024231}, {"content": "Title: Coronavirus Disease 2019 (COVID-19) Spread and Pharmacovigilance Implications: Expert Opinion Content: The Coronavirus Disease 2019 (COVID-19) is rapidly spreading throughout the world after emerging in China in December 2019. Currently, there are no approved treatments for COVID-19 based on large clinical trial data, and hence, management involves infection prevention and control measures and supportive care. With anecdotal reports and in vitro studies suggesting that certain medicines already in use for treatment of other conditions could be viable treatment options, there has been an increased demand for these therapies which could have adverse consequences on patients and healthcare systems. Toxicity from these medicines resulting from a mad rush for them at community pharmacies and pressure on physicians to prescribe for individuals who do not have the infection are worth noting. Furthermore, the indiscriminate use of these medicines could result in viral resistance as well as acute shortage such that patients who routinely take them for other conditions may not get them.", "qid": 17, "docid": "06yilajc", "rank": 96, "score": 0.7661263942718506}, {"content": "Title: Clinical trials impacted by the COVID-19 pandemic: Adaptive designs to the rescue? Content: Very recently the new pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified and the coronavirus disease 2019 (COVID-19) declared a pandemic by the World Health Organization. The pandemic has a number of consequences for the ongoing clinical trials in non-COVID-19 conditions. Motivated by four currently ongoing clinical trials in a variety of disease areas we illustrate the challenges faced by the pandemic and sketch out possible solutions including adaptive designs. Guidance is provided on (i) where blinded adaptations can help; (ii) how to achieve type I error rate control, if required; (iii) how to deal with potential treatment effect heterogeneity; (iv) how to utilize early readouts; and (v) how to utilize Bayesian techniques. In more detail approaches to resizing a trial affected by the pandemic are developed including considerations to stop a trial early, the use of group-sequential designs or sample size adjustment. All methods considered are implemented in a freely available R shiny app. Furthermore, regulatory and operational issues including the role of data monitoring committees are discussed.", "qid": 17, "docid": "s8p0g4r1", "rank": 97, "score": 0.7660715579986572}, {"content": "Title: Systematic Review of the Registered Clinical Trials of Coronavirus Disease 2019 (COVID-19) Content: Background: Since the outbreak of coronavirus disease 2019 (COVID-19), many researchers in China have immediately carried out clinical research scheme of the COVID-19. But, there is still a lack of systematic review of registered clinical trials. Therefore, we conducted a systematic review of the clinical trials of COVID-19 to summarize the characteristics of the COVID-19 registered clinical trials. Methods: This study is based on the recommendations of the PRISMA in the Cochrane handbook. The databases from the Chinese Clinical Registration Center and the ClinicalTrials.gov were searched to collect the registered clinical trials of COVID-19. The retrieval inception date is February 9, 2020. Two researchers independently selected the literature based on inclusion and exclusion criteria, extracted data and evaluated the risk of bias. Results: A total of 75 registered clinical trials (63 interventional studies and 12 observational studies) of COVID-19 were obtained. A majority of clinical trials were sponsored by Chinese hospitals. Only 11 trials have begun to recruit patients, and none of the registered clinical trials had been completed; 34 trials were early clinical exploratory trials or in a pre-experiment stage, 15 trials belonged to phrase \u2162 and 4 trials were phrase \u2163. The methods of intervention included traditional Chinese medicine involving 26 trials, Western medicine involving 30 trials, and integrated traditional Chinese medicine and Western medicine involving 19 trials. The subjects were mainly non-critical adult patients (\u2265 18 years old). The median sample size of the trials was 100 (IQR: 60 - 200), and the median execute time of the trials was 179 d (IQR: 94 - 366 d). The main outcomes were clinical observation and examinations. Overall, both the methodology quality of interventional trials and observational studies were low. Conclusions: Disorderly and intensive clinical trials of COVID-19 using traditional Chinese medicine and western medicine are ongoing or will being carried out in China. However, based on the low methodology quality and small sample size and long studies execute time, we will not be able to obtain reliable, high-quality clinical evidence about COVID-19 treatment in the near future. Improving the quality of study design, prioritizing promising drugs, and using different designs and statistical methods are worth advocating and recommending for the clinical trials of COVID-19 in China.", "qid": 17, "docid": "iwsa760n", "rank": 98, "score": 0.7655301094055176}, {"content": "Title: Is it Ethically Appropriate to Continue Surgical Clinical Trials During the COVID-19 Pandemic? EDITED BY DR SARR Content: COVID-19 has greatly impacted surgical care and decision-making. The status of surgical clinical trials during this pandemic has not been addressed. We provide a framework and recommendations for the management of patients involved in surgical clinical trials.", "qid": 17, "docid": "i400ynjp", "rank": 99, "score": 0.7654510736465454}, {"content": "Title: Endemic and emerging coronavirus pulmonary infections Content: Coronaviruses are a well-known cause of upper and lower respiratory disease, and since 2002 have been a recognized source of potential pandemic spread. Over the past two decades, since the Severe Acute Respiratory Syndrome (SARS) outbreak, a large body of research has accumulated on the virology, clinical symptoms and signs, and experimental treatments of Coronaviruses. In 2020, a new form of Coronaviruses (SARS-CoV-2) emerged and spread rapidly throughout the globe. Given the wide-ranging clinical presentations of those infected with SARS-CoV-2, other viruses might be overlooked when evaluating at-risk patients. Furthermore, due to suboptimal testing capabilities, an early clinical diagnosis is not always possible. Here, we present a case of a patient with pneumonia thought to be caused by SARS-CoV-2 only to be found to have another Coronavirus. This emphasizes the need to be vigilant when evaluating patients with viral-like respiratory infections.", "qid": 17, "docid": "mz4dmxwt", "rank": 100, "score": 0.7654445767402649}]}
{"query": "what are the best masks for preventing infection by Covid-19?", "hits": [{"content": "Title: Medical mask or N95 respirator: When and how to use? Content: COVID-19 pandemic is now a global threat on human health reaching up to 2 million infected people all around the World. Since its first recognition in Wuhan, many topics were discussed intensively about COVID-19, both in the public and scientific community. Personal protective equipments and especially masks were among the hottest topics during this pandemic. Regardless of which mask is used, performing hand hygiene frequently with an alcohol-based hand rub or with soap and water if hands are dirty; is the most effective preventive measure for COVID-19. The type of mask used when caring for COVID-19 patients will vary according to the setting, type of personnel/person, and activity. Although the main transmission route for COVID-19 is droplets, during aerosol generating procedures airborne transmission may occur. Keeping the distancing and medical masks and eye protection during close contact efficiently protects against respiratory diseases transmitted via droplets. Airborne precautions include goggles and respiratory protection with the use of an N95 or an equivalent mask respirator to prevent airborne transmission.", "qid": 18, "docid": "6wxjm7m0", "rank": 1, "score": 0.8023801445960999}, {"content": "Title: Medical mask or N95 respirator: When and how to use? Content: COVID-19 pandemic is now a global threat to human health reaching up to 2 million infected people all around the world. Since its first recognition in Wuhan, many topics were discussed intensively about COVID-19, both in the public and scientific community. Personal protective equipment, especially masks, has been among the hottest topics during this pandemic. Regardless of which mask is used, performing hand hygiene frequently with an alcohol-based hand rub or with soap and water if hands are dirty is the most effective preventive measure for COVID-19. The type of mask used when caring for COVID-19 patients will vary according to the setting, type of personnel/person, and activity. Although the main transmission route for COVID-19 is droplets, during aerosol generating procedures airborne transmission may occur. Keeping the distancing and medical masks and eye protection during close contact efficiently protects against respiratory diseases transmitted via droplets. Airborne precautions include goggles and respiratory protection with the use of an N95 or an equivalent mask respirator to prevent airborne transmission.", "qid": 18, "docid": "r1oqwdkz", "rank": 2, "score": 0.8008401393890381}, {"content": "Title: Comprehensive review of mask utility and challenges during the COVID-19 pandemic. Content: Masks are widely discussed during the course of the ongoing COVID-19 pandemic. Most hospitals have implemented universal masking for their healthcare workers, and the Center for Disease Control currently advises even the general public to wear cloth masks when outdoors. The pertinent need for masks arises from plausible dissemination of the SARS-CoV-2 through close contacts, as well as the possibility of virus transmission from asymptomatic, pre-symptomatic, and mildly symptomatic individuals. Given current global shortages in personal protective equipment, the efficacy of various types of masks: N95 respirators, surgical masks, and cloth masks are researched. To accommodate limited supplies, techniques for extended use, reuse, and sterilization of masks are strategized. However, masks alone may not greatly slow down the COVID-19 pandemic unless they are coupled with adequate social distancing, diligent hand hygiene, and other proven preventive measures.", "qid": 18, "docid": "3ttcfhm3", "rank": 3, "score": 0.7868388891220093}, {"content": "Title: Strategy of using personal protective equipment during aerosol generating medical procedures with COVID-19 Content: \u2022 Compared the effectiveness and cost-effectiveness between masks and respirators for the COVID-19 transmission; \u2022 Discussed the strategy to avoid severe nosocomial infection through aerosol-generating medical procedures; \u2022 Suggestions for healthcare workers to choose proper personal protective equipment.", "qid": 18, "docid": "62pnddks", "rank": 4, "score": 0.7822884917259216}, {"content": "Title: Rationeel gebruik van ademhalingsbeschermingsmaskers./ [Rational use of respiratory protective equipment: advice for health care professionals in time of COVID-19] Content: The current COVID-19 pandemic has led to a worldwide shortage of respiratory protective equipment. In order to offer maximum protection against infection for all healthcare workers, we need to optimise our use of the available equipment. This article provides practical advice on which type of mask is indicated in what specific situation, what requirements the mask should meet and how to optimise the local workflow, including the re-use of masks after decontamination.", "qid": 18, "docid": "31fnbch7", "rank": 5, "score": 0.7800672054290771}, {"content": "Title: [Rational use of respiratory protective equipment: advice for health care professionals in time of COVID-19]. Content: The current COVID-19 pandemic has led to a worldwide shortage of respiratory protective equipment. In order to offer maximum protection against infection for all healthcare workers, we need to optimise our use of the available equipment. This article provides practical advice on which type of mask is indicated in what specific situation, what requirements the mask should meet and how to optimise the local workflow, including the re-use of masks after decontamination.", "qid": 18, "docid": "nk95dyln", "rank": 6, "score": 0.7800672054290771}, {"content": "Title: Comprehensive review of mask utility and challenges during the COVID-19 pandemic Content: Masks are widely discussed during the course of the ongoing COVID-19 pandemic Most hospitals have implemented universal masking for their healthcare workers, and the Center for Disease Control currently advises even the general public to wear cloth masks when outdoors The pertinent need for masks arises from plausible dissemination of the SARS-CoV-2 through close contacts, as well as the possibility of virus transmission from asymptomatic, pre-symptomatic, and mildly symptomatic individuals Given current global shortages in personal protective equipment, the efficacy of various types of masks: N95 respirators, surgical masks, and cloth masks are researched To accommodate limited supplies, techniques for extended use, reuse, and sterilization of masks are strategized However, masks alone may not greatly slow down the COVID-19 pandemic unless they are coupled with adequate social distancing, diligent hand hygiene, and other proven preventive measures", "qid": 18, "docid": "7qj00qi9", "rank": 7, "score": 0.778810977935791}, {"content": "Title: Correspondence: Angiotensin-converting enzyme 2 coated nanoparticles containing respiratory masks, chewing gums and nasal filters may be used for protection against COVID-19 infection Content: \u2022 World has encountered a novel pandemic called as COVID-19. \u2022 All people need protective items such as masks and gloves worldwide. \u2022 Preventing COVID-19 infection has become the most important issue. \u2022 ACE2 containing nanomaterials may be used in the respiratory masks, gloves and clothes. \u2022 Using nanotechnology to prevent this pandemic may be hope for fighting against COVID-19.", "qid": 18, "docid": "g477u9k1", "rank": 8, "score": 0.7718220949172974}, {"content": "Title: Use of N95, Surgical, and Cloth Masks to Prevent COVID-19 in Health Care and Community Settings: Living Practice Points From the American College of Physicians (Version 1) Content: Controversy exists around the appropriate types of masks and the situations in which they should be used in community and health care settings for the prevention of SARS-CoV-2 infection. In this article, the American College of Physicians (ACP) provides recommendations based on the best available evidence through 14 April 2020 on the effectiveness of N95 respirators, surgical masks, and cloth masks in reducing transmission of infection. The ACP plans periodic updates of these recommendations on the basis of ongoing surveillance of the literature for 1 year from the initial search date.", "qid": 18, "docid": "f4sd7vbi", "rank": 9, "score": 0.7700598239898682}, {"content": "Title: A simple model to show the relative risk of viral aerosol infection and the benefit of wearing masks in different settings with implications for Covid-19 . Content: Background . Widespread use of masks in the general population is being used in many countries for Covid-19 . There has been reluctance on the part of the WHO and some governments to recommend this . Methodology . A basic model has been constructed to show the relative risk of aerosol from normal breathing in various situations together with the benefit from use of masks which is multiplicative . Results . Social distancing at 2 metres is validated but in confined areas is time limited and the use of masks in the absence of extremely good ventilation is important. Where social distancing is not possible at all times or an infectious person is in a confined area for a prolonged period there is a higher risk of infection requiring protection . Conclusions . The use of masks should be factored into models and used at an early stage as widespread use of more efficient masks could have a large impact on control and spread of infection . Public health planning requires stockpiling masks and encouraging everyone to have suitable masks in their household when supplies are normalised . The use of a cloth mask will be better than no protection at all .", "qid": 18, "docid": "sqr11fpv", "rank": 10, "score": 0.7682252526283264}, {"content": "Title: 'Masking the evidence': perspectives of the COVID-19 pandemic Content: The COVID-19 pandemic presents a severe and acute public health emergency around the world. The event of the pandemic has seen an upsurge in the general public wearing of disposable surgical masks (DSM) and other types of face masks. The World Health Organisation of mask wearing has been widely debated in the press a(WHO) have changed their advice, to now recommend the routine wearing of fabric masks by the general public as a means of preventing the spread of COVID-19 (WHO 2020a).", "qid": 18, "docid": "sjenehbl", "rank": 11, "score": 0.764570951461792}, {"content": "Title: The face mask: How a real protection becomes a psychological symbol during Covid-19? Content: 'The Mask' has become a byword and a precious possession universally. Except for its use by the medical fraternity, answers to the common questions-whether it provides enough protection, which type is optimal for the general public and who really needs to don it, remain poorly understood. For a frontline healthcare worker, wearing mask is a necessity as an important person protection equipment, it is perhaps the most-powerful psychological symbol for the general public. Surprisingly, it even undermines all other recommended practices of infection control and breaking the transmission chain of Covid-19, like hand washing, personal hygiene and social distancing. 'The mask' has evolved with time and yet there is a need to further improve the design for safety, tolerability and comfort. In this review we present the journey of face mask, originating from the first masks aimed at stopping the bad smell to its industrial use to its all-important place in the medical field. Various types of face masks, their filtration efficiency, reusability and current recommendations for their use are presented.", "qid": 18, "docid": "svtux4dk", "rank": 12, "score": 0.7613270878791809}, {"content": "Title: The Face Mask How a Real Protection becomes a Psychological Symbol during Covid-19? Content: 'The Mask' has become a byword and a precious possession universally. Except for its use by the medical fraternity, answers to the common questions-whether it provides enough protection, which type is optimal for the general public and who really needs to don it, remain poorly understood. For a frontline healthcare worker, wearing mask is a necessity as an important person protection equipment, it is perhaps the most-powerful psychological symbol for the general public. Surprisingly, it even undermines all other recommended practices of infection control and breaking the transmission chain of Covid-19, like hand washing, personal hygiene and social distancing. 'The mask' has evolved with time and yet there is a need to further improve the design for safety, tolerability and comfort. In this review we present the journey of face mask, originating from the first masks aimed at stopping the bad smell to its industrial use to its all-important place in the medical field. Various types of face masks, their filtration efficiency, reusability and current recommendations for their use are presented.", "qid": 18, "docid": "uq6kj3qi", "rank": 13, "score": 0.7613270878791809}, {"content": "Title: Facial protection in the era of COVID-19: A narrative review Content: We live in extraordinary times, where COVID-19 pandemic has brought the whole world to a screeching halt. Tensions and contradictions that surround the pandemic ridden world include the availability, and the lack thereof, various facial protection measures to mitigate the viral spread. Here, we comprehensively explore the different types of facial protection measures, including masks, needed both for the public and the healthcare workers (HCW). We discuss the anatomy, the critical issues of disinfection and reusability of masks, the alternative equipment available for the protection of the facial region from airborne diseases, such as face shields and powered air-purifying respirators (PAPR), and the skin health impact of prolonged wearing of facial protection by HCW. Clearly, facial protection, either in the form of masks or alternates, appears to have mitigated the pandemic as seen from the minimal COVID-19 spread in countries where public mask wearing is strictly enforced. On the contrary, the healthcare systems, that appear to have been unprepared for emergencies of this nature, should be appropriately geared to handle the imbalance of supply and demand of personal protective equipment including face masks. These are two crucial lessons we can learn from this tragic experience.", "qid": 18, "docid": "6n5gnow1", "rank": 14, "score": 0.7606655359268188}, {"content": "Title: \u2018Masking the evidence\u2019: perspectives of the COVID\u201019 pandemic Content: The COVID\u201019 pandemic presents a severe and acute public health emergency around the world. The event of the pandemic has seen an upsurge in the general public wearing of disposable surgical masks (DSM) and other types of face masks. The World Health Organisation of mask wearing has been widely debated in the press a(WHO) have changed their advice, to now recommend the routine wearing of fabric masks by the general public as a means of preventing the spread of COVID\u201019 (WHO 2020a).", "qid": 18, "docid": "f9syysdw", "rank": 15, "score": 0.7581496238708496}, {"content": "Title: Mascarillas como equipo de protecci\u00f3n individual durante la pandemia de Covid-19: C\u00f3mo, cu\u00e1ndo y cu\u00e1les deben utilizarse Content: Abstract Background and objective: In the COVID-19 pandemic, the demand of masks has been increased by health professionals and the general population. In this context, it is necessary to summarize the features and indications of the different types of masks. Patients or Materials and methods: To consult and to compile the different recommendations disseminated by prestigious institutions such as the World Health Organization, the European Center for Disease Prevention, the Center for Evidence-Based Medicine, or the Ministry of Health of the Government of Spain has been reviewed. Results: The institutions consulted recommend reserving FFP respirators for healthcare workers, especially when carrying out aerosol-generating procedures (AGPs) (minimum FFP2 protection) and consider some reutilization systems during times of scarcity. The use of surgical masks is recommended to professionals who do not perform AGPs and to the symptomatic population but exist variations in its indications intended for the general healthy population. Conclusions: In the context of shortage of personal protective equipment due to the COVID -19 pandemic, a prioritization and rationalization of the use of each type of mask should be established according to the user and the activity performed.", "qid": 18, "docid": "gmofvknn", "rank": 16, "score": 0.75679612159729}, {"content": "Title: The N-95 mask: invaluable ally in the battle against the COVID-19 pandemic Content: The present COVID-19 pandemic, caused by the airborne SARS-CoV-2 virus, has highlighted the vital importance of appropriate personal protective equipment for all exposed health care workers The single most important part of this armor is the N-95 mask With the awareness that the virus is spread by both droplets and through the aerosolized route, the N-95 provides protection that a surgical mask cannot match This timely review looks at the special advantages that an N-95 offers over a surgical mask with specific reference to the COVID-19 epidemic It also emphasizes the crucial importance of ensuring quality masks with a proper fit Finally, with acute scarcities of N-95 masks being reported from hospitals globally, it reviews recent literature which attempts to prolong the life of these masks with extended use, reuse and decontamination of used masks", "qid": 18, "docid": "i1w2snyy", "rank": 17, "score": 0.7567145824432373}, {"content": "Title: Facial protection in the era of COVID-19: a narrative review Content: We live in extraordinary times, where COVID-19 pandemic has brought the whole world to a screeching halt. Tensions and contradictions that surround the pandemic ridden world include the availability, and the lack thereof, various facial protection measures to mitigate the viral spread. Here, we comprehensively explore the different type of facial protection measures, including masks, needed both for the pubic and the health care workers (HCW). We discuss the anatomy, the critical issues of disinfection and reusability of masks, the alternative equipment available for the protection of the facial region from airborne diseases, such as face shields and powered air purifying respirators (PAPR), and the skin-health impact of prolonged wearing of facial protection by HCW. Clearly, facial protection, either in the form of masks or alternates, appears to have mitigated the pandemic as seen from the minimal COVID-19 spread in countries where public mask wearing is strictly enforced. On the contrary, the healthcare systems, that appear to have been unprepared for emergencies of this nature, should be appropriately geared to handle the imbalance of supply and demand of personal protective equipment including face masks. These are two crucial lessons we can learn from this tragic experience.", "qid": 18, "docid": "uep2tfnu", "rank": 18, "score": 0.7544652223587036}, {"content": "Title: COVID\u201019: Face masks and human\u2010to\u2010human transmission Content: In December 2019, transmission of the novel coronavirus (SARS-CoV-2) that causes coronavirus disease 2019(COVID-19) occurred in Wuhan, China1 .And later the virus began to be transmitted from person to person2 .Face masks are a type of personal protective equipment used to prevent the spread of respiratory infections\uff0cit may be effective at helping prevent transmission of respiratory viruses and bacteria3 .Here, we share a case of face masks are be used to prevent the transmission of COVID-19 infection.", "qid": 18, "docid": "wni08lks", "rank": 19, "score": 0.7529334425926208}, {"content": "Title: Disposable masks: Disinfection and sterilization for reuse, and non-certified manufacturing, in the face of shortages during the COVID-19 pandemic Content: The COVID-19 pandemic is posing a huge global health threat. To deal with this problem, in addition to research and work in the medical field, the main health measures being taken in the workplace and at home involve the establishment of safety protocols, which include distance measures, hygiene and the use of personal protective equipment, such as masks, etc. The WHO still does not recommend the use of masks for the general population. However, their successful use in China, South Korea and the Czech Republic has encouraged their widespread use, and the shortage that already existed. This has caused that companies and individuals are looking at the best way to reuse them, and to manufacture, homemade or not, of non-certified masks. This paper is based on two objectives: to consult the scientific literature to identify the main strategies for disinfecting them, and to determine the effectiveness of non-certified disposable masks. A rapid review has been conducted in which the main publications and other information available online have been analyzed. Results showed that the most promising methods are those that use hydrogen peroxide vapor, ultraviolet radiation, moist heat, dry heat and ozone gas. Soapy water, alcohol, bleach immersion, ethylene oxide, ionizing radiation, microwave, high temperature, autoclave or steam are not fully recommended. Regarding the effectiveness of surgical masks compared to PPE, the former have been seen to be slightly less effective than PPE. As for other types of masks the effectiveness of homemade or non-certified masks is very low.", "qid": 18, "docid": "lncsfohg", "rank": 20, "score": 0.7527808547019958}, {"content": "Title: Simple Economical Solution for Personal Protection Equipment (Face Mask/Shield) for Health Care Staff During COVID 19 Content: Coronavirus disease 2019 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. It has taken a toll of lots of lives since its outbreak. Infection prevention at present is an appropriate control measure in addition to other measure like hand hygiene and personal protective equipment (PPE). In our country with a large population, supplying PPE to all the health care workers of all hospitals definitely is an economic burden. Hence we have come up with an economic and simple solution for face mask. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12070-020-01863-4) contains supplementary material, which is available to authorized users.", "qid": 18, "docid": "05vx82oo", "rank": 21, "score": 0.7512004375457764}, {"content": "Title: Facial protection in the era of COVID\u201019: a narrative review Content: We live in extraordinary times, where COVID\u201019 pandemic has brought the whole world to a screeching halt. Tensions and contradictions that surround the pandemic ridden world include the availability, and the lack thereof, various facial protection measures to mitigate the viral spread. Here, we comprehensively explore the different type of facial protection measures, including masks, needed both for the pubic and the health care workers (HCW). We discuss the anatomy, the critical issues of disinfection and reusability of masks, the alternative equipment available for the protection of the facial region from airborne diseases, such as face shields and powered air purifying respirators (PAPR), and the skin\u2010health impact of prolonged wearing of facial protection by HCW. Clearly, facial protection, either in the form of masks or alternates, appears to have mitigated the pandemic as seen from the minimal COVID\u201019 spread in countries where public mask wearing is strictly enforced. On the contrary, the healthcare systems, that appear to have been unprepared for emergencies of this nature, should be appropriately geared to handle the imbalance of supply and demand of personal protective equipment including face masks. These are two crucial lessons we can learn from this tragic experience.", "qid": 18, "docid": "kqlra788", "rank": 22, "score": 0.7510049343109131}, {"content": "Title: Role of respirators in controlling the spread of novel coronavirus (COVID-19) amongst dental healthcare providers: a review Content: During the ongoing COVID-19 pandemic, healthcare professionals are at the forefront of managing the highly infectious coronavirus. As the most common route of transmission is via aerosols and droplet inhalation, it is critical for healthcare workers to have the correct personal protective equipment (PPE) including gowns, masks and goggles. Surgical masks are not effective in preventing the influenza and SARS, so they are unlikely to be able to resist contaminated aerosols from entering the respiratory system. Therefore, it is vital to use respirators which have been proven to offer better protection against droplets, aerosols and fluid penetration and which form a tight seal around the mouth and nose. Various types of respirators are used in healthcare settings, such as half-mask filtering facepiece respirators (FFRs) and powered air-purifying respirators (PAPRs). The most commonly used FFR is the N95 disposable respirator, which is tight fitting and has a 95% or above particle filtering efficiency for a median particle size of 0.3 \u00b5m. This review discusses respirators, their purpose, types, clinical efficiency and proper donning and doffing techniques.", "qid": 18, "docid": "gprvoecp", "rank": 23, "score": 0.7492058277130127}, {"content": "Title: Universal Masking during Covid-19 Pandemic - Current Evidence and Controversies Content: The emergence of coronavirus disease 19 pandemic and novel research on the high transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised controversies over the use of face masks to prevent community transmission. Specific regulations need to be fulfilled to use a face mask as part of the personal protective equipment and high quality of evidence supporting its use to prevent respiratory viral infections, including SARS-CoV-2, is lacking. However, its widespread use is becoming a standard practice in some countries and discrepancies between health authorities on their policy have led to controversy. The aim of this review is to provide an outlook on recent research in this matter and areas of opportunity.", "qid": 18, "docid": "fdkqs3rg", "rank": 24, "score": 0.7490957379341125}, {"content": "Title: UNIVERSAL MASKING DURING COVID-19 PANDEMIC - CURRENT EVIDENCE AND CONTROVERSIES. Content: The emergence of coronavirus disease 19 pandemic and novel research on the high transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised controversies over the use of face masks to prevent community transmission. Specific regulations need to be fulfilled to use a face mask as part of the personal protective equipment and high quality of evidence supporting its use to prevent respiratory viral infections, including SARS-CoV-2, is lacking. However, its widespread use is becoming a standard practice in some countries and discrepancies between health authorities on their policy have led to controversy. The aim of this review is to provide an outlook on recent research in this matter and areas of opportunity.", "qid": 18, "docid": "cvulb9t6", "rank": 25, "score": 0.7490957379341125}, {"content": "Title: Importance of face masks for COVID-19 - a call for effective public education Content: Considerable debates about the general community use of face masks for protection against COVID-19 stemmed out from differing views taken by health authorities. Misconceptions and stigmatization towards the use of face masks may hinder the containment of the COVID-19 pandemic. We address this previous debate by analyzing the advice on the community use of masks across different credible health authorities: countries that promoted the use of masks acknowledged that masks are effective, but also explained the importance of their proper use along with other hygiene measures. In contrast, authorities that recommended against the community use of masks mainly cited shortage of supplies, the argument that the public do not have the adequate skills to wear them, or that wearing masks might reduce compliance with other important behaviors. We suggest promoting effective behavioral changes in personal protective measures by teaching microbiological knowledge instead of just listing out the \"dos-and-don'ts\".", "qid": 18, "docid": "wee1133a", "rank": 26, "score": 0.7490415573120117}, {"content": "Title: Cloth Masks May Prevent Transmission of COVID-19: An Evidence-Based, Risk-Based Approach Content: As the COVID-19 pandemic progressed across the world, governments, international agencies, policymakers, and public health officials began recommending widespread use of nonmedical cloth masks to reduce the transmission of SARS-CoV-2. The authors of this article suggest that there is convincing evidence to support this recommendation.", "qid": 18, "docid": "8je46886", "rank": 27, "score": 0.7482991814613342}, {"content": "Title: A rapid systematic review of the efficacy of face masks and respirators against coronaviruses and other respiratory transmissible viruses for the community, healthcare workers and sick patients Content: BACKGROUND: The pandemic of COVID-19 is growing, and a shortage of masks and respirators has been reported globally. Policies of health organizations for healthcare workers are inconsistent, with a change in policy in the US for universal face mask use. The aim of this study was to review the evidence around the efficacy of masks and respirators for healthcare workers, sick patients and the general public. METHODS: A systematic review of randomized controlled clinical trials on use of respiratory protection by healthcare workers, sick patients and community members was conducted. Articles were searched on Medline and Embase using key search terms. RESULTS: A total of 19 randomised controlled trials were included in this study - 8 in community settings, 6 in healthcare settings and 5 as source control. Most of these randomised controlled trials used different interventions and outcome measures. In the community, masks appeared to be effective with and without hand hygiene, and both together are more protective. Randomised controlled trials in health care workers showed that respirators, if worn continually during a shift, were effective but not if worn intermittently. Medical masks were not effective, and cloth masks even less effective. When used by sick patients randomised controlled trials suggested protection of well contacts. CONCLUSION: The study suggests that community mask use by well people could be beneficial, particularly for COVID-19, where transmission may be pre-symptomatic. The studies of masks as source control also suggest a benefit, and may be important during the COVID-19 pandemic in universal community face mask use as well as in health care settings. Trials in healthcare workers support the use of respirators continuously during a shift. This may prevent health worker infections and deaths from COVID-19, as aerosolisation in the hospital setting has been documented.", "qid": 18, "docid": "in16u4pm", "rank": 28, "score": 0.748023509979248}, {"content": "Title: Low-cost measurement of facemask efficacy for filtering expelled droplets during speech Content: Mandates for mask use in public during the recent COVID-19 pandemic, worsened by global shortage of commercial supplies, have led to widespread use of homemade masks and mask alternatives. It is assumed that wearing such masks reduces the likelihood for an infected person to spread the disease, but many of these mask designs have not been tested in practice. We have applied a simple optical measurement method to evaluate the efficacy of masks to reduce the transmission of respiratory droplets during regular speech. We compare a variety of commonly available mask types and observe that some mask types approach the performance of standard surgical masks, while some mask alternatives, such as neck fleece or bandanas, offer very little protection. Our measurement setup is inexpensive and can be built and operated by non-experts, allowing for rapid evaluation of mask performance during speech, sneezing, or coughing.", "qid": 18, "docid": "oyxxji7r", "rank": 29, "score": 0.7478311061859131}, {"content": "Title: Face masks for all and all for face masks in the COVID-19 pandemic: community level production to face the global shortage and shorten the epidemic Content: The current COVID-19 pandemic caused a global shortage of medical masks, leaving most exposed health personnel without appropriate protection.Since the beginning of the outbreak, the WHO has revised several times the recommendations on general use of facemasks. In various countries, the public was advised to wear facemasks, in order to ensure them to healthcare workers. Until recently, WHO recommended to limit the use of facemasks to symptomatic people and advised against off-standard solutions. Moreover, recommendations differ among and within countries, causing public confusion and individual initiative.There is wide consensus that universal appropriate use of masks may contribute both to contain the epidemic and to reduce the burden on national procurement, if a community production approach is followed. Especially in low-middle income countries, due to the scarce capacity of national industrial production or import, the use of masks produced at community level may become the only viable option.For the purpose ad hoc guidelines will be needed.Current knowledge and experience call for further and updated review of global and national guidelines in order to provide clear and consistent criteria to ensure the widest availability and appropriate use of facial protection, bearing in mind populations in socio-economic disadvantaged settings.", "qid": 18, "docid": "sd7ozaif", "rank": 30, "score": 0.747268795967102}, {"content": "Title: Face masks for all and all for face masks in the COVID-19 pandemic: community level production to face the global shortage and shorten the epidemic. Content: The current COVID-19 pandemic caused a global shortage of medical masks, leaving most exposed health personnel without appropriate protection.Since the beginning of the outbreak, the WHO has revised several times the recommendations on general use of facemasks. In various countries, the public was advised to wear facemasks, in order to ensure them to healthcare workers. Until recently, WHO recommended to limit the use of facemasks to symptomatic people and advised against off-standard solutions. Moreover, recommendations differ among and within countries, causing public confusion and individual initiative.There is wide consensus that universal appropriate use of masks may contribute both to contain the epidemic and to reduce the burden on national procurement, if a community production approach is followed. Especially in low-middle income countries, due to the scarce capacity of national industrial production or import, the use of masks produced at community level may become the only viable option.For the purpose ad hoc guidelines will be needed.Current knowledge and experience call for further and updated review of global and national guidelines in order to provide clear and consistent criteria to ensure the widest availability and appropriate use of facial protection, bearing in mind populations in socio-economic disadvantaged settings.", "qid": 18, "docid": "krh7p1tg", "rank": 31, "score": 0.7472687363624573}, {"content": "Title: A RAPID SYSTEMATIC REVIEW OF THE EFFICACY OF FACE MASKS AND RESPIRATORS AGAINST CORONAVIRUSES AND OTHER RESPIRATORY TRANSMISSIBLE VIRUSES FOR THE COMMUNITY, HEALTHCARE WORKERS AND SICK PATIENTS Content: ABSTRACT Background The pandemic of COVID-19 is growing, and a shortage of masks and respirators has been reported globally. Policies of health organizations for healthcare workers are inconsistent, with a change in policy in the US for universal face mask use. The aim of this study was to review the evidence around the efficacy of masks and respirators for healthcare workers, sick patients and the general public. Methods A systematic review of randomized controlled clinical trials on use of respiratory protection by healthcare workers, sick patients and community members was conducted. Articles were searched on Medline and Embase using key search terms. Results A total of 19 randomised controlled trials were included in this study \u2013 8 in community settings, 6 in healthcare settings and 5 as source control. Most of these randomised controlled trials used different interventions and outcome measures. In the community, masks appeared to be more effective than hand hygiene alone, and both together are more protective. Randomised controlled trials in health care workers showed that respirators, if worn continually during a shift, were effective but not if worn intermittently. Medical masks were not effective, and cloth masks even less effective. When used by sick patients randomised controlled trials suggested protection of well contacts. Conclusion The study suggests that community mask use by well people could be beneficial, particularly for COVID-19, where transmission may be pre-symptomatic. The studies of masks as source control also suggest a benefit, and may be important during the COVID-19 pandemic in universal community face mask use as well as in health care settings. Trials in healthcare workers support the use of respirators continuously during a shift. This may prevent health worker infections and deaths from COVID-19, as aerosolisation in the hospital setting has been documented.", "qid": 18, "docid": "h7ftu3ax", "rank": 32, "score": 0.7471131086349487}, {"content": "Title: Role of respirators in controlling the spread of novel coronavirus (COVID\u201019) amongst dental healthcare providers: a review Content: During the ongoing COVID\u201019 pandemic, healthcare professionals are at the forefront of managing the highly infectious coronavirus. As the most common route of transmission is via aerosols and droplet inhalation, it is critical for healthcare workers to have the correct personal protective equipment (PPE) including gowns, masks and goggles. Surgical masks are not effective in preventing the influenza and SARS, so they are unlikely to be able to resist contaminated aerosols from entering the respiratory system. Therefore, it is vital to use respirators which have been proven to offer better protection against droplets, aerosols and fluid penetration and which form a tight seal around the mouth and nose. Various types of respirators are used in healthcare settings, such as half\u2010mask filtering facepiece respirators (FFRs) and powered air\u2010purifying respirators (PAPRs). The most commonly used FFR is the N95 disposable respirator, which is tight fitting and has a 95% or above particle filtering efficiency for a median particle size of 0.3 \u00b5m. This review discusses respirators, their purpose, types, clinical efficiency and proper donning and doffing techniques.", "qid": 18, "docid": "b27xeyy3", "rank": 33, "score": 0.7462035417556763}, {"content": "Title: Simple Economical Solution for Personal Protection Equipment (Face Mask/Shield) for Health Care Staff During COVID 19 Content: Coronavirus disease 2019 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. It has taken a toll of lots of lives since its outbreak. Infection prevention at present is an appropriate control measure in addition to other measure like hand hygiene and personal protective equipment (PPE). In our country with a large population, supplying PPE to all the health care workers of all hospitals definitely is an economic burden. Hence we have come up with an economic and simple solution for face mask.", "qid": 18, "docid": "1jpf9kc4", "rank": 34, "score": 0.7459547519683838}, {"content": "Title: Medical masks and Respirators for the Protection of Healthcare Workers from SARS-CoV-2 and other viruses Content: The use of medical masks and respirators as personal protective equipment is pivotal to reducing the level of biological hazard to which healthcare workers are exposed during the outbreak of highly diffusible pathogens, such as the recent novel coronavirus SARS-CoV-2. Unfortunately, during this pandemic, supplies are rapidly running out worldwide, with potential consequences for the rate of occupational infections. Also, knowledge about specific characteristics of respirators is of utmost importance to select the proper type according to the clinical setting. A wide variety of literature is available on the topic, but mostly based on Influenza viruses infection models. Clinical evidence on the use of respirators is poor and interest in the topic has not been constant over time. A better understanding of SARS-CoV-2 transmission is needed, together with high-quality clinical data on the use of respirators or alternative devices. Moreover, healthcare workers, regardless of their level of experience, should receive specific training. This review aims to summarize the available evidence on the use of medical masks and respirators in the context of viral infections, especially the current coronavirus disease 2019 (COVID-19).", "qid": 18, "docid": "uuau3n7s", "rank": 35, "score": 0.7452878952026367}, {"content": "Title: Do Face Masks Create a False Sense of Security? A COVID-19 Dilemma Content: Face masks have become an emblem of the public response to COVID-19, with many governments mandating their use in public spaces. The logic is that face masks are low cost and might help prevent some transmission. However, from the start, the assumption that face masks are \"low cost\" was questioned. Early on, there were warnings of the opportunity cost of public use of medical masks given shortages of personal protective equipment for healthcare providers. This led to recommendations for cloth masks and other face coverings, with little evidence of their ability to prevent transmission. However, there may also be a high cost to these recommendations if people rely on face masks in place of other more effective ways to break transmission, such as staying home. We use SafeGraph smart device location data to show that the representative American in states that have face mask mandates spent 20-30 minutes less time at home, and increase visits to a number of commercial locations, following the mandate. Since the reproductive rate of SAR-COV2, the pathogen that causes COVID-19 is hovering right around one, such substitution behavior could be the difference between controlling the epidemic and a resurgence of cases.", "qid": 18, "docid": "1c3fpazy", "rank": 36, "score": 0.7452144622802734}, {"content": "Title: Rational use of face mask in a tertiary care hospital setting during COVID-19 pandemic: An observational study Content: Masks play a role in the protection of health-care workers (HCWs) from acquiring respiratory infections, including coronavirus disease 2019 (COVID-19) in health-care settings. This observational study was conducted among 382 HCWs in a tertiary care setting over a period of 1 month. Descriptive analysis was done to assess the rational and recommended use of masks/respirators during COVID-19 pandemic using a structured observation checklist as a survey tool. A total of 374 HCWs were included, 64.9% of whom were using face masks rationally as mentioned per risk area categorization with a predominance of triple-layered mask during all 4 weeks. Overall, 64.1% used masks correctly. Clear guidelines and strategies can help to increase the compliance of HCWs with rational use of face masks.", "qid": 18, "docid": "57zwd3y6", "rank": 37, "score": 0.7450379133224487}, {"content": "Title: Rational use of face mask in a tertiary care hospital setting during COVID-19 pandemic: An observational study. Content: Masks play a role in the protection of health-care workers (HCWs) from acquiring respiratory infections, including coronavirus disease 2019 (COVID-19) in health-care settings. This observational study was conducted among 382 HCWs in a tertiary care setting over a period of 1 month. Descriptive analysis was done to assess the rational and recommended use of masks/respirators during COVID-19 pandemic using a structured observation checklist as a survey tool. A total of 374 HCWs were included, 64.9% of whom were using face masks rationally as mentioned per risk area categorization with a predominance of triple-layered mask during all 4 weeks. Overall, 64.1% used masks correctly. Clear guidelines and strategies can help to increase the compliance of HCWs with rational use of face masks.", "qid": 18, "docid": "t2e4bxsu", "rank": 38, "score": 0.7450379133224487}, {"content": "Title: Importance of face masks for COVID-19 \u2013 a call for effective public education Content: Considerable debates about the general community use of face masks for protection against COVID-19 stemmed out from differing views taken by health authorities. Misconceptions and stigmatization towards the use of face masks may hinder the containment of the COVID-19 pandemic. We address this previous debate by analyzing the advice on the community use of masks across different credible health authorities: countries that promoted the use of masks acknowledged that masks are effective, but also explained the importance of their proper use along with other hygiene measures. In contrast, authorities that recommended against the community use of masks mainly cited shortage of supplies, the argument that the public do not have the adequate skills to wear them, or that wearing masks might reduce compliance with other important behaviors. We suggest promoting effective behavioral changes in personal protective measures by teaching microbiological knowledge instead of just listing out the \u201cdos-and-don\u2019ts\u201d.", "qid": 18, "docid": "p2ufydgs", "rank": 39, "score": 0.7449246644973755}, {"content": "Title: Face mask use in the general population and optimal resource allocation during the COVID-19 pandemic Content: The ongoing novel coronavirus disease (COVID-19) pandemic has rapidly spread in early 2020, causing tens of thousands of deaths, over a million cases and widespread socioeconomic disruption. With no vaccine available and numerous national healthcare systems reaching or exceeding capacity, interventions to limit transmission are urgently needed. While there is broad agreement that travel restrictions and closure of non-essential businesses and schools are beneficial in limiting local and regional spread, recommendations around the use of face masks for the general population are less consistent internationally. In this study, we examined the role of face masks in mitigating the spread of COVID-19 in the general population, using epidemic models to estimate the total reduction of infections and deaths under various scenarios. In particular, we examined the optimal deployment of face masks when resources are limited, and explored a range of supply and demand dynamics. We found that face masks, even with a limited protective effect, can reduce infections and deaths, and can delay the peak time of the epidemic. We consistently found that a random distribution of masks in the population was a suboptimal strategy when resources were limited. Prioritizing coverage among the elderly was more beneficial, while allocating a proportion of available resources for diagnosed infected cases provided further mitigation under a range of scenarios. In summary, face mask use, particularly for a pathogen with relatively common asymptomatic carriage, can effectively provide some mitigation of transmission, while balancing provision between vulnerable healthy persons and symptomatic persons can optimize mitigation efforts when resources are limited.", "qid": 18, "docid": "qdamvwxl", "rank": 40, "score": 0.7447496056556702}, {"content": "Title: Reply to Zhang et al.: Slowing the rate of spread of COVID-19 Content: Zhang et al. (2020) reported that mandating face coverings in public is necessary to decrease the rate of new COVID-19 infections. We present a counterexample that disproves this finding. We agree with Zhang et al. that masks can be an important element in reducing virus transmission and that widespread use may be essential for returning to full activity. However, their analysis neglects the potential importance of physical distancing for limiting COVID-19 transmission by misattributing its effect to mask requirements. A full suite of epidemiological tools is necessary in these challenging times.", "qid": 18, "docid": "8t8psk46", "rank": 41, "score": 0.7443612217903137}, {"content": "Title: Medical masks and Respirators for the Protection of Healthcare Workers from SARS-CoV-2 and other viruses Content: Abstract The use of medical masks and respirators as personal protective equipment is pivotal to reducing the level of biological hazard to which healthcare workers are exposed during the outbreak of highly diffusible pathogens, such as the recent novel coronavirus SARS-CoV-2. Unfortunately, during this pandemic, supplies are rapidly running out worldwide, with potential consequences for the rate of occupational infections. Also, knowledge about specific characteristics of respirators is of utmost importance to select the proper type according to the clinical setting. A wide variety of literature is available on the topic, but mostly based on Influenza viruses infection models. Clinical evidence on the use of respirators is poor and interest in the topic has not been constant over time. A better understanding of SARS-CoV-2 transmission is needed, together with high-quality clinical data on the use of respirators or alternative devices. Moreover, healthcare workers, regardless of their level of experience, should receive specific training. This review aims to summarize the available evidence on the use of medical masks and respirators in the context of viral infections, especially the current coronavirus disease 2019 (COVID-19).", "qid": 18, "docid": "86rb6hov", "rank": 42, "score": 0.742682695388794}, {"content": "Title: Mask use during COVID-19: A risk adjusted strategy() Content: In the context of Coronavirus Disease (2019) (COVID-19) cases globally, there is a lack of consensus across cultures on whether wearing face masks is an effective physical intervention against disease transmission. This study 1) illustrates transmission routes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); 2) addresses controversies surrounding the mask from perspectives of attitude, effectiveness, and necessity of wearing the mask with evidence that the use of mask would effectively interrupt the transmission of infectious diseases in both hospital settings and community settings; and 3) provides suggestion that the public should wear the mask during COVID-19 pandemic according to local context. To achieve this goal, government should establish a risk adjusted strategy of mask use to scientifically publicize the use of masks, guarantee sufficient supply of masks, and cooperate for reducing health resources inequities.", "qid": 18, "docid": "iaiosjlu", "rank": 43, "score": 0.742476224899292}, {"content": "Title: Mask use during COVID-19: A risk adjusted strategy Content: In the context of Coronavirus Disease (2019) (COVID-19) cases globally, there is a lack of consensus across cultures on whether wearing face masks is an effective physical intervention against disease transmission. This study 1) illustrates transmission routes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); 2) addresses controversies surrounding the mask from perspectives of attitude, effectiveness, and necessity of wearing the mask with evidence that the use of mask would effectively interrupt the transmission of infectious diseases in both hospital settings and community settings; and 3) provides suggestion that the public should wear the mask during COVID-19 pandemic according to local context. To achieve this goal, government should establish a risk adjusted strategy of mask use to scientifically publicize the use of masks, guarantee sufficient supply of masks, and cooperate for reducing health resources inequities.", "qid": 18, "docid": "6tod4abn", "rank": 44, "score": 0.742476224899292}, {"content": "Title: COVID-19: emerging protective measures Content: The COVID-19 (Coronavirus disease 2019) spreads primarily through droplets of saliva or discharge from the nose. COVID-19 is predominantly considered as an unavoidable pandemic, and scientists are very curious about how to provide the best protection to the public before a vaccine can be made available. There is an urge to manufacture a greater number of masks to prevent any aerosol with microbes. Hence, we aim to develop an efficient viral inactivation system by exploiting active compounds from naturally occurring medicinal plants and infusing them into nanofiber-based respiratory masks. Our strategy is to develop fibrous filtration with three-layered masks using the compounds from medicinal plants for viral deactivation. These masks will be beneficial not just to healthcare workers but common citizens as well. In the absence of vaccination, productive masks can be worn to prevent transmission of airborne pathogenic aerosols and control diseases.", "qid": 18, "docid": "qi8x5yaq", "rank": 45, "score": 0.7413923740386963}, {"content": "Title: COVID-19: emerging protective measures. Content: The COVID-19 (Coronavirus disease 2019) spreads primarily through droplets of saliva or discharge from the nose. COVID-19 is predominantly considered as an unavoidable pandemic, and scientists are very curious about how to provide the best protection to the public before a vaccine can be made available. There is an urge to manufacture a greater number of masks to prevent any aerosol with microbes. Hence, we aim to develop an efficient viral inactivation system by exploiting active compounds from naturally occurring medicinal plants and infusing them into nanofiber-based respiratory masks. Our strategy is to develop fibrous filtration with three-layered masks using the compounds from medicinal plants for viral deactivation. These masks will be beneficial not just to healthcare workers but common citizens as well. In the absence of vaccination, productive masks can be worn to prevent transmission of airborne pathogenic aerosols and control diseases.", "qid": 18, "docid": "tfrawa9z", "rank": 46, "score": 0.7413923740386963}, {"content": "Title: Who is wearing a mask? Gender-, age-, and location-related differences during the COVID-19 pandemic Content: Masks are an effective tool in combatting the spread of COVID-19 but wearing them remains controversial and has not been studied in the United States. To understand the demographics of mask wearers in the US, we observed shoppers (n = 5517) entering retail stores. 41.5% of the observed sample wore a mask. The odds of an individual wearing a mask increased significantly with age, and was also 1.5x greater for females than males. Additionally, the odds of observing a mask on an urban or suburban shopper were ~4x that for rural areas. Thus, gender, age, and location factor into whether American shoppers wear a mask or face covering. Regardless, all demographics wore masks at substantially lesser rates than required to stop the spread of COVID-19.", "qid": 18, "docid": "f4uh73j7", "rank": 47, "score": 0.7413651943206787}, {"content": "Title: The scientific rationale for the use of simple masks or improvised facial coverings to trap exhaled aerosols and possibly reduce the breathborne spread of COVID-19 Content: The medical community agrees that breathborne infectious materials can be spread with exhaled aerosols and that asymptomatic people, i.e., those showing no symptoms, could be unknowingly infectious. With the current worldwide pandemic of the respiratory coronavirus disease 2019 (COVID-19), various health bodies and governments are recommending that the population wear some form of mask or improvised facial covers while out in public in an effort to reduce the spread of disease . The general concept is that more accessible masks or mask-like materials (scarves, bandanas, etc.) could serve to reduce the amount of infectious aerosol from infected people, and reduce the viral load in the environment. This editorial addresses the underlying scientific rationale that such inexpensive or improvised could indeed serve to reduce the emissions of infectious aerosol by the mechanism of surface adhesion and particle kinetics in addition to the filtration effect.", "qid": 18, "docid": "m17j5u0y", "rank": 48, "score": 0.7411102056503296}, {"content": "Title: Risk of SARS-CoV-2 transmission by aerosols, the rational use of masks, and protection of healthcare workers from COVID-19 Content: OBJECTIVES: To determine the risk of SARS-CoV-2 transmission by aerosols, to provide evidence on the rational use of masks, and to discuss additional measures important for the protection of healthcare workers from COVID-19. METHODS: Literature review and expert opinion. SHORT CONCLUSION: SARS-CoV-2, the pathogen causing COVID-19, is considered to be transmitted via droplets rather than aerosols, but droplets with strong directional airflow support may spread further than 2 m. High rates of COVID-19 infections in healthcare-workers (HCWs) have been reported from several countries. Respirators such as filtering face piece (FFP) 2 masks were designed to protect HCWs, while surgical masks were originally intended to protect patients (e.g., during surgery). Nevertheless, high quality standard surgical masks (type II/IIR according to European Norm EN 14683) appear to be as effective as FFP2 masks in preventing droplet-associated viral infections of HCWs as reported from influenza or SARS. So far, no head-to-head trials with these masks have been published for COVID-19. Neither mask type completely prevents transmission, which may be due to inappropriate handling and alternative transmission pathways. Therefore, compliance with a bundle of infection control measures including thorough hand hygiene is key. During high-risk procedures, both droplets and aerosols may be produced, reason why respirators are indicated for these interventions.", "qid": 18, "docid": "9uxfxry4", "rank": 49, "score": 0.740676999092102}, {"content": "Title: Teach, and teach and teach: does the average citizen use masks correctly during daily activities? Results from an observational study with more than 12,000 participants Content: COVID-19 is a new disease with no treatment and no vaccine so far. The pandemic is still growing in many areas. Among the core measures to prevent disease spread is the use of face masks. We observed 12,588 people in five Brazilian cities within the Baixada Santista metropolitan area. Even though this is densely populated region and heavily impacted by COVID-19 with a high risk population, only 45.1% of the observed population wore in face masks in a correct way, and another 15.5% simply did not use masks at all. The remainder used masks incorrectly, which is evidence of the worst scenario of people believing that they are protected when they are not. This is among the first studies, to the best of our knowledge, that measures real life compliance with face masks during this COVID-19 pandemic. It is our conclusion that it is paramount to first control the virus before allowing people back in the streets. We should not assume that people will wear masks properly. Equally important is to instruct and sensitize people on how to use face masks and why it is important.", "qid": 18, "docid": "ej76fsxa", "rank": 50, "score": 0.7401399612426758}, {"content": "Title: Effectiveness of Cloth Masks for Protection Against Severe Acute Respiratory Syndrome Coronavirus 2 Content: Cloth masks have been used in healthcare and community settings to protect the wearer from respiratory infections. The use of cloth masks during the coronavirus disease (COVID-19) pandemic is under debate. The filtration effectiveness of cloth masks is generally lower than that of medical masks and respirators; however, cloth masks may provide some protection if well designed and used correctly. Multilayer cloth masks, designed to fit around the face and made of water-resistant fabric with a high number of threads and finer weave, may provide reasonable protection. Until a cloth mask design is proven to be equally effective as a medical or N95 mask, wearing cloth masks should not be mandated for healthcare workers. In community settings, however, cloth masks may be used to prevent community spread of infections by sick or asymptomatically infected persons, and the public should be educated about their correct use.", "qid": 18, "docid": "tcijnphu", "rank": 51, "score": 0.7400903701782227}, {"content": "Title: Effectiveness of Cloth Masks for Protection Against Severe Acute Respiratory Syndrome Coronavirus 2. Content: Cloth masks have been used in healthcare and community settings to protect the wearer from respiratory infections. The use of cloth masks during the coronavirus disease (COVID-19) pandemic is under debate. The filtration effectiveness of cloth masks is generally lower than that of medical masks and respirators; however, cloth masks may provide some protection if well designed and used correctly. Multilayer cloth masks, designed to fit around the face and made of water-resistant fabric with a high number of threads and finer weave, may provide reasonable protection. Until a cloth mask design is proven to be equally effective as a medical or N95 mask, wearing cloth masks should not be mandated for healthcare workers. In community settings, however, cloth masks may be used to prevent community spread of infections by sick or asymptomatically infected persons, and the public should be educated about their correct use.", "qid": 18, "docid": "xtraspw2", "rank": 52, "score": 0.7400903701782227}, {"content": "Title: To mask or not to mask children to overcome COVID-19 Content: It has been reported that asymptomatic people can transmit the new coronavirus disease 2019 (COVID-19) and become important sources of COVID-19. To reduce the role of asymptomatic or poorly symptomatic people in COVID-19, universal use of face masks in addition to hand hygiene and safety distance seems extremely useful. Consequently, preparing the healthy child to use face masks is strongly needed. To obtain maximal compliance, reasons for mask wearing without attempts of removing must be clearly explained. Moreover, child\u2019s will must not be forced. Conclusion: On the basis of clinical findings, we think that the universal use of facial masks seems necessary when people have to go out in their everyday lives. In addition to the availability of masks of different sizes capable of adapting perfectly to the face, it is necessary that the use of masks in children is preceded by a strong parental work and school lessons on this issue and other hygiene topics with the main aim to obtain child cooperation.", "qid": 18, "docid": "ahhrs3sy", "rank": 53, "score": 0.7396553754806519}, {"content": "Title: A Review of Current Interventions for COVID-19 Prevention Content: Abstract The recent outbreak of CoVID-19 is declared as a global public health emergency of international concern by the World Health Organization (WHO). A fresh figure of 2268011 positive cases and 155185 death records (till April 18th 2020) across the worldwide signify the severity of this viral infection. CoVID-19 infection is a pandemic, surface to surface communicable disease with a case fatality rate of 3.4% as estimated by WHO up to March 3rd 2020. Unfortunately, the current unavailability of an effective antiviral drug and approved vaccine, worsen the situation more critical. Implementation of an effective preventive measure is the only option left to counteract CoVID-19. Further, a retrospective analysis provides evidence that contemplates the decisive role of preventive measures in controlling severe acute respiratory syndrome (SARS) outbreak in 2003. A statistical surveillance report of WHO reflects, maintaining a coherent infection, prevention and control guideline resulted in a 30% reduction in healthcare-associated infections. The effectiveness of preventive measures completely relies on the strength of surface disinfectants, the composition of hand sanitizer, appropriate material for the manufacture of personal protective equipment (PPE). This review enlightens the various preventive measures such as a suitable selection of surface disinfectants, appropriate hand sanitization, and empowering the PPE that could be a potential intervention to fight against CoVID-19.", "qid": 18, "docid": "qud4bj12", "rank": 54, "score": 0.739323079586029}, {"content": "Title: Masking the general population might attenuate COVID-19 outbreaks Content: The effect of masking the general population on a COVID-19 epidemic is estimated by computer simulation using two separate state-of-the-art web-based softwares, one of them calibrated for the SARS-CoV-2 virus. The questions addressed are these: 1. Can mask use by the general population limit the spread of SARS-CoV-2 in a country? 2. What types of masks exist, and how elaborate must a mask be to be effective against COVID-19? 3. Does the mask have to be applied early in an epidemic? 4. A brief general discussion of masks and some possible future research questions regarding masks and SARS-CoV-2. Results are as follows: (1) The results indicate that any type of mask, even simple home-made ones, may be effective. Masks use seems to have an effect in lowering new patients even the protective effect of each mask (here dubbed\"one-mask protection\") is low. Strict adherence to mask use does not appear to be critical. However, increasing the one-mask protection to>50% was found to be advantageous. Masks seemed able to reduce overflow of capacity, e.g. of intensive care. As the default parameters of the software included another intervention, it seems possible to combine mask and other interventions. (2) Masks do seem to reduce the number of new cases even if introduced at a late stage in an epidemic. However, early implementation helps reduce the cumulative and total number of cases. (3) The simulations suggest that it might be possible to eliminate a COVID-19 outbreak by widespread mask use during a limited period. The results from these simulations are encouraging, but do not necessarily represent the real-life situation, so it is suggested that clinical trials of masks are now carried out while continuously monitoring effects and side-effects.", "qid": 18, "docid": "ugkxxaeb", "rank": 55, "score": 0.7393085956573486}, {"content": "Title: Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community Settings: A Living Rapid Review Content: BACKGROUND: Recommendations on masks for preventing coronavirus disease 2019 (COVID-19) vary. PURPOSE: To examine the effectiveness of N95, surgical, and cloth masks in community and health care settings for preventing respiratory virus infections, and effects of reuse or extended use of N95 masks. DATA SOURCES: Multiple electronic databases, including the World Health Organization COVID-19 database and medRxiv preprint server (2003 through 14 April 2020; surveillance through 2 June 2020), and reference lists. STUDY SELECTION: Randomized trials of masks and risk for respiratory virus infection, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and observational studies of mask use and coronavirus infection risk were included. New evidence will be incorporated by using living review methods. DATA EXTRACTION: One reviewer abstracted data and assessed methodological limitations; a second reviewer provided verification. DATA SYNTHESIS: 39 studies (18 randomized controlled trials and 21 observational studies; 33 867 participants) were included. No study evaluated reuse or extended use of N95 masks. Evidence on SARS-CoV-2 was limited to 2 observational studies with serious limitations. Community mask use was possibly associated with decreased risk for SARS-CoV-1 infection in observational studies. In high- or moderate-risk health care settings, observational studies found that risk for infection with SARS-CoV-1 and Middle East respiratory syndrome coronavirus probably decreased with mask use versus nonuse and possibly decreased with N95 versus surgical mask use. Randomized trials in community settings found possibly no difference between N95 versus surgical masks and probably no difference between surgical versus no mask in risk for influenza or influenza-like illness, but compliance was low. In health care settings, N95 and surgical masks were probably associated with similar risks for influenza-like illness and laboratory-confirmed viral infection; clinical respiratory illness had inconsistency. Bothersome symptoms were common. LIMITATIONS: There were few SARS-CoV-2 studies, observational studies have methodological limitations, and the review was done by using streamlined methods. CONCLUSION: Evidence on mask effectiveness for respiratory infection prevention is stronger in health care than community settings. N95 respirators might reduce SARS-CoV-1 risk versus surgical masks in health care settings, but applicability to SARS-CoV-2 is uncertain. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. Update Alerts: The authors have specified in the Methods section the interval and stop date for updates to this Living Review. As Annals receives updates, they will appear in the Comments section of the article on Annals.org. Reader inquiries about updates that are not available at approximately the specified intervals should be submitted as Comments to the article.", "qid": 18, "docid": "j0lpy07l", "rank": 56, "score": 0.7383792400360107}, {"content": "Title: Medical masks vs N95 respirators for preventing COVID-19 in healthcare workers: A systematic review and meta-analysis of randomized trials Content: BACKGROUND: Respiratory protective devices are critical in protecting against infection in healthcare workers at high risk of novel 2019 coronavirus disease (COVID-19); however, recommendations are conflicting and epidemiological data on their relative effectiveness against COVID-19 are limited. PURPOSE: To compare medical masks to N95 respirators in preventing laboratory-confirmed viral infection and respiratory illness including coronavirus specifically in healthcare workers. DATA SOURCES: MEDLINE, Embase, and CENTRAL from January 1, 2014, to March 9, 2020. Update of published search conducted from January 1, 1990, to December 9, 2014. STUDY SELECTION: Randomized controlled trials (RCTs) comparing the protective effect of medical masks to N95 respirators in healthcare workers. DATA EXTRACTION: Reviewer pair independently screened, extracted data, and assessed risk of bias and the certainty of the evidence. DATA SYNTHESIS: Four RCTs were meta-analyzed adjusting for clustering. Compared with N95 respirators; the use of medical masks did not increase laboratory-confirmed viral (including coronaviruses) respiratory infection (OR 1.06; 95% CI 0.90-1.25; I2 = 0%; low certainty in the evidence) or clinical respiratory illness (OR 1.49; 95% CI: 0.98-2.28; I2 = 78%; very low certainty in the evidence). Only one trial evaluated coronaviruses separately and found no difference between the two groups (P = .49). LIMITATIONS: Indirectness and imprecision of available evidence. CONCLUSIONS: Low certainty evidence suggests that medical masks and N95 respirators offer similar protection against viral respiratory infection including coronavirus in healthcare workers during non-aerosol-generating care. Preservation of N95 respirators for high-risk, aerosol-generating procedures in this pandemic should be considered when in short supply.", "qid": 18, "docid": "8khrecrf", "rank": 57, "score": 0.7379075884819031}, {"content": "Title: Associations between wearing masks, washing hands, and social distancing practices, and risk of COVID-19 infection in public: a cohort-based case-control study in Thailand Content: Objective. To investigate whether wearing masks, washing hands and social distancing practices are associated with lower risk of COVID-19 infection. Design. A retrospective cohort-based case-control study. All participants were retrospectively interviewed by phone about their preventive measures against COVID-19 infection. Setting. Thailand, using the data from contact tracing of COVID-19 patients associated with nightclub, boxing stadium and state enterprise office clusters from the Surveillance Rapid Response Team, Department of Disease Control, Ministry of Public Health. Contacts were tested for COVID-19 using PCR assays per national contact tracing guidelines. Participants. A cohort of 1,050 asymptomatic contacts of COVID-19 patients between 1 and 31 March 2020. Main outcome measures. Diagnosis of COVID-19 by 21 April 2020. Odds ratios for COVID-19 infection and population attributable fraction were calculated. Exposure. The study team retrospectively asked about wearing masks, washing hands, and social distancing practices during the contact period through telephone interviews. Results. Overall, 211 (20%) were diagnosed with COVID-19 by 21 Apr 2020 (case group) while 839 (80%) were not (control group). Fourteen percent of cases (29/210) and 24% of controls (198/823) reported wearing either non-medical or medical masks all the time during the contact period. Wearing masks all the time (adjusted odds ratio [aOR] 0.23; 95%CI 0.09-0.60) was associated with lower risk of COVID-19 infections compared to not wearing masks, while wearing masks sometimes (aOR 0.87; 95%CI 0.41-1.84) was not. Shortest distance of contact >1 meter (aOR 0.15; 95%CI 0.04-0.63), duration of close contact [\u2264]15 minutes (aOR 0.24; 95%CI 0.07-0.90) and washing hands often (aOR 0.33; 95%CI 0.13-0.87) were significantly associated with lower risk of infection. Sharing a cigarette (aOR 3.47; 95%CI 1.09-11.02) was associated with higher risk of infection. Type of mask was not independently associated with risk of infection. Those who wore masks all the time were more likely to wash hands and practice social distancing. We estimated that if everyone wore a mask all the time, washed hands often, did not share a dish, cup or cigarette, had shortest distance of contact >1 meter and had duration of close contact [\u2264]15 minutes, cases would have been reduced by 84%. Conclusions. Our findings support consistently wearing non-medical masks, washing hands, and social distancing in public to prevent COVID-19 infections.", "qid": 18, "docid": "l8y9r8cp", "rank": 58, "score": 0.7379055023193359}, {"content": "Title: Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community Settings: A Living Rapid Review Content: BACKGROUND: Recommendations on masks for preventing coronavirus disease 2019 (COVID-19) vary. PURPOSE: To examine the effectiveness of N95, surgical, and cloth masks in community and health care settings for preventing respiratory virus infections, and effects of reuse or extended use of N95 masks. DATA SOURCES: Multiple electronic databases, including the World Health Organization COVID-19 database and medRxiv preprint server (2003 through 14 April 2020; surveillance through 2 June 2020), and reference lists. STUDY SELECTION: Randomized trials of masks and risk for respiratory virus infection, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and observational studies of mask use and coronavirus infection risk were included. New evidence will be incorporated by using living review methods. DATA EXTRACTION: One reviewer abstracted data and assessed methodological limitations; a second reviewer provided verification. DATA SYNTHESIS: 39 studies (18 randomized controlled trials and 21 observational studies; 33 867 participants) were included. No study evaluated reuse or extended use of N95 masks. Evidence on SARS-CoV-2 was limited to 2 observational studies with serious limitations. Community mask use was possibly associated with decreased risk for SARS-CoV-1 infection in observational studies. In high- or moderate-risk health care settings, observational studies found that risk for infection with SARS-CoV-1 and Middle East respiratory syndrome coronavirus probably decreased with mask use versus nonuse and possibly decreased with N95 versus surgical mask use. Randomized trials in community settings found possibly no difference between N95 versus surgical masks and probably no difference between surgical versus no mask in risk for influenza or influenza-like illness, but compliance was low. In health care settings, N95 and surgical masks were probably associated with similar risks for influenza-like illness and laboratory-confirmed viral infection; clinical respiratory illness had inconsistency. Bothersome symptoms were common. LIMITATIONS: There were few SARS-CoV-2 studies, observational studies have methodological limitations, and the review was done by using streamlined methods. CONCLUSION: Evidence on mask effectiveness for respiratory infection prevention is stronger in health care than community settings. N95 respirators might reduce SARS-CoV-1 risk versus surgical masks in health care settings, but applicability to SARS-CoV-2 is uncertain. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.", "qid": 18, "docid": "kshjqsdj", "rank": 59, "score": 0.7375727295875549}, {"content": "Title: Analysis of national and international guidelines on respiratory protection equipment for COVID-19 in healthcare settings. Content: Introduction Consistent guidelines on respiratory protection for healthcare professionals combined with improved global supply chains are critical to protect staff and patients from COVID-19. We summarized and compared the guidelines published by national and international societies/organizations on facemasks and respirators to prevent COVID-19 in healthcare settings. Methods From the 1st January to the 2nd April 2020, guidelines published in four countries (France, Germany, United States, United Kingdom), and two international organizations (US and European Center for Diseases Control, and World Health Organization) were reviewed to analyze the mask and respirators recommended as PPE for the care of patients during the COVID-19 outbreak. Guidelines were eligible for analysis if they (1) included specific guidelines, (2) were written for HCP protection, (3) targeting healthcare settings. The strategy recommended for optimizing supplies and overcoming shortages was collected. Observations The guidelines publication process on respiratory protections varied greatly across countries. Some referred to a unique guide whereas others saw the issue of multiple recommendations by various societies and organization. In term of chronology, most guidelines were published in March with either downgraded (US and European CDC), relatively stable (WHO, Germany, and UK), or a mixing of high and low level equipment (France). The recommendation of respirators was universally recommended for aerosol generating procedures (AGP) across countries, although the type of respirators and what constituted an AGP was variable. Some guidance maintained the use of N95/99 for all contact with confirmed COVID-19 cases (i.e. Germany) whereas others, recommended a surgical mask (i.e. WHO, UK, France). The strategies to overcome shortage of respiratory protection equipment were based on minimizing the need and rationalizing the use, but also prolonging their use, reusing them after cleaning/sterilization, or using cloth masks. Conclusions Stable and consistent guidelines inside and across countries, clearly detailing the respiratory protection type, and the circumstances in which they need to be used may prevent the confusion among frontline staff, and avoid shortage.", "qid": 18, "docid": "wahcfox7", "rank": 60, "score": 0.7363379001617432}, {"content": "Title: A Review of Current Interventions for COVID-19 Prevention Content: The recent outbreak of CoVID-19 is declared as a global public health emergency of international concern by the World Health Organization (WHO). A fresh figure of 2268011 positive cases and 155185 death records (till April 18th 2020) across the worldwide signify the severity of this viral infection. CoVID-19 infection is a pandemic, surface to surface communicable disease with a case fatality rate of 3.4% as estimated by WHO up to March 3rd 2020. Unfortunately, the current unavailability of an effective antiviral drug and approved vaccine, worsen the situation more critical. Implementation of an effective preventive measure is the only option left to counteract CoVID-19. Further, a retrospective analysis provides evidence that contemplates the decisive role of preventive measures in controlling severe acute respiratory syndrome (SARS) outbreak in 2003. A statistical surveillance report of WHO reflects, maintaining a coherent infection, prevention and control guideline resulted in a 30% reduction in healthcare-associated infections. The effectiveness of preventive measures completely relies on the strength of surface disinfectants, the composition of hand sanitizer, appropriate material for the manufacture of personal protective equipment (PPE). This review enlightens the various preventive measures such as a suitable selection of surface disinfectants, appropriate hand sanitization, and empowering the PPE that could be a potential intervention to fight against CoVID-19.", "qid": 18, "docid": "xfwseuxu", "rank": 61, "score": 0.7363256216049194}, {"content": "Title: [Management and prevention of common skin problems during epidemic prevention and control of COVID-19] Content: In the ongoing fight against the epidemic of COVID-19, the medical staff has been under tremendous pressure. Wearing the protective equipment (masks, goggles, and protective screens) with a poor breathability for a long time causes various skin problems, such as allergies, excessive skin hydration, local mechanical injuries, and even secondary infections. In addition, in a closed environment, compression and friction aggravate skin reactions, which may compromise duty performance of the medical staff. It is therefore essential to provide timely treatment opinions and prevention methods for common skin problems. We also give suggestions concerning the preparation of medical kit for skin protection in the epidemic area.", "qid": 18, "docid": "c7lt52b4", "rank": 62, "score": 0.7358130812644958}, {"content": "Title: [Management and prevention of common skin problems during epidemic prevention and control of COVID-19]. Content: In the ongoing fight against the epidemic of COVID-19, the medical staff has been under tremendous pressure. Wearing the protective equipment (masks, goggles, and protective screens) with a poor breathability for a long time causes various skin problems, such as allergies, excessive skin hydration, local mechanical injuries, and even secondary infections. In addition, in a closed environment, compression and friction aggravate skin reactions, which may compromise duty performance of the medical staff. It is therefore essential to provide timely treatment opinions and prevention methods for common skin problems. We also give suggestions concerning the preparation of medical kit for skin protection in the epidemic area.", "qid": 18, "docid": "8zn56jem", "rank": 63, "score": 0.7358130812644958}, {"content": "Title: Is wearing a face mask safe for people with epilepsy? Content: Since December 2019, the world has been experiencing a catastrophic pandemic of coronavirus disease (COVID-19) caused by SARS-CoV2. This virus primarily targets the human respiratory system. Available information suggests that people with epilepsy (PWE) are not at higher risk of being infected by the virus, nor of more severe COVID-19 manifestations, as a result of the epilepsy alone. However, COVID-19 is a serious disease that currently has no effective treatment or vaccine. A face mask is probably effective in preventing the spread of a respiratory pathogen, at least to some extent. So, should we recommend wearing a face mask to all during a pandemic of respiratory infectious disease (e.g., COVID-19) without any precautions or exemptions? While concrete evidence is lacking, if we consider that wearing a face mask may simulate hyperventilation, at least to some extent, we would probably avoid recommending this practice indiscriminately to all PWE. On the other hand, in the absence of any proven treatment or vaccine to combat COVID-19, prevention is the best available strategy and it is probably not reasonable to suggest avoid wearing face masks in PWE under any circumstances. Logically, PWE do not need to wear a face mask most of the time, as long as there is no close contact with others, especially during intense physical activities such as exercise. To the contrary, it is probably more advantageous to wear a face mask in crowded locations, with intermittent breaks in safe locations, away from others.", "qid": 18, "docid": "lq7bh1sl", "rank": 64, "score": 0.7349231839179993}, {"content": "Title: Would everyone wearing face masks help us slow the pandemic? Content: As cases of coronavirus disease 2019 (COVID-19) ballooned last month, people in Europe and North America scrambled to get their hands on surgical masks to protect themselves Health officials jumped in to discourage them, worried about the limited supply of masks for health care personnel \u201cSeriously people-STOP BUYING MASKS!\u201d began a 29 February tweet from U S Surgeon General Jerome Adams The World Health Organization and U S Centers for Disease Control and Prevention (CDC) have both said that only people with COVID-19 symptoms and those caring for them should wear masks But some health experts, including the director of the Chinese Center for Disease Control and Prevention, think that\u2019s a mistake Health authorities in parts of Asia have encouraged all citizens to wear masks in public to prevent the spread of the virus, regardless of whether they have symptoms And the Czech Republic took the uncommon step last week of making nose and mouth coverings mandatory in public spaces, prompting a grassroots drive to hand make masks", "qid": 18, "docid": "ydazitgp", "rank": 65, "score": 0.7341209053993225}, {"content": "Title: Can wearing face masks in public affect transmission route and viral load in COVID-19? Content: The mandatory face mask wearing was implemented in the Czech Republic and Slovakia shortly after the COVID-19 outbreak in Central Europe. So far, the number of COVID-19-associated deaths per 100,000 individuals is far lower in these countries as compared with other neighbouring or close countries. The use of face masks in public may not protect the general public from contracting the virus, however, presumptively decreases the viral load and contributes to a favourable clinical outcome in COVID-19 disease. A certain time is required for antigen-specific T cells and B cells to fully develop. Obligatory face mask wearing in public favours the virus transmission through oral mucosa and/or conjunctival epithelium, which enables the adaptive immune responses to evolve. In the case of inhalation of high loads of SARS-CoV-2, the time for the development of fully protective adaptive immune responses seems to be insufficient. Then, a less specific and more damaging innate immune response prevails.", "qid": 18, "docid": "p93u753c", "rank": 66, "score": 0.7339260578155518}, {"content": "Title: Medical masks vs N95 respirators for preventing COVID\u201019 in healthcare workers: A systematic review and meta\u2010analysis of randomized trials Content: BACKGROUND: Respiratory protective devices are critical in protecting against infection in healthcare workers at high risk of novel 2019 coronavirus disease (COVID\u201019); however, recommendations are conflicting and epidemiological data on their relative effectiveness against COVID\u201019 are limited. PURPOSE: To compare medical masks to N95 respirators in preventing laboratory\u2010confirmed viral infection and respiratory illness including coronavirus specifically in healthcare workers. DATA SOURCES: MEDLINE, Embase, and CENTRAL from January 1, 2014, to March 9, 2020. Update of published search conducted from January 1, 1990, to December 9, 2014. STUDY SELECTION: Randomized controlled trials (RCTs) comparing the protective effect of medical masks to N95 respirators in healthcare workers. DATA EXTRACTION: Reviewer pair independently screened, extracted data, and assessed risk of bias and the certainty of the evidence. DATA SYNTHESIS: Four RCTs were meta\u2010analyzed adjusting for clustering. Compared with N95 respirators; the use of medical masks did not increase laboratory\u2010confirmed viral (including coronaviruses) respiratory infection (OR 1.06; 95% CI 0.90\u20101.25; I (2) = 0%; low certainty in the evidence) or clinical respiratory illness (OR 1.49; 95% CI: 0.98\u20102.28; I (2) = 78%; very low certainty in the evidence). Only one trial evaluated coronaviruses separately and found no difference between the two groups (P = .49). LIMITATIONS: Indirectness and imprecision of available evidence. CONCLUSIONS: Low certainty evidence suggests that medical masks and N95 respirators offer similar protection against viral respiratory infection including coronavirus in healthcare workers during non\u2013aerosol\u2010generating care. Preservation of N95 respirators for high\u2010risk, aerosol\u2010generating procedures in this pandemic should be considered when in short supply.", "qid": 18, "docid": "1aqf98e0", "rank": 67, "score": 0.7336246371269226}, {"content": "Title: What face mask for what use in the context of COVID-19 pandemic? The French guidelines Content: Summary In the context of the COVID-19 pandemic, wearing a face mask has become usual and ubiquitous, in both hospitals and community. However, the general public is consuming surgical or filtering face piece (FFP) masks irrespective of their specificity, leading to global supply shortage for the most exposed persons, which are healthcare workers. This underlines the urgent need to clarify the indications of the different categories of mask, in order to rationalize their use. The study herein specifies the French position for the rational use of respiratory protective equipment for healthcare workers.", "qid": 18, "docid": "4mx9t5td", "rank": 68, "score": 0.7334955930709839}, {"content": "Title: Progress and Perspective of Antiviral Protective Material Content: Public health events caused by viruses pose a significant risk to humans worldwide. From December 2019 till now, the rampant novel 2019 coronavirus (SAR-CoV-2) has hugely impacted China and over world. Regarding a commendable means of protection, mask technology is relatively mature, though most of the masks cannot effectively resist the viral infections. The key material of the mask is a non-woven material, which makes the barrier of virus through filtration. Due to the lack of the ability to kill the viruses, masks are prone to cross-infection and become an additional source of infection after being discarded. If the filteration and antiviral effects can be simultaneously integrated into the mask, it will be more effcient, work for a longer time and create less difficulty in post-treatment. This mini-review presents the advances in antiviral materials, different mechanisms of their activity, and their potential applications in personal protective fabrics. Furthermore, the article addresses the future challenges and directions of mask technology.", "qid": 18, "docid": "18crkfzj", "rank": 69, "score": 0.7326931953430176}, {"content": "Title: The use of facemasks by the general population to prevent transmission of Covid 19 infection: A systematic review. Content: Background The pandemic of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), has become a serious worldwide public health emergency. This systematic review aims to summarize the available evidence regarding the role of face mask in community settings in slowing the spread of respiratory viruses such as SARS- CoV-2. Methods The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used for this review. A literature search using PUBMED, Google Scholar, and Cochrane database were performed using Medical subject heading (MeSH) words from the year 2000-2020. The articles focused on the use of masks and N95 respirators in healthcare workers were excluded. Results A total of 305 records were identified, out of which 14 articles were included in the review based upon quality and eligibility criteria. All the articles mentioned about the role of face masks in preventing the spread of respiratory viruses like influenza, SARS, and SARS-CoV-2, in the community or experimental setting. Studies also suggested that early initiation of face mask usage was more effective. Masks were also reported to be more effective in viruses that transmit easily from asymptomatic individuals, as is now known in SARS-CoV-2. Conclusion Theoretical, experimental, and clinical evidence suggested that usage of face masks in a general population offered significant benefit in preventing the spread of respiratory viruses especially in the pandemic situation, but its utility is limited by inconsistent adherence to mask usage.", "qid": 18, "docid": "f7rcijh4", "rank": 70, "score": 0.731975793838501}, {"content": "Title: Revisi\u00f3n r\u00e1pida del uso de cubrebocas quir\u00fargicos en \u00e1mbito comunitario e infecciones respiratorias agudas./ [Rapid review of the use of community-wide surgical masks and acute respiratory infections] Content: OBJECTIVE: To assess the effectiveness of using surgical masks in community settings to reduce the probability of infection by SARS-CoV-2 or other acute viral respiratory infection, compared to not using surgical masks. MATERIALS AND METHODS: We followed the Cochrane rapid review methodology. The search strategy encompasses one academic database and pre-prints until April 1, 2020. Titles and abstracts were reviewed by one investigator. The full text review was divided among three researchers. The results were synthesized in a narrative way. RESULTS: 713 manuscripts were identified, of which 21 met the inclusion criteria. Of six systematic reviews, four found no reduction in the probability of transmission. Experimental home studies found no differences in the probability of contagion associated with the use of mouth masks. Only one modeling study estimated a 20% reduction in the incidence of acute respiratory disease, assuming that 10 to 50% of the population use the surgical masks correctly. CONCLUSIONS: The scientific evidence is inconclusive to recommend or discourage the use of surgical masks at the population level. Considering the potential negative effects, official recommendations should await for the results of natural experiments currently occurring in countries that have recommended the use of face masks at the population level.", "qid": 18, "docid": "gy9u32i2", "rank": 71, "score": 0.7318649291992188}, {"content": "Title: [RISK ASSESSMENT FOR AEROSOL INFECTION BY THE NEW CORONA VIRUS AND PROTECTION BY RESPIRATORS]. Content: INTRODUCTION SARS-CoV-2 is dispersed from patients by talking, coughing and sneezing. The generated micro-droplets aerosols can travel up to 8 meters, stay suspended for long periods and preserve viral infectivity for a median of 2.7 hours. An unprotected person exposed to this cloud, might inhale a considerable amount of infectious viral doses, which will attach to the ACE 2 receptors on alveoli epithelium, resulting in infection. N95 respirators and surgical masks block 95% and 50-60% respectively of inhalable particles and protect the wearer from infection. Surgical masks and N95 without exhalation valve, protect both the wearer and the environment from carriers and sick people.", "qid": 18, "docid": "k47m3e92", "rank": 72, "score": 0.7310981154441833}, {"content": "Title: Virus transmission during orthopedic surgery on patients with COVID-19 - a brief narrative review Content: Background and purpose - COVID-19 is among the most impactful pandemics that the society has experienced. Orthopedic surgery involves procedures generating droplets and aerosols and there is concern amongst surgeons that otherwise rational precautionary principles are being set aside due to lack of scientific evidence and a shortage of personal protective equipment (PPE). This narrative review attempts to translate relevant knowledge into practical recommendations for healthcare workers involved in orthopedic surgery on patients with known or suspected COVID-19.Patients and methods - We unsystematically searched in PubMed, reference lists, and the WHO's web page for relevant publications concerning problems associated with the PPE used in perioperative practice when a patient is COVID-19 positive or suspected to be. A specific search for literature regarding COVID-19 was extended to include publications from the SARS epidemic in 2002/3.Results - Transmission of infectious viruses from patient to surgeon during surgery is possible, but does not appear to be a considerable problem in clinical practice. Seal-leakage is a problem with surgical masks. Due to the lack of studies and reports, the possibility of transmission of SARS-CoV-2 from patient to surgeon during droplet- and aerosol-generating procedures is unknown.Interpretation - Surgical masks should be used only in combination with a widely covering visor and when a respirator (N95, FFP2, P3) is not made available. Furthermore, basic measures to reduce shedding of droplets and aerosols during surgery and correct and consistent use of personal protective equipment is important.", "qid": 18, "docid": "ll4azyq7", "rank": 73, "score": 0.7309659719467163}, {"content": "Title: Virus transmission during orthopedic surgery on patients with COVID-19 - a brief narrative review. Content: Background and purpose - COVID-19 is among the most impactful pandemics that the society has experienced. Orthopedic surgery involves procedures generating droplets and aerosols and there is concern amongst surgeons that otherwise rational precautionary principles are being set aside due to lack of scientific evidence and a shortage of personal protective equipment (PPE). This narrative review attempts to translate relevant knowledge into practical recommendations for healthcare workers involved in orthopedic surgery on patients with known or suspected COVID-19.Patients and methods - We unsystematically searched in PubMed, reference lists, and the WHO's web page for relevant publications concerning problems associated with the PPE used in perioperative practice when a patient is COVID-19 positive or suspected to be. A specific search for literature regarding COVID-19 was extended to include publications from the SARS epidemic in 2002/3.Results - Transmission of infectious viruses from patient to surgeon during surgery is possible, but does not appear to be a considerable problem in clinical practice. Seal-leakage is a problem with surgical masks. Due to the lack of studies and reports, the possibility of transmission of SARS-CoV-2 from patient to surgeon during droplet- and aerosol-generating procedures is unknown.Interpretation - Surgical masks should be used only in combination with a widely covering visor and when a respirator (N95, FFP2, P3) is not made available. Furthermore, basic measures to reduce shedding of droplets and aerosols during surgery and correct and consistent use of personal protective equipment is important.", "qid": 18, "docid": "huxbyvfd", "rank": 74, "score": 0.7309659719467163}, {"content": "Title: [risk Assessment for Aerosol Infection by the New Corona Virus and Protection by Respirators] Content: INTRODUCTION: SARS-CoV-2 is dispersed from patients by talking, coughing and sneezing. The generated micro-droplets aerosols can travel up to 8 meters, stay suspended for long periods and preserve viral infectivity for a median of 2.7 hours. An unprotected person exposed to this cloud, might inhale a considerable amount of infectious viral doses, which will attach to the ACE 2 receptors on alveoli epithelium, resulting in infection. N95 respirators and surgical masks block 95% and 50-60% respectively of inhalable particles and protect the wearer from infection. Surgical masks and N95 without exhalation valve, protect both the wearer and the environment from carriers and sick people.", "qid": 18, "docid": "xlsqikjt", "rank": 75, "score": 0.7308377623558044}, {"content": "Title: Silk fabric as a protective barrier for personal protective equipment and as a functional material for face coverings during the COVID-19 pandemic Content: Background The worldwide shortage of single-use N95 respirators and surgical masks due to the COVID-19 pandemic has forced many health care personnel to prolong the use of their existing equipment as much as possible. In many cases, workers cover respirators with available masks in an attempt to extend their effectiveness against the virus. Due to low mask supplies, many people instead are using face coverings improvised from common fabrics. Our goal was to determine what fabrics would be most effective in both practices. Methods and findings We examined the hydrophobicity of fabrics (silk, cotton, polyester), as measured by their resistance to the penetration of small and aerosolized water droplets, an important transmission avenue for the virus causing COVID-19. We also examined the breathability of these fabrics and their ability to maintain hydrophobicity despite undergoing repeated cleaning. Tests were done when fabrics were fashioned as an overlaying barrier and also when constructed as do-it-yourself face coverings. As a protective barrier and face covering, silk is more effective at impeding the penetration and absorption of droplets due to its greater hydrophobicity relative to other tested fabrics. Silk face coverings repelled droplets as well as masks, but unlike masks they are hydrophobic and can be readily sterilized for immediate reuse. Conclusions Silk is an effective hydrophobic barrier to droplets, more breathable than other fabrics that trap humidity, and are readily re-useable via cleaning. Therefore, silk can serve as an effective material for protecting respirators under clinical conditions and as a material for face coverings.", "qid": 18, "docid": "akffx93g", "rank": 76, "score": 0.7304690480232239}, {"content": "Title: Can Masks Be Reused After Hot Water Decontamination During the COVID-19 Pandemic? Content: Masks have become one of the most indispensable pieces of personal protective equipment and are important strategic products during the coronavirus disease 2019 (COVID-19) pandemic. Due to the huge mask demand\u2013supply gap all over the world, the development of user-friendly technologies and methods is urgently needed to effectively extend the service time of masks. In this article, we report a very simple approach for the decontamination of masks for multiple reuse during the COVID-19 pandemic. Used masks were soaked in hot water at a temperature greater than 56 \u00b0C for 30 min, based on a recommended method to kill COVID-19 virus by the National Health Commission of the People\u2019s Republic of China. The masks were then dried using an ordinary household hair dryer to recharge the masks with electrostatic charge to recover their filtration function (the so-called \u201chot water decontamination + charge regeneration\u201d method). Three kinds of typical masks (disposable medical masks, surgical masks, and KN95-grade masks) were treated and tested. The filtration efficiencies of the regenerated masks were almost maintained and met the requirements of the respective standards. These findings should have important implications for the reuse of polypropylene masks during the COVID-19 pandemic. The performance evolution of masks during human wear was further studied, and a company (Zhejiang Runtu Co., Ltd.) applied this method to enable their workers to extend the use of masks. Mask use at the company was reduced from one mask per day per person to one mask every three days per person, and 122 500 masks were saved during the period from 20 February to 30 March 2020. Furthermore, a new method for detection of faulty masks based on the penetrant inspection of fluorescent nanoparticles was established, which may provide scientific guidance and technical methods for the future development of reusable masks, structural optimization, and the formulation of comprehensive performance evaluation standards.", "qid": 18, "docid": "oyxkzzs8", "rank": 77, "score": 0.7299683094024658}, {"content": "Title: What face mask for what use in the context of COVID-19 pandemic? The French guidelines Content: In the context of the COVID-19 pandemic, wearing a face mask has become usual and ubiquitous, in both hospitals and community. However, the general public is consuming surgical or filtering face piece (FFP) masks irrespective of their specificity, leading to global supply shortage for the most exposed persons, which are healthcare workers. This underlines the urgent need to clarify the indications of the different categories of mask, in order to rationalize their use. The study herein specifies the French position for the rational use of respiratory protective equipment for healthcare workers.", "qid": 18, "docid": "ndy59p5p", "rank": 78, "score": 0.7295858860015869}, {"content": "Title: Waste Not, Want Not: Re-Usability of N95 Masks Content: As the spread of COVID-19 illnesses continues to escalate amidst a substandard supply of protective equipment for health care providers, the question of extended use or reuse of N95 masks has emerged. As well, the relative effectiveness of the N95 compared to other mask types have been entertained. A recent article by Abd-Elsayed and Karri aim to put these topics into focus. Additionally, personal correspondence between Drs. Richard Prielipp (University of Minnesota Department of Anesthesiology) and Peter Tsai (inventor of the N95 mask) offers perspectives on managing the reuse of this central element of protective equipment.", "qid": 18, "docid": "u6vpa1ih", "rank": 79, "score": 0.72929447889328}, {"content": "Title: [Rapid review of the use of community-wide surgical masks and acute respiratory infections]. Content: OBJECTIVE To assess the effectiveness of using surgical masks in community settings to reduce the probability of infection by SARS-CoV-2 or other acute viral respiratory infection, compared to not using surgical masks. MATERIALS AND METHODS We followed the Cochrane rapid review methodology. The search strategy encompasses one academic database and pre-prints until April 1, 2020. Titles and abstracts were reviewed by one investigator. The full text review was divided among three researchers. The results were synthesized in a narrative way. RESULTS 713 manuscripts were identified, of which 21 met the inclusion criteria. Of six systematic reviews, four found no reduction in the probability of transmission. Experimental home studies found no differences in the probability of contagion associated with the use of mouth masks. Only one modeling study estimated a 20% reduction in the incidence of acute respiratory disease, assuming that 10 to 50% of the population use the surgical masks correctly. CONCLUSIONS The scientific evidence is inconclusive to recommend or discourage the use of surgical masks at the population level. Considering the potential negative effects, official recommendations should await for the results of natural experiments currently occurring in countries that have recommended the use of face masks at the population level.", "qid": 18, "docid": "1r6eg1hh", "rank": 80, "score": 0.7292839884757996}, {"content": "Title: Testing for coverage from personal protective equipment: Public Health England's guidance does not protect healthcare workers from droplet spray. Content: In order to reduce transmission of the SARS-CoV-2 virus, healthcare workers in the UK are advised to wear personal protective equipment (PPE). When undertaking aerosol-generating procedures, Public Health England recommends the use of gloves, gown, filtering mask and full-face visor or goggles . Despite this, uncertainty remains regarding the role of some items of PPE, such as hoods and visors .", "qid": 18, "docid": "sf4vkrnw", "rank": 81, "score": 0.728829026222229}, {"content": "Title: The history and value of face masks Content: In the human population, social contacts are a key for transmission of bacteria and viruses. The use of face masks seems to be critical to prevent the transmission of SARS-CoV-2 for the period, in which therapeutic interventions are lacking. In this review, we describe the history of masks from the middle age to modern times.", "qid": 18, "docid": "jyju71r1", "rank": 82, "score": 0.7286468148231506}, {"content": "Title: Masks and closed-loop ventilators prevent environmental contamination by COVID-19 patients in negative-pressure environments Content: Herein, we report that nosocomial infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be mitigated by using surgical masks and closed looped ventilation for both non-critical and critical patients. These preventive measures resulted in no viral contamination of surfaces in negative pressure environments.", "qid": 18, "docid": "7r9lcw7c", "rank": 83, "score": 0.7276929616928101}, {"content": "Title: Masks and closed-loop ventilators prevent environmental contamination by COVID-19 patients in negative-pressure environments Content: Abstract Herein, we report that nosocomial infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be mitigated by using surgical masks and closed looped ventilation for both non-critical and critical patients. These preventive measures resulted in no viral contamination of surfaces in negative pressure environments.", "qid": 18, "docid": "q5egb5nz", "rank": 84, "score": 0.7268790602684021}, {"content": "Title: How to Produce Cheap and Easy Custom-Made Sterilizable Filtering Facepiece 2/3 Masks for Healthcare Providers During Pandemic COVID-19 Emergency Content: On January 8, 2020, a novel coronavirus was officially announced as the causative pathogen of coronavirus disease (COVID-19) by the Chinese Center for Disease Control and Prevention.On February 26, COVID-19 has been recognized in 34 countries, with a total of 80,239 laboratory-confirmed patients and 2700 deaths.Protecting healthcare workers from infectious hazards is paramount to ensuring their safety in delivering health care.In addition, being able to protect healthcare workers, constituting the front-line response against high-threat respiratory pathogens, such as severe acute respiratory syndrome coronavirus 2, is important for reducing secondary transmission in healthcare-associated outbreaks.Authors present a simple, reliable, and cheap protocol to produce a custom-made sterilizable filtering facepiece 2/3 masks for healthcare providers during pandemic COVID-19 emergency.", "qid": 18, "docid": "2w05l8r6", "rank": 85, "score": 0.7267948389053345}, {"content": "Title: How to Produce Cheap and Easy Custom-Made Sterilizable Filtering Facepiece 2/3 Masks for Healthcare Providers During Pandemic COVID-19 Emergency. Content: On January 8, 2020, a novel coronavirus was officially announced as the causative pathogen of coronavirus disease (COVID-19) by the Chinese Center for Disease Control and Prevention.On February 26, COVID-19 has been recognized in 34 countries, with a total of 80,239 laboratory-confirmed patients and 2700 deaths.Protecting healthcare workers from infectious hazards is paramount to ensuring their safety in delivering health care.In addition, being able to protect healthcare workers, constituting the front-line response against high-threat respiratory pathogens, such as severe acute respiratory syndrome coronavirus 2, is important for reducing secondary transmission in healthcare-associated outbreaks.Authors present a simple, reliable, and cheap protocol to produce a custom-made sterilizable filtering facepiece 2/3 masks for healthcare providers during pandemic COVID-19 emergency.", "qid": 18, "docid": "y5dalgsz", "rank": 86, "score": 0.7267948389053345}, {"content": "Title: The use of exhaled nitric oxide and peak expiratory flow to demonstrate improved breathability and antimicrobial properties of novel face mask made with sustainable filter paper and Folium Plectranthii amboinicii oil: additional option for mask shortage during COVID-19 pandemic Content: BACKGROUND: Medical face masks are integral personal protective equipment against infectious airborne disease and become scarce during epidemic outbreaks such as COVID-19. A novel, sustainably manufactured face mask with antimicrobial and anti-inflammatory properties from oil of Folium Plectranthii amboinicii can be an effective alternative to internationally sold masks. METHODS: This prospective, randomized study assigned subjects (n=67) to either conventional surgical face mask or Lamdong Medical College (LMC) face mask for three hours. Fractional concentration of nitric oxide in exhaled breath (FE(NO)) and peak expiratory flow (PEF) was measured before and after mask use. Subjective reporting on respiratory symptoms was also analyzed. Masks were then incubated and analyzed for microorganism growth. RESULTS: Subjects assigned the LMC mask had a lowered FE(NO) (p<0.05) compared to conventional face masks after mask wearing. Subjects with LMC mask use reported higher comfortability (p<0.05), breathability (p<0.05), and lower allergy symptoms (p<0.05). The LMC mask has visually less microorganism growth in the cultured medium, measured by sterile ring radius. CONCLUSIONS: The LMC face mask is a renewably manufactured personal protective tool with antibacterial capacity that can serve as an effective alternative to internationally sold surgical face mask during shortage of mask due to COVID-19.", "qid": 18, "docid": "gocycb7u", "rank": 87, "score": 0.7259585857391357}, {"content": "Title: Efficacy of face mask in preventing respiratory virus transmission: A systematic review and meta-analysis Content: BACKGROUND: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. RESULTS: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24-0.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11-0.37) and 47% (OR = 0.53, 95% CI = 0.36-0.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials and observational studies. CONCLUSIONS: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak.", "qid": 18, "docid": "b4znk2wr", "rank": 88, "score": 0.7258694171905518}, {"content": "Title: Why N95 Should Be the Standard for All COVID-19 Inpatient Care Content: Guidelines differ in their guidance on the use of N95 respirators versus medical masks for frontline health care workers working with patients with COVID-19, particularly when aerosolized procedures are not involved. This article makes the case that the existing data are inconclusive regarding the comparative effectiveness of N95 versus medical masks and could be misinterpreted. The authors suggest a reevaluation of this evidence or acknowledgement of these deficiencies in the setting of guidelines.", "qid": 18, "docid": "xpwv8xlv", "rank": 89, "score": 0.7258655428886414}, {"content": "Title: Efficacy of face mask in preventing respiratory virus transmission: A systematic review and meta-analysis Content: BACKGROUND: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. RESULTS: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24\u20130.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11\u20130.37) and 47% (OR = 0.53, 95% CI = 0.36\u20130.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials and observational studies. CONCLUSIONS: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak.", "qid": 18, "docid": "x9sfgtim", "rank": 90, "score": 0.725670576095581}, {"content": "Title: Textile Masks and Surface Covers\u2014A Spray Simulation Method and a \u201cUniversal Droplet Reduction Model\u201d Against Respiratory Pandemics Content: The main form of COVID-19 transmission is via \u201coral-respiratory droplet contamination\u201d (droplet: very small drop of liquid) produced when individuals talk, sneeze, or cough. In hospitals, health-care workers wear facemasks as a minimum medical \u201cdroplet precaution\u201d to protect themselves. Due to the shortage of masks during the pandemic, priority is given to hospitals for their distribution. As a result, the availability/use of medical masks is discouraged for the public. However, for asymptomatic individuals, not wearing masks in public could easily cause the spread of COVID-19. The prevention of \u201cenvironmental droplet contamination\u201d (EnvDC) from coughing/sneezing/speech is fundamental to reducing transmission. As an immediate solution to promote \u201cpublic droplet safety,\u201d we assessed household textiles to quantify their potential as effective environmental droplet barriers (EDBs). The synchronized implementation of a universal \u201ccommunity droplet reduction solution\u201d is discussed as a model against COVID-19. Using a bacterial-suspension spray simulation model of droplet ejection (mimicking a sneeze), we quantified the extent by which widely available clothing fabrics reduce the dispersion of droplets onto surfaces within 1.8 m, the minimum distance recommended for COVID-19 \u201csocial distancing.\u201d All textiles reduced the number of droplets reaching surfaces, restricting their dispersion to <30 cm, when used as single layers. When used as double-layers, textiles were as effective as medical mask/surgical-cloth materials, reducing droplet dispersion to <10 cm, and the area of circumferential contamination to ~0.3%. The synchronized implementation of EDBs as a \u201ccommunity droplet reduction solution\u201d (i.e., face covers/scarfs/masks and surface covers) will reduce COVID-19 EnvDC and thus the risk of transmitting/acquiring COVID-19.", "qid": 18, "docid": "hl956i02", "rank": 91, "score": 0.7256263494491577}, {"content": "Title: The effect of behavior of wearing masks on epidemic dynamics Content: Recently, COVID-19 has attracted a lot of attention of researchers from different fields. Wearing masks is a frequently adopted precautionary measure. In this paper, we investigate the effect of behavior of wearing masks on epidemic dynamics in the context of COVID-19. At each time, every susceptible individual chooses whether to wear a mask or not in the next time step, which depends on an evaluation of the potential costs and perceived risk of infection. When the cost of infection is high, the majority of the population choose to wear masks, where global awareness plays a significant role. However, if the mask source is limited, global awareness may give rise to a negative result. In this case, more mask source should be allocated to the individuals with high risk of infection.", "qid": 18, "docid": "2iokkog5", "rank": 92, "score": 0.7255918979644775}, {"content": "Title: Visualizing the effectiveness of face masks in obstructing respiratory jets Content: The use of face masks in public settings has been widely recommended by public health officials during the current COVID-19 pandemic. The masks help mitigate the risk of cross-infection via respiratory droplets; however, there are no specific guidelines on mask materials and designs that are most effective in minimizing droplet dispersal. While there have been prior studies on the performance of medical-grade masks, there are insufficient data on cloth-based coverings, which are being used by a vast majority of the general public. We use qualitative visualizations of emulated coughs and sneezes to examine how material- and design-choices impact the extent to which droplet-laden respiratory jets are blocked. Loosely folded face masks and bandana-style coverings provide minimal stopping-capability for the smallest aerosolized respiratory droplets. Well-fitted homemade masks with multiple layers of quilting fabric, and off-the-shelf cone style masks, proved to be the most effective in reducing droplet dispersal. These masks were able to curtail the speed and range of the respiratory jets significantly, albeit with some leakage through the mask material and from small gaps along the edges. Importantly, uncovered emulated coughs were able to travel notably farther than the currently recommended 6-ft distancing guideline. We outline the procedure for setting up simple visualization experiments using easily available materials, which may help healthcare professionals, medical researchers, and manufacturers in assessing the effectiveness of face masks and other personal protective equipment qualitatively.", "qid": 18, "docid": "ohkki0ke", "rank": 93, "score": 0.7251607179641724}, {"content": "Title: Potential ocular and systemic COVID-19 prophylaxis approaches for healthcare professionals Content: The COVID-19 pandemic has brought with it, innumerable challenges in healthcare, both through the direct burden of morbidity and mortality of the disease, and also by the curtailing of other essential albeit less emergency medical services to reduce the risk of community spread. Reports from around the world are showing mounting number of cases even in healthcare professionals spite of usage of adequate personal protective equipment. There are a number of factors which could account for this, be it the affinity of the virus to the respiratory and other mucosa or to patient risk factors for developing severe forms of the disease. In view of the growing need for resuming other medical services, it is essential to find newer ways to protect ourselves better, whether by systemic or topical mucosal prophylaxis with various medications or lifestyle changes promoting wellbeing and immunity. This article discusses additional prophylactic measures including drug repurposing or new indication paradigms to render protection. Certain medications such as chloroquine, trehalose, antihistaminics, and interferons used topically for various ocular conditions with reasonably good safety records are known to have anti-viral properties. Hence, can be harnessed in preventing SARS-CoV-2 attachment, entry, and/or replication in host cells. Similarly, use of hypertonic saline for nasal and oral mucosa and dietary changes are possible methods of improving our resistance. These additional prophylactic measures can be cautiously explored by healthcare professionals to protect themselves and their patients.", "qid": 18, "docid": "tywfjnvm", "rank": 94, "score": 0.7249746918678284}, {"content": "Title: Potential ocular and systemic COVID-19 prophylaxis approaches for healthcare professionals. Content: The COVID-19 pandemic has brought with it, innumerable challenges in healthcare, both through the direct burden of morbidity and mortality of the disease, and also by the curtailing of other essential albeit less emergency medical services to reduce the risk of community spread. Reports from around the world are showing mounting number of cases even in healthcare professionals spite of usage of adequate personal protective equipment. There are a number of factors which could account for this, be it the affinity of the virus to the respiratory and other mucosa or to patient risk factors for developing severe forms of the disease. In view of the growing need for resuming other medical services, it is essential to find newer ways to protect ourselves better, whether by systemic or topical mucosal prophylaxis with various medications or lifestyle changes promoting wellbeing and immunity. This article discusses additional prophylactic measures including drug repurposing or new indication paradigms to render protection. Certain medications such as chloroquine, trehalose, antihistaminics, and interferons used topically for various ocular conditions with reasonably good safety records are known to have anti-viral properties. Hence, can be harnessed in preventing SARS-CoV-2 attachment, entry, and/or replication in host cells. Similarly, use of hypertonic saline for nasal and oral mucosa and dietary changes are possible methods of improving our resistance. These additional prophylactic measures can be cautiously explored by healthcare professionals to protect themselves and their patients.", "qid": 18, "docid": "qnaqyyjq", "rank": 95, "score": 0.7249746918678284}, {"content": "Title: Brief research report: Bidirectional impact of imperfect mask use on reproduction number of COVID-19: A next generation matrix approach() Content: The use of masks as a means of reducing transmission of COVID-19 outside healthcare settings has proved controversial. Masks are thought to have two modes of effect: they prevent infection with COVID-19 in wearers; and prevent transmission by individuals with subclinical infection. We used a simple next-generation matrix approach to estimate the conditions under which masks would reduce the reproduction number of COVID-19 under a threshold of 1. Our model takes into account the possibility of assortative mixing, where mask users interact preferentially with other mask users. We make 3 key observations: 1. Masks, even with suboptimal efficacy in both prevention of acquisition and transmission of infection, could substantially decrease the reproduction number for COVID-19 if widely used. 2. Widespread masking may be sufficient to suppress epidemics where R has been brought close to 1 via other measures (e.g., distancing). 3. \u201cAssortment\u201d within populations (the tendency for interactions between masked individuals to be more likely than interactions between masked and unmasked individuals) would rapidly erode the impact of masks. As such, mask uptake needs to be fairly universal to have an effect. This simple model suggests that widespread uptake of masking could be determinative in suppressing COVID-19 epidemics in regions with R(t) at or near 1.", "qid": 18, "docid": "dt2pew66", "rank": 96, "score": 0.7246116399765015}, {"content": "Title: HUMAN CORONAVIRUS DATA FROM FOUR CLINICAL TRIALS OF MASKS AND RESPIRATORS Content: There are few published data on the protection of masks or respirators against coronavirus infections. This is an important research question to inform the response to the COVID-19 epidemic. The transmission modes of human coronaviruses are similar, thought to be by droplet, contact and sometimes airborne routes. There are several randomised clinical trials of masks and respirators, but most used clinical endpoints or tested only for influenza. In four trials which we conducted, we tested for human coronaviruses, but only composite viral endpoints were reported in the trials. We reviewed and analysed the coronavirus data from four of our trials. Laboratory-confirmed coronavirus infections were identified in our community household trial (1 case), health worker trials (8 cases) and trial of mask use by sick patients (19 cases). No coronavirus infections were transmitted in households to parents who wore P2 or surgical masks, but one child with coronavirus infection transmitted infection to a parent in the control arm. No transmissions to close contacts occurred when worn by sick patients with coronavirus infections. There was a higher risk of coronavirus infection in HCWs who wore a mask compared to a respirator, but the difference was not statistically significant. These are the only available data on coronavirus infections associated with mask or respirator use. More clinical trials are needed to assess the efficacy of respiratory protection against coronavirus infections.", "qid": 18, "docid": "vjg2auh7", "rank": 97, "score": 0.7245314121246338}, {"content": "Title: Human Coronavirus Data from Four Clinical Trials of Masks and Respirators Content: There are few published data on the protection of masks or respirators against coronavirus infections. This is an important research question to inform the response to the COVID-19 epidemic. The transmission modes of human coronaviruses are similar, thought to be by droplet, contact and sometimes airborne routes. There are several randomised clinical trials of masks and respirators, but most used clinical endpoints or tested only for influenza. In four trials which we conducted, we tested for human coronaviruses, but only composite viral endpoints were reported in the trials. We reviewed and analysed the coronavirus data from four of our trials. Laboratory-confirmed coronavirus infections were identified in our community household trial (1 case), health worker trials (8 cases) and trial of mask use by sick patients (19 cases). No coronavirus infections were transmitted in households to parents who wore P2 or surgical masks, but one child with coronavirus infection transmitted infection to a parent in the control arm. No transmissions to close contacts occurred when worn by sick patients with coronavirus infections. There was a higher risk of coronavirus infection in HCWs who wore a mask compared to a respirator, but the difference was not statistically significant. These are the only available data on coronavirus infections associated with mask or respirator use. More clinical trials are needed to assess the efficacy of respiratory protection against coronavirus infections.", "qid": 18, "docid": "gey0nidn", "rank": 98, "score": 0.7245314121246338}, {"content": "Title: The use of face masks during the COVID\u201019 pandemic in Poland: A survey study of 2315 young adults Content: Face masks wearing during the coronavirus disease 2019 (COVID\u201019) pandemic became ubiquitous. The aim of our study was to assess the use of face masks among young adults during the current viral pandemic. The survey was based on specially created Google Forms and posted on numerous Facebook groups for young people in Poland. Seven days were considered as a recall period. A total of 2315 answers were obtained, 2307 were finally analysis, as eight questionnaires were removed because of data incompleteness. 60.4% of responders declared using the face masks. Those who reported an atopic predisposition wore face masks significantly (P = .007) more commonly (65.5% and 57.7%, respectively). Cloth masks (46.2%) appeared to be most popular ones, followed by surgical masks (39.2%), respirators (N95 and FFP) (13.3%), half\u2010face elastomeric respirators (0.8%) and full\u2010face respirators (0.4%). Females significantly more frequently (P = .0001) used cloth masks; respirators, half\u2010face elastomeric respirators and full\u2010face respirators were used more commonly by males (P < .0001, P = .001 and P = .001, respectively). 23.9% of responders who used single\u2010use mask wore it again. Moreover, 73.6% participants declared mask decontamination; however, the procedures were not always appropriate. We suggest that our results may be of help in construction of general public education campaigns on the proper use of face masks.", "qid": 18, "docid": "9lgg5gya", "rank": 99, "score": 0.7240943908691406}, {"content": "Title: To mask or not to mask children to overcome COVID-19 Content: It has been reported that asymptomatic people can transmit the new coronavirus disease 2019 (COVID-19) and become important sources of COVID-19. To reduce the role of asymptomatic or poorly symptomatic people in COVID-19, universal use of face masks in addition to hand hygiene and safety distance seems extremely useful. Consequently, preparing the healthy child to use face masks is strongly needed. To obtain maximal compliance, reasons for mask wearing without attempts of removing must be clearly explained. Moreover, child's will must not be forced.Conclusion: On the basis of clinical findings, we think that the universal use of facial masks seems necessary when people have to go out in their everyday lives. In addition to the availability of masks of different sizes capable of adapting perfectly to the face, it is necessary that the use of masks in children is preceded by a strong parental work and school lessons on this issue and other hygiene topics with the main aim to obtain child cooperation.What is Known:\u00e2\u0080\u00a2 Asymptomatic people can transmit and become important sources of COVID-19.\u00e2\u0080\u00a2 Asymptomatic cases are common also in pediatrics.What is New:\u00e2\u0080\u00a2 Universal use of face masks for success against COVID-19 seems necessary also in pediatric age when people have to go out in their everyday lives.\u00e2\u0080\u00a2 In addition to the availability of masks of different sizes capable of adapting perfectly to the face, it is necessary that the use of masks in children is preceded by a strong parental work and school lessons with the main aim to obtain child cooperation.", "qid": 18, "docid": "ckqdh4pg", "rank": 100, "score": 0.723987877368927}]}
{"query": "what type of hand sanitizer is needed to destroy Covid-19?", "hits": [{"content": "Title: Efficient inactivation of SARS-CoV-2 by WHO-recommended hand rub formulations and alcohols Content: The recent emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 is a major burden for health care systems worldwide. It is important to address if the current infection control instructions based on active ingredients are sufficient. We therefore determined the virucidal activity of two alcohol-based hand rub solutions for hand disinfection recommended by the World Health Organization (WHO), as well as commercially available alcohols. Efficient SARS-CoV-2 inactivation was demonstrated for all tested alcohol-based disinfectants. These findings show the successful inactivation of SARS-CoV-2 for the first time and provide confidence in its use for the control of COVID-19. Importance The current COVID-19 outbreak puts a huge burden on the world\u2019s health care systems. Without effective therapeutics or vaccines being available, effective hygiene measure are of utmost importance to prevent viral spreading. It is therefore crucial to evaluate current infection control strategies against SARS-CoV-2. We show the inactivation of the novel coronavirus for the first time and endorse the importance of disinfectant-based hand hygiene to reduce SARS-CoV-2 transmission.", "qid": 19, "docid": "c1n994j6", "rank": 1, "score": 0.8104120492935181}, {"content": "Title: Hand Sanitizers: A Review of Ingredients, Mechanisms of Action, Modes of Delivery, and Efficacy Against Coronaviruses Content: BACKGROUND: The emergence of the novel virus, SARS-CoV-2, has posed unprecedented challenges to public health around the world. Currently, strategies to deal with COVID-19 are purely supportive and preventative, aimed at reducing transmission. An effective and simple method for reducing transmission of infections in the public or healthcare settings is hand hygiene. Unfortunately, little is known regarding the efficacy of hand sanitizers against SARS-CoV-2. METHODS: In this review, an extensive literature search was performed to succinctly summarize the primary active ingredients and mechanisms of action of hand sanitizers, compare the effectiveness and compliance of gel and foam sanitizers, and predict whether alcohol and non-alcohol hand sanitizers would be effective against SARS-CoV-2. RESULTS: Most alcohol based hand sanitizers are effective at inactivating enveloped viruses, including coronaviruses. With what is currently known in the literature, one may not confidently suggest one mode of hand sanitizing delivery over the other. When hand washing with soap and water is unavailable, a sufficient volume of sanitizer is necessary to ensure complete hand coverage, and compliance is critical for appropriate hand hygiene. CONCLUSIONS: By extrapolating effectiveness of hand sanitizers on viruses of similar structure to SARS-CoV-2, this virus should be effectively inactivated with current hand hygiene products, though future research should attempt to determine this directly.", "qid": 19, "docid": "y777xosr", "rank": 2, "score": 0.8083386421203613}, {"content": "Title: COVID-19 and frequent use of hand sanitizers; human health and environmental hazards by exposure pathways Content: Till date no medication or vaccine is available to cope with the COVID-19 infection and infection rate is increasing drastically across the globe. Only preventive measures and healthy life style with efficient immune system have been suggested by WHO to fight and stay safe from COVID-19. WHO recommended alcohol based hand sanitizers for frequent hand hygiene, which are mainly made up from ethanol, isopropyl alcohols, hydrogen peroxides in different combinations. These preparations may become toxic to human health and environment when misused. These chemicals have known toxic and hazardous impact on environment when released by evaporation. In early five months of 2020, American Association of Poison Control Center reported 9504 alcoholic hand sanitizer exposure cases in children under the age of 12 years and recognized that even a small amount of alcohol can cause alcohol poisoning in children that is responsible for confusion, vomiting and drowsiness, and in severe cases, respiratory arrest and death. Furthermore, frequent usage of said hand sanitizers has reported increased chance of antimicrobial resistance and chance of other viral diseases. Current review is designed with main objective to highlight the toxic and serious health risks to human health and environment by frequent using hand hygiene products with alcohols based formulations.", "qid": 19, "docid": "eevs62xf", "rank": 3, "score": 0.8082085847854614}, {"content": "Title: Hand Sanitizers: A Review on Formulation Aspects, Adverse Effects, and Regulations Content: Hand hygiene is of utmost importance as it may be contaminated easily from direct contact with airborne microorganism droplets from coughs and sneezes. Particularly in situations like pandemic outbreak, it is crucial to interrupt the transmission chain of the virus by the practice of proper hand sanitization. It can be achieved with contact isolation and strict infection control tool like maintaining good hand hygiene in hospital settings and in public. The success of the hand sanitization solely depends on the use of effective hand disinfecting agents formulated in various types and forms such as antimicrobial soaps, water-based or alcohol-based hand sanitizer, with the latter being widely used in hospital settings. To date, most of the effective hand sanitizer products are alcohol-based formulations containing 62%\u201395% of alcohol as it can denature the proteins of microbes and the ability to inactivate viruses. This systematic review correlated with the data available in Pubmed, and it will investigate the range of available hand sanitizers and their effectiveness as well as the formulation aspects, adverse effects, and recommendations to enhance the formulation efficiency and safety. Further, this article highlights the efficacy of alcohol-based hand sanitizer against the coronavirus.", "qid": 19, "docid": "d26y5291", "rank": 4, "score": 0.8068109750747681}, {"content": "Title: Hand Sanitizers: A Review on Formulation Aspects, Adverse Effects, and Regulations Content: Hand hygiene is of utmost importance as it may be contaminated easily from direct contact with airborne microorganism droplets from coughs and sneezes. Particularly in situations like pandemic outbreak, it is crucial to interrupt the transmission chain of the virus by the practice of proper hand sanitization. It can be achieved with contact isolation and strict infection control tool like maintaining good hand hygiene in hospital settings and in public. The success of the hand sanitization solely depends on the use of effective hand disinfecting agents formulated in various types and forms such as antimicrobial soaps, water-based or alcohol-based hand sanitizer, with the latter being widely used in hospital settings. To date, most of the effective hand sanitizer products are alcohol-based formulations containing 62%-95% of alcohol as it can denature the proteins of microbes and the ability to inactivate viruses. This systematic review correlated with the data available in Pubmed, and it will investigate the range of available hand sanitizers and their effectiveness as well as the formulation aspects, adverse effects, and recommendations to enhance the formulation efficiency and safety. Further, this article highlights the efficacy of alcohol-based hand sanitizer against the coronavirus.", "qid": 19, "docid": "i0ll585x", "rank": 5, "score": 0.8062257170677185}, {"content": "Title: COVID-19 and frequent use of hand sanitizers; human health and environmental hazards by exposure pathways Content: Abstract Till date no medication or vaccine is available to cope with the COVID-19 infection and infection rate is increasing drastically across the globe. Only preventive measures and healthy life style with efficient immune system have been suggested by WHO to fight and stay safe from COVID-19. WHO recommended alcohol based hand sanitizers for frequent hand hygiene, which are mainly made up from ethanol, isopropyl alcohols, hydrogen peroxides in different combinations. These preparations may become toxic to human health and environment when misused. These chemicals have known toxic and hazardous impact on environment when released by evaporation. In early five months of 2020, American Association of Poison Control Center reported 9504 alcoholic hand sanitizer exposure cases in children under the age of 12 years and recognized that even a small amount of alcohol can cause alcohol poisoning in children that is responsible for confusion, vomiting and drowsiness, and in severe cases, respiratory arrest and death. Furthermore, frequent usage of said hand sanitizers has reported increased chance of antimicrobial resistance and chance of other viral diseases. Current review is designed with main objective to highlight the toxic and serious health risks to human health and environment by frequent using hand hygiene products with alcohols based formulations.", "qid": 19, "docid": "hma2kvn2", "rank": 6, "score": 0.8050433397293091}, {"content": "Title: A Review of Current Interventions for COVID-19 Prevention Content: Abstract The recent outbreak of CoVID-19 is declared as a global public health emergency of international concern by the World Health Organization (WHO). A fresh figure of 2268011 positive cases and 155185 death records (till April 18th 2020) across the worldwide signify the severity of this viral infection. CoVID-19 infection is a pandemic, surface to surface communicable disease with a case fatality rate of 3.4% as estimated by WHO up to March 3rd 2020. Unfortunately, the current unavailability of an effective antiviral drug and approved vaccine, worsen the situation more critical. Implementation of an effective preventive measure is the only option left to counteract CoVID-19. Further, a retrospective analysis provides evidence that contemplates the decisive role of preventive measures in controlling severe acute respiratory syndrome (SARS) outbreak in 2003. A statistical surveillance report of WHO reflects, maintaining a coherent infection, prevention and control guideline resulted in a 30% reduction in healthcare-associated infections. The effectiveness of preventive measures completely relies on the strength of surface disinfectants, the composition of hand sanitizer, appropriate material for the manufacture of personal protective equipment (PPE). This review enlightens the various preventive measures such as a suitable selection of surface disinfectants, appropriate hand sanitization, and empowering the PPE that could be a potential intervention to fight against CoVID-19.", "qid": 19, "docid": "qud4bj12", "rank": 7, "score": 0.8011988997459412}, {"content": "Title: Hand sanitisers amid CoViD-19: A critical review of alcohol-based products on the market and formulation approaches to respond to increasing demand Content: The world is facing a medical crisis amid the CoViD-19 pandemic and the role of adequate hygiene and hand sanitisers is inevitable in controlling the spread of infection in public places and healthcare institutions. There has been a great surge in demand for hand sanitisation products leading to shortages in their supply. A consequent increase of substandard products in the market has raised safety concerns. This article, therefore, presents a critical review of hand sanitation approaches and products available on the market in light of the scientific evidence available to date. This review also provides a range of hand sanitisation product formulations, and manufacturing instructions to allow for extemporaneous preparations at the community and hospital pharmacies during this urgent crisis. In addition, this emergent situation is expected to continue, hence hand sanitisers will be in demand for an extended time, and the availability and purchase of substandard products on the market create an ongoing safety concern. Therefore, this article shall also provide various commercial organisations, interested in stepping forward the production and marketing of hand sanitisers, with a guide on the development of products of standardised ingredients and formulations.", "qid": 19, "docid": "rv2akbj8", "rank": 8, "score": 0.7995122671127319}, {"content": "Title: Hand sanitisers amid CoViD-19: A critical review of alcohol-based products on the market and formulation approaches to respond to increasing demand. Content: The world is facing a medical crisis amid the CoViD-19 pandemic and the role of adequate hygiene and hand sanitisers is inevitable in controlling the spread of infection in public places and healthcare institutions. There has been a great surge in demand for hand sanitisation products leading to shortages in their supply. A consequent increase of substandard products in the market has raised safety concerns. This article, therefore, presents a critical review of hand sanitation approaches and products available on the market in light of the scientific evidence available to date. This review also provides a range of hand sanitisation product formulations, and manufacturing instructions to allow for extemporaneous preparations at the community and hospital pharmacies during this urgent crisis. In addition, this emergent situation is expected to continue, hence hand sanitisers will be in demand for an extended time, and the availability and purchase of substandard products on the market create an ongoing safety concern. Therefore, this article shall also provide various commercial organisations, interested in stepping forward the production and marketing of hand sanitisers, with a guide on the development of products of standardised ingredients and formulations.", "qid": 19, "docid": "d6v5mkj7", "rank": 9, "score": 0.7995122671127319}, {"content": "Title: A Review of Current Interventions for COVID-19 Prevention Content: The recent outbreak of CoVID-19 is declared as a global public health emergency of international concern by the World Health Organization (WHO). A fresh figure of 2268011 positive cases and 155185 death records (till April 18th 2020) across the worldwide signify the severity of this viral infection. CoVID-19 infection is a pandemic, surface to surface communicable disease with a case fatality rate of 3.4% as estimated by WHO up to March 3rd 2020. Unfortunately, the current unavailability of an effective antiviral drug and approved vaccine, worsen the situation more critical. Implementation of an effective preventive measure is the only option left to counteract CoVID-19. Further, a retrospective analysis provides evidence that contemplates the decisive role of preventive measures in controlling severe acute respiratory syndrome (SARS) outbreak in 2003. A statistical surveillance report of WHO reflects, maintaining a coherent infection, prevention and control guideline resulted in a 30% reduction in healthcare-associated infections. The effectiveness of preventive measures completely relies on the strength of surface disinfectants, the composition of hand sanitizer, appropriate material for the manufacture of personal protective equipment (PPE). This review enlightens the various preventive measures such as a suitable selection of surface disinfectants, appropriate hand sanitization, and empowering the PPE that could be a potential intervention to fight against CoVID-19.", "qid": 19, "docid": "xfwseuxu", "rank": 10, "score": 0.7915939092636108}, {"content": "Title: The pandemic of COVID-19 and its implications for the purity and authenticity of alcohol-based hand sanitizers: The health risks associated with falsified sanitizers and recommendations for regulatory and public health bodies Content: Abstract With the beginning of the pandemic of COVID-19 throughout the world, the demand and consumption of hand sanitizers has increased, which had led to a sharp crunch in these products at all levels. This shortage has led to an increase in the prevalence of falsified alcohol-based hand sanitizers, including the illegal addition of methanol to hand sanitizers and the production of hand sanitizers with an alcohol concentration of less than 60%. These findings indicate that regulatory and public health bodies should take an active role in ensuring the safety and quality of antimicrobial products such as alcohol-based hand sanitizers at every stage of the products\u2019 lifecycle, including distribution, manufacture and import.", "qid": 19, "docid": "20ipkh78", "rank": 11, "score": 0.7910813093185425}, {"content": "Title: The pandemic of COVID-19 and its implications for the purity and authenticity of alcohol-based hand sanitizers: The health risks associated with falsified sanitizers and recommendations for regulatory and public health bodies Content: With the beginning of the pandemic of COVID-19 throughout the world, the demand and consumption of hand sanitizers has increased, which had led to a sharp crunch in these products at all levels. This shortage has led to an increase in the prevalence of falsified alcohol-based hand sanitizers, including the illegal addition of methanol to hand sanitizers and the production of hand sanitizers with an alcohol concentration of less than 60%. These findings indicate that regulatory and public health bodies should take an active role in ensuring the safety and quality of antimicrobial products such as alcohol-based hand sanitizers at every stage of the products' lifecycle, including distribution, manufacture and import.", "qid": 19, "docid": "uhhk4t7f", "rank": 12, "score": 0.7816219925880432}, {"content": "Title: Sanitizer aerosol-driven ocular surface disease (SADOSD)-A COVID-19 repercussion? Content: Since the onset of the COVID-19 pandemic, there has been an advisory for regular and thorough cleaning of hands besides other measures such as social distancing and self-isolation. The rationale for the same is to prevent the transfer of the virus from hands that have come in contact with fomites. While both alcohol-based hand rubs (ABHR) or washing with soap and water are claimed to have been effective, hand sanitizers have gained more popularity due to the ease of use. The increased frequency of ABHR use and the aerosols generated pose a potential threat to the skin and exposed mucosal surfaces, especially that of the eye due to the proximity of use. The adverse effects of alcohol in these sanitizers can be manifold. An allergic or inflammatory response can occur depending on the predisposing or preexisting conditions. This article describes the risks, underlying mechanisms, and preventive measures for sanitizer aerosol-driven ocular surface disease.", "qid": 19, "docid": "yjg54yyk", "rank": 13, "score": 0.7792884111404419}, {"content": "Title: European Task Force on Contact Dermatitis statement on coronavirus 19 disease (COVID-19) outbreak and the risk of adverse cutaneous reactions. Content: Among the basic protective measures against COVID-19, the need to wash hands frequently and in a prolonged way using soap, and to regularly use alcohol-based hand sanitizers is well established for the whole population. Healthcare workers in general, and particularly those involved in the direct care of COVID-19 patients, have to wear personal protective equipment (PPE) daily for many hours and also accomplish general preventive measurements outside their work. Cutaneous adverse reactions can develop that need to be prevented, identified and therapeutically managed. According to the data reported by Lin et al 1 , based in the experience from healthcare workers in Wuhan, adverse skin reactions were reported in 74% of responders (n=376) to a general survey. The most commonly reported types of eruptions were skin dryness or desquamation (68.6%), papules or erythema (60.4%) and maceration (52,9%).", "qid": 19, "docid": "gfyup5aj", "rank": 14, "score": 0.7792308330535889}, {"content": "Title: Hidden threat lurking behind the alcohol sanitizers in COVID-19 outbreak Content: The ongoing COVID-19 pandemic has made various challenges for communications all over the world. Nowadays hand hygiene practices with alcohol sanitizers are an unavoidable reality for many people, which cause skin dryness and flaking. The current short communication has been explained about monitoring the quality control of alcohol concentrations and hand rub formulation, which needs more attention and should consider meticulous in this crisis.", "qid": 19, "docid": "z6cda4o2", "rank": 15, "score": 0.7781901359558105}, {"content": "Title: Inactivation of Severe Acute Respiratory Syndrome Coronavirus 2 by WHO-Recommended Hand Rub Formulations and Alcohols Content: Infection control instructions call for use of alcohol-based hand rub solutions to inactivate severe acute respiratory syndrome coronavirus 2. We determined the virucidal activity of World Health Organization\u2013recommended hand rub formulations, at full strength and multiple dilutions, and of the active ingredients. All disinfectants demonstrated efficient virus inactivation.", "qid": 19, "docid": "b0nkhsvv", "rank": 16, "score": 0.7765385508537292}, {"content": "Title: Inactivation of Severe Acute Respiratory Syndrome Coronavirus 2 by WHO-Recommended Hand Rub Formulations and Alcohols Content: Infection control instructions call for use of alcohol-based hand rub solutions to inactivate severe acute respiratory syndrome coronavirus 2. We determined the virucidal activity of World Health Organization-recommended hand rub formulations, at full strength and multiple dilutions, and of the active ingredients. All disinfectants demonstrated efficient virus inactivation.", "qid": 19, "docid": "1v8wwn0d", "rank": 17, "score": 0.775733470916748}, {"content": "Title: Hidden threat lurking behind the alcohol sanitizers in COVID\u201019 outbreak Content: The ongoing COVID\u201019 pandemic has made various challenges for communications all over the world. Nowadays hand hygiene practices with alcohol sanitizers are an unavoidable reality for many people, which cause skin dryness and flaking. The current short communication has been explained about monitoring the quality control of alcohol concentrations and hand rub formulation, which needs more attention and should consider meticulous in this crisis.", "qid": 19, "docid": "hx8c0mxj", "rank": 18, "score": 0.7741439938545227}, {"content": "Title: Frequent Hand Washing for COVID-19 Prevention Can Cause Hand Dermatitis: Management Tips Content: Coronavirus disease 2019 (COVID-19) continues to spread globally, outpacing the capacity and resources of health systems worldwide. A therapeutic vaccine is not yet on the rise, and preventive measures are the current approach to restraint the transmission of cases. As the virus is highly contagious via respiratory route (droplets from infected persons, widely spread by coughing or sneezing) and via contact with contaminated surfaces, community transmission and spread can be decreased through the practice of regular and diligent hand hygiene. Frequent hand washing implies a prolonged exposure to water and other chemical or physical agents and may induce several pathophysiologic changes, such as epidermal barrier disruption, impairment of keratinocytes, the subsequent release of proinflammatory cytokines, activation of the skin immune system, and delayed-type hypersensitivity reactions. Adverse dermatologic effects, such as excessive skin dryness or even contact dermatitis (particularly the irritant subtype and, to a lesser extent, the allergic subtype), can occur, especially in individuals with a history of atopic dermatitis. These skin conditions are perfectly manageable, and applying a moisturizer immediately after washing hands or after using a portable hand sanitizer is the cornerstone in preventing the development of eczematous changes in the hands. In the current global context, the potential occurrence of these dermatological adverse events should in no way cause people to deviate from strict hand hygiene rules.", "qid": 19, "docid": "irmwqjfh", "rank": 19, "score": 0.7703661322593689}, {"content": "Title: COVID-19 Global Pandemic Planning: Decontamination and Reuse Processes for N95 Respirators Content: Coronavirus disease 2019 (COVID-19) is an illness caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was first identified as a cluster of respiratory illness in Wuhan City, Hubei Province, China in December 2019, and has rapidly spread across the globe to greater than 200 countries. Healthcare providers are at an increased risk for contracting the disease due to occupational exposure and require appropriate personal protective equipment (PPE), including N95 respirators. The rapid worldwide spread of high numbers of COVID-19 cases has facilitated the need for a substantial supply of PPE that is largely unavailable in many settings, thereby creating critical shortages. Creative solutions for the decontamination and safe reuse of PPE to protect our frontline healthcare personnel are essential. Here, we describe the development of a process that began in late February 2020 for selecting and implementing the use of hydrogen peroxide vapor (HPV) as viable method to reprocess N95 respirators. Since pre-existing HPV decontamination chambers were not available, we optimized the sterilization process in an operating room after experiencing initial challenges in other environments. Details are provided about the prioritization and implementation of processes for collection and storage, pre-processing, HPV decontamination, and post-processing of filtering facepiece respirators (FFRs). Important lessons learned from this experience include, developing an adequate reserve of PPE for effective reprocessing and distribution, and identifying a suitable location with optimal environmental controls (i.e., operating room). Collectively, information presented here provides a framework for other institutions considering decontamination procedures for N95 respirators.", "qid": 19, "docid": "arivuags", "rank": 20, "score": 0.770159125328064}, {"content": "Title: Hand Hygiene Among Health Care Workers During COVID-19 Pandemic: Challenges and Recommendations Content: In-hospital transmission is one of the main routes of the 2019 novel coronavirus (SARS-CoV-2) spreading among health care workers (HCWs) who are the frontline fighters. However, coming into contact with COVID-19-positive patients is unavoidable. Therefore, hand hygiene is of utmost importance for the prevention of COVID-19 among HCWs. This purpose can be achieved by applying alcohol-based hand rubs, washing hands properly with soap and water, and applying other antiseptic agents. Nevertheless, regular hand hygiene could also be challenging, because water, detergents, and disinfectants may predispose HCWs to hand dermatitis. The current article reviews the risk factors for the development of hand dermatitis, with further focus on the most common agents used among HCWs. In addition, the risk of occupational hand dermatitis for each agent is evaluated to increase awareness of this common condition. Finally, some recommendations are discussed to reduce the effect of hand dermatitis on HCWs.", "qid": 19, "docid": "odfssrr6", "rank": 21, "score": 0.7665635347366333}, {"content": "Title: Hand Hygiene Among Health Care Workers During COVID-19 Pandemic: Challenges and Recommendations. Content: In-hospital transmission is one of the main routes of the 2019 novel coronavirus (SARS-CoV-2) spreading among health care workers (HCWs) who are the frontline fighters. However, coming into contact with COVID-19-positive patients is unavoidable. Therefore, hand hygiene is of utmost importance for the prevention of COVID-19 among HCWs. This purpose can be achieved by applying alcohol-based hand rubs, washing hands properly with soap and water, and applying other antiseptic agents. Nevertheless, regular hand hygiene could also be challenging, because water, detergents, and disinfectants may predispose HCWs to hand dermatitis. The current article reviews the risk factors for the development of hand dermatitis, with further focus on the most common agents used among HCWs. In addition, the risk of occupational hand dermatitis for each agent is evaluated to increase awareness of this common condition. Finally, some recommendations are discussed to reduce the effect of hand dermatitis on HCWs.", "qid": 19, "docid": "ji5pqh47", "rank": 22, "score": 0.7665635347366333}, {"content": "Title: Hypochlorous acid \u2013 a review Content: The surgeon needs to have an inexpensive, available, non-toxic, and practical disinfectant that is effective in sanitizing against the CoVID-19 virus. The purpose of this paper is to review the evidence for using hypochlorous acid (HOCl) in the office setting on a daily basis. The methods used to assemble recommendations were to review the literature including evidence for this solution when used in different locations and industries other than the oral-maxillofacial clinic facility. The results indicate that this material can be used with a high predictability for disinfecting against the CoVID-19 virus.", "qid": 19, "docid": "joi5xr8o", "rank": 23, "score": 0.7658801078796387}, {"content": "Title: Dry Taps? A Synthesis of Alternative \u201cWash\u201d Methods in the Absence of Water and Sanitizers in the Prevention of Coronavirus in Low-Resource Settings Content: Objective: Social distancing and hand washing with soap and water have been advocated as the main proactive measures against the spread of coronavirus. We sought to find out what other alternative materials and methods would be used among populations without running water and who may not afford alcohol-based sanitizers. Results: We reviewed studies that reported use of sand, soil, ash, soda ash, seawater, alkaline materials, and sunlight as possible alternatives to handwashing with soap and water. We identified the documented mechanism of actions of these alternative wash methods on both inanimate surfaces and at cellular levels. The consideration of use of these alternative locally available in situations of unavailability of soap and water and alcohol-based sanitizers is timely in the face of coronavirus pandemic. Further randomized studies need to be carried out to evaluate the effectiveness of these alternatives in management of SARS-Cov-2.", "qid": 19, "docid": "nl55rm8o", "rank": 24, "score": 0.7651501893997192}, {"content": "Title: Dry Taps? A Synthesis of Alternative \"Wash\" Methods in the Absence of Water and Sanitizers in the Prevention of Coronavirus in Low-Resource Settings Content: Objective: Social distancing and hand washing with soap and water have been advocated as the main proactive measures against the spread of coronavirus. We sought to find out what other alternative materials and methods would be used among populations without running water and who may not afford alcohol-based sanitizers. Results: We reviewed studies that reported use of sand, soil, ash, soda ash, seawater, alkaline materials, and sunlight as possible alternatives to handwashing with soap and water. We identified the documented mechanism of actions of these alternative wash methods on both inanimate surfaces and at cellular levels. The consideration of use of these alternative locally available in situations of unavailability of soap and water and alcohol-based sanitizers is timely in the face of coronavirus pandemic. Further randomized studies need to be carried out to evaluate the effectiveness of these alternatives in management of SARS-Cov-2.", "qid": 19, "docid": "ojh3vgrb", "rank": 25, "score": 0.7651501893997192}, {"content": "Title: Ultraviolet-C and other methods of decontamination of filtering facepiece N-95 respirators during the COVID-19 pandemic Content: During global health emergencies such as the current COVID-19 pandemic, the decontamination of single-use personal protective equipment (PPE) becomes a necessary means to keep up with the growing demand from healthcare workers and patients alike. Many unverified methods are being considered, which can pose the risk of incomplete decontamination and lead to catastrophic results. Several factors come into play when determining the suitability of such methods including the quality of the decontamination technique, the targeted pathogen, cost, ease of installation and use, rate of sterilization, and the surface or material to be sterilized. The germicidal properties of ultraviolet-C are well known. This review will cover the most commonly described methods for the sterilization of N95 respirators, namely, ultraviolet germicidal irradiation, hydrogen peroxide vaporization, microwave-generated steaming, and dry heating. These techniques have been tested previously and have demonstrated efficacy in reducing or inactivating viral and bacterial pathogens, although testing against SARS-CoV-2 specifically has not been done. Moreover, it must be emphasized that proper disposal after a single use is still ideal under normal circumstances.", "qid": 19, "docid": "t1xp9e23", "rank": 26, "score": 0.7639552354812622}, {"content": "Title: Ultraviolet-C and other methods of decontamination of filtering facepiece N-95 respirators during the COVID-19 pandemic. Content: During global health emergencies such as the current COVID-19 pandemic, the decontamination of single-use personal protective equipment (PPE) becomes a necessary means to keep up with the growing demand from healthcare workers and patients alike. Many unverified methods are being considered, which can pose the risk of incomplete decontamination and lead to catastrophic results. Several factors come into play when determining the suitability of such methods including the quality of the decontamination technique, the targeted pathogen, cost, ease of installation and use, rate of sterilization, and the surface or material to be sterilized. The germicidal properties of ultraviolet-C are well known. This review will cover the most commonly described methods for the sterilization of N95 respirators, namely, ultraviolet germicidal irradiation, hydrogen peroxide vaporization, microwave-generated steaming, and dry heating. These techniques have been tested previously and have demonstrated efficacy in reducing or inactivating viral and bacterial pathogens, although testing against SARS-CoV-2 specifically has not been done. Moreover, it must be emphasized that proper disposal after a single use is still ideal under normal circumstances.", "qid": 19, "docid": "wc24ty89", "rank": 27, "score": 0.7639552354812622}, {"content": "Title: Homegrown Ultraviolet Germicidal Irradiation for Hospital-Based N95 Decontamination during the COVID-19 Pandemic Content: Coronavirus disease (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is responsible for the 2020 global pandemic and characterized by high transmissibility and morbidity. Healthcare workers (HCWs) are at risk of contracting COVID-19, and this risk is mitigated through the use of personal protective equipment such as N95 Filtering Facepiece Respirators (FFRs). The high demand for FFRs is not currently met by global supply chains, potentially placing HCWs at increased exposure risk. Effective FFR decontamination modalities exist, which could maintain respiratory protection for HCWs in the midst of the current pandemic, through the decontamination and re-use of FFRs. Here, we present a locally-implemented ultraviolet-C germicidal irradiation (UVGI)-based FFR decontamination pathway, utilizing a home-built UVGI array assembled entirely with previously existing components available at our institution. We provide recommendations on the construction of similar systems, as well as guidance and strategies towards successful institutional implementation of FFR decontamination.", "qid": 19, "docid": "zje20bzz", "rank": 28, "score": 0.7635932564735413}, {"content": "Title: The importance of the minimum dosage necessary for UVC decontamination of N95 respirators during the COVID\u201019 pandemic Content: The World Health Organization (WHO) recently released a press report highlighting the severe shortage of personal protective equipment (PPE) that is endangering healthcare workers worldwide during the COVID-19 pandemic.1 To meet this urgent need, healthcare institutions across the world have begun to utilize the germicidal properties of ultraviolet C (UVC) to decontaminate N95 respirators so that they can be reused.2 It is clearly crucial that the dose of UVC delivered is sufficient to kill any viable SARS-CoV-2, the causative virus of the COVID-19 pandemic, that may be present on the respirators.", "qid": 19, "docid": "hmdq2g3u", "rank": 29, "score": 0.7611595988273621}, {"content": "Title: Using effective hand hygiene practice to prevent and control infection Content: Decontamination using hand hygiene remains one of the most important and effective methods for reducing healthcare-associated infections and cross-infection between patients. In 1860, Florence Nightingale wrote that nurses should wash their hands frequently throughout the day, demonstrating an early awareness of the effectiveness of this simple procedure. The COVID-19 pandemic has demonstrated that effectively applied hand hygiene is a vital intervention that can be used to prevent the spread of disease. This article details the correct procedure required for effective hand hygiene and emphasises the need for nurses to keep up to date with evidence-based guidelines. The article also outlines the differences between hand decontamination using alcohol-based hand gels and soap and water, and the complex factors that can interfere with effective hand hygiene compliance.", "qid": 19, "docid": "k5lz7ql7", "rank": 30, "score": 0.7605941295623779}, {"content": "Title: Using effective hand hygiene practice to prevent and control infection. Content: Decontamination using hand hygiene remains one of the most important and effective methods for reducing healthcare-associated infections and cross-infection between patients. In 1860, Florence Nightingale wrote that nurses should wash their hands frequently throughout the day, demonstrating an early awareness of the effectiveness of this simple procedure. The COVID-19 pandemic has demonstrated that effectively applied hand hygiene is a vital intervention that can be used to prevent the spread of disease. This article details the correct procedure required for effective hand hygiene and emphasises the need for nurses to keep up to date with evidence-based guidelines. The article also outlines the differences between hand decontamination using alcohol-based hand gels and soap and water, and the complex factors that can interfere with effective hand hygiene compliance.", "qid": 19, "docid": "4jx0oq65", "rank": 31, "score": 0.7605941295623779}, {"content": "Title: Using heat to kill SARS-CoV-2 Content: The current coronavirus pandemic has reached global proportions and requires unparalleled collective and individual efforts to slow its spread. One critically important issue is the proper sterilization of physical objects that have been contaminated by the virus. Here, we review the currently existing literature on thermal inactivation of coronavirus (SARS-CoV-2) and present preliminary guideless on temperatures and exposure durations required to sterilize. We also compare these temperatures/exposure durations with potential household appliances that may be thought capable of performing sterilization.", "qid": 19, "docid": "0p0iyhc2", "rank": 32, "score": 0.7604235410690308}, {"content": "Title: Strategies for the reuse of N95 and N99 respiratory masks during the COVID-19 pandemic Content: The COVID-19 pandemic presents a strain of unprecedented scale on health systems around the world. In order to reliably protect medical personnel, and thus to contain the spread of the pandemic, it is essential to provide N95 or N99 (European FFP2 or FFP3) respiratory masks (FFRs). Such masks are currently in extreme shortage: To guarantee their supply sufficiently and for all cases, it would absolutely necessary to reuse them. In recent years, the scientific literature has laid out various possibilities to disinfect the FFRs for their reuse several times. We identify the most promising disinfection methods for the current critical situation (internationally) and project further methods and modifications beyond these.", "qid": 19, "docid": "hwvb979y", "rank": 33, "score": 0.7596169710159302}, {"content": "Title: Effect of various decontamination procedures on disposable N95 mask integrity and SARS-CoV-2 infectivity Content: The COVID-19 pandemic has created a high demand on personal protective equipment, including disposable N95 masks. Given the need for mask reuse, we tested the feasibility of vaporized hydrogen peroxide (VHP), ultraviolet light (UV), and ethanol decontamination strategies on N95 mask integrity and the ability to remove the infectious potential of SARS-CoV-2. FIT test data showed functional degradation by both ethanol and UV decontamination to different degrees. VHP treated masks showed no significant change in function after two treatments. We also report a single SARS-CoV-2 virucidal experiment using Vero E6 cell infection. We hope our data will guide further research for evidenced-based decisions for disposable N95 mask reuse and help protect caregivers from SARS-CoV-2 and other pathogens.", "qid": 19, "docid": "tq9kjozt", "rank": 34, "score": 0.7578688859939575}, {"content": "Title: Decontamination Methods for Reuse of Filtering Facepiece Respirators. Content: Importance The novel coronavirus disease 2019 (COVID-19) has proven to be highly infectious, putting health care professionals around the world at increased risk. Furthermore, there are widespread shortages of necessary personal protective equipment (PPE) for these individuals. Filtering facepiece respirators, such as the N95 respirator, intended for single use, can be reused in times of need. We explore the evidence for decontamination or sterilization of N95 respirators for health care systems seeking to conserve PPE while maintaining the health of their workforce. Observations The filtration properties and fit of N95 respirators must be preserved to function adequately over multiple uses. Studies have shown that chemical sterilization using soap and water, alcohols, and bleach render the respirator nonfunctional. Decontamination with microwave heat and high dry heat also result in degradation of respirator material. UV light, steam, low-dry heat, and commercial sterilization methods with ethylene oxide or vaporized hydrogen peroxide appear to be viable options for successful decontamination. Furthermore, since the surface viability of the novel coronavirus is presumed to be 72 hours, rotating N95 respirator use and allowing time decontamination of the respirators is also a reasonable option. We describe a protocol and best practice recommendations for redoffing decontaminated N95 and rotating N95 respirator use. Conclusions and Relevance COVID-19 presents a high risk for health care professionals, particularly otolaryngologists, owing to the nature of viral transmission, including possible airborne transmission and high viral load in the upper respiratory tract. Proper PPE is effective when used correctly, but in times of scarce resources, institutions may turn to alternative methods of preserving and reusing filtering facepiece respirators. Based on studies conducted on the decontamination of N95 respirators after prior outbreaks, there are several options for institutions to consider for both immediate and large-scale implementation.", "qid": 19, "docid": "ipw9dvxf", "rank": 35, "score": 0.7571949362754822}, {"content": "Title: COVID-19 global pandemic planning: Decontamination and reuse processes for N95 respirators Content: Coronavirus disease 2019 (COVID-19) is an illness caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was first identified as a cluster of respiratory illness in Wuhan City, Hubei Province, China, in December 2019, and has rapidly spread across the globe to greater than 200 countries. Healthcare providers are at an increased risk for contracting the disease due to occupational exposure and require appropriate personal protective equipment (PPE), including N95 respirators. The rapid worldwide spread of high numbers of COVID-19 cases has facilitated the need for a substantial supply of PPE that is largely unavailable in many settings, thereby creating critical shortages. Creative solutions for the decontamination and safe reuse of PPE to protect our frontline healthcare personnel are essential. Here, we describe the development of a process that began in late February 2020 for selecting and implementing the use of hydrogen peroxide vapor (HPV) as viable method to reprocess N95 respirators. Since pre-existing HPV decontamination chambers were not available, we optimized the sterilization process in an operating room after experiencing initial challenges in other environments. Details are provided about the prioritization and implementation of processes for collection and storage, pre-processing, HPV decontamination, and post-processing of filtering facepiece respirators. Important lessons learned from this experience include, developing an adequate reserve of PPE for effective reprocessing and distribution, and identifying a suitable location with optimal environmental controls (i.e. operating room). Collectively, information presented here provides a framework for other institutions considering decontamination procedures for N95 respirators. IMPACT STATEMENT: There is a critical shortage of personal protective equipment (PPE) around the globe. This article describes the safe collection, storage, and decontamination of N95 respirators using hydrogen peroxide vapor (HPV). This article is unique because it describes the HPV process in an operating room, and is therefore, a deployable method for many healthcare settings. Results presented here offer creative solutions to the current PPE shortage.", "qid": 19, "docid": "md4ilfik", "rank": 36, "score": 0.7570537328720093}, {"content": "Title: Surfactant-based prophylaxis and therapy against COVID-19: a possibility Content: Hand hygiene by washing with soap and water is recommended for the prevention of COVID-19 spread. Soaps and detergents are explained to act by damaging viral spike glycoproteins (peplomers) or by washing out the virus through entrapment in the micelles. Technically, soaps come under a functional category of molecules known as surfactants. Surfactants are widely used in pharmaceutical formulations as excipients. We wonder why surfactants are still not tried for prophylaxis or therapy against COVID-19. That too when many of them have proven antiviral properties. Moreover, lung surfactants have already shown benefits in respiratory viral infections. Therefore, we postulate that surfactant-based prophylaxis and therapy would be promising. We believe that our hypothesis would stimulate debate or new research exploring the possibility of surfactant-based prophylaxis and therapy against COVID-19. The success of a surfactant-based technique would save the world from any such pandemic in the future too.", "qid": 19, "docid": "ud4rh1a8", "rank": 37, "score": 0.7568840980529785}, {"content": "Title: Surfactant-based prophylaxis and therapy against COVID-19: A possibility Content: Hand hygiene by washing with soap and water is recommended for the prevention of COVID-19 spread. Soaps and detergents are explained to act by damaging viral spike glycoproteins (peplomers) or by washing out the virus through entrapment in the micelles. Technically, soaps come under a functional category of molecules known as surfactants. Surfactants are widely used in pharmaceutical formulations as excipients. We wonder why surfactants are still not tried for prophylaxis or therapy against COVID-19? That too when many of them have proven antiviral properties. Moreover, lung surfactants have already shown benefits in respiratory viral infections. Therefore, we postulate that surfactant-based prophylaxis and therapy would be promising. We believe that our hypothesis would stimulate debate or new research exploring the possibility of surfactant-based prophylaxis and therapy against COVID-19. The success of a surfactant-based technique would save the world from any such pandemic in the future too.", "qid": 19, "docid": "mtq8kubd", "rank": 38, "score": 0.7565699815750122}, {"content": "Title: Acidified sodium chlorite solution: A potential prophylaxis to mitigate impact of multiple exposures to COVID-19 in frontline health-care providers Content: Limited availability of personal protective equipment is endangering first-line health-care providers treating patients with presumed or confirmed COVID-19 infections. This editorial has multiple objectives in regard to this reality: First, to raise awareness of the need for safe and effective prophylaxis to protect health-care providers with insufficient personal protective equipment from repeated exposures to COVID-19. Second, to summarize the scientific evidence in support of solutions of acidified sodium chlorite (ASC) and its daughter compounds, chlorous acid and chlorine dioxide, as potential targets for said prophylactic use. Third, to propose a regimented protocol using commercially available solutions of ASC having sufficient concentrations of chlorine dioxide for virucidal activity to support safe and effective prophylactic use. And fourth, to raise awareness of and compare other potential prophylactic options currently under investigation.", "qid": 19, "docid": "ydaz744x", "rank": 39, "score": 0.7565207481384277}, {"content": "Title: Chitra Ultraviolet-C-Based Facemask Disposal Bin Content: Used face masks are hazardous waste and must be discarded immediately upon removal. Instead of throwing used masks into the disposal bin, disinfecting the masks is essential to break the chain of infection spread. The development of this device was attempted for COVID-19 management, with the following focus: (1) solution which have sufficient science background established so that extensive experimental validation need not be attempted during the lockdown period in India. (2) Provide solution which could be replicated with local resources and minimum material movement. Therefore, in response to the pressing societal demand we designed, prototyped, verified and validated an UV-C-based multipurpose disinfection device. The device after safety and efficacy evaluation as per the Indian Council of Medical Research (ICMR) guidelines for novel COVID-19 solutions, received Central Drugs Control Standard Organization (CDSCO) registration as non-notified medical device for commercialization.", "qid": 19, "docid": "c0lsetbb", "rank": 40, "score": 0.7561540007591248}, {"content": "Title: Can N95 Respirators Be Reused after Disinfection? How Many Times? Content: The coronavirus disease 2019 (COVID-19) pandemic has led to a major shortage of N95 respirators, which are essential for protecting healthcare professionals and the general public who may come into contact with the virus. Thus, it is essential to determine how we can reuse respirators and other personal protective equipment in these urgent times. We investigated multiple commonly used disinfection schemes on media with particle filtration efficiency of 95%. Heating was recently found to inactivate the virus in solution within 5 min at 70 \u00b0C and is among the most scalable, user-friendly methods for viral disinfection. We found that heat (&#8804;85 \u00b0C) under various humidities (&#8804;100% relative humidity, RH) was the most promising, nondestructive method for the preservation of filtration properties in meltblown fabrics as well as N95-grade respirators. At 85 \u00b0C, 30% RH, we were able to perform 50 cycles of heat treatment without significant changes in the filtration efficiency. At low humidity or dry conditions, temperatures up to 100 \u00b0C were not found to alter the filtration efficiency significantly within 20 cycles of treatment. Ultraviolet (UV) irradiation was a secondary choice, which was able to withstand 10 cycles of treatment and showed small degradation by 20 cycles. However, UV can potentially impact the material strength and subsequent sealing of respirators. Finally, treatments involving liquids and vapors require caution, as steam, alcohol, and household bleach all may lead to degradation of the filtration efficiency, leaving the user vulnerable to the viral aerosols.", "qid": 19, "docid": "mp6vfgky", "rank": 41, "score": 0.7556066513061523}, {"content": "Title: Decontamination Methods for Reuse of Filtering Facepiece Respirators Content: Importance: The novel coronavirus disease 2019 (COVID-19) has proven to be highly infectious, putting health care professionals around the world at increased risk. Furthermore, there are widespread shortages of necessary personal protective equipment (PPE) for these individuals. Filtering facepiece respirators, such as the N95 respirator, intended for single use, can be reused in times of need. We explore the evidence for decontamination or sterilization of N95 respirators for health care systems seeking to conserve PPE while maintaining the health of their workforce. Observations: The filtration properties and fit of N95 respirators must be preserved to function adequately over multiple uses. Studies have shown that chemical sterilization using soap and water, alcohols, and bleach render the respirator nonfunctional. Decontamination with microwave heat and high dry heat also result in degradation of respirator material. UV light, steam, low-dry heat, and commercial sterilization methods with ethylene oxide or vaporized hydrogen peroxide appear to be viable options for successful decontamination. Furthermore, since the surface viability of the novel coronavirus is presumed to be 72 hours, rotating N95 respirator use and allowing time decontamination of the respirators is also a reasonable option. We describe a protocol and best practice recommendations for redoffing decontaminated N95 and rotating N95 respirator use. Conclusions and Relevance: COVID-19 presents a high risk for health care professionals, particularly otolaryngologists, owing to the nature of viral transmission, including possible airborne transmission and high viral load in the upper respiratory tract. Proper PPE is effective when used correctly, but in times of scarce resources, institutions may turn to alternative methods of preserving and reusing filtering facepiece respirators. Based on studies conducted on the decontamination of N95 respirators after prior outbreaks, there are several options for institutions to consider for both immediate and large-scale implementation.", "qid": 19, "docid": "8e3fg0o6", "rank": 42, "score": 0.7549394369125366}, {"content": "Title: Preventing adverse cutaneous reactions from amplified hygiene practices during the COVID-19 pandemic: how dermatologists can help through anticipatory guidance Content: The COVID-19 pandemic has swept the globe with more than 2,000,000 confirmed cases of SARS-CoV-2 infection in 184 countries and territories. According to the Centers for Disease Control and Prevention (CDC), two crucial actions can reduce the risk of person-to-person viral transmission: frequent hand washing and surface decontamination with specific environmental protection agency (EPA)-registered disinfectants. As hygiene recommendations evolve during the COVID-19 pandemic and community members adopt changing practices, dermatologists are likely to see a rise in adverse cutaneous reactions from prolonged irritant exposures and widespread use of antimicrobials. The purposes of this report are to familiarize dermatologists with the hygiene practices recommended for COVID-19 prevention, to highlight adverse cutaneous reactions associated with repeated exposures to detergents and disinfectants, and to discuss strategies which patients can implement during the COVID-19 pandemic to minimize skin irritation white still performing hygiene practices effectively.", "qid": 19, "docid": "9ouinct4", "rank": 43, "score": 0.7545296549797058}, {"content": "Title: Using heat to kill SARS\u2010CoV\u20102 Content: The current coronavirus pandemic has reached global proportions and requires unparalleled collective and individual efforts to slow its spread. One critically important issue is the proper sterilization of physical objects that have been contaminated by the virus. Here, we review the currently existing literature on thermal inactivation of coronavirus (SARS\u2010CoV\u20102) and present preliminary guideless on temperatures and exposure durations required to sterilize. We also compare these temperatures/exposure durations with potential household appliances that may be thought capable of performing sterilization.", "qid": 19, "docid": "v7rlxiy1", "rank": 44, "score": 0.75422203540802}, {"content": "Title: Acidified Sodium Chlorite Solution: A Potential Prophylaxis to Mitigate Impact of Multiple Exposures to COVID-19 in Frontline Healthcare Providers. Content: Limited availability of personal protective equipment is endangering first-line healthcare providers treating patients with presumed or confirmed COVID-19 infections. This editorial has multiple objectives in regard to this reality: First, to raise awareness of the need for safe and effective prophylaxis to protect health care providers with insufficient personal protective equipment from repeated exposures to COVID-19. Second, to summarize the scientific evidence in support of solutions of acidified sodium chlorite (ASC) and its daughter compounds, chlorous acid and chlorine dioxide as potential targets for said prophylactic use. Third, to propose a regimented protocol using commercially available solutions of ASC having sufficient concentrations of chlorine dioxide for virucidal activity to support safe and effective prophylactic use. And fourth, to raise awareness of, and compare, other potential prophylactic options currently under investigation.", "qid": 19, "docid": "arvkw0sf", "rank": 45, "score": 0.7541841864585876}, {"content": "Title: Covid-19 and the N95 respirator shortage: Closing the gap Content: Due to extreme shortages of personal protective equipment caused by the COVID-19 pandemic, many healthcare workers will be forced to recycle protective masks intended for disposal after a single use. We propose investigating the use of ultraviolet germicidal irradiation to sterilize masks of SARS-CoV-2 for safer reuse.", "qid": 19, "docid": "1vav13al", "rank": 46, "score": 0.7517600655555725}, {"content": "Title: DESINFECTANTES Y ANTIS\u00c9PTICOS FRENTE AL CORONAVIRUS: S\u00cdNTESIS DE EVIDENCIAS Y RECOMENDACIONES Content: Resumen Objetivo: Sintetizar la evidencia disponible sobre el uso de antis\u00e9pticos y desinfectantes ante la infecci\u00f3n de COVID-19 M\u00e9todo: B\u00fasqueda bibliogr\u00e1fica en las principales bases de datos (WOS, CCC, DIIDW, KJD, MEDLINE, RSCI, SCIELO, PubMed, BMJ Best Practice, Cochrane Library, UptoDate) y en web de organismos oficiales en marzo de 2020, mediante descriptores y truncamientos. La b\u00fasqueda se limit\u00f3 a revisiones publicadas entre 2016-2020. Resultados: Se identificaron 36 documentos (sin duplicados) de los que se seleccionaron, por pertinencia y especificidad 17, a los que se a\u00f1adi\u00f3 un documento de la de lectura de la bibliograf\u00eda. En los documentos finalmente utilizados, no se localizaron evidencias, pero s\u00ed experiencias y recomendaciones de inter\u00e9s, destacando la importancia de la desinfecci\u00f3n del material, del ambiente y de manera muy significativa de las manos. Conclusi\u00f3n: No se aprecian claras evidencias, ni se identifican claras recomendaciones de usar uno u otro antis\u00e9ptico, aunque se resalta la acci\u00f3n del hipoclorito de sodio, el etanol y el per\u00f3xido de hidr\u00f3geno frente a otros como el cloruro de benzalconio, el digluconato de clorhexidina, la povidona yodada y el alcohol \u00e9tilico diluido. Especialmente se da importancia a utilizarlos en la higiene de manos, el uso de equipos de protecci\u00f3n y de la desinfecci\u00f3n del entorno. Abstract Objective: To synthesize the available evidence on the use of antiseptics and disinfectants in the face of VIDOC-19 infection Method: Bibliographic search in the main databases (WOS, CCC, DIIDW, KJD, MEDLINE, RSCI, SCIELO, PubMed, BMJ Best Practice, Cochrane Library, UptoDate) and on the web of official bodies in March 2020, using descriptors and truncations. The search was limited to reviews published between 2016-2020. Results: Thirty-six papers were identified (no duplicates) of which 17 were selected for relevance and specificity and one paper was added from the literature review. In the documents finally used, no evidence was located, but experiences and recommendations of interest were found, highlighting the importance of material, environmental and, very significantly, hand disinfection. Conclusion: There is no clear evidence, nor are there clear recommendations for the use of one or another antiseptic, although the action of sodium hypochlorite, ethanol and hydrogen peroxide is highlighted in comparison to others such as benzalkonium chloride, chlorhexidine digluconate, povidoeyodine and diluted ethyl alcohol. Particular importance is attached to their use in hand hygiene, the use of protective equipment and environmental disinfection.", "qid": 19, "docid": "y0eowc92", "rank": 47, "score": 0.7512271404266357}, {"content": "Title: Can N95 Respirators Be Reused after Disinfection? How Many Times? Content: [Image: see text] The coronavirus disease 2019 (COVID-19) pandemic has led to a major shortage of N95 respirators, which are essential for protecting healthcare professionals and the general public who may come into contact with the virus. Thus, it is essential to determine how we can reuse respirators and other personal protective equipment in these urgent times. We investigated multiple commonly used disinfection schemes on media with particle filtration efficiency of 95%. Heating was recently found to inactivate the virus in solution within 5 min at 70 \u00b0C and is among the most scalable, user-friendly methods for viral disinfection. We found that heat (\u226485 \u00b0C) under various humidities (\u2264100% relative humidity, RH) was the most promising, nondestructive method for the preservation of filtration properties in meltblown fabrics as well as N95-grade respirators. At 85 \u00b0C, 30% RH, we were able to perform 50 cycles of heat treatment without significant changes in the filtration efficiency. At low humidity or dry conditions, temperatures up to 100 \u00b0C were not found to alter the filtration efficiency significantly within 20 cycles of treatment. Ultraviolet (UV) irradiation was a secondary choice, which was able to withstand 10 cycles of treatment and showed small degradation by 20 cycles. However, UV can potentially impact the material strength and subsequent sealing of respirators. Finally, treatments involving liquids and vapors require caution, as steam, alcohol, and household bleach all may lead to degradation of the filtration efficiency, leaving the user vulnerable to the viral aerosols.", "qid": 19, "docid": "mx7xyd76", "rank": 48, "score": 0.7502830028533936}, {"content": "Title: Ozone Treatment for Elimination of Bacteria and SARS-CoV-2 for Medical Environments Content: Pathogenic bacteria and viruses in medical environments can lead to treatment complications and hospital-acquired infections (HAIs), and current cleaning protocols do not address hard-to-access areas or that may be beyond line-of-sight treatment such as with ultraviolet radiation. At the time of writing, the ongoing pandemic of the novel coronavirus known as novel coronavirus (2019-nCoV) has claimed over 4 million cases worldwide and is expected to have multiple peaks, with possible resurgences throughout 2020. It is therefore imperative that disinfection methods in the meantime be employed to keep up with the supply of personal protective equipment (PPE) and sterilize a wide array of surfaces as quarantine lockdowns begin to be lifted. Here, we tested the efficacy of Sani Sport ozone devices as a means to treat hospital equipment and surfaces for killing bacteria, degrading synthetic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, and RNA from non-replicative capsid enclosed SARS-CoV-2. We observed a rapid killing of medically-relevant and environmental bacteria (Escherichia coli, Enterococcus faecalis, Bacillus subtlis, and Deinococcus radiodurans) across four surfaces (blankets, catheter, remotes, and syringes) within 30 minutes, and up to a 99% reduction in viable bacteria at the end of 2-hour treatment cycles. Significant RNA degradation of synthetic SARS-CoV-2 RNA was seen an hour into the ozone treatment as compared to non-treated controls and a non-replicative form of the virus was shown to have significant RNA degradation at 30 minutes compared to a no treatment control and RNA degradation could be reliably detected at 10,000 and 1,000 copies of virus per sample. These results show the strong promise of ozone treatment for reducing risk of infection and HAIs.", "qid": 19, "docid": "k8hjo5yu", "rank": 49, "score": 0.7495620846748352}, {"content": "Title: N95 Mask Decontamination using Standard Hospital Sterilization Technologies Content: The response to the COVID19 epidemic is generating severe shortages of personal protective equipment around the world. In particular, the supply of N95 respirator masks has become severely depleted with supplies having to be rationed and health care workers having to use masks for prolonged periods in many countries. We sought to test the ability of 4 different decontamination methods including autoclave treatment, ethylene oxide gassing, ionized hydrogen peroxide fogging and vaporized hydrogen peroxide exposure to decontaminate 4 different N95 masks of experimental contamination with SARS-CoV-2 or vesicular stomatitis virus as a surrogate. In addition, we sought to determine whether masks would tolerate repeated cycles of decontamination while maintaining structural and functional integrity. We found that one cycle of treatment with all modalities was effective in decontamination and was associated with no structural or functional deterioration. Vaporized hydrogen peroxide treatment was tolerated to at least 5 cycles by masks. Most notably, standard autoclave treatment was associated with no loss of structural or functional integrity to a minimum of 10 cycles for the 3 pleated mask models. The molded N95 mask however tolerated only 1 cycle. This last finding may be of particular use to institutions globally due to the virtually universal accessibility of autoclaves in health care settings.", "qid": 19, "docid": "fp9q8ayj", "rank": 50, "score": 0.7484842538833618}, {"content": "Title: Are Quaternary Ammonium Compounds, the Workhorse Disinfectants, Effective against Severe Acute Respiratory Syndrome-Coronavirus-2? Content: A novel virus named Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) emerged from Wuhan, China in late 2019. Since then, the virus has quickly spread worldwide, leading the World Health Organization to declare it as a pandemic; by the end of April 2020, the number of cases exceeded 3 million. Due to the high infectivity rate, SARS-CoV-2 is difficult to contain, making disinfectant protocols vital, especially for essential, highly trafficked areas such as hospitals, grocery stores, and delivery centers. According to the Centers for Disease Control and Prevention, best practices to slow the spread rely on good hand hygiene, including proper handwashing practices as well as the use of alcohol-based hand sanitizers. However, they provide warning against sanitizing products containing benzalkonium chloride (BAC), which has sparked concern in both the scientific community as well as the general public as BAC, a common quaternary ammonium compound (QAC), is ubiquitous in soaps and cleaning wipes as well as hospital sanitation kits. This viewpoint aims to highlight the outdated and incongruous data in the evaluation of BAC against the family of known coronaviruses and points to the need for further evaluation of the efficacy of QACs against coronaviruses.", "qid": 19, "docid": "9ksiyyqe", "rank": 51, "score": 0.7484006881713867}, {"content": "Title: Povidone-Iodine Demonstrates Rapid In Vitro Virucidal Activity Against SARS-CoV-2, The Virus Causing COVID-19 Disease Content: INTRODUCTION: As of 22 June 2020, Severe Acute Respiratory Syndrome (SARS)-coronavirus (CoV)-2 has infected more than 8.95 million people worldwide, causing > 468,000 deaths. The virus is transmitted through respiratory droplets and physical contact from contaminated surfaces to the mucosa. Hand hygiene and oral decontamination among other measures are key to preventing the spread of the virus. We report the in vitro virucidal activity of topical and oral povidone-iodine (PVP-I) products against SARS-CoV-2. METHODS: Suspension assays were used to assess the virucidal activity of PVP-I against SARS-CoV-2. Products were tested at a contact time of 30 s for virucidal activity. Viral titres were calculated using the Spearman\u2013K\u00e4rber method and reported as median tissue culture infectious dose (TCID(50))/mL. RESULTS: All four products [antiseptic solution (PVP-I 10%), skin cleanser (PVP-I 7.5%), gargle and mouth wash (PVP-I 1%) and throat spray (PVP-I 0.45%)] achieved \u2265 99.99% virucidal activity against SARS-CoV-2, corresponding to \u2265 4 log(10) reduction of virus titre, within 30 s of contact. CONCLUSION: This study provides evidence of rapid and effective virucidal activity of PVP-I against SARS-CoV-2. PVP-I-based products are widely available for medical and personal use for hand hygiene and oral decontamination, and could be readily integrated into coronavirus disease, COVID-19, infection control measures in hospital and community settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40121-020-00316-3) contains supplementary material, which is available to authorized users.", "qid": 19, "docid": "h1i3dg1x", "rank": 52, "score": 0.7474645972251892}, {"content": "Title: Tailoring of the ongoing water, sanitation and hygiene interventions for prevention and control of COVID-19 Content: Water, sanitation, and hygiene (WASH) interventions remain to be important in the prevention of further spread of coronavirus disease-2019 (COVID-19). Basic hygiene interventions such as handwashing with water and soap (HWWS) when applied consistently will deactivate and remove the virus particles from the hands. Realizing the efforts that have been made by countries world over in controlling the COVID-19, this letter seeks to discuss how the available WASH services can be used in the fight against further spread of COVID-19. The letter highlights the challenges being faced by the current WASH services in middle- and low-income countries and suggests measures that can be employed to strengthen the WASH services in this period of the COVID-19 pandemic.", "qid": 19, "docid": "5uc76djv", "rank": 53, "score": 0.7473517656326294}, {"content": "Title: UV-C Tower for point-of-care decontamination of filtering facepiece respirators Content: Filtering facepiece respirators (FFR) are critical for protecting essential personnel and limiting the spread of disease. Due to the current COVID-19 pandemic, FFR supplies are dwindling in many health systems, necessitating re-use of potentially contaminated FFR. Multiple decontamination solutions have been developed to meet this pressing need, including systems designed for bulk decontamination of FFR using vaprous hydrogen peroxide or UV-C radiation. However, the large scale on which these devices operate may not be logistically practical for small or rural health care settings or for ad hoc use at points-of-care. Here, we present the Synchronous UV Decontamination System (SUDS), a novel device for rapidly deployable, point-of-care decontamination using UV-C germicidal irradiation. We designed a compact, easy-to-use device capable of delivering over 2 J/cm^2 of UV-C radiation in one minute. This short decontamination time should enable care-providers to incorporate decontamination of FFR into a normal donning and doffing routine following patient encounters.", "qid": 19, "docid": "m44zcsk5", "rank": 54, "score": 0.7470266819000244}, {"content": "Title: Evaluation of an Electrostatic Spray Disinfectant Technology for Rapid Decontamination of Portable Equipment and Large Open Areas in the Era of SARS-CoV-2 Content: In the setting of the coronavirus disease 2019 pandemic, efficient methods are needed to decontaminate shared portable devices and large open areas such as waiting rooms. We found that wheelchairs, portable equipment, and waiting room chairs were frequently contaminated with potential pathogens. After minimal manual pre-cleaning of areas with visible soiling, application of a dilute sodium hypochlorite disinfectant using an electrostatic sprayer provided rapid and effective decontamination and eliminated the benign virus bacteriophage MS2 from inoculated surfaces.", "qid": 19, "docid": "j7pmb3mk", "rank": 55, "score": 0.7468468546867371}, {"content": "Title: Evaluation of an electrostatic spray disinfectant technology for rapid decontamination of portable equipment and large open areas in the era of SARS-CoV-2 Content: In the setting of the coronavirus disease 2019 pandemic, efficient methods are needed to decontaminate shared portable devices and large open areas such as waiting rooms. We found that wheelchairs, portable equipment, and waiting room chairs were frequently contaminated with potential pathogens. After minimal manual precleaning of areas with visible soiling, application of a dilute sodium hypochlorite disinfectant using an electrostatic sprayer provided rapid and effective decontamination and eliminated the benign virus bacteriophage MS2 from inoculated surfaces.", "qid": 19, "docid": "zpu4pyy5", "rank": 56, "score": 0.7463167309761047}, {"content": "Title: Povidone-Iodine Demonstrates Rapid In Vitro Virucidal Activity Against SARS-CoV-2, The Virus Causing COVID-19 Disease Content: INTRODUCTION: As of 22 June 2020, Severe Acute Respiratory Syndrome (SARS)-coronavirus (CoV)-2 has infected more than 8.95 million people worldwide, causing > 468,000 deaths. The virus is transmitted through respiratory droplets and physical contact from contaminated surfaces to the mucosa. Hand hygiene and oral decontamination among other measures are key to preventing the spread of the virus. We report the in vitro virucidal activity of topical and oral povidone-iodine (PVP-I) products against SARS-CoV-2. METHODS: Suspension assays were used to assess the virucidal activity of PVP-I against SARS-CoV-2. Products were tested at a contact time of 30 s for virucidal activity. Viral titres were calculated using the Spearman-K\u00e4rber method and reported as median tissue culture infectious dose (TCID50)/mL. RESULTS: All four products [antiseptic solution (PVP-I 10%), skin cleanser (PVP-I 7.5%), gargle and mouth wash (PVP-I 1%) and throat spray (PVP-I 0.45%)] achieved &#8805; 99.99% virucidal activity against SARS-CoV-2, corresponding to &#8805; 4 log10 reduction of virus titre, within 30 s of contact. CONCLUSION: This study provides evidence of rapid and effective virucidal activity of PVP-I against SARS-CoV-2. PVP-I-based products are widely available for medical and personal use for hand hygiene and oral decontamination, and could be readily integrated into coronavirus disease, COVID-19, infection control measures in hospital and community settings.", "qid": 19, "docid": "99hf7rlf", "rank": 57, "score": 0.746251106262207}, {"content": "Title: COVID-19 pandemic and personal protective equipment shortage: protective efficacy comparing masks and scientific methods for respirator reuse Content: Abstract Background and Aims The abrupt outbreak of COVID-19 and its rapid spread over many health care systems in the world led to personal protective equipment (PPE) shortening, which cannot be faced only by the reduction in their consumption nor by the expensive and time-requiring implementation of their production. It is thus necessary to promote PPE rational use, highlighting possible differences in terms of efficacy among them and promoting an effective technique to reuse them. Methods A literature search was performed on PubMed, Scopus, Cochrane database, and Google Scholar and from 25 top cited papers, 15 were selected for relevance and impact. Results Most studies on prior respiratory virus epidemic to date suggest surgical masks not to be inferior compared with N95 respirators in terms of protective efficacy among health care workers. The use of N95 respirators should be then limited in favor of high-risk situations. Concerning respirators reuse, highly energetic short-wave ultraviolet germicidal irradiation (UVGI) at 254 nm was proficiently applied to determine N95 respirators decontamination from viral respiratory agents, but it requires careful consideration of the type of respirator and of the biological target. Conclusions Rational use and successful reuse of respirators can help facing PPE shortening during a pandemic. Further evidences testing UVGI and other decontamination techniques are an unmet need. The definitive answer to pandemic issues can be found in artificial intelligence and deep learning: these groundbreaking modalities could help in identifying high-risk patients and in suggesting appropriate types and use of PPE.", "qid": 19, "docid": "xn8jzzsd", "rank": 58, "score": 0.7459484934806824}, {"content": "Title: Application of Biosafety Principles in Laboratory Analysis of Clinical Samples from Patients with COVID-19 Content: COVID-19 poses a great challenge to clinical and diagnostic services around the world. The need of biosafety practices can never be emphasised more than under current circumstances. The four pillars of biosafety namely, leadership, standard operating procedures, personal protective equipment (PPE) and engineering controls must be employed for effective and safe practices in the clinical setting in general and laboratory settings in particular. Risk assessment must be carried out before meeting up the diagnostic challenge for COVID-19 and essential biorisk management measures are required to be taken. In our resource-poor settings, we need to adapt safe but cost-effective and improvised solutions to ensure safe handling of clinical samples from COVID-19 patients in the laboratories. The correct use of PPE and their suitable alternatives are available for selection and use. Disinfection of the lab areas and safe disposal of the clinical samples from such patients is also of paramount importance.", "qid": 19, "docid": "8h4adfqi", "rank": 59, "score": 0.7458640933036804}, {"content": "Title: Application of Biosafety Principles in Laboratory Analysis of Clinical Samples from Patients with COVID-19. Content: COVID-19 poses a great challenge to clinical and diagnostic services around the world. The need of biosafety practices can never be emphasised more than under current circumstances. The four pillars of biosafety namely, leadership, standard operating procedures, personal protective equipment (PPE) and engineering controls must be employed for effective and safe practices in the clinical setting in general and laboratory settings in particular. Risk assessment must be carried out before meeting up the diagnostic challenge for COVID-19 and essential biorisk management measures are required to be taken. In our resource-poor settings, we need to adapt safe but cost-effective and improvised solutions to ensure safe handling of clinical samples from COVID-19 patients in the laboratories. The correct use of PPE and their suitable alternatives are available for selection and use. Disinfection of the lab areas and safe disposal of the clinical samples from such patients is also of paramount importance.", "qid": 19, "docid": "7z2cq8gq", "rank": 60, "score": 0.7458640933036804}, {"content": "Title: Challenges and solutions for addressing critical shortage of supply chain for personal and protective equipment (PPE) arising from Coronavirus disease (COVID19) pandemic \u2013 Case study from the Republic of Ireland Content: Abstract Coronavirus (COVID-19) is highly infectious agent that causes fatal respiratory illnesses, which is of great global public health concern. Currently, there is no effective vaccine for tackling this COVID19 pandemic where disease countermeasures rely upon preventing or slowing person-to-person transmission. Specifically, there is increasing efforts to prevent or reduce transmission to front-line healthcare workers (HCW). However, there is growing international concern regarding the shortage in supply chain of critical one-time-use personal and protective equipment (PPE). PPE are heat sensitive and are not, by their manufacturer's design, intended for reprocessing. Most conventional sterilization technologies used in hospitals, or in terminal medical device sterilization providers, cannot effectively reprocess PPE due to the nature and severity of sterilization modalities. Contingency planning for PPE stock shortage is important. Solutions in the Republic of Ireland include use of smart communication channels to improve supply chain, bespoke production of PPE to meets gaps, along with least preferred option, use of sterilization or high-level disinfection for PPE reprocessing. Reprocessing PPE must consider material composition, functionality post treatment, along with appropriate disinfection. Following original manufacturer of PPE and regulatory guidance is important. Technologies deployed in the US, and for deployment in the Republic of Ireland, are eco-friendly, namely vaporised hydrogen peroxide (VH2O2), such as for filtering facepiece respirators and UV irradiation and High-level liquid disinfection (Actichlor+) is also been pursed in Ireland. Safeguarding supply chain of PPE will sustain vital healthcare provision and will help reduce mortality.", "qid": 19, "docid": "zg63v8hh", "rank": 61, "score": 0.7454918622970581}, {"content": "Title: Efficacy of a novel iodine complex solution, CupriDyne, in inactivating SARS-CoV-2 Content: The coronavirus known as SARS-CoV-2, which causes COVID-19 disease, is presently responsible for a global pandemic wherein more than 3.5 million people have been infected and more than 250,000 killed to-date. There is currently no vaccine for COVID-19, leaving governments and public health agencies with little defense against the virus aside from advising or enforcing best practices for virus transmission prevention, which include hand-washing, physical distancing, use of face covers, and use of effective disinfectants. In this study, a novel iodine complex called CupriDyne\u00ae was assessed for its ability to inactivate SARS-CoV-2. CupriDyne was shown to be effective in inactivating the virus in a time-dependent manner, reducing virus titers by 99% (2 logs) after 30 minutes, and reducing virus titers to below the detection limit after 60 minutes. The novel iodine complex tested herein offers a safe and gentle alternative to conventional disinfectants for use on indoor and outdoor surfaces.", "qid": 19, "docid": "d8xtacyj", "rank": 62, "score": 0.7454347610473633}, {"content": "Title: Medical mask or N95 respirator: When and how to use? Content: COVID-19 pandemic is now a global threat to human health reaching up to 2 million infected people all around the world. Since its first recognition in Wuhan, many topics were discussed intensively about COVID-19, both in the public and scientific community. Personal protective equipment, especially masks, has been among the hottest topics during this pandemic. Regardless of which mask is used, performing hand hygiene frequently with an alcohol-based hand rub or with soap and water if hands are dirty is the most effective preventive measure for COVID-19. The type of mask used when caring for COVID-19 patients will vary according to the setting, type of personnel/person, and activity. Although the main transmission route for COVID-19 is droplets, during aerosol generating procedures airborne transmission may occur. Keeping the distancing and medical masks and eye protection during close contact efficiently protects against respiratory diseases transmitted via droplets. Airborne precautions include goggles and respiratory protection with the use of an N95 or an equivalent mask respirator to prevent airborne transmission.", "qid": 19, "docid": "r1oqwdkz", "rank": 63, "score": 0.7449239492416382}, {"content": "Title: Effectiveness of Ultraviolet-C Light and a High-Level Disinfection Cabinet for Decontamination of N95 Respirators Content: BACKGROUND: Shortages of personal protective equipment (PPE) including N95 respirators are an urgent concern in the setting of the global COVID-19 pandemic. Decontamination of PPE could be useful to maintain adequate supplies, but there is uncertainty regarding the efficacy of decontamination technologies. METHODS: A modification of the American Society for Testing and Materials standard quantitative carrier disk test method (ASTM E-2197-11) was used to examine the effectiveness of 3 methods, including ultraviolet-C (UV-C) light, a high-level disinfection cabinet that generates aerosolized peracetic acid and hydrogen peroxide, and dry heat at 70\u00b0C for 30 minutes. We assessed the decontamination of 3 commercial N95 respirators inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and bacteriophages MS2 and Phi6; the latter is an enveloped RNA virus used as a surrogate for coronaviruses. Three and 6 log(10) reductions on respirators were considered effective for decontamination and disinfection, respectively. RESULTS: UV-C administered as a 1-minute cycle in a UV-C box or a 30-minute cycle by a room decontamination device reduced contamination but did not meet criteria for decontamination of the viruses from all sites on the N95s. The high-level disinfection cabinet was effective for decontamination of the N95s and achieved disinfection with an extended 31-minute cycle. Dry heat at 70\u00b0C for 30 minutes was not effective for decontamination of the bacteriophages. CONCLUSIONS: UV-C could be useful to reduce contamination on N95 respirators. However, the UV-C technologies studied did not meet pre-established criteria for decontamination under the test conditions used. The high-level disinfection cabinet was more effective and met criteria for disinfection with an extended cycle.", "qid": 19, "docid": "k7sltus2", "rank": 64, "score": 0.7447818517684937}, {"content": "Title: Comparison of In Vitro Inactivation of SARS CoV-2 with Hydrogen Peroxide and Povidone-Iodine Oral Antiseptic Rinses Content: PURPOSE: To evaluate the in vitro inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with hydrogen peroxide (H2 O2 ) and povidone-iodine (PVP-I) oral antiseptic rinses at clinically recommended concentrations and contact times. MATERIALS AND METHODS: SARS-CoV-2, USA-WA1/2020 strain virus stock was prepared prior to testing by growing in Vero 76 cells. The culture media for prepared virus stock was minimum essential medium (MEM) with 2% fetal bovine serum (FBS) and 50 \u00b5g/mL gentamicin. Test compounds consisting of PVP-I oral rinse solutions and H2 O2 aqueous solutions were mixed directly with the virus solution so that the final concentration was 50% of the test compound and 50% of the virus solution. Thus PVP-I was tested at concentrations of 0.5%, 1.25% and 1.5%, and H2 O2 was tested at 3% and 1.5% concentrations to represent clinically recommended concentrations. Ethanol and water were evaluated in parallel as standard positive and negative controls. All samples were tested at contact periods of 15 seconds and 30 seconds. Surviving virus from each sample was then quantified by standard end-point dilution assay and the log reduction value of each compound compared to the negative control was calculated. RESULTS: After the 15-second and 30-second contact times, PVP-I oral antiseptic rinse at all 3 concentrations of 0.5%, 1.25% and 1.5% completely inactivated SARS-CoV-2. The H2 O2 solutions at concentrations of 1.5% and 3.0% showed minimal viricidal activity after 15 seconds and 30 seconds of contact time. CONCLUSIONS: SARS-CoV-2 virus was completely inactivated by PVP-I oral antiseptic rinse in vitro, at the lowest concentration of 0.5 % and at the lowest contact time of 15 seconds. Hydrogen peroxide at the recommended oral rinse concentrations of 1.5% and 3.0% was minimally effective as a viricidal agent after contact times as long as 30 seconds. Therefore, preprocedural rinsing with diluted PVP-I in the range of 0.5% to 1.5% may be preferred over hydrogen peroxide during the COVID-19 pandemic. This article is protected by copyright. All rights reserved.", "qid": 19, "docid": "w6w1f9zt", "rank": 65, "score": 0.7446504831314087}, {"content": "Title: Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents Content: Summary Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62\u201371% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05\u20130.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.", "qid": 19, "docid": "k9xhphpl", "rank": 66, "score": 0.7444977760314941}, {"content": "Title: Challenges and solutions for addressing critical shortage of supply chain for personal and protective equipment (PPE) arising from Coronavirus disease (COVID19) pandemic - Case study from the Republic of Ireland Content: Coronavirus (COVID-19) is highly infectious agent that causes fatal respiratory illnesses, which is of great global public health concern. Currently, there is no effective vaccine for tackling this COVID19 pandemic where disease countermeasures rely upon preventing or slowing person-to-person transmission. Specifically, there is increasing efforts to prevent or reduce transmission to front-line healthcare workers (HCW). However, there is growing international concern regarding the shortage in supply chain of critical one-time-use personal and protective equipment (PPE). PPE are heat sensitive and are not, by their manufacturer's design, intended for reprocessing. Most conventional sterilization technologies used in hospitals, or in terminal medical device sterilization providers, cannot effectively reprocess PPE due to the nature and severity of sterilization modalities. Contingency planning for PPE stock shortage is important. Solutions in the Republic of Ireland include use of smart communication channels to improve supply chain, bespoke production of PPE to meets gaps, along with least preferred option, use of sterilization or high-level disinfection for PPE reprocessing. Reprocessing PPE must consider material composition, functionality post treatment, along with appropriate disinfection. Following original manufacturer of PPE and regulatory guidance is important. Technologies deployed in the US, and for deployment in the Republic of Ireland, are eco-friendly, namely vaporised hydrogen peroxide (VH2O2), such as for filtering facepiece respirators and UV irradiation and High-level liquid disinfection (Actichlor+) is also been pursed in Ireland. Safeguarding supply chain of PPE will sustain vital healthcare provision and will help reduce mortality.", "qid": 19, "docid": "csdxxblg", "rank": 67, "score": 0.7443612813949585}, {"content": "Title: Medical mask or N95 respirator: When and how to use? Content: COVID-19 pandemic is now a global threat on human health reaching up to 2 million infected people all around the World. Since its first recognition in Wuhan, many topics were discussed intensively about COVID-19, both in the public and scientific community. Personal protective equipments and especially masks were among the hottest topics during this pandemic. Regardless of which mask is used, performing hand hygiene frequently with an alcohol-based hand rub or with soap and water if hands are dirty; is the most effective preventive measure for COVID-19. The type of mask used when caring for COVID-19 patients will vary according to the setting, type of personnel/person, and activity. Although the main transmission route for COVID-19 is droplets, during aerosol generating procedures airborne transmission may occur. Keeping the distancing and medical masks and eye protection during close contact efficiently protects against respiratory diseases transmitted via droplets. Airborne precautions include goggles and respiratory protection with the use of an N95 or an equivalent mask respirator to prevent airborne transmission.", "qid": 19, "docid": "6wxjm7m0", "rank": 68, "score": 0.7443200945854187}, {"content": "Title: Rapid evidence summary on SARS-CoV-2 survivorship and disinfection, and a reusable PPE protocol using a double-hit process Content: In the COVID-19 pandemic caused by SARS-CoV-2, hospitals are stretched beyond capacity. There are widespread reports of dwindling supplies of personal protective equipment (PPE), which are paramount to protect frontline medical/nursing staff and to minimize further spread of the virus. We carried out a rapid review to summarize the existing evidence on SARS-CoV-2 survivorship and methods to disinfect PPE gear, particularly N95 filtering facepiece respirators (FFR). In the absence of data on SARS-CoV-2, we focused on the sister virus SARS-CoV-1. We propose a two-step disinfection process, which is conservative in the absence of robust evidence on SARS-CoV-2. This disinfection protocol is based on an initial storage of PPE for \u22654 days, followed by ultraviolet light (UVC), dry heat treatment, or chemical disinfection. Importantly, each of the two steps is based on independent disinfection mechanisms, so that our proposed protocol is a multiplicative system, maximising the efficacy of our disinfection process. This method could be rapidly implemented in other healthcare settings, while testing of each method is undertaken, increasing the frontline supply of PPE, and avoiding many of the upstream issues of supply chain disruption currently being faced.", "qid": 19, "docid": "d48u5w0h", "rank": 69, "score": 0.7441867589950562}, {"content": "Title: Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents Content: Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62-71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05-0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.", "qid": 19, "docid": "ssq0dwmn", "rank": 70, "score": 0.7438032627105713}, {"content": "Title: Coronaviruses widespread on nonliving surfaces: important questions and promising answers Content: The world is facing, while writing this review, a global pandemic due to one of the types of the coronaviruses (i.e., COVID-19), which is a new virus. Among the most important reasons for the transmission of infection between humans is the presence of this virus active on the surfaces and materials. Here, we addressed important questions such as do coronaviruses remain active on the inanimate surfaces? Do the types of inanimate surfaces affect the activity of coronaviruses? What are the most suitable ingredients that used to inactivate viruses? This review article addressed many of the works that were done in the previous periods on the survival of many viruses from the coronaviruses family on various surfaces such as steel, glass, plastic, Teflon, ceramic tiles, silicon rubber and stainless steel copper alloys, Al surface, sterile sponges, surgical gloves and sterile latex. The impacts of environmental conditions such as temperature and humidity were presented and discussed. The most important active ingredients that can deactivate viruses on the surfaces were reported here. We hope that these active ingredients will have the same effect on COVID-19.", "qid": 19, "docid": "fxx5vrg0", "rank": 71, "score": 0.7434126138687134}, {"content": "Title: Coronaviruses widespread on nonliving surfaces: important questions and promising answers. Content: The world is facing, while writing this review, a global pandemic due to one of the types of the coronaviruses (i.e., COVID-19), which is a new virus. Among the most important reasons for the transmission of infection between humans is the presence of this virus active on the surfaces and materials. Here, we addressed important questions such as do coronaviruses remain active on the inanimate surfaces? Do the types of inanimate surfaces affect the activity of coronaviruses? What are the most suitable ingredients that used to inactivate viruses? This review article addressed many of the works that were done in the previous periods on the survival of many viruses from the coronaviruses family on various surfaces such as steel, glass, plastic, Teflon, ceramic tiles, silicon rubber and stainless steel copper alloys, Al surface, sterile sponges, surgical gloves and sterile latex. The impacts of environmental conditions such as temperature and humidity were presented and discussed. The most important active ingredients that can deactivate viruses on the surfaces were reported here. We hope that these active ingredients will have the same effect on COVID-19.", "qid": 19, "docid": "9xv9t5ba", "rank": 72, "score": 0.7434126138687134}, {"content": "Title: Perioperative COVID-19 Defense: An Evidence-Based Approach for Optimization of Infection Control and Operating Room Management Content: We describe an evidence-based approach for optimization of infection control and operating room management during the Coronavirus Disease 2019 (COVID-19) pandemic. Confirmed modes of viral transmission are primarily, but not exclusively, contact with contaminated environmental surfaces and aerosolization. Evidence-based improvement strategies for attenuation of residual environmental contamination involve a combination of deep cleaning with surface disinfectants and ultraviolet light (UV-C). (1) Place alcohol-based hand rubs on the intravenous (IV) pole to the left of the provider. Double glove during induction. (2) Place a wire basket lined with a zip closure plastic bag on the IV pole to the right of the provider. Place all contaminated instruments in the bag (eg, laryngoscope blades and handles) and close. Designate and maintain clean and dirty areas. After induction of anesthesia, wipe down all equipment and surfaces with disinfection wipes that contain a quaternary ammonium compound and alcohol. Use a top-down cleaning sequence adequate to reduce bioburden. Treat operating rooms using UV-C. (3) Decolonize patients using preprocedural chlorhexidine wipes, 2 doses of nasal povidone-iodine within 1 hour of incision, and chlorhexidine mouth rinse. (4) Create a closed lumen IV system and use hub disinfection. (5) Provide data feedback by surveillance of Enterococcus, Staphylococcusaureus, Klebsiella, Acinetobacter, Pseudomonas, and Enterobacter spp. (ESKAPE)transmission. (6) To reduce the use of surgical masks and to reduce potential COVID-19 exposure, use relatively long (eg, 12hours) staff shifts. If there are 8 essential cases to be done (each lasting 1\u20132 hours), the ideal solution is to have 2 teams complete the 8 cases, not 8 first case starts. (7) Do 1 case in each operating room daily, with terminal cleaning after each case including UV-C or equivalent. (8) Do not have patients go into a large, pooled phase I postanesthesia care unit because of the risk of contaminating facility at large along with many staff. Instead, have most patients recover in the room where they had surgery as is done routinely in Japan. These 8 programmatic recommendations stand on a substantial body of empirical evidence characterizing the epidemiology of perioperative transmission and infection development made possible by support from the Anesthesia Patient Safety Foundation (APSF).", "qid": 19, "docid": "7km43hig", "rank": 73, "score": 0.7419404983520508}, {"content": "Title: Potential utilities of mask\u2010wearing and instant hand hygiene for fighting SARS\u2010CoV\u20102 Content: The surge of patients in the pandemic of COVID\u201019 caused by the novel coronavirus SARS\u2010CoV\u20102 may overwhelm the medical systems of many countries. Mask\u2010wearing and handwashing can slow the spread of the virus, but currently, masks are in shortage in many countries, and timely handwashing is often impossible. In this study, the efficacy of three types of masks and instant hand wiping was evaluated using the avian influenza virus to mock the coronavirus. Virus quantification was performed using real\u2010time reverse transcription\u2010polymerase chain reaction. Previous studies on mask\u2010wearing were reviewed. The results showed that instant hand wiping using a wet towel soaked in water containing 1.00% soap powder, 0.05% active chlorine, or 0.25% active chlorine from sodium hypochlorite removed 98.36%, 96.62%, and 99.98% of the virus from hands, respectively. N95 masks, medical masks, and homemade masks made of four\u2010layer kitchen paper and one\u2010layer cloth could block 99.98%, 97.14%, and 95.15% of the virus in aerosols. Medical mask\u2010wearing which was supported by many studies was opposed by other studies possibly due to erroneous judgment. With these data, we propose the approach of mask\u2010wearing plus instant hand hygiene (MIH) to slow the exponential spread of the virus. This MIH approach has been supported by the experiences of seven countries in fighting against COVID\u201019. Collectively, a simple approach to slow the exponential spread of SARS\u2010CoV\u20102 was proposed with the support of experiments, literature review, and control experiences.", "qid": 19, "docid": "2otax3zq", "rank": 74, "score": 0.7417376041412354}, {"content": "Title: Perioperative COVID-19 Defense: An Evidence-Based Approach for Optimization of Infection Control and Operating Room Management Content: We describe an evidence-based approach for optimization of infection control and operating room management during the coronavirus disease 2019 (COVID-19) pandemic. Confirmed modes of viral transmission are primarily, but not exclusively, contact with contaminated environmental surfaces and aerosolization. Evidence-based improvement strategies for attenuation of residual environmental contamination involve a combination of deep cleaning with surface disinfectants and ultraviolet light (UV-C). (1) Place alcohol-based hand rubs on the intravenous (IV) pole to the left of the provider. Double glove during induction. (2) Place a wire basket lined with a zip closure plastic bag on the IV pole to the right of the provider. Place all contaminated instruments in the bag (eg, laryngoscope blades and handles) and close. Designate and maintain clean and dirty areas. After induction of anesthesia, wipe down all equipment and surfaces with disinfection wipes that contain a quaternary ammonium compound and alcohol. Use a top-down cleaning sequence adequate to reduce bioburden. Treat operating rooms using UV-C. (3) Decolonize patients using preprocedural chlorhexidine wipes, 2 doses of nasal povidone-iodine within 1 hour of incision, and chlorhexidine mouth rinse. (4) Create a closed lumen IV system and use hub disinfection. (5) Provide data feedback by surveillance of Enterococcus, Staphylococcus aureus, Klebsiella, Acinetobacter, Pseudomonas, and Enterobacter spp. (ESKAPE) transmission. (6) To reduce the use of surgical masks and to reduce potential COVID-19 exposure, use relatively long (eg, 12 hours) staff shifts. If there are 8 essential cases to be done (each lasting 1-2 hours), the ideal solution is to have 2 teams complete the 8 cases, not 8 first case starts. (7) Do 1 case in each operating room daily, with terminal cleaning after each case including UV-C or equivalent. (8) Do not have patients go into a large, pooled phase I postanesthesia care unit because of the risk of contaminating facility at large along with many staff. Instead, have most patients recover in the room where they had surgery as is done routinely in Japan. These 8 programmatic recommendations stand on a substantial body of empirical evidence characterizing the epidemiology of perioperative transmission and infection development made possible by support from the Anesthesia Patient Safety Foundation (APSF).", "qid": 19, "docid": "wcqxqkqw", "rank": 75, "score": 0.741707980632782}, {"content": "Title: Potential utilities of mask-wearing and instant hand hygiene for fighting SARS-CoV-2 Content: The surge of patients in the pandemic of COVID-19 caused by the novel coronavirus SARS-CoV-2 may overwhelm the medical systems of many countries. Mask-wearing and handwashing can slow the spread of the virus, but currently, masks are in shortage in many countries, and timely handwashing is often impossible. In this study, the efficacy of three types of masks and instant hand wiping was evaluated using the avian influenza virus to mock the coronavirus. Virus quantification was performed using real-time reverse transcription-polymerase chain reaction. Previous studies on mask-wearing were reviewed. The results showed that instant hand wiping using a wet towel soaked in water containing 1.00% soap powder, 0.05% active chlorine, or 0.25% active chlorine from sodium hypochlorite removed 98.36%, 96.62%, and 99.98% of the virus from hands, respectively. N95 masks, medical masks, and homemade masks made of four-layer kitchen paper and one-layer cloth could block 99.98%, 97.14%, and 95.15% of the virus in aerosols. Medical mask-wearing which was supported by many studies was opposed by other studies possibly due to erroneous judgment. With these data, we propose the approach of mask-wearing plus instant hand hygiene (MIH) to slow the exponential spread of the virus. This MIH approach has been supported by the experiences of seven countries in fighting against COVID-19. Collectively, a simple approach to slow the exponential spread of SARS-CoV-2 was proposed with the support of experiments, literature review, and control experiences.", "qid": 19, "docid": "v0trjjni", "rank": 76, "score": 0.741150975227356}, {"content": "Title: Analysis of an improved workflow of endoscope reprocessing for bedside endoscopic diagnosis and treatment on COVID-19 patients Content: Severe cases infected with the coronavirus disease 2019 (COVID-19), named by the World Health Organization (WHO) on Feb. 11, 2020, tend to present a hypercatabolic state because of severe systemic consumption, and are susceptible to stress ulcers and even life-threatening gastrointestinal bleeding. Endoscopic diagnosis and treatment constitute an irreplaceable part in the handling of severe COVID-19 cases. Endoscopes, as reusable precision instruments with complicated structures, require more techniques than other medical devices in cleaning, disinfection, sterilization, and other reprocessing procedures. From 2016 to 2019, health care-acquired infection caused by improper endoscope reprocessing has always been among the top 5 on the list of top 10 health technology hazards issued by the Emergency Care Research Institute. Considering the highly infective nature of COVID-19 and the potential aerosol contamination therefrom, it is of pivotal significance to ensure that endoscopes are strictly reprocessed between uses. In accordance with the national standard \"Regulation for Cleaning and Disinfection Technique of Flexible Endoscope (WS507-2016),\" we improved the workflow of endoscope reprocessing including the selection of chemicals in an effort to ensure quality control throughout the clinical management towards COVID-19 patients. Based on the experience we attained from the 12 severe COVID-19 cases in our hospital who underwent endoscopy 23 times in total, the article provides an improved version of endoscopic reprocessing guidelines for bedside endoscopic diagnosis and treatment on COVID-19 patients for reference.", "qid": 19, "docid": "j01yxp62", "rank": 77, "score": 0.7410043478012085}, {"content": "Title: Synergistic effects of anionic surfactants on coronavirus (SARS-CoV-2) virucidal efficiency of sanitizing fluids to fight COVID-19 Content: Our surrounding environment, especially often-touched contaminated surfaces, plays an important role in the transmission of pathogens in society. The shortage of effective sanitizing fluids, however, became a global challenge quickly after the coronavirus disease-19 (COVID-19) outbreak in December 2019. In this study, we present the effect of surfactants on coronavirus (SARS-CoV-2) virucidal efficiency in sanitizing fluids. Sodium dodecylbenzenesulfonate (SDBS), sodium laureth sulfate (SLS), and two commercial dish soap and liquid hand soap were studied with the goal of evaporation rate reduction in sanitizing liquids to maximize surface contact time. Twelve fluids with different recipes composed of ethanol, isopropanol, SDBS, SLS, glycerin, and water of standardized hardness (WSH) were tested for their evaporation time and virucidal efficiency. Evaporation time increased by 17-63% when surfactant agents were added to the liquid. In addition, surfactant incorporation enhanced the virucidal efficiency between 15-27% according to the 4-field test in the EN 16615:2015 European Standard method. Most importantly, however, we found that surfactant addition provides a synergistic effect with alcohols to inactivate the SARS-CoV-2 virus. This study provides a simple, yet effective solution to improve the virucidal efficiency of commonly used sanitizers.", "qid": 19, "docid": "0qfoc553", "rank": 78, "score": 0.7409984469413757}, {"content": "Title: Virucidal effect against Coronavirus SARS-CoV-2 of a silver nanocluster/silica composite sputtered coating Content: Abstract During the current pandemic of COVID-19 caused by the new Coronavirus SARS-CoV-2, the confinement measures slowed down the contagion, but did not completely avoid the disease diffusion for health workers, patients and the remaining population. The individual protection equipment (e.g. facial masks), filters for air conditioning systems and for medical respiratory devices do not possess an intrinsic antimicrobial/virucidal action and they are susceptible to microbial/viral colonization. An efficient antimicrobial/virucidal technology on air filtering media is crucial for maintaining a safe air environment and protecting people, in particular when lockdown is eased. This short communication reports about the virucidal effect, preliminary verified towards Coronavirus SARS-CoV-2, of a silver nanocluster/silica composite sputtered coating, directly applicated on a FFP3 mask.", "qid": 19, "docid": "1221ty23", "rank": 79, "score": 0.7409530878067017}, {"content": "Title: Aerosolized Hydrogen Peroxide Decontamination of N95 Respirators, with Fit-Testing and Virologic Confirmation of Suitability for Re-Use During the COVID-19 Pandemic Content: In response to the current urgent demand for N95 respirators by healthcare workers responding to the COVID-19 pandemic, with particular emphasis on needs within local medical systems, we initiated an N95 decontamination study using aerosolized hydrogen peroxide or aHP (7% H2O2 solution), via the Pathogo Curis\u00ae (Curis) decontamination system. The study has thus far included 10 cycles of respirator decontamination, with periodic qualitative and quantitative fit testing to verify ongoing respirator integrity through the decontamination process, and support a statistical evaluation of successful respirator fit. In addition, we have conducted virologic testing of respirator surfaces and materials to demonstrate a rigorous verification of decontamination. Given that the current pandemic entails a respiratory viral pathogen, it is critical to address these aspects of respirator safety for reuse. These measures are intended to provide a foundation for a suitable decontamination process, which maintains N95 function, and supports safe respirator reuse by healthcare providers. Current results from both respirator fit testing and virologic testing indicate that the process is effective on the basis of zero failure rate on fit-testing of selected respirators, and on complete decontamination of multiple virus species by aHP treatment, comparable to that observed with commercial spore-based biological indicators of sterilization.", "qid": 19, "docid": "d1crwbuz", "rank": 80, "score": 0.7407883405685425}, {"content": "Title: Principles and Practice of SARS-CoV-2 Decontamination of N95 Masks with UV-C Content: A mainstay of personal protective equipment (PPE) during the COVID-19 pandemic is the N95 filtering facepiece respirator. N95 respirators are commonly used to protect healthcare workers from respiratory pathogens, including the novel coronavirus SARS-CoV-2, and are increasingly employed by other frontline workers and the general public. Under routine circumstances, these masks are disposable, single-use items, but extended use and reuse practices have been broadly enacted to alleviate critical supply shortages during the COVID-19 pandemic. While extended-time single use presents a low risk of pathogen transfer, repeated donning and doffing of potentially contaminated masks presents increased risk of pathogen transfer. Therefore, efficient and safe decontamination methods for N95 masks are needed to reduce the risk of reuse and mitigate local supply shortages. Here we review the available literature concerning use of germicidal ultraviolet-C (UV-C) light to decontaminate N95 masks. We propose a practical method for repeated point-of-use decontamination, using commercially-available UV-C crosslinker boxes from molecular biology laboratories or a simple low-cost, custom-designed and fabricated device to expose each side of the mask to 800-1200 mJ/cm2 of UV-C. We measure the dose that penetrated to the interior of the respirators and model the potential germicidal action on SARS-CoV-2. Our experimental results, in combination with modeled data, suggest that a two-minute UV-C treatment cycle should induce a >3-log-order reduction in viral bioburden on the surface of the respirators, and a 2-log order reduction throughout the interior. The resulting exposure is 100-fold less than the dose expected to damage the masks, facilitating repeated decontamination. As such, UV-C germicidal irradiation (UVGI) is a practical strategy for small-scale point-of-use decontamination of N95s.", "qid": 19, "docid": "5atqn157", "rank": 81, "score": 0.7407633066177368}, {"content": "Title: Knowledge and Practices Regarding Safe Household Cleaning and Disinfection for COVID-19 Prevention \u2014 United States, May 2020 Content: A recent report described a sharp increase in calls to poison centers related to exposures to cleaners and disinfectants since the onset of the coronavirus disease 2019 (COVID-19) pandemic (1). However, data describing cleaning and disinfection practices within household settings in the United States are limited, particularly concerning those practices intended to prevent transmission of SARS-CoV-2, the virus that causes COVID-19. To provide contextual and behavioral insight into the reported increase in poison center calls and to inform timely and relevant prevention strategies, an opt-in Internet panel survey of 502 U.S. adults was conducted in May 2020 to characterize knowledge and practices regarding household cleaning and disinfection during the COVID-19 pandemic. Knowledge gaps were identified in several areas, including safe preparation of cleaning and disinfectant solutions, use of recommended personal protective equipment when using cleaners and disinfectants, and safe storage of hand sanitizers, cleaners, and disinfectants. Thirty-nine percent of respondents reported engaging in nonrecommended high-risk practices with the intent of preventing SARS-CoV-2 transmission, such as washing food products with bleach, applying household cleaning or disinfectant products to bare skin, and intentionally inhaling or ingesting these products. Respondents who engaged in high-risk practices more frequently reported an adverse health effect that they believed was a result of using cleaners or disinfectants than did those who did not report engaging in these practices. Public messaging should continue to emphasize evidence-based, safe practices such as hand hygiene and recommended cleaning and disinfection of high-touch surfaces to prevent transmission of SARS-CoV-2 in household settings (2). Messaging should also emphasize avoidance of high-risk practices such as unsafe preparation of cleaning and disinfectant solutions, use of bleach on food products, application of household cleaning and disinfectant products to skin, and inhalation or ingestion of cleaners and disinfectants.", "qid": 19, "docid": "ydv0hc0m", "rank": 82, "score": 0.74028080701828}, {"content": "Title: Knowledge and Practices Regarding Safe Household Cleaning and Disinfection for COVID-19 Prevention - United States, May 2020 Content: A recent report described a sharp increase in calls to poison centers related to exposures to cleaners and disinfectants since the onset of the coronavirus disease 2019 (COVID-19) pandemic (1). However, data describing cleaning and disinfection practices within household settings in the United States are limited, particularly concerning those practices intended to prevent transmission of SARS-CoV-2, the virus that causes COVID-19. To provide contextual and behavioral insight into the reported increase in poison center calls and to inform timely and relevant prevention strategies, an opt-in Internet panel survey of 502 U.S. adults was conducted in May 2020 to characterize knowledge and practices regarding household cleaning and disinfection during the COVID-19 pandemic. Knowledge gaps were identified in several areas, including safe preparation of cleaning and disinfectant solutions, use of recommended personal protective equipment when using cleaners and disinfectants, and safe storage of hand sanitizers, cleaners, and disinfectants. Thirty-nine percent of respondents reported engaging in nonrecommended high-risk practices with the intent of preventing SARS-CoV-2 transmission, such as washing food products with bleach, applying household cleaning or disinfectant products to bare skin, and intentionally inhaling or ingesting these products. Respondents who engaged in high-risk practices more frequently reported an adverse health effect that they believed was a result of using cleaners or disinfectants than did those who did not report engaging in these practices. Public messaging should continue to emphasize evidence-based, safe practices such as hand hygiene and recommended cleaning and disinfection of high-touch surfaces to prevent transmission of SARS-CoV-2 in household settings (2). Messaging should also emphasize avoidance of high-risk practices such as unsafe preparation of cleaning and disinfectant solutions, use of bleach on food products, application of household cleaning and disinfectant products to skin, and inhalation or ingestion of cleaners and disinfectants.", "qid": 19, "docid": "8766d0lw", "rank": 83, "score": 0.74028080701828}, {"content": "Title: Comparison of In Vitro Inactivation of SARS CoV\u20102 with Hydrogen Peroxide and Povidone\u2010Iodine Oral Antiseptic Rinses Content: PURPOSE: To evaluate the in vitro inactivation of severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) with hydrogen peroxide (H(2)O(2)) and povidone\u2010iodine (PVP\u2010I) oral antiseptic rinses at clinically recommended concentrations and contact times. MATERIALS AND METHODS: SARS\u2010CoV\u20102, USA\u2010WA1/2020 strain virus stock was prepared prior to testing by growing in Vero 76 cells. The culture media for prepared virus stock was minimum essential medium (MEM) with 2% fetal bovine serum (FBS) and 50 \u03bcg/mL gentamicin. Test compounds consisting of PVP\u2010I oral rinse solutions and H(2)O(2) aqueous solutions were mixed directly with the virus solution so that the final concentration was 50% of the test compound and 50% of the virus solution. Thus PVP\u2010I was tested at concentrations of 0.5%, 1.25% and 1.5%, and H(2)O(2) was tested at 3% and 1.5% concentrations to represent clinically recommended concentrations. Ethanol and water were evaluated in parallel as standard positive and negative controls. All samples were tested at contact periods of 15 seconds and 30 seconds. Surviving virus from each sample was then quantified by standard end\u2010point dilution assay and the log reduction value of each compound compared to the negative control was calculated. RESULTS: After the 15\u2010second and 30\u2010second contact times, PVP\u2010I oral antiseptic rinse at all 3 concentrations of 0.5%, 1.25% and 1.5% completely inactivated SARS\u2010CoV\u20102. The H(2)O(2) solutions at concentrations of 1.5% and 3.0% showed minimal viricidal activity after 15 seconds and 30 seconds of contact time. CONCLUSIONS: SARS\u2010CoV\u20102 virus was completely inactivated by PVP\u2010I oral antiseptic rinse in vitro, at the lowest concentration of 0.5 % and at the lowest contact time of 15 seconds. Hydrogen peroxide at the recommended oral rinse concentrations of 1.5% and 3.0% was minimally effective as a viricidal agent after contact times as long as 30 seconds. Therefore, preprocedural rinsing with diluted PVP\u2010I in the range of 0.5% to 1.5% may be preferred over hydrogen peroxide during the COVID\u201019 pandemic. This article is protected by copyright. All rights reserved", "qid": 19, "docid": "7hxhdzri", "rank": 84, "score": 0.7400144934654236}, {"content": "Title: Microwave-Generated Steam Decontamination of N95 Respirators Utilizing Universally Accessible Materials Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a severe, international shortage of N95 respirators, which are essential to protect health care providers from infection. Given the contemporary limitations of the supply chain, it is imperative to identify effective means of decontaminating, reusing, and thereby conserving N95 respirator stockpiles. To be effective, decontamination must result in sterilization of the N95 respirator without impairment of respirator filtration or user fit. Although numerous methods of N95 decontamination exist, none are universally accessible. In this work, we describe a microwave-generated steam decontamination protocol for N95 respirators for use in health care systems of all sizes, geographies, and means. Using widely available glass containers, mesh from commercial produce bags, a rubber band, and a 1,100-W commercially available microwave, we constructed an effective, standardized, and reproducible means of decontaminating N95 respirators. Employing this methodology against MS2 phage, a highly conservative surrogate for SARS-CoV-2 contamination, we report an average 6-log(10) plaque-forming unit (PFU) (99.9999%) and a minimum 5-log(10) PFU (99.999%) reduction after a single 3-min microwave treatment. Notably, quantified respirator fit and function were preserved, even after 20 sequential cycles of microwave steam decontamination. This method provides a valuable means of effective decontamination and reuse of N95 respirators by frontline providers facing urgent need.", "qid": 19, "docid": "mzsv126u", "rank": 85, "score": 0.7399997711181641}, {"content": "Title: Proposal for a EN 149 acceptable reprocessing method for FFP2 respirators in times of severe shortage Content: Introduction: Transmission of SARS-CoV-2 to health care workers (HCW) poses a major burden in the current COVID-19 pandemic. Unprotected exposure to a COVID-19 patient is a key risk factor for HCWs. Transmission mainly occurs by droplet transmission, or by aerosol generating procedures. Respirators such as filtering face piece masks (FFP2), also called respirators, are required to prevent transmission during aerosol generating procedures, as part of the personal protective equipment (PPE) for HCWs. However, many HCW were infected due to lack of PPE, or failure to use them. Therefore, the worldwide shortage of respirators triggered the development of reprocessing used FFP2 respirators or N95 respirators as standard in the US. Our proposal with H2O2 plasma sterilization for decontamination allows to reprocess FFP2, while they still meet the filtration efficiency required by EN 149. The protocol is simple, uses available resources in hospitals and can be rapidly implemented to decrease the shortage of respirators during this crisis. The goal of the study was the evaluate if respirators can be reprocessed and still fulfill the requirements for filtration efficiency outlined by EN 149. Methods: Used FFP2 respirators - Model 3 M Aura&#8482; 1862+ - were sterilized using a low temperature process hydrogen peroxide (H2O2), V-PRO\u00ae maX Low Temperature, a FDA (Food and Drug Administration) approved method to decontaminate FFP2 respirators. Decontaminated respirators were further checked for residual peroxide by a single-gas detector for H2O2. The total inward leakage of the protective respirators was quantitatively tested with 10 test persons in an atmosphere charged with paraffin aerosol according to the European Standard EN 149. The fit factor was calculated as the inverse of the total inward leakage. Results: Ten new and ten decontaminated FFP2 respirators were tested for filtration efficiency. None of the respirators exceeded the maximum acceptable concentration of peroxide. More than 4000 respirators have been reprocessed so far, at cost of approximately 0.3 Euro/piece. Conclusions: FFP2 respirators can be safely reprocessed once after decontamination with plasma peroxide sterilization, whereafter they still fulfill EN 149 requirements. This allows to almost double the current number of available FFP2 respirators.", "qid": 19, "docid": "sltv66cy", "rank": 86, "score": 0.7398677468299866}, {"content": "Title: Disinfection of corona virus in histopathology laboratories Content: Severe acute respiratory syndrome (SARS CoV\u20102/COVID\u201019) is a highly contagious and deadly disease caused by a virus belonging to the coronaviridae family. Researchers working in histopathology laboratories, dealing with morbid samples, are particularly vulnerable to infection unless they have very strong immunity. Hence, a proper precautionary protocol is required for the safety of the laboratory staff. The current review highlights the biological and physical agents that can be used to inactivate the virus and disinfect the surrounding environment in the laboratory.", "qid": 19, "docid": "ocu69od2", "rank": 87, "score": 0.7395815253257751}, {"content": "Title: Proposal for a EN 149 acceptable reprocessing method for FFP2 respirators in times of severe shortage Content: INTRODUCTION: Transmission of SARS-CoV-2 to health care workers (HCW) poses a major burden in the current COVID-19 pandemic. Unprotected exposure to a COVID-19 patient is a key risk factor for HCWs. Transmission mainly occurs by droplet transmission, or by aerosol generating procedures. Respirators such as filtering face piece masks (FFP2), also called respirators, are required to prevent transmission during aerosol generating procedures, as part of the personal protective equipment (PPE) for HCWs. However, many HCW were infected due to lack of PPE, or failure to use them. Therefore, the worldwide shortage of respirators triggered the development of reprocessing used FFP2 respirators or N95 respirators as standard in the US. Our proposal with H(2)O(2) plasma sterilization for decontamination allows to reprocess FFP2, while they still meet the filtration efficiency required by EN 149. The protocol is simple, uses available resources in hospitals and can be rapidly implemented to decrease the shortage of respirators during this crisis. The goal of the study was the evaluate if respirators can be reprocessed and still fulfill the requirements for filtration efficiency outlined by EN 149. METHODS: Used FFP2 respirators \u2013 Model 3 M Aura\u2122 1862+ \u2212 were sterilized using a low temperature process hydrogen peroxide (H(2)O(2)), V-PRO\u00ae maX Low Temperature, a FDA (Food and Drug Administration) approved method to decontaminate FFP2 respirators. Decontaminated respirators were further checked for residual peroxide by a single-gas detector for H(2)O(2). The total inward leakage of the protective respirators was quantitatively tested with 10 test persons in an atmosphere charged with paraffin aerosol according to the European Standard EN 149. The fit factor was calculated as the inverse of the total inward leakage. RESULTS: Ten new and ten decontaminated FFP2 respirators were tested for filtration efficiency. None of the respirators exceeded the maximum acceptable concentration of peroxide. More than 4000 respirators have been reprocessed so far, at cost of approximately 0.3 Euro/piece. CONCLUSIONS: FFP2 respirators can be safely reprocessed once after decontamination with plasma peroxide sterilization, whereafter they still fulfill EN 149 requirements. This allows to almost double the current number of available FFP2 respirators.", "qid": 19, "docid": "20phdc4u", "rank": 88, "score": 0.7391624450683594}, {"content": "Title: Disinfection of corona virus in histopathology laboratories Content: Severe acute respiratory syndrome (SARS CoV-2/COVID-19) is a highly contagious and deadly disease caused by a virus belonging to the coronaviridae family. Researchers working in histopathology laboratories, dealing with morbid samples, are particularly vulnerable to infection unless they have very strong immunity. Hence, a proper precautionary protocol is required for the safety of the laboratory staff. The current review highlights the biological and physical agents that can be used to inactivate the virus and disinfect the surrounding environment in the laboratory.", "qid": 19, "docid": "e87jj1g4", "rank": 89, "score": 0.7388943433761597}, {"content": "Title: Decontamination of face masks and filtering facepiece respirators via ultraviolet germicidal irradiation, hydrogen peroxide vaporisation, and use of dry heat inactivates an infectious SARS-CoV-2 surrogate virus. Content: Background: In the context of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the supply of personal protective equipment remains under severe strain. To address this issue, re-use of surgical face masks and filtering facepiece respirators has been recommended; prior decontamination is paramount to their re-use. Aim: We aim to provide information on the effects of three decontamination procedures on porcine respiratory coronavirus (PRCV)-contaminated masks and respirators, presenting a stable model for infectious coronavirus decontamination of these typically single-use-only products. Methods: Surgical masks and filtering facepiece respirator coupons and straps were inoculated with infectious PRCV and submitted to three decontamination treatments, UV irradiation, H2O2 vaporisation, and dry heat treatment. Viruses were recovered from sample materials and viral titres were measured in swine testicle cells. Findings: UV irradiation, H2O2 vaporisation and dry heat reduced infectious PRCV by more than three orders of magnitude on mask and respirator coupons and rendered it undetectable in all decontamination assays. Conclusion: This is the first description of stable disinfection of face masks and filtering facepiece respirators contaminated with an infectious SARS-CoV-2 surrogate using UV irradiation, H2O2 vaporisation and dry heat treatment. The three methods permit demonstration of a loss of infectivity by more than three orders of magnitude of an infectious coronavirus in line with the FDA policy regarding face masks and respirators. It presents advantages of uncomplicated manipulation and utilisation in a BSL2 facility, therefore being easily adaptable to other respirator and mask types.", "qid": 19, "docid": "g5rk0v1n", "rank": 90, "score": 0.7382735013961792}, {"content": "Title: Characterization of a novel, low-cost, scalable ozone gas system for sterilization of N95 respirators and other COVID-19 related use cases. Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an elusive and highly pathogenic agent, has resulted in the ongoing COVID-19 pandemic affecting numerous populations worldwide. New studies investigating the tenacity of SARS-CoV-2 have highlighted its ability to persist on a myriad of surfaces for several days, including gowns and shoes. As a result, there is a global need for sterilization of a variety of potentially-contaminated items, ranging from clothing to personal protective equipment like face coverings. To this end, we have designed and constructed a cost-effective, scalable, and sustainable sterilization system that uses ozone gas to inactivate viral particles. We sought to determine the efficacy of the system in the sterilization of viral particles as well as its ability to sterilize N95 respirators for reuse. N95 respirators inoculated with P22 bacteriophage and sterilized in the ozone system showed a 6-log10 reduction in viral load when treated at 25 ppm for 150 minutes. Further, N95 respirators treated with five 150-minute cycles at 35 ppm for a total concentration-time product (CT) of 26,250 ppm*min in the ozone system showed comparable filtration efficiency to untreated N95 respirators in a 50 to 200 nmr particulate challenge filtration test. Interestingly, the surgical N95 respirators tested showed complete inactivation of fluid resistance and degradation of the elasticity of polyisoprene straps after five cycles in the sterilization system. Taken together, these data suggest that while our ozone system may negatively affect certain protective aspects of surgical N95 respirators, it does effectively sterilize viral particles and can be utilized for a multitude of other use cases, including sterilizing polypropylene face coverings after potential SARS-CoV-2 contamination. In addition to providing long-term environmental benefits, deployment of this system during the ongoing pandemic reduces the risk of COVID-19 community transmission while conserving monetary resources otherwise spent on the continuous purchase of disposable face coverings.", "qid": 19, "docid": "hm1108y6", "rank": 91, "score": 0.7381299734115601}, {"content": "Title: Mobile Virology Research and Diagnostic Laboratory (MVRDL: BSL-3) for COVID-19 Screening, Virus Culturing and Vaccine Development Content: In order to prevent spread of COVID-19, World Health Organization (WHO) has specified that measures such as cleaning hands regularly with alcohol-based hand sanitizer or washing with soap and water, avoiding touching nose, eyes, mouth and social distancing should be followed by people. Another important measure for containing spread is by Testing\u2013Testing and Testing. To conduct real-time reverse transcription polymerase chain reaction (rRT-PCR) test for diagnosing COVID-19. Possibility to test up to 2000 samples per day. For virus culturing for drug screening, convalescent plasma-derived therapy. To aid in the development of vaccine and development of diagnostic kits.", "qid": 19, "docid": "fjiffj86", "rank": 92, "score": 0.7378352880477905}, {"content": "Title: Analysis of an improved workflow of endoscope reprocessing for bedside endoscopic diagnosis and treatment on COVID-19 patients Content: Severe cases infected with the coronavirus disease 2019 (COVID-19), named by the World Health Organization (WHO) on Feb. 11, 2020, tend to present a hypercatabolic state because of severe systemic consumption, and are susceptible to stress ulcers and even life-threatening gastrointestinal bleeding. Endoscopic diagnosis and treatment constitute an irreplaceable part in the handling of severe COVID-19 cases. Endoscopes, as reusable precision instruments with complicated structures, require more techniques than other medical devices in cleaning, disinfection, sterilization, and other reprocessing procedures. From 2016 to 2019, health care-acquired infection caused by improper endoscope reprocessing has always been among the top 5 on the list of top 10 health technology hazards issued by the Emergency Care Research Institute. Considering the highly infective nature of COVID-19 and the potential aerosol contamination therefrom, it is of pivotal significance to ensure that endoscopes are strictly reprocessed between uses. In accordance with the national standard \u201cRegulation for Cleaning and Disinfection Technique of Flexible Endoscope (WS507-2016),\u201d we improved the workflow of endoscope reprocessing including the selection of chemicals in an effort to ensure quality control throughout the clinical management towards COVID-19 patients. Based on the experience we attained from the 12 severe COVID-19 cases in our hospital who underwent endoscopy 23 times in total, the article provides an improved version of endoscopic reprocessing guidelines for bedside endoscopic diagnosis and treatment on COVID-19 patients for reference. ELECTRONIC SUPPLEMENTARY MATERIALS: The online version of this article (10.1631/jzus.B2000109) contains supplementary materials, which are available to authorized users", "qid": 19, "docid": "agb8hvmk", "rank": 93, "score": 0.7373042106628418}, {"content": "Title: Onset of occupational hand eczema among healthcare workers during the SARS\u2010CoV\u20102 pandemic \u2013 comparing a single surgical site with a COVID\u201019 intensive care unit Content: BACKGROUND: Due to the COVID\u201019 outbreak, hygiene regulations have been intensified and hand sanitation has gained special attention. OBJECTIVE: To investigate the onset of hand eczema during the COVID\u201019 pandemic in health care workers (HCWs) directly involved in intensive care of COVID\u201019 patients and HCWs without direct contact. Hereby, we aim at increasing awareness with regard to occupational hand eczema and preventive measures that can be undertaken. METHODS: A survey was distributed amongst 114 HCWs at a single surgical site and at a COVID\u201019 intensive care unit of the university hospital LMU Munich, Germany. Participants were questioned with regard to the daily frequency of hand hygiene prior to and during the pandemic. Participants self\u2010reported onset of hand eczema and associated symptoms. RESULTS: Our study revealed a significant increase of hand washing, disinfection and use of hand cream across all participants (P\u2010value<.001), regardless of having direct contact with COVID\u201019 patients. A high prevalence of symptoms associated with acute hand dermatitis was found in 90.4% across all HCWs, whereas hand eczema itself was underreported (14.9%). CONCLUSION: The increase of hand sanitation during the COVID\u201019 pandemic impairs the skin of the hands across all HCWs, independent of direct intensive care of affected patients. This article is protected by copyright. All rights reserved.", "qid": 19, "docid": "hr5su8z3", "rank": 94, "score": 0.7366381287574768}, {"content": "Title: COVID-19: emerging protective measures Content: The COVID-19 (Coronavirus disease 2019) spreads primarily through droplets of saliva or discharge from the nose. COVID-19 is predominantly considered as an unavoidable pandemic, and scientists are very curious about how to provide the best protection to the public before a vaccine can be made available. There is an urge to manufacture a greater number of masks to prevent any aerosol with microbes. Hence, we aim to develop an efficient viral inactivation system by exploiting active compounds from naturally occurring medicinal plants and infusing them into nanofiber-based respiratory masks. Our strategy is to develop fibrous filtration with three-layered masks using the compounds from medicinal plants for viral deactivation. These masks will be beneficial not just to healthcare workers but common citizens as well. In the absence of vaccination, productive masks can be worn to prevent transmission of airborne pathogenic aerosols and control diseases.", "qid": 19, "docid": "qi8x5yaq", "rank": 95, "score": 0.7366272807121277}, {"content": "Title: COVID-19: emerging protective measures. Content: The COVID-19 (Coronavirus disease 2019) spreads primarily through droplets of saliva or discharge from the nose. COVID-19 is predominantly considered as an unavoidable pandemic, and scientists are very curious about how to provide the best protection to the public before a vaccine can be made available. There is an urge to manufacture a greater number of masks to prevent any aerosol with microbes. Hence, we aim to develop an efficient viral inactivation system by exploiting active compounds from naturally occurring medicinal plants and infusing them into nanofiber-based respiratory masks. Our strategy is to develop fibrous filtration with three-layered masks using the compounds from medicinal plants for viral deactivation. These masks will be beneficial not just to healthcare workers but common citizens as well. In the absence of vaccination, productive masks can be worn to prevent transmission of airborne pathogenic aerosols and control diseases.", "qid": 19, "docid": "tfrawa9z", "rank": 96, "score": 0.7366272807121277}, {"content": "Title: Correspondence: Angiotensin-converting enzyme 2 coated nanoparticles containing respiratory masks, chewing gums and nasal filters may be used for protection against COVID-19 infection Content: \u2022 World has encountered a novel pandemic called as COVID-19. \u2022 All people need protective items such as masks and gloves worldwide. \u2022 Preventing COVID-19 infection has become the most important issue. \u2022 ACE2 containing nanomaterials may be used in the respiratory masks, gloves and clothes. \u2022 Using nanotechnology to prevent this pandemic may be hope for fighting against COVID-19.", "qid": 19, "docid": "g477u9k1", "rank": 97, "score": 0.7364961504936218}, {"content": "Title: Is Alcohol in Hand Sanitizers Absorbed Through the Skin or Lungs? Implications for Disulfiram Treatment. Content: AIM In view of the increase in the use of ethanol-containing hand sanitizers throughout the world due to the current COVID-19 pandemic, we wished to review the possible risks to patients treated with disulfiram, following a case report in which an apparent DER (disulfiram-ethanol reaction) was attributed to the cutaneous absorption of alcohol from hand sanitizers as well as by inhalation of vapour. METHOD Simple experiments to assess the levels of absorption by each route separately. RESULTS Our results strongly suggest that while amounts of alcohol sufficient to cause a DER may be inhaled when hand sanitizers are used in confined spaces, absorption can be avoided by dispersal of the fumes, and absorption from the skin alone does not occur in pharmacologically significant quantities. CONCLUSION Warnings about absorption of alcohol through the skin from hand sanitizers and products such as perfumes, deodorants and after-shave (whose use is often warned against when disulfiram is prescribed) should be modified accordingly.", "qid": 19, "docid": "ld141phd", "rank": 98, "score": 0.736224889755249}, {"content": "Title: Efficacy of moist heat decontamination against various pathogens for the reuse of N95 respirators in the COVID-19 emergency Content: Decontamination of N95 respirators has become critical to alleviate PPE shortages for healthcare workers in the current COVID-19 emergency. The factors that are considered for the effective reuse of these masks are the fit, filter efficiency and decontamination/disinfection level both for SARS-CoV2, which is the causative virus for COVID-19, and for other organisms of concern in the hospital environment such as Staphylococcus aureus or Clostridium difficile. The efficacy of inactivation or eradication against various pathogens should be evaluated thoroughly to understand the level of afforded disinfection. Methods commonly used in the sterilization of medical devices such as ionizing radiation, vaporized hydrogen peroxide, and ethylene oxide can provide a high level of disinfection, defined as a 6 log10 reduction, against bacterial spores, considered the most resistant microorganisms. CDC guidance on the decontamination and reuse of N95s also includes the use of moist heat (60{degrees}C, 80% relative humidity, 15-30 min) as a possible recommendation based on literature showing preservation of fit efficiency and inactivation of H1N1 on spiked masks. Here, we explored the efficacy of using moist heat under these conditions as a decontamination method for an N95 respirator (3M 1860S, St. Paul, MN) against various pathogens with different resistance; enveloped RNA viruses, Gram (+/-) bacteria, and non-enveloped viruses.", "qid": 19, "docid": "q0c3qvad", "rank": 99, "score": 0.7358877658843994}, {"content": "Title: Can Nanotechnology and Materials Science Help the Fight against SARS-CoV-2? Content: Since 2004, we have been developing nanomaterials with antimicrobial properties, the so-called nanoantimicrobials. When the coronavirus disease 2019 (COVID-19) emerged, we started investigating new and challenging routes to nanoantivirals. The two fields have some important points of contact. We would like to share with the readership our vision of the role a (nano)materials scientist can play in the fight against the COVID-19 pandemic. As researchers specifically working on surfaces and nanomaterials, in this letter we underline the importance of nanomaterial-based technological solutions in several aspects of the fight against the virus. While great resources are understandably being dedicated to treatment and diagnosis, more efforts could be dedicated to limit the virus spread. Increasing the efficacy of personal protection equipment, developing synergistic antiviral coatings, are only two of the cases discussed. This is not the first nor the last pandemic: our nanomaterials community may offer several technological solutions to challenge the ongoing and future global health emergencies. Readers\u2019 feedback and suggestions are warmly encouraged.", "qid": 19, "docid": "eyi5fmd4", "rank": 100, "score": 0.7358336448669434}]}
{"query": "what is the origin of COVID-19", "hits": [{"content": "Title: Origin of Novel Coronavirus (COVID-19): A Computational Biology Study using Artificial Intelligence Content: Origin of the COVID-19 virus has been intensely debated in the scientific community since the first infected cases were detected in December 2019. The disease has caused a global pandemic, leading to deaths of thousands of people across the world and thus finding origin of this novel coronavirus is important in responding and controlling the pandemic. Recent research results suggest that bats or pangolins might be the original hosts for the virus based on comparative studies using its genomic sequences. This paper investigates the COVID-19 virus origin by using artificial intelligence (AI) and raw genomic sequences of the virus. More than 300 genome sequences of COVID-19 infected cases collected from different countries are explored and analysed using unsupervised clustering methods. The results obtained from various AI-enabled experiments using clustering algorithms demonstrate that all examined COVID-19 virus genomes belong to a cluster that also contains bat and pangolin coronavirus genomes. This provides evidences strongly supporting scientific hypotheses that bats and pangolins are probable hosts for the COVID-19 virus. At the whole genome analysis level, our findings also indicate that bats are more likely the hosts for the COVID-19 virus than pangolins.", "qid": 1, "docid": "4dtk1kyh", "rank": 1, "score": 0.8399519324302673}, {"content": "Title: The Human Coronavirus Disease COVID-19: Its Origin, Characteristics, and Insights into Potential Drugs and Its Mechanisms Content: The emerging coronavirus disease (COVID-19) swept across the world, affecting more than 200 countries and territories. Genomic analysis suggests that the COVID-19 virus originated in bats and transmitted to humans through unknown intermediate hosts in the Wuhan seafood market, China, in December of 2019. This virus belongs to the Betacoronavirus group, the same group of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV), and for the similarity, it was named SARS-CoV-2. Given the lack of registered clinical therapies or vaccines, many physicians and scientists are investigating previously used clinical drugs for COVID-19 treatment. In this review, we aim to provide an overview of the CoVs origin, pathogenicity, and genomic structure, with a focus on SARS-CoV-2. Besides, we summarize the recently investigated drugs that constitute an option for COVID-19 treatment.", "qid": 1, "docid": "utsr0zv7", "rank": 2, "score": 0.8187129497528076}, {"content": "Title: [What is the origin of SARS-CoV-2?] Content: Every time a pandemic occurs, dozens of theories emerge to attribute the origin of the event to different facts. The COVID-19 pandemic that has hit virtually all the globe has been no exception. What is known so far about the origin of the virus that causes COVID 19? The first investigations on the origin of this disease have determined that it is a new type of virus, the origin of which is most likely zoonotic.", "qid": 1, "docid": "dv9m19yk", "rank": 3, "score": 0.8113434910774231}, {"content": "Title: Understanding Coronavirus Content: Since the identification of the first cases of the coronavirus in December 2019 in Wuhan, China, there has been a significant amount of confusion regarding the origin and spread of the so-called 'coronavirus', officially named SARS-CoV-2, and the cause of the disease COVID-19 Conflicting messages from the media and officials across different countries and organizations, the abundance of disparate sources of information, unfounded conspiracy theories on the origins of the newly emerging virus and the inconsistent public health measures across different countries, have all served to increase the level of anxiety in the population Where did the virus come from? How is it transmitted? How does it cause disease? Is it like flu? What is a pandemic? What can we do to stop its spread? Written by a leading expert, this concise and accessible introduction provides answers to the most common questions surrounding coronavirus for a general audience", "qid": 1, "docid": "hmvo5b0q", "rank": 4, "score": 0.8093574643135071}, {"content": "Title: Possibility of transmission through dogs being a contributing factor to the extreme Covid-19 outbreak in North Italy Content: Covid\u201119 origin and transmission to humans. Covid\u201119 infection began in Wuhan (Hubei, China) in December, 2019. Although to date it is considered that Covid\u201119 originates from bats (96.2% overall genome sequence identity) (1), the type of intermediate animals that caused the transmission to humans remains unknown (2-4). Zhou et al (1) mentioned that 'Direct contact with intermediate host animals or consumption of wild animals was suspected to be the main route of SARS\u2011CoV\u20112 transmission. However, the source(s) and transmission routine(s) of SARS\u2011CoV\u20112 remain elusive' (1).", "qid": 1, "docid": "k9lcpjyo", "rank": 5, "score": 0.8090444207191467}, {"content": "Title: Zoonotic origins of human coronavirus 2019 (HCoV-19 / SARS-CoV-2): why is this work important? Content: The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by infection with human coronavirus 2019 (HCoV-19 / SARS-CoV-2 / 2019-nCoV), is a global threat to the human population. Here, we briefly summarize the available data for the zoonotic origins of HCoV-19, with reference to the other two epidemics of highly virulent coronaviruses, SARS-CoV and MERS-CoV, which cause severe pneumonia in humans. We propose to intensify future efforts for tracing the origins of HCoV-19, which is a very important scientific question for the control and prevention of the pandemic.", "qid": 1, "docid": "75773gwg", "rank": 6, "score": 0.8040145039558411}, {"content": "Title: Pandemia COVID-19, la nueva emergencia sanitaria de preocupaci\u00f3n internacional: una revisi\u00f3n./ [Pandemic COVID-19, the new health emergency of international concern: a review] Content: In late December 2019, some cases of atypical pneumonia, at that time of unknown origin, were reported in Wuhan, China. Days later, the etiologic agent was identified as a new coronavirus. This new coronavirus was called SARS-CoV-2 and the disease it produces was named COVID-19. The origin of this new virus is presumed zoonotic, with bats being its probable vector. Due to the rapid number of infections and deaths that occurred first in China and later around the world, the infection of this virus quickly went from being an isolated outbreak in a Chinese region to becoming a health emergency of international concern and later, a pandemic. The purpose of this review is to study the most relevant and current information on the pathogen, as well as epidemiology, pathology, clinical features, transmission, prevention, and treatment of the disease.", "qid": 1, "docid": "x3sb1o4u", "rank": 7, "score": 0.7978615760803223}, {"content": "Title: The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak Content: Coronavirus disease (COVID-19) is caused by SARS-COV2 and represents the causative agent of a potentially fatal disease that is of great global public health concern. Based on the large number of infected people that were exposed to the wet animal market in Wuhan City, China, it is suggested that this is likely the zoonotic origin of COVID-19. Person-to-person transmission of COVID-19 infection led to the isolation of patients that were subsequently administered a variety of treatments. Extensive measures to reduce person-to-person transmission of COVID-19 have been implemented to control the current outbreak. Special attention and efforts to protect or reduce transmission should be applied in susceptible populations including children, health care providers, and elderly people. In this review, we highlights the symptoms, epidemiology, transmission, pathogenesis, phylogenetic analysis and future directions to control the spread of this fatal disease.", "qid": 1, "docid": "sh7lrdou", "rank": 8, "score": 0.7933164834976196}, {"content": "Title: [Editorial] Possibility of transmission through dogs being a contributing factor to the extreme Covid\u00ad19 outbreak in North Italy Content: Covid\u00ad19 origin and transmission to humans. Covid\u00ad19 infection began in Wuhan (Hubei, China) in December, 2019. Although to date it is considered that Covid\u00ad19 originates from bats (96.2% overall genome sequence identity) (1), the type of intermediate animals that caused the transmission to humans remains unknown (2-4). Zhou et al (1) mentioned that 'Direct contact with intermediate host animals or consumption of wild animals was suspected to be the main route of SARS\u00adCoV\u00ad2 transmission. However, the source(s) and transmission routine(s) of SARS\u00adCoV\u00ad2 remain elusive' (1).", "qid": 1, "docid": "jwxt4ygt", "rank": 9, "score": 0.7931073904037476}, {"content": "Title: The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak Content: Abstract Coronavirus disease (COVID-19) is caused by SARS-COV2 and represents the causative agent of a potentially fatal disease that is of great global public health concern. Based on the large number of infected people that were exposed to the wet animal market in Wuhan City, China, it is suggested that this is likely the zoonotic origin of COVID-19. Person-to-person transmission of COVID-19 infection led to the isolation of patients that were subsequently administered a variety of treatments. Extensive measures to reduce person-to-person transmission of COVID-19 have been implemented to control the current outbreak. Special attention and efforts to protect or reduce transmission should be applied in susceptible populations including children, health care providers, and elderly people. In this review, we highlights the symptoms, epidemiology, transmission, pathogenesis, phylogenetic analysis and future directions to control the spread of this fatal disease.", "qid": 1, "docid": "xuczplaf", "rank": 10, "score": 0.7908065319061279}, {"content": "Title: Higher prevalence of asymptomatic or mild COVID\u201019 in children, claims and clues Content: The current pandemic of COVID-19 has generated many challenging questions for the scientific community, ranging from queries about the origin of the virus to its pathogenesis and clinical management. This article is protected by copyright. All rights reserved.", "qid": 1, "docid": "n15i01tn", "rank": 11, "score": 0.786024808883667}, {"content": "Title: Tracking the origin of early COVID-19 cases in Canada Content: The original coronavirus disease (COVID-19) outbreak in Wuhan, China has become a global pandemic. By tracking the earliest 118 COVID-19 cases in Canada, we produced a Voronoi treemap to show the travel origins of the country's earliest COVID-19 cases. By March 11, 2020, even though the majority (64.1%) of the world's COVID-19 confirmed cases still had their origin in China, only 7.6% of Canada's first 118 COVID-19 cases arose due in travelers to China. The most commonly reported travel history among the 118 cases originated from the Middle East, the United States, and Europe. Thus, in retrospect, broadening of early screening tools and travel restrictions to countries and regions outside China may help control global COVID-19 spread.", "qid": 1, "docid": "kgifmjvb", "rank": 12, "score": 0.7835733890533447}, {"content": "Title: Tracking the origin of early COVID-19 cases in Canada Content: Abstract The original coronavirus disease (COVID-19) outbreak in Wuhan, China has become a global pandemic. By tracking the earliest 118 COVID-19 cases in Canada, we produced a Voronoi treemap to show the travel origins of the country\u2019s earliest COVID-19 cases. By March 11, 2020, even though the majority (64.1%) of the world\u2019s COVID-19 confirmed cases still had their origin in China, only 7.6% of Canada\u2019s first 118 COVID-19 cases arose due in travelers to China. The most commonly reported travel history among the 118 cases originated from the Middle East, the United States, and Europe. Thus, in retrospect, broadening of early screening tools and travel restrictions to countries and regions outside China may help control global COVID-19 spread.", "qid": 1, "docid": "wmfcey6f", "rank": 13, "score": 0.7828253507614136}, {"content": "Title: SARS-COV-2 and Male Reproductive Health Content: Critical challenges for the public and private health, research, and medical communities have been posed by the COVID-19 outbreak. Some of these challenges are related to the possible adverse effects of SARS-CoV-2 on male reproductive health, and whether other potential modes of transmission may occur, such as sexual transmission. Moreover, concerns have been raised in terms of whether the COVID-19 outbreak may have an impact on fertility worldwide. In this study, we will discuss the origins of SARS-CoV-2. We will further describe its mechanism of action, diagnosis, symptoms, and potential effects on the male reproductive system.", "qid": 1, "docid": "nyhup6sq", "rank": 14, "score": 0.7818657159805298}, {"content": "Title: SARS-COV-2 and Male Reproductive Health. Content: Critical challenges for the public and private health, research, and medical communities have been posed by the COVID-19 outbreak. Some of these challenges are related to the possible adverse effects of SARS-CoV-2 on male reproductive health, and whether other potential modes of transmission may occur, such as sexual transmission. Moreover, concerns have been raised in terms of whether the COVID-19 outbreak may have an impact on fertility worldwide. In this study, we will discuss the origins of SARS-CoV-2. We will further describe its mechanism of action, diagnosis, symptoms, and potential effects on the male reproductive system.", "qid": 1, "docid": "sz21ualp", "rank": 15, "score": 0.7818657159805298}, {"content": "Title: The genetic landscape of COVID-19: A South Asian perspective Content: COVID-19 has taken the world by storm in the ongoing pandemic. The virus responsible for COVID-19 disease is 'severe acute respiratory syndrome coronavirus-2' SARS-CoV-2, an enveloped RNA beta-coronavirus from the family Coronaviridae. There have been similar beta-coronavirus disease outbreaks previously: Severe acute respiratory syndrome (SARS - 2002) and Middle East respiratory syndrome (MERS - 2012) epidemics. SARS-CoV-2 origins have been traced to bat reservoirs. A virus with a high capacity for mutation, SARS-CoV-2 poses unique challenges both in the current form of disease control and management, while also leaving the door open for future novel diseases and pandemics. An understanding of the virion structure and genomic organisation will help us in understanding their origins and likely course of future evolution. Moreover, novel cost-effective methodologies for genetic surveillance may help in mitigating the emergence of these viral infections in future. In this manuscript, the authors have detailed the unique aspects of the SARS-CoV-2 virus genome and its clinical implications.", "qid": 1, "docid": "q2gwajdj", "rank": 16, "score": 0.7798981070518494}, {"content": "Title: The genetic landscape of COVID-19: A South Asian perspective. Content: COVID-19 has taken the world by storm in the ongoing pandemic. The virus responsible for COVID-19 disease is 'severe acute respiratory syndrome coronavirus-2' SARS-CoV-2, an enveloped RNA beta-coronavirus from the family Coronaviridae. There have been similar beta-coronavirus disease outbreaks previously: Severe acute respiratory syndrome (SARS - 2002) and Middle East respiratory syndrome (MERS - 2012) epidemics. SARS-CoV-2 origins have been traced to bat reservoirs. A virus with a high capacity for mutation, SARS-CoV-2 poses unique challenges both in the current form of disease control and management, while also leaving the door open for future novel diseases and pandemics. An understanding of the virion structure and genomic organisation will help us in understanding their origins and likely course of future evolution. Moreover, novel cost-effective methodologies for genetic surveillance may help in mitigating the emergence of these viral infections in future. In this manuscript, the authors have detailed the unique aspects of the SARS-CoV-2 virus genome and its clinical implications.", "qid": 1, "docid": "ja2s5cxy", "rank": 17, "score": 0.7798981070518494}, {"content": "Title: Going viral \u2013 Covid-19 impact assessment: A perspective beyond clinical practice Content: In the realm of infectious diseases, a global outbreak is a worst-case scenario In the past, outbreaks such as plague, Spanish flu, severe acute respiratory syndrome, and H1N1 (swine flu) have caused great human suffering The novel coronavirus, christened as Covid-19, is a zoonotic disease which originated from the Wuhan province in China and spread like wildfire killing people and devastating the global economy Mammoth efforts are still on to control this viral strain from further spread Cities have been blocked, air travel banned, ships have been quarantined, and panic-stricken people have been evacuated from China As Covid-19 continues to ravage countries across the globe, this article is an effort to provide an overview of the impact of Covid-19 and tickle wits of intellectuals to think how easily a nanometer organism can virtually bring down superpowers of the world", "qid": 1, "docid": "6yfj4co0", "rank": 18, "score": 0.775684118270874}, {"content": "Title: Where are we with understanding of COVID-19? Content: Coronavirus disease 2019 caused by SARS-CoV-2 originated from China and spread across every corner of the world. The scientific interest on COVID-19 increased after WHO declared it a pandemic in the early February of 2020. In fact, this pandemic has had a worldwide impact on economy, health, and lifestyle like no other in the last 100 years. SARS-CoV-2 belongs to Coronaviridae family and causes the deadliest clinical manifestations when compared to other viruses in the family. COVID-19 is an emerging zoonotic disease that has resulted in over 383,000 deaths around the world. Scientists are scrambling for ideas to develop treatment and prevention strategies to thwart the disease condition. In this review, we have attempted to summarize the latest information on the virus, disease, prevention, and treatment strategies. The future looks promising.", "qid": 1, "docid": "rtw8m00s", "rank": 19, "score": 0.7750437259674072}, {"content": "Title: Concerns related to COVID\u201019 pandemic among patients with inflammatory bowel disease and its influence on patient management Content: A novel coronavirus, currently identified as COVID-19, was recently defined as the cause of a cluster of patients with pneumonia of unknown origin that was initially reported from Wuhan, Hubei province, People's Republic of China.", "qid": 1, "docid": "47pszpgp", "rank": 20, "score": 0.7746508121490479}, {"content": "Title: Novel coronavirus disease (COVID-19): a pandemic (epidemiology, pathogenesis and potential therapeutics) Content: The coronavirus disease (COVID-19) is highly pathogenic viral infection caused by SARS-CoV-2. Currently, COVID-19 has caused global health concern. It is assumed that COVID-19 has zoonotic origin based on the large number of infected people who were exposed to the wet market in Wuhan City, China. The phylogenetic analysis has revealed that SARS-CoV-2 has significant sequence similarity with severe acute respiratory syndrome-like (SARS-like) bat viruses, thus bats could be primary possible reservoir. The intermediate host and there subsequent transfer is not known yet, although human to human transfer is widely confirmed. The transmission of COVID-19 infection from one person to another resulted in the isolation of patients who were subsequently given a variety of treatments. To monitor the current outbreak, robust steps have been taken around the globe to reduce the transmission of COVID-19 infection particularly banning international and domestic flights, inducting lockdowns in vulnerable areas, social distancing etc. No clinically approved antiviral drug or vaccine against COVID-19 is reported yet. However, in clinical trials, few broad-spectrum antiviral drugs were evaluated against COVID-19 infection which resulted in clinical recovery. In this article emergence and pathogenicity of COVID-19 infection along with potential therapeutic strategies are analyzed to combat the COVID-19 pandemic.", "qid": 1, "docid": "958u08vb", "rank": 21, "score": 0.773969292640686}, {"content": "Title: COVID-19 and the clinical hematology laboratory Content: The ongoing COVID-19 pandemic originated in Wuhan, Hubei Province, China, in December 2019. The etiologic agent is a novel coronavirus of presumed zoonotic origin with structural similarity to the viruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Like SARS and MERS, COVID-19 infection manifests most frequently with lower respiratory symptoms. A minority of patients progress to acute respiratory distress syndrome/ diffuse alveolar damage. In addition to its central role in the diagnosis of COVID-19 infection, the clinical laboratory provides critical information to clinicians regarding prognosis, disease course, and response to therapy. The purpose of this review is to (a) provide background context about the origins and course of the pandemic, (b) discuss the laboratory's role in the diagnosis of COVID-19 infection, (c) summarize the current state of biomarker analysis in COVID-19 infection, with an emphasis on markers derived from the hematology laboratory, (d) comment on the impact of COVID-19 on hematology laboratory safety, and (e) describe the impact the pandemic has had on organized national and international educational activities worldwide.", "qid": 1, "docid": "deee71uw", "rank": 22, "score": 0.7734798192977905}, {"content": "Title: The COVID-19 Pandemic and Paradigm Change in Global Scientific Research Content: The current pandemic has rocked the lives of human beings every-where in ways never imagined, forcing us to question where our civilization is headed. In this article, we explore and discuss scien-tifi c evidence that helps explain recent events in the context of the COVID-19 pandemic.COVID-19 is caused by infection with a zoonotic-origin novel virus, SARS-CoV-2, that is genetically close to two coronavirus types iso-lated in bats. The transmission dynamics to humans from the original and intermediary hosts remain poorly understood, but it is highly likely that the SARS-CoV-2 virus infected humans after undergoing an inter-species transfer from bats to an intermediate species, and from there to human beings. Crossing the species barrier is largely fostered by industrial-scale agricultural practices that simplify original ecosystem connections by reducing biodiversity, facilitating the emergence of new infectious diseases. The scientifi c community has played an exemplary role in responding to this global emergency, working to fi nd timely, relevant solutions for governments and society as a whole. We need to take this opportunity to promote a global and open science that delves into the interrelation-ships of the biological, environmental, social and economic dimen-sions of this and other diseases while questioning current modes of production and their impact on the environment, and thus on human health worldwide. Keywords: Coronavirus infections; communicable diseases; zoonoses; ecosystems; technology, industry, and agriculture; pandemics; global health; Mexico.", "qid": 1, "docid": "xndojxqk", "rank": 23, "score": 0.7733437418937683}, {"content": "Title: The COVID-19 Pandemic and Paradigm Change in Global Scientific Research. Content: The current pandemic has rocked the lives of human beings every-where in ways never imagined, forcing us to question where our civilization is headed. In this article, we explore and discuss scien-tifi c evidence that helps explain recent events in the context of the COVID-19 pandemic.COVID-19 is caused by infection with a zoonotic-origin novel virus, SARS-CoV-2, that is genetically close to two coronavirus types iso-lated in bats. The transmission dynamics to humans from the original and intermediary hosts remain poorly understood, but it is highly likely that the SARS-CoV-2 virus infected humans after undergoing an inter-species transfer from bats to an intermediate species, and from there to human beings. Crossing the species barrier is largely fostered by industrial-scale agricultural practices that simplify original ecosystem connections by reducing biodiversity, facilitating the emergence of new infectious diseases. The scientifi c community has played an exemplary role in responding to this global emergency, working to fi nd timely, relevant solutions for governments and society as a whole. We need to take this opportunity to promote a global and open science that delves into the interrelation-ships of the biological, environmental, social and economic dimen-sions of this and other diseases while questioning current modes of production and their impact on the environment, and thus on human health worldwide. Keywords: Coronavirus infections; communicable diseases; zoonoses; ecosystems; technology, industry, and agriculture; pandemics; global health; Mexico.", "qid": 1, "docid": "ccxj4s6j", "rank": 24, "score": 0.7733437418937683}, {"content": "Title: SARS-CoV-2 and COVID-19: A genetic, epidemiological, and evolutionary perspective Content: In less than five months, COVID-19 has spread from a small focus in Wuhan, China, to more than 5 million people in almost every country in the world, dominating the concern of most governments and public health systems. The social and political distresses caused by this epidemic will certainly impact our world for a long time to come. Here, we synthesize lessons from a range of scientific perspectives rooted in epidemiology, virology, genetics, ecology and evolutionary biology so as to provide perspective on how this pandemic started, how it is developing, and how best we can stop it.", "qid": 1, "docid": "xljdm4zi", "rank": 25, "score": 0.7723991274833679}, {"content": "Title: COVID-19 from mysterious enemy to an environmental detection process: a critical review Content: The recent global emergence of an unusual viral pneumonia of COVID-19 epidemic was firstly started in Wuhan city, Hubei province in China in December 2019. Regrettably, it is still sweeping the planet, and it cannot be controlled up till now. By May 2020, the unexpected spread of this disaster had caused more than 3,759,967 cases and 259,474 deaths in 114 countries from Asia to the Middle East, Europe, and the USA. Considering its fatal nature, it has evolved as a major challenge for the world. This is necessitating a quick and steep intervention in order to save millions of people\u2019s lives across the globe. The knowledge about the nature and evolution of the COVID-19 virus in water, soils, and other environmental compartments can be addressed through wastewater and sewage. Wastewater-based epidemiology approach can be used as an early indicator of the infection within a specific population. The basic aim of this review article is trying to provide a prompt, and valuable reference guides about COVID-19. Some important questions were addressed, such as, its origin, transmission, clinical symptoms, diagnosis, environmental aspects, and the possible indoors and outdoors airborne transmission minimization strategies that may benefit specialists.", "qid": 1, "docid": "nhhtfh8q", "rank": 26, "score": 0.7706754207611084}, {"content": "Title: Pangolins Harbor SARS-CoV-2-Related Coronaviruses Content: The pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has posed a severe threat to global public health. Yet, the origin of SARS-CoV-2 remains mysterious. Several recent studies (e.g., Lam et al ., Xiao et al .) identified SARS-CoV-2-related viruses in pangolins, providing novel insights into the evolution and diversity of SARS-CoV-2-related viruses.", "qid": 1, "docid": "k9yus2sv", "rank": 27, "score": 0.7703287601470947}, {"content": "Title: Pangolins Harbor SARS-CoV-2-Related Coronaviruses Content: The pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has posed a severe threat to global public health. Yet, the origin of SARS-CoV-2 remains mysterious. Several recent studies (e.g., Lam et al.,Xiao et al.) identified SARS-CoV-2-related viruses in pangolins, providing novel insights into the evolution and diversity of SARS-CoV-2-related viruses.", "qid": 1, "docid": "pfv7q4v6", "rank": 28, "score": 0.7703287601470947}, {"content": "Title: Ten challenging questions about SARS-CoV-2 and COVID-19 Content: INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently introduced as a global public health problem by the World Health Organization (WHO). The virus outbreak has been documented around the world. Updating data in different aspects of the virus could force us to revise our idea about the main questions concerning coronavirus disease-19 (COVID-19). AREAS COVERED: Although our knowledge about the SARS-CoV-2 and COVID-19 is largely based on the very limited data, the information is growing rapidly. The renewed answers to the specific research questions concerning updating data not only reveal gaps for future research but also re-categorized our information. Here, we attempt to briefly discuss 10 important questions about SARS-CoV-2 and COVID-19. EXPERT OPINION: Since our knowledge about different aspects of SARS-CoV-2 appears to be in its infancy and is rapidly changing, the provision of the right data is more difficult in this regard. However, we try to rely on results from more extensive research to answer the main questions about this new virus. Therefore, further studies, particularly in the context of the virus pathogenesis, diagnosis, treatment, and vaccine development, are warranted.", "qid": 1, "docid": "tst7ss76", "rank": 29, "score": 0.7689529657363892}, {"content": "Title: Current Status of Epidemiology, Diagnosis, Therapeutics, and Vaccines for Novel Coronavirus Disease 2019 (COVID-19) Content: Coronavirus disease 2019 (COVID-19), which causes serious respiratory illness such as pneumonia and lung failure, was first reported in Wuhan, the capital of Hubei, China. The etiological agent of COVID-19 has been confirmed as a novel coronavirus, now known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is most likely originated from zoonotic coronaviruses, like SARS-CoV, which emerged in 2002. Within a few months of the first report, SARS-CoV-2 had spread across China and worldwide, reaching a pandemic level. As COVID-19 has triggered enormous human casualties and serious economic loss posing global threat, an understanding of the ongoing situation and the development of strategies to contain the virus's spread are urgently needed. Currently, various diagnostic kits to test for COVID-19 are available and several repurposing therapeutics for COVID-19 have shown to be clinically effective. In addition, global institutions and companies have begun to develop vaccines for the prevention of COVID-19. Here, we review the current status of epidemiology, diagnosis, treatment, and vaccine development for COVID-19.", "qid": 1, "docid": "2lxs9laj", "rank": 30, "score": 0.7687758803367615}, {"content": "Title: Current Status of Epidemiology, Diagnosis, Therapeutics, and Vaccines for Novel Coronavirus Disease 2019 (COVID-19). Content: Coronavirus disease 2019 (COVID-19), which causes serious respiratory illness such as pneumonia and lung failure, was first reported in Wuhan, the capital of Hubei, China. The etiological agent of COVID-19 has been confirmed as a novel coronavirus, now known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is most likely originated from zoonotic coronaviruses, like SARS-CoV, which emerged in 2002. Within a few months of the first report, SARS-CoV-2 had spread across China and worldwide, reaching a pandemic level. As COVID-19 has triggered enormous human casualties and serious economic loss posing global threat, an understanding of the ongoing situation and the development of strategies to contain the virus's spread are urgently needed. Currently, various diagnostic kits to test for COVID-19 are available and several repurposing therapeutics for COVID-19 have shown to be clinically effective. In addition, global institutions and companies have begun to develop vaccines for the prevention of COVID-19. Here, we review the current status of epidemiology, diagnosis, treatment, and vaccine development for COVID-19.", "qid": 1, "docid": "p3681yit", "rank": 31, "score": 0.7687758803367615}, {"content": "Title: Ten challenging questions about SARS-CoV-2 and COVID-19. Content: INTRODUCTION Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently introduced as a global public health problem by the World Health Organization (WHO). The virus outbreak has been documented around the world. Updating data in different aspects of the virus could force us to revise our idea about the main questions concerning coronavirus disease-19 (COVID-19). AREAS COVERED Although our knowledge about the SARS-CoV-2 and COVID-19 is largely based on the very limited data, the information is growing rapidly. The renewed answers to the specific research questions concerning updating data not only reveal gaps for future research but also re-categorized our information. Here, we attempt to briefly discuss ten important questions about SARS-CoV-2 and COVID-19. EXPERT OPINION Since our knowledge about different aspects of SARS-CoV-2 appears to be in its infancy and is rapidly changing, the provision of the right data is more difficult in this regard. However, we try to rely on results from more extensive research to answer the main questions about this new virus. Therefore, further studies, particularly in the context of the virus pathogenesis, diagnosis, treatment, and vaccine development, are warranted.", "qid": 1, "docid": "l7riy8ox", "rank": 32, "score": 0.7682652473449707}, {"content": "Title: Deaths in healthcare workers due to COVID\u201019: the need for robust data and analysis Content: The novel coronavirus SARS-CoV-2 has rapidly spread across the world from its origin in Wuhan, China in late 2019. The resultant disease (COVID-19) has placed an enormous burden on healthcare systems because of the high transmission rates, prevalence of severe disease and mortality [1]. The risk of viral transmission to healthcare workers has been a concern since the start of the outbreak and the first person to raise concerns about the illness to the international community was Dr Li Wen-Liang, an ophthalmologist in Wuhan who sadly died of the disease that he likely contracted whilst at work [2].", "qid": 1, "docid": "2po918ec", "rank": 33, "score": 0.7680075168609619}, {"content": "Title: Origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19) Content: Coronavirus has emerged as a global health threat due to its accelerated geographic spread over the last two decades. This article reviews the current state of knowledge concerning the origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19). Historically, it has caused two pandemics: severe acute respiratory syndrome and Middle East respiratory syndrome followed by the present COVID-19 that emerged from China. The virus is believed to be acquired from zoonotic source and spreads through direct and contact transmission. The symptomatic phase manifests with fever, cough and myalgia to severe respiratory failure. The diagnosis is confirmed using reverse transcriptase PCR. Management of COVID-19 is mainly by supportive therapy along with mechanical ventilation in severe cases. Preventive strategies form the major role in reducing the public spread of virus along with successful disease isolation and community containment. Development of a vaccine to eliminate the virus from the host still remains an ongoing challenge.", "qid": 1, "docid": "3ll2tlzr", "rank": 34, "score": 0.767829179763794}, {"content": "Title: COVID\u201019 and the clinical hematology laboratory Content: The ongoing COVID\u201019 pandemic originated in Wuhan, Hubei Province, China in December 2019. The etiologic agent is a novel coronavirus of presumed zoonotic origin with structural similarity to the viruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Like SARS and MERS, COVID\u201019 infection manifests most frequently with lower respiratory symptoms. A minority of patients progress to acute respiratory distress syndrome/ diffuse alveolar damage. In addition to its central role in the diagnosis of COVID\u201019 infection, the clinical laboratory provides critical information to clinicians regarding prognosis, disease course, and response to therapy. The purpose of this review is to 1) provide background context about the origins and course of the pandemic 2) discuss the laboratory\u2019s role in the diagnosis of COVID\u201019 infection 3) summarize the current state of biomarker analysis in COVID\u201019 infection, with an emphasis on markers derived from the hematology laboratory 4) comment on the impact of COVID\u201019 on hematology laboratory safety, and 5) describe the impact the pandemic has had on organized national and international educational activities worldwide.", "qid": 1, "docid": "wco27nop", "rank": 35, "score": 0.7664749622344971}, {"content": "Title: Coronavirus disease 2019 (COVID-19): current status and future perspectives Content: Coronavirus disease 2019 (COVID-19) originated in the city of Wuhan, Hubei Province, Central China, and has spread quickly to 72 countries to date. COVID-19 is caused by a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [previously provisionally known as 2019 novel coronavirus (2019-nCoV)]. At present, the newly identified SARS-CoV-2 has caused a large number of deaths with tens of thousands of confirmed cases worldwide, posing a serious threat to public health. However, there are no clinically approved vaccines or specific therapeutic drugs available for COVID-19. Intensive research on the newly emerged SARS-CoV-2 is urgently needed to elucidate the pathogenic mechanisms and epidemiological characteristics and to identify potential drug targets, which will contribute to the development of effective prevention and treatment strategies. Hence, this review will focus on recent progress regarding the structure of SARS-CoV-2 and the characteristics of COVID-19, such as the aetiology, pathogenesis and epidemiological characteristics.", "qid": 1, "docid": "m4y8tf6u", "rank": 36, "score": 0.7664576768875122}, {"content": "Title: The need to manage the risk of thromboembolism in COVID-19 patients Content: COVID-19 first appeared in Wuhan, Hubei Province, China, in December 2019. Thought to be of zoonotic origin, it has been named SARS-CoV-2 (COVID-19) and has spread rapidly. As of April 20, 2020, there have been >2.4 million cases recorded worldwide. The inflammatory process, cytokine storm, and lung injury that are associated with COVID-19 can put patients at an increased risk of thrombosis. The total incidence of thrombotic events in COVID-19 patients is currently uncertain. Those with more severe disease and with other risk factors, including increasing age, male sex, obesity, cancer, comorbidities, and intensive care unit admission, are at higher risk of these events. However, there is little international guidance on managing these risks in COVID-19 patients. In this paper, we explore the current evidence and theories surrounding thrombosis in these unique patients and reflect on experience from our center.", "qid": 1, "docid": "e9dianoi", "rank": 37, "score": 0.7660868763923645}, {"content": "Title: COVID\u201019: a brief history and treatments in development Content: Coronavirus disease (COVID\u201019) is now dominating the lives of everyone, and its history is constantly being rewritten. This article gives a brief account of the story so far: where SARS\u2010CoV\u20102 might have originated, how it compares with other viruses that cause major respiratory disease, and some of the treatments and vaccines currently being investigated to combat it.", "qid": 1, "docid": "qp4efhwq", "rank": 38, "score": 0.7643003463745117}, {"content": "Title: Could India be the origin of next COVID-19 like epidemic? Content: Abstract The COVID-19 global pandemic is not even over yet but it has already taught us a lot of lessons - the hard way. The vast majority of the global community has blamed the Chinese Illegal wildlife markets for the origin of this pandemic. Through careful scientific analysis, I have explained in this article that we don't need such wildlife markets for these kinds of outbreaks to occur in the future. I have also explained how India which is the second-most populous country in the world, could be the origin of the next outbreak, even though such wildlife markets are either very rare or do not exist at all in India.", "qid": 1, "docid": "zd7smm8r", "rank": 39, "score": 0.7642123699188232}, {"content": "Title: To alert coinfection of COVID-19 and dengue virus in developing countries in the dengue-endemic area Content: Coronavirus disease 2019 (CoVID-19) is a new outbreak infectious disease caused by SARS-CoV-2, which was originated from Wuhan in China and has now spread to the whole world. At the meantime, dengue was endemic in the Southeast Asia and South America, and a part of the patients shared the same symptoms, so, we write this paper to alert the clinicians to distinguish these two diseases.", "qid": 1, "docid": "0oiq44gl", "rank": 40, "score": 0.7635972499847412}, {"content": "Title: The need to manage the risk of thromboembolism in COVID-19 patients Content: COVID-19 first presented in Wuhan, Hubei Province, China, in December 2019. Thought to be of zoonotic origin, it has been named SARS-CoV-2 (COVID-19) and has spread rapidly. As of April 20(th), 2020, there have been more than 2.4 million cases recorded worldwide. The inflammatory process, cytokine storm, and lung injury that are associated with COVID-19 can put patients at an increased risk of thrombosis. It is uncertain what the total incidences of thrombotic events in COVID-19 patients is currently at. Those with more severe disease and with other risk factors, including increasing age, male sex, obesity, cancer, comorbidities, and intensive care unit admission, are at higher risk of these events. However, there is little international guidance on managing these risks in COVID-19 patients. In this paper, we explore the current evidence and theories surrounding thrombosis in these unique patients and reflect on experience from our center.", "qid": 1, "docid": "dckuhrlf", "rank": 41, "score": 0.7632919549942017}, {"content": "Title: Characterizing the transmission and identifying the control strategy for COVID-19 through epidemiological modeling Content: The outbreak of the novel coronavirus disease, COVID-19, originating from Wuhan, China in early December, has infected more than 70,000 people in China and other countries and has caused more than 2,000 deaths. As the disease continues to spread, the biomedical society urgently began identifying effective approaches to prevent further outbreaks. Through rigorous epidemiological analysis, we characterized the fast transmission of COVID-19 with a basic reproductive number 5.6 and proved a sole zoonotic source to originate in Wuhan. No changes in transmission have been noted across generations. By evaluating different control strategies through predictive modeling and Monte carlo simulations, a comprehensive quarantine in hospitals and quarantine stations has been found to be the most effective approach. Government action to immediately enforce this quarantine is highly recommended.", "qid": 1, "docid": "rr7r7ef0", "rank": 42, "score": 0.7631587386131287}, {"content": "Title: SARS-CoV-2 (COVID-19) by the numbers Content: The COVID-19 pandemic is a harsh reminder of the fact that, whether in a single human host or a wave of infection across continents, viral dynamics is often a story about the numbers. In this article we provide a one-stop, curated graphical source for the key numbers (based mostly on the peer-reviewed literature) about the SARS-CoV-2 virus that is responsible for the pandemic. The discussion is framed around two broad themes: i) the biology of the virus itself; ii) the characteristics of the infection of a single human host.", "qid": 1, "docid": "d7qrip2k", "rank": 43, "score": 0.7625980377197266}, {"content": "Title: Early COVID-19 infection after lung transplantation Content: COVID-19, the clinical syndrome caused by the novel coronavirus, SARS-CoV-2, continues to rapidly spread, leading to significant stressors on global healthcare infrastructure. The manifestations of COVID-19 in solid organ transplant recipients are only beginning to be understood with cases reported to date in transplant recipients on chronic immunosuppression. Herein, we report the first case of COVID-19 in a lung transplant recipient in the immediate posttransplant period, and we describe the epidemiologic challenges in identifying the source of infection in this unique situation.", "qid": 1, "docid": "x3667e6s", "rank": 44, "score": 0.7622332572937012}, {"content": "Title: Using open-source intelligence to detect early signals of COVID-19 in China, Descriptive study Content: BACKGROUND: COVID-19 in China was first reported to the World Health Organization on December 31st 2019. The first cases were officially identified around December 8th 2019. The origin of COVID-19 is not confirmed, but half the early cases were linked to a seafood market in Wuhan. The first two documented cases did not attend the seafood market. News reports, social media and informal sources may contain information about outbreaks prior to formal notification. OBJECTIVE: To identify early signals of pneumonia and/or severe acute respiratory illness (SARI) in China, prior to official recognition of the COVID 19 outbreak in December 2019, using open source data. METHODS: In order to capture early reports we searched an open source epidemic observatory, Epiwatch from 1st October2019 in China, for severe acute respiratory illness (SARI) or pneumonia related illnesses. Google and Chinese search engine Baidu were used. RESULTS: There was an increase in reports following the official notification of COVID 19 to WHO on December 31 2019, and a retracted report on December 26th 2019. A report of severe pneumonia was identified on November 22 2019 in Xiangyang, Index patient was retrospectively identified on 17 November. CONCLUSIONS: The lack of reports of a SARI outbreaks prior to December 31st, with a retracted report on December 26th suggests media censorship, given formal reports that cases began on December 8th. However, the findings also support relatively recent origin of COVID-19 in November 2019. The case reported on November 22nd was transferred to Wuhan approximately 1 incubation period before the first reported cases on December 8th, and should be further investigated, as only half of the early cases had exposure to the seafood market. It has since been reported that another case of COVID 19 has been retrospectively identified in Hubei on November 17th, confirming that the infection was present prior to December.", "qid": 1, "docid": "m4ctyt7p", "rank": 45, "score": 0.7620089650154114}, {"content": "Title: COVID-19 breakthroughs: separating fact from fiction Content: The newly recognised coronavirus SARS-CoV-2, causative agent of COVID-19, has caused a pandemic with huge ramifications for human interactions around the globe. As expected, research efforts to understand the virus and curtail the disease are moving at a frantic pace alongside the spread of rumours, speculations and falsehoods. In this article, we aim to clarify the current scientific view behind several claims or controversies related to COVID-19. Starting with the origin of the virus, we then discuss the effect of ibuprofen and nicotine on the severity of the disease. We highlight the knowledge on fomites and SARS-CoV-2 and discuss the evidence and explications for a disproportionately stronger impact of COVID-19 on ethnic minorities, including a potential protective role for vitamin D. We further review what is known about the effects of SARS-CoV-2 infection in children, including their role in transmission of the disease, and conclude with the science on different mortality rates between different countries and whether this hints at the existence of more pathogenic cohorts of SARS-CoV-2.", "qid": 1, "docid": "l2wzr3w1", "rank": 46, "score": 0.7620036602020264}, {"content": "Title: Origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19). Content: Coronavirus has emerged as a global health treat due to its accelerated geographic spread over the last two decades. This article reviews the current state of knowledge concerning the origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19). Historically, it has caused two pandemics: severe acute respiratory syndrome and Middle East respiratory syndrome followed by the present COVID-19 that emerged from China. The virus is believed to be acquired from zoonotic source and spreads through direct and contact transmission. The symptomatic phase manifests with fever, cough and myalgia to severe respiratory failure. The diagnosis is confirmed using reverse transcriptase PCR. Management of COVID-19 is mainly by supportive therapy along with mechanical ventilation in severe cases. Preventive strategies form the major role in reducing the public spread of virus along with successful disease isolation and community containment. Development of a vaccine to eliminate the virus from the host still remains an ongoing challenge.", "qid": 1, "docid": "e6h1qvdk", "rank": 47, "score": 0.7616039514541626}, {"content": "Title: A Genomic Perspective on the Origin and Emergence of SARS-CoV-2 Content: The ongoing pandemic of a new human coronavirus, SARS-CoV-2, has generated enormous global concern. We and others in China were involved in the initial genome sequencing of the virus. Herein, we describe what genomic data reveal about the emergence SARS-CoV-2 and discuss the gaps in our understanding of its origins.", "qid": 1, "docid": "5hio4lgc", "rank": 48, "score": 0.7613526582717896}, {"content": "Title: Liver transplantation in an ICU dominated by COVID-19 Content: The Letter from D'Antiga L about concerns of transplanting patients in the context of COVID19 pandemic is very interesting [1]. COVID-19 designates the infection caused by the SARS-Cov2 virus. This illness originated in December, 2019, in Wuhan, China. Since then, it has been identified in more than 150 countries. The first case of COVID-19 in Portugal was notified in March 02, 2020.", "qid": 1, "docid": "8a6flxl6", "rank": 49, "score": 0.7609827518463135}, {"content": "Title: Liver transplantation in an ICU dominated by COVID-19. Content: The Letter from D'Antiga L about concerns of transplanting patients in the context of COVID19 pandemic is very interesting [1]. COVID-19 designates the infection caused by the SARS-Cov2 virus. This illness originated in December, 2019, in Wuhan, China. Since then, it has been identified in more than 150 countries. The first case of COVID-19 in Portugal was notified in March 02, 2020.", "qid": 1, "docid": "6ck2ntid", "rank": 50, "score": 0.7609827518463135}, {"content": "Title: Could India be the origin of next COVID-19 like epidemic? Content: The COVID-19 global pandemic is not even over yet but it has already taught us a lot of lessons - the hard way. The vast majority of the global community has blamed the Chinese Illegal wildlife markets for the origin of this pandemic. Through careful scientific analysis, I have explained in this article that we don't need such wildlife markets for these kinds of outbreaks to occur in the future. I have also explained how India which is the second-most populous country in the world, could be the origin of the next outbreak, even though such wildlife markets are either very rare or do not exist at all in India.", "qid": 1, "docid": "cniyembt", "rank": 51, "score": 0.7604763507843018}, {"content": "Title: Insights into molecular evolution recombination of pandemic SARS-CoV-2 using Saudi Arabian sequences Content: The recently emerged SARS-CoV-2 (Coronaviridae; Betacoronavirus) is the underlying cause of COVID-19 disease. Here we assessed SARS-CoV2 from the Kingdom of Saudi Arabia alongside sequences of SARS-CoV, bat SARS-like CoVs and MERS-CoV, the latter currently detected in this region. Phylogenetic analysis, natural selection investigation and genome recombination analysis were performed. Our analysis showed that all Saudi SARS-CoV-2 sequences are of the same origin and closer proximity to bat SARS-like CoVs, followed by SARS-CoVs, however quite distant to MERS-CoV. Moreover, genome recombination analysis revealed two recombination events between SARS-CoV-2 and bat SARS-like CoVs. This was further assessed by S gene recombination analysis. These recombination events may be relevant to the emergence of this novel virus. Moreover, positive selection pressure was detected between SARS-CoV-2, bat SL-CoV isolates and human SARS-CoV isolates. However, the highest positive selection occurred between SARS-CoV-2 isolates and 2 bat-SL-CoV isolates (Bat-SL-RsSHC014 and Bat-SL-CoVZC45). This further indicates that SARS-CoV-2 isolates were adaptively evolved from bat SARS-like isolates, and that a virus with originating from bats triggered this pandemic. This study thuds sheds further light on the origin of this virus. AUTHOR SUMMARY The emergence and subsequent pandemic of SARS-CoV-2 is a unique challenge to countries all over the world, including Saudi Arabia where cases of the related MERS are still being reported. Saudi SARS-CoV-2 sequences were found to be likely of the same or similar origin. In our analysis, SARS-CoV-2 were more closely related to bat SARS-like CoVs rather than to MERS-CoV (which originated in Saudi Arabia) or SARS-CoV, confirming other phylogenetic efforts on this pathogen. Recombination and positive selection analysis further suggest that bat coronaviruses may be at the origin of SARS-CoV-2 sequences. The data shown here give hints on the origin of this virus and may inform efforts on transmissibility, host adaptation and other biological aspects of this virus.", "qid": 1, "docid": "wim5q9a5", "rank": 52, "score": 0.7596150636672974}, {"content": "Title: The Story behind COVID-19: Animal Diseases at the Crossroads of Wildlife, Livestock and Human Health Content: A number of virological, epidemiological and ethnographic arguments suggest that COVID-19 has a zoonotic origin. The pangolin, a species threatened with extinction due to poaching for both culinary purposes and traditional Chinese pharmacopoeia, is now suspected of being the \u201cmissing link\u201d in the transmission to humans of a virus that probably originated in a species of bat. Our predation of wild fauna and the reduction in their habitats have thus ended up creating new interfaces that favour the transmission of pathogens (mainly viruses) to humans. Domesticated animals and wild fauna thus constitute a reservoir for almost 80% of emerging human diseases (SARS-CoV, MERS-CoV, Ebola). These diseases are all zoonotic in origin. As if out of a Chinese fairy tale, the bat and the pangolin have taught us a lesson: within an increasingly interdependent world, environmental crises will become ever more intertwined with health crises. Questions relating to public health will no longer be confined to the secrecy of the physician\u2019s consulting room or the sanitised environment of the hospital. They are now being played out in the arena of international trade, ports and airports and distribution networks. Simply put, all human activity creates new interfaces that facilitate the transmission of pathogens from an animal reservoir to humans. This pluri-disciplinary article highlights that environmental changes, such as the reduction in habitats for wild fauna and the intemperate trade in fauna, are the biggest causes of the emergence of new diseases. Against this background, it reviews the different measures taken to control, eradicate and prevent the emergence of animal diseases in a globalised world.", "qid": 1, "docid": "105q161g", "rank": 53, "score": 0.7593295574188232}, {"content": "Title: Importation of SARS-CoV-2 infection leads to major COVID-19 epidemic in Taiwan Content: OBJECTIVE: COVID-19 has recently become a pandemic affecting many countries worldwide. This study aims to evaluate the current status of COVID-19 in Taiwan and analyze the source of infection. METHODS: National data regarding SARS-CoV-2 infection were obtained from Taiwan. CDC at the end of April 2020. These data were subjected to analysis of the current status and correlation between indigenous and imported COVID-19 cases. A phylogenetic tree was created to analyze the phylogeny of Taiwanese SARS-CoV-2 isolates. RESULTS: The first case of SARS-CoV-2 infection in Taiwan was detected on January 21, 2020. Epidemiological data indicate that by April 30, there were a total of 429 COVID-19 confirmed cases with the death rate of 1.3%. Most cases were identified as imported (79.9%; 343/429), with the majority originating from the United States of America (22.1%) and the United Kingdom (17.6%). Results from phylogenetic tree analyses indicate that the Taiwanese SARS-CoV-2 isolates were clustered with the SARS-CoV-2 isolates from other countries (bootstrap value 98%) and sub-clustered with bat SARS-like coronaviruses (bootstrap value 99%). CONCLUSION: This study suggests that the importation of SARS-CoV-2 infection was the primary risk-factor resulting in the COVID-19 epidemic in Taiwan.", "qid": 1, "docid": "giu9j0k1", "rank": 54, "score": 0.7593189477920532}, {"content": "Title: The cardiovascular burden of coronavirus disease 2019 (COVID-19) with a focus on congenital heart disease Content: Abstract Coronavirus disease 2019 (COVID-19), caused by a novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first described in a cluster of patients presenting with pneumonia symptoms in Wuhan, China, in December of 2019. Over the past few months, COVID-19 has developed into a worldwide pandemic, with over 400,000 documented cases globally as of March 24, 2020. The SARS-CoV-2 virus is most likely of zoonotic origin, but has been shown to have effective human-to-human transmission. COVID-19 results in mild symptoms in the majority of infected patients, but can cause severe lung injury, cardiac injury, and death. Given the novel nature of COVID-19, no established treatment beyond supportive care exists currently, but extensive public-health measures to reduce person-to-person transmission of COVID-19 have been implemented globally to curb the spread of disease, reduce the burden on healthcare systems, and protect vulnerable populations, including the elderly and those with underlying medical comorbidities. Since this is an emerging infectious disease, there is, as of yet, limited data on the effects of this infection on patients with cardiovascular disease, particularly so for those with congenital heart disease. We summarize herewith the early experience with COVID-19 and consider the potential applicability to and implications for patients with cardiovascular disease in general and congenital heart disease in particular.", "qid": 1, "docid": "ky33ju30", "rank": 55, "score": 0.7587327361106873}, {"content": "Title: Analysis of the Hosts and Transmission Paths of SARS-CoV-2 in the COVID-19 Outbreak Content: The severe respiratory disease COVID-19 was initially reported in Wuhan, China, in December 2019, and spread into many provinces from Wuhan. The corresponding pathogen was soon identified as a novel coronavirus named SARS-CoV-2 (formerly, 2019-nCoV). As of 2 May, 2020, over 3 million COVID-19 cases had been confirmed, and 235,290 deaths had been reported globally, and the numbers are still increasing. It is important to understand the phylogenetic relationship between SARS-CoV-2 and known coronaviruses, and to identify its hosts for preventing the next round of emergency outbreak. In this study, we employ an effective alignment-free approach, the Natural Vector method, to analyze the phylogeny and classify the coronaviruses based on genomic and protein data. Our results show that SARS-CoV-2 is closely related to, but distinct from the SARS-CoV branch. By analyzing the genetic distances from the SARS-CoV-2 strain to the coronaviruses residing in animal hosts, we establish that the most possible transmission path originates from bats to pangolins to humans.", "qid": 1, "docid": "i14gkdw0", "rank": 56, "score": 0.7578778266906738}, {"content": "Title: Using open-source intelligence to detect early signals of COVID-19 in China, Descriptive study. Content: BACKGROUND COVID-19 in China was first reported to the World Health Organization on December 31st 2019. The first cases were officially identified around December 8th 2019. The origin of COVID-19 is not confirmed, but half the early cases were linked to a seafood market in Wuhan. The first two documented cases did not attend the seafood market. News reports, social media and informal sources may contain information about outbreaks prior to formal notification. OBJECTIVE To identify early signals of pneumonia and/or severe acute respiratory illness (SARI) in China, prior to official recognition of the COVID 19 outbreak in December 2019, using open source data. METHODS In order to capture early reports we searched an open source epidemic observatory, Epiwatch from 1st October2019 in China, for severe acute respiratory illness (SARI) or pneumonia related illnesses. Google and Chinese search engine Baidu were used. RESULTS There was an increase in reports following the official notification of COVID 19 to WHO on December 31 2019, and a retracted report on December 26th 2019. A report of severe pneumonia was identified on November 22 2019 in Xiangyang, Index patient was retrospectively identified on 17 November. CONCLUSIONS The lack of reports of a SARI outbreaks prior to December 31st, with a retracted report on December 26th suggests media censorship, given formal reports that cases began on December 8th. However, the findings also support relatively recent origin of COVID-19 in November 2019. The case reported on November 22nd was transferred to Wuhan approximately 1 incubation period before the first reported cases on December 8th, and should be further investigated, as only half of the early cases had exposure to the seafood market. It has since been reported that another case of COVID 19 has been retrospectively identified in Hubei on November 17th, confirming that the infection was present prior to December. CLINICALTRIAL", "qid": 1, "docid": "w9yibx5o", "rank": 57, "score": 0.7573933005332947}, {"content": "Title: The SARS-CoV-2 outbreak: What we know Content: There is a current worldwide outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; the pathogen called SARS-CoV-2; previously 2019-nCoV), which originated from Wuhan in China and has now spread to 6 continents including 66 countries, as of 24:00 on March 2, 2020. Governments are under increased pressure to stop the outbreak from spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak site and from laboratories supporting the investigation. This paper aggregates and consolidates the epidemiology, clinical manifestations, diagnosis, treatments and preventions of this new type of coronavirus.", "qid": 1, "docid": "950x4b9a", "rank": 58, "score": 0.7572767734527588}, {"content": "Title: Virus outbreak crosses boundaries Content: Summary The current outbreak of coronavirus disease COVID-19 is showing up vulnerabilities in many aspects of the globalised world we live in. The suggestion that it may have originated in the endangered pangolin also puts animal trafficking in the spotlight. The human\u2013wildlife interface remains an important risk factor for further disease outbreaks. Michael Gross reports.", "qid": 1, "docid": "4vnheihi", "rank": 59, "score": 0.7567307949066162}, {"content": "Title: Bioinformatic analysis indicates that SARS-CoV-2 is unrelated to known artificial coronaviruses Content: OBJECTIVE: SARS-CoV-2 is responsible for the present coronavirus pandemic and some suggestions were made about its possible artificial origin. We, therefore, compared SARS-CoV-2 with such known viruses that were prepared in the laboratory and other relevant natural strains to estimate their genetic relatedness. MATERIALS AND METHODS: BLAST and clustalW were used to identify and align viral sequences of SARS-CoV-2 to other animal coronaviruses (human, bat, mouse, pangolin) and related artificial constructs. Phylogenetics trees were then prepared using iTOL. RESULTS: Our study supports the notion that known artificial coronaviruses, including the chimeric SL-SHC014-MA15 synthesized in 2015, differ too much from SARS-CoV-2 to hypothesize an artificial origin of the latter. On the contrary, our data support the natural origin of the COVID-19 virus, likely derived from bats, possibly transferred to pangolins, before spreading to man. CONCLUSIONS: Speculations about the artificial origin of SARS-CoV-2 are most likely unfounded. On the contrary, when carefully handled, engineered organisms provide a unique opportunity to study biological systems in a controlled fashion. Biotechnology is a powerful tool to advance medical research and should not be abandoned because of irrational fears.", "qid": 1, "docid": "icwvm7jp", "rank": 60, "score": 0.7566047310829163}, {"content": "Title: Predicting COVID-19 distribution in Mexico through a discrete and time-dependent Markov chain and an SIR-like model Content: COVID-19 is an emergent viral infection which rose in December 2019 in a city in the Chinese province of Hubei, Wuhan; the viral aetiology of this infection is now known as COVID-19 virus, which belongs to the Betacoronavirus genus. This virus produces the syndrome of acute respiratory stress that h as been witnessed in other coronaviruses, such as that MERS-CoV in Middle East countries or SARS-CoV which was seen in 2002 and 2003 in China. This virus mediates its entry through its spike (S) proteins interacting with ACE2 receptors in lung epithelial cells, and may promote an inflammatory response by means of inflammasome NLRP3 activation and unfolded protein response (these are possibly consequence of the envelope E protein of COVID-19 virus). Efforts have been made worldwide to prevent further spread of the disease, but in March 2020 the WHO declared it a pandemic emergency and Mexico started to report its first cases. In this paper we attempt to summarize the biological features of the virus and the possible pathophysiological mechanisms of its disease, as well as a stochastic model characterizing the probability distribution of cases in Mexico by states and the estimated number of cases in Mexico through a differential equation model (modified SIR model), thus will we be able to characterize the disease and its course in Mexico in order to display more preparedness and promote more logical actions by both the policy makers as well as the general population.", "qid": 1, "docid": "jlv5llys", "rank": 61, "score": 0.7561502456665039}, {"content": "Title: COVID-19 infection: the China and Italy perspectives Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Since its first report in December 2019, despite great efforts made in almost every country worldwide, this disease continues to spread globally, especially in most parts of Europe, Iran, and the United States. Here, we update the recent understanding in clinical characteristics, diagnosis strategies, as well as clinical management of COVID-19 in China as compared to Italy, with the purpose to integrate the China experience with the global efforts to outline references for prevention, basic research, treatment as well as final control of the disease. Being the first two countries we feel appropriate to evaluate the evolution of the disease as well as the early result of the treatment, in order to offer a different baseline to other countries. It is also interesting to compare two countries, with a very significant difference in population, where the morbidity and mortality has been so different, and unrelated to the size of the country.", "qid": 1, "docid": "tl8z1ri5", "rank": 62, "score": 0.7557743787765503}, {"content": "Title: COVID\u201019 breakthroughs: separating fact from fiction Content: The newly recognised coronavirus SARS\u2010CoV\u20102, causative agent of COVID\u201019, has caused a pandemic with huge ramifications for human interactions around the globe. As expected, research efforts to understand the virus and curtail the disease are moving at a frantic pace alongside the spread of rumours, speculations and falsehoods. In this article, we aim to clarify the current scientific view behind several claims or controversies related to COVID\u201019. Starting with the origin of the virus, we then discuss the effect of ibuprofen and nicotine on the severity of the disease. We highlight the knowledge on fomites and SARS\u2010CoV\u20102 and discuss the evidence and explications for a disproportionately stronger impact of COVID\u201019 on ethnic minorities, including a potential protective role for vitamin D. We further review what is known about the effects of SARS\u2010CoV\u20102 infection in children, including their role in transmission of the disease, and conclude with the science on different mortality rates between different countries and whether this hints at the existence of more pathogenic cohorts of SARS\u2010CoV\u20102.", "qid": 1, "docid": "ipl6189w", "rank": 63, "score": 0.7555837631225586}, {"content": "Title: Coast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States Content: The novel coronavirus SARS-CoV-2 was first detected in the Pacific Northwest region of the United States in January 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the United States, we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated effects of federal travel restrictions. This study provides evidence of widespread sustained transmission of SARS-CoV-2 within the United States and highlights the critical need for local surveillance.", "qid": 1, "docid": "y3lr8obh", "rank": 64, "score": 0.7553865909576416}, {"content": "Title: The cardiovascular burden of coronavirus disease 2019 (COVID-19) with a focus on congenital heart disease Content: Coronavirus disease 2019 (COVID-19), caused by a novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first described in a cluster of patients presenting with pneumonia symptoms in Wuhan, China, in December of 2019. Over the past few months, COVID-19 has developed into a worldwide pandemic, with over 400,000 documented cases globally as of March 24, 2020. The SARS-CoV-2 virus is most likely of zoonotic origin, but has been shown to have effective human-to-human transmission. COVID-19 results in mild symptoms in the majority of infected patients, but can cause severe lung injury, cardiac injury, and death. Given the novel nature of COVID-19, no established treatment beyond supportive care exists currently, but extensive public-health measures to reduce person-to-person transmission of COVID-19 have been implemented globally to curb the spread of disease, reduce the burden on healthcare systems, and protect vulnerable populations, including the elderly and those with underlying medical comorbidities. Since this is an emerging infectious disease, there is, as of yet, limited data on the effects of this infection on patients with cardiovascular disease, particularly so for those with congenital heart disease. We summarize herewith the early experience with COVID-19 and consider the potential applicability to and implications for patients with cardiovascular disease in general and congenital heart disease in particular.", "qid": 1, "docid": "7wusbdmm", "rank": 65, "score": 0.7543419599533081}, {"content": "Title: Coronavirus disease 2019 (COVID-19): current status and future perspectives Content: ABSTRACT Coronavirus disease 2019 (COVID-19) originated in the city of Wuhan, Hubei Province, Central China, and has spread quickly to 72 countries to date. COVID-19 is caused by a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [previously provisionally known as 2019 novel coronavirus (2019-nCoV)]. At present, the newly identified SARS-CoV-2 has caused a large number of deaths with tens of thousands of confirmed cases worldwide, posing a serious threat to public health. However, there are no clinically approved vaccines or specific therapeutic drugs available for COVID-19. Intensive research on the newly emerged SARS-CoV-2 is urgently needed to elucidate the pathogenic mechanisms and epidemiological characteristics and to identify potential drug targets, which will contribute to the development of effective prevention and treatment strategies. Hence, this review will focus on recent progress regarding the structure of SARS-CoV-2 and the characteristics of COVID-19, such as the aetiology, pathogenesis and epidemiological characteristics.", "qid": 1, "docid": "jbtrdvhe", "rank": 66, "score": 0.7543323040008545}, {"content": "Title: Influenza\u2010like illnesses caused by a cluster of imported Italian COVID\u201019 Content: The ongoing pandemic of 2019 corona\u2010virus disease (COVID\u201019) is caused by an emerging family of SARS\u2010CoV\u20102, threatening human health worldwide. Here we report a cluster of Italian COVID\u201019 imported to Lishui City, China. Of all the eight patients, 7 consistently display cough, a representative sign of influenza\u2010like illness (ILI), and the remaining one is a cryptic case. This further our understanding a full spectrum of COVID\u201019 repertoire. This article is protected by copyright. All rights reserved.", "qid": 1, "docid": "0jtb46tu", "rank": 67, "score": 0.7542773485183716}, {"content": "Title: COVID-19 under spotlight: A close look at the origin, transmission, diagnosis, and treatment of the 2019-nCoV disease Content: Months after the outbreak of a new flu-like disease in China, the entire world is now in a state of caution. The subsequent less-anticipated propagation of the novel coronavirus disease, formally known as COVID-19, not only made it to headlines by an overwhelmingly high transmission rate and fatality reports, but also raised an alarm for the medical community all around the globe. Since the causative agent, SARS-CoV-2, is a recently discovered species, there is no specific medicine for downright treatment of the infection. This has led to an unprecedented societal fear of the newly born disease, adding a psychological aspect to the physical manifestation of the virus. Herein, the COVID-19 structure, epidemiology, pathogenesis, etiology, diagnosis, and therapy have been reviewed.", "qid": 1, "docid": "y3uzb4dx", "rank": 68, "score": 0.7541191577911377}, {"content": "Title: Reorganization of a Northern Italy dermatology department during the COVID-19 pandemic: is it temporary or the beginning of a new era in dermatology? Content: COVID-19 outbreak, caused by the Coronavirus SARS-CoV2, started in December 2019 in Wuhan, Hubei, China and then has rapidly spread to the whole world becoming a pandemic. In February 2020, COVID-19 has reached Europe and, in particular, it has roughly hit Italy and, subsequently, other countries and continents. Consequently, hospitals have started to intensively reduce elective activities to face the high numbers of COVID-19 patients' admissions. In Italy, all the non-urgent clinical appointments (such as primary prevention visits and elective surgeries) have been postponed. We describe the reorganization of our Northern Italy dermatology department during COVID-19 pandemic, including teledermatology strategies. Considering the unknown duration of this emergency scenario we wonder if this is just a temporary measure or the beginning of a new era in dermatology departments' organization?", "qid": 1, "docid": "98k853uo", "rank": 69, "score": 0.7541043162345886}, {"content": "Title: Opportunities, Challenges and Directions in Science and Technology for Tackling COVID-19 Content: The ongoing global crisis due to Coronavirus disease-2019 (COVID-19) pandemic has caused an enormous socioeconomic burden. A novel coronavirus causing severe acute respiratory syndrome (SARS-CoV-2) that evolved from a virus infecting bats is responsible for COVID-19, first reported in the Chinese city of Wuhan. In the absence of any specific scientifically proven and clinically tested drug or vaccine against SARS-CoV-2, the virus is wreaking havoc across the world, claiming more than 2,50,000 lives in less than 5 months, and posed a global health emergency. The scientific community is relentlessly working on the design and testing of vaccines and antiviral drugs against the novel coronavirus, several of which have reached advanced stages of testing and are undergoing clinical trials. Here we discuss the recent advances and developments in understanding the etiology and epidemiology of the COVID-19 pandemic, the factors influencing the disease transmission, and the countermeasures adopted to combat and stop further spread of the disease.", "qid": 1, "docid": "1ythzigc", "rank": 70, "score": 0.7540160417556763}, {"content": "Title: SARS-CoV-2 variants: Relevance for symptom granularity, epidemiology, immunity (herd, vaccines), virus origin and containment? Content: The origin of the SARS-CoV-2 virus remains enigmatic. It is likely to be a continuum resulting from inevitable mutations and recombination events. These genetic changes keep developing in the present epidemic. Mutations tending to deplete the genome in its cytosine content will progressively lead to attenuation as a consequence of Muller's ratchet, but this is counteracted by recombination when different mutants co-infect the same host, in particular, in clusters of infection. Monitoring as a function of time the genome sequences in closely related cases is critical to anticipate the future of SARS-CoV-2 and hence of COVID-19.", "qid": 1, "docid": "mtngelbr", "rank": 71, "score": 0.7535859942436218}, {"content": "Title: Is SARS-CoV-2 a new Frankenstein monster virus? Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus of beta coronavirus genus originated in Wuhan, China in December 2019, resulted in the pandemic spread of Corona Virus Disease 2019 (COVID-19) worldwide. This genus also contains SARS-CoV (originated in China 2002-2003) and MERS-CoV (found in Saudi Arabia 2012). The nucleotide sequences of SARS-CoV-2 is closer to SARS-CoV (with approximately 80% identity) than to MERS-CoV. Despite these similarities, SARS-CoV-2 has two main features over the other coronaviruses. The first is the high contagious rate and the second is the immune response evasion. The higher transmission ability makes this virus quickly spread worldwide with a high mortality rate and more economic losses. This review will provide an overview of the current knowledge on the role of some viral and host cell factors in higher transmission and contagious spread of SARS-CoV-2.", "qid": 1, "docid": "3f9dbwd2", "rank": 72, "score": 0.7531715631484985}, {"content": "Title: World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19) Content: An unprecedented outbreak of pneumonia of unknown aetiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus was identified as the causative agent and was subsequently termed COVID-19 by the World Health Organization (WHO). Considered a relative of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), COVID-19 is caused by a betacoronavirus named SARS-CoV-2 that affects the lower respiratory tract and manifests as pneumonia in humans. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with 90,870 laboratory-confirmed cases and over 3,000 deaths worldwide. In response to this global outbreak, we summarise the current state of knowledge surrounding COVID-19.", "qid": 1, "docid": "mq4b2rw2", "rank": 73, "score": 0.7529656887054443}, {"content": "Title: The SARS-CoV-2 outbreak: What we know Content: Abstract There is a current worldwide outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; the pathogen called SARS-CoV-2; previously 2019-nCoV), which originated from Wuhan in China and has now spread to 6 continents including 66 countries, as of 24:00 on March 2, 2020. Governments are under increased pressure to stop the outbreak from spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak site and from laboratories supporting the investigation. This paper aggregates and consolidates the epidemiology, clinical manifestations, diagnosis, treatments and preventions of this new type of coronavirus.", "qid": 1, "docid": "5fg87lvu", "rank": 74, "score": 0.7528657913208008}, {"content": "Title: COVID-19 breakthroughs: separating fact from fiction Content: The newly recognised coronavirus SARS-CoV-2, causative agent of coronavirus disease (COVID-19), has caused a pandemic with huge ramifications for human interactions around the globe. As expected, research efforts to understand the virus and curtail the disease are moving at a frantic pace alongside the spread of rumours, speculations and falsehoods. In this article, we aim to clarify the current scientific view behind several claims or controversies related to COVID-19. Starting with the origin of the virus, we then discuss the effect of ibuprofen and nicotine on the severity of the disease. We highlight the knowledge on fomites and SARS-CoV-2 and discuss the evidence and explications for a disproportionately stronger impact of COVID-19 on ethnic minorities, including a potential protective role for vitamin D. We further review what is known about the effects of SARS-CoV-2 infection in children, including their role in transmission of the disease, and conclude with the science on different mortality rates between different countries and whether this hints at the existence of more pathogenic cohorts of SARS-CoV-2.", "qid": 1, "docid": "41378qru", "rank": 75, "score": 0.7524858713150024}, {"content": "Title: Bioinformatic analysis indicates that SARS-CoV-2 is unrelated to known artificial coronaviruses. Content: OBJECTIVE SARS-CoV-2 is responsible for the present coronavirus pandemic and some suggestions were made about its possible artificial origin. We, therefore, compared SARS-CoV-2 with such known viruses that were prepared in the laboratory and other relevant natural strains to estimate their genetic relatedness. MATERIALS AND METHODS BLAST and clustalW were used to identify and align viral sequences of SARS-CoV-2 to other animal coronaviruses (human, bat, mouse, pangolin) and related artificial constructs. Phylogenetics trees were then prepared using iTOL. RESULTS Our study supports the notion that known artificial coronaviruses, including the chimeric SL-SHC014-MA15 synthesized in 2015, differ too much from SARS-CoV-2 to hypothesize an artificial origin of the latter. On the contrary, our data support the natural origin of the COVID-19 virus, likely derived from bats, possibly transferred to pangolins, before spreading to man. CONCLUSIONS Speculations about the artificial origin of SARS-CoV-2 are most likely unfounded. On the contrary, when carefully handled, engineered organisms provide a unique opportunity to study biological systems in a controlled fashion. Biotechnology is a powerful tool to advance medical research and should not be abandoned because of irrational fears.", "qid": 1, "docid": "deajwhx0", "rank": 76, "score": 0.7522687911987305}, {"content": "Title: The History of Investigation and Modern Classification of Coronaviruses (nidovirales: Coronaviridae) ;\u0438\u0441\u0442\u043e\u0440\u0438\u044f \u0418\u0437\u0443\u0447\u0435\u043d\u0438\u044f \u0418 \u0421\u043e\u0432\u0440\u0435\u043c\u0435\u043d\u043d\u0430\u044f \u041a\u043b\u0430\u0441\u0441\u0438\u0444\u0438\u043a\u0430\u0446\u0438\u044f \u041a\u043e\u0440\u043e\u043d\u0430\u0432\u0438\u0440\u0443\u0441\u043e\u0432 (nidovirales: Coronaviridae) Content: An epidemic of COVID-19 (Coronavirus disease 2019) etiologically associated with the SARS-CoV-2 (Severe acute respiratory syndrome-related coronavirus 2) that occurred at the turn of 2019-2020 firstly in Wuhan (Hubei province of China) and then spread to many countries around the world has generated a new wave of interest in coronaviruses The first coronaviruses \u00e2\u20ac\u201c representatives of the family Coronaviridae from the order Nidovirales \u00e2\u20ac\u201c were discovered in the first half of the last century The first human coronavirus, HCoV-B814, was isolated in 1965 and to date it has not been preserved in virological collections Over the past time, there has been a repeated layering of obsolete names By the beginning of the XXI century coronaviruses were a serious veterinary problem but it was believed that epidemic coronaviruses were not especially dangerous The scientific community had to revise these views for the very first time in 2002, when SARS-CoV (Severe acute respiratory syndrome-related coronavirus) virus entered the human population from the bats in Southeast Asia, and then in 2012 \u00e2\u20ac\u201c when natural foci of the MERS-CoV (Middle East respiratory syndrome-related coronavirus) were discovered on the territory of the Arabian Peninsula As a result of increased interest in coronaviruses a large number of new members of the Coronaviridae were discovered in the first two decades of the XXI century, which required several revisions of the taxonomic structure of this family This review is devoted to the history of studying coronaviruses and the system of their modern classification, which has developed at the beginning of 2020 in accordance with the latest recommendations of the International Committee on Taxonomy of Viruses ;\u00d0\u2019\u00d0\u00be\u00d0\u00b7\u00d0\u00bd\u00d0\u00b8\u00d0\u00ba\u00d1\u02c6\u00d0\u00b0\u00d1\u008f \u00d0\u00bd\u00d0\u00b0 \u00d1\u20ac\u00d1\u0192\u00d0\u00b1\u00d0\u00b5\u00d0\u00b6\u00d0\u00b5 2019-2020 \u00d0\u00b3\u00d0\u00b3 \u00d1\u0081\u00d0\u00bd\u00d0\u00b0\u00d1\u2021\u00d0\u00b0\u00d0\u00bb\u00d0\u00b0 \u00d0\u00b2 \u00d0\u00b3 \u00d0\u00a3\u00d1\u2026\u00d0\u00b0\u00d0\u00bd\u00d1\u0152 (\u00d0\u00ba\u00d0\u00b8\u00d1\u201a\u00d0\u00b0\u00d0\u00b9\u00d1\u0081\u00d0\u00ba\u00d0\u00be\u00d0\u00b9 \u00d0\u00bf\u00d1\u20ac\u00d0\u00be\u00d0\u00b2\u00d0\u00b8\u00d0\u00bd\u00d1\u2020\u00d0\u00b8\u00d0\u00b8 \u00d0\u00a5\u00d1\u0192\u00d0\u00b1\u00d1\u008d\u00d0\u00b9) \u00d0\u00b8 \u00d1\u20ac\u00d0\u00b0\u00d1\u0081\u00d0\u00bf\u00d1\u20ac\u00d0\u00be\u00d1\u0081\u00d1\u201a\u00d1\u20ac\u00d0\u00b0\u00d0\u00bd\u00d0\u00b8\u00d0\u00b2\u00d1\u02c6\u00d0\u00b0\u00d1\u008f\u00d1\u0081\u00d1\u008f \u00d0\u00b7\u00d0\u00b0\u00d1\u201a\u00d0\u00b5\u00d0\u00bc \u00d0\u00b2\u00d0\u00be \u00d0\u00bc\u00d0\u00bd\u00d0\u00be\u00d0\u00b3\u00d0\u00b8\u00d0\u00b5 \u00d1\u0081\u00d1\u201a\u00d1\u20ac\u00d0\u00b0\u00d0\u00bd\u00d1\u2039 \u00d0\u00bc\u00d0\u00b8\u00d1\u20ac\u00d0\u00b0 \u00d1\u008d\u00d0\u00bf\u00d0\u00b8\u00d0\u00b4\u00d0\u00b5\u00d0\u00bc\u00d0\u00b8\u00d1\u008f COVID-19 (Coronavirus disease 2019), \u00d1\u008d\u00d1\u201a\u00d0\u00b8\u00d0\u00be\u00d0\u00bb\u00d0\u00be\u00d0\u00b3\u00d0\u00b8\u00d1\u2021\u00d0\u00b5\u00d1\u0081\u00d0\u00ba\u00d0\u00b8 \u00d1\u0081\u00d0\u00b2\u00d1\u008f\u00d0\u00b7\u00d0\u00b0\u00d0\u00bd\u00d0\u00bd\u00d0\u00b0\u00d1\u008f \u00d1\u0081 \u00d0\u00b2\u00d0\u00b8\u00d1\u20ac\u00d1\u0192\u00d1\u0081\u00d0\u00be\u00d0\u00bc \u00d1\u201a\u00d1\u008f\u00d0\u00b6\u00d1\u2018\u00d0\u00bb\u00d0\u00be\u00d0\u00b3\u00d0\u00be \u00d0\u00be\u00d1\u0081\u00d1\u201a\u00d1\u20ac\u00d0\u00be\u00d0\u00b3\u00d0\u00be \u00d1\u20ac\u00d0\u00b5\u00d1\u0081\u00d0\u00bf\u00d0\u00b8\u00d1\u20ac\u00d0\u00b0\u00d1\u201a\u00d0\u00be\u00d1\u20ac\u00d0\u00bd\u00d0\u00be\u00d0\u00b3\u00d0\u00be \u00d1\u0081\u00d0\u00b8\u00d0\u00bd\u00d0\u00b4\u00d1\u20ac\u00d0\u00be\u00d0\u00bc\u00d0\u00b0 2\u00e2\u20ac\u2018\u00d0\u00b3\u00d0\u00be \u00d1\u201a\u00d0\u00b8\u00d0\u00bf\u00d0\u00b0 (SARS-CoV-2 \u00e2\u20ac\u201c Severe acute respiratory syndrome 2), \u00d0\u00bf\u00d0\u00be\u00d1\u20ac\u00d0\u00be\u00d0\u00b4\u00d0\u00b8\u00d0\u00bb\u00d0\u00b0 \u00d0\u00bd\u00d0\u00be\u00d0\u00b2\u00d1\u0192\u00d1\u017d \u00d0\u00b2\u00d0\u00be\u00d0\u00bb\u00d0\u00bd\u00d1\u0192 \u00d0\u00b8\u00d0\u00bd\u00d1\u201a\u00d0\u00b5\u00d1\u20ac\u00d0\u00b5\u00d1\u0081\u00d0\u00b0 \u00d0\u00ba \u00d0\u00ba\u00d0\u00be\u00d1\u20ac\u00d0\u00be\u00d0\u00bd\u00d0\u00b0\u00d0\u00b2\u00d0\u00b8\u00d1\u20ac\u00d1\u0192\u00d1\u0081\u00d0\u00b0\u00d0\u00bc \u00d0\u0178\u00d0\u00b5\u00d1\u20ac\u00d0\u00b2\u00d1\u2039\u00d0\u00b5 \u00d0\u00ba\u00d0\u00be\u00d1\u20ac\u00d0\u00be\u00d0\u00bd\u00d0\u00b0\u00d0\u00b2\u00d0\u00b8\u00d1\u20ac\u00d1\u0192\u00d1\u0081\u00d1\u2039 \u00e2\u20ac\u201c \u00d0\u00bf\u00d1\u20ac\u00d0\u00b5\u00d0\u00b4\u00d1\u0081\u00d1\u201a\u00d0\u00b0\u00d0\u00b2\u00d0\u00b8\u00d1\u201a\u00d0\u00b5\u00d0\u00bb\u00d0\u00b8 \u00d1\u0081\u00d0\u00b5\u00d0\u00bc\u00d0\u00b5\u00d0\u00b9\u00d1\u0081\u00d1\u201a\u00d0\u00b2\u00d0\u00b0 Coronaviridae \u00d0\u00b8\u00d0\u00b7 \u00d0\u00be\u00d1\u201a\u00d1\u20ac\u00d1\u008f\u00d0\u00b4\u00d0\u00b0 Nidovirales \u00e2\u20ac\u201c \u00d0\u00b1\u00d1\u2039\u00d0\u00bb\u00d0\u00b8 \u00d0\u00be\u00d1\u201a\u00d0\u00ba\u00d1\u20ac\u00d1\u2039\u00d1\u201a\u00d1\u2039 \u00d0\u00b5\u00d1\u2030\u00d1\u2018 \u00d0\u00b2 \u00d0\u00bf\u00d0\u00b5\u00d1\u20ac\u00d0\u00b2\u00d0\u00be\u00d0\u00b9 \u00d0\u00bf\u00d0\u00be\u00d0\u00bb\u00d0\u00be\u00d0\u00b2\u00d0\u00b8\u00d0\u00bd\u00d0\u00b5 \u00d0\u00bf\u00d1\u20ac\u00d0\u00be\u00d1\u02c6\u00d0\u00bb\u00d0\u00be\u00d0\u00b3\u00d0\u00be \u00d0\u00b2\u00d0\u00b5\u00d0\u00ba\u00d0\u00b0 \u00d0\u0178\u00d0\u00b5\u00d1\u20ac\u00d0\u00b2\u00d1\u2039\u00d0\u00b9 \u00d0\u00ba\u00d0\u00be\u00d1\u20ac\u00d0\u00be\u00d0\u00bd\u00d0\u00b0\u00d0\u00b2\u00d0\u00b8\u00d1\u20ac\u00d1\u0192\u00d1\u0081 \u00d1\u2021\u00d0\u00b5\u00d0\u00bb\u00d0\u00be\u00d0\u00b2\u00d0\u00b5\u00d0\u00ba\u00d0\u00b0, HCoV-B814, \u00d0\u00b1\u00d1\u2039\u00d0\u00bb \u00d0\u00b8\u00d0\u00b7\u00d0\u00be\u00d0\u00bb\u00d0\u00b8\u00d1\u20ac\u00d0\u00be\u00d0\u00b2\u00d0\u00b0\u00d0\u00bd \u00d0\u00b2 1965 \u00d0\u00b3 \u00d0\u00b8 \u00d0\u00ba \u00d0\u00bd\u00d0\u00b0\u00d1\u0081\u00d1\u201a\u00d0\u00be\u00d1\u008f\u00d1\u2030\u00d0\u00b5\u00d0\u00bc\u00d1\u0192 \u00d0\u00b2\u00d1\u20ac\u00d0\u00b5\u00d0\u00bc\u00d0\u00b5\u00d0\u00bd \u00d0\u00bd\u00d0\u00b5 \u00d1\u0081\u00d0\u00be\u00d1\u2026\u00d1\u20ac\u00d0\u00b0\u00d0\u00bd\u00d0\u00b8\u00d0\u00bb\u00d1\u0081\u00d1\u008f \u00d0\u00b2 \u00d0\u00b2\u00d0\u00b8\u00d1\u20ac\u00d1\u0192\u00d1\u0081\u00d0\u00be\u00d0\u00bb\u00d0\u00be\u00d0\u00b3\u00d0\u00b8\u00d1\u2021\u00d0\u00b5\u00d1\u0081\u00d0\u00ba\u00d0\u00b8\u00d1\u2026 \u00d0\u00ba\u00d0\u00be\u00d0\u00bb\u00d0\u00bb\u00d0\u00b5\u00d0\u00ba\u00d1\u2020\u00d0\u00b8\u00d1\u008f\u00d1\u2026 \u00d0\u2014\u00d0\u00b0 \u00d0\u00bf\u00d1\u20ac\u00d0\u00be\u00d1\u02c6\u00d0\u00b5\u00d0\u00b4\u00d1\u02c6\u00d0\u00b5\u00d0\u00b5 \u00d0\u00b2\u00d1\u20ac\u00d0\u00b5\u00d0\u00bc\u00d1\u008f 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\u00d0\u00bf\u00d0\u00be\u00d1\u0081\u00d0\u00b2\u00d1\u008f\u00d1\u2030\u00d1\u2018\u00d0\u00bd \u00d0\u00b8\u00d1\u0081\u00d1\u201a\u00d0\u00be\u00d1\u20ac\u00d0\u00b8\u00d0\u00b8 \u00d0\u00b8\u00d0\u00b7\u00d1\u0192\u00d1\u2021\u00d0\u00b5\u00d0\u00bd\u00d0\u00b8\u00d1\u008f \u00d0\u00ba\u00d0\u00be\u00d1\u20ac\u00d0\u00be\u00d0\u00bd\u00d0\u00b0\u00d0\u00b2\u00d0\u00b8\u00d1\u20ac\u00d1\u0192\u00d1\u0081\u00d0\u00be\u00d0\u00b2 \u00d0\u00b8 \u00d1\u0081\u00d0\u00b8\u00d1\u0081\u00d1\u201a\u00d0\u00b5\u00d0\u00bc\u00d0\u00b5 \u00d0\u00b8\u00d1\u2026 \u00d1\u0081\u00d0\u00be\u00d0\u00b2\u00d1\u20ac\u00d0\u00b5\u00d0\u00bc\u00d0\u00b5\u00d0\u00bd\u00d0\u00bd\u00d0\u00be\u00d0\u00b9 \u00d0\u00ba\u00d0\u00bb\u00d0\u00b0\u00d1\u0081\u00d1\u0081\u00d0\u00b8\u00d1\u201e\u00d0\u00b8\u00d0\u00ba\u00d0\u00b0\u00d1\u2020\u00d0\u00b8\u00d0\u00b8, \u00d0\u00ba\u00d0\u00be\u00d1\u201a\u00d0\u00be\u00d1\u20ac\u00d0\u00b0\u00d1\u008f \u00d1\u0081\u00d0\u00bb\u00d0\u00be\u00d0\u00b6\u00d0\u00b8\u00d0\u00bb\u00d0\u00b0\u00d1\u0081\u00d1\u0152 \u00d0\u00bd\u00d0\u00b0 \u00d0\u00bd\u00d0\u00b0\u00d1\u2021\u00d0\u00b0\u00d0\u00bb\u00d0\u00be 2020 \u00d0\u00b3 \u00d0\u00b2 \u00d1\u0081\u00d0\u00be\u00d0\u00be\u00d1\u201a\u00d0\u00b2\u00d0\u00b5\u00d1\u201a\u00d1\u0081\u00d1\u201a\u00d0\u00b2\u00d0\u00b8\u00d0\u00b5 \u00d1\u0081 \u00d0\u00bf\u00d0\u00be\u00d1\u0081\u00d0\u00bb\u00d0\u00b5\u00d0\u00b4\u00d0\u00bd\u00d0\u00b8\u00d0\u00bc\u00d0\u00b8 \u00d1\u20ac\u00d0\u00b5\u00d0\u00ba\u00d0\u00be\u00d0\u00bc\u00d0\u00b5\u00d0\u00bd\u00d0\u00b4\u00d0\u00b0\u00d1\u2020\u00d0\u00b8\u00d1\u008f\u00d0\u00bc\u00d0\u00b8 \u00d0\u0153\u00d0\u00b5\u00d0\u00b6\u00d0\u00b4\u00d1\u0192\u00d0\u00bd\u00d0\u00b0\u00d1\u20ac\u00d0\u00be\u00d0\u00b4\u00d0\u00bd\u00d0\u00be\u00d0\u00b3\u00d0\u00be \u00d0\u0161\u00d0\u00be\u00d0\u00bc\u00d0\u00b8\u00d1\u201a\u00d0\u00b5\u00d1\u201a\u00d0\u00b0 \u00d0\u00bf\u00d0\u00be \u00d1\u201a\u00d0\u00b0\u00d0\u00ba\u00d1\u0081\u00d0\u00be\u00d0\u00bd\u00d0\u00be\u00d0\u00bc\u00d0\u00b8\u00d0\u00b8 \u00d0\u00b2\u00d0\u00b8\u00d1\u20ac\u00d1\u0192\u00d1\u0081\u00d0\u00be\u00d0\u00b2", "qid": 1, "docid": "mmddnj5v", "rank": 77, "score": 0.7521530389785767}, {"content": "Title: COVID-19 from the perspective of an immunologist. Content: COVID-19 is an infectious disease caused by a coronavirus SARS-CoV-2. COVID-19 has a number of similarities to SARS and MERS diseases. Its highly contagious nature is particularly due to the rapid spread of the disease through asymptomatic individuals; however, the worlds most contagious infectious disease is still considered measles. Scientific data have revealed the interactions between COVID-19 and the immune system. These findings may contribute to the development of novel preventive and therapeutic approaches. Just as coronavirus itself the reports about the disease have massively spread through media and public contributing to overall public fear and stress. This promotion of non-scientific evidence and misinformation through social media might have also a devastating impact on the individuals immune system. Data regarding the mortality rates of COVID-19 have achieved unprecedented media and public engagements, however, the true facts about the disease prevention, immunomodulation and novel treatments are often left unsaid. We present the most recent facts about COVID-19 disease and its interactions with the immune system.", "qid": 1, "docid": "mwpbrbqu", "rank": 78, "score": 0.7519294023513794}, {"content": "Title: Aktu\u00e1ln\u00ed problematika COVID-19 z pohledu imunologa./ COVID-19 from the perspective of an immunologist Content: COVID-19 is an infectious disease caused by a coronavirus SARS-CoV-2. COVID-19 has a number of similarities to SARS and MERS diseases. Its highly contagious nature is particularly due to the rapid spread of the disease through asymptomatic individuals; however, the worlds most contagious infectious disease is still considered measles. Scientific data have revealed the interactions between COVID-19 and the immune system. These findings may contribute to the development of novel preventive and therapeutic approaches. Just as coronavirus itself the reports about the disease have massively spread through media and public contributing to overall public fear and stress. This promotion of non-scientific evidence and misinformation through social media might have also a devastating impact on the individuals immune system. Data regarding the mortality rates of COVID-19 have achieved unprecedented media and public engagements, however, the true facts about the disease prevention, immunomodulation and novel treatments are often left unsaid. We present the most recent facts about COVID-19 disease and its interactions with the immune system.", "qid": 1, "docid": "pfyqjrwk", "rank": 79, "score": 0.7519292235374451}, {"content": "Title: Brief Review on COVID-19: The 2020 Pandemic Caused by SARS-CoV-2 Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the coronavirus disease of 2019 (COVID-19). First identified in Wuhan (Hubei, China) in December of 2019, it has since been declared a pandemic by the World Health Organization in March of 2020. In this study, we will provide a brief review of viral origin, identification, symptoms, transmission, diagnosis, and potential treatment strategies for the newly identified SARS-CoV-2 strain.", "qid": 1, "docid": "v8i97mbx", "rank": 80, "score": 0.7516942620277405}, {"content": "Title: Coast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States Content: Summary The novel coronavirus SARS-CoV-2 was first detected in the Pacific Northwest region of the United States in January 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the United States, we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated effects of federal travel restrictions. This study provides evidence of widespread sustained transmission of SARS-CoV-2 within the United States and highlights the critical need for local surveillance.", "qid": 1, "docid": "bakwk4tm", "rank": 81, "score": 0.751639723777771}, {"content": "Title: Spillover of SARS-CoV-2 into novel wild hosts in North America: A conceptual model for perpetuation of the pathogen Content: There is evidence that the current outbreak of the novel coronavirus SARS-CoV-2, which causes COVID-19, is of animal origin. As with a number of zoonotic pathogens, there is a risk of spillover into novel hosts. Here, we propose a hypothesized conceptual model that illustrates the mechanism whereby the SARS-CoV-2 could spillover from infected humans to naive wildlife hosts in North America. This proposed model is premised on transmission of SARS-CoV-2 from human feces through municipal waste water treatment plants into the natural aquatic environment where potential wildlife hosts become infected. We use the existing literature on human coronaviruses, including SARS CoV, to support the potential pathways and mechanisms in the conceptual model. Although we focus on North America, our conceptual model could apply to other parts of the globe as well.", "qid": 1, "docid": "0lywkro9", "rank": 82, "score": 0.7516310214996338}, {"content": "Title: World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19) Content: Abstract An unprecedented outbreak of pneumonia of unknown aetiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus was identified as the causative agent and was subsequently termed COVID-19 by the World Health Organization (WHO). Considered a relative of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), COVID-19 is caused by a betacoronavirus named SARS-CoV-2 that affects the lower respiratory tract and manifests as pneumonia in humans. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with 90,870 laboratory-confirmed cases and over 3,000 deaths worldwide. In response to this global outbreak, we summarise the current state of knowledge surrounding COVID-19.", "qid": 1, "docid": "iudq5jdu", "rank": 83, "score": 0.7515777349472046}, {"content": "Title: COVID-19: animals, veterinary and zoonotic links Content: Coronavirus disease 2019 (COVID-19), has spread over 210 countries and territories beyond China shortly. On February 29, 2020, the World Health Organization (WHO) denoted it in a high-risk category, and on March 11, 2020, this virus was designated pandemic, after its declaration being a Public Health International Emergency on January 30, 2020. World over high efforts are being made to counter and contain this virus. The COVID-19 outbreak once again proves the potential of the animal-human interface to act as the primary source of emerging zoonotic diseases. Even though the circumstantial evidence suggests the possibility of an initial zoonotic emergence, it is too early to confirm the role of intermediate hosts such as snakes, pangolins, turtles, and other wild animals in the origin of SARS-CoV-2, in addition to bats, the natural hosts of multiple coronaviruses such as SARS-CoV and MERS-CoV. The lessons learned from past episodes of MERS-CoV and SARS-CoV are being exploited to retort this virus. Best efforts are being taken up by worldwide nations to implement effective diagnosis, strict vigilance, heightened surveillance, and monitoring, along with adopting appropriate preventive and control strategies. Identifying the possible zoonotic emergence and the exact mechanism responsible for its initial transmission will help us to design and implement appropriate preventive barriers against the further transmission of SARS-CoV-2. This review discusses in brief about the COVID-19/SARS-CoV-2 with a particular focus on the role of animals, the veterinary and associated zoonotic links along with prevention and control strategies based on One-health approaches.", "qid": 1, "docid": "85cdy3f9", "rank": 84, "score": 0.7513174414634705}, {"content": "Title: COVID-19: animals, veterinary and zoonotic links. Content: Coronavirus disease 2019 (COVID-19), has spread over 210 countries and territories beyond China shortly. On February 29, 2020, the World Health Organization (WHO) denoted it in a high-risk category, and on March 11, 2020, this virus was designated pandemic, after its declaration being a Public Health International Emergency on January 30, 2020. World over high efforts are being made to counter and contain this virus. The COVID-19 outbreak once again proves the potential of the animal-human interface to act as the primary source of emerging zoonotic diseases. Even though the circumstantial evidence suggests the possibility of an initial zoonotic emergence, it is too early to confirm the role of intermediate hosts such as snakes, pangolins, turtles, and other wild animals in the origin of SARS-CoV-2, in addition to bats, the natural hosts of multiple coronaviruses such as SARS-CoV and MERS-CoV. The lessons learned from past episodes of MERS-CoV and SARS-CoV are being exploited to retort this virus. Best efforts are being taken up by worldwide nations to implement effective diagnosis, strict vigilance, heightened surveillance, and monitoring, along with adopting appropriate preventive and control strategies. Identifying the possible zoonotic emergence and the exact mechanism responsible for its initial transmission will help us to design and implement appropriate preventive barriers against the further transmission of SARS-CoV-2. This review discusses in brief about the COVID-19/SARS-CoV-2 with a particular focus on the role of animals, the veterinary and associated zoonotic links along with prevention and control strategies based on One-health approaches.", "qid": 1, "docid": "3uvuo4sf", "rank": 85, "score": 0.7513174414634705}, {"content": "Title: Susceptibility of ferrets, cats, dogs, and different domestic animals to SARS-coronavirus-2 Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the infectious disease COVID-19, which was first reported in Wuhan, China in December, 2019. Despite the tremendous efforts to control the disease, COVID-19 has now spread to over 100 countries and caused a global pandemic. SARS-CoV-2 is thought to have originated in bats; however, the intermediate animal sources of the virus are completely unknown. Here, we investigated the susceptibility of ferrets and animals in close contact with humans to SARS-CoV-2. We found that SARS-CoV-2 replicates poorly in dogs, pigs, chickens, and ducks, but efficiently in ferrets and cats. We found that the virus transmits in cats via respiratory droplets. Our study provides important insights into the animal reservoirs of SARS-CoV-2 and animal management for COVID-19 control.", "qid": 1, "docid": "mo4luyx6", "rank": 86, "score": 0.7512302994728088}, {"content": "Title: On the assessment of more reliable COVID-19 infected number: the italian case. Content: COVID-19 (SARS-CoV-2) is the most recent pandemic disease the world is currently managing. It started in China at the end of 2019, and it is diffusing throughout Italy, one of the most affected countries, and it is currently spreading through European countries and USA. Patients affected by COVID-19 are identified employing medical swabs applied mainly to (i) citizens with COVID-19 symptoms such as flu or high temperature, or (ii) citizens that had contacts with COVID-19 patients. A percentage of COVID-19 affected patients needs hospitalisation, whereas a portion needs to be treated in Intensive Care Units (ICUs). Nevertheless, it is a matter of current intuition that COVID-19 infected citizens are more than those detected, and sometime the infection is detected too late. Thus there are many efforts in both tracking people activities as well as diffusing low cost reliable COVID-19 tests for early detection. Starting from mortality rates of diseases caused by viruses in the same family (e.g. MERS, SARS, H1N1), we study the relations between the number of COVID-19 infections and the number of deaths, through Italian regions. We thus assess several infections being higher than the ones currently measured. We thus focus on the characterisation of the pandemic diffusion by estimating the infected number of patients versus the number of death. We use such an estimated number of infections, to foresee the effects of restriction actions adopted by governments to constrain virus diffusion. We finally think that our model can support the healthcare system to react when COVID-19 is increasing.", "qid": 1, "docid": "7hqn997j", "rank": 87, "score": 0.7506629228591919}, {"content": "Title: Emergence of a novel human coronavirus threatening human health Content: In late December 2019, a cluster of patients with \u2018atypical pneumonia\u2019 of unknown etiology was reported in Wuhan, China. A novel human coronavirus, now provisionally called \u2018SARS-CoV-2\u2019, was identified as the cause of this disease, now named \u2018COVID-19\u2019.", "qid": 1, "docid": "nugginc9", "rank": 88, "score": 0.750504732131958}, {"content": "Title: South Korea's COVID-19 Infection Status: From the Perspective of Reconfirmation after Complete Recovery Content: COVID-19 started to occur in South Korea by an inflow of the virus from abroad, when a traveler from Wuhan, China, was first confirmed on January 19th, 2020 Although South Korea reduced the number of newly confirmed cases and is on the way to stabilizing the situation with its disease prevention policies, problems remain The main issue is the reconfirmation of the virus after recovery South Korean experts believe the reconfirmed cases are caused by reactivation of the virus inside the patients' body, rather than by virus reinfection after recovery When considering reconfirmed COVID-19 cases, it is important to keep social distancing even after treating the infection Despite no cases of reconfirmed patients infecting others having been reported yet, reexamination of patients after recovery is thought to be pivotal to prevent reactivation", "qid": 1, "docid": "8xsvj98z", "rank": 89, "score": 0.7502751350402832}, {"content": "Title: SARS-CoV-2 (COVID 19) Infection in Hypertensive Patients and in Patients With Cardiac Disease Content: COVID 19, caused by the SARS-CoV-2 virus, a newly discovered coronavirus, has caused the global pandemic of early 2020. The first case was described in December 2019 in Wuhan, China, and by March 2020, most countries around the world have put in place some of the strictest restrictions seen in decades in order to slow down the spread of the disease. Patients with pre-existing hypertension and cardiovascular comorbidities were reported to be at an increased risk of serious infections caused by SARS-CoV-2. Considering that those are among the most common chronic medical conditions in the Western world, the potential impact of it is huge. The proposed mechanism behind those associations is the expression of angiotensin converting enzyme II (ACE II) in those patients. Furthermore, the association between ACE inhibitors/AR blockers, which are among the most frequently prescribed medications, and serious cases of COVID 19 has been studied with the same mechanism in mind. The reports on the association between hypertension and COVID 19 morbidity and mortality are less clear, and the International Society of Hypertension even claims that there is none. The reports on the association between heart failure or coronary disease and COVID 19 are more uniform, and all seem to point to a greater risk from serious infections faced by patients with those comorbidities. A significant effort will need to be invested by the scientific community into finding strategies for protecting those patients from contracting the virus in the first place and then, once infected, into developing management plans aimed at preserving cardiac function as much as possible.", "qid": 1, "docid": "xw817l53", "rank": 90, "score": 0.749824047088623}, {"content": "Title: Papa Giovanni XXIII Bergamo Hospital at the time of the COVID-19 outbreak: letter from the warfront. Content: In early December 2019, the 2019 novel coronavirus (COVID-19) was identified as the agent responsible for the first pneumonia cases of unknown origin in Wuhan, the capital of the Hubei region in China. The virus has been identified as a novel enveloped RNA betacoronavirus2 , that has been promptly named SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). The World Health Organization (WHO), on January 12, 2020 declared the COVID-19 a public health emergency of international concern. On March 11, the WHO made the assessment that COVID-19 can be characterized as a pandemic.", "qid": 1, "docid": "d11cj86k", "rank": 91, "score": 0.7497581243515015}, {"content": "Title: Epidemiological data from the COVID-19 outbreak, real-time case information Content: Cases of a novel coronavirus were first reported in Wuhan, Hubei province, China, in December 2019 and have since spread across the world. Epidemiological studies have indicated human-to-human transmission in China and elsewhere. To aid the analysis and tracking of the COVID-19 epidemic we collected and curated individual-level data from national, provincial, and municipal health reports, as well as additional information from online reports. All data are geo-coded and, where available, include symptoms, key dates (date of onset, admission, and confirmation), and travel history. The generation of detailed, real-time, and robust data for emerging disease outbreaks is important and can help to generate robust evidence that will support and inform public health decision making.", "qid": 1, "docid": "irt0wmt2", "rank": 92, "score": 0.7496245503425598}, {"content": "Title: Fatal Superimposed Bacterial Sepsis in a Healthy Coronavirus (COVID-19) Patient Content: Coronavirus disease 2019 (COVID-19) is a highly infectious disease caused by the newly discovered coronavirus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). The novel coronavirus first emerged in Wuhan, China, in December 2019 and has led to a global pandemic. The virus mainly spreads through respiratory droplets from an infected person, but environmental contamination can also act as a source of infection, making social distancing an important key in containing the spread of infection. Those with underlying health conditions are more susceptible to complications such as acute respiratory distress syndrome, which can be fatal. However, healthy individuals experience a mild flu-like illness or may be asymptomatic, recuperating from the infection even without any particular intervention. We present a case of a healthy COVID positive individual, with no underlying comorbidities, who rapidly deteriorated overnight on readmission to the hospital after initial discharge and succumbed to this disease due to a superimposed bacterial infection with COVID pneumonia. This case report highlights the importance of educating COVID-19 positive patients about the precautions, as well as signs and symptoms of a superimposed bacterial infection, when their plan of care is in a home setting. It also emphasizes the potential role of checking procalcitonin levels as a part of routine laboratory investigation at initial presentation in all suspected as well as confirmed COVID-19 cases to rule out an on-going bacterial infection that can prove fatal in the course of the disease.", "qid": 1, "docid": "e05ywn5e", "rank": 93, "score": 0.7495357990264893}, {"content": "Title: Understanding novel COVID-19: Its impact on organ failure and risk assessment for diabetic and cancer patients Content: The current pandemic outbreak of COVID-19 originated from Wuhan, China. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with significant mortality and morbidity rate. The severe risk factors are commonly detected in patients of older age and with medical comorbidities like cancer and diabetes. Scientists and doctors have scrambled to gain knowledge about the novel virus and its pathophysiology in order to discover possible therapeutic regimens and vaccines for COVID-19. The therapeutic strategies like targeting the viral genome emphasize the promising approach to target COVID-19. Additionally, blocking the receptor, ACE2 via the neutralizing antibodies for viral escape that prevents it from entering into the cells provides another therapeutic regimen. In this review article, we have presented the effect of SARS-CoV-2 infection in comorbid patients and discussed organ failure caused by this virus. Based on the data available from the scientific literature and ongoing clinical trials, we have focused on therapeutic strategies. We hope that we would fill the gaps that puzzled the researchers and clinicians with the best of our knowledge collected for the betterment of the patients for the coming future.", "qid": 1, "docid": "m0vqst1q", "rank": 94, "score": 0.7494180798530579}, {"content": "Title: Occupational health responses to COVID-19: What lessons can we learn from SARS? Content: On 31 December 2019, the World Health Organization (WHO) received reports of pneumonia cases of unknown etiology in the city of Wuhan in Hubei Province, China. The agent responsible was subsequently identified as a coronavirus-SARS-CoV-2. The WHO declared this disease as a Public Health Emergency of International Concern at the end of January 2020. This event evoked a sense of d\u00e9j\u00e0 vu, as it has many similarities to the outbreak of severe acute respiratory syndrome (SARS) of 2002-2003. Both illnesses were caused by a zoonotic novel coronavirus, both originated during winter in China and both spread rapidly all over the world. However, the case-fatality rate of SARS (9.6%) is higher than that of COVID-19 (<4%). Another zoonotic novel coronavirus, MERS-CoV, was responsible for the Middle East respiratory syndrome, which had a case-fatality rate of 34%. Our experiences in coping with the previous coronavirus outbreaks have better equipped us to face the challenges posed by COVID-19, especially in the health care setting. Among the insights gained from the past outbreaks were: outbreaks caused by viruses are hazardous to healthcare workers; the impact of the disease extends beyond the infection; general principles of prevention and control are effective in containing the disease; the disease poses both a public health as well as an occupational health threat; and emerging infectious diseases pose a continuing threat to the world. Given the perspectives gained and lessons learnt from these past events, we should be better prepared to face the current COVID-19 outbreak.", "qid": 1, "docid": "tr7h36i9", "rank": 95, "score": 0.748833179473877}, {"content": "Title: Co-infection with Influenza A and COVID-19 Content: COVID-19, also called severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2), originated in Wuhan, China. It has caused significant morbidity and mortality worldwide and has been declared a global pandemic by the WHO. Influenza occurs mainly during the winter, with the burden of disease determined by several factors, including the effectiveness of the vaccine that season, the characteristics of the circulating viruses, and how long the season lasts. We describe the case of a 66-year-old woman who was diagnosed with influenza A and COVID-19 co-infection. LEARNING POINTS: COVID-19 can co-occur with other viral infections. Some of these co-infections have active treatments, while supportive treatment is the mainstay of treatment for others.", "qid": 1, "docid": "9i024s08", "rank": 96, "score": 0.7488236427307129}, {"content": "Title: Novel coronavirus 2019 (COVID-19): Emergence and implications for emergency care Content: A novel coronavirus (COVID-19) causing acute illness with severe symptoms has been isolated in Wuhan, Hubei Province, China. Since its emergence, cases have been found worldwide, reminiscent of severe acute respiratory syndrome and Middle East respiratory syndrome outbreaks over the past 2 decades. Current understanding of this epidemic remains limited due to its rapid development and available data. While occurrence outside mainland China remains low, the likelihood of increasing cases globally continues to rise. Given this potential, it is imperative that emergency clinicians understand the preliminary data behind the dynamics of this disease, recognize possible presentations of patients, and understand proposed treatment modalities.", "qid": 1, "docid": "xncs76xv", "rank": 97, "score": 0.7483781576156616}, {"content": "Title: COVID-19: A Risk Assessment Perspective Content: [Image: see text] COVID-19 is a newly emerging viral respiratory disease first identified in Wuhan, China, in December 2019. The disease is caused by the coronavirus SARS-CoV-2, which is related to the viruses that cause SARS and MERS. While the case fatality ratio for COVID-19 (5%) is far lower than that for SARS (11%) and MERS (34%), COVID-19 is spreading relatively uncontrolled at this time across the globe. In contrast, SARS appears to be contained, and MERS is controlled. This paper will explore why COVID-19 is able to progress to a global pandemic that affects our daily lives to an extent not known in recent history. The COVID-19 outbreak and spread will be examined based on the current literature, using a researcher\u2019s perspective of risk assessment and risk mitigation; this approach will be related to public health.", "qid": 1, "docid": "ip16lh2a", "rank": 98, "score": 0.7478788495063782}, {"content": "Title: Coronavirus Disease 2019 (COVID-19): Clinical Perspectives and Ongoing Challenges Content: BACKGROUND: Emerging infectious diseases pose a great hazard to public health and the global economy A novel coronavirus, SARS-CoV-2, causing coronavirus disease 2019 (COVID-19), emerged from Wuhan, China, in December 2019 Since then, it has spread globally causing a global health emergency of inconceivable magnitude, with significant morbidity and mortality There is the need for clinicians and health care providers to understand and gain knowledge of the different aspects of the disease as it evolves OBJECTIVE: We reviewed existing literature on COVID-19 in order to present a synopsis of current understanding of the disease METHODS: Using PubMed, Embase and Medline, articles published between January and April 2020 on Coronavirus disease 2019 (COVID-19), and resources from World Health Organisation were analyzed in order to have an understanding of the clinical characteristics, transmission dynamics, virology, diagnostic possibilities, prevention, management approach, controversies and impact of COVID-19 on the healthcare workforce RESULTS: Our review revealed that COVID-19 patients present with a myriad of symptoms, ranging from mild to severe respiratory disease, which can often be fatal The mode of transmission via droplet infections makes it unduly contagious and difficult to control Currently, antiviral drugs or vaccines are being developed to manage this condition CONCLUSION: There is urgent need for potent antivirals and vaccine to manage those infected with COVID 19 and prevent infection Global efforts need to be unified in combating this public health emergency and flattening the curve of spread", "qid": 1, "docid": "rugijb30", "rank": 99, "score": 0.7476840019226074}, {"content": "Title: Dynamics of the COVID-19 -- Comparison between the Theoretical Predictions and Real Data Content: A new coronavirus disease, called COVID-19, appeared in the Chinese region of Wuhan at the end of last year; since then the virus spread to other countries, including most of Europe. We propose a differential equation governing the evolution of the COVID-19. This dynamic equation also describes the evolution of the number of infected people for 13 common respiratory viruses (including the SARS-CoV-2). We validate our theoretical predictions with experimental data for Italy, Belgium and Luxembourg, and compare them with the predictions of the logistic model. We find that our predictions are in good agreement with the real world since the beginning of the appearance of the COVID-19; this is not the case for the logistic model that only applies to the first days. The second part of the work is devoted to modelling the descending phase, i.e. the decrease of the number of people tested positive for COVID-19. Also in this case, we propose a new set of dynamic differential equations that we solved numerically. We use our differential equations parametrised with experimental data to make several predictions, such as the date when Italy, Belgium, and Luxembourg will reach a peak number of SARS-CoV-2 infected people. The descending curves provide valuable information such as the duration of the COVID-19 epidemic in a given Country and therefore when it will be possible to return to normal life.", "qid": 1, "docid": "f40bfqa5", "rank": 100, "score": 0.7475292086601257}]}
{"query": "how does the coronavirus respond to changes in the weather", "hits": [{"content": "Title: On the global trends and spread of the COVID-19 outbreak: preliminary assessment of the potential relation between location-specific temperature and UV index Content: The novel coronavirus, since its first outbreak in December, has, up till now, affected approximately 114,542 people across 115 countries. Many international agencies are devoting efforts to enhance the understanding of the evolving COVID-19 outbreak on an international level, its influences, and preparedness. At present, COVID-19 appears to affect individuals through person-to-person means, like other commonly found cold or influenza viruses. It is widely known and acknowledged that viruses causing influenza peak during cold temperatures and gradually subside in the warmer temperature, owing to their seasonality. Thus, COVID-19, due to its regular flu-like symptoms, is also expected to show similar seasonality and subside as the global temperatures rise in the northern hemisphere with the onset of spring. Despite these speculations, however, the systematic analysis in the global perspective of the relation between COVID-19 spread and meteorological parameters is unavailable. Here, by analyzing the region- and city-specific affected global data and corresponding meteorological parameters, we show that there is an optimum range of temperature and UV index strongly affecting the spread and survival of the virus, whereas precipitation, relative humidity, cloud cover, etc. have no effect on the virus. Unavailability of pharmaceutical interventions would require greater preparedness and alert for the effective control of COVID-19. Under these conditions, the information provided here could be very helpful for the global community struggling to fight this global crisis. It is, however, important to note that the information presented here clearly lacks any physiological evidences, which may merit further investigation. Thus, any attempt for management, implementation, and evaluation strategies responding to the crisis arising due to the COVID-19 outbreak must not consider the evaluation presented here as the foremost factor.", "qid": 2, "docid": "4ry9b68l", "rank": 1, "score": 0.7792955636978149}, {"content": "Title: Air transportation, population density and temperature predict the spread of COVID-19 in Brazil Content: There is evidence that COVID-19, the disease caused by the betacoronavirus SARS-CoV-2, is sensitive to environmental conditions. However, such conditions often correlate with demographic and socioeconomic factors at larger spatial extents, which could confound this inference. We evaluated the effect of meteorological conditions (temperature, solar radiation, air humidity and precipitation) on 292 daily records of cumulative number of confirmed COVID-19 cases across the 27 Brazilian capital cities during the 1st month of the outbreak, while controlling for an indicator of the number of tests, the number of arriving flights, population density, proportion of elderly people and average income. Apart from increasing with time, the number of confirmed cases was mainly related to the number of arriving flights and population density, increasing with both factors. However, after accounting for these effects, the disease was shown to be temperature sensitive: there were more cases in colder cities and days, and cases accumulated faster at lower temperatures. Our best estimate indicates that a 1 \u00b0C increase in temperature has been associated with a decrease in confirmed cases of 8%. The quality of the data and unknowns limit the analysis, but the study reveals an urgent need to understand more about the environmental sensitivity of the disease to predict demands on health services in different regions and seasons.", "qid": 2, "docid": "bpv7p7zo", "rank": 2, "score": 0.778999388217926}, {"content": "Title: Seasonality and uncertainty in COVID-19 growth rates Content: The virus causing COVID-19 has spread rapidly worldwide and threatens millions of lives. It remains unknown if summer weather will reduce its continued spread, thereby alleviating strains on hospitals and providing time for vaccine development. Early insights from laboratory studies of related coronaviruses predicted that COVID-19 would decline at higher temperatures, humidity, and ultraviolet light. Using current, fine-scaled weather data and global reports of infection we developed a model that explained 36% of variation in early growth rates before intervention, with 17% based on weather or demography and 19% based on country-specific effects. We found that ultraviolet light was most strongly associated with lower COVID-19 growth rates. Projections suggest that, in the absence of intervention, COVID-19 will decrease temporarily during summer, rebound by autumn, and peak next winter. However, uncertainty remains high and the probability of a weekly doubling rate remained >20% throughout the summer in the absence of control. Consequently, aggressive policy interventions will likely be needed in spite of seasonal trends.", "qid": 2, "docid": "0vlzwksu", "rank": 3, "score": 0.7755322456359863}, {"content": "Title: Roles of meteorological conditions in COVID-19 transmission on a worldwide scale Content: The novel coronavirus (SARS-CoV-2/ 2019-nCoV) identified in Wuhan, China, in December 2019 has caused great damage to public health and economy worldwide with over 140,000 infected cases up to date. Previous research has suggested an involvement of meteorological conditions in the spread of droplet-mediated viral diseases, such as influenza. However, as for the recent novel coronavirus, few studies have discussed systematically about the role of daily weather in the epidemic transmission of the virus. Here, we examine the relationships of meteorological variables with the severity of the outbreak on a worldwide scale. The confirmed case counts, which indicates the severity of COVID-19 spread, and four meteorological variables, i.e., air temperature, relative humidity, wind speed, and visibility, were collected daily between January 20 and March 11 (52 days) for 430 cities and districts all over China, 21 cities/ provinces in Italy, 21 cities/ provinces in Japan, and 51 other countries around the world. Four different time delays of weather (on the day, 3 days ago, 7 days ago, and 14 days ago) as to the epidemic situation were taken for modeling and we finally chose the weather two weeks ago to model against the daily epidemic situation as its correlated with the outbreak best. Taken Chinese cities as a discovery dataset, it was suggested that temperature, wind speed, and relative humidity combined together could best predict the epidemic situation. The meteorological model could well predict the outbreak around the world with a high correlation (r2>0.6) with the real data. Using this model, we further predicted the possible epidemic situation in the future 12 days in several high-latitude cities with potential outbreak. This model could provide more information for government's future decisions on COVID-19 outbreak control.", "qid": 2, "docid": "3svnvozz", "rank": 4, "score": 0.774075984954834}, {"content": "Title: A spatio-temporal analysis for exploring the effect of temperature on COVID-19 early evolution in Spain Content: The new SARS-CoV-2 coronavirus, which causes the COVID-19 disease, was reported in Wuhan, China, in December 2019. This new pathogen has spread rapidly around more than 200 countries, in which Spain has one of the world's highest mortality rates so far. Previous studies have supported an epidemiological hypothesis that weather conditions may affect the survival and spread of droplet-mediated viral diseases. However, some contradictory studies have also been reported in the same research line. In addition, many of these studies have been performed considering only meteorological factors, which can limit the reliability of the results. Herein, we report a spatio-temporal analysis for exploring the effect of daily temperature (mean, minimum and maximum) on the accumulated number of COVID-19 cases in the provinces of Spain. Non-meteorological factors such as population density, population by age, number of travellers and number of companies have also been considered for the analysis. No evidence suggesting a reduction in COVID-19 cases at warmer mean, minimum and maximum temperatures has been found. Nevertheless, these results need to be interpreted cautiously given the existing uncertainty about COVID-19 data, and should not be extrapolated to temperature ranges other than those analysed here for the early evolution period.", "qid": 2, "docid": "t4kdxnhy", "rank": 5, "score": 0.7724359631538391}, {"content": "Title: Effect of Temperature on the Transmission of COVID-19: A Machine Learning Case Study in Spain Content: The novel coronavirus (COVID-19) has already spread to almost every country in the world and has infected over 3 million people. To understand the transmission mechanism of this highly contagious virus, it is necessary to study the potential factors, including meteorological conditions. Here, we present a machine learning approach to study the effect of temperature, humidity and wind speed on the number of infected people in the three most populous autonomous communities in Spain. We find that there is a moderate inverse correlation between temperature and the daily number of infections. This correlation manifests for temperatures recorded up to 6 days before the onset, which corresponds well to the known mean incubation period of COVID-19. We also show that the correlation for humidity and wind speed is not significant.", "qid": 2, "docid": "r9yrr45q", "rank": 6, "score": 0.7705304026603699}, {"content": "Title: The role of absolute humidity on transmission rates of the COVID-19 outbreak Content: A novel coronavirus (COVID-19) was identified in Wuhan, Hubei Province, China, in December 2019 and has caused over 40,000 cases worldwide to date. Previous studies have supported an epidemiological hypothesis that cold and dry (low absolute humidity) environments facilitate the survival and spread of droplet-mediated viral diseases, and warm and humid (high absolute humidity) environments see attenuated viral transmission (i.e., influenza). However, the role of absolute humidity in transmission of COVID-19 has not yet been established. Here, we examine province-level variability of the basic reproductive numbers of COVID-19 across China and find that changes in weather alone (i.e., increase of temperature and humidity as spring and summer months arrive in the North Hemisphere) will not necessarily lead to declines in COVID-19 case counts without the implementation of extensive public health interventions.", "qid": 2, "docid": "zvngy7zz", "rank": 7, "score": 0.770012617111206}, {"content": "Title: The Weather Impacts the Outbreak of COVID-19 in Mainland China Content: Recent literature has suggested that climate conditions have considerably significant influences on the transmission of coronavirus COVID-19. However, there is a lack of comprehensive study that investigates the relationships between multiple weather factors and the development of COVID-19 pandemic while excluding the impact of social factors. In this paper, we study the relationships between six main weather factors and the infection statistics of COVID-19 on 250 cities in Mainland China. Our correlation analysis using weather and infection statistics indicates that all the studied weather factors are correlated with the spread of COVID-19, where precipitation shows the strongest correlation. We also build a weather-aware predictive model that forecasts the number of infected cases should there be a second wave of the outbreak in Mainland China. Our predicted results show that cities located in different geographical areas are likely to be challenged with the second wave of COVID-19 at very different time periods and the severity of the outbreak varies to a large degree, in correspondence with the varying weather conditions.", "qid": 2, "docid": "akb96git", "rank": 8, "score": 0.7694807052612305}, {"content": "Title: Meteorological impacts on the incidence of COVID-19 in the U.S. Content: Since the World Health Organization has declared the current outbreak of the novel coronavirus (COVID-19) a global pandemic, some have been anticipating that the mitigation could happen in the summer like seasonal influenza, while medical solutions are still in a slow progress. Experimental studies have revealed a few evidences that coronavirus decayed quickly under the exposure of heat and humidity. This study aims to carry out an epidemiological investigation to establish the association between meteorological factors and COVID-19 in high risk areas of the United States (U.S.). We analyzed daily new confirmed cases of COVID-19 and seven meteorological measures in top 50 U.S. counties with the most accumulative confirmed cases from March 22, 2020 to April 22, 2020. Our analyses indicate that each meteorological factor and COVID-19 more likely have a nonlinear association rather than a linear association over the wide ranges of temperature, relative humidity, and precipitation observed. Average temperature, minimum relative humidity, and precipitation were better predictors to address the meteorological impact on COVID-19. By including all the three meteorological factors in the same model with their lagged effects up to 3 days, the overall impact of the average temperature on COVID-19 was found to peak at 68.45 \u00b0F and decrease at higher degrees, though the overall relative risk percentage (RR %) reduction did not become significantly negative up to 85 \u00b0F. There was a generally downward trend of RR % with the increase of minimum relative humidity; nonetheless, the trend reversed when the minimum relative humidity exceeded 91.42%. The overall RR % of COVID-19 climbed to the highest level of 232.07% (95% confidence interval = 199.77, 267.85) with 1.60 inches of precipitation, and then started to decrease. When precipitation exceeded 1.85 inches, its impact on COVID-19 became significantly negative. Our findings alert people to better have self-protection during the pandemic rather than expecting that the natural environment can curb coronavirus for human beings.", "qid": 2, "docid": "miyvn7vd", "rank": 9, "score": 0.7694461345672607}, {"content": "Title: Impact of weather on COVID-19 pandemic in Turkey Content: The coronavirus pandemic, which has numerous global implications, has led people to believe that nothing will be the same as before. The present day is dominated by studies on determining the factors that affect, taking preventive actions, and trying to find an effective treatment on top priority. Meteorological parameters are among the crucial factors affecting infectious diseases. The present study examines the correlation between weather and coronavirus disease 2019 (COVID-19) by considering nine cities in Turkey. In this regard, temperature (\u00b0C), dew point (\u00b0C), humidity (%), and wind speed (mph) are considered as parameters of weather. Research states that the incubation period of COVID-19 varies from 1\u00e2\u0080\u00afday to 14\u00e2\u0080\u00afdays. Therefore, the effects of each parameter within 1, 3, 7, and 14\u00e2\u0080\u00afdays are examined. In addition, the population is included as an effective parameter for evaluation. The analyses are conducted based on Spearman's correlation coefficients. The results showed that the highest correlations were observed for population, wind speed 14\u00e2\u0080\u00afdays ago, and temperature on the day, respectively. The study results may guide authorities and decision-makers on taking specific measures for the cities.", "qid": 2, "docid": "ds3nmssp", "rank": 10, "score": 0.7692861557006836}, {"content": "Title: Impact of weather on COVID-19 pandemic in Turkey Content: Abstract The coronavirus pandemic, which has numerous global implications, has led people to believe that nothing will be the same as before. The present day is dominated by studies on determining the factors that affect, taking preventive actions, and trying to find an effective treatment on top priority. Meteorological parameters are among the crucial factors affecting infectious diseases. The present study examines the correlation between weather and coronavirus disease 2019 (COVID-19) by considering nine cities in Turkey. In this regard, temperature (\u00b0C), dew point (\u00b0C), humidity (%), and wind speed (mph) are considered as parameters of weather. Research states that the incubation period of COVID-19 varies from 1 day to 14 days. Therefore, the effects of each parameter within 1, 3, 7, and 14 days are examined. In addition, the population is included as an effective parameter for evaluation. The analyses are conducted based on Spearman's correlation coefficients. The results showed that the highest correlations were observed for population, wind speed 14 days ago, and temperature on the day, respectively. The study results may guide authorities and decision-makers on taking specific measures for the cities.", "qid": 2, "docid": "jxa9h27b", "rank": 11, "score": 0.7683260440826416}, {"content": "Title: A close look at the biology of SARS-CoV-2, and the potential influence of weather conditions and seasons on COVID-19 case spread Content: BACKGROUND: There is sufficient epidemiological and biological evidence of increased human susceptibility to viral pathogens such as Middle East respiratory syndrome coronavirus, respiratory syncytial virus, human metapneumovirus and influenza virus, in cold weather. The pattern of outbreak of the coronavirus disease 2019 (COVID-19) in China during the flu season is further proof that meteorological conditions may potentially influence the susceptibility of human populations to coronaviruses, a situation that may become increasingly evident as the current global pandemic of COVID-19 unfolds. MAIN BODY: A very rapid spread and high mortality rates have characterized the COVID-19 pandemic in countries north of the equator where air temperatures have been seasonally low. It is unclear if the currently high rates of COVID-19 infections in countries of the northern hemisphere will wane during the summer months, or if fewer people overall will become infected with COVID-19 in countries south of the equator where warmer weather conditions prevail through most of the year. However, apart from the influence of seasons, evidence based on the structural biology and biochemical properties of many enveloped viruses similar to the novel severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 (aetiology of COVID-19), support the higher likelihood of the latter of the two outcomes. Other factors that may potentially impact the rate of virus spread include the effectiveness of infection control practices, individual and herd immunity, and emergency preparedness levels of countries. CONCLUSION: This report highlights the potential influence of weather conditions, seasons and non-climatological factors on the geographical spread of cases of COVID-19 across the globe.", "qid": 2, "docid": "eiek6olk", "rank": 12, "score": 0.7665159106254578}, {"content": "Title: A spatio-temporal analysis for exploring the effect of temperature on COVID-19 early evolution in Spain Content: Abstract The new SARS-CoV-2 coronavirus, which causes the COVID-19 disease, was reported in Wuhan, China, in December 2019. This new pathogen has spread rapidly around more than 200 countries, in which Spain has one of the world's highest mortality rates so far. Previous studies have supported an epidemiological hypothesis that weather conditions may affect the survival and spread of droplet-mediated viral diseases. However, some contradictory studies have also been reported in the same research line. In addition, many of these studies have been performed considering only meteorological factors, which can limit the reliability of the results. Herein, we report a spatio-temporal analysis for exploring the effect of daily temperature (mean, minimum and maximum) on the accumulated number of COVID-19 cases in the provinces of Spain. Non-meteorological factors such as population density, population by age, number of travellers and number of companies have also been considered for the analysis. No evidence suggesting a reduction in COVID-19 cases at warmer mean, minimum and maximum temperatures has been found. Nevertheless, these results need to be interpreted cautiously given the existing uncertainty about COVID-19 data, and should not be extrapolated to temperature ranges other than those analysed here for the early evolution period.", "qid": 2, "docid": "azcr8jf3", "rank": 13, "score": 0.7661189436912537}, {"content": "Title: Will the COVID-19 pandemic slow down in the Northern hemisphere by the onset of summer? An epidemiological hypothesis Content: The COVID-19 pandemic has affected most countries of the world. As corona viruses are highly prevalent in the cold season, the question remains whether or not the pandemic will improve with increasing temperatures in the Northern hemisphere. We use data from a primary care registry of almost 15,000 patients over 20 years to retrieve information on viral respiratory infection outbreaks. Our analysis suggests that the severity of the pandemic will be softened by the seasonal change to summer.", "qid": 2, "docid": "iztm1z6g", "rank": 14, "score": 0.7659640908241272}, {"content": "Title: Does temperature and humidity influence the spread of Covid-19?: A preliminary report Content: INTRODUCTION: Climate change has been known to influence infectious diseases. The reason for this being the fact; disease agents and their vectors each have particular environments that are optimal for growth, survival, transport, and dissemination. MATERIALS AND METHODS: The WHO's website was accessed to look for the Novel Coronavirus (COVID-19) situation dashboard and comprehensively study and assess the report. An attempt was made to look for countries, areas or territories with maximum and minimum number of cases of lab confirmed COVID cases. Further, we entered the words \u201cClimate\u201c in google for each of the aforementioned countries and searched for the results. A comparison was established by including countries from both the hemispheres (northern and southern). The preliminary analysis was based on the reports from countries with established testing facilities for Covid-19. RESULTS: The report suggests that countries with higher number of cases are the countries with cold weather. These are also the countries with low humidity which could be favoring the transmission and survival of the SARS-COV-2. CONCLUSIONS: The results though preliminary point to a pattern which favors the hypothesis that the extensive spread of Covid-19 maybe limited by temperature and humidity.", "qid": 2, "docid": "ws03xsho", "rank": 15, "score": 0.7655733823776245}, {"content": "Title: Correlation of the global spread of coronavirus disease-19 with atmospheric air temperature Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus that may be sensitive to heat. We assessed whether the spread of coronavirus disease 2019 (COVID-19) correlates with air temperature. We also studied whether additional climate, geographical, and population variables were correlated. The total number of confirmed COVID-19 cases and mortality rates reported in each country between 1st Jan and 31st Mar 2020 were compared with the country's three-month average atmospheric air temperature, precipitation and latitude. Spearman's correlation coefficient (rs) was used to identify significant correlations. Our analysis included a total of 748,555 confirmed COVID-19 cases worldwide. The total number of patients with COVID-19 decreased with increasing atmospheric air temperature (rs = -0.54, 95%CI: [-0.64, -0.42]; P <0.001) and increased with an increasing latitude (rs =0.60, 95%CI: [0.48, 0.70]; P <0.001). Our findings justify further studies to examine the effect of air temperature on infectivity of SAR-CoV-2.", "qid": 2, "docid": "foha7ozb", "rank": 16, "score": 0.7642258405685425}, {"content": "Title: Association between ambient temperature and COVID-19 infection in 122 cities from China Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a severe public health problem globally. Both epidemiological and laboratory studies have shown that ambient temperature could affect the transmission and survival of coronaviruses. This study aimed to determine whether the temperature is an essential factor in the infection caused by this novel coronavirus. METHODS: Daily confirmed cases and meteorological factors in 122 cities were collected between January 23, 2020, to February 29, 2020. A generalized additive model (GAM) was applied to explore the nonlinear relationship between mean temperature and COVID-19 confirmed cases. We also used a piecewise linear regression to determine the relationship in detail. RESULTS: The exposure-response curves suggested that the relationship between mean temperature and COVID-19 confirmed cases was approximately linear in the range of <3 \u00b0C and became flat above 3 \u00b0C. When mean temperature (lag0-14) was below 3 \u00b0C, each 1 \u00b0C rise was associated with a 4.861% (95% CI: 3.209-6.513) increase in the daily number of COVID-19 confirmed cases. These findings were robust in our sensitivity analyses. CONCLUSIONS: Our results indicate that mean temperature has a positive linear relationship with the number of COVID-19 cases with a threshold of 3 \u00b0C. There is no evidence supporting that case counts of COVID-19 could decline when the weather becomes warmer, which provides useful implications for policymakers and the public.", "qid": 2, "docid": "y1rlk8th", "rank": 17, "score": 0.7635491490364075}, {"content": "Title: Temperature Decreases Spread Parameters of the New Covid-19 Case Dynamics Content: (1) Background: The virulence of coronavirus diseases due to viruses like SARS-CoV or MERS-CoV decreases in humid and hot weather. The putative temperature dependence of infectivity by the new coronavirus SARS-CoV-2 or covid-19 has a high predictive medical interest. (2) Methods: External temperature and new covid-19 cases in 21 countries and in the French administrative regions were collected from public data. Associations between epidemiological parameters of the new case dynamics and temperature were examined using an ARIMA model. (3) Results: We show that, in the first stages of the epidemic, the velocity of contagion decreases with country- or region-wise temperature. (4) Conclusions: Results indicate that high temperatures diminish initial contagion rates, but seasonal temperature effects at later stages of the epidemy remain questionable. Confinement policies and other eviction rules should account for climatological heterogeneities, in order to adapt the public health decisions to possible geographic or seasonal gradients.", "qid": 2, "docid": "03s9spbi", "rank": 18, "score": 0.7626461982727051}, {"content": "Title: Substantial Changes in Nitrate Oxide and Ozone after Excluding Meteorological Impacts during the COVID-19 Outbreak in Mainland China Content: [Image: see text] The COVID-19 outbreak in China led to dramatic changes in human activities resulting from the sudden infection prevention and control measures. Here, we use ground-level observations and model simulations to examine the nationwide spatial\u2013temporal variations of six air pollutants before and after the initiation of First-Level Public Health Emergency Response. The level of ambient NO(2) declined significantly, and in most cities, the decline was dominated by reduced emissions. Meanwhile, the level of O(3) increased significantly during this period, and the nonmeteorological factors explained the increase. For the other air pollutants (PM(2.5), SO(2), and CO), the observed declines on the national scale were obviously affected by the meteorological conditions. In Wuhan, significant declines were found for air pollutants except O(3) and emissions dominated the changes, while in Beijing during the same period, only the level of NO(2) significantly declined. This study clearly shows that the meteorological changes contributed substantially to the observed changes in most air pollutants, and this must be considered in evaluating the impacts of pollutant source changes on air quality during the specific event and in assessing source-oriented risks.", "qid": 2, "docid": "4bz7xeev", "rank": 19, "score": 0.7623773813247681}, {"content": "Title: Effects of temperature and humidity on the daily new cases and new deaths of COVID-19 in 166 countries Content: The coronavirus disease 2019 (COVID-19) pandemic is the defining global health crisis of our time and the greatest challenge facing the world. Meteorological parameters are reportedly crucial factors affecting respiratory infectious disease epidemics; however, the effect of meteorological parameters on COVID-19 remains controversial. This study investigated the effects of temperature and relative humidity on daily new cases and daily new deaths of COVID-19, which has useful implications for policymakers and the public. Daily data on meteorological conditions, new cases and new deaths of COVID-19 were collected for 166 countries (excluding China) as of March 27, 2020. Log-linear generalized additive model was used to analyze the effects of temperature and relative humidity on daily new cases and daily new deaths of COVID-19, with potential confounders controlled for, including wind speed, median age of the national population, Global Health Security Index, Human Development Index and population density. Our findings revealed that temperature and relative humidity were both negatively related to daily new cases and deaths. A 1 \u00b0C increase in temperature was associated with a 3.08% (95% CI: 1.53%, 4.63%) reduction in daily new cases and a 1.19% (95% CI: 0.44%, 1.95%) reduction in daily new deaths, whereas a 1% increase in relative humidity was associated with a 0.85% (95% CI: 0.51%, 1.19%) reduction in daily new cases and a 0.51% (95% CI: 0.34%, 0.67%) reduction in daily new deaths. The results remained robust when different lag structures and the sensitivity analysis were used. These findings provide preliminary evidence that the COVID-19 pandemic may be partially suppressed with temperature and humidity increases. However, active measures must be taken to control the source of infection, block transmission and prevent further spread of COVID-19.", "qid": 2, "docid": "axn5dgkh", "rank": 20, "score": 0.7621601819992065}, {"content": "Title: Effects of meteorological conditions and air pollution on COVID-19 transmission: Evidence from 219 Chinese cities. Content: The spatial distribution of the COVID-19 infection in China cannot be explained solely by geographical distance and regulatory stringency. In this research we investigate how meteorological conditions and air pollution, as concurring factors, impact COVID-19 transmission, using data on new confirmed cases from 219 prefecture cities from January 24 to February 29, 2020. Results revealed a kind of nonlinear dose-response relationship between temperature and coronavirus transmission. We also found that air pollution indicators are positively correlated with new confirmed cases, and the coronavirus further spreads by 5-7% as the AQI increases by 10 units. Further analysis based on regional divisions revealed that in northern China the negative effects of rising temperature on COVID-19 is counteracted by aggravated air pollution. In the southern cities, the ambient temperature and air pollution have a negative interactive effect on COVID-19 transmission, implying that rising temperature restrains the facilitating effects of air pollution and that they jointly lead to a decrease in new confirmed cases. These results provide implications for the control and prevention of this disease and for the anticipation of another possible pandemic.", "qid": 2, "docid": "o6q2rkv7", "rank": 21, "score": 0.7617706060409546}, {"content": "Title: Effects of meteorological conditions and air pollution on COVID-19 transmission: Evidence from 219 Chinese cities Content: The spatial distribution of the COVID-19 infection in China cannot be explained solely by geographical distance and regulatory stringency. In this research we investigate how meteorological conditions and air pollution, as concurring factors, impact COVID-19 transmission, using data on new confirmed cases from 219 prefecture cities from January 24 to February 29, 2020. Results revealed a kind of nonlinear dose-response relationship between temperature and coronavirus transmission. We also found that air pollution indicators are positively correlated with new confirmed cases, and the coronavirus further spreads by 5-7% as the AQI increases by 10 units. Further analysis based on regional divisions revealed that in northern China the negative effects of rising temperature on COVID-19 is counteracted by aggravated air pollution. In the southern cities, the ambient temperature and air pollution have a negative interactive effect on COVID-19 transmission, implying that rising temperature restrains the facilitating effects of air pollution and that they jointly lead to a decrease in new confirmed cases. These results provide implications for the control and prevention of this disease and for the anticipation of another possible pandemic.", "qid": 2, "docid": "4j47etsu", "rank": 22, "score": 0.761770486831665}, {"content": "Title: Weathering the pandemic: How the Caribbean Basin can use viral and environmental patterns to predict, prepare, and respond to COVID-19 Content: The 2020 coronavirus pandemic is developing at different paces throughout the world. Some areas, like the Caribbean Basin, have yet to see the virus strike at full force. When it does, there is reasonable evidence to suggest the consequent COVID-19 outbreaks will overwhelm healthcare systems and economies. This is particularly concerning in the Caribbean as pandemics can have disproportionately higher mortality impacts on lower and middle-income countries. Preliminary observations from our team and others suggest that temperature and climatological factors could influence the spread of this novel coronavirus, making spatiotemporal predictions of its infectiousness possible. This review studies geographic and time-based distribution of known respiratory viruses in the Caribbean Basin in an attempt to foresee how the pandemic will develop in this region. This review is meant to aid in planning short- and long-term interventions to manage outbreaks at the international, national, and subnational levels in the region.", "qid": 2, "docid": "w5kjmw88", "rank": 23, "score": 0.7617459297180176}, {"content": "Title: Eco-epidemiological assessment of the COVID-19 epidemic in China, January\u2013February 2020 Content: Background: The outbreak of COVID-19 in China in early 2020 provides a rich data source for exploring the ecological determinants of this new infection, which may be of relevance as the pandemic develops. Objectives: Assessing the spread of the COVID-19 across China, in relation to associations between cases and ecological factors including population density, temperature, solar radiation and precipitation. Methods: Open-access COVID-19 case data include 18,069 geo-located cases in China during January and February 2020, which were mapped onto a 0.25\u00b0 latitude/longitude grid together with population and weather data (temperature, solar radiation and precipitation). Of 15,539 grid cells, 559 (3.6%) contained at least one case, and these were used to construct a Poisson regression model of cell-weeks. Weather parameters were taken for the preceding week given the established 5\u20137 day incubation period for COVID-19. The dependent variable in the Poisson model was incident cases per cell-week and exposure was cell population, allowing for clustering of cells over weeks, to give incidence rate ratios. Results: The overall COVID-19 incidence rate in cells with confirmed cases was 0.12 per 1,000. There was a single confirmed case in 113/559 (20.2%) of cells, while two grid cells recorded over 1,000 confirmed cases. Weekly means of maximum daily temperature varied from \u221228.0\u00b0C to 30.1\u00b0C, minimum daily temperature from \u221242.4\u00b0C to 23.0\u00b0C, maximum solar radiation from 0.04 to 2.74 MJm(\u22122) and total precipitation from 0 to 72.6 mm. Adjusted incidence rate ratios suggested brighter, warmer and drier conditions were associated with lower incidence. Conclusion: Though not demonstrating cause and effect, there were appreciable associations between weather and COVID-19 incidence during the epidemic in China. This does not mean the pandemic will go away with summer weather but demonstrates the importance of using weather conditions in understanding and forecasting the spread of COVID-19.", "qid": 2, "docid": "be7gxvl7", "rank": 24, "score": 0.7611572742462158}, {"content": "Title: Eco-epidemiological assessment of the COVID-19 epidemic in China, January-February 2020 Content: Background: The outbreak of COVID-19 in China in early 2020 provides a rich data source for exploring the ecological determinants of this new infection, which may be of relevance as the pandemic develops.Objectives: Assessing the spread of the COVID-19 across China, in relation to associations between cases and ecological factors including population density, temperature, solar radiation and precipitation.Methods: Open-access COVID-19 case data include 18,069 geo-located cases in China during January and February 2020, which were mapped onto a 0.25\u00b0 latitude/longitude grid together with population and weather data (temperature, solar radiation and precipitation). Of 15,539 grid cells, 559 (3.6%) contained at least one case, and these were used to construct a Poisson regression model of cell-weeks. Weather parameters were taken for the preceding week given the established 5-7 day incubation period for COVID-19. The dependent variable in the Poisson model was incident cases per cell-week and exposure was cell population, allowing for clustering of cells over weeks, to give incidence rate ratios.Results: The overall COVID-19 incidence rate in cells with confirmed cases was 0.12 per 1,000. There was a single confirmed case in 113/559 (20.2%) of cells, while two grid cells recorded over 1,000 confirmed cases. Weekly means of maximum daily temperature varied from -28.0\u00b0C to 30.1\u00b0C, minimum daily temperature from -42.4\u00b0C to 23.0\u00b0C, maximum solar radiation from 0.04 to 2.74 MJm-2 and total precipitation from 0 to 72.6 mm. Adjusted incidence rate ratios suggested brighter, warmer and drier conditions were associated with lower incidence.Conclusion: Though not demonstrating cause and effect, there were appreciable associations between weather and COVID-19 incidence during the epidemic in China. This does not mean the pandemic will go away with summer weather but demonstrates the importance of using weather conditions in understanding and forecasting the spread of COVID-19.", "qid": 2, "docid": "upw6fulv", "rank": 25, "score": 0.7604049444198608}, {"content": "Title: The Challenge of Using Epidemiological Case Count Data: The Example of Confirmed COVID-19 Cases and the Weather Content: The publicly available data on COVID-19 cases provides an opportunity to better understand this new disease. However, strong attention needs to be paid to the limitations of the data to avoid making inaccurate conclusions. This article, which focuses on the relationship between the weather and COVID-19, raises the concern that the same factors influencing the spread of the disease might also affect the number of tests performed and who gets tested. For example, weather conditions impact the prevalence of respiratory diseases with symptoms similar to COVID-19, and this will likely influence the number of tests performed. This general limitation could severely undermine any similar analysis using existing COVID-19 data or similar epidemiological data, which could, therefore, mislead decision-makers on questions of great policy relevance.", "qid": 2, "docid": "0jm73t0s", "rank": 26, "score": 0.7597148418426514}, {"content": "Title: Impact of weather indicators on the COVID-19 outbreak: A multi-state study in India Content: The present study examines the impact of weather indicators on the COVID-19 outbreak in the majorly affected states of India. In this study, we hypothesize that the weather indicators could significantly influence the impact of the corona virus. The Kendall and Spearman rank correlation tests were chosen to conduct the statistical analysis. In this regard, we compiled a daily dataset including confirmed case counts, Recovered case counts, Deceased cases, Average Temperature, Maximum Relative Humidity, Maximum Wind Speed for six most affected states of India during the period of March 25, 2020 to April 24, 2020. We investigated that the average Humidity and Average Temperature seven days ago play a significant role in the recovery of coronavirus cases. The rise in average temperature will improve the recovery rate in the days to come. The cities with very high humidity levels or dry weather conditions have high probabilities of recovery from COVID-19. The findings of this research will help the policymakers to identify risky geographic areas and enforce timely preventive measures.", "qid": 2, "docid": "yi57n8nc", "rank": 27, "score": 0.7586591243743896}, {"content": "Title: COVID-19: Effects of weather conditions on the propagation of respiratory droplets Content: As the number of confirmed cases of Coronavirus disease 2019 (COVID-19) continues to increase, there has been a rising concern regarding the effect of weather conditions, especially over the upcoming summer, on the transmission of this disease. In this study, we assess the transmission of COVID-19 under different weather conditions by investigating the propagation of infectious respiratory droplets. A comprehensive mathematical model is established to explore their evaporation, heat transfer and kinematics under different temperature, humidity and ventilation conditions. The transmitting pathway of COVID-19 through respiratory droplets is divided into short-range droplet contacts and long-range aerosol exposure. We show that the effect of weather conditions is not monotonic: low temperature and high humidity facilitate droplet contact transmission, while high temperature and low humidity promote the formation of aerosol particles and accumulation of particles with a diameter of 2.5 m or less (PM2.5). Our model suggests that the 6 ft of social distance recommended by the Center for Disease Control and Prevention (CDC) may be insufficient in certain environmental conditions, as the droplet spreading distance can be as long as 6 m (19.7 ft) in cold and humid weather. The results of this study suggest that the current pandemic may not ebb in the summer of the northern hemisphere without proper intervention, as there is an increasing chance of aerosol transmission. We also emphasize that the meticulous design of building ventilation systems is critical in containing both the droplet contact infections and aerosol exposures.", "qid": 2, "docid": "tyhtdawb", "rank": 28, "score": 0.7577334642410278}, {"content": "Title: Effects of temperature and humidity on the daily new cases and new deaths of COVID-19 in 166 countries Content: Abstract The coronavirus disease 2019 (COVID-19) pandemic is the defining global health crisis of our time and the greatest challenge facing the world. Meteorological parameters are reportedly crucial factors affecting respiratory infectious disease epidemics; however, the effect of meteorological parameters on COVID-19 remains controversial. This study investigated the effects of temperature and relative humidity on daily new cases and daily new deaths of COVID-19, which has useful implications for policymakers and the public. Daily data on meteorological conditions, new cases and new deaths of COVID-19 were collected for 166 countries (excluding China) as of March 27, 2020. Log-linear generalized additive model was used to analyze the effects of temperature and relative humidity on daily new cases and daily new deaths of COVID-19, with potential confounders controlled for, including wind speed, median age of the national population, Global Health Security Index, Human Development Index and population density. Our findings revealed that temperature and relative humidity were both negatively related to daily new cases and deaths. A 1 \u00b0C increase in temperature was associated with a 3.08% (95% CI: 1.53%, 4.63%) reduction in daily new cases and a 1.19% (95% CI: 0.44%, 1.95%) reduction in daily new deaths, whereas a 1% increase in relative humidity was associated with a 0.85% (95% CI: 0.51%, 1.19%) reduction in daily new cases and a 0.51% (95% CI: 0.34%, 0.67%) reduction in daily new deaths. The results remained robust when different lag structures and the sensitivity analysis were used. These findings provide preliminary evidence that the COVID-19 pandemic may be partially suppressed with temperature and humidity increases. However, active measures must be taken to control the source of infection, block transmission and prevent further spread of COVID-19.", "qid": 2, "docid": "q3abp9o7", "rank": 29, "score": 0.7562764883041382}, {"content": "Title: Eco-epidemiological assessment of the COVID-19 epidemic in China, January-February 2020 Content: Background: The outbreak of COVID-19 in China in early 2020 provides a rich data source for exploring the ecological determinants of this new infection, which may be of relevance elsewhere. Objectives: Assessing the spread of the COVID-19 across China, in relation to associations between cases and ecological factors including population density, temperature, solar radiation and precipitation. Methods: Open-access COVID-19 case data include 18,069 geo-located cases in China during January and February 2020, which were mapped onto a 0.25\u00b0 latitude/longitude grid together with population and weather data (temperature, solar radiation and precipitation). Of 15,539 grid cells, 559 (3.6%) contained at least one case, and these were used to construct a Poisson regression model of cell-weeks. Weather parameters were taken for the preceding week given the established 5-7 day incubation period for COVID-19. The dependent variable in the Poisson model was incident cases per cell-week and exposure was cell population, allowing for clustering of cells over weeks, to give incidence rate ratios. Results: The overall COVID-19 incidence rate in cells with confirmed cases was 0.12 per 1,000. There was a single case in 113/559 (20.2%) of cells, while two grid cells recorded over 1,000 cases. Weekly means of maximum daily temperature varied from -28.0 to 30.1 \u00b0C, minimum daily temperature from -42.4 to 23.0 \u00b0C, maximum solar radiation from 0.04 to 2.74 MJm-2 and total precipitation from 0 to 72.6 mm. Adjusted incidence rate ratios suggested brighter, warmer and drier conditions were associated with lower incidence. Conclusion: Though not demonstrating cause and effect, there were appreciable associations between weather and COVID-19 incidence during the epidemic in China. This does not mean the pandemic will go away with summer weather but demonstrates the importance of using weather conditions in understanding and forecasting the spread of COVID-19.", "qid": 2, "docid": "r141na6j", "rank": 30, "score": 0.7560316324234009}, {"content": "Title: Effects of temperature variation and humidity on the death of COVID-19 in Wuhan, China Content: Meteorological parameters are the important factors influencing the infectious diseases such as severe acute respiratory syndrome (SARS) and influenza. This study aims to explore the association between Corona Virus Disease 2019 (COVID-19) deaths and weather parameters. In this study, we collected the daily death numbers of COVID-19, meteorological parameters and air pollutant data from 20 January 2020 to 29 February 2020 in Wuhan, China. Generalized additive model was applied to explore the effect of temperature, humidity and diurnal temperature range on the daily death counts of COVID-19. There were 2299 COVID-19 death counts in Wuhan during the study period. A positive association with COVID-19 daily death counts was observed for diurnal temperature range (r = 0.44), but negative association for relative humidity (r = -0.32). In addition, one unit increase in diurnal temperature range was only associated with a 2.92% (95% CI: 0.61%, 5.28%) increase in COVID-19 deaths in lag 3. However, both 1 unit increase of temperature and absolute humidity were related to the decreased COVID-19 death in lag 3 and lag 5, with the greatest decrease both in lag 3 [-7.50% (95% CI: -10.99%, -3.88%) and -11.41% (95% CI: -19.68%, -2.29%)]. In summary, this study suggests the temperature variation and humidity may also be important factors affecting the COVID-19 mortality.", "qid": 2, "docid": "r65in69l", "rank": 31, "score": 0.7550752758979797}, {"content": "Title: Weathering the pandemic: How the Caribbean Basin can use viral and environmental patterns to predict, prepare and respond to COVID\u201019 Content: The 2020 coronavirus pandemic is developing at different paces throughout the world. Some areas, like the Caribbean Basin, have yet to see the virus strike at full force. When it does, there is reasonable evidence to suggest the consequent COVID\u201019 outbreaks will overwhelm healthcare systems and economies. This is particularly concerning in the Caribbean as pandemics can have disproportionately higher mortality impacts on lower and middle income countries. Preliminary observations from our team and others suggest that temperature and climatological factors could influence the spread of this novel coronavirus, making spatiotemporal predictions of its infectiousness possible. This review studies geographic and time\u2010based distribution of known respiratory viruses in the Caribbean Basin in an attempt to foresee how the pandemic will develop in this region. This review is meant to aid in planning short\u2010 and long\u2010term interventions to manage outbreaks at the international, national and sub\u2010national levels in the region. This article is protected by copyright. All rights reserved.", "qid": 2, "docid": "gan10za0", "rank": 32, "score": 0.7550485134124756}, {"content": "Title: Effects of weather and policy intervention on COVID-19 infection in Ghana Content: Even though laboratory and epidemiological studies have demonstrated the effects of ambient temperature on the transmission and survival of coronaviruses, not much has been done on the effects of weather on the spread of COVID-19. This study investigates the effects of temperature, humidity, precipitation, wind speed and the specific government policy intervention of partial lockdown on the new cases of COVID-19 infection in Ghana. Daily data on confirmed cases of COVID-19 from March 13, 2020 to April 21, 2020 were obtained from the official website of Our World in Data (OWID) dedicated to COVID-19 while satellite climate data for the same period was obtained from the official website of NASA's Prediction of Worldwide Energy Resources (POWER) project. Considering the nature of the data and the objectives of the study, a time series generalized linear model which allows for regressing on past observations of the response variable and covariates was used for model fitting. The results indicate significant effects of maximum temperature, relative humidity and precipitation in predicting new cases of the disease. Also, results of the intervention analysis indicate that the null hypothesis of no significant effect of the specific policy intervention of partial lockdown should be rejected (p-value=0.0164) at a 5\\% level of significance. These findings provide useful insights for policymakers and the public.", "qid": 2, "docid": "lu11wvcm", "rank": 33, "score": 0.7550373077392578}, {"content": "Title: Short-Term Effects of Ambient Ozone, PM(2.5,) and Meteorological Factors on COVID-19 Confirmed Cases and Deaths in Queens, New York Content: The outbreak of coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, has been rapidly increasing in the United States. Boroughs of New York City, including Queens county, turn out to be the epicenters of this infection. According to the data provided by the New York State Department of Health, most of the cases of new COVID-19 infections in New York City have been found in the Queens county where 42,023 people have tested positive, and 3221 people have died as of 20 April 2020. Person-to-person transmission and travels were implicated in the initial spread of the outbreaks, but factors related to the late phase of rapidly spreading outbreaks in March and April are still uncertain. A few previous studies have explored the links between air pollution and COVID-19 infections, but more data is needed to understand the effects of short-term exposures of air pollutants and meteorological factors on the spread of COVID-19 infections, particularly in the U.S. disease epicenters. In this study, we have focused on ozone and PM(2.5), two major air pollutants in New York City, which were previously found to be associated with respiratory viral infections. The aim of our regression modeling was to explore the associations among ozone, PM(2.5), daily meteorological variables (wind speed, temperature, relative humidity, absolute humidity, cloud percentages, and precipitation levels), and COVID-19 confirmed new cases and new deaths in Queens county, New York during March and April 2020. The results from these analyses showed that daily average temperature, daily maximum eight-hour ozone concentration, average relative humidity, and cloud percentages were significantly and positively associated with new confirmed cases related to COVID-19; none of these variables showed significant associations with new deaths related to COVID-19. The findings indicate that short-term exposures to ozone and other meteorological factors can influence COVID-19 transmission and initiation of the disease, but disease aggravation and mortality depend on other factors.", "qid": 2, "docid": "mfnwuwfd", "rank": 34, "score": 0.7548683881759644}, {"content": "Title: Will COVID-19 pandemic diminish by summer-monsoon in India? Lesson from the first lockdown Content: The novel Coronavirus (2019-nCoV) was identified in Wuhan, Hubei Province, China, in December 2019 and has created a medical emergency worldwide. It has spread rapidly to multiple countries and has been declared a pandemic by the World Health Organization. In India, it is already reported more than 18 thousand cases and more than 600 deaths due to Coronavirus disease 2019 (COVID-19) till April 20, 2020. Previous studies on various viral infections like influenza have supported an epidemiological hypothesis that the cold and dry (low absolute humidity) environments favor the survival and spread of droplet-mediated viral diseases. These viral transmissions found attenuated in warm and humid (high absolute humidity) environments. However, the role of temperature, humidity, and absolute humidity in the transmission of COVID-19 has not yet been well established. Therefore the study to investigate the meteorological condition for incidence and spread of COVID-19 infection, to predict the epidemiology of the infectious disease, and to provide a scientific basis for prevention and control measures against the new disease is required for India. In this work, we analyze the local weather patterns of the Indian region affected by the COVID-19 virus for March and April months, 2020. We have investigated the effect of meteorological parameters like Temperature, relative humidity, and absolute humidity on the rate of spread of COVID-19 using daily confirm cases in India. We have used daily averaged meteorological data for the last three years (2017-2019) for March and April month and the same for the year 2020 for March 1 to April 15. We found a positive association (Pearsons r=0.56) between temperature and daily COVID-19 cases over India. We found a negative association of humidity (RH and AH) with daily COVID-19 Cases (Persons r=-0.62, -0.37). We have also investigated the role of aerosol in spreading the pandemic across India because its possible airborne nature. For this, we have investigated the association of aerosols (AOD) and other pollutions (NO2) with COVID-19 cases during the study period and also during the first lockdown period (25 March-15 April) in India. We found a negative association in March when there were few cases, but in April, it shows positive association when the number of cases is more (for AOD it was r=-0.41 and r=0.28 respectively). During the lockdown period, aerosols (AOD) and other pollutants (NO2; an indicator of PM2.5) reduced sharply with a percentage drop of about 36 and 37, respectively. This reduction may have reduced the risk for COVID-19 through air transmission due to the unavailability of aerosol particles as a base. HYSPLIT forward trajectory model also shows that surface aerosols may travel up to 4 km according to wind and direction within three h of its generation. If coronavirus becomes airborne as suggested by many studies, then it may have a higher risk of transmission by aerosols particles. So relaxing in the lockdown and environmental rules in terms of pollutant emissions from power plants, factories, and other facilities would be a wrong choice and could result in more COVID-19 incidences and deaths in India. Therefore the current study, although limited, suggests that it is doubtful that the spread of COVID-19 would slow down in India due to meteorological factors, like high temperature and high humidity. Because a large number of cases have already been reported in the range of high Tem, high Relative, and high absolute humidity regions of India. Thus our results in no way suggest that COVID-19 would not spread in warm, humid regions or during summer/monsoon. So effective public health interventions should be implemented across India to slow down the transmission of COVID-19. If COVID-19 is indeed sensitive to environmental factors, it could be tested in the coming summer-monsoon for India. So the only summer is not going to help India until monsoon is coming. Only government mitigations strategies would be helpful, whether its lockdown, aggressive and strategic testing, medical facilities, imposing social distancing, encouraging to use face mask or monitoring by a mobile application (Aarogya Setu).", "qid": 2, "docid": "1x66nxgx", "rank": 35, "score": 0.7545080780982971}, {"content": "Title: Weather Conditions and COVID-19 Transmission: Estimates and Projections Content: Background: Understanding and projecting the spread of COVID-19 requires reliable estimates of how weather components are associated with the transmission of the virus. Prior research on this topic has been inconclusive. Identifying key challenges to reliable estimation of weather impact on transmission we study this question using one of the largest assembled databases of COVID-19 infections and weather. Methods: We assemble a dataset that includes virus transmission and weather data across 3,739 locations from December 12, 2019 to April 22, 2020. Using simulation, we identify key challenges to reliable estimation of weather impacts on transmission, design a statistical method to overcome these challenges, and validate it in a blinded simulation study. Using this method and controlling for location-specific response trends we estimate how different weather variables are associated with the reproduction number for COVID-19. We then use the estimates to project the relative weather-related risk of COVID-19 transmission across the world and in large cities. Results: We show that the delay between exposure and detection of infection complicates the estimation of weather impact on COVID-19 transmission, potentially explaining significant variability in results to-date. Correcting for that distributed delay and offering conservative estimates, we find a negative relationship between temperatures above 25 degrees Celsius and estimated reproduction number ([R]), with each degree Celsius associated with a 3.1% (95% CI, 1.5% to 4.8%) reduction in [R]. Higher levels of relative humidity strengthen the negative effect of temperature above 25 degrees. Moreover, one millibar of additional pressure increases [R] by approximately 0.8 percent (95% CI, 0.6% to 1%) at the median pressure (1016 millibars) in our sample. We also find significant positive effects for wind speed, precipitation, and diurnal temperature on [R]. Sensitivity analysis and simulations show that results are robust to multiple assumptions. Despite conservative estimates, weather effects are associated with a 43% change in [R] between the 5th and 95th percentile of weather conditions in our sample. Conclusions: These results provide evidence for the relationship between several weather variables and the spread of COVID-19. However, the (conservatively) estimated relationships are not strong enough to seasonally control the epidemic in most locations.", "qid": 2, "docid": "526elsrf", "rank": 36, "score": 0.7544856071472168}, {"content": "Title: Short-term effects of specific humidity and temperature on COVID-19 morbidity in select US cities Content: Little is known about the environmental conditions that drive the spatiotemporal patterns of SARS-CoV-2. Preliminary research suggests an association with meteorological parameters. However, the relationship with temperature and humidity is not yet apparent for COVID-19 cases in US cities first impacted. The objective of this study is to evaluate the association between COVID-19 cases and meteorological parameters in select US cities. A case-crossover design with a distributed lag nonlinear model was used to evaluate the contribution of ambient temperature and specific humidity on COVID-19 cases in select US cities. The case-crossover examines each COVID case as its own control at different time periods (before and after transmission occurred). We modeled the effect of temperature and humidity on COVID-19 transmission using a lag period of 7 days. A subset of 8 cities were evaluated for the relationship with meteorological parameters and 5 cities were evaluated in detail. Short-term exposure to humidity was positively associated with COVID-19 transmission in 4 cities. The associations were small with 3 out of 4 cities exhibiting higher COVID19 transmission with specific humidity that ranged from 6 to 9 g/kg. Our results suggest that weather should be considered in infectious disease modeling efforts. Future work is needed over a longer time period and across different locations to clearly establish the weather-COVID19 relationship.", "qid": 2, "docid": "x5ou9406", "rank": 37, "score": 0.7538741827011108}, {"content": "Title: The Seasonal End of Human Coronavirus Hospital Admissions with Implications for SARS-CoV-2 Content: The seasonality of influenza viruses and endemic human coronaviruses was tracked over an 8-year period to assess key epidemiologic reduction points in disease incidence for an urban area in the northeast United States. Patients admitted to a pediatric hospital with worsening respiratory symptoms were tested using a multiplex PCR assay from nasopharyngeal swabs. The additive seasonal effects of outdoor temperatures and indoor relative humidity (RH) were evaluated. The 8-year average peak activity of human coronaviruses occurred in the first week of January, when droplet and contact transmission was enabled by the low indoor RH of 20-30%. Previous studies have shown that an increase in RH to 50% has been associated with markedly reduced viability and transmission of influenza virus and animal coronaviruses. As disease incidence was reduced by 50% in early March, to 75% in early April, to greater than 99% at the end of April, a relationship was observed from colder temperatures in January with a low indoor RH to a gradual increase in outdoor temperatures in April with an indoor RH of 45-50%. As a lipid-bound, enveloped virus with similar size characteristics to endemic human coronaviruses, SARS-CoV-2 should be subject to the same dynamics of reduced viability and transmission with increased humidity. In addition to the major role of social distancing, the transition from lower to higher indoor RH with increasing outdoor temperatures could have an additive effect on the decrease in SARS-CoV-2 cases in May. Over the 8-year period of this study, human coronavirus activity was either zero or >99% reduction in the months of June through September, and the implication would be that SARS-Cov-2 may follow a similar pattern.", "qid": 2, "docid": "3xw4qjoy", "rank": 38, "score": 0.7535475492477417}, {"content": "Title: Role of temperature and humidity in the modulation of the doubling time of COVID-19 cases Content: COVID-19 is having a great impact on public health, mortality and economy worldwide, in spite of the efforts to prevent its epidemy. The SARS-CoV-2 genome is different from that of MERS-CoV and SARS-CoV, although also expected to spread differently according to meteorological conditions. Our main goal is to investigate the role of some meteorological variables on the expansion of this outbreak. In this study, an exponential model relating the number of accumulated confirmed cases and time was considered. The rate of COVID-19 spread, using as criterion the doubling time of the number of confirmed cases, was used as dependent variable in a linear model that took four independent meteorological variables: temperature, humidity, precipitation and wind speed. Only China cases were considered, to control both cultural aspects and containment policies. Confirmed cases and the 4 meteorological variables were gathered between January 23 and March 1 (39 days) for the 31 provinces of Mainland China. Several periods of time were sampled for each province, obtaining more than one value for the rate of disease progression. Two different periods of time were tested, of 12 and 15 days, along with 3 and 5 different starting points in time, randomly chosen. The median value for each meteorological variable was computed, using the same time period; models with adjusted R square above 0.75 were selected. The rate of progression and doubling time were computed and used to fit a linear regression model. Models were evaluated using alpha=0.05. Results indicate that the doubling time correlates positively with temperature and inversely with humidity, suggesting that a decrease in the rate of progression of COVID-19 with the arrival of spring and summer in the north hemisphere. A 20oC increase is expected to delay the doubling time in 1.8 days. Those variables explain 18% of the variation in disease doubling time; the remaining 82% may be related to containment measures, general health policies, population density, transportation or cultural aspects.", "qid": 2, "docid": "qz2joxys", "rank": 39, "score": 0.7525899410247803}, {"content": "Title: Multiple drivers of the COVID-19 spread: role of climate, international mobility, and region-specific conditions Content: The novel Coronavirus Disease 2019 (COVID-19) has spread quickly across the globe. Here, we evaluated the role of climate (temperature and precipitation), region-specific susceptibility (BCG vaccination, malaria infection, and elderly population) and international traveller population (human mobility) in shaping the geographical patterns of COVID-19 cases across 1,055 countries/regions, and examined the sequential shift of multiple drivers of the accumulated cases from December, 2019 to April 12, 2020. The accumulated numbers of COVID-19 cases (per 1 million population) were well explained by a simple regression model. The explanatory power (R2) of the model increased up to > 70% in April 2020 as the COVID-19 spread progressed. Climate, host mobility, and host susceptibility largely explained the variance of the COVID-19 cases (per 1 million population), and their explanatory power improved as the pandemic progressed; the relative importance of host mobility and host susceptibility have been greater than that of climate. The number of days from outbreak onset showed greater explanatory power in the earlier stages of COVID-19 spread but rapidly lost its influence. Our findings demonstrate that the COVID-19 pandemic is deterministically driven by climate suitability, cross-border human mobility, and region-specific susceptibility. The present distribution of COVID-19 cases has not reached an equilibrium and is changing daily, especially in the Southern Hemisphere. Nevertheless, the present results, based on mapping the spread of COVID-19 and identifying multiple drivers of this outbreak trajectory, may contribute to a better understanding of the COVID-19 disease transmission risk and the measures against long-term epidemic.", "qid": 2, "docid": "d9zu9an6", "rank": 40, "score": 0.7523462772369385}, {"content": "Title: Determinants of the infection rate of the COVID-19 in the U.S. using ANFIS and virus optimization algorithm (VOA) Content: Recently, anovel coronavirus virus disease (COVID-19) has become a serious concern for global public health hazards. Infectious disease outbreaks such as COVID-19can also significantly affect the sustainable development of urban areas. Several factors such as population density and climatology parameters could potentially affect the spread of the COVID-19. In this study, a combination of the virus optimization algorithm (VOA) and adaptive network-based fuzzy inference system (ANFIS) to investigate the effects of various climate-related factors and population density on the spread of the COVID-19. For this purpose, data on the climate-related factors and the confirmed infected cases by the COVID-19across the U.S counties was used.The results show that the variable defined for the population density had the most significant impact on the performance of the developed models, which is an indication of the importance social distancing in reducing the infection rate and spread rate of the COVID-19. Among the climatology parameters, an increase in the maximum temperature was found to reduce the infection rate. Average temperature, minimum temperature, precipitation, and average wind speed were not found to significantly affect the spread of the COVID-19 while an increase in the relative humidity was found to slightly increase the infection rate. The findings of this research show that it could be expected to have reduced infection rate over the summer season. However, it should be noted that the models developed in this study were based on limited one-month data. Future investigation can benefit from using more comprehensive data covering a wider range for the input variables.", "qid": 2, "docid": "w8gjfomz", "rank": 41, "score": 0.7518746852874756}, {"content": "Title: A multi-hazards earth science perspective on the COVID-19 pandemic: the potential for concurrent and cascading crises Content: Meteorological and geophysical hazards will concur and interact with coronavirus disease (COVID-19) impacts in many regions on Earth. These interactions will challenge the resilience of societies and systems. A comparison of plausible COVID-19 epidemic trajectories with multi-hazard time-series curves enables delineation of multi-hazard scenarios for selected countries (United States, China, Australia, Bangladesh) and regions (Texas). In multi-hazard crises, governments and other responding agents may be required to make complex, highly compromised, hierarchical decisions aimed to balance COVID-19 risks and protocols with disaster response and recovery operations. Contemporary socioeconomic changes (e.g. reducing risk mitigation measures, lowering restrictions on human activity to stimulate economic recovery) may alter COVID-19 epidemiological dynamics and increase future risks relating to natural hazards and COVID-19 interactions. For example, the aggregation of evacuees into communal environments and increased demand on medical, economic, and infrastructural capacity associated with natural hazard impacts may increase COVID-19 exposure risks and vulnerabilities. COVID-19 epidemiologic conditions at the time of a natural hazard event might also influence the characteristics of emergency and humanitarian responses (e.g. evacuation and sheltering procedures, resource availability, implementation modalities, and assistance types). A simple epidemic phenomenological model with a concurrent disaster event predicts a greater infection rate following events during the pre-infection rate peak period compared with post-peak events, highlighting the need for enacting COVID-19 counter measures in advance of seasonal increases in natural hazards. Inclusion of natural hazard inputs into COVID-19 epidemiological models could enhance the evidence base for informing contemporary policy across diverse multi-hazard scenarios, defining and addressing gaps in disaster preparedness strategies and resourcing, and implementing a future-planning systems approach into contemporary COVID-19 mitigation strategies. Our recommendations may assist governments and their advisors to develop risk reduction strategies for natural and cascading hazards during the COVID-19 pandemic.", "qid": 2, "docid": "2bew6jko", "rank": 42, "score": 0.7516851425170898}, {"content": "Title: Effect of weather on COVID-19 spread in the US: A prediction model for India in 2020 Content: The effect of weather on COVID-19 spread is poorly understood. Recently, few studies have claimed that warm weather can possibly slowdown the global pandemic, which has already affected over 1.6 million people worldwide. Clarification of such relationships in the worst affected country, the US, can be immensely beneficial to understand the role of weather in transmission of the disease in the highly populated countries, such as India. We collected the daily data of new cases in 50 US states between Jan 1-Apr 9, 2020 and also the corresponding weather information (i.e., temperature (T) and absolute humidity (AH)). Distribution modeling of new cases across AH and T, helped identify the narrow and vulnerable AH range. We validated the results for 10-day intervals against monthly observations, and also worldwide trends. The results were used to predict Indian regions which would be vulnerable to weather based spread in upcoming months of 2020. COVID-19 spread in the US is significant for states with 4 < AH < 6 g/m3 and number of new cases > 10,000, irrespective of the chosen time intervals for study parameters. These trends are consistent with worldwide observations, but do not correlate well with India so far possibly due the total cases reported per interval < 10,000. The results clarify the relationship between weather parameters and COVID-19 spread. The vulnerable weather parameters will help classify the risky geographic areas in different countries. Specifically, with further reporting of new cases in India, prediction of states with high risk of weather based spread will be apparent.", "qid": 2, "docid": "q2mn9y70", "rank": 43, "score": 0.7512754201889038}, {"content": "Title: Temperature, Humidity, and Latitude Analysis to Estimate Potential Spread and Seasonality of Coronavirus Disease 2019 (COVID-19) Content: Importance: Coronavirus disease 2019 (COVID-19) infection has resulted in a global crisis. Investigating the potential association of climate and seasonality with the spread of this infection could aid in preventive and surveillance strategies. Objective: To examine the association of climate with the spread of COVID-19 infection. Design, Setting, and Participants: This cohort study examined climate data from 50 cities worldwide with and without substantial community spread of COVID-19. Eight cities with substantial spread of COVID-19 (Wuhan, China; Tokyo, Japan; Daegu, South Korea; Qom, Iran; Milan, Italy; Paris, France; Seattle, US; and Madrid, Spain) were compared with 42 cities that have not been affected or did not have substantial community spread. Data were collected from January to March 10, 2020. Main Outcomes and Measures: Substantial community transmission was defined as at least 10 reported deaths in a country as of March 10, 2020. Climate data (latitude, mean 2-m temperature, mean specific humidity, and mean relative humidity) were obtained from ERA-5 reanalysis. Results: The 8 cities with substantial community spread as of March 10, 2020, were located on a narrow band, roughly on the 30\u00b0 N to 50\u00b0 N corridor. They had consistently similar weather patterns, consisting of mean temperatures of between 5 and 11 \u00b0C, combined with low specific humidity (3-6 g/kg) and low absolute humidity (4-7 g/m3). There was a lack of substantial community establishment in expected locations based on proximity. For example, while Wuhan, China (30.8\u00b0 N) had 3136 deaths and 80\u00e2\u0080\u00af757 cases, Moscow, Russia (56.0\u00b0 N), had 0 deaths and 10 cases and Hanoi, Vietnam (21.2\u00b0 N), had 0 deaths and 31 cases. Conclusions and Relevance: In this study, the distribution of substantial community outbreaks of COVID-19 along restricted latitude, temperature, and humidity measurements was consistent with the behavior of a seasonal respiratory virus. Using weather modeling, it may be possible to estimate the regions most likely to be at a higher risk of substantial community spread of COVID-19 in the upcoming weeks, allowing for concentration of public health efforts on surveillance and containment.", "qid": 2, "docid": "7gs2hynl", "rank": 44, "score": 0.7508037090301514}, {"content": "Title: The correlation between the spread of COVID-19 infections and weather variables in 30 Chinese provinces and the impact of Chinese government mitigation plans Content: On February 1, 2020, China announced a novel coronavirus CoVID-19 outbreak to the public. CoVID-19 was classified as an epidemic by the World Health Organization (WHO). Although the disease was discovered and concentrated in Hubei Province, China, it was exported to all of the other Chinese provinces and spread globally. As of this writing, all plans have failed to contain the novel coronavirus disease, and it has continued to spread to the rest of the world. This study aimed to explore and interpret the effect of environmental and metrological variables on the spread of coronavirus disease in 30 provinces in China, as well as to investigate the impact of new China regulations and plans to mitigate further spread of infections. This article forecasts the size of the disease spreading based on time series forecasting. The growing size of CoVID-19 in China for the next 210 days is estimated by predicting the expected confirmed and recovered cases. The results revealed that weather conditions largely influence the spread of coronavirus in most of the Chinese provinces. This study has determined that increasing temperature and short-wave radiation would positively increase the number of confirmed cases, mortality rate, and recovered cases. The findings of this study agree with the results of our previous study.", "qid": 2, "docid": "al7gffw2", "rank": 45, "score": 0.7500587701797485}, {"content": "Title: The correlation between the spread of COVID-19 infections and weather variables in 30 Chinese provinces and the impact of Chinese government mitigation plans. Content: On February 1, 2020, China announced a novel coronavirus CoVID-19 outbreak to the public. CoVID-19 was classified as an epidemic by the World Health Organization (WHO). Although the disease was discovered and concentrated in Hubei Province, China, it was exported to all of the other Chinese provinces and spread globally. As of this writing, all plans have failed to contain the novel coronavirus disease, and it has continued to spread to the rest of the world. This study aimed to explore and interpret the effect of environmental and metrological variables on the spread of coronavirus disease in 30 provinces in China, as well as to investigate the impact of new China regulations and plans to mitigate further spread of infections. This article forecasts the size of the disease spreading based on time series forecasting. The growing size of CoVID-19 in China for the next 210 days is estimated by predicting the expected confirmed and recovered cases. The results revealed that weather conditions largely influence the spread of coronavirus in most of the Chinese provinces. This study has determined that increasing temperature and short-wave radiation would positively increase the number of confirmed cases, mortality rate, and recovered cases. The findings of this study agree with the results of our previous study.", "qid": 2, "docid": "6a9to2w9", "rank": 46, "score": 0.7500587701797485}, {"content": "Title: Short-Term Effects of Ambient Ozone, PM2.5, and Meteorological Factors on COVID-19 Confirmed Cases and Deaths in Queens, New York Content: The outbreak of coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, has been rapidly increasing in the United States. Boroughs of New York City, including Queens county, turn out to be the epicenters of this infection. According to the data provided by the New York State Department of Health, most of the cases of new COVID-19 infections in New York City have been found in the Queens county where 42,023 people have tested positive, and 3221 people have died as of 20 April 2020. Person-to-person transmission and travels were implicated in the initial spread of the outbreaks, but factors related to the late phase of rapidly spreading outbreaks in March and April are still uncertain. A few previous studies have explored the links between air pollution and COVID-19 infections, but more data is needed to understand the effects of short-term exposures of air pollutants and meteorological factors on the spread of COVID-19 infections, particularly in the U.S. disease epicenters. In this study, we have focused on ozone and PM2.5, two major air pollutants in New York City, which were previously found to be associated with respiratory viral infections. The aim of our regression modeling was to explore the associations among ozone, PM2.5, daily meteorological variables (wind speed, temperature, relative humidity, absolute humidity, cloud percentages, and precipitation levels), and COVID-19 confirmed new cases and new deaths in Queens county, New York during March and April 2020. The results from these analyses showed that daily average temperature, daily maximum eight-hour ozone concentration, average relative humidity, and cloud percentages were significantly and positively associated with new confirmed cases related to COVID-19; none of these variables showed significant associations with new deaths related to COVID-19. The findings indicate that short-term exposures to ozone and other meteorological factors can influence COVID-19 transmission and initiation of the disease, but disease aggravation and mortality depend on other factors.", "qid": 2, "docid": "g6i86tdj", "rank": 47, "score": 0.7497714757919312}, {"content": "Title: Singapore COVID-19 Pandemic Response as a Successful Model Framework for Low-Resource Health Care Settings in Africa? Content: The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus continues to spread and evolve across the planet. The crosscutting impacts of the virus, individual country responses to the virus, and the state of preparedness of local public health systems greatly vary across the world. The ostensibly late arrival of the virus in Africa has allowed learning, innovation, and adaptation of methods that have been successful in the early-hit countries. This article analyzes how Singapore has responded to the COVID-19 pandemic and proposes that adaptations of the Singapore pandemic response model would bode well for Africa's response to the COVID-19 pandemic in ways that also take into account regional differences in health care infrastructures, socioeconomic resilience, poverty, and the vast population diversity in the African continent. As the pandemic evolves, the lessons learned in Asia, in particular, and the emerging new experiences in African countries should inform, ideally in real time, how best to steer the world populations into safety, including those in low-resource health care settings. Finally, we note that the current COVID-19 pandemic is also a test for our collective ability to scale and surge public health in response to future and likely equally challenging zoonosis infections that jump from animals to humans, not to mention climate change-related planetary health calamities in the 21st century. Hence, what we learn effectively from the current COVID-19 pandemic shall have broad, enduring, and intergenerational relevance for the future of planetary heath and society.", "qid": 2, "docid": "2y4sjdtm", "rank": 48, "score": 0.7492837905883789}, {"content": "Title: Temperature, Humidity, and Latitude Analysis to Estimate Potential Spread and Seasonality of Coronavirus Disease 2019 (COVID-19) Content: IMPORTANCE: Coronavirus disease 2019 (COVID-19) infection has resulted in a global crisis. Investigating the potential association of climate and seasonality with the spread of this infection could aid in preventive and surveillance strategies. OBJECTIVE: To examine the association of climate with the spread of COVID-19 infection. DESIGN, SETTING, AND PARTICIPANTS: This cohort study examined climate data from 50 cities worldwide with and without substantial community spread of COVID-19. Eight cities with substantial spread of COVID-19 (Wuhan, China; Tokyo, Japan; Daegu, South Korea; Qom, Iran; Milan, Italy; Paris, France; Seattle, US; and Madrid, Spain) were compared with 42 cities that have not been affected or did not have substantial community spread. Data were collected from January to March 10, 2020. MAIN OUTCOMES AND MEASURES: Substantial community transmission was defined as at least 10 reported deaths in a country as of March 10, 2020. Climate data (latitude, mean 2-m temperature, mean specific humidity, and mean relative humidity) were obtained from ERA-5 reanalysis. RESULTS: The 8 cities with substantial community spread as of March 10, 2020, were located on a narrow band, roughly on the 30\u00b0 N to 50\u00b0 N corridor. They had consistently similar weather patterns, consisting of mean temperatures of between 5 and 11 \u00b0C, combined with low specific humidity (3-6 g/kg) and low absolute humidity (4-7 g/m(3)). There was a lack of substantial community establishment in expected locations based on proximity. For example, while Wuhan, China (30.8\u00b0 N) had 3136 deaths and 80 757 cases, Moscow, Russia (56.0\u00b0 N), had 0 deaths and 10 cases and Hanoi, Vietnam (21.2\u00b0 N), had 0 deaths and 31 cases. CONCLUSIONS AND RELEVANCE: In this study, the distribution of substantial community outbreaks of COVID-19 along restricted latitude, temperature, and humidity measurements was consistent with the behavior of a seasonal respiratory virus. Using weather modeling, it may be possible to estimate the regions most likely to be at a higher risk of substantial community spread of COVID-19 in the upcoming weeks, allowing for concentration of public health efforts on surveillance and containment.", "qid": 2, "docid": "to9awvi9", "rank": 49, "score": 0.7488234043121338}, {"content": "Title: A chemical cocktail during the COVID-19 outbreak in Beijing, China: Insights from six-year aerosol particle composition measurements during the Chinese New Year holiday Content: The rapidly spread coronavirus disease (COVID-19) has limited people's outdoor activities and hence caused substantial reductions in anthropogenic emissions around the world. However, the air quality in some megacities has not been improved as expected due to the complex responses of aerosol chemistry to the changes in precursors and meteorology. Here we demonstrate the responses of primary and secondary aerosol species to the changes in anthropogenic emissions during the COVID-19 outbreak in Beijing, China along with the Chinese New Year (CNY) holiday effects on air pollution by using six-year aerosol particle composition measurements. Our results showed large reductions in primary aerosol species associated with traffic, cooking and coal combustion emissions by 30\u201350% on average during the CNY, while the decreases in secondary aerosol species were much small (5\u201312%). These results point towards a future challenge in mitigating secondary air pollution because the reduced gaseous precursors may not suppress secondary aerosol formation efficiently under stagnant meteorological conditions. By analyzing the long-term measurements from 2012 to 2020, we found considerable increases in the ratios of nitrate to sulfate, secondary to primary OA, and sulfur and nitrogen oxidation capacity despite the overall decreasing trends in mass concentrations of most aerosol species, suggesting that the decreases in anthropogenic emissions have facilitated secondary formation processes during the last decade. Therefore, a better understanding of the mechanisms driving the chemical responses of secondary aerosol to the changes in anthropogenic emissions under complex meteorological environment is essential for future mitigation of air pollution in China.", "qid": 2, "docid": "tyxsyoli", "rank": 50, "score": 0.7482707500457764}, {"content": "Title: A country comparison of place-based activity response to COVID-19 policies Content: The emergence of the novel Coronavirus Disease in late 2019 (COVID-19) and subsequent pandemic led to an immense disruption in the daily lives of almost everyone on the planet. Faced with the consequences of inaction, most national governments responded with policies that restricted the activities conducted by their inhabitants. As schools and businesses shuttered, the mobility of these people decreased. This reduction in mobility, and related activities, was recorded through ubiquitous location-enabled personal mobile devices. Patterns emerged that varied by place-based activity. In this work the differences in these place-based activity patterns are investigated across nations, specifically focusing on the relationship between government enacted policies and changes in community activity patterns. We show that people's activity response to government action varies widely both across nations as well as regionally within them. Three assessment measures are devised and the results correlate with a number of global indices. We discuss these findings and the relationship between government action and residents' response.", "qid": 2, "docid": "hnrok48n", "rank": 51, "score": 0.747243344783783}, {"content": "Title: Causal empirical estimates suggest COVID-19 transmission rates are highly seasonal Content: Nearly every country is now combating the 2019 novel coronavirus (COVID-19). It has been hypothesized that if COVID-19 exhibits seasonality, changing temperatures in the coming months will shift transmission patterns around the world. Such projections, however, require an estimate of the relationship between COVID-19 and temperature at a global scale, and one that isolates the role of temperature from confounding factors, such as public health capacity. This paper provides the first plausibly causal estimates of the relationship between COVID-19 transmission and local temperature using a global sample comprising of 166,686 confirmed new COVID-19 cases from 134 countries from January 22, 2020 to March 15, 2020. We find robust statistical evidence that a 1\u00b0C increase in local temperature reduces transmission by 13% [-21%, -4%, 95%CI]. In contrast, we do not find that specific humidity or precipitation influence transmission. Our statistical approach separates effects of climate variation on COVID-19 transmission from other potentially correlated factors, such as differences in public health responses across countries and heterogeneous population densities. Using constructions of expected seasonal temperatures, we project that changing temperatures between March 2020 and July 2020 will cause COVID-19 transmission to fall by 43% on average for Northern Hemisphere countries and to rise by 71% on average for Southern Hemisphere countries. However, these patterns reverse as the boreal winter approaches, with seasonal temperatures in January 2021 increasing average COVID-19 transmission by 59% relative to March 2020 in northern countries and lowering transmission by 2% in southern countries. These findings suggest that Southern Hemisphere countries should expect greater transmission in the coming months. Moreover, Northern Hemisphere countries face a crucial window of opportunity: if contagion-containing policy interventions can dramatically reduce COVID-19 cases with the aid of the approaching warmer months, it may be possible to avoid a second wave of COVID-19 next winter.", "qid": 2, "docid": "vc2eheb6", "rank": 52, "score": 0.7468377351760864}, {"content": "Title: Relationship between Average Daily Temperature and Average Cumulative Daily Rate of Confirmed Cases of COVID-19 Content: The rapid outbreak of the new Coronavirus (COVID-19) pandemic and the spread of the virus worldwide, especially in the Northern Hemisphere, have prompted various investigations about the impact of environmental factors on the rate of development of this epidemic. Different studies have called the attention to various parameters that may have influenced the spread of the virus, and in particular, the impact of climatic parameters has been emphasized. The main purpose of this study is to investigate the correlation between the average daily temperature and the rate of coronavirus epidemic growth in the infected regions. The main hypothesis object of our research is that between regions exhibiting a significant difference in the mean daily temperature, a significant difference is also observed in the average cumulative daily rate of confirmed cases, and that this does not happen if there is no significant difference in mean daily temperature. To test this research hypothesis, we carried on the case study of three regions in each of five countries and analyzed the correlation through F-test, and Independent-Samples T-Test. In all five selected countries, we found that when there is a significant difference in the daily mean temperature between two regions of a country, a significant difference exists also in the average cumulative daily rate of confirmed cases. Conversely, if there are no significant differences in the mean daily temperature of two regions in the same country, no significant difference is observed in the average cumulative daily rate of confirmed cases for these regions.", "qid": 2, "docid": "ekal5251", "rank": 53, "score": 0.746462345123291}, {"content": "Title: A mechanism-based parameterisation scheme to investigate the association between transmission rate of COVID-19 and meteorological factors on plains in China Content: The novel coronavirus disease 2019 (COVID-19), which first emerged in Hubei province, China, has become a pandemic. However, data regarding the effects of meteorological factors on its transmission are limited and inconsistent. A mechanism-based parameterisation scheme was developed to investigate the association between the scaled transmission rate (STR) of COVID-19 and the meteorological parameters in 20 provinces/municipalities located on the plains in China. We obtained information on the scale of population migrated from Wuhan, the world epicentre of the COVID-19 outbreak, into the study provinces/municipalities using mobile-phone positioning system and big data techniques. The highest STRs were found in densely populated metropolitan areas and in cold provinces located in north-eastern China. Population density had a non-linear relationship with disease spread (linearity index, 0.9). Among various meteorological factors, only temperature was significantly associated with the STR after controlling for the effect of population density. A negative and exponential relationship was identified between the transmission rate and the temperature (correlation coefficient, -0.56; 99% confidence level). The STR increased substantially as the temperature in north-eastern China decreased below 0 \u00b0C (the STR ranged from 3.5 to 12.3 when the temperature was between -9.41 \u00b0C and -13.87 \u00b0C), whilst the STR showed less temperature dependence in the study areas with temperate weather conditions (the STR was 1.21 \u00b1 0.57 when the temperature was above 0 \u00b0C). Therefore, a higher population density was linearly whereas a lower temperature (<0 \u00b0C) was exponentially associated with an increased transmission rate of COVID-19. These findings suggest that the mitigation of COVID-19 spread in densely populated and/or cold regions will be a great challenge.", "qid": 2, "docid": "o2lr936b", "rank": 54, "score": 0.7462678551673889}, {"content": "Title: The Wider Impacts of the Coronavirus Pandemic on the NHS Content: The coronavirus pandemic has had huge impacts on the National Health Service (NHS). Patients suffering from the illness have placed unprecedented demands on acute care, particularly on Intensive Care Units (ICUs). This has led to an effort to dramatically increase the resources available to NHS hospitals in treating these patients, involving re\u2010organisation of hospital facilities, redeployment of existing staff and a drive to bring in recently retired and newly graduated staff to fight the pandemic. These increases in demand and changes to supply have had large knock\u2010on effects on the care provided to the wider population. This paper discusses likely implications for healthcare delivery in the short and medium term of the responses to the coronavirus pandemic, focusing primarily on the implications for non\u2010coronavirus patients. Patterns of past care suggest those most likely to be affected by these disruptions will be older individuals and those living in more deprived areas, potentially exacerbating pre\u2010existing health inequalities. Effects are likely to persist into the longer\u2010run, with particular challenges around recruitment and ongoing staff shortages. This article is protected by copyright. All rights reserved", "qid": 2, "docid": "h72v5o8u", "rank": 55, "score": 0.7462464570999146}, {"content": "Title: Association of COVID-19 pandemic with meteorological parameters over Singapore Content: Meteorological parameters are the critical factors affecting the transmission of infectious diseases such as Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), and influenza. Consequently, infectious disease incidence rates are likely to be influenced by the weather change. This study investigates the role of Singapore's hot tropical weather in COVID-19 transmission by exploring the association between meteorological parameters and the COVID-19 pandemic cases in Singapore. This study uses the secondary data of COVID-19 daily cases from the webpage of Ministry of Health (MOH), Singapore. Spearman and Kendall rank correlation tests were used to investigate the correlation between COVID-19 and meteorological parameters. Temperature, dew point, relative humidity, absolute humidity, and water vapor showed positive significant correlation with COVID-19 pandemic. These results will help the epidemiologists to understand the behavior of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus against meteorological variables. This study finding would be also a useful supplement to help the local healthcare policymakers, Center for Disease Control (CDC), and the World Health Organization (WHO) in the process of strategy making to combat COVID-19 in Singapore.", "qid": 2, "docid": "pwul6lco", "rank": 56, "score": 0.7460967302322388}, {"content": "Title: Distribution of the SARS-CoV-2 Pandemic and Its Monthly Forecast Based on Seasonal Climate Patterns Content: This paper investigates whether the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) pandemic could have been favored by specific weather conditions and other factors. It is found that the 2020 winter weather in the region of Wuhan (Hubei, Central China)\u2014where the virus first broke out in December and spread widely from January to February 2020\u2014was strikingly similar to that of the Northern Italian provinces of Milan, Brescia and Bergamo, where the pandemic broke out from February to March. The statistical analysis was extended to cover the United States of America, which overtook Italy and China as the country with the highest number of confirmed COronaVIrus Disease 19 (COVID-19) cases, and then to the entire world. The found correlation patterns suggest that the COVID-19 lethality significantly worsens (4 times on average) under weather temperatures between 4 \u00b0C and 12 \u00b0C and relative humidity between 60% and 80%. Possible co-factors such as median population age and air pollution were also investigated suggesting an important influence of the former but not of the latter, at least, on a synoptic scale. Based on these results, specific isotherm world maps were generated to locate, month by month, the world regions that share similar temperature ranges. From February to March, the 4\u201312 \u00b0C isotherm zone extended mostly from Central China toward Iran, Turkey, West-Mediterranean Europe (Italy, Spain and France) up to the United State of America, optimally coinciding with the geographic regions most affected by the pandemic from February to March. It is predicted that in the spring, as the weather gets warm, the pandemic will likely worsen in northern regions (United Kingdom, Germany, East Europe, Russia and North America) while the situation will likely improve in the southern regions (Italy and Spain). However, in autumn, the pandemic could come back and affect the same regions again. The Tropical Zone and the entire Southern Hemisphere, but in restricted colder southern regions, could avoid a strong pandemic because of the sufficiently warm weather during the entire year and because of the lower median age of their population. Google-Earth-Pro interactive-maps covering the entire world are provided as supplementary files.", "qid": 2, "docid": "26gf4q1v", "rank": 57, "score": 0.7453315258026123}, {"content": "Title: Containing the Spread of Coronavirus Disease 2019 (COVID-19): Meteorological Factors and Control Strategies Content: The novel coronavirus disease 2019 (COVID-19) has spread globally and the meteorological factors vary greatly across the world. Understanding the effect of meteorological factors and control strategies on COVID-19 transmission is critical to contain the epidemic. Using individual-level data in mainland China, Hong Kong, and Singapore, and the number of confirmed cases in other regions, we explore the effect of temperature, relative humidity, and control measures on the spread of COVID-19. We found that high temperature mitigates the transmission of the disease. High relative humidity promotes COVID-19 transmission when temperature is low, but tends to reduce transmission when temperature is high. Implementing classical control measures can dramatically slow the spread of the disease. However, due to the occurrence of pre-symptomatic infections, the effect of the measures to shorten onset-to-isolation time is markedly reduced and the importance of contact tracing and quarantine and social distancing increases. The analytic results also highlight the importance of early intervention to contain the spread of COVID-19.", "qid": 2, "docid": "vxy41zov", "rank": 58, "score": 0.7452989220619202}, {"content": "Title: A mechanism-based parameterisation scheme to investigate the association between transmission rate of COVID-19 and meteorological factors on plains in China Content: The novel coronavirus disease 2019 (COVID-19), which first emerged in Hubei province, China, has become a pandemic. However, data regarding the effects of meteorological factors on its transmission are limited and inconsistent. A mechanism-based parameterisation scheme was developed to investigate the association between the scaled transmission rate (STR) of COVID-19 and the meteorological parameters in 20 provinces/municipalities located on the plains in China. We obtained information on the scale of population migrated from Wuhan, the world epicentre of the COVID-19 outbreak, into the study provinces/municipalities using mobile-phone positioning system and big data techniques. The highest STRs were found in densely populated metropolitan areas and in cold provinces located in north-eastern China. Population density had a non-linear relationship with disease spread (linearity index, 0.9). Among various meteorological factors, only temperature was significantly associated with the STR after controlling for the effect of population density. A negative and exponential relationship was identified between the transmission rate and the temperature (correlation coefficient, \u22120.56; 99% confidence level). The STR increased substantially as the temperature in north-eastern China decreased below 0 \u00b0C (the STR ranged from 3.5 to 12.3 when the temperature was between \u22129.41 \u00b0C and \u221213.87 \u00b0C), whilst the STR showed less temperature dependence in the study areas with temperate weather conditions (the STR was 1.21 \u00b1 0.57 when the temperature was above 0 \u00b0C). Therefore, a higher population density was linearly whereas a lower temperature (<0 \u00b0C) was exponentially associated with an increased transmission rate of COVID-19. These findings suggest that the mitigation of COVID-19 spread in densely populated and/or cold regions will be a great challenge.", "qid": 2, "docid": "u82bwjuz", "rank": 59, "score": 0.7451200485229492}, {"content": "Title: COVID-19 and Environmental factors. A PRISMA-compliant systematic review Content: The emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its airborne spread via droplets. The impact of environmental factors on the coronavirus disease 2019 (COVID-19) outbreak is under consideration. We therefore reviewed the literature on all available information about the impact of environmental factors on human coronaviruses. Temperature, humidity and other environmental factors have been recorded as environmental drivers of the COVID-19 outbreak in China and in other countries. Higher temperatures might be positive to decrease the COVID-19 incidence. In our review, the analysis of 23 studies show evidence that high temperature and high humidity reduce the COVID-19 transmission. However, further studies concerning other environmental (namely meteorological) factors role should be conducted in order to further prove this correlation. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.", "qid": 2, "docid": "yw0nk7fo", "rank": 60, "score": 0.7445980310440063}, {"content": "Title: Effects of temperature variation and humidity on the death of COVID-19 in Wuhan, China Content: Abstract Meteorological parameters are the important factors influencing the infectious diseases such as severe acute respiratory syndrome (SARS) and influenza. This study aims to explore the association between Corona Virus Disease 2019 (COVID-19) deaths and weather parameters. In this study, we collected the daily death numbers of COVID-19, meteorological parameters and air pollutant data from 20 January 2020 to 29 February 2020 in Wuhan, China. Generalized additive model was applied to explore the effect of temperature, humidity and diurnal temperature range on the daily death counts of COVID-19. There were 2299 COVID-19 death counts in Wuhan during the study period. A positive association with COVID-19 daily death counts was observed for diurnal temperature range (r = 0.44), but negative association for relative humidity (r = \u22120.32). In addition, one unit increase in diurnal temperature range was only associated with a 2.92% (95% CI: 0.61%, 5.28%) increase in COVID-19 deaths in lag 3. However, both 1 unit increase of temperature and absolute humidity were related to the decreased COVID-19 death in lag 3 and lag 5, with the greatest decrease both in lag 3 [\u22127.50% (95% CI: \u221210.99%, \u22123.88%) and \u221211.41% (95% CI: \u221219.68%, \u22122.29%)]. In summary, this study suggests the temperature variation and humidity may also be important factors affecting the COVID-19 mortality.", "qid": 2, "docid": "6anr4xdw", "rank": 61, "score": 0.7443837523460388}, {"content": "Title: Models of transmission of COVID-19 with time under the influence of meteorological determinants Content: Based on the statistical analyses of the data on the number of confirmed COVID-19 cases and meteorological determinants in some of the severely affected cities in Spain, Italy and the USA, some models are constructed showing the relationship of I' (the number of infected individuals divided by the total population of a city) with temperature, relative humidity, wind velocity and time. Three models are based on the data before lockdown/travel restrictions in these cities, and the other three models are based on data both before and after lockdown/travel restrictions. These models, in general, indicate that the transmission of COVID-19 could be relatively high either for elevated temperatures with lower relative humidity or for lower temperatures with higher relative humidity conditions. Although one model indicates exponential increase in number of infection cases with time, the more statistically significant models show that the number of cases varies quadratically with time. We have discussed in short, how all these features could be linked with the alterations of structural characteristics of the SARS-CoV-2 virus. Finally, the possibility of natutal disappearance of COVID-19 pandemic, at the global level, has been discussed in the context of the most statistically significant model.", "qid": 2, "docid": "cga8v8fb", "rank": 62, "score": 0.7441293001174927}, {"content": "Title: A multi-hazards earth science perspective on the COVID-19 pandemic: the potential for concurrent and cascading crises Content: Meteorological and geophysical hazards will concur and interact with coronavirus disease (COVID-19) impacts in many regions on Earth. These interactions will challenge the resilience of societies and systems. A comparison of plausible COVID-19 epidemic trajectories with multi-hazard time-series curves enables delineation of multi-hazard scenarios for selected countries (United States, China, Australia, Bangladesh) and regions (Texas). In multi-hazard crises, governments and other responding agents may be required to make complex, highly compromised, hierarchical decisions aimed to balance COVID-19 risks and protocols with disaster response and recovery operations. Contemporary socioeconomic changes (e.g. reducing risk mitigation measures, lowering restrictions on human activity to stimulate economic recovery) may alter COVID-19 epidemiological dynamics and increase future risks relating to natural hazards and COVID-19 interactions. For example, the aggregation of evacuees into communal environments and increased demand on medical, economic, and infrastructural capacity associated with natural hazard impacts may increase COVID-19 exposure risks and vulnerabilities. COVID-19 epidemiologic conditions at the time of a natural hazard event might also influence the characteristics of emergency and humanitarian responses (e.g. evacuation and sheltering procedures, resource availability, implementation modalities, and assistance types). A simple epidemic phenomenological model with a concurrent disaster event predicts a greater infection rate following events during the pre-infection rate peak period compared with post-peak events, highlighting the need for enacting COVID-19 counter measures in advance of seasonal increases in natural hazards. Inclusion of natural hazard inputs into COVID-19 epidemiological models could enhance the evidence base for informing contemporary policy across diverse multi-hazard scenarios, defining and addressing gaps in disaster preparedness strategies and resourcing, and implementing a future-planning systems approach into contemporary COVID-19 mitigation strategies. Our recommendations may assist governments and their advisors to develop risk reduction strategies for natural and cascading hazards during the COVID-19 pandemic. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10669-020-09772-1) contains supplementary material, which is available to authorized users.", "qid": 2, "docid": "pjbpbf1w", "rank": 63, "score": 0.7440626621246338}, {"content": "Title: Covid-19: implications for prehospital, emergency and hospital care in patients with acute coronary syndromes Content: Hospitals play a critical role in providing communities with essential medical care during all types of disaster. Depending on their scope and nature, disasters can lead to a rapidly increasing service demand that can overwhelm the functional capacity and safety of hospitals and the healthcare system at large. Planning during the community outbreak of coronavirus disease 2019 (Covid-19) is critical for maintaining healthcare services during our response. This paper describes, besides general measures in times of a pandemic, also the necessary changes in the invasive diagnosis and treatment of patients presenting with different entities of acute coronary syndromes including structural adaptations (networks, spokes and hub centres) and therapeutic adjustments.", "qid": 2, "docid": "loczu0lc", "rank": 64, "score": 0.7440008521080017}, {"content": "Title: Meteorological Conditions and Covid-19 in Large U.S. Cities Content: To determine whether prevalence of Coronavirus disease 2019 (Covid-19) is modulated by meteorological conditions, we herein conducted meta-regression of data in large U.S. cities. We selected 33 large U.S. cities with a population of >500,000. The integrated numbers of confirmed Covid-19 cases in the country to which the city belongs on 14 May 2020, the estimated population in 2019 in the country, and monthly meteorological conditions at the city for 4 months (from January to April 2020) were obtained. Meteorological conditions consisted of mean temperature (F), total precipitation (inch), mean wind speed (MPH), mean sky cover, and mean relative humidity (%). Monthly data for 4 months were averaged or integrated. The Covid-19 prevalence was defined as the integrated number of Covid-19 cases divided by the population. Random-effects meta-regression was performed by means of OpenMetaAnalyst. In a meta-regression graph, Covid-19 prevalence (plotted as the logarithm transformed prevalence on the y-axis) was depicted as a function of a given factor (plotted as a meteorological datum on the x-axis). A slope of the meta-regression line was significantly negative (coefficient, -0.069; P < 0.001) for the mean temperature and significantly positive for the mean wind speed (coefficient, 0.174; P = 0.027) and the sky cover (coefficient, 2.220; P = 0.023). In conclusion, lower temperature and higher wind speed/sky cover may be associated with higher Covid-19 prevalence, which should be confirmed by further epidemiological researches adjusting for various risk and protective factors (in addition to meteorological conditions) of Covid-19.", "qid": 2, "docid": "7usv3ljo", "rank": 65, "score": 0.7439409494400024}, {"content": "Title: Mitigating the twin threats of climate-driven Atlantic hurricanes and COVID-19 transmission. Content: The co-occurrence of the 2020 Atlantic hurricane season and the ongoing Coronavirus Disease 2019 (COVID-19) pandemic creates complex dilemmas for protecting populations from these intersecting threats. Climate change is likely contributing to stronger, wetter, slower-moving, and more dangerous hurricanes. Climate-driven hazards underscore the imperative for timely warning, evacuation, and sheltering of storm-threatened populations - proven life-saving protective measures that gather evacuees together inside durable enclosed spaces when a hurricane approaches. Meanwhile, the rapid acquisition of scientific knowledge regarding how COVID-19 spreads has guided mass anti-contagion strategies including lockdowns, sheltering-at-home, physical distancing, donning personal protective equipment, conscientious hand washing, and hygiene practices. These life-saving strategies, credited with preventing millions of COVID-19 cases, separate and move people apart. Enforcement coupled with fear of contracting COVID-19 have motivated high levels of adherence to these stringent regulations. How will populations react when warned to shelter from an oncoming Atlantic hurricane while COVID-19 is actively circulating in the community? Emergency managers, healthcare providers, and public health preparedness professionals must create viable solutions to confront these potential scenarios: elevated rates of hurricane-related injury and mortality among persons who refuse to evacuate due to fear of COVID-19, and resurgence of COVID-19 cases among hurricane evacuees who shelter together.", "qid": 2, "docid": "ess14nld", "rank": 66, "score": 0.743706226348877}, {"content": "Title: Predictive Modeling on the Number of Covid-19 Death Toll in the United States Considering the Effects of Coronavirus-Related Changes and Covid-19 Recovered Cases Content: COVID-19 is caused by a coronavirus called SARS-CoV-2. Many countries around the world implemented their own policies and restrictions designed to limit the spread of Covid-19 in recent months. Businesses and schools transitioned into working and learning remotely. In the United States, many states were under strict orders to stay home at least in the month of April. In recent weeks, there are some significant changes related restrictions include social-distancing, reopening states, and staying-at-home orders. The United States surpassed 2 million coronavirus cases on Monday, June 15, 2020 less than five months after the first case was confirmed in the country. The virus has killed at least 115,000 people in the United States as of Monday, June 15, 2020, according to data from Johns Hopkins University. With the recent easing of coronavirus-related restrictions and changes on business and social activity such as stay-at-home, social distancing since late May 2020 hoping to restore economic and business activities, new Covid-19 outbreaks are on the rise in many states across the country. Some researchers expressed concern that the process of easing restrictions and relaxing stay-at-home orders too soon could quickly surge the number of infected Covid-19 cases as well as the death toll in the United States. Some of these increases, however, could be due to more testing sites in the communities while others may be are the results of easing restrictions due to recent reopening and changed policies, though the number of daily death toll does not appear to be going down in recent days due to Covid-19 in the U.S. This raises the challenging question: * How can policy decision-makers and community leaders make the decision to implement public policies and restrictions and keep or lift staying-at-home orders of ongoing Covid-19 pandemic for their communities in a scientific way? In this study, we aim to develop models addressing the effects of recent Covid-19 related changes in the communities such as reopening states, practicing social-distancing, and staying-at-home orders. Our models account for the fact that changes to these policies which can lead to a surge of coronavius cases and deaths, especially in the United States. Specifically, in this paper we develop a novel generalized mathematical model and several explicit models considering the effects of recent reopening states, staying-at-home orders and social-distancing practice of different communities along with a set of selected indicators such as the total number of coronavirus recovered and new cases that can estimate the daily death toll and total number of deaths in the United States related to Covid-19 virus. We compare the modeling results among the developed models based on several existing criteria. The model also can be used to predict the number of death toll in Italy and the United Kingdom (UK). The results show very encouraging predictability for the proposed models in this study. The model predicts that 128,500 to 140,100 people in the United States will have died of Covid-19 by July 4, 2020. The model also predicts that between 137,900 and 154,000 people will have died of Covid-19 by July 31, and 148,500 to 169,700 will have died by the end of August 2020, as a result of the SARS-CoV-2 coronavirus that causes COVID-19 based on the Covid-19 death data available on June 13, 2020. The model also predicts that 34,900 to 37,200 people in Italy will have died of Covid-19 by July 4, and 36,900 to 40,400 people will have died by the end of August based on the data available on June 13, 2020. The model also predicts that between 43,500 and 46,700 people in the United Kingdom will have died of Covid-19 by July 4, and 48,700 to 51,900 people will have died by the end of August, as a result of the SARS-CoV-2 coronavirus that causes COVID-19 based on the data available on June 13, 2020. The model can serve as a framework to help policy makers a scientific approach in quantifying decision-makings related to Covid-19 affairs.", "qid": 2, "docid": "4o8bedj8", "rank": 67, "score": 0.7434006929397583}, {"content": "Title: Distribution of the SARS-CoV-2 Pandemic and Its Monthly Forecast Based on Seasonal Climate Patterns Content: This paper investigates whether the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) pandemic could have been favored by specific weather conditions and other factors. It is found that the 2020 winter weather in the region of Wuhan (Hubei, Central China)-where the virus first broke out in December and spread widely from January to February 2020-was strikingly similar to that of the Northern Italian provinces of Milan, Brescia and Bergamo, where the pandemic broke out from February to March. The statistical analysis was extended to cover the United States of America, which overtook Italy and China as the country with the highest number of confirmed COronaVIrus Disease 19 (COVID-19) cases, and then to the entire world. The found correlation patterns suggest that the COVID-19 lethality significantly worsens (4 times on average) under weather temperatures between 4 &#8728; C and 12 &#8728; C and relative humidity between 60% and 80%. Possible co-factors such as median population age and air pollution were also investigated suggesting an important influence of the former but not of the latter, at least, on a synoptic scale. Based on these results, specific isotherm world maps were generated to locate, month by month, the world regions that share similar temperature ranges. From February to March, the 4-12 &#8728; C isotherm zone extended mostly from Central China toward Iran, Turkey, West-Mediterranean Europe (Italy, Spain and France) up to the United State of America, optimally coinciding with the geographic regions most affected by the pandemic from February to March. It is predicted that in the spring, as the weather gets warm, the pandemic will likely worsen in northern regions (United Kingdom, Germany, East Europe, Russia and North America) while the situation will likely improve in the southern regions (Italy and Spain). However, in autumn, the pandemic could come back and affect the same regions again. The Tropical Zone and the entire Southern Hemisphere, but in restricted colder southern regions, could avoid a strong pandemic because of the sufficiently warm weather during the entire year and because of the lower median age of their population. Google-Earth-Pro interactive-maps covering the entire world are provided as supplementary files.", "qid": 2, "docid": "04rbtmmi", "rank": 68, "score": 0.7432464957237244}, {"content": "Title: Taking the pulse of COVID-19: A spatiotemporal perspective Content: The sudden outbreak of the Coronavirus disease (COVID-19) swept across the world in early 2020, triggering the lockdowns of several billion people across many countries, including China, Spain, India, the U.K., Italy, France, Germany, and most states of the U.S. The transmission of the virus accelerated rapidly with the most confirmed cases in the U.S., and New York City became an epicenter of the pandemic by the end of March. In response to this national and global emergency, the NSF Spatiotemporal Innovation Center brought together a taskforce of international researchers and assembled implemented strategies to rapidly respond to this crisis, for supporting research, saving lives, and protecting the health of global citizens. This perspective paper presents our collective view on the global health emergency and our effort in collecting, analyzing, and sharing relevant data on global policy and government responses, geospatial indicators of the outbreak and evolving forecasts; in developing research capabilities and mitigation measures with global scientists, promoting collaborative research on outbreak dynamics, and reflecting on the dynamic responses from human societies.", "qid": 2, "docid": "fm19j30n", "rank": 69, "score": 0.7429150342941284}, {"content": "Title: Association between ambient temperature and COVID-19 infection in 122 cities from China Content: Abstract Background Coronavirus disease 2019 (COVID-19) has become a severe public health problem globally. Both epidemiological and laboratory studies have shown that ambient temperature could affect the transmission and survival of coronaviruses. This study aimed to determine whether the temperature is an essential factor in the infection caused by this novel coronavirus. Methods Daily confirmed cases and meteorological factors in 122 cities were collected between January 23, 2020, to February 29, 2020. A generalized additive model (GAM) was applied to explore the nonlinear relationship between mean temperature and COVID-19 confirmed cases. We also used a piecewise linear regression to determine the relationship in detail. Results The exposure-response curves suggested that the relationship between mean temperature and COVID-19 confirmed cases was approximately linear in the range of <3 \u00b0C and became flat above 3 \u00b0C. When mean temperature (lag0\u201314) was below 3 \u00b0C, each 1 \u00b0C rise was associated with a 4.861% (95% CI: 3.209\u20136.513) increase in the daily number of COVID-19 confirmed cases. These findings were robust in our sensitivity analyses. Conclusions Our results indicate that mean temperature has a positive linear relationship with the number of COVID-19 cases with a threshold of 3 \u00b0C. There is no evidence supporting that case counts of COVID-19 could decline when the weather becomes warmer, which provides useful implications for policymakers and the public.", "qid": 2, "docid": "u19e9j2w", "rank": 70, "score": 0.7427657842636108}, {"content": "Title: The most eagerly awaited summer of the Anthropocene: A perspective of SARS-CoV-2 decay and seasonal change Content: To date, the world perhaps has never waited for the summer so impatiently in the entire Anthropocene, owing to the debate whether increasing temperature and humidity will decrease the environmental endurance of SARS-CoV-2. We present the perspective on the seasonal change on SARS-CoV-2 decay and COVID-19 spread. Our arguments are based on: i) structural similarity of coronavirus with several enteric viruses, and its vulnerability; ii) reports related to decay of those similar transmissible gastroenteritis viruses (TGEV) like norovirus and iii) improvement in the human immunity during summer with respect to winter. We present reasons why we can be optimistic about the slowdown of corona in the upcoming summer.", "qid": 2, "docid": "9v83g7dj", "rank": 71, "score": 0.7422964572906494}, {"content": "Title: New Coronavirus Infection (Covid-19): Clinical and Epidemiological Aspects ;\u041d\u043e\u0432\u0430\u044f \u043a\u043e\u0440\u043e\u043d\u0430\u0432\u0438\u0440\u0443\u0441\u043d\u0430\u044f \u0438\u043d\u0444\u0435\u043a\u0446\u0438\u044f (COVID-19): \u043a\u043b\u0438\u043d\u0438\u043a\u043e-\u044d\u043f\u0438\u0434\u0435\u043c\u0438\u043e\u043b\u043e\u0433\u0438\u0447\u0435\u0441\u043a\u0438\u0435 \u0430\u0441\u043f\u0435\u043a\u0442\u044b Content: Environmental change, climate warming, population density increase, high migration activity of the population and other factors provoke the emergence and spread of new infections around the world The emergence in December 2019 of diseases caused by the new coronavirus (\u00abcoronavirus disease 2019\u00bb) has already gone down in history as an emergency of international importance It is known that the most common clinical manifestation of a new infection is pneumonia, and also in a significant part of patients \u2014 respiratory distress syndrome Our article provides a brief analytical review of these temporary guidelines Ministry of Health of the Russian Federation \u00abPrevention, Diagnosis and Treatment of a New Coronavirus Infection (COVID-19)\u00bb, version 3 (03 03 20) and other published sources The team of authors expresses the hope that these data will be useful to doctors in providing medical care to patients with a new coronary virus infection, as well as to teachers in preparing students and residents Source: Ministry of Health of the Russian Federation Temporary guidelines \u00abPrevention, diagnosis and treatment of new coronavirus infection (COVID-19)\u00bb, version 4 (27 03 20) Available on: https://static-3 rosminzdrav ru/system/attachments/attaches/000/049/881/original/COVID19_recomend_v4 pdf 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\u0440\u0435\u043a\u043e\u043c\u0435\u043d\u0434\u0430\u0446\u0438\u0438 \u00ab\u041f\u0440\u043e\u0444\u0438\u043b\u0430\u043a\u0442\u0438\u043a\u0430, \u0434\u0438\u0430\u0433\u043d\u043e\u0441\u0442\u0438\u043a\u0430 \u0438 \u043b\u0435\u0447\u0435\u043d\u0438\u0435 \u043d\u043e\u0432\u043e\u0439 \u043a\u043e\u0440\u043e\u043d\u0430\u0432\u0438\u0440\u0443\u0441\u043d\u043e\u0439 \u0438\u043d\u0444\u0435\u043a\u0446\u0438\u0438 (COVID-19)\u00bb, \u0432\u0435\u0440\u0441\u0438\u044f 4 (27 03 20) \u0414\u043e\u0441\u0442\u0443\u043f\u043d\u043e \u043d\u0430: https://static-3 rosminzdrav ru/system/attachments/attaches/000/049/881/original/COVID19_recomend_v pdf", "qid": 2, "docid": "kqj4wwx5", "rank": 72, "score": 0.7421291470527649}, {"content": "Title: Air quality changes during the COVID-19 lockdown over the Yangtze River Delta Region: An insight into the impact of human activity pattern changes on air pollution variation Content: The outbreak of COVID-19 has spreaded rapidly across the world. To control the rapid dispersion of the virus, China has imposed national lockdown policies to practise social distancing. This has led to reduced human activities and hence primary air pollutant emissions, which caused improvement of air quality as a side-product. To investigate the air quality changes during the COVID-19 lockdown over the YRD Region, we apply the WRF-CAMx modelling system together with monitoring data to investigate the impact of human activity pattern changes on air quality. Results show that human activities were lowered significantly during the period: industrial operations, VKT, constructions in operation, etc. were significantly reduced, leading to lowered SO2, NOx, PM2.5 and VOCs emissions by approximately 16-26%, 29-47%, 27-46% and 37-57% during the Level I and Level II response periods respectively. These emission reduction has played a significant role in the improvement of air quality. Concentrations of PM2.5, NO2 and SO2 decreased by 31.8%, 45.1% and 20.4% during the Level I period; and 33.2%, 27.2% and 7.6% during the Level II period compared with 2019. However, ozone did not show any reduction and increased greatly. Our results also show that even during the lockdown, with primary emissions reduction of 15%-61%, the daily average PM2.5 concentrations range between 15 and 79 \u00b5g m-3, which shows that background and residual pollutions are still high. Source apportionment results indicate that the residual pollution of PM2.5 comes from industry (32.2-61.1%), mobile (3.9-8.1%), dust (2.6-7.7%), residential sources (2.1-28.5%) in YRD and 14.0-28.6% contribution from long-range transport coming from northern China. This indicates that in spite of the extreme reductions in primary emissions, it cannot fully tackle the current air pollution. Re-organisation of the energy and industrial strategy together with trans-regional joint-control for a full long-term air pollution plan need to be further taken into account.", "qid": 2, "docid": "25rrzrgw", "rank": 73, "score": 0.7419984340667725}, {"content": "Title: Susceptible supply limits the role of climate in the early SARS-CoV-2 pandemic Content: Preliminary evidence suggests that climate may modulate the transmission of SARS-CoV-2. Yet it remains unclear whether seasonal and geographic variations in climate can substantially alter the pandemic trajectory, given high susceptibility is a core driver. Here, we use a climate-dependent epidemic model to simulate the SARS-CoV-2 pandemic probing different scenarios based on known coronavirus biology. We find that while variations in weather may be important for endemic infections, during the pandemic stage of an emerging pathogen the climate drives only modest changes to pandemic size. A preliminary analysis of non-pharmaceutical control measures indicates that they may moderate the pandemic-climate interaction via susceptible depletion. Our findings suggest, without effective control measures, strong outbreaks are likely in more humid climates and summer weather will not substantially limit pandemic growth.", "qid": 2, "docid": "aiwxlxzt", "rank": 74, "score": 0.7416415214538574}, {"content": "Title: Impact of meteorological factors on the COVID-19 transmission: A multi-city study in China Content: The purpose of the present study is to explore the associations between novel coronavirus disease 2019 (COVID-19) case counts and meteorological factors in 30 provincial capital cities of China. We compiled a daily dataset including confirmed case counts, ambient temperature (AT), diurnal temperature range (DTR), absolute humidity (AH) and migration scale index (MSI) for each city during the period of January 20th to March 2nd, 2020. First, we explored the associations between COVID-19 confirmed case counts, meteorological factors, and MSI using non-linear regression. Then, we conducted a two-stage analysis for 17 cities with more than 50 confirmed cases. In the first stage, generalized linear models with negative binomial distribution were fitted to estimate city-specific effects of meteorological factors on confirmed case counts. In the second stage, the meta-analysis was conducted to estimate the pooled effects. Our results showed that among 13 cities that have less than 50 confirmed cases, 9 cities locate in the Northern China with average AT below 0 \u00b0C, 12 cities had average AH below 4 g/m3, and one city (Haikou) had the highest AH (14.05 g/m3). Those 17 cities with 50 and more cases accounted for 90.6% of all cases in our study. Each 1 \u00b0C increase in AT and DTR was related to the decline of daily confirmed case counts, and the corresponding pooled RRs were 0.80 (95% CI: 0.75, 0.85) and 0.90 (95% CI: 0.86, 0.95), respectively. For AH, the association with COVID-19 case counts were statistically significant in lag 07 and lag 014. In addition, we found the all these associations increased with accumulated time duration up to 14 days. In conclusions, meteorological factors play an independent role in the COVID-19 transmission after controlling population migration. Local weather condition with low temperature, mild diurnal temperature range and low humidity likely favor the transmission.", "qid": 2, "docid": "c32lvwcc", "rank": 75, "score": 0.7416013479232788}, {"content": "Title: Effect of weather on COVID-19 spread in the US: A prediction model for India in 2020 Content: Abstract The effect of weather on COVID-19 spread is poorly understood. Recently, few studies have claimed that warm weather can possibly slowdown the global pandemic, which has already affected over 1.6 million people worldwide. Clarification of such relationships in the worst affected country, the US, can be immensely beneficial to understand the role of weather in transmission of the disease in the highly populated countries, such as India. We collected the daily data of new cases in 50 US states between Jan 1\u2013Apr 9, 2020 and also the corresponding weather information (i.e., temperature (T) and absolute humidity (AH)). Distribution modeling of new cases across AH and T, helped identify the narrow and vulnerable AH range. We validated the results for 10-day intervals against monthly observations, and also worldwide trends. The results were used to predict Indian regions which would be vulnerable to weather based spread in upcoming months of 2020. COVID-19 spread in the US is significant for states with 4 < AH < 6 g/m3 and number of new cases > 10,000, irrespective of the chosen time intervals for study parameters. These trends are consistent with worldwide observations, but do not correlate well with India so far possibly due the total cases reported per interval < 10,000. The results clarify the relationship between weather parameters and COVID-19 spread. The vulnerable weather parameters will help classify the risky geographic areas in different countries. Specifically, with further reporting of new cases in India, prediction of states with high risk of weather based spread will be apparent.", "qid": 2, "docid": "1llox90t", "rank": 76, "score": 0.7413779497146606}, {"content": "Title: Short-term effects of weather parameters on COVID-19 morbidity in select US cities Content: Abstract Little is known about the environmental conditions that drive the spatiotemporal patterns of SARS-CoV-2, and preliminary research suggests an association with weather parameters. However, the relationship with temperature and humidity is not yet apparent for COVID-19 cases in US cities first impacted. The objective of this study is to evaluate the association between COVID-19 cases and weather parameters in select US cities. A case-crossover design with a distributed lag nonlinear model was used to evaluate the contribution of ambient temperature and specific humidity on COVID-19 cases in select US cities. The case-crossover examines each COVID case as its own control at different time periods (before and after transmission occurred). We modeled the effect of temperature and humidity on COVID-19 transmission using a lag period of 7 days. A subset of 8 cities were evaluated for the relationship with weather parameters and 5 cities were evaluated in detail. Short-term exposure to humidity was positively associated with COVID-19 transmission in 4 cities. The associations were small with \u00be cities exhibiting higher COVID19 transmission with specific humidity that ranged from 6 to 9 g/kg. Our results suggest that weather should be considered in infectious disease modeling efforts and future work is needed over a longer time period and across different locations to clearly establish the weather-COVID19 relationship.", "qid": 2, "docid": "dbtc0bo3", "rank": 77, "score": 0.7405205965042114}, {"content": "Title: Containing the spread of coronavirus disease 2019 (COVID-19): Meteorological factors and control strategies Content: Abstract The novel coronavirus disease 2019 (COVID-19) has spread globally and the meteorological factors vary greatly across the world. Understanding the effect of meteorological factors and control strategies on COVID-19 transmission is critical to contain the epidemic. Using individual-level data in mainland China, Hong Kong, and Singapore, and the number of confirmed cases in other regions, we explore the effect of temperature, relative humidity, and control measures on the spread of COVID-19. We find that high temperature mitigates the transmission of the disease. High relative humidity promotes COVID-19 transmission when temperature is low, but tends to reduce transmission when temperature is high. Implementing classical control measures can dramatically slow the spread of the disease. However, due to the occurrence of pre-symptomatic infections, the effect of the measures to shorten treatment time is markedly reduced and the importance of contact quarantine and social distancing increases.", "qid": 2, "docid": "6imghzg1", "rank": 78, "score": 0.7403932809829712}, {"content": "Title: Temperature significantly changes COVID-19 transmission in (sub)tropical cities of Brazil Content: The coronavirus disease 2019 (COVID-19) outbreak has become a severe public health issue. The novelty of the virus prompts a search for understanding of how ecological factors affect the transmission and survival of the virus. Several studies have robustly identified a relationship between temperature and the number of cases. However, there is no specific study for a tropical climate such as Brazil. This work aims to determine the relationship of temperature to COVID-19 infection for the state capital cities of Brazil. Cumulative data with the daily number of confirmed cases was collected from February 27 to April 1, 2020, for all 27 state capital cities of Brazil affected by COVID-19. A generalized additive model (GAM) was applied to explore the linear and nonlinear relationship between annual average temperature compensation and confirmed cases. Also, a polynomial linear regression model was proposed to represent the behavior of the growth curve of COVID-19 in the capital cities of Brazil. The GAM dose-response curve suggested a negative linear relationship between temperatures and daily cumulative confirmed cases of COVID-19 in the range from 16.8 \u00b0C to 27.4 \u00b0C. Each 1 \u00b0C rise of temperature was associated with a -4.8951% (t = -2.29, p = 0.0226) decrease in the number of daily cumulative confirmed cases of COVID-19. A sensitivity analysis assessed the robustness of the results of the model. The predicted R-squared of the polynomial linear regression model was 0.81053. In this study, which features the tropical temperatures of Brazil, the variation in annual average temperatures ranged from 16.8 \u00b0C to 27.4 \u00b0C. Results indicated that temperatures had a negative linear relationship with the number of confirmed cases. The curve flattened at a threshold of 25.8 \u00b0C. There is no evidence supporting that the curve declined for temperatures above 25.8 \u00b0C. The study had the goal of supporting governance for healthcare policymakers.", "qid": 2, "docid": "dekdf7vu", "rank": 79, "score": 0.7403411269187927}, {"content": "Title: Predict the next moves of COVID-19: reveal the temperate and tropical countries scenario Content: The spread of COVID-19 engulfs almost all the countries and territories of the planet, and infections and fatality are increasing rapidly. The first epi-center of its' massive spread was in Wuhan, Hubei province, China having a temperate weather, but the spread has got an unprecedented momentum in European temperate countries mainly in Italy and Spain (as of March 30, 2020). However, Malaysia and Singapore and the neighboring tropical countries of China got relatively low spread and fatality that created a research interest on whether there are potential impacts of weather condition on COVID-19 spread. Adopting the SIR (Susceptible Infected Removed) deviated model to predict potential cases and death in the coming days from COVID-19 was done using the secondary and official sources of data. This study shows that COVID-19 spread and fatality tend to be high across the world but compared to tropical countries, it is going to be incredibly high in the temperate countries having lower temperature (7-16\u00b0C) and humidity (80-90%) in last March. However, some literature predicted that this might not to be true, rather irrespective of weather conditions there might be a continuous spread and death. Moreover, a large number of asymptotic COVID-19 carrier in both temperate and tropical countries may re-outbreak in the coming winter. Therefore, a comprehensive global program with the leadership of WHO for testing of entire population of the world is required, which will be very useful for the individual states to take proper political action, social movement and medical services.", "qid": 2, "docid": "xcacty89", "rank": 80, "score": 0.7399529814720154}, {"content": "Title: Environments, Behaviors, and Inequalities: Reflecting on the Impacts of the Influenza and Coronavirus Pandemics in the United States Content: In the past century, dramatic shifts in demographics, globalization and urbanization have facilitated the rapid spread and transmission of infectious diseases across continents and countries. In a matter of weeks, the 2019 coronavirus pandemic devastated communities worldwide and reinforced the human perception of frailty and mortality. Even though the end of this pandemic story has yet to unfold, there is one parallel that is undeniable when a comparison is drawn between the 2019 coronavirus and the 1918 influenza pandemics. The public health response to disease outbreaks has remained nearly unchanged in the last 101 years. Furthermore, the role of environments and human behaviors on the effect and response to the coronavirus pandemic has brought to light many of the historic and contemporaneous inequalities and injustices that plague the United States. Through a reflection of these pandemic experiences, the American burden of disparity and disproportionality on morbidity, mortality and overall social determinants of health has been examined. Finally, a reimagination of a post-coronavirus existence has also been presented along with a discussion of possible solutions and considerations for moving forward to a new and better normal.", "qid": 2, "docid": "tel8guc6", "rank": 81, "score": 0.7398319244384766}, {"content": "Title: Association of COVID-19 pandemic with meteorological parameters over Singapore Content: Abstract Meteorological parameters are the critical factors affecting the transmission of infectious diseases such as Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), and influenza. Consequently, infectious disease incidence rates are likely to be influenced by the weather change. This study investigates the role of Singapore's hot tropical weather in COVID-19 transmission by exploring the association between meteorological parameters and the COVID-19 pandemic cases in Singapore. This study uses the secondary data of COVID-19 daily cases from the webpage of Ministry of Health (MOH), Singapore. Spearman and Kendall rank correlation tests were used to investigate the correlation between COVID-19 and meteorological parameters. Temperature, dew point, relative humidity, absolute humidity, and water vapor showed positive significant correlation with COVID-19 pandemic. These results will help the epidemiologists to understand the behavior of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus against meteorological variables. This study finding would be also a useful supplement to help the local healthcare policymakers, Center for Disease Control (CDC), and the World Health Organization (WHO) in the process of strategy making to combat COVID-19 in Singapore.", "qid": 2, "docid": "1bxt21za", "rank": 82, "score": 0.739659309387207}, {"content": "Title: The COVID-19 pandemic's impact on U.S. electricity demand and supply: an early view from the data Content: After the onset of the recent COVID-19 pandemic, a number of studies reported on possible changes in electricity consumption trends. The overall theme of these reports was that ``electricity use has decreased during the pandemic, but the power grid is still reliable''---mostly due to reduced economic activity. In this paper we analyze electricity data upto end of May 2020, examining both electricity demand and variables that can indicate stress on the power grid, such as peak demand and demand ramp-rate. We limit this study to three states in the USA: New York, California, and Florida. The results indicate that the effect of the pandemic on electricity demand is not a simple reduction from comparable time frames, and there are noticeable differences among regions. The variables that can indicate stress on the grid also conveyed mixed messages: some indicate an increase in stress, some indicate a decrease, and some do not indicate any clear difference. A positive message is that some of the changes that were observed around the time stay-at-home orders were issued appeared to revert back by May 2020. A key challenge in ascribing any observed change to the pandemic is correcting for weather. We provide a weather-correction method, apply it to a small city-wide area, and discuss the implications of the estimated changes in demand. The weather correction exercise underscored that weather-correction is as challenging as it is important.", "qid": 2, "docid": "mja93ena", "rank": 83, "score": 0.7396575212478638}, {"content": "Title: Weather variables impact on COVID-19 incidence Content: We test the hypothesis of COVID-19 contagion being influenced by meteorological parameters such as temperature or humidity. We analysed data at high spatial resolution (regions in Italy and counties in the USA) and found that while at low resolution this might seem the case, at higher resolution no correlation is found. Our results are consistent with a poor outdoors transmission of the disease. However, a possible indirect correlation between good weather and a decrease in disease spread may occur, as people spend longer time outdoors.", "qid": 2, "docid": "hadnxjeo", "rank": 84, "score": 0.7394751310348511}, {"content": "Title: Seasonality of infectious diseases and severe acute respiratory syndrome\u2013what we don't know can hurt us Content: Summary The novel severe acute respiratory syndrome (SARS) coronavirus caused severe disease and heavy economic losses before apparently coming under complete control. Our understanding of the forces driving seasonal disappearance and recurrence of infectious diseases remains fragmentary, thus limiting any predictions about whether, or when, SARS will recur. It is true that most established respiratory pathogens of human beings recur in wintertime, but a new appreciation for the high burden of disease in tropical areas reinforces questions about explanations resting solely on cold air or low humidity. Seasonal variation in host physiology may also contribute. Newly emergent zoonotic diseases such as ebola or pandemic strains of influenza have recurred in unpredictable patterns. Most established coronaviruses exhibit winter seasonality, with a unique ability to establish persistent infections in a minority of infected animals. Because SARS coronavirus RNA can be detected in the stool of some individuals for at least 9 weeks, recurrence of SARS from persistently shedding human or animal reservoirs is biologically plausible.", "qid": 2, "docid": "ax87r0bj", "rank": 85, "score": 0.739391565322876}, {"content": "Title: The dark cloud with a silver lining: Assessing the impact of the SARS COVID-19 pandemic on the global environment Content: The Severe Acute Respiratory Syndrome-Coronavirus Disease 2019 (COVID-19) pandemic caused by a novel coronavirus known as SARS-CoV-2 has caused tremendous suffering and huge economic losses. We hypothesized that extreme measures of partial-to-total shutdown might have influenced the quality of the global environment because of decreased emissions of atmospheric pollutants. We tested this hypothesis using satellite imagery, climatic datasets (temperature, and absolute humidity), and COVID-19 cases available in the public domain. While the majority of the cases were recorded from Western countries, where mortality rates were strongly positively correlated with age, the number of cases in tropical regions was relatively lower than European and North American regions, possibly attributed to faster human-to-human transmission. There was a substantial reduction in the level of nitrogen dioxide (NO2: 0.00002 mol m-2), a low reduction in CO (<0.03 mol m-2), and a low-to-moderate reduction in Aerosol Optical Depth (AOD: ~0.1-0.2) in the major hotspots of COVID-19 outbreak during February-March 2020, which may be attributed to the mass lockdowns. Our study projects an increasing coverage of high COVID-19 hazard at absolute humidity levels ranging from 4 to 9 g m-3 across a large part of the globe during April-July 2020 due to a high prospective meteorological suitability for COVID-19 spread. Our findings suggest that there is ample scope for restoring the global environment from the ill-effects of anthropogenic activities through temporary shutdown measures.", "qid": 2, "docid": "uuhwpjis", "rank": 86, "score": 0.7392105460166931}, {"content": "Title: 21-Day Lockdown in India Dramatically Reduced Air Pollution Indices in Lucknow and New Delhi, India Content: In December 2019, the outbreak of viral disease labeled as Novel Coronavirus started in Wuhan, China, which later came to be known as Covid-19. The disease has spread in almost every part of the world and has been declared a global pandemic in March 2020 by World Health Organization (WHO). The corona virus outbreak has emerged as one of the deadliest pandemics of all time in human history. The ongoing pandemic of COVID-19 has forced several countries of the world to observe complete lockdown forcing people to live in their homes. India also faced the phase of total lockdown for 21 days (in first phase) to avoid the spread of coronavirus to the maximum possible extent. This lockdown impacted the pollution levels of environment and improved air and water quality in the short span owing to very less human activities. The present work scientifically analyzed the available data for primary air pollutants (PM(2.5), NO(2), SO(2) and CO) from two major Indian cities, Lucknow and New Delhi. The analysis was based on air quality data for before lockdown and after lockdown (first phase of 21 days) periods of 21 days each. The results showed significant decline in the studied air pollution indices and demonstrated improvement of air quality in both the cities. The major impact was seen in the levels of PM(2.5), NO(2) and CO. The levels of SO(2) showed less significant decline during the lockdown period. The results are presented with future perspectives to mitigate air pollution in near future by adopting the short and periodical lockdown as a tool. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00128-020-02895-w) contains supplementary material, which is available to authorized users.", "qid": 2, "docid": "prl8xbnm", "rank": 87, "score": 0.7390550374984741}, {"content": "Title: Optimal temperature zone for the dispersal of COVID-19 Content: It is essential to know the environmental parameters within which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can survive to understand its global dispersal pattern. We found that 60.0% of the confirmed cases of coronavirus disease 2019 (COVID-19) occurred in places where the air temperature ranged from 5 \u00b0C to 15 \u00b0C, with a peak in cases at 11.54 \u00b0C. Moreover, approximately 73.8% of the confirmed cases were concentrated in regions with absolute humidity of 3 g/m3 to 10 g/m3. SARS-CoV-2 appears to be spreading toward higher latitudes. Our findings suggest that there is an optimal climatic zone in which the concentration of SARS-CoV-2 markedly increases in the ambient environment (including the surfaces of objects). These results strongly imply that the COVID-19 pandemic may spread cyclically and outbreaks may recur in large cities in the mid-latitudes in autumn 2020.", "qid": 2, "docid": "gdl4l9xo", "rank": 88, "score": 0.7390194535255432}, {"content": "Title: Effects of the COVID-19 Pandemic on Population Mobility under Mild Policies: Causal Evidence from Sweden Content: Sweden has adopted far less restrictive social distancing policies than most countries following the COVID-19 pandemic. This paper uses data on all mobile phone users, from one major Swedish mobile phone network, to examine the impact of the Coronavirus outbreak under the Swedish mild recommendations and restrictions regime on individual mobility and if changes in geographical mobility vary over different socio-economic strata. Having access to data for January-March in both 2019 and 2020 enables the estimation of causal effects of the COVID-19 outbreak by adopting a Difference-in-Differences research design. The paper reaches four main conclusions: (i) The daytime population in residential areas increased significantly (64 percent average increase); (ii) The daytime presence in industrial and commercial areas decreased significantly (33 percent average decrease); (iii) The distance individuals move from their homes during a day was substantially reduced (38 percent decrease in the maximum distance moved and 36 percent increase in share of individuals who move less than one kilometer from home); (iv) Similar reductions in mobility were found for residents in areas with different socioeconomic and demographic characteristics. These results show that mild government policies can compel people to adopt social distancing behavior.", "qid": 2, "docid": "lb3j1buz", "rank": 89, "score": 0.7390172481536865}, {"content": "Title: Anomalous atmospheric circulation favored the spread of COVID-19 in Europe Content: The current pandemic caused by the coronavirus SARS-CoV-2 is having negative health, social and economic consequences worldwide. In Europe, the pandemic started to develop strongly at the end of February and beginning of March 2020. It has subsequently spread over the continent, with special virulence in northern Italy and inland Spain. In this study we show that an unusual persistent anticyclonic situation prevailing in southwestern Europe during February 2020 (i.e. anomalously strong positive phase of the North Atlantic and Arctic Oscillations) could have resulted in favorable conditions, in terms of air temperature and humidity, in Italy and Spain for a quicker spread of the virus compared with the rest of the European countries. It seems plausible that the strong atmospheric stability and associated dry conditions that dominated in these regions may have favored the virus's propagation, by short-range droplet transmission as well as likely by long-range aerosol (airborne) transmission.", "qid": 2, "docid": "frlc6694", "rank": 90, "score": 0.7390031814575195}, {"content": "Title: Meteorological factors and domestic new cases of coronavirus disease (COVID-19) in nine Asian cities: A time-series analysis Content: AIM To investigate the associations of meteorological factors and the daily new cases of coronavirus disease (COVID-19) in nine Asian cities. METHOD Pearson correlation and generalized additive modeling were performed to assess the relationships between daily new COVID-19 cases and meteorological factors (daily average temperature and relative humidity) with the most updated data currently available. RESULTS The Pearson correlation showed that daily new confirmed cases of COVID-19 were more correlated with the average temperature than with relative humidity. Daily new confirmed cases were negatively correlated with the average temperature in Beijing (r=-0.565, P<0.01), Shanghai (r=-0.471, P<0.01), and Guangzhou (r=-0.530, P<0.01) , yet in contrast, positively correlated with that in Japan (r=0.441, P<0.01). In most of the cities (Shanghai, Guangzhou, Hong Kong, Seoul, Tokyo, and Kuala Lumpur), generalized additive modeling analysis showed the number of daily new confirmed cases was positively associated with both average temperature and relative humidity, especially in lagged 3d model, where a positive influence of temperature on the daily new confirmed cases was discerned in 5 cities except in Beijing, Wuhan, Korea, and Malaysia. Nevertheless, the results were inconsistent across cities and lagged time, suggesting meteorological factors were unlikely to greatly influence the COVID-19 epidemic. CONCLUSION The associations between meteorological factors and the number of COVID-19 daily cases are inconsistent across cities and lagged time. Large-scale public health measures and expanded regional research are still required until a vaccine becomes available and herd immunity is established.", "qid": 2, "docid": "g9umdcn2", "rank": 91, "score": 0.7385759353637695}, {"content": "Title: ICU admissions and in-hospital deaths linked to covid-19 in the Paris region are correlated with previously observed ambient temperature Content: OBJECTIVE To study the effect of weather on severity indicators of coronavirus disease 2019 (covid-19). DESIGN Ecological study. SETTING Paris region. POPULATION Severely ill patients with covid-19. MAIN OUTCOME MEASURES Daily covid-19-related intensive care unit (ICU) admission and in-hospital deaths in the Paris region, and the daily weather characteristics of Paris midtown. RESULTS Daily ICU admissions and in-hospital deaths were strongly and negatively correlated to ambient temperatures, with a time lag. The highest Pearson correlation coefficients and statistically significant P values were found 8 days before occurrence of ICU admissions and 15 days before deaths. CONCLUSIONS The study findings show a strong effect of previously observed ambient temperature that has an effect on severity indicators of covid-19.", "qid": 2, "docid": "gmlbbw9u", "rank": 92, "score": 0.7385587096214294}, {"content": "Title: Adapting to the Coronavirus Disease 2019 Pandemic in New York City Content: The coronavirus disease 2019 has and continues to overwhelm the medical establishment in New York City. It has moved faster and had rates of mortality higher than what were initially forecast. All departments within large hospital systems have had to learn lessons and adapt in real time to the crisis. We share our experience and what we have learned as it pertains to this pandemic and hope that it aides, guides, and influences other departments of physical medicine and rehabilitation regarding their potential roles and areas of growth during this time.", "qid": 2, "docid": "fzvxa03d", "rank": 93, "score": 0.7383514046669006}, {"content": "Title: Observed and Potential Impacts of the COVID-19 Pandemic on the Environment Content: Various environmental factors influence the outbreak and spread of epidemic or even pandemic events which, in turn, may cause feedbacks on the environment. The novel coronavirus disease (COVID-19) was declared a pandemic on 13 March 2020 and its rapid onset, spatial extent and complex consequences make it a once-in-a-century global disaster. Most countries responded by social distancing measures and severely diminished economic and other activities. Consequently, by the end of April 2020, the COVID-19 pandemic has led to numerous environmental impacts, both positive such as enhanced air and water quality in urban areas, and negative, such as shoreline pollution due to the disposal of sanitary consumables. This study presents an early overview of the observed and potential impacts of the COVID-19 on the environment. We argue that the effects of COVID-19 are determined mainly by anthropogenic factors which are becoming obvious as human activity diminishes across the planet, and the impacts on cities and public health will be continued in the coming years.", "qid": 2, "docid": "pr1j71r9", "rank": 94, "score": 0.738281786441803}, {"content": "Title: Mental Health and Behavior of College Students During the Early Phases of the COVID-19 Pandemic: Longitudinal Smartphone and Ecological Momentary Assessment Study Content: BACKGROUND: The vast majority of people worldwide have been impacted by coronavirus disease (COVID-19). In addition to the millions of individuals who have been infected with the disease, billions of individuals have been asked or required by local and national governments to change their behavioral patterns. Previous research on epidemics or traumatic events suggests that this can lead to profound behavioral and mental health changes; however, researchers are rarely able to track these changes with frequent, near-real-time sampling or compare their findings to previous years of data for the same individuals. OBJECTIVE: By combining mobile phone sensing and self-reported mental health data among college students who have been participating in a longitudinal study for the past 2 years, we sought to answer two overarching questions. First, have the behaviors and mental health of the participants changed in response to the COVID-19 pandemic compared to previous time periods? Second, are these behavior and mental health changes associated with the relative news coverage of COVID-19 in the US media? METHODS: Behaviors such as the number of locations visited, distance traveled, duration of phone usage, number of phone unlocks, sleep duration, and sedentary time were measured using the StudentLife smartphone sensing app. Depression and anxiety were assessed using weekly self-reported ecological momentary assessments of the Patient Health Questionnaire-4. The participants were 217 undergraduate students, with 178 (82.0%) students providing data during the Winter 2020 term. Differences in behaviors and self-reported mental health collected during the Winter 2020 term compared to previous terms in the same cohort were modeled using mixed linear models. RESULTS: During the first academic term impacted by COVID-19 (Winter 2020), individuals were more sedentary and reported increased anxiety and depression symptoms (P<.001) relative to previous academic terms and subsequent academic breaks. Interactions between the Winter 2020 term and the week of the academic term (linear and quadratic) were significant. In a mixed linear model, phone usage, number of locations visited, and week of the term were strongly associated with increased amount of COVID-19-related news. When mental health metrics (eg, depression and anxiety) were added to the previous measures (week of term, number of locations visited, and phone usage), both anxiety (P<.001) and depression (P=.03) were significantly associated with COVID-19-related news. CONCLUSIONS: Compared with prior academic terms, individuals in the Winter 2020 term were more sedentary, anxious, and depressed. A wide variety of behaviors, including increased phone usage, decreased physical activity, and fewer locations visited, were associated with fluctuations in COVID-19 news reporting. While this large-scale shift in mental health and behavior is unsurprising, its characterization is particularly important to help guide the development of methods to reduce the impact of future catastrophic events on the mental health of the population.", "qid": 2, "docid": "yzzv8fag", "rank": 95, "score": 0.7381854057312012}, {"content": "Title: High Temperature and High Humidity Reduce the Transmission of COVID-19 Content: With the ongoing global pandemic of COVID-19, a question is whether the coming summer in the northern hemisphere will reduce the transmission intensity of COVID-19 with increased humidity and temperature. In this paper, we investigate this problem using the data from the cases with symptom-onset dates from January 19 to February 10, 2020 for 100 Chinese cities, and cases with confirmed dates from March 15 to April 25 for 1,005 U.S. counties. Statistical analysis is performed to assess the relationship between the transmissibility of COVID-19 and the temperature/humidity, by controlling for various demographic, socio-economic, geographic, healthcare and policy factors and correcting for cross-sectional correlation. We find a similar influence of the temperature and relative humidity on effective reproductive number (R values) of COVID-19 for both China and the U.S. before lockdown in both countries: one-degree Celsius increase in temperature reduces R value by about 0.023 (0.026 (95% CI [-0.0395,-0.0125]) in China and 0.020 (95% CI [-0.0311, -0.0096]) in the U.S.), and one percent relative humidity rise reduces R value by 0.0078 (0.0076 (95% CI [-0.0108,-0.0045]) in China and 0.0080 (95% CI [-0.0150,-0.0010]) in the U.S.). If assuming a 30 degree and 25 percent increase in temperature and relative humidity from winter to summer in the northern hemisphere, we expect the R values to decline about 0.89 (0.69 by temperature and 0.20 by humidity). Given the notion that the non-intervened R values are around 2.5 to 3, only weather factors cannot make the R values below their critical condition of R<1, under which the epidemic diminishes gradually. Therefore, public health intervention such as social distancing is crucial to block the transmission of COVID-19 even in summer.", "qid": 2, "docid": "it0vccw3", "rank": 96, "score": 0.7381265163421631}, {"content": "Title: Letter to the Editor: Note on published research on the effects of COVID-19 on the environment without sufficient depth of science Content: Dear Editor-in-Chief: We have given two articles published recently in Science of the Total Environment by Mandal and Pal (2020) and Zambrano-Monserrate et al. (2020) a thorough reading. Both articles present a significant association between the novel Coronavirus (COVID-19) social distancing policies and improvement in environmental quality such as air pollution, land surface temperature, and noise. Both articles present good research, complemented by detailed explanations and displays, yet we have a few concerns that affect the interpretation and meaning of the results.", "qid": 2, "docid": "ir5o7slp", "rank": 97, "score": 0.7380653619766235}, {"content": "Title: The role of climate during the COVID-19 epidemic in New South Wales, Australia Content: Previous research has identified a relationship between climate and occurrence of SARS-CoV and MERS-CoV cases, information that can be used to reduce the risk of infection. Using COVID-19 notification and postcode data from New South Wales, Australia during the exponential phase of the epidemic in 2020, we used time series analysis to investigate the relationship between 749 cases of locally acquired COVID-19 and daily rainfall, 9 a.m. and 3 p.m. temperature, and 9 a.m. and 3 p.m. relative humidity. Lower 9 a.m. relative humidity (but not rainfall or temperature) was associated with increased case occurrence; a reduction in relative humidity of 1% was predicted to be associated with an increase of COVID-19 cases by 6.11%. During periods of low relative humidity, the public health system should anticipate an increased number of COVID-19 cases.", "qid": 2, "docid": "zbxo87y9", "rank": 98, "score": 0.7380259037017822}, {"content": "Title: COVID-19 transmission in Mainland China is associated with temperature and humidity: a time-series analysis Content: COVID-19 has become a pandemic. The influence of meteorological factors on the transmission and spread of COVID-19 if of interest. This study sought to examine the associations of daily average temperature (AT) and relative humidity (ARH) with the daily count of COVID-19 cases in 30 Chinese provinces (in Hubei from December 1, 2019 to February 11, 2020 and in other provinces from January 20, 2020 to Februarys 11, 2020). A Generalized Additive Model (GAM) was fitted to quantify the province-specific associations between meteorological variables and the daily cases of COVID-19 during the study periods. In the model, the 14-day exponential moving averages (EMAs) of AT and ARH, and their interaction were included with time trend and health-seeking behavior adjusted. Their spatial distributions were visualized. AT and ARH showed significantly negative associations with COVID-19 with a significant interaction between them (0.04, 95% confidence interval: 0.004-0.07) in Hubei. Every 1\u00b0C increase in the AT led to a decrease in the daily confirmed cases by 36% to 57% when ARH was in the range from 67% to 85.5%. Every 1% increase in ARH led to a decrease in the daily confirmed cases by 11% to 22% when AT was in the range from 5.04\u00b0C to 8.2\u00b0C. However, these associations were not consistent throughout Mainland China.", "qid": 2, "docid": "1p941spn", "rank": 99, "score": 0.737852931022644}, {"content": "Title: Effects of temperature variation and humidity on the mortality of COVID-19 in Wuhan Content: Object Meteorological parameters are the important factors influencing the infectious diseases like severe acute respiratory syndrome (SARS). This study aims to explore the association between coronavirus disease (COVID-19) death and weather parameters. Methods In this study, we collected the daily death number of COVID-19, meteorological and air pollutant data from 20 January, 2020 to 29 February, 2020 in Wuhan, China. Then, the generalized additive model was applied to explore the impact of temperature, humidity and diurnal temperature range on daily mortality of COVID-19. Results There were in total 2299 COVID-19 mortality counts in Wuhan. A positive association with COVID-19 mortality was observed for diurnal temperature range (r = 0.44), but negative association for relative humidity (r = -0.32). In addition, each 1 unit increase in diurnal temperature range was only associated with a 2.92% (95% CI: 0.61%, 5.28%) increase in COVID-19 mortality at lag 3. However, both per 1 unit increase of temperature and absolute humidity were related to the decreased COVID-19 mortality at lag 3 and lag 5, respectively. Conclusion In summary, this study suggests the temperature variation and humidity may be important factors affecting the COVID-19 mortality.", "qid": 2, "docid": "f53i4n02", "rank": 100, "score": 0.7377992272377014}]}
{"query": "will SARS-CoV2 infected people develop immunity? Is cross protection possible?", "hits": [{"content": "Title: A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease Content: The duration and nature of immunity generated in response to SARS-CoV-2 infection is unknown. Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARSCoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The timescale of protection is a critical determinant of the future impact of the pathogen. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. The dynamics of immunity and nature of protection are relevant to discussions surrounding therapeutic use of convalescent sera as well as efforts to identify individuals with protective immunity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV-1, MERS-CoV and human endemic coronaviruses (HCoVs). We reviewed 1281 abstracts and identified 322 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While studies of SARS-CoV-2 are necessary to determine immune responses to it, evidence from other coronaviruses can provide clues and guide future research.", "qid": 3, "docid": "yzffm05r", "rank": 1, "score": 0.8110251426696777}, {"content": "Title: SARS-CoV-2 infection protects against rechallenge in rhesus macaques Content: An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies aimed at ending the global COVID-19 pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. Following initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log(10) reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with primary infection. Anamnestic immune responses following rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against re-exposure in nonhuman primates.", "qid": 3, "docid": "car394ou", "rank": 2, "score": 0.7957352995872498}, {"content": "Title: SARS-CoV-2 infection protects against rechallenge in rhesus macaques Content: An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies aimed at ending the global COVID-19 pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. Following initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with primary infection. Anamnestic immune responses following rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against re-exposure in nonhuman primates.", "qid": 3, "docid": "t3sjv4hv", "rank": 3, "score": 0.7946010828018188}, {"content": "Title: COVID\u201019 is milder in children possibly due to cross immunity Content: It has been unclear why the new severe acute respiratory syndrome coronavirus (sars\u2010CoV\u20102) hits a small minority hard, while the vast majority of children appear to be protected and develop mild or no disease (1,2). The editorial by Brodin suggests some possible mechanisms why it is so (1). I would like to emphasize the significance of cross immunity due to previous exposure to seasonal coronavirus; it may be a plausible explanation for why children appear to be protected (2,3).", "qid": 3, "docid": "wfftfkam", "rank": 4, "score": 0.7923737168312073}, {"content": "Title: Lack of cross-neutralization by SARS patient sera towards SARS-CoV-2 Content: Despite initial findings indicating that SARS-CoV and SARS-CoV-2 are genetically related belonging to the same virus species and that the two viruses used the same entry receptor, angiotensin-converting enzyme 2 (ACE2), our data demonstrated that there is no detectable cross-neutralization by SARS patient sera against SARS-CoV-2. We also found that there are significant levels of neutralizing antibodies in recovered SARS patients 9-17 years after initial infection. These findings will be of significant use in guiding the development of serologic tests, formulating convalescent plasma therapy strategies, and assessing the longevity of protective immunity for SARS-related coronaviruses in general as well as vaccine efficacy.", "qid": 3, "docid": "buwz6lu3", "rank": 5, "score": 0.7876706719398499}, {"content": "Title: Lack of cross-neutralization by SARS patient sera towards SARS-CoV-2 Content: Despite initial findings indicating that SARS-CoV and SARS-CoV-2 are genetically related belonging to the same virus species and that the two viruses used the same entry receptor, angiotensin-converting enzyme 2 (ACE2), our data demonstrated that there is no detectable cross-neutralization by SARS patient sera against SARS-CoV-2. We also found that there are significant levels of neutralizing antibodies in recovered SARS patients 9\u201317 years after initial infection. These findings will be of significant use in guiding the development of serologic tests, formulating convalescent plasma therapy strategies, and assessing the longevity of protective immunity for SARS-related coronaviruses in general as well as vaccine efficacy.", "qid": 3, "docid": "8i1u1a9t", "rank": 6, "score": 0.7876587510108948}, {"content": "Title: Children's vaccines do not induce cross reactivity against SARS-CoV. Content: In contrast with adults, children infected by severe acute respiratory syndrome-corona virus (SARS-CoV) develop milder clinical symptoms. Because of this, it is speculated that children vaccinated with various childhood vaccines might develop cross immunity against SARS-CoV. Antisera and T cells from mice immunised with various vaccines were used to determine whether they developed cross reactivity against SARS-CoV. The results showed no marked cross reactivity against SARS-CoV, which implies that the reduced symptoms among children infected by SARS-CoV may be caused by other factors.", "qid": 3, "docid": "eo4ehcjv", "rank": 7, "score": 0.7839589715003967}, {"content": "Title: Long-term and herd immunity against SARS-CoV-2: implications from current and past knowledge Content: Effective herd immunity against SARS-CoV-2 will be determined on many factors: the percentage of the immune population, the length and effectiveness of the immune response and the stability of the viral epitopes. The required percentage of immune individuals has been estimated to be 50-66% of the population which, given the current infection rates, will take long to be achieved. Furthermore, data from SARS-CoV suggest that the duration of immunity may not be sufficiently significant, while the immunity response against SARS-CoV-2 may not be efficiently effective in all patients, as relapses have already been reported. In addition, the development of mutant strains, which has already been documented, can cause the reemergence of the epidemic. In conclusion, the development of an effective vaccine is an urgent necessity, as long-term natural immunity to SARS-CoV-2 may not be sufficient for the control of the current and future outbreaks.", "qid": 3, "docid": "pcyscqux", "rank": 8, "score": 0.7813278436660767}, {"content": "Title: Seropr\u00e4valenz und SARS-CoV-2-Testung in Gesundheitsberufen Content: The SARS-CoV\u20112 causes a disease spectrum that includes asymptomatic and mildly symptomatic infections with subclinical manifestations but which can nevertheless still be potentially contagious. Evidence from SARS-CoV\u20112 infected macaque monkeys and from studies with seasonal coronaviruses suggests that the infection is likely to produce an immunity that is protective for a certain period of time. Available test methods enable a high degree of reliability, e.g. if high-quality serological methods are combined. Although individual test results have to be interpreted with caution, serosurveillance in a tertiary eye care center and large eye research institute can reduce anxiety and provide clarity regarding the actual number of (unreported) SARS-CoV\u20112 infections.", "qid": 3, "docid": "u4sy1sjr", "rank": 9, "score": 0.7809975147247314}, {"content": "Title: Long-term and herd immunity against SARS-CoV-2: implications from current and past knowledge Content: Effective herd immunity against SARS-CoV-2 will be determined on many factors: the percentage of the immune population, the length and effectiveness of the immune response and the stability of the viral epitopes. The required percentage of immune individuals has been estimated to be 50\u201366% of the population which, given the current infection rates, will take long to be achieved. Furthermore, data from SARS-CoV suggest that the duration of immunity may not be sufficiently significant, while the immunity response against SARS-CoV-2 may not be efficiently effective in all patients, as relapses have already been reported. In addition, the development of mutant strains, which has already been documented, can cause the reemergence of the epidemic. In conclusion, the development of an effective vaccine is an urgent necessity, as long-term natural immunity to SARS-CoV-2 may not be sufficient for the control of the current and future outbreaks.", "qid": 3, "docid": "6jr3z9wx", "rank": 10, "score": 0.7800896167755127}, {"content": "Title: Seropr\u00e4valenz und SARS-CoV-2-Testung in Gesundheitsberufen./ [Seroprevalence and SARS-CoV-2 testing in healthcare occupations] Content: The SARS-CoV\u00ad2 causes a disease spectrum that includes asymptomatic and mildly symptomatic infections with subclinical manifestations but which can nevertheless still be potentially contagious. Evidence from SARS-CoV\u00ad2 infected macaque monkeys and from studies with seasonal coronaviruses suggests that the infection is likely to produce an immunity that is protective for a certain period of time. Available test methods enable a high degree of reliability, e.g. if high-quality serological methods are combined. Although individual test results have to be interpreted with caution, serosurveillance in a tertiary eye care center and large eye research institute can reduce anxiety and provide clarity regarding the actual number of (unreported) SARS-CoV\u00ad2 infections.", "qid": 3, "docid": "rlpe6tpm", "rank": 11, "score": 0.7789769172668457}, {"content": "Title: Characterization of anti-viral immunity in recovered individuals infected by SARS-CoV-2 Content: The WHO has declared SARS-CoV-2 outbreak a public health emergency of international concern. However, to date, there was hardly any study in characterizing the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. In this study, we collected blood from COVID-19 patients who have recently become virus-free and therefore were discharged, and analyzed their SARS-CoV-2-specific antibody and T cell responses. We observed SARS-CoV-2-specific humoral and cellular immunity in the patients. Both were detected in newly discharged patients, suggesting both participate in immune-mediated protection to viral infection. However, follow-up patients (2 weeks post discharge) exhibited high titers of IgG antibodies, but with low levels of virus-specific T cells, suggesting that they may enter a quiescent state. Our work has thus provided a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It has also implications in designing an effective vaccine to protect and treat SARS-CoV-2 infection.", "qid": 3, "docid": "dptgg05n", "rank": 12, "score": 0.7739085555076599}, {"content": "Title: Intrafamilial Exposure to SARS-CoV-2 Induces Cellular Immune Response without Seroconversion Content: Background. In the background of the current COVID-19 pandemic, serological tests are being used to assess past infection and immunity against SARS-CoV-2. This knowledge is paramount to determine the transmission dynamics of SARS-CoV-2 through the post pandemic period. Several individuals belonging to households with an index COVID-19 patient, reported symptoms of COVID-19 but discrepant serology results. Methods. Here we investigated the humoral and cellular immune responses against SARS-CoV-2 in seven families, including nine index patients and eight contacts, who had evidence of serological discordances within the households. Ten unexposed healthy donors were enrolled as controls. Results. All index patients recovered from a mild COVID-19. They all developed anti-SARS-CoV-2 antibodies and a significant T cell response detectable up to 69 days after symptom onset. Six of the eight contacts reported COVID-19 symptoms within 1 to 7 days after the index patients but all were SARS-CoV-2 seronegative. Six out of eight contacts developed a SARS-CoV-2-specific T cell response against structural and/or accessory proteins that lasts up to 80 days post symptom onset suggesting a past SARS-CoV-2 infection. Conclusion. Exposure to SARS-CoV-2 can induce virus-specific T cell responses without seroconversion. T cell responses may be more sensitive indicators of SARS-Co-V-2 exposure than antibodies. Our results indicate that epidemiological data relying only on the detection of SARS-CoV-2 antibodies may lead to a substantial underestimation of prior exposure to the virus", "qid": 3, "docid": "eml8uilb", "rank": 13, "score": 0.7736914157867432}, {"content": "Title: Immunity after COVID-19: protection or sensitization ? Content: Motivated by historical and present clinical observations, we discuss the possible unfavorable evolution of the immunity (similar to documented antibody-dependent enhancement scenarios) after a first infection with COVID-19. More precisely we ask the question of how the epidemic outcomes are affected if the initial infection does not provide immunity but rather sensitization to future challenges. We first provide background comparison with the 2003 SARS epidemic. Then we use a compartmental epidemic model structured by immunity level (taken here as age classes) that we fit on available data; this allows to derive quantitative insights into the future number of severe cases and deaths.", "qid": 3, "docid": "g6g34uvh", "rank": 14, "score": 0.7727413177490234}, {"content": "Title: Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals Content: Summary The World Health Organization has declared SARS-CoV-2 virus outbreak a world-wide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in 8 newly discharged patients. Follow-up analysis on another cohort of 6 patients 2 weeks post discharge also revealed high titers of IgG antibodies. In all 14 patients tested, 13 displayed serum neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It has also implications in developing an effective vaccine to SARS-CoV-2 infection.", "qid": 3, "docid": "0tn06al2", "rank": 15, "score": 0.7695493698120117}, {"content": "Title: Expected immune recognition of COVID-19 virus by memory from earlier infections with common coronaviruses in a large part of the world population Content: SARS-CoV-2 is the coronavirus agent of the COVID-19 pandemic causing high mortalities. In contrast, the widely spread human coronaviruses OC43, HKU1, 229E, and NL63 tend to cause only mild symptoms. The present study shows, by in silico analysis, that these common human viruses are expected to induce immune memory against SARS-CoV-2 by sharing protein fragments (antigen epitopes) for presentation to the immune system by MHC class I. A list of such epitopes is provided. The number of these epitopes and the prevalence of the common coronaviruses suggest that a large part of the world population has some degree of specific immunity against SARS-CoV-2 already, even without having been infected by that virus. For inducing protection, booster vaccinations enhancing existing immunity are less demanding than primary vaccinations against new antigens. Therefore, for the discussion on vaccination strategies against COVID-19, the available immune memory against related viruses should be part of the consideration.", "qid": 3, "docid": "majelie8", "rank": 16, "score": 0.7679215669631958}, {"content": "Title: Cross-immunity between respiratory coronaviruses may limit COVID-19 fatalities Content: Of the seven coronaviruses associated with disease in humans, SARS-CoV, MERS-CoV and SARS-CoV-2 cause considerable mortality but also share significant sequence homology, and potentially antigenic epitopes capable of inducing an immune response. The degree of similarity is such that perhaps prior exposure to one virus could confer partial immunity to another. Indeed, data suggests a considerable amount of cross-reactivity and recognition by the hosts immune response between different coronavirus infections. While the ongoing COVID-19 outbreak rapidly overwhelmed medical facilities of particularly Europe and North America, accounting for 78% of global deaths, only 8% of deaths have occurred in Asia where the outbreak originated. Interestingly, Asia and the Middle East have previously experienced multiple rounds of coronavirus infections, perhaps suggesting buildup of acquired immunity to the causative SARS-CoV-2 that underlies COVID-19. This article hypothesizes that a causative factor underlying such low morbidity in these regions is perhaps (at least in part) due to acquired immunity from multiple rounds of coronavirus infections and discusses the mechanisms and recent evidence to support such assertions. Further investigations of such phenomenon would allow us to examine strategies to confer protective immunity, perhaps aiding vaccine development.", "qid": 3, "docid": "01q4pu9k", "rank": 17, "score": 0.7673031091690063}, {"content": "Title: Can an effective SARS-CoV-2 vaccine be developed for the older population? Content: The emergence of SARS-CoV-2 and its inordinately rapid spread is posing severe challenges to the wellbeing of millions of people worldwide, health care systems and the global economy. While many younger people experience no or mild symptoms on infection, older adults are highly susceptible to life-threatening respiratory and systemic conditions which demand a full understanding and leveraging of knowledge of the differences between immunity in young and old people. Consequently, we welcome papers addressing any issues relevant to immunity and ageing in the context of SARS-CoV-2, and will endeavour to fast-track peer-review. We aim to provide a platform exclusively for discussions of individual and age differences in susceptibility and immune responses to COVID caused by SARS-CoV-2 infection and how to prevent or reduce severity of disease in older adults.", "qid": 3, "docid": "fi1ldwe8", "rank": 18, "score": 0.766057550907135}, {"content": "Title: New IgM seroconversion and positive RT\u2010PCR test after exposure to the virus in recovered COVID\u201019 patient Content: To date, understanding whether acquired immunity and presence of anti SARS\u2010Cov2 antibodies protects against reinfection is one the most important focus of the scientific community [1\u20102]. Several studies suggest that acquired immunity may protect upon further exposure to SARS\u2010COV2 [3\u20106]. Contrary to this picture, we describe a case of a patient recovered from COVID\u201019 pneumonia with positive serology, followed up by 6 negative nasopharyngeal swab\u2010PCR tests performed along 1 month, who later on, after exposure to the virus, presented another positive RT\u2010PCR test and a second IgM seroconversion. This report opens up several possible interpretations. This article is protected by copyright. All rights reserved.", "qid": 3, "docid": "38mhmxvd", "rank": 19, "score": 0.7657761573791504}, {"content": "Title: SARS-CoV-2 epitopes are recognized by a public and diverse repertoire of human T-cell receptors Content: Understanding the determinants of adaptive immune response to SARS-CoV-2 is critical for fighting the ongoing COVID-19 pandemic. Here we assayed both antibody and T-cell reactivity to SARS-CoV-2 antigens in COVID-19 convalescent patients and healthy donors sampled before and during the pandemic. Our results show that while anti-SARS-CoV-2 antibodies can distinguish convalescent patients from healthy donors, the magnitude of T-cell response was more pronounced in healthy donors sampled during COVID-19 pandemic than in donors sampled before the outbreak. This hints at the possibility that some individuals have encountered the virus but were protected by T-cell cross-reactivity observed. A public and diverse T-cell response was observed for two A*02-restricted SARS-CoV-2 epitopes, revealing a set of T-cell receptor motifs displaying germline-encoded features. Bulk CD4+ and CD8+ T-cell response to SARS-CoV-2 glycoprotein S is characterized by multiple groups of homologous T-cell receptor sequences some of which are shared across multiple donors, indicating the existence of immunodominant epitopes. Overall, our findings indicate that T cells form an efficient response to SARS-CoV-2 and alongside the antibodies can serve as a useful biomarker for surveying SARS-CoV-2 exposure and immunity. We hope that data, including the set of specific T-cell receptors identified in this study can serve as a basis for future developments of SARS-CoV-2 vaccinations and monitoring.", "qid": 3, "docid": "ioihqf0r", "rank": 20, "score": 0.7652239799499512}, {"content": "Title: Seroprevalence of IgG antibodies to SARS-coronavirus in asymptomatic or subclinical population groups. Content: We systematically reviewed the current understanding of human population immunity against SARS-CoV in different groups, settings and geography. Our meta-analysis, which included all identified studies except those on wild animal handlers, yielded an overall seroprevalence of 0.10% [95% confidence interval (CI) 0.02-0.18]. Health-care workers and others who had close contact with SARS patients had a slightly higher degree of seroconversion (0.23%, 95% CI 0.02-0.45) compared to healthy blood donors, others from the general community or non-SARS patients recruited from the health-care setting (0.16%, 95% CI 0-0.37). When analysed by the two broad classes of testing procedures, it is clear that serial confirmatory test protocols resulted in a much lower estimate (0.050%, 95% CI 0-0.15) than single test protocols (0.20%, 95% CI 0.06-0.34). Potential epidemiological and laboratory pitfalls are also discussed as they may give rise to false or inconsistent results in measuring the seroprevalence of IgG antibodies to SARS-CoV.", "qid": 3, "docid": "j8ta21zr", "rank": 21, "score": 0.7644342184066772}, {"content": "Title: Lessons for COVID-19 immunity from other coronavirus infections Content: Abstract A key goal to controlling COVID-19 is developing an effective vaccine. Development of a vaccine requires knowledge of what constitutes a protective immune response and also features that might be pathogenic. Protective and pathogenic aspects of the response to SARS-CoV-2 are not well understood, partly because the virus has infected humans for only 6 months. However, insight into coronavirus immunity can be informed by previous studies of immune responses to non-human coronaviruses, to common cold coronaviruses, and to SARS-CoV and MERS-CoV. Here we review the literature describing these responses and discuss their relevance to the SARS-CoV-2 immune response.", "qid": 3, "docid": "s6v4bgev", "rank": 22, "score": 0.7642529606819153}, {"content": "Title: T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV Content: Abstract Over 12 years have elapsed since severe acute respiratory syndrome (SARS) triggered the first global alert for coronavirus infections. Virus transmission in humans was quickly halted by public health measures and human infections of SARS coronavirus (SARS-CoV) have not been observed since. However, other coronaviruses still pose a continuous threat to human health, as exemplified by the recent emergence of Middle East respiratory syndrome (MERS) in humans. The work on SARS-CoV widens our knowledge on the epidemiology, pathophysiology and immunology of coronaviruses and may shed light on MERS coronavirus (MERS-CoV). It has been confirmed that T-cell immunity plays an important role in recovery from SARS-CoV infection. Herein, we summarize T-cell immunological studies of SARS-CoV and discuss the potential cross-reactivity of the SARS-CoV-specific immunity against MERS-CoV, which may provide useful recommendations for the development of broad-spectrum vaccines against coronavirus infections.", "qid": 3, "docid": "wh9vvgv2", "rank": 23, "score": 0.7641401290893555}, {"content": "Title: Distinct systems serology features in children, elderly and COVID patients Content: SARS-CoV-2, the pandemic coronavirus that causes COVID-19, has infected millions worldwide, causing unparalleled social and economic disruptions. COVID-19 results in higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive coronavirus immunological responses, induced by circulating human coronaviruses, is critical to understand such divergent clinical outcomes. The cross-reactivity of coronavirus antibody responses of healthy children (n=89), adults (n=98), elderly (n=57), and COVID-19 patients (n=19) were analysed by systems serology. While moderate levels of cross-reactive SARS-CoV-2 IgG, IgM, and IgA were detected in healthy individuals, we identified serological signatures associated with SARS-CoV-2 antigen-specific Fc{gamma} receptor binding, which accurately distinguished COVID-19 patients from healthy individuals and suggested that SARS-CoV-2 induces qualitative changes to antibody Fc upon infection, enhancing Fc{gamma} receptor engagement. Vastly different serological signatures were observed between healthy children and elderly, with markedly higher cross-reactive SARS-CoV-2 IgA and IgG observed in elderly, whereas children displayed elevated SARS-CoV-2 IgM, including receptor binding domain-specific IgM with higher avidity. These results suggest that less-experienced humoral immunity associated with higher IgM, as observed in children, may have the potential to induce more potent antibodies upon SARS-CoV-2 infection. These key insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.", "qid": 3, "docid": "8nbmrjrw", "rank": 24, "score": 0.7633540034294128}, {"content": "Title: Infection with novel coronavirus (SARS-CoV-2) causes pneumonia in Rhesus macaques Content: The 2019 novel coronavirus (SARS-CoV-2) outbreak is a major challenge for public health. SARS-CoV-2 infection in human has a broad clinical spectrum ranging from mild to severe cases, with a mortality rate of ~6.4% worldwide (based on World Health Organization daily situation report). However, the dynamics of viral infection, replication and shedding are poorly understood. Here, we show that Rhesus macaques are susceptible to the infection by SARS-CoV-2. After intratracheal inoculation, the first peak of viral RNA was observed in oropharyngeal swabs one day post infection (1 d.p.i.), mainly from the input of the inoculation, while the second peak occurred at 5 d.p.i., which reflected on-site replication in the respiratory tract. Histopathological observation shows that SARS-CoV-2 infection can cause interstitial pneumonia in animals, characterized by hyperemia and edema, and infiltration of monocytes and lymphocytes in alveoli. We also identified SARS-CoV-2 RNA in respiratory tract tissues, including trachea, bronchus and lung; and viruses were also re-isolated from oropharyngeal swabs, bronchus and lung, respectively. Furthermore, we demonstrated that neutralizing antibodies generated from the primary infection could protect the Rhesus macaques from a second-round challenge by SARS-CoV-2. The non-human primate model that we established here provides a valuable platform to study SARS-CoV-2 pathogenesis and to evaluate candidate vaccines and therapeutics.", "qid": 3, "docid": "xbnp6tgz", "rank": 25, "score": 0.7630550861358643}, {"content": "Title: Infection with novel coronavirus (SARS-CoV-2) causes pneumonia in Rhesus macaques. Content: The 2019 novel coronavirus (SARS-CoV-2) outbreak is a major challenge for public health. SARS-CoV-2 infection in human has a broad clinical spectrum ranging from mild to severe cases, with a mortality rate of ~6.4% worldwide (based on World Health Organization daily situation report). However, the dynamics of viral infection, replication and shedding are poorly understood. Here, we show that Rhesus macaques are susceptible to the infection by SARS-CoV-2. After intratracheal inoculation, the first peak of viral RNA was observed in oropharyngeal swabs one day post infection (1 d.p.i.), mainly from the input of the inoculation, while the second peak occurred at 5 d.p.i., which reflected on-site replication in the respiratory tract. Histopathological observation shows that SARS-CoV-2 infection can cause interstitial pneumonia in animals, characterized by hyperemia and edema, and infiltration of monocytes and lymphocytes in alveoli. We also identified SARS-CoV-2 RNA in respiratory tract tissues, including trachea, bronchus and lung; and viruses were also re-isolated from oropharyngeal swabs, bronchus and lung, respectively. Furthermore, we demonstrated that neutralizing antibodies generated from the primary infection could protect the Rhesus macaques from a second-round challenge by SARS-CoV-2. The non-human primate model that we established here provides a valuable platform to study SARS-CoV-2 pathogenesis and to evaluate candidate vaccines and therapeutics.", "qid": 3, "docid": "97tb8eas", "rank": 26, "score": 0.7630550861358643}, {"content": "Title: Human coronavirus reinfection dynamics: lessons for SARS-CoV-2 Content: In the current SARS-CoV-2 pandemic a key unsolved question is the quality and duration of acquired immunity in recovered individuals. This is crucial to solve, however SARS-CoV-2 has circulated for under five months, precluding a direct study. We therefore monitored 10 subjects over a time span of 35 years (1985-2020), providing a total of 2473 follow up person-months, and determined a) their antibody levels following infection by any of the four seasonal human coronaviruses, and b) the time period after which reinfections by the same virus can occur. An alarmingly short duration of protective immunity to coronaviruses was found by both analyses. We saw frequent reinfections at 12 months post-infection and a substantial reduction in antibody levels as soon as 6 months post-infection.", "qid": 3, "docid": "u5nxm9tu", "rank": 27, "score": 0.7630364298820496}, {"content": "Title: Universal coronavirus vaccines: the time to start is now Content: The continued explosive spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) despite aggressive public health measures has triggered an unprecedented international vaccine effort. However, correlates of protection, which can help guide intelligent vaccine design, are not known for SARS-CoV-2. Research on influenza immunity and vaccine development may provide valuable lessons for coronavirus efforts, especially considering similarities in rapid evolutionary potential. The apparent inevitability of future novel coronavirus outbreaks must prompt work on a universal coronavirus vaccine.", "qid": 3, "docid": "yrrz7oef", "rank": 28, "score": 0.7626218199729919}, {"content": "Title: Is Global BCG Vaccination Coverage Relevant To The Progression Of SARS-CoV-2 Pandemic? Content: Abstract The lower than expected number of SARS-CoV-2 cases in countries with fragile health systems is puzzling. Herein, we hypothesize that BCG vaccination policies adopted by different countries might influence the SARS-CoV-2 transmission patterns and/or COVID-19 associated morbidity and mortality through the vaccine\u2019s capacity to confer heterologous protection. We also postulate that until a specific vaccine is developed, SARS-CoV-2 vulnerable populations could be immunized with BCG vaccines to attain heterologous nonspecific protection from the new coronavirus.", "qid": 3, "docid": "uei9zw6q", "rank": 29, "score": 0.7622576951980591}, {"content": "Title: Reflection on lower rates of COVID-19 in children: does childhood immunizations offer unexpected protection? Content: The incidence of COVID-19 in children and teenagers is only about 2% in China. Children had mild symptoms and hardly infected other children or adults. It is worth considering that children are the most vulnerable to respiratory pathogens, but fatal SARS-like virus had not caused severe cases among them. According to the pathological studies of COVID-19 and SARS, a sharp decrease in T lymphocytes leads to the breakdown of the immune system. The cellular immune system of children differs from that of adults may be the keystone of atypical clinical manifestations or even covert infection. The frequent childhood vaccinations and repeated pathogens infections might be resulting in trained immunity of innate immune cells, immune fitness of adaptive immune cells or cross-protection of antibodies in the children. Therefore, due to lack of specific vaccine, some vaccines for tuberculosis, influenza and pneumonia may have certain application potential for the front-line health workers in the prevention and control of COVID-19. However, for high-risk susceptible populations, such as the elderly with basic diseases such as hypertension and diabetes, it is necessary to explore the acclimatization effect of the planned immune process on their immunity to achieve the trained immunity or immune fitness, so as to improve their own antiviral ability.", "qid": 3, "docid": "rpq62xhl", "rank": 30, "score": 0.7617200613021851}, {"content": "Title: Perspectives of Immune Therapy in Coronavirus Disease 2019 Content: The global fight against coronavirus disease 2019 (COVID-19) is largely based on strategies to boost immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent its severe course and complications. The human defence may include antibodies which interact with SARS-CoV-2 and neutralize its aggressive actions on multiple organ systems. Protective cross-reactivity of antibodies against measles and other known viral infections has been postulated, primarily as a result of the initial observations of asymptomatic and mild COVID-19 in children. Uncontrolled case series have demonstrated virus-neutralizing effect of convalescent plasma, supporting its efficiency at early stages of contracting SARS-CoV-2. Given the variability of the virus structure, the utility of convalescent plasma is limited to the geographic area of its preparation, and for a short period of time. Intravenous immunoglobulin may also be protective in view of its nonspecific antiviral and immunomodulatory effects. Finally, human monoclonal antibodies may interact with some SARS-CoV-2 proteins, inhibiting the virus-receptor interaction and prevent tissue injury. The improved understanding of the host antiviral responses may help develop safe and effective immunotherapeutic strategies against COVID-19 in the foreseeable future.", "qid": 3, "docid": "0l86swz1", "rank": 31, "score": 0.7600971460342407}, {"content": "Title: The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic. Content: BACKGROUND: : SARS-CoV-2 viral infection causes COVID-19 that can result in severe acute respiratory distress syndrome (ARDS), which can cause significant mortality, leading to concern that immunosuppressive treatments for multiple sclerosis and other disorders have significant risks for both infection and ARDS. OBJECTIVE: : To examine the biology that potentially underpins immunity to the SARS-Cov-2 virus and the immunity-induced pathology related to COVID-19 and determine how this impinges on the use of current disease modifying treatments in multiple sclerosis. OBSERVATIONS: : Although information about the mechanisms of immunity are scant, it appears that monocyte/macrophages and then CD8 T cells are important in eliminating the SARS-CoV-2 virus. This may be facilitated via anti-viral antibody responses that may prevent re-infection. However, viral escape and infection of leucocytes to promote lymphopenia, apparent CD8 T cell exhaustion coupled with a cytokine storm appears to contribute to the damage in ARDS. IMPLICATIONS: : In contrast to ablative haematopoietic stem cell therapy, most multiple-sclerosis-related disease modifying therapies do not particularly target the innate immune system and few have any major long-term impact on CD8 T cells to limit protection against COVID-19. In addition, few block the formation of immature B cells within lymphoid tissue that will provide antibody-mediated protection from (re)infection. However, adjustments to dosing schedules may help de-risk the chance of infection further and reduce the concerns of people with MS being treated during the COVID-19 pandemic.", "qid": 3, "docid": "mpf6lxxr", "rank": 32, "score": 0.7598973512649536}, {"content": "Title: The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic Content: BACKGROUND: SARS-CoV-2 viral infection causes COVID-19 that can result in severe acute respiratory distress syndrome (ARDS), which can cause significant mortality, leading to concern that immunosuppressive treatments for multiple sclerosis and other disorders have significant risks for both infection and ARDS. OBJECTIVE: To examine the biology that potentially underpins immunity to the SARS-Cov-2 virus and the immunity-induced pathology related to COVID-19 and determine how this impinges on the use of current disease modifying treatments in multiple sclerosis. OBSERVATIONS: Although information about the mechanisms of immunity are scant, it appears that monocyte/macrophages and then CD8 T cells are important in eliminating the SARS-CoV-2 virus. This may be facilitated via anti-viral antibody responses that may prevent re-infection. However, viral escape and infection of leucocytes to promote lymphopenia, apparent CD8 T cell exhaustion coupled with a cytokine storm and vascular pathology appears to contribute to the damage in ARDS. IMPLICATIONS: In contrast to ablative haematopoietic stem cell therapy, most multiple-sclerosis-related disease modifying therapies do not particularly target the innate immune system and few have any major long-term impact on CD8 T cells to limit protection against COVID-19. In addition, few block the formation of immature B cells within lymphoid tissue that will provide antibody-mediated protection from (re)infection. However, adjustments to dosing schedules may help de-risk the chance of infection further and reduce the concerns of people with MS being treated during the COVID-19 pandemic.", "qid": 3, "docid": "j67b1leq", "rank": 33, "score": 0.7598286271095276}, {"content": "Title: Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period Content: It is urgent to understand the future of severe acute respiratory syndrome\u2013coronavirus 2 (SARS-CoV-2) transmission. We used estimates of seasonality, immunity, and cross-immunity for betacoronaviruses OC43 and HKU1 from time series data from the USA to inform a model of SARS-CoV-2 transmission. We projected that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after the initial, most severe pandemic wave. Absent other interventions, a key metric for the success of social distancing is whether critical care capacities are exceeded. To avoid this, prolonged or intermittent social distancing may be necessary into 2022. Additional interventions, including expanded critical care capacity and an effective therapeutic, would improve the success of intermittent distancing and hasten the acquisition of herd immunity. Longitudinal serological studies are urgently needed to determine the extent and duration of immunity to SARS-CoV-2. Even in the event of apparent elimination, SARS-CoV-2 surveillance should be maintained since a resurgence in contagion could be possible as late as 2024.", "qid": 3, "docid": "f5p37j7g", "rank": 34, "score": 0.7596730589866638}, {"content": "Title: Grundlagen der Replikation und der Immunologie von SARS-CoV-2 Content: Coronaviruses are a genetically highly variable family of viruses that infect vertebrates and have succeeded in infecting humans many times by overcoming the species barrier. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially appeared in China at the end of 2019, exhibits a high infectivity and pathogenicity compared to other coronaviruses. As the viral coat and other viral components are recognized as being foreign by the immune system, this can lead to initial symptoms, which are induced by the very efficiently working immune defense system via the respiratory epithelium. During severe courses a systemically expressed proinflammatory cytokine storm and subsequent changes in the coagulation and complement systems can occur. Virus-specific antibodies, the long-term expression of which is ensured by the formation of B memory cell clones, generate a specific immune response that is also detectable in blood (seroconversion). Specifically effective cytotoxic CD8+ T\u2011cell populations are also formed, which recognize viral epitopes as pathogen-specific patterns in combination with MHC presentation on the cell surface of virus-infected cells and destroy these cells. At the current point in time it is unclear how regular, robust and durable this immune status is constructed. Experiences with other coronavirus infections (SARS and Middle East respiratory syndrome, MERS) indicate that the immunity could persist for several years. Based on animal experiments, already acquired data on other coronavirus types and plausibility assumptions, it can be assumed that seroconverted patients have an immunity of limited duration and only a very low risk of reinfection. Knowledge of the molecular mechanisms of viral cycles and immunity is an important prerequisite for the development of vaccination strategies and development of effective drugs.", "qid": 3, "docid": "neq2vqym", "rank": 35, "score": 0.7594936490058899}, {"content": "Title: Grundlagen der Replikation und der Immunologie von SARS-CoV-2./ [Basic principles of replication and immunology of SARS-CoV-2] Content: Coronaviruses are a genetically highly variable family of viruses that infect vertebrates and have succeeded in infecting humans many times by overcoming the species barrier. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially appeared in China at the end of 2019, exhibits a high infectivity and pathogenicity compared to other coronaviruses. As the viral coat and other viral components are recognized as being foreign by the immune system, this can lead to initial symptoms, which are induced by the very efficiently working immune defense system via the respiratory epithelium. During severe courses a systemically expressed proinflammatory cytokine storm and subsequent changes in the coagulation and complement systems can occur. Virus-specific antibodies, the long-term expression of which is ensured by the formation of B memory cell clones, generate a specific immune response that is also detectable in blood (seroconversion). Specifically effective cytotoxic CD8+ T\u00adcell populations are also formed, which recognize viral epitopes as pathogen-specific patterns in combination with MHC presentation on the cell surface of virus-infected cells and destroy these cells. At the current point in time it is unclear how regular, robust and durable this immune status is constructed. Experiences with other coronavirus infections (SARS and Middle East respiratory syndrome, MERS) indicate that the immunity could persist for several years. Based on animal experiments, already acquired data on other coronavirus types and plausibility assumptions, it can be assumed that seroconverted patients have an immunity of limited duration and only a very low risk of reinfection. Knowledge of the molecular mechanisms of viral cycles and immunity is an important prerequisite for the development of vaccination strategies and development of effective drugs.", "qid": 3, "docid": "r6y70to9", "rank": 36, "score": 0.759476900100708}, {"content": "Title: Cross-reactive neutralization of SARS-CoV-2 by serum antibodies from recovered SARS patients and immunized animals Content: The current COVID-19 pandemic, caused by a novel coronavirus SARS-CoV-2, poses serious threats to public health and social stability, calling for urgent need for vaccines and therapeutics. SARS-CoV-2 is genetically close to SARS-CoV, thus it is important to define the between antigenic cross-reactivity and neutralization. In this study, we firstly analyzed 20 convalescent serum samples collected from SARS-CoV infected individuals during the 2003 SARS outbreak. All patient sera reacted strongly with the S1 subunit and receptor-binding domain (RBD) of SARS-CoV, cross-reacted with the S ectodomain, S1, RBD, and S2 proteins of SARS-CoV-2, and neutralized both SARS-CoV and SARS-CoV-2 S protein-driven infections. Multiple panels of antisera from mice and rabbits immunized with a full-length S and RBD immunogens of SARS-CoV were also characterized, verifying the cross-reactive neutralization against SARS-CoV-2. Interestingly, we found that a palm civet SARS-CoV-derived RBD elicited more potent cross-neutralizing responses in immunized animals than the RBD from a human SARS-CoV strain, informing a strategy to develop a universe vaccine against emerging CoVs. Summary Serum antibodies from SARS-CoV infected patients and immunized animals cross-neutralize SARS-CoV-2 suggests strategies for universe vaccines against emerging CoVs.", "qid": 3, "docid": "7jwhypgs", "rank": 37, "score": 0.7592587471008301}, {"content": "Title: Antibody Dependent Enhancement Due to Original Antigenic Sin and the Development of SARS Content: Human coronavirus (HCoV) is one of the most common causes of respiratory tract infections throughout the world. Two phenomena observed so far in the development of the SARS-CoV-2 pandemic deserve further attention. First, the relative absence of clinical signs of infections in children, second, the early appearance of IgG in certain patients. From the point of view of immune system physiology, such an early rise of specific IgG is expected in secondary immune responses when memory to a cross-reactive antigen is present, usually from an earlier infection with a coronavirus. It is actually typical for the immune system to respond, to what it already knows, a phenomenon that has been observed in many infections with closely related viruses and has been termed \u201coriginal antigenic sin.\u201d The question then arises whether such cross-reactive antibodies are protective or not against the new virus. The worst scenario would be when such cross-reactive memory antibodies to related coronaviruses would not only be non-protective but even enhance infection and the clinical course. Such a phenomenon of antibody dependent enhancement (ADE) has already been described in several viral infections. Thus, the development of IgG against SARS-CoV-2 in the course of COVID-19 might not be a simple sign of viral clearance and developing protection against the virus. On the contrary, due to cross-reaction to related coronavirus strains from earlier infections, in certain patients IgG might enhance clinical progression due to ADE. The patient's viral history of coronavirus infection might be crucial to the development of the current infection with SARS-CoV-2. Furthermore, it poses a note of caution when treating COVID-19 patients with convalescent sera.", "qid": 3, "docid": "7k24r3p5", "rank": 38, "score": 0.7587982416152954}, {"content": "Title: Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections Content: The World Health Organization has recently declared the ongoing outbreak of COVID-19, which is caused by a novel coronavirus SARS-CoV-2, as pandemic. There is currently a lack of knowledge in the antibody response elicited from SARS-CoV-2 infection. One major immunological question is concerning the antigenic differences between SARS-CoV-2 and SARS-CoV. We address this question by using plasma from patients infected by SARS-CoV-2 or SARS-CoV, and plasma obtained from infected or immunized mice. Our results show that while cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the live viruses is rare, indicating the presence of non-neutralizing antibody response to conserved epitopes in the spike. Whether these non-neutralizing antibody responses will lead to antibody-dependent disease enhancement needs to be addressed in the future. Overall, this study not only addresses a fundamental question regarding the antigenicity differences between SARS-CoV-2 and SARS-CoV, but also has important implications in vaccine", "qid": 3, "docid": "ukz73rp2", "rank": 39, "score": 0.7585360407829285}, {"content": "Title: Discrete SIRIR modelling using empirical infection data shows that SARS-CoV-2 infection provides short-term immunity Content: The novel coronavirus SARS-CoV-2, which causes the COVID-19 disease, is now a global pandemic. Since December 2019, it has infected millions of people, caused the deaths of hundreds of thousands, and resulted in incalculable social and economic damage. Understanding the infectivity and transmission dynamics of the virus is essential for understanding how best to reduce mortality whilst ensuring minimal social restrictions to the lives of the general population. Anecdotal evidence is available, but detailed studies have not yet revealed whether infection with the virus results in immunity. In this work, we have extended the generic SIR framework to analyse empirical infection and fatality data from different regions to investigate the reinfection frequency of the disease. Our model predicts that cases of reinfection should have been observed by now if primary SARS-CoV-2 infection did not protect from subsequent exposure in the short term, however, no such cases have been documented. This work, therefore, provides a useful insight for serological testing strategies, lockdown easing and vaccine design.", "qid": 3, "docid": "el7mdliy", "rank": 40, "score": 0.7583455443382263}, {"content": "Title: Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections Content: Summary The World Health Organization has declared the ongoing outbreak of COVID-19, which is caused by a novel coronavirus SARS-CoV-2, as pandemic. There is currently a lack of knowledge about the antibody response elicited from SARS-CoV-2 infection. One major immunological question concerns antigenic differences between SARS-CoV-2 and SARS-CoV. We address this question by analyzing plasma from patients infected by SARS-CoV-2 or SARS-CoV, and from infected or immunized mice. Our results show that, while cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the live viruses may be rare, indicating the presence of non-neutralizing antibody response to conserved epitopes in the spike. Whether such low or non-neutralizing antibody response leads to antibody-dependent disease enhancement needs to be addressed in the future. Overall, this study not only addresses a fundamental question regarding antigenicity differences between SARS-CoV-2 and SARS-CoV, but also has implications for immunogen design and vaccine development.", "qid": 3, "docid": "mxafg0t9", "rank": 41, "score": 0.7574136853218079}, {"content": "Title: Antibody profiling of COVID-19 patients in an urban low-incidence region in Northern Germany Content: This explorative monocentric study shows IgA and IgG antibody profiles from 110 patients with self-reported mild to moderate, or no COVID-19 related symptoms after laboratory-confirmed infection with SARS-CoV-2. The study region is in an urban and well-defined environment in a low-incidence region in Northern Germany. We found that approx. 70 % of the patients developed sustainable antibodies 3 weeks or later after the infection. In about 30 % of the patients with mild to moderate symptoms, no significant antibodies could be detected in two consecutive analyses. Conversely, out of ten patients without symptoms, four were repeatedly positive. Expectedly, six had no specific antibodies. The data indicate that antibody-positivity is a useful indicator of a previous SARS-CoV-2 infection. Negative antibodies do not rule out SARS-CoV-2 infection. Future studies need to determine the functionality of the antibodies in terms of personal protection and ability to transmit the virus.", "qid": 3, "docid": "4888p05u", "rank": 42, "score": 0.7564213275909424}, {"content": "Title: Kinetics of viral load and antibody response in relation to COVID-19 severity Content: The SARS-CoV-2 is the causative agent for COVID-19 pneumonia. Little is known about the kinetics, tissue distribution, cross-reactivity and neutralization antibody response in COVID-19 patients. Two groups of RT-PCR confirmed COVID-19 patients were enrolled in this study, including 12 severe patients in ICUs who needed mechanical ventilation and 11 mild patients in isolation wards. Serial clinical samples were collected for laboratory detection. Results showed that most of the severe patients had viral shedding in a variety of tissues for 20~40 days post onset of disease (8/12, 66.7%); while the majority of mild patients had viral shedding restricted to the respiratory tract and had no detectable virus RNA after 10 days post-onset (9/11, 81.8%). Mild patients showed significantly lower IgM response compared with that of the severe group. IgG responses were detected in most patients in both severe and mild groups at 9 days post onset and remained high level throughout the study. Antibodies cross-reactive to SARS-CoV and SARS-CoV-2 were detected in COVID-19 patients but not in MERS patients. High-levels of neutralizing antibodies were induced after about 10 days post onset in both severe and mild patients which were higher in the severe group. SARS-CoV-2 pseudotype neutralization test and focus reduction neutralization test with authentic virus showed consistent results. Sera from COVID-19 patients, but not convalescent SARS and MERS patients inhibited SARS-CoV-2 entry. Anti-SARS-CoV-2 S and N IgG level exhibited moderate correlation with neutralization titers in patients' plasma. This study improves our understanding of immune response in human after SARS-CoV-2 infection.", "qid": 3, "docid": "vtvdk8qj", "rank": 43, "score": 0.7564205527305603}, {"content": "Title: Kinetics of viral load and antibody response in relation to COVID-19 severity. Content: The SARS-CoV-2 is the causative agent for COVID-19 pneumonia. Little is known about the kinetics, tissue distribution, cross-reactivity and neutralization antibody response in COVID-19 patients. Two groups of RT-PCR confirmed COVID-19 patients were enrolled in this study, including 12 severe patients in ICUs who needed mechanical ventilation and 11 mild patients in isolation wards. Serial clinical samples were collected for laboratory detection. Results showed that most of the severe patients had viral shedding in a variety of tissues for 20~40 days post onset of disease (8/12, 66.7%); while the majority of mild patients had viral shedding restricted to the respiratory tract and had no detectable virus RNA after 10 days post-onset (9/11, 81.8%). Mild patients showed significantly lower IgM response compared with that of the severe group. IgG responses were detected in most patients in both severe and mild groups at 9 days post onset and remained high level throughout the study. Antibodies cross-reactive to SARS-CoV and SARS-CoV-2 were detected in COVID-19 patients but not in MERS patients. High-levels of neutralizing antibodies were induced after about 10 days post onset in both severe and mild patients which were higher in the severe group. SARS-CoV-2 pseudotype neutralization test and focus reduction neutralization test with authentic virus showed consistent results. Sera from COVID-19 patients, but not convalescent SARS and MERS patients inhibited SARS-CoV-2 entry. Anti-SARS-CoV-2 S and N IgG level exhibited moderate correlation with neutralization titers in patients' plasma. This study improves our understanding of immune response in human after SARS-CoV-2 infection.", "qid": 3, "docid": "ehe1uj7i", "rank": 44, "score": 0.7564205527305603}, {"content": "Title: Protective Adaptive Immunity Against Severe Acute Respiratory Syndrome Coronaviruses 2 (SARS-CoV-2) and Implications for Vaccines Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging human coronavirus responsible for coronavirus disease 2019 (COVID-19), a predominantly respiratory disease that has become a global pandemic. Millions of people worldwide are suffering from COVID-19, and hundreds of thousands of those infected have died. Nevertheless, many more people who have been infected with SARS-CoV-2 are asymptomatic or suffer a mild disease characterized by dry cough and mild fever. This new pandemic poses a threat to public health on a global scale, and an intervention to prevent continued spread of SARS-CoV-2 virus is of the utmost importance. To assess preventive and therapeutic strategies, it is imperative to understand the pathogenesis and immune response against SARS-CoV-2. In this review, we concentrate on the protective adaptive immune response elicited by this novel coronavirus as well as requirements for a successful vaccine inducing optimal protection.", "qid": 3, "docid": "bcqdm2b1", "rank": 45, "score": 0.7561659216880798}, {"content": "Title: Antibody Dependent Enhancement Due to Original Antigenic Sin and the Development of SARS Content: Human coronavirus (HCoV) is one of the most common causes of respiratory tract infections throughout the world. Two phenomena observed so far in the development of the SARS-CoV-2 pandemic deserve further attention. First, the relative absence of clinical signs of infections in children, second, the early appearance of IgG in certain patients. From the point of view of immune system physiology, such an early rise of specific IgG is expected in secondary immune responses when memory to a cross-reactive antigen is present, usually from an earlier infection with a coronavirus. It is actually typical for the immune system to respond, to what it already knows, a phenomenon that has been observed in many infections with closely related viruses and has been termed \"original antigenic sin.\" The question then arises whether such cross-reactive antibodies are protective or not against the new virus. The worst scenario would be when such cross-reactive memory antibodies to related coronaviruses would not only be non-protective but even enhance infection and the clinical course. Such a phenomenon of antibody dependent enhancement (ADE) has already been described in several viral infections. Thus, the development of IgG against SARS-CoV-2 in the course of COVID-19 might not be a simple sign of viral clearance and developing protection against the virus. On the contrary, due to cross-reaction to related coronavirus strains from earlier infections, in certain patients IgG might enhance clinical progression due to ADE. The patient's viral history of coronavirus infection might be crucial to the development of the current infection with SARS-CoV-2. Furthermore, it poses a note of caution when treating COVID-19 patients with convalescent sera.", "qid": 3, "docid": "nacxjt2f", "rank": 46, "score": 0.7560814619064331}, {"content": "Title: Cross-reactive Antibody Response between SARS-CoV-2 and SARS-CoV Infections Content: The World Health Organization has declared the ongoing outbreak of COVID-19, which is caused by a novel coronavirus SARS-CoV-2, a pandemic. There is currently a lack of knowledge about the antibody response elicited from SARS-CoV-2 infection. One major immunological question concerns antigenic differences between SARS-CoV-2 and SARS-CoV. We address this question by analyzing plasma from patients infected by SARS-CoV-2 or SARS-CoV and from infected or immunized mice. Our results show that, although cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the live viruses may be rare, indicating the presence of a non-neutralizing antibody response to conserved epitopes in the spike. Whether such low or non-neutralizing antibody response leads to antibody-dependent disease enhancement needs to be addressed in the future. Overall, this study not only addresses a fundamental question regarding antigenicity differences between SARS-CoV-2 and SARS-CoV but also has implications for immunogen design and vaccine development.", "qid": 3, "docid": "72fokkad", "rank": 47, "score": 0.755895733833313}, {"content": "Title: Detection of SARS-CoV-2-Specific Humoral and Cellular Immunity in COVID-19 Convalescent Individuals Content: The World Health Organization has declared SARS-CoV-2 virus outbreak a worldwide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free, and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in eight newly discharged patients. Follow-up analysis on another cohort of six patients 2 weeks post discharge also revealed high titers of immunoglobulin G (IgG) antibodies. In all 14 patients tested, 13 displayed serum-neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It also has implications in developing an effective vaccine to SARS-CoV-2 infection.", "qid": 3, "docid": "53j3ly3v", "rank": 48, "score": 0.7558078765869141}, {"content": "Title: SARS-CoV-2: An immunogenetics call to arms. Content: Susceptibility to viral infection, development of immunity, response to treatment and patient clinical outcomes are all under the control of heritable factors in the host. In the context of the current SARS-Cov-2 pandemic, this review considers existing immunogenetic knowledge of virus-immune system interactions. A major focus is to highlight areas in which work is required in order to improve understanding of antiviral immune responses and to move towards improved patient management.", "qid": 3, "docid": "t6ohub5r", "rank": 49, "score": 0.7553550004959106}, {"content": "Title: Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals Content: Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide \"megapools,\" circulating SARS-CoV-2-specific CD8+ and CD4+ T cells were identified in \u00e2\u0088\u00bc70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike, and N proteins each accounted for 11%-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a, and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2-reactive CD4+ T cells in \u00e2\u0088\u00bc40%-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating \"common cold\" coronaviruses and SARS-CoV-2.", "qid": 3, "docid": "wxti06ng", "rank": 50, "score": 0.7547203302383423}, {"content": "Title: The dynamics of humoral immune responses following SARS-CoV-2 infection and the potential for reinfection Content: SARS-CoV-2 is a novel coronavirus that is the causative agent of coronavirus infectious disease 2019 (COVID-19). As of 17 April 2020, it has infected 2\u00e2\u0080\u008a114\u00e2\u0080\u008a269 people, resulting in 145\u00e2\u0080\u008a144 deaths. The timing, magnitude and longevity of humoral immunity is not yet understood for SARS-CoV-2. Nevertheless, understanding this is urgently required to inform the likely future dynamics of the pandemic, to guide strategies to allow relaxation of social distancing measures and to understand how to deploy limiting vaccine doses when they become available to achieve maximum impact. SARS-CoV-2 is the seventh human coronavirus to be described. Four human coronaviruses circulate seasonally and cause common colds. Two other coronaviruses, SARS and MERS, have crossed from animal sources into humans but have not become endemic. Here we review what is known about the human humoral immune response to epidemic SARS CoV and MERS CoV and to the seasonal, endemic coronaviruses. Then we summarize recent, mostly non-peer reviewed, studies into SARS-CoV-2 serology and reinfection in humans and non-human primates and summarize current pressing research needs.", "qid": 3, "docid": "fzdmcahf", "rank": 51, "score": 0.7545343637466431}, {"content": "Title: SARS-CoV-2 seroconversion in health care workers Content: Background The correlates of protection against SARS-CoV-2 and their longevity remain unclear. Studies in severely ill individuals have identified robust cellular and humoral immune responses against the virus. Asymptomatic infection with SARS-CoV-2 has also been described, but it is unknown whether this is sufficient to produce antibody responses. Methods We performed a cross-sectional study recruiting 554 health care workers from University Hospitals Birmingham NHS Foundation Trust who were at work and asymptomatic. Participants were tested for current infection with SARS-CoV-2 by nasopharyngeal swab for real-time polymerase chain reaction and for seroconversion by the measurement of anti-SARS-CoV-2 spike glycoprotein antibodies by enzyme linked immunosorbent assay. Results were interpreted in the context of previous, self-reported symptoms of illness consistent with COVID-19. Results The point prevalence of infection with SARS-CoV-2, determined by the detection of SARS-CoV-2 RNA on nasopharnygeal swab was 2.39% (n=13/544). Serum was available on 516 participants. The overall rate of seroconversion in the cohort was 24.4% (n=126/516). Individuals who had previously experienced a symptomatic illness consistent with COVID-19 had significantly greater seroconversion rates than those who had remained asymptomatic (37.5% vs 17.1%, {chi}2 =21.1034, p<0.0001). In the week preceding peak COVID-19-related mortality at UHBFT, seroconversion rates amongst those who were suffering from symptomatic illnesses peaked at 77.8%. Prior symptomatic illness generated quantitatively higher antibody responses than asymptomatic seroconversion. Seroconversion rates were highest amongst those working in housekeeping (34.5%), acute medicine (33.3%) and general internal medicine (30.3%) with lower rates observed in participants working in intensive care (14.8%) and emergency medicine (13.3%). Conclusions In a large cross-sectional seroprevalence study of health-care workers, we demonstrate that asymptomatic seroconversion occurs, however prior symptomatic illness is associated with quantitatively higher antibody responses. The identification that the potential for seroconversion in health-care workers can associate differentially with certain hospital departments may inform future infection control and occupational health practices.", "qid": 3, "docid": "2a12nsnl", "rank": 52, "score": 0.7545189261436462}, {"content": "Title: Lack of Reinfection in Rhesus Macaques Infected with SARS-CoV-2 Content: A global pandemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is ongoing spread. It remains unclear whether the convalescing patients have a risk of reinfection. Rhesus macaques were rechallenged with SARS-CoV-2 during an early recovery phase from initial infection characterized by weight loss, interstitial pneumonia and systemic viral dissemination mainly in respiratory and gastrointestinal tracts. The monkeys rechallenged with the identical SARS-CoV-2 strain have failed to produce detectable viral dissemination, clinical manifestations and histopathological changes. A notably enhanced neutralizing antibody response might contribute the protection of rhesus macaques from the reinfection by SARS-CoV-2. Our results indicated that primary SARS-CoV-2 infection protects from subsequent reinfection. One Sentence Summary Neutralizing antibodies against SARS-CoV-2 might protect rhesus macaques which have undergone an initial infection from reinfection during early recovery days.", "qid": 3, "docid": "q4m2uj6r", "rank": 53, "score": 0.754199743270874}, {"content": "Title: Projecting the transmission dynamics of SARS-CoV-2 through the post-pandemic period Content: There is an urgent need to project how transmission of the novel betacoronavirus SARS-CoV-2 will unfold in coming years. These dynamics will depend on seasonality, the duration of immunity, and the strength of cross-immunity to/from the other human coronaviruses. Using data from the United States, we measured how these factors affect transmission of human betacoronaviruses HCoV-OC43 and HCoV-HKU1. We then built a mathematical model to simulate transmission of SARS-CoV-2 through the year 2025. We project that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after an initial pandemic wave. We summarize the full range of plausible transmission scenarios and identify key data still needed to distinguish between them, most importantly longitudinal serological studies to determine the duration of immunity to SARS-CoV-2.", "qid": 3, "docid": "f4hj35dr", "rank": 54, "score": 0.7541399598121643}, {"content": "Title: Gaining insights on immune responses to the novel coronavirus, COVID-19 and therapeutic challenges Content: SARS-CoV-2 is a new member of coronaviruses that its sudden spreading put the health care system of most countries in a tremendous shock. For controlling of the new infection, COVID-19, many efforts have been done and are ongoing to defeat this virus in the combat field. In this review, we focused on how the immune system behaves toward the virus and the relative possible consequences during their interactions. Then the therapeutic steps and potential vaccine candidates have been described in a hope to provide a better prospective of effective treatment and preventive strategies to the novel SARS-CoV in near future.", "qid": 3, "docid": "59cuhfi5", "rank": 55, "score": 0.7539846301078796}, {"content": "Title: SARS-CoV-2 reactive T cells in uninfected individuals are likely expanded by beta-coronaviruses Content: The current pandemic is caused by the SARS-CoV-2 virus and large progress in understanding the pathology of the virus has been made since its emergence in late 2019. Several reports indicate short lasting immunity against endemic coronaviruses, which contrasts repeated reports that biobanked venous blood contains SARS-CoV-2 reactive T cells even before the outbreak in Wuhan. This suggests there exists a preformed T cell memory in individuals not exposed to the pandemic virus. Given the similarity of SARS-CoV-2 to other members of the Coronaviridae family, the endemic coronaviruses appear likely candidates to generate this T cell memory. However, given the apparent poor immunological memory created by the endemic coronaviruses, other immunity against other common pathogens might offer an alternative explanation. Here, we utilize a combination of epitope prediction and similarity to common human pathogens to identify potential sources of the SARS-CoV-2 T cell memory. We find that no common human virus, other than beta-coronaviruses, can explain the pre-existing SARS-CoV-2 reactive T cells in uninfected individuals. Our study suggests OC43 and HKU1 are the most likely pathogens giving rise to SARS-CoV-2 preformed immunity.", "qid": 3, "docid": "guzohu7y", "rank": 56, "score": 0.7535053491592407}, {"content": "Title: Coronaviruses pandemics: Can neutralizing antibodies help? Content: For the first time in Homo sapiens history, possibly, most of human activities is stopped by coronavirus disease 2019 (COVID-19). Nearly eight billion people of this world are facing a great challenge, maybe not \"to be or not to be\" yet, but unpredictable. What happens to other major pandemics in the past, and how human beings went through these hurdles? The human body is equipped with the immune system that can recognize, respond and fight against pathogens such as viruses. Following the innate response, immune system processes the adaptive response by which each pathogen is encoded and recorded in memory system. The humoral reaction containing cytokines and antibodies is expected to activate when the pathogens come back. Exploiting this nature of body protection, neutralizing antibodies have been investigated. Learning from past, in parallel to SARS-CoV-2, other coronaviruses SARS-CoV and MERS-CoV who caused previous pandemics, are recalled in this review. We here propose insights of origin and characteristics and perspective for the future of antibodies development.", "qid": 3, "docid": "ad6ztoba", "rank": 57, "score": 0.7530634999275208}, {"content": "Title: The importance of naturally attenuated SARS-CoV-2in the fight against COVID-19 Content: The current SARS-CoV-2 pandemic is wreaking havoc throughout the world and has rapidly become a global health emergency. A central question concerning COVID-19 is why some individuals become sick and others not. Many have pointed already at variation in risk factors between individuals. However, the variable outcome of SARS-CoV-2 infections may, at least in part, be due also to differences between the viral subspecies with which individuals are infected. A more pertinent question is how we are to overcome the current pandemic. A vaccine against SARS-CoV-2 would offer significant relief, although vaccine developers have warned that design, testing and production of vaccines may take a year if not longer. Vaccines are based on a handful of different designs (i), but the earliest vaccines were based on the live, attenuated virus. As has been the case for other viruses during earlier pandemics, SARS-CoV-2 will mutate and may naturally attenuate over time (ii). What makes the current pandemic unique is that, thanks to state-of-the-art nucleic acid sequencing technologies, we can follow in detail how SARS-CoV-2 evolves while it spreads. We argue that knowledge of naturally emerging attenuated SARS-CoV-2 variants across the globe should be of key interest in our fight against the pandemic.", "qid": 3, "docid": "9fnghyn4", "rank": 58, "score": 0.7524579167366028}, {"content": "Title: The Importance of Advancing SARS-CoV-2 Vaccines in Children Content: While the role of children in the chain of transmission of SARS-CoV-2 remains to be fully defined, they likely play an important role based on our knowledge of other respiratory viruses. Children are more likely to be asymptomatic or have milder symptoms and less likely to present for healthcare and be tested for SARS-CoV-2; thus, our current estimates are likely under-representative of the true burden of SARS-CoV-2 in children. Given the potential direct benefit of a SARS-CoV-2 vaccine in children and the substantial indirect benefit through community protection or 'herd immunity', we argue that planning and implementation of SARS-CoV-2 vaccines should include children. Furthermore, community protection occurred after widespread implementation of prior childhood vaccines against Streptococcus pneumoniae, rubella and rotavirus. We detail considerations for vaccine clinical trials, potential barriers to the implementation of widespread vaccination and argue why children would be an ideal target population for vaccination.", "qid": 3, "docid": "olim73m8", "rank": 59, "score": 0.7519515156745911}, {"content": "Title: Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals Content: Summary Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide \u2018megapools\u2019, circulating SARS-CoV-2\u2212specific CD8+ and CD4+ T cells were identified in \u223c70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike and N proteins each accounted for 11-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2\u2212reactive CD4+ T cells in \u223c40-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating \u2018common cold\u2019 coronaviruses and SARS-CoV-2.", "qid": 3, "docid": "isivkz8b", "rank": 60, "score": 0.7517845630645752}, {"content": "Title: Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques Content: Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It currently remains unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes. Comparing the humoral and cellular immunity between primary infection and rechallenge revealed notably enhanced neutralizing antibody and immune responses. Our results suggest that primary SARS-CoV-2 exposure protects against subsequent reinfection in rhesus macaques.", "qid": 3, "docid": "tdorhy8x", "rank": 61, "score": 0.7514164447784424}, {"content": "Title: Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques. Content: Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It currently remains unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes. Comparing the humoral and cellular immunity between primary infection and rechallenge revealed notably enhanced neutralizing antibody and immune responses. Our results suggest that primary SARS-CoV-2 exposure protects against subsequent reinfection in rhesus macaques.", "qid": 3, "docid": "5dbuxvc4", "rank": 62, "score": 0.7514163851737976}, {"content": "Title: DNA vaccine protection against SARS-CoV-2 in rhesus macaques Content: The global COVID-19 pandemic caused by the SARS-CoV-2 virus has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 Spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. Following vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log(10) reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.", "qid": 3, "docid": "w9zyshzb", "rank": 63, "score": 0.7512155771255493}, {"content": "Title: Protective immunity after COVID-19 has been questioned: what can we do without SARS-CoV-2-IgG detection? Content: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a severe acute respiratory syndrome that is called COVID-19. Clinical manifestations of COVID-19 include diarrhea, pneumonia, lymphopenia, exhausted lymphocytes, and pro-inflammatory cytokine production. Immunology is part of the process of clinical evolution, but there are some questions around immunity-based protection: (1) why some infected people have only mild symptoms of the disease or are asymptomatic; (2) why delayed and weak antibody responses are associated with severe outcomes; and (3) why positivity in molecular tests does not represent protective antibody IgG. Perhaps T cell responses may be the key to solving those questions. SARS-CoV-2-specific memory T cells persist in peripheral blood and may be capable of providing effective information about protective immunity. The T cells studies can be helpful in elucidating the pathways for development of vaccines, therapies, and diagnostics for COVID-19 and for filling these immunology knowledge gaps.", "qid": 3, "docid": "rsz7ch2a", "rank": 64, "score": 0.750842809677124}, {"content": "Title: Analysis of Serologic Cross-Reactivity Between Common Human Coronaviruses and SARS-CoV-2 Using Coronavirus Antigen Microarray Content: The current practice for diagnosis of SARS-CoV-2 infection relies on PCR testing of nasopharyngeal or respiratory specimens in a symptomatic patient at high epidemiologic risk. This testing strategy likely underestimates the true prevalence of infection, creating the need for serologic methods to detect infections missed by the limited testing to date. Here, we describe the development of a coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2, in addition to SARS-CoV, MERS-CoV, common human coronavirus strains, and other common respiratory viruses. A preliminary study of human sera collected prior to the SARS-CoV-2 pandemic demonstrates overall high IgG reactivity to common human coronaviruses and low IgG reactivity to epidemic coronaviruses including SARS-CoV-2, with some cross-reactivity of conserved antigenic domains including S2 domain of spike protein and nucleocapsid protein. This array can be used to answer outstanding questions regarding SARS-CoV-2 infection, including whether baseline serology for other coronaviruses impacts disease course, how the antibody response to infection develops over time, and what antigens would be optimal for vaccine development.", "qid": 3, "docid": "lw12h047", "rank": 65, "score": 0.7502328157424927}, {"content": "Title: Coronaviruses pandemics: Can neutralizing antibodies help? Content: For the first time in Homo sapiens history, possibly, most of human activities is stopped by coronavirus disease 2019 (COVID-19). Nearly eight billion people of this world are facing a great challenge, maybe not \u201cto be or not to be\u201d yet, but unpredictable. What happens to other major pandemics in the past, and how human beings went through these hurdles? The human body is equipped with the immune system that can recognize, respond and fight against pathogens such as viruses. Following the innate response, immune system processes the adaptive response by which each pathogen is encoded and recorded in memory system. The humoral reaction containing cytokines and antibodies is expected to activate when the pathogens come back. Exploiting this nature of body protection, neutralizing antibodies have been investigated. Learning from past, in parallel to SARS-CoV-2, other coronaviruses SARS-CoV and MERS-CoV who caused previous pandemics, are recalled in this review. We here propose insights of origin and characteristics and perspective for the future of antibodies development.", "qid": 3, "docid": "qhelk6u6", "rank": 66, "score": 0.7498406767845154}, {"content": "Title: The Importance Of Naturally Attenuated Sars\u2010Cov\u20102 In The Fight Against Covid\u201019 Content: The current SARS\u2010CoV\u20102 pandemic is wreaking havoc throughout the world and has rapidly become a global health emergency. A central question concerning COVID\u201019 is why some individuals become sick and others not. Many have pointed already at variation in risk factors between individuals. However, the variable outcome of SARS\u2010CoV\u20102 infections may, at least in part, be due also to differences between the viral subspecies with which individuals are infected. A more pertinent question is how we are to overcome the current pandemic. A vaccine against SARS\u2010CoV\u20102 would offer significant relief, although vaccine developers have warned that design, testing, and production of vaccines may take a year if not longer. Vaccines are based on a handful of different designs (1), but the earliest vaccines were based on live, attenuated virus. As has been the case for other viruses during earlier pandemics, SARS\u2010CoV\u20102 will mutate and may naturally attenuate over time (2). What makes the current pandemic unique is that, thanks to state\u2010of\u2010the\u2010art nucleic acid sequencing technologies, we can follow in detail how SARS\u2010CoV\u20102 evolves while it spreads. We argue that knowledge of naturally emerging attenuated SARS\u2010CoV\u20102 variants across the globe should be of key interest in our fight against the pandemic. This article is protected by copyright. All rights reserved.", "qid": 3, "docid": "kh54yctx", "rank": 67, "score": 0.7494977116584778}, {"content": "Title: Evidence Supporting Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 While Presymptomatic or Asymptomatic Content: Recent epidemiologic, virologic, and modeling reports support the possibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission from persons who are presymptomatic (SARS-CoV-2 detected before symptom onset) or asymptomatic (SARS-CoV-2 detected but symptoms never develop). SARS-CoV-2 transmission in the absence of symptoms reinforces the value of measures that prevent the spread of SARS-CoV-2 by infected persons who may not exhibit illness despite being infectious. Critical knowledge gaps include the relative incidence of asymptomatic and symptomatic SARS-CoV-2 infection, the public health interventions that prevent asymptomatic transmission, and the question of whether asymptomatic SARS-CoV-2 infection confers protective immunity.", "qid": 3, "docid": "g12i1jig", "rank": 68, "score": 0.7493191957473755}, {"content": "Title: The dynamics of humoral immune responses following SARS-CoV-2 infection and the potential for reinfection. Content: SARS-CoV-2 is a novel coronavirus that is the causative agent of coronavirus infectious disease 2019 (COVID-19). As of 17 April 2020, it has infected 2 114 269 people, resulting in 145 144 deaths. The timing, magnitude and longevity of humoral immunity is not yet understood for SARS-CoV-2. Nevertheless, understanding this is urgently required to inform the likely future dynamics of the pandemic, to guide strategies to allow relaxation of social distancing measures and to understand how to deploy limiting vaccine doses when they become available to achieve maximum impact. SARS-CoV-2 is the seventh human coronavirus to be described. Four human coronaviruses circulate seasonally and cause common colds. Two other coronaviruses, SARS and MERS, have crossed from animal sources into humans but have not become endemic. Here we review what is known about the human humoral immune response to epidemic SARS CoV and MERS CoV and to the seasonal, endemic coronaviruses. Then we summarize recent, mostly non-peer reviewed, studies into SARS-CoV-2 serology and reinfection in humans and non-human primates and summarize current pressing research needs.", "qid": 3, "docid": "ipw96f03", "rank": 69, "score": 0.7493181228637695}, {"content": "Title: T cells found in COVID-19 patients \u2018bode well\u2019 for long-term immunity Content: SARS-CoV-2, the virus that causes COVID-19, has been unclear Now, two studies reveal that infected people harbor T cells that target the virus\u2014and may help them recover Both studies also found that some people never infected with SARS-CoV-2 have these cellular defenses, most likely because they were previously infected with other coronaviruses \u201cThis is encouraging data,\u201d says virologist Angela Rasmussen of Columbia University Although the studies don\u2019t clarify whether people who clear a SARS-CoV-2 infection can ward off the virus in the future, both identified strong T cell responses to it, which \u201cbodes well for the development of long-term protective immunity,\u201d Rasmussen says The findings could also help researchers create better vaccines", "qid": 3, "docid": "88px7oq2", "rank": 70, "score": 0.749224841594696}, {"content": "Title: The immune vulnerability landscape of the 2019 Novel Coronavirus, SARS-CoV-2 Content: The outbreak of the 2019 Novel Coronavirus (SARS-CoV-2) rapidly spread from Wuhan, China to more than 150 countries, areas or territories, causing staggering number of infections and deaths. A systematic profiling of the immune vulnerability landscape of SARS-CoV-2, which can bring critical insights into the immune clearance mechanism, peptide vaccine development, and antiviral antibody development, is lacking. In this study, we investigated the potential of the SARS-CoV-2 viral proteins to induce class I and II MHC presentation and to form linear antibody epitopes. We created an online database to broadly share the predictions as a resource for the research community. Using this resource, we showed that genetic variations in SARS- CoV-2, though still few for the moment, already follow the pattern of mutations in related coronaviruses, and could alter the immune vulnerability landscape of this virus. Importantly, we discovered evidence that SARS-CoV-2, along with related coronaviruses, used mutations to evade attack from the human immune system. Overall, we present an immunological resource for SARS-CoV-2 that could promote both therapeutic development and mechanistic research.", "qid": 3, "docid": "xetzg7gp", "rank": 71, "score": 0.7490837574005127}, {"content": "Title: FAR AWAY FROM HERD IMMUNITY TO SARS-CoV-2: results from a survey in healthy blood donors in South Eastern Italy Content: Here we present results from a survey on anti-SARS-CoV-2 seroprevalence in healthy blood donors from a low incidence COVID-19 area (Apulia region, South Eastern Italy). Among 904 subjects tested, only in 9 cases (0.99%) antibodies against SARS-CoV-2 were demonstrated. All the 9 seropositive patients were negative for the research of viral RNA by RT-PCR in nasopharyngeal swab. These data, along with those recently reported from other countries, clearly show that we are very far from herd immunity and that the containment measures are at the moment the only realistic instrument we have to slow the spread of the pandemic.", "qid": 3, "docid": "cxtzf5oe", "rank": 72, "score": 0.7490720152854919}, {"content": "Title: The Importance of Advancing SARS-CoV-2 Vaccines in Children Content: While the role of children in the chain of transmission of SARS-CoV-2 remains to be fully defined, they likely play an important role based on our knowledge of other respiratory viruses. Children are more likely to be asymptomatic or have milder symptoms and less likely to present for healthcare and be tested for SARS-CoV-2; thus, our current estimates are likely under-representative of the true burden of SARS-CoV-2 in children. Given the potential direct benefit of a SARS-CoV-2 vaccine in children and the substantial indirect benefit through community protection or \u2018herd immunity\u2019, we argue that planning and implementation of SARS-CoV-2 vaccines should include children. Furthermore, community protection occurred after widespread implementation of prior childhood vaccines against Streptococcus pneumoniae, rubella and rotavirus. We detail considerations for vaccine clinical trials, potential barriers to the implementation of widespread vaccination and argue why children would be an ideal target population for vaccination.", "qid": 3, "docid": "962kva7g", "rank": 73, "score": 0.7488845586776733}, {"content": "Title: Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period Content: It is urgent to understand the future of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) transmission. We used estimates of seasonality, immunity, and cross-immunity for human coronavirus OC43 (HCoV-OC43) and HCoV-HKU1 using time-series data from the United States to inform a model of SARS-CoV-2 transmission. We projected that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after the initial, most severe pandemic wave. Absent other interventions, a key metric for the success of social distancing is whether critical care capacities are exceeded. To avoid this, prolonged or intermittent social distancing may be necessary into 2022. Additional interventions, including expanded critical care capacity and an effective therapeutic, would improve the success of intermittent distancing and hasten the acquisition of herd immunity. Longitudinal serological studies are urgently needed to determine the extent and duration of immunity to SARS-CoV-2. Even in the event of apparent elimination, SARS-CoV-2 surveillance should be maintained because a resurgence in contagion could be possible as late as 2024.", "qid": 3, "docid": "kxsy16bc", "rank": 74, "score": 0.7484937906265259}, {"content": "Title: Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection Content: COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. The T cell response is a critical part of both individual and herd immunity to SARS-CoV-2 and the efficacy of developed vaccines. However neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T cell response nor the diversity of resulting immune memory are well understood. In this study we use longitudinal high-throughput T cell receptor sequencing to track changes in the T cell repertoire following two mild cases of COVID-19 infection. In both donors we identified SARS-CoV-2-responding CD4+ and CD8+ T cell clones. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones, suggesting the existence of immunodominant epitopes. We show that in both donors the majority of infection-reactive clonotypes acquire memory phenotypes. Certain CD4+ clones were detected in the memory fraction at the pre-infection timepoint, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2.", "qid": 3, "docid": "4akxfetl", "rank": 75, "score": 0.7479978799819946}, {"content": "Title: Symptoms and immunoglobulin development in hospital staff exposed to a SARS-CoV-2 outbreak Content: BACKGROUND: Worldwide, the number of SARS-CoV-2 infections is increasing. Serological immunoglobulin tests may help to better understand the development of immune mechanisms against SARS-CoV-2 in COVID-19 cases and exposed but asymptomatic individuals. The aim of this study was to investigate exposure to SARS-CoV-2, symptoms, and antibody responses in a large sample of healthcare workers following a COVID-19 outbreak. METHODS: A COVID-19 outbreak among staff members of a major German children's and women's hospital was followed by massive RT-PCR SARS-CoV-2 tests and provided the opportunity to study symptoms, chains of infection, and SARS-CoV-2-specific antibody responses (IgG and IgA) by ELISA. Study participants were classified as COVID-19 cases, and persons with close, moderate, or no exposure to SARS-CoV-2 in the clinical setting, respectively. RESULTS: Out of 201 study participants, 31 were COVID-19 cases. While most study participants experienced many symptoms indicative for SARS-CoV-2 infection, anosmia and coughing were remarkably more frequent in COVID-19 cases. Approximately 80% of COVID-19 cases developed some specific antibody response (IgA and IgG) approximately 3 weeks after onset of symptoms. Subjects in the non-COVID-19 groups had also elevated IgG (1.8%) and IgA values (7.6%) irrespective of contact history with cases. CONCLUSION: We found that a significant number of diseased did not develop relevant antibody responses three weeks after symptom onset. Our data also suggest that exposure to COVID-19 positive co-workers in a hospital setting is not leading to the development of measurable immune responses in a significant proportion of asymptomatic contact persons.", "qid": 3, "docid": "gcil6lem", "rank": 76, "score": 0.7478615045547485}, {"content": "Title: Humoral immune response and prolonged PCR positivity in a cohort of 1343 SARS-CoV 2 patients in the New York City region Content: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The percentage of infected individuals who seroconvert is still an open question. In addition, it has been shown in some individuals that viral genome can still be detected at considerable time post symptom resolution. Here we investigated both seroconversion and PCR-positivity in a large cohort of convalescent serum donors in New York City. Methods: Individuals with confirmed or suspected SARS-CoV-2 infection were screened via PCR for presence of viral genome and via enzyme-linked immunosorbent assay for presence of anti SARS-CoV-2 spike antibodies. Results: All but three confirmed SARS-CoV-2 patients seroconverted to the SARS-CoV-2 spike while only 37.4% of suspected SARS-CoV-2 patients seroconverted. PCR-positivity was detected up to 28 days from symptom resolution. Conclusions: Here we show that the vast majority of confirmed COVID19 patients seroconvert, potentially providing immunity to reinfection. We also report that in a large proportion of individuals, viral genome can be detected via PCR in the upper respiratory tract for weeks post symptom resolution, but it is unclear if this signal represents infectious virus.", "qid": 3, "docid": "0phcscz8", "rank": 77, "score": 0.7476680278778076}, {"content": "Title: Serologic cross-reactivity of SARS-CoV-2 with endemic and seasonal Betacoronaviruses Content: In order to properly understand the spread of SARS-CoV-2 infection and development of humoral immunity, researchers have evaluated the presence of serum antibodies of people worldwide experiencing the pandemic. These studies rely on the use of recombinant proteins from the viral genome in order to identify serum antibodies that recognize SARS-CoV-2 epitopes. Here, we discuss the cross-reactivity potential of SARS-CoV-2 antibodies with the full spike proteins of four other Betacoronaviruses that cause disease in humans, MERS-CoV, SARS-CoV, HCoV-OC43, and HCoV-HKU1. Using enzyme-linked immunosorbent assays (ELISAs), we detected the potential cross-reactivity of antibodies against SARS-CoV-2 towards the four other coronaviruses, with the strongest cross-recognition between SARS-CoV-2 and SARS /MERS-CoV antibodies, as expected based on sequence homology of their respective spike proteins. Further analysis of cross-reactivity could provide informative data that could lead to intelligently designed pan-coronavirus therapeutics or vaccines.", "qid": 3, "docid": "yigj0u3n", "rank": 78, "score": 0.7472138404846191}, {"content": "Title: Immunology of COVID-19: mechanisms, clinical outcome, diagnostics and perspectives - a report of the European Academy of Allergy and Clinical Immunology (EAACI) Content: With the worldwide spread of the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) resulting in declaration of a pandemic by the World Health Organization (WHO) on March 11, 2020, the SARS-CoV-2-induced Coronavirus disease-19 (COVID-19) has become one of the main challenges of our times. The high infection rate and the severe disease course led to major safety and social restriction measures worldwide. There is an urgent need of unbiased expert knowledge guiding the development of efficient treatment and prevention strategies. This report summarizes current immunological data on mechanisms associated with the SARS-CoV-2 infection and COVID-19 development and progression to the most severe forms. We characterize the differences between adequate innate and adaptive immune response in mild disease and the deep immune dysfunction in the severe multi-organ disease. The similarities of the human immune response to SARS-CoV-2 and the SARS-CoV and MERS-CoV are underlined. We also summarize known and potential SARS-CoV-2 receptors on epithelial barriers, immune cells, endothelium and clinically involved organs such as lung, gut, kidney, cardiovascular and neuronal system. Finally, we discuss the known and potential mechanisms underlying the involvement of comorbidities, gender and age in development of COVID-19. Consequently, we highlight the knowledge gaps and urgent research requirements to provide a quick roadmap for ongoing and needed COVID-19 studies.", "qid": 3, "docid": "65m5b0ii", "rank": 79, "score": 0.7471790313720703}, {"content": "Title: Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection Content: COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cell response is a critical part of both individual and herd immunity to SARS-CoV-2 and the efficacy of developed vaccines. However neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T cell response nor the diversity of resulting immune memory are well understood. In this study we use longitudinal high-throughput T cell receptor sequencing to track changes in the T cell repertoire following two mild cases of COVID-19 infection. In both donors we identified SARS-CoV-2-responding CD4+ and CD8+ T cell clones. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones, suggesting the existence of immunodominant epitopes. We show that in both donors the majority of infection-reactive clonotypes acquire memory phenotypes. Certain CD4+ clones were detected in the memory fraction at the pre-infection timepoint, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2.", "qid": 3, "docid": "fglyfz8p", "rank": 80, "score": 0.7467515468597412}, {"content": "Title: Prevalence of IgG antibodies to SARS-CoV-2 in Wuhan -implications for the ability to produce long-lasting protective antibodies against SARS-CoV-2 Content: Background It is to be determined whether people infected with SARS-CoV-2 will develop long-term immunity against SARS-CoV-2 and retain long-lasting protective antibodies after the infection is resolved. This study was to explore to explore the outcomes of IgG antibodies to SARS-CoV-2 in four groups of individuals in Wuhan, China. Methods We included the following four groups of individuals who received both COVID-19 IgM/IgG tests and RT-PCR tests for SARS-CoV-2 from February 29, 2020 to April 29, 2020: 1470 hospitalized patients with COVID-19 from Leishenshan Hospital, Zhongnan Hospital of Wuhan University, and Wuhan No. 7 Hospital, 3832 healthcare providers without COVID-19 diagnosis, 19555 general workers, and 1616 other patients to be admitted to the hospital (N=26473). COVID-19 patients who received IgM/IgG tests <21 days after symptom onset were excluded. Results IgG prevalence was 89.8% (95% CI 88.2-91.3%) in COVID-19 patients, 4.0% (95% CI 3.4-4.7%) in healthcare providers, 4.6 (95% CI 4.3-4.9 %) in general workers, and 1.0% in other patients (p all <0.001 for comparisons with COVID-19 patients). IgG prevalence increased significantly by age among healthcare workers and general workers. Prevalence of IgM antibodies to SARS-CoV-2 was 31.4% in COVID-19 patients, 1.5% in healthcare providers, 1.3% in general workers, and 0.2% in other patients. Conclusions Very few healthcare providers had IgG antibodies to SARS-CoV-2, though a significant proportion of them had been infected with the virus. After SARS-CoV-2 infection, people are unlikely to produce long-lasting protective antibodies against this virus.", "qid": 3, "docid": "066rysjh", "rank": 81, "score": 0.7465639710426331}, {"content": "Title: Immunologic aspects of characteristics, diagnosis, and treatment of coronavirus disease 2019 (COVID-19) Content: On March 11, 2020, the World Health Organization declared the worldwide spread of the infectious disease COVID-19, caused by a new strain of coronavirus, SARS-CoV-2, as a pandemic. Like in all other infectious diseases, the host immune system plays a key role in our defense against SARS-CoV-2 infection. However, viruses are able to evade the immune attack and proliferate and, in susceptible individuals, cause severe inflammatory response known as cytokine storm, particularly in the lungs. The advancement in our understanding of the mechanisms underlying the host immune responses promises to facilitate the development of approaches for prevention or treatment of diseases. Components of immune system, such as antibodies, can also be used to develop sensitive and specific diagnostic methods as well as novel therapeutic agents. In this review, we summarize our knowledge about how the host mounts immune responses to infection by SARS-CoV-2. We also describe the diagnostic methods being used for COVID-19 identification and summarize the current status of various therapeutic strategies, including vaccination, being considered for treatment of the disease.", "qid": 3, "docid": "nwu4tdgh", "rank": 82, "score": 0.7463980317115784}, {"content": "Title: Immunology of COVID\u201019: mechanisms, clinical outcome, diagnostics and perspectives \u2013 a report of the European Academy of Allergy and Clinical Immunology (EAACI) Content: With the worldwide spread of the novel Severe Acute Respiratory Syndrome Coronavirus\u20102 (SARS\u2010CoV\u20102) resulting in declaration of a pandemic by the World Health Organization (WHO) on March 11, 2020, the SARS\u2010CoV\u20102\u2010induced Coronavirus disease\u201019 (COVID\u201019) has become one of the main challenges of our times. The high infection rate and the severe disease course led to major safety and social restriction measures worldwide. There is an urgent need of unbiased expert knowledge guiding the development of efficient treatment and prevention strategies. This report summarizes current immunological data on mechanisms associated with the SARS\u2010CoV\u20102 infection and COVID\u201019 development and progression to the most severe forms. We characterize the differences between adequate innate and adaptive immune response in mild disease and the deep immune dysfunction in the severe multi\u2010organ disease. The similarities of the human immune response to SARS\u2010CoV\u20102 and the SARS\u2010CoV and MERS\u2010CoV are underlined. We also summarize known and potential SARS\u2010CoV\u20102 receptors on epithelial barriers, immune cells, endothelium and clinically involved organs such as lung, gut, kidney, cardiovascular and neuronal system. Finally, we discuss the known and potential mechanisms underlying the involvement of comorbidities, gender and age in development of COVID\u201019. Consequently, we highlight the knowledge gaps and urgent research requirements to provide a quick roadmap for ongoing and needed COVID\u201019 studies.", "qid": 3, "docid": "y8ry0cbg", "rank": 83, "score": 0.7462360858917236}, {"content": "Title: DNA vaccine protection against SARS-CoV-2 in rhesus macaques Content: The global COVID-19 pandemic caused by the SARS-CoV-2 virus has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 Spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. Following vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.", "qid": 3, "docid": "pfjq2m42", "rank": 84, "score": 0.7460088729858398}, {"content": "Title: Symptoms and immunoglobulin development in hospital staff exposed to a SARS-CoV-2 outbreak. Content: BACKGROUND Worldwide, the number of SARS-CoV-2 infections is increasing. Serological immunoglobulin tests may help to better understand the development of immune mechanisms against SARS-CoV-2 in COVID-19 cases and exposed but asymptomatic individuals. The aim of this study was to investigate exposure to SARS-CoV-2, symptoms and antibody responses in a large sample of health care workers following a COVID-19 outbreak. METHODS A COVID-19 outbreak among staff members of a major German children's and women's hospital was followed by massive RT-PCR SARS-CoV-2 tests and provided the opportunity to study symptoms, chains of infection and SARS-CoV-2 specific antibody responses (IgG and IgA) by ELISA. Study participants were classified as COVID-19 cases, and persons with close, moderate or no exposure to SARS-CoV-2 in the clinical setting, respectively. RESULTS Out of 201 study participants, 31 were COVID-19 cases. While most study participants experienced many symptoms indicative for SARS-CoV-2 infection, anosmia and coughing were remarkably more frequent in COVID-19 cases. Approximately 80% of COVID-19 cases developed some specific antibody response (IgA and IgG) approximately 3 weeks after onset of symptoms. Subjects in the non COVID-19 groups had also elevated IgG (1.8%) and IgA values (7.6%) irrespective of contact history with cases. CONCLUSION We found that a significant number of diseased did not develop relevant antibody responses three weeks after symptom onset. Our data also suggests that exposure to COVID-19 positive co-workers in a hospital setting is not leading to the development of measurable immune responses in a significant proportion of asymptomatic contact-persons.", "qid": 3, "docid": "l11epnl4", "rank": 85, "score": 0.7457910776138306}, {"content": "Title: Dynamics of IgG seroconversion and pathophysiology of COVID-19 infections Content: We report dynamics of seroconversion to SARS-CoV-2 infections detected by IgG ELISA in 177 individuals diagnosed by RT-PCR. Longitudinal analysis identifies 2-7% of individuals who do not seroconvert even weeks after infection. They are younger and less severely affected than seroconverters. Higher antibody responses are associated with symptomatic disease, older age, ethnicity, increased co-morbidity and higher inflammatory markers such as C Reactive Protein. Antibody responses do not decline during follow up almost to 2 months. Serological assays increase understanding of disease severity. Their application in regular surveillance will clarify the duration and protective nature of humoral responses to SARS-CoV.", "qid": 3, "docid": "pkr3immj", "rank": 86, "score": 0.7456339001655579}, {"content": "Title: Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies Content: The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the available SARS-CoV-2 sequences (as of 9 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.", "qid": 3, "docid": "7i52vltp", "rank": 87, "score": 0.7454404830932617}, {"content": "Title: Trained immunity: a tool for reducing susceptibility and severity of SARS-CoV-2 infection Content: Abstract SARS-CoV-2 infection is mild in the majority of individuals, but progresses into severe pneumonia in a small proportion of patients. The increased susceptibility to severe disease in the elderly and individuals with co-morbidities argues for an initial defect in anti-viral host defense mechanisms. Long-term boosting of innate immune responses, also termed \u2018trained immunity\u2019, by certain live vaccines (BCG, oral polio vaccine, measles) induces heterologous protection against infections, through epigenetic, transcriptional and functional reprogramming of innate immune cells. We propose that induction of trained immunity by whole microorganism vaccines may represent an important tool for reducing susceptibility and severity to SARS-CoV-2.", "qid": 3, "docid": "dqs21e0q", "rank": 88, "score": 0.7454139590263367}, {"content": "Title: CD8+ T cell cross-reactivity against SARS-CoV-2 conferred by other coronavirus strains and influenza virus Content: While individuals infected with coronavirus disease 2019 (COVID-19) manifested a broad range in susceptibility and severity to the disease, the pre-existing immune memory of related pathogens can influence the disease outcome. Here, we investigated the potential extent of T cell cross-reactivity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be conferred by other coronaviruses and influenza virus, and generated a map of public and private predicted CD8+ T cell epitopes between coronaviruses. Moreover, to assess the potential risk of self-reactivity and/or diminished T cell response for peptides identical or highly similar to the host, we identified predicted epitopes with high sequence similarity with human proteome. Lastly, we compared predicted epitopes from coronaviruses with epitopes from influenza virus deposited in IEDB to support vaccine development against different virus strains. We believe the comprehensive in silico profile of private and public predicted epitopes across coronaviruses and influenza viruses will facilitate design of vaccines capable of protecting against various viral infections.", "qid": 3, "docid": "x8asawcv", "rank": 89, "score": 0.7453808188438416}, {"content": "Title: Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies Content: The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the 120 available SARS-CoV-2 sequences (as of 21 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.", "qid": 3, "docid": "ojs5e7n9", "rank": 90, "score": 0.7452053427696228}, {"content": "Title: SARS-CoV-2-specific antibody detection in healthcare workers in Germany with direct contact to COVID-19 patients Content: BACKGROUND: The novel coronavirus SARS-CoV-2 is associated with a severe respiratory manifestation, COVID-19, and presents a challenge for healthcare systems worldwide. Healthcare workers are a vulnerable cohort for SARS-CoV-2 infection due to frequent and close contact to patients with COVID-19. STUDY DESIGN: Serum samples from 316 healthcare workers of the University Hospital Essen, Germany were tested for SARS-CoV-2-IgG antibodies. A questionnaire was used to collect demographic and clinical data. Healthcare workers were grouped depending on the frequency of contact to COVID-19 patients in high-risk-group (n = 244) with daily contact to known or suspected SARS-CoV-2 positive patients, intermediated-risk-group (n = 37) with daily contact to patients without known or suspected SARS-CoV-2 infection at admission and low-risk-group (n = 35) without patient contact. RESULTS: In 5 of 316 (1.6%) healthcare workers SARS-CoV-2-IgG antibodies could be detected. The seroprevalence was higher in the intermediate-risk-group vs. high-risk-group vs. 2/37 (5.4%) vs. (3/244 (1.2%), p = 0.13). Four of the five subject were tested negative for SARS-CoV-2 via PCR. One (20%) subject was not tested via PCR since he was asymptomatic. CONCLUSION: The overall seroprevalence of SARS-CoV-2 in healthcare workers of a tertiary hospital in Germany is low (1.6%). The data indicate that the local hygiene standard might be effective.", "qid": 3, "docid": "kriro0t4", "rank": 91, "score": 0.7451714277267456}, {"content": "Title: SARS-CoV-2 viral load and antibody responses: the case for convalescent plasma therapy Content: Most patients with COVID-19 lack antibody to SARS-CoV-2 in the first 10 days of illness while the virus drives disease pathogenesis. SARS-CoV-2 antibody deficiency in the setting of a tissue viral burden suggests that using an antibody as a therapeutic agent would augment the antiviral immune response. In this issue of the JCI, Wang and collaborators describe the kinetics of viral load and antibody responses of 23 individuals with COVID-19 with mild and severe disease. The researchers found: 1) individuals with mild and severe disease produced neutralizing IgG to SARS-CoV-2 10 days after disease onset; 2) SARS-CoV-2 persisted longer in those with severe disease; and 3) there was cross-reactivity between antibodies to SARS-CoV-1 and SARS-CoV-2, but only antibodies from patients with COVID-19 neutralized SARS-CoV-2. These observations provide important information on the serological response to SARS-CoV-2 of hospitalized patients with COVID-19 that can inform the use of convalescent plasma therapy.", "qid": 3, "docid": "tckjc7os", "rank": 92, "score": 0.7451004981994629}, {"content": "Title: SARS-CoV-2 viral load and antibody responses: the case for convalescent plasma therapy. Content: Most patients with COVID-19 lack antibody to SARS-CoV-2 in the first 10 days of illness while the virus drives disease pathogenesis. SARS-CoV-2 antibody deficiency in the setting of a tissue viral burden suggests that using an antibody as a therapeutic agent would augment the antiviral immune response. In this issue of the JCI, Wang and collaborators describe the kinetics of viral load and antibody responses of 23 individuals with COVID-19 with mild and severe disease. The researchers found: 1) individuals with mild and severe disease produced neutralizing IgG to SARS-CoV-2 10 days after disease onset; 2) SARS-CoV-2 persisted longer in those with severe disease; and 3) there was cross-reactivity between antibodies to SARS-CoV-1 and SARS-CoV-2, but only antibodies from patients with COVID-19 neutralized SARS-CoV-2. These observations provide important information on the serological response to SARS-CoV-2 of hospitalized patients with COVID-19 that can inform the use of convalescent plasma therapy.", "qid": 3, "docid": "xp09u1tq", "rank": 93, "score": 0.7451004981994629}, {"content": "Title: Different pattern of pre-existing SARS-COV-2 specific T cell immunity in SARS-recovered and uninfected individuals Content: Memory T cells induced by previous infections can influence the course of new viral infections. Little is known about the pattern of SARS-CoV-2 specific pre-existing memory T cells in human. Here, we first studied T cell responses to structural (nucleocapsid protein, NP) and non-structural (NSP-7 and NSP13 of ORF1) regions of SARS-CoV-2 in convalescent from COVID-19 (n=24). In all of them we demonstrated the presence of CD4 and CD8 T cells recognizing multiple regions of the NP protein. We then show that SARS-recovered patients (n=23), 17 years after the 2003 outbreak, still possess long-lasting memory T cells reactive to SARS-NP, which displayed robust cross-reactivity to SARS-CoV-2 NP. Surprisingly, we observed a differential pattern of SARS-CoV-2 specific T cell immunodominance in individuals with no history of SARS, COVID-19 or contact with SARS/COVID-19 patients (n=18). Half of them (9/18) possess T cells targeting the ORF-1 coded proteins NSP7 and 13, which were rarely detected in COVID-19- and SARS-recovered patients. Epitope characterization of NSP7-specific T cells showed recognition of protein fragments with low homology to \u201ccommon cold\u201d human coronaviruses but conserved among animal betacoranaviruses. Thus, infection with betacoronaviruses induces strong and long-lasting T cell immunity to the structural protein NP. Understanding how pre-existing ORF-1-specific T cells present in the general population impact susceptibility and pathogenesis of SARS-CoV-2 infection is of paramount importance for the management of the current COVID-19 pandemic.", "qid": 3, "docid": "05djnz4p", "rank": 94, "score": 0.7444994449615479}, {"content": "Title: Anaesthesia and COVID-19: infection control Content: The world is currently facing an unprecedented healthcare crisis caused by a pandemic novel beta coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The pathogen is spread by human-to-human transmission via droplets exposure and contact transfer, causing mild symptoms in the majority of cases, but critical illness, bilateral viral pneumonia, and acute respiratory distress syndrome (ARDS) in a minority. Currently, controlling infection to prevent the spread of SARS-CoV-2 is the primary public healthcare intervention used. The pace of transmission and global scale of SARS-CoV-2 infections has implications for strategic oversight, resource management, and responsiveness in infection control. This article presents a summary of learning points in epidemiological infection control from the SARS epidemic, alongside a review of evidence connecting current understanding of the virologic and environmental contamination properties of SARS-CoV-2. We present suggestions for how personal protective equipment policies relate to the viral pandemic context and how the risk of transmission by and to anaesthetists, intensivists, and other healthcare workers can be minimised.", "qid": 3, "docid": "htlix2oo", "rank": 95, "score": 0.7444294691085815}, {"content": "Title: SARS-CoV-2 infection leads to acute infection with dynamic cellular and inflammatory flux in the lung that varies across nonhuman primate species Content: There are no known cures or vaccines for COVID-19, the defining pandemic of this era. Animal models are essential to fast track new interventions and nonhuman primate (NHP) models of other infectious diseases have proven extremely valuable. Here we compare SARS-CoV-2 infection in three species of experimentally infected NHPs (rhesus macaques, baboons, and marmosets). During the first 3 days, macaques developed clinical signatures of viral infection and systemic inflammation, coupled with early evidence of viral replication and mild-to-moderate interstitial and alveolar pneumonitis, as well as extra-pulmonary pathologies. Cone-beam CT scans showed evidence of moderate pneumonia, which progressed over 3 days. Longitudinal studies showed that while both young and old macaques developed early signs of COVID-19, both groups recovered within a two-week period. Recovery was characterized by low-levels of viral persistence in the lung, suggesting mechanisms by which individuals with compromised immune systems may be susceptible to prolonged and progressive COVID-19. The lung compartment contained a complex early inflammatory milieu with an influx of innate and adaptive immune cells, particularly interstitial macrophages, neutrophils and plasmacytoid dendritic cells, and a prominent Type I-interferon response. While macaques developed moderate disease, baboons exhibited prolonged shedding of virus and extensive pathology following infection; and marmosets demonstrated a milder form of infection. These results showcase in critical detail, the robust early cellular immune responses to SARS-CoV-2 infection, which are not sterilizing and likely impact development of antibody responses. Thus, various NHP genera recapitulate heterogeneous progression of COVID-19. Rhesus macaques and baboons develop different, quantifiable disease attributes making them immediately available essential models to test new vaccines and therapies.", "qid": 3, "docid": "i94yyqwa", "rank": 96, "score": 0.7443441152572632}, {"content": "Title: Individual variation in susceptibility or exposure to SARS-CoV-2 lowers the herd immunity threshold Content: As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads, the susceptible subpopulation is depleted causing the incidence of new cases to decline. Variation in individual susceptibility or exposure to infection exacerbates this effect. Individuals that are more susceptible or more exposed tend to be infected earlier, depleting the susceptible subpopulation of those who are at higher risk of infection. This selective depletion of susceptibles intensifies the deceleration in incidence. Eventually, susceptible numbers become low enough to prevent epidemic growth or, in other words, the herd immunity threshold (HIT) is reached. Although estimates vary, simple calculations suggest that herd immunity to SARS-CoV-2 requires 60-70% of the population to be immune. By fitting epidemiological models that allow for heterogeneity to SARS-CoV-2 outbreaks across the globe, we show that variation in susceptibility or exposure to infection reduces these estimates. Accurate measurements of heterogeneity are therefore of paramount importance in controlling the COVID-19 pandemic.", "qid": 3, "docid": "aky3bja0", "rank": 97, "score": 0.7441160082817078}, {"content": "Title: SARS-CoV-2-specific antibody detection in healthcare workers in Germany with direct contact to COVID-19 patients Content: BACKGROUND: The novel coronavirus SARS-CoV-2 is associated with a severe respiratory manifestation, COVID-19, and presents a challenge for healthcare systems worldwide. Healthcare workers are a vulnerable cohort for SARS-CoV-2 infection due to frequent and close contact to patients with COVID-19. STUDY DESIGN: Serum samples from 316 healthcare workers of the University Hospital Essen, Germany were tested for SARS-CoV-2-IgG antibodies. A questionnaire was used to collect demographic and clinical data. Healthcare workers were grouped depending on the frequency of contact to COVID-19 patients in high-risk-group (n = 244) with daily contact to known or suspected SARS-CoV-2 positive patients, intermediated-risk-group (n = 37) with daily contact to patients without known or suspected SARS-CoV-2 infection at admission and low-risk-group (n = 35) without patient contact. RESULTS: In 5 of 316 (1.6 %) healthcare workers SARS-CoV-2-IgG antibodies could be detected. The seroprevalence was higher in the intermediate-risk-group vs. high-risk-group (2/37 (5.4 %) vs. 3/244 (1.2 %), p = 0.13). Four of the five subject were tested negative for SARS-CoV-2 via PCR. One (20 %) subject was not tested via PCR since he was asymptomatic. CONCLUSION: The overall seroprevalence of SARS-CoV-2 in healthcare workers of a tertiary hospital in Germany is low (1.6 %). The data indicate that the local hygiene standard might be effective.", "qid": 3, "docid": "jem2bhcg", "rank": 98, "score": 0.7440446019172668}, {"content": "Title: Perceived versus proven SARS-CoV-2 specific immune responses in health care workers Content: Uncertain rates of asymptomatic infections have raised concerns about potentially high rates of thus far undiagnosed SARS-CoV-2 infections. Serological testing for SARS-CoV-2 specific IgG can be helpful in identification of asymptomatic infections. We report baseline results of the CVOID-19 Contact (CoCo) Study, which follows 217 frontline healthcare workers at a university hospital and performs weekly SARS-CoV-2 specific serology (IgA/IgG). The majority of participants had direct contact to patients with infectious respiratory diseases. Study participants estimated their personal likelihood of having had a SARS-CoV-2 infection with a mean of 20.9% (range 0 to 90%). In contrast, anti-SARS-CoV-2-IgG prevalence was in the range of 1-2% among health care workers. The CoCo Study is not fully representative for other hospitals and the sensitivity of anti-SARS-CoV-2 serology in low prevalence conditions may require further improvement. Taken together, low rates of SARS-CoV-2 specific IgG in healthcare workers in Northern Germany are in sharp contrast to the high personal risk perception. Regular anti-SARS-CoV-2 IgG testing of health-care workers may aid in monitoring the pandemic, assessing the quality of immune responses, directing resources for protective measures, and assuring CVID-19 care in the long run.", "qid": 3, "docid": "x5g3qjs2", "rank": 99, "score": 0.7439670562744141}, {"content": "Title: Within host dynamics of SARS-CoV-2 in humans: Modeling immune responses and antiviral treatments Content: In December 2019, a newly discovered SARS-CoV-2 virus was emerged from China and propagated worldwide as a pandemic. In the absence of preventive medicine or a ready to use vaccine, mathematical models can provide useful scientific insights about transmission patterns and targets for drug development. In this study, we propose a within-host mathematical model of SARS-CoV-2 infection considering innate and adaptive immune responses. We analyze the equilibrium points of the proposed model and obtain an expression of the basic reproduction number. We then numerically show the existence of a transcritical bifurcation. The proposed model is calibrated to real viral load data of two COVID-19 patients. Using the estimated parameters, we perform global sensitivity analysis with respect to the peak of viral load. Finally, we study the efficacy of antiviral drugs and vaccination on the dynamics of SARS-CoV-2 infection. Our results suggest that blocking the production of the virus by infected cells decreases the viral load more than reducing the infection rate of healthy cells. Vaccination is also found useful but during the vaccine development phase, blocking virus production from infected cells can be targeted for antiviral drug development.", "qid": 3, "docid": "42yo0yjy", "rank": 100, "score": 0.7439076900482178}]}
{"query": "what causes death from Covid-19?", "hits": [{"content": "Title: Causes of Death and Comorbidities in Patients with COVID-19 Content: Infection by the new corona virus strain SARS-CoV-2 and its related syndrome COVID-19 has caused several hundreds of thousands of deaths worldwide. Patients of higher age and with preexisting chronic health conditions are at an increased risk of fatal disease outcome. However, detailed information on causes of death and the contribution of comorbidities to death yet is missing. Here, we report autopsy findings on causes of death and comorbidities of 26 decedents that had clinically presented with severe COVID-19. We found that septic shock and multi organ failure was the most common immediate cause of death, often due to suppurative pulmonary infection. Respiratory failure due to diffuse alveolar damage presented as the most immediate cause of death in fewer cases. Several comorbidities, such as hypertension, ischemic heart disease, and obesity were present in the vast majority of patients. Our findings reveal that causes of death were directly related to COVID-19 in the majority of decedents, while they appear not to be an immediate result of preexisting health conditions and comorbidities. We therefore suggest that the majority of patients had died of COVID-19 with only contributory implications of preexisting health conditions to the mechanism of death.", "qid": 4, "docid": "9yb9a9vz", "rank": 1, "score": 0.8127292990684509}, {"content": "Title: Sudden cardiac death in COVID-19 patients, a report of three cases Content: The mortality rate of coronavirus disease-19 (COVID-19) has been reported as 1\u20136% in most studies. The cause of most deaths has been acute pneumonia. Nevertheless, it has been noted that cardiovascular failure can also lead to death. Three COVID-19 patients were diagnosed based on reverse transcriptase-polymerase chain reaction of a nasopharyngeal swab test and radiological examinations in our hospital. The patients received medications at the discretion of the treating physician. In this case series, chest computed tomography scans and electrocardiograms, along with other diagnostic tests were used to evaluate these individuals. Sudden cardiac death in COVID-19 patients is not common, but it is a major concern. So, it is recommended to monitor cardiac condition in selected patients with COVID-19.", "qid": 4, "docid": "378cfb23", "rank": 2, "score": 0.7877460718154907}, {"content": "Title: Sudden cardiac death in COVID-19 patients, a report of three cases Content: The mortality rate of coronavirus disease-19 (COVID-19) has been reported as 1-6% in most studies. The cause of most deaths has been acute pneumonia. Nevertheless, it has been noted that cardiovascular failure can also lead to death. Three COVID-19 patients were diagnosed based on reverse transcriptase-polymerase chain reaction of a nasopharyngeal swab test and radiological examinations in our hospital. The patients received medications at the discretion of the treating physician. In this case series, chest computed tomography scans and electrocardiograms, along with other diagnostic tests were used to evaluate these individuals. Sudden cardiac death in COVID-19 patients is not common, but it is a major concern. So, it is recommended to monitor cardiac condition in selected patients with COVID-19.", "qid": 4, "docid": "u9omhsgu", "rank": 3, "score": 0.7868778109550476}, {"content": "Title: The COVID-19 Cytokine Storm; What We Know So Far Content: COVID-19 is a rapidly spreading global threat that has been declared as a pandemic by the WHO. COVID-19 is transmitted via droplets or direct contact and infects the respiratory tract resulting in pneumonia in most of the cases and acute respiratory distress syndrome (ARDS) in about 15 % of the cases. Mortality in COVID-19 patients has been linked to the presence of the so-called \u201ccytokine storm\u201d induced by the virus. Excessive production of proinflammatory cytokines leads to ARDS aggravation and widespread tissue damage resulting in multi-organ failure and death. Targeting cytokines during the management of COVID-19 patients could improve survival rates and reduce mortality.", "qid": 4, "docid": "ne1qvf5g", "rank": 4, "score": 0.7835136651992798}, {"content": "Title: Cardiovascular comorbidities and complications associated with coronavirus disease 2019 Content: Coronavirus disease 2019 (COVID-19) has caused a devastating global pandemic and continues to overwhelm the health-care facilities and shatter the economies of countries worldwide. Although it primarily affects the lungs, it shares a strong interplay with the cardiovascular system. The presence of underlying cardiovascular disease and its risk factors (diabetes, hypertension) predispose the patients to increased severity and mortality associated with COVID-19. On the other hand, COVID-19 itself leads to various cardiovascular complications, which increase its associated morbidity and mortality in affected patients. It is, therefore, prudent to review the rapidly evolving data in this field and understand the mechanisms behind the cardiovascular involvement of this lethal disease.", "qid": 4, "docid": "o6a30irm", "rank": 5, "score": 0.7807585000991821}, {"content": "Title: The COVID-19 Cytokine Storm; What We Know So Far Content: COVID-19 is a rapidly spreading global threat that has been declared as a pandemic by the WHO. COVID-19 is transmitted via droplets or direct contact and infects the respiratory tract resulting in pneumonia in most of the cases and acute respiratory distress syndrome (ARDS) in about 15 % of the cases. Mortality in COVID-19 patients has been linked to the presence of the so-called \"cytokine storm\" induced by the virus. Excessive production of proinflammatory cytokines leads to ARDS aggravation and widespread tissue damage resulting in multi-organ failure and death. Targeting cytokines during the management of COVID-19 patients could improve survival rates and reduce mortality.", "qid": 4, "docid": "ete5n5pw", "rank": 6, "score": 0.7791861295700073}, {"content": "Title: COVID-19 pandemic: do we need systematic screening of patients with cardiovascular risk factors in Low and Middle-Income Countries (LMICs) for preventing death? Content: COVID-19 pandemic is an emergent cardiovascular risk factor and a major cause of mortality worldwide. Thromboembolism is highly suspected as a leading cause of death in these patients through vascular inflammation caused by SARS COV2. Until now there is no real treatment of COVID-19 and many proposed drugs are under clinical trials. Considering the high incidence of thromboembolic events in critically ill patients with COVID-19, prevention of this disorder should be essential in order to reduce mortality in these patients.", "qid": 4, "docid": "yml9wuer", "rank": 7, "score": 0.777553379535675}, {"content": "Title: Thromboembolic risks in patients with COVID-19: major concern to consider in our management Content: COVID-19 pandemic is an emergent cardiovascular risk factor and a major cause of mortality worldwide. Thromboembolism is highly suspected as a leading cause of death in these patients through vascular inflammation caused by SARS COV2. Until now there is no real treatment of COVID-19 and many proposed drugs are under clinical trials. Considering the high incidence of thromboembolic events in critically ill patients with COVID-19, prevention of this disorder should be essential in order to reduce mortality in these patients.", "qid": 4, "docid": "zy4nb6bo", "rank": 8, "score": 0.777553379535675}, {"content": "Title: No Autopsies on COVID-19 Deaths: A Missed Opportunity and the Lockdown of Science Content: Background: The current outbreak of COVID-19 infection, which started in Wuhan, Hubei province, China, in December 2019, is an ongoing challenge and a significant threat to public health requiring surveillance, prompt diagnosis, and research efforts to understand a new, emergent, and unknown pathogen and to develop effective therapies. Despite the increasing number of published studies on COVID-19, in all the examined studies the lack of a well-defined pathophysiology of death among patients who died following COVID-19 infection is evident. Autopsy should be considered mandatory to define the exact cause of death, thus providing useful clinical and epidemiologic information as well as pathophysiological insights to further provide therapeutic tools. Methods: A literature review was performed on PubMed database, using the key terms: \u201cCOVID-19\u201d, \u201cnCov 19\u201d, and \u201cSars Cov 2\u201d. 9709 articles were retrieved; by excluding all duplicated articles, additional criteria were then applied: articles or abstracts in English and articles containing one of the following words: \u201cdeath\u201d, \u201cdied\u201d, \u201ccomorbidity\u201d, \u201ccause of death\u201d, \u201cbiopsy\u201d, \u201cautopsy\u201d, or \u201cpathological\u201d. Results: A total of 50 articles met the inclusion criteria. However, only 7 of these studies reported autopsy-based data. Discussion: The analysis of the main data from the selected studies concerns the complete analysis of 12,954 patients, of whom 2269 died (with a mortality rate of 17.52%). Laboratory confirmation of COVID-19 infection was obtained in all cases and comorbidities were fully reported in 46 studies. The most common comorbidities were: cardiovascular diseases (hypertension and coronary artery disease), metabolic disorders (diabetes, overweight, or obesity), respiratory disorders (chronic obstructive pulmonary disease), and cancer. The most common reported complications were: acute respiratory distress syndrome (ARDS), acute kidney injury, cardiac injury, liver insufficiency, and septic shock. Only 7 papers reported histological investigations. Nevertheless, only two complete autopsies are described and the cause of death was listed as COVID-19 in only one of them. The lack of postmortem investigation did not allow a definition of the exact cause of death to determine the pathways of this infection. Based on the few histopathological findings reported in the analyzed studies, it seems to be a clear alteration of the coagulation system: frequently prothrombotic activity with consequent thromboembolism was described in COVID-19 patients. As a scientific community, we are called on to face this global threat, and to defeat it with all the available tools necessary. Despite the improvement and reinforcement of any method of study in every field of medicine and science, encouraging the autopsy practice as a tool of investigation could also therefore, help physicians to define an effective treatment to reduce mortality.", "qid": 4, "docid": "f7cy5oad", "rank": 9, "score": 0.777206301689148}, {"content": "Title: The silent deaths of the elderly in long-term care facilities during the Covid-19 pandemic: The role of forensic pathology. Content: The Covid-19 pandemic is currently a major global public health problem. We know that the elderly and people with chronic diseases contract the infection more easily and they develop clinically more serious and often lethal forms. To date, the reasons for this have been generically attributed to old age and underlying diseases. Most Covid-19 deaths occurred in long-term care facilities because the residents are elderly people with chronic illness living in close contact. Therefore, facilities have become epidemic outbreaks. Forensic knowledge is very limited because an autopsy is rarely performed. Post-mortem investigations can help increase knowledge about Covid-19 and identify any undiagnosed pathologies in life. Therefore, forensic investigations play a role in protecting a frail population. Autopsies should be encouraged on elderly people who died of Covid-19.", "qid": 4, "docid": "8k6boijg", "rank": 10, "score": 0.7742319107055664}, {"content": "Title: The silent deaths of the elderly in long-term care facilities during the Covid-19 pandemic: The role of forensic pathology Content: The Covid-19 pandemic is currently a major global public health problem. We know that the elderly and people with chronic diseases contract the infection more easily and they develop clinically more serious and often lethal forms. To date, the reasons for this have been generically attributed to old age and underlying diseases. Most Covid-19 deaths occurred in long-term care facilities because the residents are elderly people with chronic illness living in close contact. Therefore, facilities have become epidemic outbreaks. Forensic knowledge is very limited because an autopsy is rarely performed. Post-mortem investigations can help increase knowledge about Covid-19 and identify any undiagnosed pathologies in life. Therefore, forensic investigations play a role in protecting a frail population. Autopsies should be encouraged on elderly people who died of Covid-19.", "qid": 4, "docid": "nacessce", "rank": 11, "score": 0.7742317914962769}, {"content": "Title: Deep Vein Thrombosis and Pulmonary Embolism: Two Complications of COVID-19 Pneumonia? Content: Coronavirus disease 19 (COVID-19) is a worldwide infection which was recently declared a global health emergency by the WHO Emergency Committee. The most common symptoms are fever and cough, which can progress to pneumonia, acute respiratory distress syndrome (ARDS) and/or end-organ failure. Risk factors associated with ARDS and death are older age, comorbidities (e.g., hypertension, diabetes, hyperlipidaemia), neutrophilia, and organ and coagulation dysfunction. Disseminated intravascular coagulation and coagulopathy can contribute to death. Anticoagulant treatment is associated with decreased mortality in severe COVID-19 pneumonia. In this report we describe two patients with COVID-19 pneumonia who developed venous thromboembolism. LEARNING POINTS: Deep vein thrombosis and pulmonary embolism can occur in patients with COVID-19 pneumonia. Low-molecular-weight heparin prophylaxis does not decrease the risk of venous thromboembolism (VTE) in COVID-19 pneumonia. In the presence of clinical signs and/or suspicion of VTE, compression ultrasound and echocardiography should be always performed, irrespective of disease stage.", "qid": 4, "docid": "ie9dn724", "rank": 12, "score": 0.773898184299469}, {"content": "Title: Clinical presentation and course of COVID-19 Content: Information about the clinical presentation and course of COVID-19 is evolving rapidly. On presentation, cough and fever predominate, but extrapulmonary symptoms are also common; in some patients, loss of sense of smell may be an early but favorable sign. The mortality rate varies widely in different reports but should become clearer as more data are collected. Risk factors for severe disease and death include comorbid conditions such as hypertension, cardiovascular disease, diabetes mellitus, and chronic obstructive pulmonary disease. Other implicated factors include older age, obesity, end-stage renal disease, and a higher neutrophil-lymphocyte ratio.", "qid": 4, "docid": "1gp58zxg", "rank": 13, "score": 0.7644280195236206}, {"content": "Title: Risk Factors for Mortality among COVID-19 Patients Content: AIMS: COVID-19 is a current globalpandemic. However, comprehensive global data analyses for its mortality risk factors are lacking. The current investigation aimed to assess the predictors of death among COVID-19 patients from worldwide open access data. METHODS: A total of 828 confirmed cases of COVID-19 with definite outcomes were retrospectively identified from open access individual-level worldwide data. Univariate followed by multivariable regression analysis were used to evaluate the association between potential risk factors and mortality. RESULTS: Majority of the patients were males 59.1% located in Asia 69.3%. Based on the data, older age (adjusted odds ratio (aOR), 1.079; 95% confidence intervals (95% CI), 1.064-1.095 per year increase), males (aOR, 1.607; 95% CI, 1.002-2.576), patients with hypertension (aOR, 3.576; 95% CI, 1.694-7.548), diabetes mellitus (aOR, 12.234; 95% CI, 4.126-36.272), and patients located in America (aOR, 7.441; 95% CI, 3.546-15.617) were identified as the risk factors of mortality among COVID-19 patients. CONCLUSIONS: Males, advanced age, hypertension patients, diabetes mellitus patients, and patients located in America were the independent risk factors of death among COVID-19 patients. Extra attention is required to be given to these factors and additional studies on the underlying mechanisms of these effects.", "qid": 4, "docid": "k7a98s4e", "rank": 14, "score": 0.7642475962638855}, {"content": "Title: COVID-19 is an emergent disease of aging Content: COVID-19 is an ongoing pandemic caused by the SARS-CoV-2 coronavirus that poses one of the greatest challenges to public health in recent years. SARS-CoV-2 is highly contagious and often leads to severe viral pneumonia with respiratory failure and death in the elderly and subjects with pre-existing conditions, but the reason for this age dependence is unclear. Here, we found that the case fatality rate for COVID-19 grows exponentially with age in Italy, Spain, South Korea, and China, with the doubling time approaching that of all-cause human mortality. In addition, men and those with multiple age-related diseases are characterized by increased mortality. Moreover, similar mortality patterns were found for all-cause pneumonia. We further report that the gene expression of ACE2, the SARS-CoV-2 receptor, grows in the lung with age, except for subjects on a ventilator. Together, our findings establish COVID-19 as an emergent disease of aging, and age and age-related diseases as its major risk factors. In turn, this suggests that COVID-19, and deadly respiratory diseases in general, may be targeted, in addition to therapeutic approaches that affect specific pathways, by approaches that target the aging process.", "qid": 4, "docid": "uatnaro4", "rank": 15, "score": 0.7630435228347778}, {"content": "Title: COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options Content: The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) \u2014a homologue of ACE\u2014to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin\u2013angiotensin\u2013aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.", "qid": 4, "docid": "1aal6njl", "rank": 16, "score": 0.7625068426132202}, {"content": "Title: The Role of Data Registries in the Time of COVID-19. Content: On April 1, 2020, the confirmed global burden of COVID-19 was more than 900,000 with 46,413 deaths. Despite worldwide calls for social distancing and containment, the incidence of the disease continues to increase. COVID-19 is a respiratory tract infection caused by the novel coronavirus (SARS-CoV2). Preliminary analyses from the Chinese Center for Disease Control and Prevention indicated an overall case fatality rate (CFR) of 2.3%; however the CFR was higher in older adults (14.8% in those 80\u00b1 years) and 49% of all critical cases. Those with preexisting conditions (cardiovascular disease (CVD), diabetes, chronic respiratory disease, hypertension, and cancer) also had higher CRFs. In the United States, 116 million adults have hypertension, 26 million US adults have diabetes mellitus, 9% have preexisting CVD and may therefore be at greater risk of complications or adverse health outcomes from COVID-19 infection.", "qid": 4, "docid": "2tlbeqvb", "rank": 17, "score": 0.7623428106307983}, {"content": "Title: Thromboinflammation and the hypercoagulability of COVID-19. Content: The pathogenic coronavirus has been wreaking havoc worldwide since January. Infection with SARS-CoV-2 is problematic as no one has prior immunity, and no specific antiviral treatments are available. While many people with COVID-19 develop mild to moderate symptoms, some develop profound seemingly unchecked inflammatory responses leading to acute lung injury and hypoxemic respiratory failure, the most common cause for death.", "qid": 4, "docid": "svwkcuxf", "rank": 18, "score": 0.7621986865997314}, {"content": "Title: COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options Content: The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.", "qid": 4, "docid": "ubhntliy", "rank": 19, "score": 0.761456310749054}, {"content": "Title: Lifestyle at Time of COVID-19: How Could Quarantine Affect Cardiovascular Risk Content: COVID-19 is causing a global pandemic with a high number of deaths and infected people. To contain the diffusion of COVID-19 virus, governments have enforced restrictions on outdoor activities or even collective quarantine on the population. Quarantine carries some long-term effects on cardiovascular disease, mainly related to unhealthy lifestyle and anxiety.", "qid": 4, "docid": "pigamjae", "rank": 20, "score": 0.7613797187805176}, {"content": "Title: Clinical Characteristics of Hospitalized Individuals Dying with COVID-19 by Age Group in Italy Content: BACKGROUND: aim of the present study is to describe characteristics of COVID-19 related deaths and to compare the clinical phenotype and course of COVID-19 related deaths occurring in adults (< 65 years) and older adults (\u2265 65 years). METHODS: medical charts of 3,032 patients dying with COVID-19 in Italy (368 aged < 65 years and 2,664 aged \u2265 65 years) were revised to extract information on demographics, pre-existing comorbidities, and in-hospital complications leading to death. RESULTS: Older adults (\u2265 65 years) presented with a higher number of comorbidities compared to those aged < 65 years (3.3 \u00b1 1.9 vs. 2.5 \u00b1 1.8, p<0.001). Prevalence of ischemic heart disease, atrial fibrillation, heart failure, stroke, hypertension, dementia, COPD, and chronic renal failure was higher in older patients (\u2265 65 years), while obesity, chronic liver disease, and HIV infection were more common in younger adults (< 65 years); 10.9% of younger patients (< 65 years) had no comorbidities, compared to 3.2% of older patients (\u2265 65 years). The younger adults had a higher rate of non-respiratory complications than older patients including acute renal failure (30.0% vs 20.6%), acute cardiac injury (13.5% vs 10.3%) and superinfections (30.9% vs. 9.8%). CONCLUSIONS: individuals dying with COVID-19 present with high levels of comorbidities, irrespective of age group, but a small proportion of deaths occurs in healthy adults with no pre-existing conditions. Non-respiratory complications are common, suggesting that the treatment of respiratory conditions needs to be combined with strategies to prevent and mitigate the effects of non-respiratory complications.", "qid": 4, "docid": "yawjdt5h", "rank": 21, "score": 0.759759783744812}, {"content": "Title: Is death from Covid-19 a multistep process? Content: Covid-19 death has a different relationship with age than is the case for other severe respiratory pathogens. The Covid-19 death rate increases exponentially with age, and the main risk factors are age itself, as well as having underlying conditions such as hypertension, diabetes, cardiovascular disease, severe chronic respiratory disease and cancer. Furthermore, the almost complete lack of deaths in children suggests that infection alone is not sufficient to cause death; rather, one must have gone through a number of changes, either as a result of undefined aspects of aging, or as a result of chronic disease. These characteristics of Covid-19 death are consistent with the multistep model of disease, a model which has primarily been used for cancer, and more recently for amyotrophic lateral sclerosis (ALS). We applied the multi-step model to data on Covid-19 case fatality rates (CFRs) from China, South Korea, Italy, Spain and Japan. In all countries we found that a plot of ln (CFR) against ln (age) was approximately linear with a slope of about 5. As a comparison, we also conducted similar analyses for selected other respiratory diseases. SARS showed a similar log-log age-pattern to that of Covid-19, albeit with a lower slope, whereas seasonal and pandemic influenza showed quite different age-patterns. Thus, death from Covid-19 and SARS appears to follow a distinct age-pattern, consistent with a multistep model of disease that in the case of Covid-19 is probably defined by comorbidities and age producing immune-related susceptibility. Identification of these steps would be potentially important for prevention and therapy for SARS-COV-2 infection.", "qid": 4, "docid": "zl2url8z", "rank": 22, "score": 0.7591072916984558}, {"content": "Title: Risk Factors for Mortality among COVID-19 Patients Content: Abstract Aims COVID-19 is a current globalpandemic. However, comprehensive global data analyses for its mortality risk factors are lacking. The current investigation aimed to assess the predictors of death among COVID-19 patients from worldwide open access data. Methods A total of 828 confirmed cases of COVID-19 with definite outcomes were retrospectively identified from open access individual-level worldwide data. Univariate followed by multivariable regression analysis were used to evaluate the association between potential risk factors and mortality. Results Majority of the patients were males 59.1% located in Asia 69.3%. Based on the data, older age (adjusted odds ratio (aOR), 1.079; 95% confidence intervals (95% CI), 1.064-1.095 per year increase), males (aOR, 1.607; 95% CI, 1.002-2.576), patients with hypertension (aOR, 3.576; 95% CI, 1.694-7.548), diabetes mellitus (aOR, 12.234; 95% CI, 4.126-36.272), and patients located in America (aOR, 7.441; 95% CI, 3.546-15.617) were identified as the risk factors of mortality among COVID-19 patients. Conclusions Males, advanced age, hypertension patients, diabetes mellitus patients, and patients located in America were the independent risk factors of death among COVID-19 patients. Extra attention is required to be given to these factors and additional studies on the underlying mechanisms of these effects.", "qid": 4, "docid": "lp4pev8d", "rank": 23, "score": 0.7582215666770935}, {"content": "Title: Autopsy Findings and Venous Thromboembolism in Patients With COVID-19 Content: BACKGROUND: The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN: Prospective cohort study. SETTING: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19. PATIENTS: The first 12 consecutive COVID-19-positive deaths. MEASUREMENTS: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. LIMITATION: Limited sample size. CONCLUSION: The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it. PRIMARY FUNDING SOURCE: University Medical Center Hamburg-Eppendorf.", "qid": 4, "docid": "mnta55wf", "rank": 24, "score": 0.7581984996795654}, {"content": "Title: Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study Content: The aim of this study was to identify factors associated with the death of patients with COVID-19 pneumonia caused by the novel coronavirus SARS-CoV-2.All clinical and laboratory parameters were collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital (Wuhan City, Hubei Province, China) between 25 December 2019 and 7 February 2020. Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk of death of COVID-19 pneumonia patients.In total, 179 patients with COVID-19 pneumonia (97 male and 82 female) were included in the present prospective study, of whom 21 died. Univariate and multivariate logistic regression analysis revealed that age &#8805;65\u00e2\u0080 years (OR 3.765, 95% CI 1.146\u00e2\u0080\u009217.394; p=0.023), pre-existing concurrent cardiovascular or cerebrovascular diseases (OR 2.464, 95% CI 0.755\u00e2\u0080\u00928.044; p=0.007), CD3+CD8+ T-cells &#8804;75\u00e2\u0080 cells\u00b7\u00b5L-1 (OR 3.982, 95% CI 1.132\u00e2\u0080\u009214.006; p<0.001) and cardiac troponin I &#8805;0.05\u00e2\u0080 ng\u00b7mL-1 (OR 4.077, 95% CI 1.166\u00e2\u0080\u009214.253; p<0.001) were associated with an increase in risk of mortality from COVID-19 pneumonia. In a sex-, age- and comorbid illness-matched case-control study, CD3+CD8+ T-cells &#8804;75\u00e2\u0080 cells\u00b7\u00b5L-1 and cardiac troponin I &#8805;0.05\u00e2\u0080 ng\u00b7mL-1 remained as predictors for high mortality from COVID-19 pneumonia.We identified four risk factors: age &#8805;65\u00e2\u0080 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3+CD8+ T-cells &#8804;75\u00e2\u0080 cells\u00b7\u00b5L-1 and cardiac troponin I &#8805;0.05\u00e2\u0080 ng\u00b7mL-1 The latter two factors, especially, were predictors for mortality of COVID-19 pneumonia patients.", "qid": 4, "docid": "5wazfkey", "rank": 25, "score": 0.7580367922782898}, {"content": "Title: Predictors of Mortality for Patients with COVID-19 Pneumonia Caused by SARS-CoV-2: A Prospective Cohort Study Content: To identify factors associated with the death for patients with COVID-19 pneumonia caused by a novel coronavirus SARS-CoV-2. All clinical and laboratory parameters were collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital, Wuhan City, Hubei Province, China, between December 25, 2019 and February 7, 2020. Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk for death of COVID-19 pneumonia patients. A total of 179 patients with COVID-19 pneumonia (97 male and 82 female) were included in the present prospective study, of whom 21 died. Univariate and multivariate logistic regression analysis revealed that age \u226565 years (odd ratio, 3.765; 95% confidence interval, 1.146\u201217.394; p=0.023), preexisting concurrent cardiovascular or cerebrovascular diseases (2.464; 0.755\u20128.044; p=0.007), CD3(+)CD8(+) T cells \u226475 cell\u00b7\u03bcL(\u22121) (3.982; 1.132\u201214.006; p<0.001), and cardiac troponin I\u22650.05 ng\u00b7mL(\u22121) (4.077; 1.166\u201214.253; p<0.001) were associated with an increase in risk of mortality of COVID-19 pneumonia. In the sex\u2012, age\u2012, and comorbid illness-matched case study, CD3(+)CD8(+) T cells \u226475 cell\u00b7\u03bcL(\u22121) and cardiac troponin I\u22650.05 ng\u00b7mL(\u22121) remained to be the predictors for high mortality of COVID-19 pneumonia. We identified four risk factors, age \u226565 years, preexisting concurrent cardiovascular or cerebrovascular diseases, CD3(+)CD8(+) T cells \u226475 cell\u00b7\u03bcL(\u22121), and cardiac troponin I\u22650.05 ng\u00b7mL(\u22121), especially the latter two factors, were predictors for mortality of COVID-19 pneumonia patients.", "qid": 4, "docid": "h0iynw2w", "rank": 26, "score": 0.7580016851425171}, {"content": "Title: Long-Term Care Facilities as a Risk Factor for Death Due to COVID-19 Content: A large percentage of the deaths from COVID-19 occur among residents of long-term care facilities. There are two possible reasons for this phenomenon. First, the structural features of such settings may lead to death. Alternatively, it is possible that individuals in these facilities are in poorer health than those living elsewhere, and that these individuals would have died even if they had not been in these facilities. Our findings show that, controlling for the population density and the percentage of older adults in the population, there is a significant positive association between the number of long-term care beds per capita and COVID-19 mortality rates. This finding provides support for the claim that long-term care living arrangements (of older people) are a significant risk factor for dying from COVID-19.", "qid": 4, "docid": "fhuugtq5", "rank": 27, "score": 0.7577506303787231}, {"content": "Title: Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study Content: BACKGROUND: The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS\u2013CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN: Prospective cohort study. SETTING: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction\u2013confirmed diagnosis of COVID-19. PATIENTS: The first 12 consecutive COVID-19\u2013positive deaths. MEASUREMENTS: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS\u2013CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. LIMITATION: Limited sample size. CONCLUSION: The high incidence of thromboembolic events suggests an important role of COVID-19\u2013induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19\u2013related death, as well as possible therapeutic interventions to reduce it. PRIMARY FUNDING SOURCE: University Medical Center Hamburg-Eppendorf.", "qid": 4, "docid": "8efdzlc0", "rank": 28, "score": 0.7576027512550354}, {"content": "Title: Maternal mortality from COVID-19 in Mexico. Content: COVID-19, the illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the deadliest pandemic to occur in this century. Common symptoms of COVID-19 include cough, myalgia, fever, chest pain, and headache. However, its clinical presentation ranges from completely asymptomatic to acute respiratory distress syndrome.[1] Pregnant women are susceptible to community spread of COVID-19 because they cannot postpone interactions with healthcare professionals and other women receiving obstetric care.", "qid": 4, "docid": "8noxjjuh", "rank": 29, "score": 0.7573765516281128}, {"content": "Title: COVID-19 and Multiorgan Response Content: Since the outbreak and rapid spread of COVID-19 starting late December 2019, it has been apparent that disease prognosis has largely been influenced by multiorgan involvement. Comorbidities such as cardiovascular diseases have been the most common risk factors for severity and mortality. The hyperinflammatory response of the body, coupled with the plausible direct effects of severe acute respiratory syndrome on body-wide organs via angiotensin-converting enzyme 2, has been associated with complications of the disease. Acute respiratory distress syndrome, heart failure, renal failure, liver damage, shock, and multiorgan failure have precipitated death. Acknowledging the comorbidities and potential organ injuries throughout the course of COVID-19 is therefore crucial in the clinical management of patients. This paper aims to add onto the ever-emerging landscape of medical knowledge on COVID-19, encapsulating its multiorgan impact.", "qid": 4, "docid": "fmri74v7", "rank": 30, "score": 0.7567654848098755}, {"content": "Title: COVID-19: is fibrosis the killer? Content: COVID-19 is a respiratory disease A recent report in Lancet examined, retrospectively, 137 patients with COVD-19 Patients that died had elevated IL-6 levels and acute respiratory distress syndrome These data have obvious implications for how to control mortality in COVID-19", "qid": 4, "docid": "b8bl5vq5", "rank": 31, "score": 0.7563015222549438}, {"content": "Title: Why does COVID-19 disproportionately affect older people? Content: The severity and outcome of coronavirus disease 2019 (COVID-19) largely depends on a patient's age. Adults over 65 years of age represent 80% of hospitalizations and have a 23-fold greater risk of death than those under 65. In the clinic, COVID-19 patients most commonly present with fever, cough and dyspnea, and from there the disease can progress to acute respiratory distress syndrome, lung consolidation, cytokine release syndrome, endotheliitis, coagulopathy, multiple organ failure and death. Comorbidities such as cardiovascular disease, diabetes and obesity increase the chances of fatal disease, but they alone do not explain why age is an independent risk factor. Here, we present the molecular differences between young, middle-aged and older people that may explain why COVID-19 is a mild illness in some but life-threatening in others. We also discuss several biological age clocks that could be used in conjunction with genetic tests to identify both the mechanisms of the disease and individuals most at risk. Finally, based on these mechanisms, we discuss treatments that could increase the survival of older people, not simply by inhibiting the virus, but by restoring patients' ability to clear the infection and effectively regulate immune responses.", "qid": 4, "docid": "sct14hzu", "rank": 32, "score": 0.7561942338943481}, {"content": "Title: On Tuberculosis and COVID-19 co-infection Content: COVID-19 may boost tuberculosis given infection and mortality, further studies are needed", "qid": 4, "docid": "hxte1gc1", "rank": 33, "score": 0.7561014890670776}, {"content": "Title: Microvascular disease confers additional risk to COVID-19 infection Content: The majority of fatalities thus far in the COVID-19 pandemic have been attributed to pneumonia. As expected, the fatality rate reported in China is higher in people with chronic pulmonary disease (6.3%) and those who have cancer (5.6%). According to the American College of Cardiology Clinical Bulletin \"COVID-19 Clinical Guidance for the CV Care Team\", there is a significantly higher fatality rate in people who are elderly (8.0% 70-79 years; 14.8% &#8805;80 years), diabetic (7.3%), hypertensive (6.0%), or have known cardiovascular disease (CVD) (10.5%). We propose a biological reason for the higher mortality risk in these populations that is apparent. We further present a set of pathophysiological reasons for the heightened danger that could lead to therapies for enhanced management and prevention.", "qid": 4, "docid": "qd4dic30", "rank": 34, "score": 0.7557277679443359}, {"content": "Title: Why does COVID-19 disproportionately affect older people? Content: The severity and outcome of coronavirus disease 2019 (COVID-19) largely depends on a patient\u2019s age. Adults over 65 years of age represent 80% of hospitalizations and have a 23-fold greater risk of death than those under 65. In the clinic, COVID-19 patients most commonly present with fever, cough and dyspnea, and from there the disease can progress to acute respiratory distress syndrome, lung consolidation, cytokine release syndrome, endotheliitis, coagulopathy, multiple organ failure and death. Comorbidities such as cardiovascular disease, diabetes and obesity increase the chances of fatal disease, but they alone do not explain why age is an independent risk factor. Here, we present the molecular differences between young, middle-aged and older people that may explain why COVID-19 is a mild illness in some but life-threatening in others. We also discuss several biological age clocks that could be used in conjunction with genetic tests to identify both the mechanisms of the disease and individuals most at risk. Finally, based on these mechanisms, we discuss treatments that could increase the survival of older people, not simply by inhibiting the virus, but by restoring patients\u2019 ability to clear the infection and effectively regulate immune responses.", "qid": 4, "docid": "u4thvebq", "rank": 35, "score": 0.7549251317977905}, {"content": "Title: Comorbid Chronic Diseases and Acute Organ Injuries Are Strongly Correlated with Disease Severity and Mortality among COVID-19 Patients: A Systemic Review and Meta-Analysis Content: The recent outbreak of COVID-19 has been rapidly spreading on a global scale. To date, there is no specific vaccine against the causative virus, SARS-CoV-2, nor is there an effective medicine for treating COVID-19, thus raising concerns with respect to the effect of risk factors such as clinical course and pathophysiological parameters on disease severity and outcome in patients with COVID-19. By extracting and analyzing all available published clinical data, we identified several major clinical characteristics associated with increased disease severity and mortality among patients with COVID-19. Specifically, preexisting chronic conditions such as hypertension, cardiovascular disease, chronic kidney disease, and diabetes are strongly associated with an increased risk of developing severe COVID-19; surprisingly, however, we found no correlation between chronic liver disease and increased disease severity. In addition, we found that both acute cardiac injury and acute kidney injury are highly correlated with an increased risk of COVID-19-related mortality. Given the high risk of comorbidity and the high mortality rate associated with tissue damage, organ function should be monitored closely in patients diagnosed with COVID-19, and this approach should be included when establishing new guidelines for managing these high-risk patients. Moreover, additional clinical data are needed in order to determine whether a supportive therapy can help mitigate the development of severe, potentially fatal complications, and further studies are needed to identify the pathophysiology and the mechanism underlying this novel coronavirus-associated infectious disease. Taken together, these findings provide new insights regarding clinical strategies for improving the management and outcome of patients with COVID-19.", "qid": 4, "docid": "mez1k8t0", "rank": 36, "score": 0.7549160718917847}, {"content": "Title: COVID-19 Pandemic: Is Chronic Inflammation a Major Cause of Death? Content: Abstract Background. Today humanity is facing another infectious threat: a newly emerging virus SARS-CoV-2 causing COVID-19. It was already described that COVID-19 mortality among elderly people and people with such underlying conditions as obesity, cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes s increased. Dysregulation of the immune responses vital for antiviral defense, which are typical for chronic inflammation, led us to a hypothesis that chronic inflammation is the main risk factor for increased susceptibility and mortality from COVID-19. Method. Based on the available information for 126 countries, statistical analysis to find out whether the difference in incidence and mortality within countries can be explained by the existing chronic inflammation among the countries population, was conducted. Results. A positive correlation between the percentage of people dying from chronic noncommunicable diseases and COVID-19 incidence (p<0.001) and mortality (p<0.001) within countries. Conclusion. The problem of COVID-19-caused high mortality rate may be a consequence of the high number of people having chronic low-grade inflammation as a precondition, and thus, one of the potential ways to reduce risk of morbidity and mortality is to focus on this widespread health problem, mainly occurring in developed countries and to take corresponding diagnostic, preventative, and treatment measures.", "qid": 4, "docid": "bmvdwa68", "rank": 37, "score": 0.7545586824417114}, {"content": "Title: Could there be a link between oral hygiene and the severity of SARS-CoV-2 infections? Content: On 30 January 2020, the World Health Organisation identified COVID-19, caused by the virus SARS-CoV-2, to be a global emergency. The risk factors already identified for developing complications from a COVID-19 infection are age, gender and comorbidities such as diabetes, hypertension, obesity and cardiovascular disease. These risk factors, however, do not account for the other 52% of deaths arising from COVID-19 in often seemingly healthy individuals. This paper investigates the potential link between SARS-CoV-2 and bacterial load, questioning whether bacteria may play a role in bacterial superinfections and complications such as pneumonia, acute respiratory distress syndrome and sepsis. The connection between COVID-19 complications and oral health and periodontal disease is also examined, as the comorbidities at highest risk of COVID-19 complications also cause imbalances in the oral microbiome and increase the risk of periodontal disease. We explore the connection between high bacterial load in the mouth and post-viral complications, and how improving oral health may reduce the risk of complications from COVID-19.", "qid": 4, "docid": "vxi3uttf", "rank": 38, "score": 0.7544598579406738}, {"content": "Title: COVID-19 Deaths: Are We Sure It Is Pneumonia? Please, Autopsy, Autopsy, Autopsy! Content: The current outbreak of COVID-19 severe respiratory disease, which started in Wuhan, China, is an ongoing challenge, and a major threat to public health that requires surveillance, prompt diagnosis, and research efforts to understand this emergent pathogen and to develop an effective response. Due to the scientific community's efforts, there is an increasing body of published studies describing the virus' biology, its transmission and diagnosis, its clinical features, its radiological findings, and the development of candidate therapeutics and vaccines. Despite the decline in postmortem examination rate, autopsy remains the gold standard to determine why and how death happens. Defining the pathophysiology of death is not only limited to forensic considerations; it may also provide useful clinical and epidemiologic insights. Selective approaches to postmortem diagnosis, such as limited postmortem sampling over full autopsy, can also be useful in the control of disease outbreaks and provide valuable knowledge for managing appropriate control measures. In this scenario, we strongly recommend performing full autopsies on patients who died with suspected or confirmed COVID-19 infection, particularly in the presence of several comorbidities. Only by working with a complete set of histological samples obtained through autopsy can one ascertain the exact cause(s) of death, optimize clinical management, and assist clinicians in pointing out a timely and effective treatment to reduce mortality. Death can teach us not only about the disease, it might also help with its prevention and, above all, treatment.", "qid": 4, "docid": "ic3tp5d0", "rank": 39, "score": 0.7544494867324829}, {"content": "Title: A geroscience perspective on COVID-19 mortality Content: A novel coronavirus, SARS-CoV-2, emerged in December 2019, leading within a few months to a global pandemic. COVID-19, the disease caused by this highly contagious virus, can have serious health consequences, though risks of complications are highly age-dependent. Rates of hospitalization and death are less than 0.1% in children, but increase to 10% or more in older people. Moreover, at all ages, men are more likely than women to suffer serious consequences from COVID-19. These patterns are familiar to the geroscience community. The effects of age and sex on mortality rates from COVID-19 mirror the effects of aging on almost all major causes of mortality. These similarities are explored here, and underscore the need to consider the role of basic biological mechanisms of aging on potential treatment and outcomes of COVID-19.", "qid": 4, "docid": "mcrf27ew", "rank": 40, "score": 0.753974974155426}, {"content": "Title: Clinical Characteristics of Hospitalized Individuals Dying with COVID-19 by Age Group in Italy Content: BACKGROUND: aim of the present study is to describe characteristics of COVID-19 related deaths and to compare the clinical phenotype and course of COVID-19 related deaths occurring in adults (< 65 years) and older adults (&#8805; 65 years). METHODS: medical charts of 3,032 patients dying with COVID-19 in Italy (368 aged < 65 years and 2,664 aged &#8805; 65 years) were revised to extract information on demographics, pre-existing comorbidities, and in-hospital complications leading to death. RESULTS: Older adults (&#8805; 65 years) presented with a higher number of comorbidities compared to those aged < 65 years (3.3 \u00b1 1.9 vs. 2.5 \u00b1 1.8, p<0.001). Prevalence of ischemic heart disease, atrial fibrillation, heart failure, stroke, hypertension, dementia, COPD, and chronic renal failure was higher in older patients (&#8805; 65 years), while obesity, chronic liver disease, and HIV infection were more common in younger adults (< 65 years); 10.9% of younger patients (< 65 years) had no comorbidities, compared to 3.2% of older patients (&#8805; 65 years). The younger adults had a higher rate of non-respiratory complications than older patients including acute renal failure (30.0% vs 20.6%), acute cardiac injury (13.5% vs 10.3%) and superinfections (30.9% vs. 9.8%). CONCLUSIONS: individuals dying with COVID-19 present with high levels of comorbidities, irrespective of age group, but a small proportion of deaths occurs in healthy adults with no pre-existing conditions. Non-respiratory complications are common, suggesting that the treatment of respiratory conditions needs to be combined with strategies to prevent and mitigate the effects of non-respiratory complications.", "qid": 4, "docid": "zl2ohake", "rank": 41, "score": 0.7535843849182129}, {"content": "Title: A Case Report of Rapidly Lethal Acute Respiratory Distress Syndrome Secondary to Coronavirus Disease 2019 Viral Pneumonia Content: As of April 2020, the coronavirus 2019 (COVID-19) pandemic has resulted in more than 210,000 deaths globally. The most common cause of death from COVID-19 is acute respiratory failure. We report the case of a 78-year-old female with a history of hypertension, cerebrovascular accident (CVA), type 2 diabetes mellitus, and sarcoidosis, who presented to the emergency department with one day of dyspnea. The patient experienced a rapid decline in respiratory function and was intubated in the intensive care unit (ICU), meeting the Berlin criteria for severe acute respiratory distress syndrome (ARDS). Chest radiography revealed diffuse bilateral coalescent opacities, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA swab test was positive for COVID-19. The patient experienced acute kidney injury with uptrending creatinine levels and remained lethargic and unresponsive throughout her ICU stay, suggestive of potential hypoxic brain injury. In light of the patient\u2019s poor clinical status, age, and significant comorbidities, prognosis was conveyed about medical futility and patient\u2019s family agreed to terminal extubation and the patient expired peacefully, exactly one week from hospital admission. This case report highlights the speed at which severe ARDS can present and contribute to end-organ dysfunction in COVID-19 patients.", "qid": 4, "docid": "q6wp6c08", "rank": 42, "score": 0.7533681988716125}, {"content": "Title: [Fatal outcome of coronavirus disease 2019 in a previously healthy 50-year-old man]. Content: In this case report, a 50-year-old man who had no medical history, presented with multiple cardiac arrests following a week with progressing symptoms of pneumonia. After achieving return of spontaneous circulation he presented with respiratory failure with severe hypoxia, septic shock, and multiple organ failure. A chest X-ray showed signs of acute respiratory distress syndrome. Despite aggressive intensive care management, the patient died 7.5 hours after admission. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was later confirmed, and the presumed cause of death was SARS-CoV-2 pneumonia. In conclusion: coronavirus disease 2019 (COVID-19) can lead to a fatal outcome in younger healthy residents, who are not treated timely in case of severe symptoms like dyspnoea.", "qid": 4, "docid": "oirh39hs", "rank": 43, "score": 0.753325343132019}, {"content": "Title: COVID-19 and Cardiovascular Disease Content: Coronavirus disease 2019 (COVID-19) is a global pandemic affecting 185 countries and >3 000 000 patients worldwide as of April 28, 2020. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2, which invades cells through the angiotensin-converting enzyme 2 receptor. Among patients with COVID-19, there is a high prevalence of cardiovascular disease, and >7% of patients experience myocardial injury from the infection (22% of critically ill patients). Although angiotensin-converting enzyme 2 serves as the portal for infection, the role of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers requires further investigation. COVID-19 poses a challenge for heart transplantation, affecting donor selection, immunosuppression, and posttransplant management. There are a number of promising therapies under active investigation to treat and prevent COVID-19.", "qid": 4, "docid": "r6kl7vb0", "rank": 44, "score": 0.7531808614730835}, {"content": "Title: COVID-19 Deaths: Are We Sure It Is Pneumonia? Please, Autopsy, Autopsy, Autopsy! Content: The current outbreak of COVID-19 severe respiratory disease, which started in Wuhan, China, is an ongoing challenge, and a major threat to public health that requires surveillance, prompt diagnosis, and research efforts to understand this emergent pathogen and to develop an effective response. Due to the scientific community\u2019s efforts, there is an increasing body of published studies describing the virus\u2019 biology, its transmission and diagnosis, its clinical features, its radiological findings, and the development of candidate therapeutics and vaccines. Despite the decline in postmortem examination rate, autopsy remains the gold standard to determine why and how death happens. Defining the pathophysiology of death is not only limited to forensic considerations; it may also provide useful clinical and epidemiologic insights. Selective approaches to postmortem diagnosis, such as limited postmortem sampling over full autopsy, can also be useful in the control of disease outbreaks and provide valuable knowledge for managing appropriate control measures. In this scenario, we strongly recommend performing full autopsies on patients who died with suspected or confirmed COVID-19 infection, particularly in the presence of several comorbidities. Only by working with a complete set of histological samples obtained through autopsy can one ascertain the exact cause(s) of death, optimize clinical management, and assist clinicians in pointing out a timely and effective treatment to reduce mortality. Death can teach us not only about the disease, it might also help with its prevention and, above all, treatment.", "qid": 4, "docid": "g2llk2p0", "rank": 45, "score": 0.7531734704971313}, {"content": "Title: Risk factors for mortality in patients with Coronavirus disease 2019 (COVID-19) infection: a systematic review and meta-analysis of observational studies Content: Purpose: Coronavirus disease 2019 (COVID-19) is an emerging disease that was first reported in Wuhan city, the capital of Hubei province in China, and has subsequently spread worldwide. Risk factors for mortality have not been well summarized. Current meta-analysis of retrospective cohort studies was done to summarize available findings on the association between age, gender, comorbidities and risk of death from COVID-19 infection.Methods: Online databases including Web of Science, PubMed, Scopus, Cochrane Library and Google scholar were searched to detect relevant publications up to 1 May 2020, using relevant keywords. To pool data, random-effects model was used. Furthermore, sensitivity analysis and publication bias test were also done.Results: In total, 14 studies with 29,909 COVID-19 infected patients and 1445 cases of death were included in the current meta-analysis. Significant associations were found between older age (&#8805;65 vs <65 years old) (pooled ORs = 4.59, 95%CIs = 2.61-8.04, p < .001), gender (male vs female) (pooled ORs = 1.50, 95%CIs = 1.06-2.12, p = .021) and risk of death from COVID-19 infection. In addition, hypertension (pooled ORs = 2.70, 95%CIs = 1.40-5.24, p = .003), cardiovascular diseases (CVDs) (pooled ORs = 3.72, 95%CIs = 1.77-7.83, p = .001), diabetes (pooled ORs = 2.41, 95%CIs = 1.05-5.51, p = .037), chronic obstructive pulmonary disease (COPD) (pooled ORs = 3.53, 95%CIs = 1.79-6.96, p < .001) and cancer (pooled ORs = 3.04, 95%CIs = 1.80-5.14, p < .001), were associated with higher risk of mortality.Conclusions: Older age (&#8805;65 years old), male gender, hypertension, CVDs, diabetes, COPD and malignancies were associated with greater risk of death from COVID-19 infection. These findings could help clinicians to identify patients with poor prognosis at an early stage.", "qid": 4, "docid": "67g8z0rc", "rank": 46, "score": 0.7531628608703613}, {"content": "Title: Influence of COVID-19 on Cerebrovascular Disease and its Possible Mechanism Content: The global spread of COVID-19 has caused a substantial societal burden and become a major global public health issue. The COVID-19 elderly population with hypertension, diabetes, cardiovascular, and cerebrovascular diseases are at risk. Mortality rates are highest in these individuals if infected with COVID-19. Although the lungs are the main organs involved in acute respiratory distress syndrome caused by COVID-19 infection, COVID-19 triggers inflammatory and immune mechanisms, inducing a \u201ccytokine storm\u201d that aggravates disease progression and may lead to death. Presently, effective drugs are lacking, although current studies have confirmed that drugs with therapeutic potential include redaciclovir, lopinavir/ritonavir combined with interferon-\u03b2, convalescent plasma, and monoclonal antibodies. Currently, the most reasonable and effective way to prevent COVID-19 is to control the source of infection, terminate routes of transmission, and protect susceptible populations. With the rise of COVID-19 in China and worldwide, further prevention, diagnosis, and treatment measures are a critical unmet need. Cerebrovascular disease has high incidence, disability rate, and fatality rate. COVID-19 patient outcomes may also be complicated with acute stroke. This paper summarizes the influence of COVID-19 on cerebrovascular disease and discusses possible pathophysiological mechanisms to provide new angles for the prevention and diagnosis of this disease.", "qid": 4, "docid": "9e3w7sv2", "rank": 47, "score": 0.752389669418335}, {"content": "Title: Predictors of mortality in hospitalized COVID-19 patients: A systematic review and meta-analysis Content: Mortality rates of coronavirus disease-2019 (COVID-19) continue to rise across the world. Information regarding the predictors of mortality in patients with COVID-19 remains scarce. Herein, we performed a systematic review of published articles, from 1 January to 24 April 2020, to evaluate the risk factors associated with mortality in COVID-19. Two investigators independently searched the articles and collected the data, in accordance with PRISMA guidelines. We looked for associations between mortality and patient characteristics, comorbidities, and laboratory abnormalities. A total of 14 studies documenting the outcomes of 4659 patients were included. The presence of comorbidities such as hypertension (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.1-3.1; P < .00001), coronary heart disease (OR, 3.8; 95% CI, 2.1-6.9; P < .00001), and diabetes (OR, 2.0; 95% CI, 1.7-2.3; P < .00001) were associated with significantly higher risk of death amongst patients with COVID-19. Those who died, compared with those who survived, differed on multiple biomarkers on admission including elevated levels of cardiac troponin (+44.2 ng/L, 95% CI, 19.0-69.4; P = .0006); C-reactive protein (+66.3 \u00b5g/mL, 95% CI, 46.7-85.9; P < .00001); interleukin-6 (+4.6 ng/mL, 95% CI, 3.6-5.6; P < .00001); D-dimer (+4.6 \u00b5g/mL, 95% CI, 2.8-6.4; P < .00001); creatinine (+15.3 \u00b5mol/L, 95% CI, 6.2-24.3; P = .001); and alanine transaminase (+5.7 U/L, 95% CI, 2.6-8.8; P = .0003); as well as decreased levels of albumin (-3.7 g/L, 95% CI, -5.3 to -2.1; P < .00001). Individuals with underlying cardiometabolic disease and that present with evidence for acute inflammation and end-organ damage are at higher risk of mortality due to COVID-19 infection and should be managed with greater intensity.", "qid": 4, "docid": "8hakjlus", "rank": 48, "score": 0.7522978186607361}, {"content": "Title: Links between air pollution and COVID-19 in England Content: In December 2019 a novel disease [coronavirus disease 19 (COVID-19) emerged in the Wuhan province of the People's Republic of China. COVID-19 is caused by a novel coronavirus (SARS-CoV-2) thought to have jumped species, from another mammal to humans. A pandemic caused by this virus is running rampant throughout the world. Thousands of cases of COVID-19 are reported in England and over 10,000 patients have died. Whilst there has been progress in managing this disease, it is not clear which factors, besides age, affect the severity and mortality of COVID-19. A recent analysis of COVID-19 in Italy identified links between air pollution and death rates. Here, we explored the correlation between three major air pollutants linked to fossil fuels and SARS-CoV-2 lethality in England. We compare up-to-date, real-time SARS-CoV-2 cases and death measurements from public databases to air pollution data monitored across over 120 sites in different regions. We found that the levels of some markers of poor air quality, nitrogen oxides and ozone, are associated with COVID-19 lethality in different English regions. We conclude that the levels of some air pollutants are linked to COVID-19 cases and morbidity. We suggest that our study provides a useful framework to guide health policy in countries affected by this pandemic.", "qid": 4, "docid": "lfl7mnd8", "rank": 49, "score": 0.7519340515136719}, {"content": "Title: COVID-19 and diabetes: Is there enough evidence? Content: The pandemic of COVID-19, a disease caused by a novel coronavirus SARS-CoV-2, is associated with significant morbidity and mortality. Recent data showed that hypertension, diabetes mellitus, cardiovascular diseases, and chronic obstructive pulmonary disease were the most prevalent comorbidities in COVID-19 patients. Additionally, data indicate that hypertension, diabetes, and cardiovascular diseases are important risk factors for progression and unfavorable outcome in COVID-19 patients. There is only limited amount of data regarding follow-up of these patients, and they provided conflicting results. The main limitation is a small number of participants and particularly those who experienced primary composite outcome (admission in intensive care unit, use of mechanical ventilation, or death). Additionally, the limited number of patients was essential obstacle for performing analysis that would include many confounding factors such as advanced age, smoking status, and obesity and potentially change conclusion. So far, there is no study that demonstrated independent predictive value of diabetes on mortality in COVID-19 patients, but there are many speculations about the association between diabetes and susceptibility to novel coronavirus, as well as its impact on progression and prognosis of COVID-19. The aim of this review article was to summarize the current knowledge about the relationship between diabetes and COVID-19 and its role in outcome in these patients.", "qid": 4, "docid": "f0pwjxfv", "rank": 50, "score": 0.7512997388839722}, {"content": "Title: Persistence of viral RNA, widespread thrombosis and abnormal cellular syncytia are hallmarks of COVID-19 lung pathology Content: COVID-19 is a deadly pulmonary disease with unique clinical features. A thorough understanding of the molecular and histological correlates of the disease is still missing, especially because post-mortem analysis of COVID-19-affected organs has been so far scant and often anecdotical. Here we report the results of the systematic analysis of 41 consecutive post-mortem samples from individuals who died of COVID-19. We found that the disease is characterized by extensive alveolar damage and thrombosis of the lung micro- and macro-vasculature. Thrombi were in different stages of organization, consistent with an ongoing, endogenous thrombotic process. In all the analyzed samples, in situ RNA hybridization showed that pneumocytes and vascular endothelial cells had massive presence of viral RNA even at the later stages of the disease. An additional feature of the disease was the presence, in the vast majority of patients, of a large number of dysmorphic pneumocytes, often forming large syncytial elements, a consequence of the fusogenic activity of the viral Spike protein, detected with specific antibodies. Despite occasional presence of virus-positive cells in the heart, no overt signs of viral infection were detected in other organs, which showed common alterations compatible with prolonged hypoxia, multifocal organ disease or previous comorbidities. In summary, COVID-19 is a unique interstitial pneumonia with extensive lung thrombosis, long-term persistence of viral replication in pneumocytes and endothelial cells, along with the presence of infected cellular syncytia in the lung. We propose that several of the COVID-19 disease features are due to the persistence of virus-infected cells in the lungs of the infected individuals for the duration of the disease.", "qid": 4, "docid": "vzm272sf", "rank": 51, "score": 0.7509870529174805}, {"content": "Title: Risk factors for mortality in patients with Coronavirus disease 2019 (COVID-19) infection: a systematic review and meta-analysis of observational studies. Content: Purpose: Coronavirus disease 2019 (COVID-19) is an emerging disease that was first reported in Wuhan city, the capital of Hubei province in China, and has subsequently spread worldwide. Risk factors for mortality have not been well summarized. Current meta-analysis of retrospective cohort studies was done to summarize available findings on the association between age, gender, comorbidities and risk of death from COVID-19 infection.Methods: Online databases including Web of Science, PubMed, Scopus, Cochrane Library and Google scholar were searched to detect relevant publications up to 1 May 2020, using relevant keywords. To pool data, random-effects model was used. Furthermore, sensitivity analysis and publication bias test were also done.Results: In total, 14 studies with 29,909 COVID-19 infected patients and 1445 cases of death were included in the current meta-analysis. Significant associations were found between older age (\u226565 vs <65 years old) (pooled ORs = 4.59, 95%CIs = 2.61-8.04, p < .001), gender (male vs female) (pooled ORs = 1.50, 95%CIs = 1.06-2.12, p = .021) and risk of death from COVID-19 infection. In addition, hypertension (pooled ORs = 2.70, 95%CIs = 1.40-5.24, p = .003), cardiovascular diseases (CVDs) (pooled ORs = 3.72, 95%CIs = 1.77-7.83, p = .001), diabetes (pooled ORs = 2.41, 95%CIs = 1.05-5.51, p = .037), chronic obstructive pulmonary disease (COPD) (pooled ORs = 3.53, 95%CIs = 1.79-6.96, p < .001) and cancer (pooled ORs = 3.04, 95%CIs = 1.80-5.14, p < .001), were associated with higher risk of mortality.Conclusions: Older age (\u226565 years old), male gender, hypertension, CVDs, diabetes, COPD and malignancies were associated with greater risk of death from COVID-19 infection. These findings could help clinicians to identify patients with poor prognosis at an early stage.", "qid": 4, "docid": "jf8elzsa", "rank": 52, "score": 0.750676155090332}, {"content": "Title: Clinical features and short-term outcomes of elderly patients with COVID-19 Content: BACKGROUND: The outbreak of Coronavirus Disease 2019 (COVID-19) has become a global public health emergency. METHODS: 204 elderly patients (&#8805;60 years old) diagnosed with COVID-19 in Renmin Hospital of Wuhan University from January 31st to February 20th, 2020 were included in this study. Clinical endpoint was in-hospital death. RESULTS: Of the 204 patients, hypertension, diabetes, cardiovascular disease, and chronic obstructive pulmonary disease (COPD) were the most common coexisting conditions. 76 patients died in the hospital. Multivariate analysis showed that dyspnea (hazards ratio (HR) 2.2, 95% confidence interval (CI) 1.414-3.517; p < 0.001), older age (HR 1.1, 95% CI 1.070-1.123; p < 0.001), neutrophilia (HR 4.4, 95% CI 1.310-15.061; p = 0.017) and elevated ultrasensitive cardiac troponin I (HR 3.9, 95% CI 1.471-10.433; p = 0.006) were independently associated with death. CONCLUSION: Although so far the overall mortality of COVID-19 is relatively low, the mortality of elderly patients is much higher. Early diagnosis and supportive care are of great importance for the elderly patients of COVID-19.", "qid": 4, "docid": "5lt6ke6v", "rank": 53, "score": 0.7502840757369995}, {"content": "Title: Risk Factors for Mortality of COVID-19 Patients Content: Background: Lethality rates of COVID-19 are so different between countries and continents. This lethality seems to be very low in Africa and Asia, but exceedingly high in western Europe and North America. Many factors could have a role in this disparity such as comorbidities. Advanced age, obesity, cardiovascular disease, diabetes and cancer were the most frequently cited in the reported COVID-19 data. The main objective was to analyse the association between the COVID-19 mortality and the mentioned factors in 164 countries. Methods: The Data of COVID-19 deaths, latitude degrees, population age distribution, cardiovascular diseases, obesity, diabetes and cancer were extracted from different online sources. For the statistical analysis, we used Spearman to measure the correlation coefficient between numbers of deaths and the mentioned factors until June 29, 2020. Results: The correlation between COVID-19 mortality and latitude, high age, obesity, CVD and number of cancer patients per 100,000 is significant at 0.01 level with r = 0.489, r=0.511, r=0.489, r=0.561 and r=0.536 respectively. The correlation between the number of deaths and diabetes is less strong than the previous ones, and the correlation coefficient is r= 0.154. Conclusion: The great lethality of COVID-19 in western Europe and North America can be explained in part by the highest of age, cancer and CVD percentage in these regions. It seems also plausible that the increased obesity in the USA and vitamin D deficiency in Europe may contribute to increasing the number of COVID-19 deaths.", "qid": 4, "docid": "izlpz4qn", "rank": 54, "score": 0.7498081922531128}, {"content": "Title: Elevated Troponin in Patients With Coronavirus Disease 2019: Possible Mechanisms Content: Coronavirus disease 2019 (COVID-19) is a pandemic that has affected more than 1.8 million people worldwide, overwhelmed health care systems owing to the high proportion of critical presentations, and resulted in more than 100,000 deaths. Since the first data analyses in China, elevated cardiac troponin has been noted in a substantial proportion of patients, implicating myocardial injury as a possible pathogenic mechanism contributing to severe illness and mortality. Accordingly, high troponin levels are associated with increased mortality in patients with COVID-19. This brief review explores the available evidence regarding the association between COVID-19 and myocardial injury.", "qid": 4, "docid": "tp66ua49", "rank": 55, "score": 0.7493640184402466}, {"content": "Title: Electrical Storm in COVID-19 Content: Abstract COVID-19 is a global pandemic caused by SARS-CoV-2. Infection is associated with significant morbidity and mortality. Individuals with pre-existing cardiovascular disease or evidence of myocardial injury are at risk for severe disease and death. Little is understood about the mechanisms of myocardial injury or life-threatening cardiovascular sequelae.", "qid": 4, "docid": "98xisxg7", "rank": 56, "score": 0.7493172883987427}, {"content": "Title: Clinical Features and Short-term Outcomes of Elderly Patients With COVID-19 Content: Abstract Background The outbreak of Coronavirus Disease 2019 (COVID-19) has become a global public health emergency. Methods 204 elderly patients (\u226560 years old) diagnosed with COVID-19 in Renmin Hospital of Wuhan University from January 31st to February 20th, 2020 were included in this study. Clinical endpoint was in-hospital death. Results Of the 204 patients, hypertension, diabetes, cardiovascular disease, and chronic obstructive pulmonary disease (COPD) were the most common coexisting conditions. 76 patients died in the hospital. Multivariate analysis showed that dyspnea (hazards ratio (HR) 2.2, 95% confidence interval (CI) 1.414 to 3.517;p < 0.001), older age (HR 1.1, 95% CI 1.070 to 1.123; p < 0.001), neutrophilia (HR 4.4, 95% CI 1.310 to 15.061; p = 0.017) and elevated ultrasensitive cardiac troponin I (HR 3.9, 95% CI 1.471 to 10.433; p = 0.006) were independently associated with death. Conclusion Although so far the overall mortality of COVID-19 is relatively low, the mortality of elderly patients is much higher. Early diagnosis and supportive care are of great importance for the elderly patients of COVID-19.", "qid": 4, "docid": "m89hgf41", "rank": 57, "score": 0.7492355108261108}, {"content": "Title: A fatal case of COVID-19 due to metabolic acidosis following dysregulate inflammatory response (cytokine storm) Content: The ongoing outbreak of COVID-19 has been expanding worldwide. As of 17 April 2020, the death toll stands at a sobering 147,027 and over two million cases, this has been straining the health care systems all over. Respiratory failure has been cited as the major cause of death but here we present a case about a patient who instead succumbed to severe metabolic acidosis with multiple organ failure.", "qid": 4, "docid": "96v8owb9", "rank": 58, "score": 0.7483004331588745}, {"content": "Title: Changing patterns of mortality during the COVID-19 pandemic: population-based modelling to understand palliative care implications Content: Background COVID-19 has directly and indirectly caused high mortality worldwide. Aim To explore patterns of mortality during the COVID-19 pandemic and implications for palliative care provision, planning, and research. Design Descriptive analysis and population-based modelling of routine data. Participants and setting All deaths registered in England and Wales between 7th March and 15th May 2020. We described the following mortality categories by age, gender and place of death: 1) baseline deaths (deaths that would typically occur in a given period) 2) COVID-19 deaths 3) additional deaths not directly attributed to COVID-19. We estimated the proportion of COVID-19 deaths among people who would be in their last year of life in the absence of the pandemic, using simple modelling with explicit assumptions. Results During the first 10 weeks of the pandemic there were 101,615 baseline deaths, 41,105 COVID-19 deaths and 14,520 additional deaths. Deaths in care homes increased by 220% compared to home and hospital deaths which increased by 77% and 90%. Hospice deaths fell by 20%. Additional deaths were among older people (86% aged [\u2265]75 years), and most occurred in care homes (56%) and at home (43%). We estimate that 44% (38% to 50%) of COVID-19 deaths occurred among people who would have been in their last year of life in the absence of the pandemic. Conclusions Healthcare systems must ensure availability of palliative care to support people with severe COVID-19 in community and hospital settings. Integrated models of palliative care in care homes are urgently needed.", "qid": 4, "docid": "mz3cvc0p", "rank": 59, "score": 0.7478982210159302}, {"content": "Title: Accelerated hyaluronan concentration as the primary driver of morbidity and mortality in high-risk COVID-19 patients: with therapeutic introduction of an oral hyaluronan inhibitor in the prevention of \"Induced Hyaluronan Storm\" Syndrome Content: Background To date, more than 161,000 people have died from the coronavirus disease 2019 (COVID-19) yet the fundamental drivers of the morbidity and mortality remain uncertain. Clinicians worldwide appear to be at a loss to know how to prevent and treat the severe respiratory distress in these patients effectively. Consequently, the fundamental mechanisms leading to death in high-risk patients with COVID-19 need to be discovered and addressed with urgency. Despite a marked drop in frequency, the post-mortem autopsy remains an essential part of both discovering the cause of death in a particular individual, but also in advancing the science and treatment of disease, especially in the case of novel pathogens such as SARS-CoV-2[2]. The goal of an autopsy is to discover the cause of death (COD) using a macro/microscopic investigation. Traditionally, the intact organs are carefully removed, inspected, and weighed. Because lung weight is often affected by the cause of death and the last breath occurs very near if not at the moments of death, the evaluation of the lungs is one of the starting points of any COD investigation[3]. Method A comprehensive search was performed to systematically review all reported autopsy findings in COVID-19 patients in order to better understand the underlying disease mechanisms resulting in death. We then compared these findings with the results of a targeted literature review of hyaluronan in relationship to acute respiratory distress syndrome (ARDS). Results In total, data from 181 autopsies were identified. From this group, 6 autopsies of COVID-19 patients were selected for a detailed review and statistical analysis. The average lung weight of those who were determined to have died as a result of SARS-CoV-2 was 2196g-approximately 2.5x normal lung weight. Hyaline membranes were consistently identified on histologic sections. A review of the literature reveals that hyaluronan has been associated with the pathophysiology of ARDS since 1967. However, its key role in driving the morbidity and mortality of the condition has heretofore not been fully recognized. Conclusions We propose that the induced hyaluronan storm syndrome or IHS, is the model that best addresses the heretofore perplexing respiratory failure that is the proximal cause of death in a minority, but ever rising number, of patients. In addition to treating and preventing IHS in currently infected individuals now; an aggressive research effort should be undertaken to discover why the majority of individuals who are exposed to the virus are either minimally or asymptomatic, while a minority of high-risk individuals rapidly progress to respiratory failure and death. Keywords Systematic review; COVID-19; SARS-CoV-2; Hyaline Membrane; Hyaluronan; Acute Respiratory Distress Syndrome; ARDS; Autopsy; IHS; Induced Hyaluronan Storm Syndrome; COD; Cause of Death", "qid": 4, "docid": "gsqzmuj5", "rank": 60, "score": 0.747877299785614}, {"content": "Title: Sudden death due to acute pulmonary embolism in a young woman with COVID-19 Content: Coronavirus disease 2019 (COVID-19) is an infectious disease that primarily affects the respiratory system, but it may cause cardiovascular complications such as thromboembolism. Rarely, pulmonary embolism may be encountered in patients with severe COVID-19 infection, especially in intensive care units. An asymptomatic young case of COVID-19 presenting with sudden death due to acute massive pulmonary embolism has not been previously described. We report a 41-year-old woman presented to emergency department with sudden death during physical activity. She had only history of diabetes mellitus and she was asymptomatic until sudden death. CT pulmonary angiography and chest CT scans revealed acute massive embolism and typical imaging findings of COVID-19 pneumonia, respectively. Interestingly, the patient had no symptoms or signs of infection and also had no risk factors for thromboembolism. COVID-19 infection appears to induce venous thromboembolism, especially pulmonary embolism. The case is remarkable in terms of showing how insidious and life-threatening COVID-19 infection can be.", "qid": 4, "docid": "qsamn8bk", "rank": 61, "score": 0.7477685213088989}, {"content": "Title: Pathophysiological characteristics and therapeutic approaches for pulmonary injury and cardiovascular complications of coronavirus disease 2019 Content: The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a major health crisis, with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) having infected over a million people around the world within a few months of its identification as a human pathogen. Initially, SARS-CoV-2 infects cells in the respiratory system and causes inflammation and cell death. Subsequently, the virus spreads out and damages other vital organs and tissues, triggering a complicated spectrum of pathophysiological changes and symptoms, including cardiovascular complications. Acting as the receptor for SARS-CoV entering mammalian cells, angiotensin converting enzyme-2 (ACE2) plays a pivotal role in the regulation of cardiovascular cell function. Diverse clinical manifestations and laboratory abnormalities occur in patients with cardiovascular injury in COVID-19, characterizing the development of this complication, as well as providing clues to diagnosis and treatment. This review provides a summary of the rapidly appearing laboratory and clinical evidence for the pathophysiology and therapeutic approaches to COVID-19 pulmonary and cardiovascular complications.", "qid": 4, "docid": "zcj4d2w0", "rank": 62, "score": 0.7477576732635498}, {"content": "Title: Clinical characteristics of 25 death cases with COVID-19: A retrospective review of medical records in a single medical center, Wuhan, China Content: OBJECTIVES: This study aims to summarize the clinical characteristics of death cases with COVID-19 and to identify critically ill patients of COVID-19 early and reduce their mortality. METHODS: The clinical records, laboratory findings and radiological assessments included chest X-ray or computed tomography were extracted from electronic medical records of 25 died patients with COVID-19 in Renmin Hospital of Wuhan University from Jan 14 to Feb 13, 2020. Two experienced clinicians reviewed and abstracted the data. RESULTS: The age and underlying diseases (hypertension, diabetes, etc.) were the most important risk factors for death of COVID-19 pneumonia. Bacterial infections may play an important role in promoting the death of patients. Malnutrition was common to severe patients. Multiple organ dysfunction can be observed, the most common organ damage was lung, followed by heart, kidney and liver. The rising of neutrophils, SAA, PCT, CRP, cTnI, D-dimer, LDH and lactate levels can be used as indicators of disease progression, as well as the decline of lymphocytes counts. CONCLUSIONS: The clinical characteristics of 25 death cases with COVID-19 we summarized, which would be helpful to identify critically ill patients of COVID-19 early and reduce their mortality.", "qid": 4, "docid": "8om7z5cc", "rank": 63, "score": 0.74773108959198}, {"content": "Title: COVID-19 and Multi-Organ Response Content: Abstract Since the outbreak and rapid spread of COVID-19 starting late December 2019, it has been apparent that disease prognosis has largely been influenced by multi-organ involvement. Comorbidities such as cardiovascular diseases have been the most common risk factors for severity and mortality. The hyperinflammatory response of the body, coupled with the plausible direct effects of SARS-CoV-2 on body-wide organs via ACE2, has been associated with complications of the disease. Acute respiratory distress syndrome, heart failure, renal failure, liver damage, shock and multi-organ failure have precipitated death. Acknowledging the comorbidities and potential organ injuries throughout the course of COVID-19 is therefore crucial in the clinical management of patients. This paper aims to add onto the ever-emerging landscape of medical knowledge on COVID-19, encapsulating its multi-organ impact.", "qid": 4, "docid": "yhynqeo1", "rank": 64, "score": 0.7476930618286133}, {"content": "Title: COVID-19: Dying is Bad--Losing Life is Worse Content: Background: COVID-19 was the leading cause of death in the United States over the three-month period March through May 2020. Another perspective is COVID-19s toll in terms of years of life lost. We calculated years of life lost for COVID-19 and other leading causes of death over those three months in the US. We also predicted years of life lost for COVID-19 and ischemic heart diseases (which includes heart attacks) for March through August 2020. Methods: Years of life lost are the sum of differences between life expectancy at age of death and age at death. Average years of life lost, years of life lost divided by the number of deaths, were also calculated. We used the COVID-19 Projections Using Machine Learning model to predict years of life lost from COVID-19 through the end of August 2020. Results: COVID-19 caused 12,035 more deaths than ischemic heart diseases during March through May 2020 but ischemic heart diseases years of life lost were 1.5% greater than those for COVID-19. Average years of life lost were 10.8 and 12.4 for COVID-19 and ischemic heart diseases, respectively. At the end of August, COVID-19 may overtake ischemic heart diseases as the leading cause of deaths and years of life lost in the US. Conclusion: Each COVID-19 death causes more than a decade of lost life in the US. We are reminded of a Danish Proverb that states \"Prediction is difficult, especially when dealing with the future.\" We suggest that while dying is bad, losing life is even worse.", "qid": 4, "docid": "gtp01rna", "rank": 65, "score": 0.7476235628128052}, {"content": "Title: Cytokine storm induced by SARS-CoV-2 Content: Coronavirus disease 2019 (COVID-19), caused by the virus designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread widely throughout the world. Despite the strict global outbreak management and quarantine measures that have been implemented, the incidence of COVID-19 continues to rise, resulting in more than 290,000 deaths and representing an extremely serious threat to human life and health. The clinical symptoms of the affected patients are heterogeneous, ranging from mild upper respiratory symptoms to severe pneumonitis and even acute respiratory distress syndrome (ARDS) or death. Systemic immune over activation due to SARS-CoV-2 infection causes the cytokine storm, which is especially noteworthy in severely ill patients with COVID-19. Pieces of evidence from current studies have shown that the cytokine storm may be an important factor in disease progression, even leading to multiple organ failure and death. This review provides an overview of the knowledge on the COVID-19 epidemiological profile, the molecular mechanisms of the SARS-CoV-2-induced cytokine storm and immune responses, the pathophysiological changes that occur during infection, the main antiviral compounds used in treatment strategies and the potential drugs for targeting cytokines, this information is presented to provide valuable guidance for further studies and for a therapeutic reduction of this excessive immune response.", "qid": 4, "docid": "bxfyse59", "rank": 66, "score": 0.7475689649581909}, {"content": "Title: Neutrophils and Neutrophil Extracellular Traps Drive Necroinflammation in COVID-19 Content: The COVID-19 pandemic is progressing worldwide with an alarming death toll. There is an urgent need for novel therapeutic strategies to combat potentially fatal complications. Distinctive clinical features of severe COVID-19 include acute respiratory distress syndrome, neutrophilia, and cytokine storm, along with severe inflammatory response syndrome or sepsis. Here, we propose the putative role of enhanced neutrophil infiltration and the release of neutrophil extracellular traps, complement activation and vascular thrombosis during necroinflammation in COVID-19. Furthermore, we discuss how neutrophilic inflammation contributes to the higher mortality of COVID-19 in patients with underlying co-morbidities such as diabetes and cardiovascular diseases. This perspective highlights neutrophils as a putative target for the immunopathologic complications of severely ill COVID-19 patients. Development of the novel therapeutic strategies targeting neutrophils may help reduce the overall disease fatality rate of COVID-19.", "qid": 4, "docid": "wtnyynez", "rank": 67, "score": 0.7473049163818359}, {"content": "Title: Neutrophils and Neutrophil Extracellular Traps Drive Necroinflammation in COVID-19. Content: The COVID-19 pandemic is progressing worldwide with an alarming death toll. There is an urgent need for novel therapeutic strategies to combat potentially fatal complications. Distinctive clinical features of severe COVID-19 include acute respiratory distress syndrome, neutrophilia, and cytokine storm, along with severe inflammatory response syndrome or sepsis. Here, we propose the putative role of enhanced neutrophil infiltration and the release of neutrophil extracellular traps, complement activation and vascular thrombosis during necroinflammation in COVID-19. Furthermore, we discuss how neutrophilic inflammation contributes to the higher mortality of COVID-19 in patients with underlying co-morbidities such as diabetes and cardiovascular diseases. This perspective highlights neutrophils as a putative target for the immunopathologic complications of severely ill COVID-19 patients. Development of the novel therapeutic strategies targeting neutrophils may help reduce the overall disease fatality rate of COVID-19.", "qid": 4, "docid": "6ri6bxfc", "rank": 68, "score": 0.7473049163818359}, {"content": "Title: Histopathology of COVID-19 pneumonia in two non-oncological, non-hospitalised cases as a reliable diagnostic benchmark Content: In lung cancer patients infected with COVID-19, pathological features are not easy to distinguish. This report presents detailed histopathological findings in two non-neoplastic subjects whose out-of-hospital deaths were caused by COVID-19 infection. These 'pure' cases differ in the time of presentation of symptoms, the phase of lung anatomopathological patterns (acute lung injury versus diffuse alveolar damage) and the mechanism of death. The results provide a valid diagnostic benchmark for evaluating the evolution of COVID-19 pneumonia.", "qid": 4, "docid": "1dbea5rl", "rank": 69, "score": 0.747267484664917}, {"content": "Title: Iron: Innocent bystander or vicious culprit in COVID-19 pathogenesis? Content: The coronavirus 2 (SARS-CoV-2) pandemic is viciously spreading through the continents with rapidly increasing mortality rates. Current management of COVID-19 is based on the premise that respiratory failure is the leading cause of mortality. However, mounting evidence links accelerated pathogenesis in gravely ill COVID-19 patients to a hyper-inflammatory state involving a cytokine storm. Several components of the heightened inflammatory state were addressed as therapeutic targets. Another key component of the heightened inflammatory state is hyper-ferritinemia which reportedly identifies patients with increased mortality risk. In spite of its strong association with mortality, it is not yet clear if hyper-ferritinemia in COVID-19 patients is merely a systemic marker of disease progression, or a key modulator in disease pathogenesis. Here we address implications of a possible role for hyper-ferritinemia, and altered iron homeostasis in COVID-19 pathogenesis, and potential therapeutic targets in this regard.", "qid": 4, "docid": "c4uiq8jd", "rank": 70, "score": 0.7470574378967285}, {"content": "Title: Predictors of mortality in hospitalized COVID\u201019 patients: A systematic review and meta\u2010analysis Content: Mortality rates of coronavirus disease 2019 (COVID\u201019) continue to rise across the world. Information regarding the predictors of mortality in COVID\u201019 patients remains scarce. Herein, we performed a systematic review of published articles, from January 1 to April 24, 2020, to evaluate the risk factors associated with mortality in COVID\u201019. Two investigators independently searched the articles and collected the data, in accordance with PRISMA guidelines. We looked for associations between mortality and patient characteristics, comorbidities, and laboratory abnormalities. A total of 14 studies documenting the outcomes of 4659 patients were included. The presence of comorbidities such as hypertension (OR 2.5; 95% CI 2.1\u20103.1; P<0.00001), coronary heart disease (OR 3.8; 95% CI 2.1\u20106.9; P<0.00001) and diabetes (OR 2.0; 95% CI 1.7\u20102.3; P<0.00001) were associated with significantly higher risk of death amongst COVID\u201019 patients. Those who died, compared to those who survived, differed on multiple biomarker levels on admission including elevated levels of cardiac troponin (+44.2 ng/L, 95% CI 19.0\u201069.4; P=0.0006); C\u2010reactive protein (+66.3 \u00b5g/mL, 95% CI 46.7\u201085.9; P<0.00001); interleukin\u20106 (+4.6 ng/mL, 95% CI 3.6\u20105.6; P<0.00001); D\u2010dimer (+4.6 \u00b5g/mL, 95% CI 2.8\u20106.4; P<0.00001); creatinine (+15.3 \u00b5mol/L, 95% CI 6.2\u201024.3; P=0.001) and alanine transaminase (+5.7 U/L, 95% CI 2.6\u20108.8; P=0.0003); as well as decreased levels of albumin (\u20103.7 g/L, 95% CI \u20105.3 to \u20102.1; P<0.00001). Individuals with underlying cardiometabolic disease and that present with evidence for acute inflammation and end\u2010organ damage are at higher risk of mortality due to COVID\u201019 infection and should be managed with greater intensity. This article is protected by copyright. All rights reserved.", "qid": 4, "docid": "obhrbxu4", "rank": 71, "score": 0.7470154166221619}, {"content": "Title: Histopathology and genetic susceptibility in COVID\u201019 pneumonia Content: The clinical features of COVID\u201019 range from a mild illness to patients with a very severe illness with acute hypoxemic respiratory failure requiring ventilation and Intensive Care Unit admission. Risk factors for a fatal disease include older age, respiratory disease, diabetes mellitus, obesity and hypertension. Little is known about the mechanisms behind observed episodes of sudden deterioration or the infrequent idiosyncratic clinical demise in otherwise healthy and young subjects. As in other diseases, the answer to some of these questions may in time be provided by genotyping as well careful clinical, serological, radiological and histopathological phenotyping, which enable mechanistic insights into the differences in pathogenesis and underlying immunological and tissue regenerative response patterns. We will aim to provide a brief overview of the existing evidence for such differences in host response and outcome, and generate hypotheses for divergent patterns and avenues for future research, by highlighting similarities and differences in histopathological appearance between COVID19 and influenza as well as previous coronavirus outbreaks, and by discussing predisposition through genetics and underlying disease.", "qid": 4, "docid": "mt939rqw", "rank": 72, "score": 0.7467113733291626}, {"content": "Title: Histopathology of COVID-19 pneumonia in two non-oncological, non-hospitalised cases as a reliable diagnostic benchmark Content: In lung cancer patients infected with COVID-19, pathological features are not easy to distinguish. This report presents detailed histopathological findings in two non-neoplastic subjects whose out-of-hospital deaths were caused by COVID-19 infection. These \u2018pure\u2019 cases differ in the time of presentation of symptoms, the phase of lung anatomopathological patterns (acute lung injury versus diffuse alveolar damage) and the mechanism of death. The results provide a valid diagnostic benchmark for evaluating the evolution of COVID-19 pneumonia.", "qid": 4, "docid": "klkpd27e", "rank": 73, "score": 0.7467045783996582}, {"content": "Title: Cardiovascular Risks in Patients with COVID-19: Potential Mechanisms and Areas of Uncertainty Content: PURPOSE OF REVIEW: COronaVirus Disease 2019 (COVID-19) has spread at unprecedented speed and scale into a global pandemic with cardiovascular risk factors and complications emerging as important disease modifiers. We aim to review available clinical and biomedical literature on cardiovascular risks of COVID-19. RECENT FINDINGS: SARS-CoV2, the virus responsible for COVID-19, enters the cell via ACE2 expressed in select organs. Emerging epidemiological evidence suggest cardiovascular risk factors are associated with increased disease severity and mortality in COVID-19 patients. Patients with a more severe form of COVID-19 are also more likely to develop cardiac complications such as myocardial injury and arrhythmia. The true incidence of and mechanism underlying these events remain elusive. SUMMARY: Cardiovascular diseases appear intricately linked with COVID-19, with cardiac complications contributing to the elevated morbidity/mortality of COVID-19. Robust epidemiologic and biologic studies are urgently needed to better understand the mechanism underlying these associations to develop better therapies.", "qid": 4, "docid": "lfjud2aq", "rank": 74, "score": 0.7460572719573975}, {"content": "Title: Iron: Innocent bystander or vicious culprit in COVID-19 pathogenesis? Content: The coronavirus 2 (SARS-CoV-2) pandemic is viciously spreading through the continents with rapidly increasing mortality rates. Current management of COVID-19 is based on that respiratory failure is the leading cause of mortality. However, mounting evidence link accelerated pathogenesis in gravely ill COVID-19 patients to a hyper-inflammatory state involving a cytokine storm. Several components of the heightened inflammatory state were addressed as therapeutic targets. Another key component of the heightened inflammatory state is hyper-ferritinemia which reportedly identifies patients with increased mortality risk. In spite of its strong association with mortality, it is not yet clear if hyper-ferritinemia in COVID-19 patients is merely a systemic marker of disease progression, or a key modulator in disease pathogenesis. Here we address implications of a possible role for hyper-ferritinemia, and altered iron homeostasis in COVID-19 pathogenesis, and potential therapeutic targets in this regard.", "qid": 4, "docid": "ucmmzhym", "rank": 75, "score": 0.7459304332733154}, {"content": "Title: The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management Content: The 2019 coronavirus disease (COVID-19) presents with a large variety of clinical manifestations ranging from asymptomatic carrier state to severe respiratory distress, multiple organ dysfunction and death. While it was initially considered primarily a respiratory illness, rapidly accumulating data suggests that COVID-19 results in a unique, profoundly prothrombotic milieu leading to both arterial and venous thrombosis. Consistently, elevated D-dimer level has emerged as an independent risk factor for poor outcomes, including death. Several other laboratory markers and blood counts have also been associated with poor prognosis, possibly due to their connection to thrombosis. At present, the pathophysiology underlying the hypercoagulable state is poorly understood. However, a growing body of data suggests that the initial events occur in the lung. A severe inflammatory response, originating in the alveoli, triggers a dysfunctional cascade of inflammatory thrombosis in the pulmonary vasculature, leading to a state of local coagulopathy. This is followed, in patients with more severe disease, by a generalized hypercoagulable state that results in macro- and microvascular thrombosis. Of concern, is the observation that anticoagulation may be inadequate in many circumstances, highlighting the need for alternative or additional therapies. Numerous ongoing studies investigating the pathophysiology of the COVID-19 associated coagulopathy may provide mechanistic insights that can direct appropriate interventional strategies.", "qid": 4, "docid": "zmp0dpv0", "rank": 76, "score": 0.7455647587776184}, {"content": "Title: Cardiovascular complications in COVID-19 Content: BACKGROUND: The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur. OBJECTIVE: This brief report evaluates cardiovascular complications in the setting of COVID-19 infection. DISCUSSION: The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death. The virus binds and enters through angiotensin-converting enzyme 2 (ACE2). COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness. The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events. Current therapies for COVID-19 may interact with cardiovascular medications. CONCLUSIONS: Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.", "qid": 4, "docid": "hl225efn", "rank": 77, "score": 0.7451560497283936}, {"content": "Title: Excess mortality and potential undercounting of COVID-19 deaths by demographic group in Ohio Content: Background: There are significant gaps in our understanding of the mortality effects of COVID-19 due to evolving diagnosis criteria, shortages of testing supplies, and challenges faced by physicians in treating patients in crisis environments. Accurate information on the number of deaths caused by COVID-19, both population wide and for demographic subgroups, is vital for policy makers and health care providers. Methods: We performed a retrospective study of weekly data for Ohio, a large American state. To estimate expected mortality in 2020 we employed data from 2010 through 2019, adjusted for secular trends and seasonality. We estimated excess mortality as the number of observed deaths less the number of expected deaths. We conducted the analysis for the entire population and by gender, race, age, and county of residence. Findings: We estimated 1,485 (95% CI 680-2,345) excess all-cause deaths in Ohio from March 15, 2020 through May 23, 2020. When limited to deaths due to natural causes, the estimated excess number of deaths increased to 2,504 (95% CI 1,633-3,221), reflecting the countervailing effect of a decrease in deaths due to external causes. While the largest number excess of deaths was observed in the 80+ age group, excess deaths comprised 45.3% (95% CI 21.8-60.9) of observed deaths in the groups corresponding to ages between 20 and 49 years old. Our estimate of 729 (95% CI 355-966) excess deaths for this group substantially exceeds the reported number of COVID-19 deaths of 51. We found elevated excess deaths for older individuals, blacks, and males. Interpretation: Our methodology addressed some of the challenges of estimating the number of deaths caused by COVID-19. Our finding of high proportional levels of excess deaths among younger age groups suggests that increases in the infection rates for this cohort may have a greater mortality impact than expected. Funding: None.", "qid": 4, "docid": "jjwz5jrr", "rank": 78, "score": 0.7448996305465698}, {"content": "Title: Mechanisms of Myocardial Injury in Coronavirus Disease 2019 Content: Coronavirus disease 2019 (COVID-19) predominantly presents with symptoms of fever, fatigue, cough and respiratory failure. However, it appears to have a unique interplay with cardiovascular disease (CVD); patients with pre-existing CVD are at highest risk for mortality from COVID-19, along with the elderly. COVID-19 contributes to cardiovascular complications including arrhythmias, myocardial dysfunction and myocardial inflammation. Although the exact mechanism of myocardial inflammation in patients with COVID-19 is not known, several plausible mechanisms have been proposed based on early observational reports. In this article, the authors summarise the available literature on mechanisms of myocardial injury in COVID-19.", "qid": 4, "docid": "h2xmxwd1", "rank": 79, "score": 0.7448974847793579}, {"content": "Title: COVID-19 Pandemic, Corona Viruses, and Diabetes Mellitus. Content: The pandemic of COVID-19, a disease caused by a novel coronavirus (CoV), SARS-CoV-2, is causing substantial morbidity and mortality. Older age and presence of diabetes mellitus, hypertension, and obesity significantly increases the risk for hospitalization and death in COVID-19 patients. In this Perspective, informed by the studies on severe acute respiratory syndrome, SARS-CoV, and Middle East respiratory syndrome, MERS-CoV, and the current literature on SARS-CoV-2, we discuss potential mechanisms by which diabetes modulates the host-viral interactions and host-immune responses. We hope to highlight gaps in knowledge that require further studies pertinent to COVID-19 in patients with diabetes.", "qid": 4, "docid": "22vz79nz", "rank": 80, "score": 0.7443903684616089}, {"content": "Title: SARS-CoV-2 infection: the role of cytokines in COVID-19 disease Content: COVID-19 disease, caused by infection with SARS-CoV-2, is related to a series of physiopathological mechanisms that mobilize a wide variety of biomolecules, mainly immunological in nature. In the most severe cases, the prognosis can be markedly worsened by the hyperproduction of mainly proinflammatory cytokines, such as IL-1, IL-6, IL-12, IFN-\u03b3, and TNF-\u03b1, preferentially targeting lung tissue. This study reviews published data on alterations in the expression of different cytokines in patients with COVID-19 who require admission to an intensive care unit. Data on the implication of cytokines in this disease and their effect on outcomes will support the design of more effective approaches to the management of COVID-19.", "qid": 4, "docid": "8u685f45", "rank": 81, "score": 0.744271457195282}, {"content": "Title: Symptom burden and clinical profile of COVID-19 deaths: a rapid systematic review and evidence summary. Content: The spread of pandemic COVID-19 has created unprecedented need for information. The pandemic is the cause of significant mortality and with this the need for rapidly disseminated information for palliative care professionals regarding the prevalence of symptoms, their intensity, their resistance or susceptibility to symptom control and the mode of death for patients. METHODS We undertook a systematic review of published evidence for symptoms in patients with COVID-19 (with a specific emphasis on symptoms at end of life) and on modes of death. Inclusion: prospective or retrospective studies detailing symptom presence and/or cause or mode of death from COVID-19. RESULTS 12 papers met the inclusion criteria and gave details of symptom burden: four of these specifically in the dying and two detailed the cause or mode of death. Cough, breathlessness, fatigue and myalgia are significant symptoms in people hospitalised with COVID-19. Dyspnoea is the most significant symptom in the dying. The mode of death was described in two papers and is predominantly through respiratory or heart failure. CONCLUSIONS There remains a dearth of information regarding symptom burden and mode of death to inform decisions regarding end-of-life care in patients dying with COVID-19. Rapid data gathering on the mode of death and the profile of symptoms in the dying and their prevalence and severity in areas where COVID-19 is prevalent will provide important intelligence for clinicians. This should be done urgently, within ethical norms and the practicalities of a public health, clinical and logistical emergency.", "qid": 4, "docid": "7ksh8c5v", "rank": 82, "score": 0.7442212104797363}, {"content": "Title: Cardiovascular Risks in Patients with COVID-19: Potential Mechanisms and Areas of Uncertainty Content: PURPOSE OF REVIEW: COronaVirus Disease 2019 (COVID-19) has spread at unprecedented speed and scale into a global pandemic with cardiovascular risk factors and complications emerging as important disease modifiers. We aim to review available clinical and biomedical literature on cardiovascular risks of COVID-19. RECENT FINDINGS: SARS-CoV2, the virus responsible for COVID-19, enters the cell via ACE2 expressed in select organs. Emerging epidemiological evidence suggest cardiovascular risk factors are associated with increased disease severity and mortality in COVID-19 patients. Patients with a more severe form of COVID-19 are also more likely to develop cardiac complications such as myocardial injury and arrhythmia. The true incidence of and mechanism underlying these events remain elusive. Cardiovascular diseases appear intricately linked with COVID-19, with cardiac complications contributing to the elevated morbidity/mortality of COVID-19. Robust epidemiologic and biologic studies are urgently needed to better understand the mechanism underlying these associations to develop better therapies.", "qid": 4, "docid": "ejsqsn59", "rank": 83, "score": 0.7442206144332886}, {"content": "Title: A man in his nineties with fever and dry cough. Content: BACKGROUND COVID-19 can cause a fatal outcome in elderly patients, as this case report illustrates. CASE PRESENTATION An active male in his nineties with a high level of function, despite several severe chronic diseases, was admitted to Oslo University Hospital after two days of fatigue, fever, dyspnoea and dry cough. He scored qSOFA 1 of 3 points due to high respiratory rate, and SIRS 2 of 4 points due to high respiratory rate and fever of 39.4\u00ba C. PCR for influenza virus was negative and he received benzylpenicillin for pneumonia. The chest X-ray taken initially showed no lung affection. On day 5 after symptom debut he was tested for COVID-19 which was positive. He had not been travelling to high-risk areas or been exposed to any known confirmed COVID-19 patients. On the same day, a chest CT scan was performed that showed ground-glass opacities. In subsequent days the patient's health rapidly deteriorated. He developed irreversible respiratory failure with hypoxia without hypercapnia despite substantial oxygen support. Chest X-ray taken on disease day 7 showed progression of consolidations. The patient died 9 days after symptom debut. INTERPRETATION This case illustrates a severe course of COVID-19 with fatal outcome. The patient was also one of the earliest admitted with COVID-19 in a Norwegian hospital and marked a new phase of the epidemic, as he had not been travelling to high-risk areas or been exposed to any confirmed COVID-19 patients.", "qid": 4, "docid": "yxps5psk", "rank": 84, "score": 0.7434444427490234}, {"content": "Title: Exposure to air pollution and COVID-19 mortality in the United States: A nationwide cross-sectional study Content: Objectives: United States government scientists estimate that COVID-19 may kill tens of thousands of Americans. Many of the pre-existing conditions that increase the risk of death in those with COVID-19 are the same diseases that are affected by long-term exposure to air pollution. We investigated whether long-term average exposure to fine particulate matter (PM2.5) is associated with an increased risk of COVID-19 death in the United States. Design: A nationwide, cross-sectional study using county-level data. Data sources: COVID-19 death counts were collected for more than 3,000 counties in the United States (representing 98% of the population) up to April 22, 2020 from Johns Hopkins University, Center for Systems Science and Engineering Coronavirus Resource Center. Main outcome measures: We fit negative binomial mixed models using county-level COVID-19 deaths as the outcome and county-level long-term average of PM2.5 as the exposure. In the main analysis, we adjusted by 20 potential confounding factors including population size, age distribution, population density, time since the beginning of the outbreak, time since state issuance of the stay-at-home order, hospital beds, number of individuals tested, weather, and socioeconomic and behavioral variables such as obesity and smoking. We included a random intercept by state to account for potential correlation in counties within the same state. We conducted more than 68 additional sensitivity analyses. Results: We found that an increase of only 1 \u03bcg/m3 in PM2.5 is associated with an 8% increase in the COVID-19 death rate (95% confidence interval [CI]: 2%, 15%). The results were statistically significant and robust to secondary and sensitivity analyses. Conclusions: A small increase in long-term exposure to PM2.5 leads to a large increase in the COVID-19 death rate. Despite the inherent limitations of the ecological study design, our results underscore the importance of continuing to enforce existing air pollution regulations to protect human health both during and after the COVID-19 crisis. The data and code are publicly available so our analyses can be updated routinely.", "qid": 4, "docid": "2q6qmex3", "rank": 85, "score": 0.7433931231498718}, {"content": "Title: Identifying novel factors associated with COVID-19 transmission and fatality using the machine learning approach Content: The COVID-19 virus has infected millions of people and resulted in hundreds of thousands of deaths worldwide. By using the logistic regression model, we identified novel critical factors associated with COVID19 cases, death, and case fatality rates in 154 countries and in the 50 U.S. states. Among numerous factors associated with COVID-19 risk, we found that the unitary state system was counter-intuitively positively associated with increased COVID-19 cases and deaths. Blood type B was a protective factor for COVID-19 risk, while blood type A was a risk factor. The prevalence of HIV, influenza and pneumonia, and chronic lower respiratory diseases was associated with reduced COVID-19 risk. Obesity and the condition of unimproved water sources were associated with increased COVID-19 risk. Other factors included temperature, humidity, social distancing, smoking, and vitamin D intake. Our comprehensive identification of the factors affecting COVID-19 transmission and fatality may provide new insights into the COVID-19 pandemic and advise effective strategies for preventing and migrating COVID-19 spread.", "qid": 4, "docid": "yl7m77fo", "rank": 86, "score": 0.7433638572692871}, {"content": "Title: Myocardial and Microvascular Injury Due to Coronavirus Disease 2019 Content: Over the past few months, health systems worldwide have been put to the test with the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though the leading clinical manifestations of the SARS-CoV-2 infection involve the respiratory tract, there is a non-negligible risk of systemic involvement leading to the onset of multi-organ failure with fatal consequences. Since the onset of COVID-19, patients with underlying cardiovascular disease have been at increased risk of poor clinical outcomes with higher death rates. Moreover, the occurrence of new-onset cardiac complications is not uncommon among patients hospitalised for COVID-19. Of importance, a significant portion of COVID-19 patients present with myocardial injury. Herein, the authors discuss the mechanisms leading to myocardial and microvascular injury in SARS-CoV-2 infection and their clinical implications.", "qid": 4, "docid": "uo88b0mk", "rank": 87, "score": 0.7432076930999756}, {"content": "Title: Current perspectives on Coronavirus 2019 (COVID-19) and cardiovascular disease: A white paper by the JAHA editors. Content: Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has infected more than 3.0 million people worldwide and killed more than 200,000 as of April 27, 2020, making it the most lethal pandemic since the Spanish flu of 1918.1, 2 COVID-19 may preferentially infect individuals with cardiovascular conditions, is more severe in subjects with cardiovascular comorbidities, may directly or indirectly affect the heart and may interact with cardiovascular medications.3 In addition, the widespread effects of the pandemic on the global healthcare system affects the routine and emergency cardiac care for patients who are, may be, or are not infected with COVID-19.", "qid": 4, "docid": "tr5whji0", "rank": 88, "score": 0.743131160736084}, {"content": "Title: Clinical characteristics of 82 cases of death from COVID-19 Content: A recently developed pneumonia caused by SARS-CoV-2 bursting in Wuhan, China, has quickly spread across the world. We report the clinical characteristics of 82 cases of death from COVID-19 in a single center. Clinical data on 82 death cases laboratory-confirmed as SARS-CoV-2 infection were obtained from a Wuhan local hospital's electronic medical records according to previously designed standardized data collection forms. All patients were local residents of Wuhan, and a large proportion of them were diagnosed with severe illness when admitted. Due to the overwhelming of our system, a total of 14 patients (17.1%) were treated in the ICU, 83% of deaths never received Critical Care Support, only 40% had mechanical ventilation support despite 100% needing oxygen and the leading cause of death being pulmonary. Most of the patients who died were male (65.9%). More than half of the patients who died were older than 60 years (80.5%), and the median age was 72.5 years. The bulk of the patients who died had comorbidities (76.8%), including hypertension (56.1%), heart disease (20.7%), diabetes (18.3%), cerebrovascular disease (12.2%), and cancer (7.3%). Respiratory failure remained the leading cause of death (69.5%), followed by sepsis/MOF (28.0%), cardiac failure (14.6%), hemorrhage (6.1%), and renal failure (3.7%). Furthermore, respiratory, cardiac, hemorrhagic, hepatic, and renal damage were found in 100%, 89%, 80.5%, 78.0%, and 31.7% of patients, respectively. On admission, lymphopenia (89.2%), neutrophilia (74.3%), and thrombocytopenia (24.3%) were usually observed. Most patients had a high neutrophil-to-lymphocyte ratio of >5 (94.5%), high systemic immune-inflammation index of >500 (89.2%), and increased C-reactive protein (100%), lactate dehydrogenase (93.2%), and D-dimer (97.1%) levels. A high level of IL-6 (>10 pg/ml) was observed in all detected patients. The median time from initial symptoms to death was 15 days (IQR 11-20), and a significant association between aspartate aminotransferase (p = 0.002), alanine aminotransferase (p = 0.037) and time from initial symptoms to death was remarkably observed. Older males with comorbidities are more likely to develop severe disease and even die from SARS-CoV-2 infection. Respiratory failure is the main cause of COVID-19, but the virus itself and cytokine release syndrome-mediated damage to other organs, including cardiac, renal, hepatic, and hemorrhagic damage, should be taken seriously as well.", "qid": 4, "docid": "jq0x08mw", "rank": 89, "score": 0.7431279420852661}, {"content": "Title: Clinical characteristics of 82 cases of death from COVID-19. Content: A recently developed pneumonia caused by SARS-CoV-2 bursting in Wuhan, China, has quickly spread across the world. We report the clinical characteristics of 82 cases of death from COVID-19 in a single center. Clinical data on 82 death cases laboratory-confirmed as SARS-CoV-2 infection were obtained from a Wuhan local hospital's electronic medical records according to previously designed standardized data collection forms. All patients were local residents of Wuhan, and a large proportion of them were diagnosed with severe illness when admitted. Due to the overwhelming of our system, a total of 14 patients (17.1%) were treated in the ICU, 83% of deaths never received Critical Care Support, only 40% had mechanical ventilation support despite 100% needing oxygen and the leading cause of death being pulmonary. Most of the patients who died were male (65.9%). More than half of the patients who died were older than 60 years (80.5%), and the median age was 72.5 years. The bulk of the patients who died had comorbidities (76.8%), including hypertension (56.1%), heart disease (20.7%), diabetes (18.3%), cerebrovascular disease (12.2%), and cancer (7.3%). Respiratory failure remained the leading cause of death (69.5%), followed by sepsis/MOF (28.0%), cardiac failure (14.6%), hemorrhage (6.1%), and renal failure (3.7%). Furthermore, respiratory, cardiac, hemorrhagic, hepatic, and renal damage were found in 100%, 89%, 80.5%, 78.0%, and 31.7% of patients, respectively. On admission, lymphopenia (89.2%), neutrophilia (74.3%), and thrombocytopenia (24.3%) were usually observed. Most patients had a high neutrophil-to-lymphocyte ratio of >5 (94.5%), high systemic immune-inflammation index of >500 (89.2%), and increased C-reactive protein (100%), lactate dehydrogenase (93.2%), and D-dimer (97.1%) levels. A high level of IL-6 (>10 pg/ml) was observed in all detected patients. The median time from initial symptoms to death was 15 days (IQR 11-20), and a significant association between aspartate aminotransferase (p = 0.002), alanine aminotransferase (p = 0.037) and time from initial symptoms to death was remarkably observed. Older males with comorbidities are more likely to develop severe disease and even die from SARS-CoV-2 infection. Respiratory failure is the main cause of COVID-19, but the virus itself and cytokine release syndrome-mediated damage to other organs, including cardiac, renal, hepatic, and hemorrhagic damage, should be taken seriously as well.", "qid": 4, "docid": "ls0x41h1", "rank": 90, "score": 0.7431279420852661}, {"content": "Title: COVID\u201019 and diabetes: Is there enough evidence? Content: The pandemic of COVID\u201019, a disease caused by a novel coronavirus SARS\u2010CoV\u20102, is associated with significant morbidity and mortality. Recent data showed that hypertension, diabetes mellitus, cardiovascular diseases, and chronic obstructive pulmonary disease were the most prevalent comorbidities in COVID\u201019 patients. Additionally, data indicate that hypertension, diabetes, and cardiovascular diseases are important risk factors for progression and unfavorable outcome in COVID\u201019 patients. There is only limited amount of data regarding follow\u2010up of these patients, and they provided conflicting results. The main limitation is a small number of participants and particularly those who experienced primary composite outcome (admission in intensive care unit, use of mechanical ventilation, or death). Additionally, the limited number of patients was essential obstacle for performing analysis that would include many confounding factors such as advanced age, smoking status, and obesity and potentially change conclusion. So far, there is no study that demonstrated independent predictive value of diabetes on mortality in COVID\u201019 patients, but there are many speculations about the association between diabetes and susceptibility to novel coronavirus, as well as its impact on progression and prognosis of COVID\u201019. The aim of this review article was to summarize the current knowledge about the relationship between diabetes and COVID\u201019 and its role in outcome in these patients.", "qid": 4, "docid": "sntawlnf", "rank": 91, "score": 0.7425581812858582}, {"content": "Title: Elevated interleukin-6 is associated with severity of COVID-19: a meta-analysis Content: Coronavirus disease 2019 (COVID-19) has spread rapidly around the world since its emergence in humans last December. Previous studies suggested that numerous markers of inflammation were elevated in patients in with severe disease relative to patients with milder conditions, and an elevated level of interleukin-6 (IL-6) was associated with a high case fatality of COVID-19 infection. This article is protected by copyright. All rights reserved.", "qid": 4, "docid": "ejj82q46", "rank": 92, "score": 0.7425473928451538}, {"content": "Title: The need for urogenital tract monitoring in COVID-19 Content: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2, which invades a cell through binding to the ACE2 receptor and TMPRSS2 priming. Patients with severe disease predominantly present with pneumonia-related symptoms. However, evidence suggests that COVID-19 infection also has implications for the urogenital tract. Thus, urogenital organs should be considered when treating COVID-19.", "qid": 4, "docid": "kec1o4ys", "rank": 93, "score": 0.7424694895744324}, {"content": "Title: COVID-19 and Older Adults: What We Know Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus that causes COVID-19 infection, has recently emerged and caused a deadly pandemic. Studies have shown that this virus causes worse outcomes and a higher mortality rate in older adults and those with comorbidities such as hypertension, cardiovascular disease, diabetes, chronic respiratory disease, and chronic kidney disease (CKD). A significant percentage of older American adults have these diseases, putting them at a higher risk of infection. Additionally, many adults with hypertension, diabetes, and CKD are placed on angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers. Studies have shown that these medications upregulate the ACE-2 receptor, the very receptor that the SARS-CoV-2 virus uses to enter host cells. Although it has been hypothesized that this may cause a further increased risk of infection, more studies on the role of these medications in COVID-19 infections are necessary. In this review, we discuss the transmission, symptomatology, and mortality of COVID-19 as they relate to older adults, and possible treatments that are currently under investigation. J Am Geriatr Soc 68:926-929, 2020.", "qid": 4, "docid": "vhfl6l6k", "rank": 94, "score": 0.7422159910202026}, {"content": "Title: SARS-CoV-2 infection: The role of cytokines in COVID-19 disease Content: COVID-19 disease, caused by infection with SARS-CoV-2, is related to a series of physiopathological mechanisms that mobilize a wide variety of biomolecules, mainly immunological in nature. In the most severe cases, the prognosis can be markedly worsened by the hyperproduction of mainly proinflammatory cytokines, such as IL-1, IL-6, IL-12, IFN-\u00ce\u00b3, and TNF-&#945;, preferentially targeting lung tissue. This study reviews published data on alterations in the expression of different cytokines in patients with COVID-19 who require admission to an intensive care unit. Data on the implication of cytokines in this disease and their effect on outcomes will support the design of more effective approaches to the management of COVID-19.", "qid": 4, "docid": "tgunokrk", "rank": 95, "score": 0.7421785593032837}, {"content": "Title: Microvascular Disease Confers Additional Risk to COVID-19 Infection Content: The majority of fatalities thus far in the COVID-19 pandemic have been attributed to pneumonia. As expected, the fatality rate reported in China is higher in people with chronic pulmonary disease (6.3%) and those who have cancer (5.6%). According to the American College of Cardiology Clinical Bulletin \u201cCOVID-19 Clinical Guidance for the CV Care Team\u201d, there is a significantly higher fatality rate in people who are elderly (8.0% 70-79 years; 14.8% \u226580 years), diabetic (7.3%), hypertensive (6.0%), or have known cardiovascular disease (CVD) (10.5%). We propose a biological reason for the higher mortality risk in these populations that is apparent. We further present a set of pathophysiological reasons for the heightened danger that could lead to therapies for enhanced management and prevention. MVD And COVID Abstract The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-Cov2) results in COVID-19 which can lead to severe illness and death. The majority of fatalities thus far in the pandemic have been attributed to pneumonia. The overall mortality risk reported as of March 28, 2020 varies from 2.3% in China, 2.7% in Iran, and 0.5% in South Korea. As expected, the fatality rate reported in China is higher in people with chronic pulmonary disease (6.3%) and those who have cancer (5.6%). According to the American College of Cardiology Clinical Bulletin \u201cCOVID-19 Clinical Guidance for the CV Care Team\u201d, there is a significantly higher fatality rate in people who are elderly (8.0% 70-79; 14.8% \u226580), diabetic (7.3%), hypertensive (6.0%), or have known cardiovascular disease (CVD) (10.5%). We propose a reason for the higher mortality risk in these populations that is not apparent. We further present a set of pathophysiological reasons for the heightened danger could lead to therapies for enhanced management and prevention.", "qid": 4, "docid": "cmcv1k62", "rank": 96, "score": 0.7421451807022095}, {"content": "Title: Dilated Cardiomyopathy Risk in Patients with Coronavirus Disease 2019: How to Identify and Characterise it Early? Content: Multiple lines of evidence have shown that elevated blood troponin is strongly associated with poor prognosis in patients with the novel coronavirus disease 2019 (COVID-19). Possible mechanisms of myocardial injury in COVID-19 include ischaemia due to circulatory and respiratory failure, epicardial or intramyocardial small coronary artery thrombotic obstruction due to increased coagulability, and myocarditis caused by systemic inflammation or direct binding of the virus to its receptor, angiotensin-converting enzyme-2 (ACE2), which is abundantly expressed in the heart. It is postulated that persistent immune activation upon viral infection increases the risk of developing dilated cardiomyopathy in COVID-19 patients.", "qid": 4, "docid": "suje0oo8", "rank": 97, "score": 0.7420237064361572}, {"content": "Title: Tobacco Smoking a Potential Risk Factor in Transmission of COVID-19 Infection Content: Corona Virus disease 2019 (COVID-19) is a global pandemic and is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) group of viruses. To date, April 25, 2020, more than 2.4 million humans are infected and more than a hundred thousand deaths have been reported from more than 200 countries from COVID-19. There is no evidence-based treatment for the infection and prevention of transmission using social distancing, isolation and hygiene measures is widely recommended. Tobacco smoking is rampant in communities around the globe and the addiction to tobacco results in deaths of more than 8 million individuals each year. As COVID-19 transmits through salivary droplets and causes severe lung pneumonia, tobacco smokers are also at high risk of severe COVID-19 infection due to poor lung function, cross-infection and susceptible hygiene habits. Smoking tobacco (cigarette, e-cigarettes or waterpipe) produces exhaled smoke, coughing or sneezing, aerosols containing SARS-CoV-2 in the surroundings and contaminating surfaces. Therefore, smoking tobacco is a possible mode of transmission for the virus for both active and passive smokers. Smoking should be considered a risk factor for the disease transmission until further availability of evidence and measures to limit its direct and indirect effects should be implemented within the community.", "qid": 4, "docid": "u1qo37mf", "rank": 98, "score": 0.7416722178459167}, {"content": "Title: The evolution of pulmonary pathology in fatal COVID-19 disease: an autopsy study with clinical correlation Content: The pandemia of coronavirus disease 2019 (COVID-19) has caused more than 355,000 confirmed deaths worldwide. However, publications on postmortem findings are scarce. We present the pulmonary findings in four cases of fatal COVID-19 with a spectrum of lung pathology reflecting disease course and duration, invasive therapies, and laboratory features. Early disease is characterized by neutrophilic, exudative capillaritis with microthrombosis and high levels of IL-1beta and IL-6. Later stages are associated with diffuse alveolar damage and ongoing intravascular thrombosis in small to medium-sized pulmonary vessels, occasionally with areas of infarction equivalents, accompanied by laboratory features of disseminated intravascular coagulation. In late stages, organizing pneumonia with extensive intra-alveolar proliferation of fibroblasts and marked metaplasia of alveolar epithelium can be observed. Viral RNA is encountered in the lung, with virus particles in endothelial cells and pneumocytes. In many patients, multi-organ failure with severe liver damage sets in finally, possibly as consequence of an early-onset pro-inflammatory cytokine storm and/or thrombotic microangiopathy.", "qid": 4, "docid": "vx5cszxg", "rank": 99, "score": 0.741584300994873}, {"content": "Title: Cardiovascular manifestations and treatment considerations in covid-19 Content: Since its recognition in December 2019, covid-19 has rapidly spread globally causing a pandemic. Pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease are associated with a greater severity and higher fatality rate of covid-19. Furthermore, covid-19 contributes to cardiovascular complications, including acute myocardial injury as a result of acute coronary syndrome, myocarditis, stress-cardiomyopathy, arrhythmias, cardiogenic shock, and cardiac arrest. The cardiovascular interactions of covid-19 have similarities to that of severe acute respiratory syndrome, Middle East respiratory syndrome and influenza. Specific cardiovascular considerations are also necessary in supportive treatment with anticoagulation, the continued use of renin-angiotensin-aldosterone system inhibitors, arrhythmia monitoring, immunosuppression or modulation, and mechanical circulatory support.", "qid": 4, "docid": "873txs85", "rank": 100, "score": 0.7414681911468506}]}
{"query": "what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies?", "hits": [{"content": "Title: Search for SARS-CoV-2 inhibitors in currently approved drugs to tackle COVID-19 pandemia Content: Different treatments are currently used for clinical management of SARS-CoV-2 infection, but little is known about their efficacy yet. Here we present ongoing results to compare currently available drugs for a variety of diseases to find out if they counteract SARS-CoV-2-induced cytopathic effect in vitro. Our goal is to prioritize antiviral activity to provide a solid evidence-driven rationale for forthcoming clinical trials. Since the most effective antiviral approaches are usually based on combined therapies that tackle the viral life cycle at different stages, we are also testing combinations of drugs that may be critical to reduce the emergence of resistant viruses. We will provide results as soon as they become available, so data should be interpreted with caution, clearly understanding the limitations of the in vitro model, that may not always reflect what could happen in vivo. Thus, our goal is to test the most active antivirals identified in adequate animal models infected with SARS-CoV-2, to add more information about possible in vivo efficacy. In turn, successful antivirals could be tested in clinical trials as treatments for infected patients, but also as pre-exposure prophylaxis to avoid novel infections until an effective and safe vaccine is developed.", "qid": 5, "docid": "ywaefpe8", "rank": 1, "score": 0.8060276508331299}, {"content": "Title: Antiviral treatment of SARS-CoV-2-infected hamsters reveals a weak effect of favipiravir and a complete lack of effect for hydroxychloroquine Content: SARS-CoV-2 rapidly spread around the globe after its emergence in Wuhan in December 2019. With no specific therapeutic and prophylactic options available, the virus was able to infect millions of people. To date, close to half a million patients succumbed to the viral disease, COVID-19. The high need for treatment options, together with the lack of small animal models of infection has led to clinical trials with repurposed drugs before any preclinical in vivo evidence attesting their efficacy was available. We used Syrian hamsters to establish a model to evaluate antiviral activity of small molecules in both an infection and a transmission setting. Upon intranasal infection, the animals developed high titers of SARS-CoV-2 in the lungs and pathology similar to that observed in mild COVID-19 patients. Treatment of SARS-CoV-2-infected hamsters with favipiravir or hydroxychloroquine (with and without azithromycin) resulted in respectively a mild or no reduction in viral RNA and infectious virus. Micro-CT scan analysis of the lungs showed no improvement compared to non-treated animals, which was confirmed by histopathology. In addition, both compounds did not prevent virus transmission through direct contact and thus failed as prophylactic treatments. By modelling the PK profile of hydroxychloroquine based on the trough plasma concentrations, we show that the total lung exposure to the drug was not the limiting factor. In conclusion, we here characterized a hamster infection and transmission model to be a robust model for studying in vivo efficacy of antiviral compounds. The information acquired using hydroxychloroquine and favipiravir in this model is of critical value to those designing (current and) future clinical trials. At this point, the data here presented on hydroxychloroquine either alone or combined with azithromycin (together with previously reported in vivo data in macaques and ferrets) provide no scientific basis for further use of the drug in humans.", "qid": 5, "docid": "aexlwq79", "rank": 2, "score": 0.8003377318382263}, {"content": "Title: Medication for COVID-19\u2014an Overview of Approaches Currently Under Study Content: BACKGROUND: With the worldwide spread of SARS-CoV-2 infection, it is becoming increasingly urgent to develop a vaccine to prevent COVID-19, as well as effective drugs to treat it. METHODS: This article is based on a selective literature search in PubMed and ClinicalTrials.gov, followed by an assessment of the ongoing clinical trials that were revealed by the search. RESULTS: A number of substances have been found to prevent the reproduction of SARS-CoV-2 in vitro. These include virustatic agents that have already been approved for the treatment of other types of viral infection, as well as drugs that are currently used for entirely different purposes. High in vitro activity has been found for the nucleotide analogue remdesivir, for the antimalarial drug chloroquine, and for nitazoxanide, a drug used to treat protozoan infections. Because the virus enters human cells by way of the membrane-associated angiotensin converting enzyme 2 (ACE2), keeping the virus from docking to this receptor is a conceivable treatment approach. Transmembrane protease serine 2 (TMPRSS2) plays a role in the fusion of the virus with cells; inhibitors of this enzyme are known as well. The potential therapeutic efficacy and tolerability of these and other active substances remain to be investigated in clinical trials. At present, more than 80 trials on COVID-10 have already been registered with ClinicalTrials.gov. Some initial findings should already be available in late April 2020. CONCLUSION: Clinical trials are now indispensable in order to determine the true clinical benefits and risks of the substances that have been found to be active against SARS-CoV-2 in vitro. There is not yet any recommendation for the therapeutic use of any particular agent beyond standard supportive treatment.", "qid": 5, "docid": "vyeescn8", "rank": 3, "score": 0.7930614352226257}, {"content": "Title: Medication for COVID-19-an Overview of Approaches Currently Under Study Content: BACKGROUND: With the worldwide spread of SARS-CoV-2 infection, it is becoming increasingly urgent to develop a vaccine to prevent COVID-19, as well as effective drugs to treat it. METHODS: This article is based on a selective literature search in PubMed and ClinicalTrials.gov, followed by an assessment of the ongoing clinical trials that were revealed by the search. RESULTS: A number of substances have been found to prevent the reproduction of SARS-CoV-2 in vitro. These include virustatic agents that have already been approved for the treatment of other types of viral infection, as well as drugs that are currently used for entirely different purposes. High in vitro activity has been found for the nucleotide analogue remdesivir, for the antimalarial drug chloroquine, and for nitazoxanide, a drug used to treat protozoan infections. Because the virus enters human cells by way of the membrane-associated angiotensin converting enzyme 2 (ACE2), keeping the virus from docking to this receptor is a conceivable treatment approach. Transmembrane protease serine 2 (TMPRSS2) plays a role in the fusion of the virus with cells; inhibitors of this enzyme are known as well. The potential therapeutic efficacy and tolerability of these and other active substances remain to be investigated in clinical trials. At present, more than 80 trials on COVID-10 have already been registered with Clinical- Trials.gov. Some initial findings should already be available in late April 2020. CONCLUSION: Clinical trials are now indispensable in order to determine the true clinical benefits and risks of the substances that have been found to be active against SARSCoV- 2 in vitro. There is not yet any recommendation for the therapeutic use of any particular agent beyond standard supportive treatment.", "qid": 5, "docid": "jd1b7asr", "rank": 4, "score": 0.7927894592285156}, {"content": "Title: Remdesivir potently inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 as the causative agent of the novel pandemic viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for safe, broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV), a monophosphoramidate prodrug of an adenosine analog, potently inhibits SARS-CoV-2 replication in human lung cells and primary human airway epithelial cultures (EC50 = 0.01 \u03bcM). Weaker activity was observed in Vero E6 cells (EC50 = 1.65 \u03bcM) due to their low capacity to metabolize RDV. To rapidly evaluate in vivo efficacy, we engineered a chimeric SARS-CoV encoding the viral target of RDV, the RNA-dependent RNA polymerase, of SARS-CoV-2. In mice infected with chimeric virus, therapeutic RDV administration diminished lung viral load and improved pulmonary function as compared to vehicle treated animals. These data provide evidence that RDV is potently active against SARS-CoV-2 in vitro and in vivo, supporting its further clinical testing for treatment of COVID-19.", "qid": 5, "docid": "ghrlj6b2", "rank": 5, "score": 0.7905219197273254}, {"content": "Title: Drug repurposing clinical trials in the search for life-saving COVID-19 therapies;research targets and methodological and ethical issues Content: Introduction: So far, there is no vaccine, nor are there effective drugs to treat COVID-19, an emerging viral respiratory infection deadlier than influenza Objective: To take a snapshot picture of planned and ongoing clinical research addressing drugs potentially useful for treating SAR-CoV-2 infections Method: A search was conducted (20 April 2020) in an international registry of clinical studies (https://ClinicalTrials gov, US NIH) After excluding observational studies and other interventions that fell outside the scope of this study, 294 research protocols (out of 516 retrieved protocols) were selected for analysis Results: Of 294 included trials, 249 were Randomized Controlled Trials (RCT), 118 of which were double-, triple- or quadruple-blinded studies The interventions (drug therapies) were compared with \"standard-of-care\" (SOC) or with the placebo plus SOC, or yet with presumed \"active\" comparators RCT focused on the primary treatment of the disease (inhibitors of viral replication) or on the therapy for resolution of hyperinflammation in pneumonia/Acute Respiratory Distress Syndrome (ARDS) and thromboembolism associated with SARS-CoV-2 The trials found in the database involve existing antiviral compounds and drugs with multiple modes of antiviral action Antiparasitic drugs, which inhibited viral replication in cell-culture assays, are being tested as well Regarding the adjunctive immunomodulatory, anti-inflammatory and antithrombotic therapies, a number of drugs with distinct pharmacological targets are under investigation in trials enrolling patients with severe COVID-19 Conclusions: Although many clinical studies of drugs for COVID-19 are planned or in progress, only a minority of them are sufficiently large, randomized and placebo-controlled trials with masking and concealment of allocation Owing to methodological limitations, only a few clinical trials found in the registry are likely to yield robust evidence of effectiveness and safety of drugs repurposable for COVID-19", "qid": 5, "docid": "a4oibkt9", "rank": 6, "score": 0.7872719764709473}, {"content": "Title: Development of remdesivir repositioning as a nucleotide analog against COVID-19 RNA dependent RNA polymerase Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative representative of a severe respiratory illness resulted in widespread human infections and deaths in nearly all of the countries since late 2019. There is no therapeutic FDA-approved drug against SARS-CoV-2 infection, although a combination of anti-viral drugs is directly being practiced in some countries. A broad-spectrum of antiviral agents are being currently evaluated in clinical trials, and in this review, we specifically focus on the application of Remdesivir (RVD) as a potential anti-viral compound against Middle East respiratory syndrome (MERS) -CoV, SARS-CoV and SARS-CoV-2. First, we overview the general information about SARS-CoV-2, followed by application of RDV as a nucleotide analogue which can potentially inhibits RNA-dependent RNA polymerase of COVs. Afterwards, we discussed the kinetics of SARS- or MERS-CoV proliferation in animal models which is significantly different compared to that in humans. Finally, some ongoing challenges and future perspective on the application of RDV either alone or in combination with other anti-viral agents against CoVs infection were surveyed to determine the efficiency of RDV in preclinical trials. As a result, this paper provides crucial evidence of the potency of RDV to prevent SARS-CoV-2 infections.Communicated by Ramaswamy H. Sarma.", "qid": 5, "docid": "kjc3j7yz", "rank": 7, "score": 0.7871139049530029}, {"content": "Title: Development of remdesivir repositioning as a nucleotide analog against COVID-19 RNA dependent RNA polymerase Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative representative of a severe respiratory illness resulted in widespread human infections and deaths in nearly all of the countries since late 2019. There is no therapeutic FDA-approved drug against SARS-CoV-2 infection, although a combination of anti-viral drugs is directly being practiced in some countries. A broad-spectrum of antiviral agents are being currently evaluated in clinical trials, and in this review, we specifically focus on the application of Remdesivir (RVD) as a potential anti-viral compound against Middle East respiratory syndrome (MERS) -CoV, SARS-CoV and SARS-CoV-2. First, we overview the general information about SARS-CoV-2, followed by application of RDV as a nucleotide analogue which can potentially inhibits RNA-dependent RNA polymerase of COVs. Afterwards, we discussed the kinetics of SARS- or MERS-CoV proliferation in animal models which is significantly different compared to that in humans. Finally, some ongoing challenges and future perspective on the application of RDV either alone or in combination with other anti-viral agents against CoVs infection were surveyed to determine the efficiency of RDV in preclinical trials. As a result, this paper provides crucial evidence of the potency of RDV to prevent SARS-CoV-2 infections. Communicated by Ramaswamy H. Sarma", "qid": 5, "docid": "2ro2p77q", "rank": 8, "score": 0.7869464159011841}, {"content": "Title: Broad anti-coronaviral activity of FDA approved drugs against SARS-CoV-2 in vitro and SARS-CoV in vivo Content: SARS-CoV-2 emerged in China at the end of 2019 and has rapidly become a pandemic with roughly 2.7 million recorded COVID-19 cases and greater than 189,000 recorded deaths by April 23rd, 2020 (www.WHO.org). There are no FDA approved antivirals or vaccines for any coronavirus, including SARS-CoV-2. Current treatments for COVID-19 are limited to supportive therapies and off-label use of FDA approved drugs. Rapid development and human testing of potential antivirals is greatly needed. A quick way to test compounds with potential antiviral activity is through drug repurposing. Numerous drugs are already approved for human use and subsequently there is a good understanding of their safety profiles and potential side effects, making them easier to fast-track to clinical studies in COVID-19 patients. Here, we present data on the antiviral activity of 20 FDA approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and MERS-CoV. We found that 17 of these inhibit SARS-CoV-2 at a range of IC50 values at non-cytotoxic concentrations. We directly follow up with seven of these to demonstrate all are capable of inhibiting infectious SARS-CoV-2 production. Moreover, we have evaluated two of these, chloroquine and chlorpromazine, in vivo using a mouse-adapted SARS-CoV model and found both drugs protect mice from clinical disease.", "qid": 5, "docid": "jbc74lcu", "rank": 9, "score": 0.786941409111023}, {"content": "Title: SARS CoV-2: Recent Reports on Antiviral Therapies Based on Lopinavir/Ritonavir, Darunavir/Umifenovir, Hydroxychloroquine, Remdesivir, Favipiravir and Other Drugs for the Treatment of the New Coronavirus. Content: Here we report on the most recent updates on experimental drugs successfully employed in the treatment of the disease caused by SARS CoV-2 coronavirus, also referred to as COVID-19 (COronaVIrus Disease 19). In particular, several cases of recovered patients have been reported after being treated with lopinavir/ritonavir (which is widely used to treat human immunodeficiency virus (HIV) infection) in combination with the anti-flu drug oseltamivir. In addition, remdesivir, which has been previously administered to Ebola virus patients, has also proven effective in the U.S. against coronavirus, while antimalarial chloroquine and hydroxychloroquine, favipiravir and co-administered darunavir and umifenovir (in patient therapies) were also recently recorded as having anti-SARS CoV-2 effects. Since the recoveries/deaths ratio in the last weeks significantly increased, especially in China, it is clear that the experimental antiviral therapy, together with the availability of intensive care unit beds in hospitals and rigorous government control measures, all play an important role in dealing with this virus. This also stresses the urgent need for the scientific community to devote its efforts to find other more specific antiviral strategies.", "qid": 5, "docid": "h450b2l5", "rank": 10, "score": 0.7848781943321228}, {"content": "Title: Development of antiviral therapy for severe acute respiratory syndrome Content: Abstract A new disease, the severe acute respiratory distress syndrome (SARS), caused by the SARS coronavirus (SARS-CoV), emerged at the beginning of 2003 and rapidly spread throughout the world. Although the disease had disappeared in June 2003 its re-emergence cannot be excluded. The development of vaccines against SARS-CoV may take years. Therefore, the availability of effective antiviral drugs against SARS-CoV may be crucial for the control of future SARS outbreaks. In this review, experimental and clinical data about potential anti-SARS drugs is summarised and discussed. Animal model studies will be needed to help to determine which interventions warrant controlled clinical testing.", "qid": 5, "docid": "9ujofcsm", "rank": 11, "score": 0.7846161127090454}, {"content": "Title: Current pharmacological treatments for SARS-COV-2: A narrative review Content: The novel coronavirus, later identified as SARS-CoV-2, originating from Wuhan in China in November 2019, quickly spread around the world becoming a pandemic. Despite the knowledge of previous coronaviruses, such as those responsible for the SARS and MERS-CoV epidemic, there is no drug or prophylaxis treatment to this day. The rapid succession of scientific findings on SARS-CoV-2 provides a significant number of potential drug targets. Nevertheless, at the same time, the high quantity of clinical data, generated by a large number of rapidly infected people, require accurate tests regarding effective medical treatments. Several in vitro and in vivo studies were rapidly initiated after the outbreak of the pandemic COVID-19. Initial clinical studies revealed the promising potential of remdesivir that demonstrated a powerful and specific in vitro antiviral activity for COVID-19. Promising effects appear to be attributable to hydroxychloroquine. Remdesivir and hydroxychloroquine are being tested in ongoing randomized trials. In contrast, oseltamivir was not effective and corticosteroids are not currently recommended. However, few data from ongoing clinical trials are identifying low molecular weight heparins, innate immune system stimulating agents, and inflammatory modulating agents as potential effective agents. The authors assume that the current pandemic will determine the need for a systematic approach based on big data analysis for identifying effective drugs to defeat SARS-Cov-2. This work is aimed to be a general reference point and to provide an overview as comprehensive as possible regarding the main clinical trials in progress at the moment.", "qid": 5, "docid": "303b23dd", "rank": 12, "score": 0.78429114818573}, {"content": "Title: In vitro data of current therapies for SARS-CoV-2. Content: BACKGROUND In December 2019, a new coronavirus, named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has emerged from China causing pneumonia outbreaks first in the Wuhan region and currently worldwide. In the light of the lack of efficient and specific treatments and the need to contain the epidemic, drug repurposing appears to be the most efficient tool to find therapeutic solution. OBJECTIVES The aim of this study was to summarize in vitro data of current agents used for the management of SARSCoV-2 all over the world. METHODS A literature search of articles from January 2000 until April 2020 was performed using MEDLINE, EMBASE and the Cochrane Library to assess in vitro data of current or putative therapies for SARS-CoV-2. RESULTS Although in vitro studies are scarce, data regarding chloroquine and hydroxychloroquine, remdesivir, nitazoxanide, teicoplanin, ivermectin, lopinavir, homoharringtonine and emetine seem promising. CONCLUSION Scientist all over the world should work together and increase their efforts in order to find feasible and efficient solutions against this new global viral threat.", "qid": 5, "docid": "de45x8q4", "rank": 13, "score": 0.7835168242454529}, {"content": "Title: A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV-2 main protease Content: The SARS coronavirus type 2 (SARS-CoV-2) emerged in late 2019 as a zoonotic virus highly transmissible between humans that has caused the COVID-19 pandemic 1,2. This pandemic has the potential to disrupt healthcare globally and has already caused high levels of mortality, especially amongst the elderly. The overall case fatality rate for COVID-19 is estimated to be \u223c2.3% overall 3 and 32.3% in hospitalized patients age 70-79 years 4. Therapeutic options for treating the underlying viremia in COVID-19 are presently limited by a lack of effective SARS-CoV-2 antiviral drugs, although steroidal anti-inflammatory treatment can be helpful. A variety of potential antiviral targets for SARS-CoV-2 have been considered including the spike protein and replicase. Based upon previous successful antiviral drug development for HIV-1 and hepatitis C, the SARS-CoV-2 main protease (Mpro) appears an attractive target for drug development. Here we show the existing pharmacopeia contains many drugs with potential for therapeutic repurposing as selective and potent inhibitors of SARS-CoV-2 Mpro. We screened a collection of \u223c6,070 drugs with a previous history of use in humans for compounds that inhibit the activity of Mpro in vitro. In our primary screen we found \u223c50 compounds with activity against Mpro (overall hit rate <0.75%). Subsequent dose validation studies demonstrated 8 dose responsive hits with an IC50 \u2264 50 \u03bcM. Hits from our screen are enriched with hepatitis C NS3/4A protease targeting drugs including Boceprevir (IC50=0.95 \u03bcM), Ciluprevir (20.77\u03bcM). Narlaprevir (IC50=1.10\u03bcM), and Telaprevir (15.25\u03bcM). These results demonstrate that some existing approved drugs can inhibit SARS-CoV-2 Mpro and that screen saturation of all approved drugs is both feasible and warranted. Taken together this work suggests previous large-scale commercial drug development initiatives targeting hepatitis C NS3/4A viral protease should be revisited because some previous lead compounds may be more potent against SARS-CoV-2 Mpro than Boceprevir and suitable for rapid repurposing.", "qid": 5, "docid": "slouuryl", "rank": 14, "score": 0.7825660705566406}, {"content": "Title: Remdesivir inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice. Content: Summary Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the novel viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV) potently inhibits SARS-CoV-2 replication in human lung cells and primary human airway epithelial cultures (EC50 = 0.01 \u03bcM). Weaker activity is observed in Vero E6 cells (EC50 = 1.65 \u03bcM) due to their low capacity to metabolize RDV. To rapidly evaluate in vivo efficacy, we engineered a chimeric SARS-CoV encoding the viral target of RDV, the RNA-dependent RNA polymerase, of SARS-CoV-2. In mice infected with chimeric virus, therapeutic RDV administration diminishes lung viral load and improves pulmonary function compared to vehicle treated animals. These data demonstrate that RDV is potently active against SARS-CoV-2 in vitro and in vivo, supporting its further clinical testing for treatment of COVID-19.", "qid": 5, "docid": "9sjdb7f3", "rank": 15, "score": 0.7814202308654785}, {"content": "Title: Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Content: Effective therapeutics to treat COVID-19 are urgently needed. While many investigational, approved, and repurposed drugs have been suggested, preclinical data from animal models can guide the search for effective treatments by ruling out treatments without in vivo efficacy. Remdesivir (GS-5734) is a nucleotide analog prodrug with broad antiviral activity1,2, that is currently investigated in COVID-19 clinical trials and recently received Emergency Use Authorization from the US Food and Drug Administration3,4. In animal models, remdesivir treatment was effective against MERS-CoV and SARS-CoV infection.2,5,6 In vitro, remdesivir inhibited replication of SARS-CoV-2.7,8 Here, we investigated the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection9. In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs and reduced virus titers in bronchoalveolar lavages 12hrs after the first treatment administration. Virus shedding from the upper respiratory tract was not reduced by remdesivir treatment. At necropsy, lung viral loads of remdesivir-treated animals were lower and there was a reduction in damage to the lungs. Thus, therapeutic remdesivir treatment initiated early during infection had a clinical benefit in SARS-CoV-2-infected rhesus macaques. Although the rhesus macaque model does not represent the severe disease observed in a proportion of COVID-19 patients, our data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to pneumonia.", "qid": 5, "docid": "1cph1uij", "rank": 16, "score": 0.7786587476730347}, {"content": "Title: Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2 Content: Effective therapeutics to treat COVID-19 are urgently needed. While many investigational, approved, and repurposed drugs have been suggested, preclinical data from animal models can guide the search for effective treatments by ruling out treatments without in vivo efficacy. Remdesivir (GS-5734) is a nucleotide analog prodrug with broad antiviral activity1,2, that is currently investigated in COVID-19 clinical trials and recently received Emergency Use Authorization from the US Food and Drug Administration3,4. In animal models, remdesivir treatment was effective against MERS-CoV and SARS-CoV infection.2,5,6 In vitro, remdesivir inhibited replication of SARS-CoV-2.7,8 Here, we investigated the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection9. In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs and reduced virus titers in bronchoalveolar lavages 12hrs after the first treatment administration. Virus shedding from the upper respiratory tract was not reduced by remdesivir treatment. At necropsy, lung viral loads of remdesivir-treated animals were lower and there was a reduction in damage to the lungs. Thus, therapeutic remdesivir treatment initiated early during infection had a clinical benefit in SARS-CoV-2-infected rhesus macaques. Although the rhesus macaque model does not represent the severe disease observed in a proportion of COVID-19 patients, our data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to pneumonia.", "qid": 5, "docid": "jxbch44o", "rank": 17, "score": 0.7786586284637451}, {"content": "Title: In vitro data of current therapies for SARS-CoV-2 Content: BACKGROUND: In December 2019, a new coronavirus, named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has emerged from China causing pneumonia outbreaks first in the Wuhan region and currently worldwide. In the light of the lack of efficient and specific treatments and the need to contain the epidemic, drug repurposing appears to be the most efficient tool to find therapeutic solution. OBJECTIVES: The aim of this study was to summarize in vitro data of current agents used for the management of SARSCoV-2 all over the world. METHODS: A literature search of articles from January 2000 until April 2020 was performed using MEDLINE, EMBASE and the Cochrane Library to assess in vitro data of current or putative therapies for SARS-CoV-2. RESULTS: Although in vitro studies are scarce, data regarding chloroquine and hydroxychloroquine, remdesivir, nitazoxanide, teicoplanin, ivermectin, lopinavir, homoharringtonine and emetine seem promising. CONCLUSION: Scientist all over the world should work together and increase their efforts in order to find feasible and efficient solutions against this new global viral threat.", "qid": 5, "docid": "kfal7g2v", "rank": 18, "score": 0.7786365747451782}, {"content": "Title: Dermatological therapies with relevance to COVID-19 Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel single-stranded RNA virus that has gripped humanity all over. It affects primarily the respiratory system, but is not limited to it, causing widespread involvement of many organ systems. The cases are still rising at an exponential rate and manifold trials are on to test different agents with the hope for potential limitation of spread and control of symptoms. Various classes of drugs have been tried; some with moderate success while many are yet to be proven to be of definite benefit. We have observed that the drugs used in dermatology practice are featured in more than a few of such studies. Here, we wish to highlight the ones that we are familiar with, which has featured at some point, in the management of this very challenging pandemic.", "qid": 5, "docid": "a2hd6d7s", "rank": 19, "score": 0.7777143716812134}, {"content": "Title: Protection from infection with severe acute respiratory syndrome coronavirus in a Chinese hamster model by equine neutralizing F(ab')2. Content: To warrant potential clinical testing, the equine anti-severe acute respiratory syndrome coronavirus (SARS-CoV) F(ab')(2) requires evaluation in as many animal models as possible. In this study, we established a new animal model, the Chinese hamster, susceptible to SARS-CoV infection. SARS-CoV could propagate effectively and sustain high levels for 1 wk in animal lungs. All animals were protected from SARS-CoV infection in preventive settings. Further, when used therapeutically this antibody led to an approximately 4-log(10) decrease in viral burden in infected animal lungs. The pathological changes in lungs correlated closely with the dose of antibody administered. The excellent preventive and therapeutic roles of equine anti-SARS-CoV F(ab')(2) in several animal models, including the novel Chinese hamster model described in this study, have provided exciting data concerning its potential clinical study.", "qid": 5, "docid": "60516gav", "rank": 20, "score": 0.7771053314208984}, {"content": "Title: The challenging pathway towards the identification of SARS-CoV-2/COVID-19 therapeutics Content: The development of therapeutic agents against SARS-CoV-2/COVID-19 faces numerous barriers and a multidisciplinary approach to evaluating drug efficacy and toxicity is essential. Experimental and preclinical data should be integrated into a comprehensive analysis, where drug potency, the timing of therapy initiation, drug combinations, variability in systemic and local drug exposure and short- and long-term toxicities represent fundamental factors for the rational identification of candidates and prioritization of clinical investigations. Although the identification of SARS-CoV-2 therapeutics is a priority, rigorous and transparent methodologies are crucial to ensure that accelerated research programmes result in high-quality and reproducible findings.", "qid": 5, "docid": "ifrgx8tx", "rank": 21, "score": 0.7765772342681885}, {"content": "Title: Small molecules targeting severe acute respiratory syndrome human coronavirus. Content: Severe acute respiratory syndrome (SARS) is an infectious disease caused by a novel human coronavirus. Currently, no effective antiviral agents exist against this type of virus. A cell-based assay, with SARS virus and Vero E6 cells, was developed to screen existing drugs, natural products, and synthetic compounds to identify effective anti-SARS agents. Of >10,000 agents tested, approximately 50 compounds were found active at 10 microM; among these compounds, two are existing drugs (Reserpine 13 and Aescin 5) and several are in clinical development. These 50 active compounds were tested again, and compounds 2-6, 10, and 13 showed active at 3 microM. The 50% inhibitory concentrations for the inhibition of viral replication (EC(50)) and host growth (CC(50)) were then measured and the selectivity index (SI = CC(50)/EC(50)) was determined. The EC(50), based on ELISA, and SI for Reserpine, Aescim, and Valinomycin are 3.4 microM (SI = 7.3), 6.0 microM (SI = 2.5), and 0.85 microM (SI = 80), respectively. Additional studies were carried out to further understand the mode of action of some active compounds, including ELISA, Western blot analysis, immunofluorescence and flow cytometry assays, and inhibition against the 3CL protease and viral entry. Of particular interest are the two anti-HIV agents, one as an entry blocker and the other as a 3CL protease inhibitor (K(i) = 0.6 microM).", "qid": 5, "docid": "biu8slfv", "rank": 22, "score": 0.7761129140853882}, {"content": "Title: Antiviral drug discovery against SARS-CoV. Content: Severe Acute Respiratory Syndrome (SARS) is a life-threatening infectious disease caused by SARS-CoV. In the 2003 outbreak, it infected more than 8,000 people worldwide and claimed the lives of more than 900 victims. The high mortality rate resulted, at least in part, from the absence of definitive treatment protocols or therapeutic agents. Although the virus spreading has been contained, due preparedness and planning, including the successful development of antiviral drugs against SARS-CoV, is necessary for possible reappearance of SARS. In this review, we have discussed currently available strategies for antiviral drug discovery and how these technologies have been utilized to identify potential antiviral agents for the inhibition of SARS-CoV replication. Moreover, progress in the drug development based on different molecular targets is also summarized, including 1) Compounds that block the S protein-ACE2-mediated viral entry; 2) Compounds targeting SARS-CoV M(pro); 3) Compounds targeting papain-like protease 2 (PLP2); 4) Compounds targeting SARS-CoV RdRp; 5) Compounds targeting SARS-CoV helicase; 6) Active compounds with unspecified targets; and 7) Research on siRNA. This review aims to provide a comprehensive account of drug discovery on SARS. The experiences with the SARS outbreak and drug discovery would certainly be an important lesson for the drug development for any new viral outbreaks that may emerge in the future.", "qid": 5, "docid": "1fy9edg3", "rank": 23, "score": 0.7756578922271729}, {"content": "Title: SARS-CoV-2: Repurposed Drugs and Novel Therapeutic Approaches-Insights into Chemical Structure-Biological Activity and Toxicological Screening Content: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic represents the primary public health concern nowadays, and great efforts are made worldwide for efficient management of this crisis Considerable scientific progress was recorded regarding SARS-CoV-2 infection in terms of genomic structure, diagnostic tools, viral transmission, mechanism of viral infection, symptomatology, clinical impact, and complications, but these data evolve constantly Up to date, neither an effective vaccine nor SARS-CoV-2 specific antiviral agents have been approved, but significant advances were enlisted in this direction by investigating repurposed approved drugs (ongoing clinical trials) or developing innovative antiviral drugs (preclinical and clinical studies) This review presents a thorough analysis of repurposed drug admitted for compassionate use from a chemical structure-biological activity perspective highlighting the ADME (absorption, distribution, metabolism, and excretion) properties and the toxicophore groups linked to potential adverse effects A detailed pharmacological description of the novel potential anti-COVID-19 therapeutics was also included In addition, a comprehensible overview of SARS-CoV-2 infection in terms of general description and structure, mechanism of viral infection, and clinical impact was portrayed", "qid": 5, "docid": "ip092sys", "rank": 24, "score": 0.7751117944717407}, {"content": "Title: Animal models for emerging coronavirus: progress and new insights Content: The emergences of coronaviruses have caused a serious global public health problem because their infection in humans caused the severe acute respiratory disease and deaths. The outbreaks of lethal coronaviruses have taken place for three times within recent two decades (SARS-CoV in 2002, MERS-CoV in 2012 and SARS-CoV-2 in 2019). Much more serious than SARS-CoV in 2002, the current SARS-CoV-2 infection has been spreading to more than 213 countries, areas or territories and causing more than two million cases up to date (17 April 2020). Unfortunately, no vaccine and specific anti-coronavirus drugs are available at present time. Current clinical treatment at hand is inadequate to suppress viral replication and inflammation, and reverse organ failure. Intensive research efforts have focused on increasing our understanding of viral biology of SARS-CoV-2, improving antiviral therapy and vaccination strategies. The animal models are important for both the fundamental research and drug discovery of coronavirus. This review aims to summarize the animal models currently available for SARS-CoV and MERS-CoV, and their potential use for the study of SARS-CoV-2. We will discuss the benefits and caveats of these animal models and present critical findings that might guide the fundamental studies and urgent treatment of SARS-CoV-2-caused diseases.", "qid": 5, "docid": "pld0clpd", "rank": 25, "score": 0.7750921249389648}, {"content": "Title: Current global vaccine and drug efforts against COVID-19: Pros and cons of bypassing animal trials Content: COVID-19 has become one of the biggest health concern, along with huge economic burden. With no clear remedies to treat the disease, doctors are repurposing drugs like chloroquine and remdesivir to treat COVID-19 patients. In parallel, research institutes in collaboration with biotech companies have identified strategies to use viral proteins as vaccine candidates for COVID-19. Although this looks promising, they still need to pass the test of challenge studies in animal models. As various models for SARS-CoV-2 are under testing phase, biotech companies have bypassed animal studies and moved to Phase I clinical trials. In view of the present outbreak, this looks a justified approach, but the problem is that in the absence of animal studies, we can never predict the outcomes in humans. Since animal models are critical for vaccine development and SARS-CoV-2 has different transmission dynamics, in this review we compare different animal models of SARS-CoV-2 with humans for their pathogenic, immune response and transmission dynamics that make them ideal models for vaccine testing for COVID-19. Another issue of using animal model is the ethics of using animals for research; thus, we also discuss the pros and cons of using animals for vaccine development studies.", "qid": 5, "docid": "3sepefqa", "rank": 26, "score": 0.7750235795974731}, {"content": "Title: Current global vaccine and drug efforts against COVID-19: Pros and cons of bypassing animal trials. Content: COVID-19 has become one of the biggest health concern, along with huge economic burden. With no clear remedies to treat the disease, doctors are repurposing drugs like chloroquine and remdesivir to treat COVID-19 patients. In parallel, research institutes in collaboration with biotech companies have identified strategies to use viral proteins as vaccine candidates for COVID-19. Although this looks promising, they still need to pass the test of challenge studies in animal models. As various models for SARS-CoV-2 are under testing phase, biotech companies have bypassed animal studies and moved to Phase I clinical trials. In view of the present outbreak, this looks a justified approach, but the problem is that in the absence of animal studies, we can never predict the outcomes in humans. Since animal models are critical for vaccine development and SARS-CoV-2 has different transmission dynamics, in this review we compare different animal models of SARS-CoV-2 with humans for their pathogenic, immune response and transmission dynamics that make them ideal models for vaccine testing for COVID-19. Another issue of using animal model is the ethics of using animals for research; thus, we also discuss the pros and cons of using animals for vaccine development studies.", "qid": 5, "docid": "oa8vzf02", "rank": 27, "score": 0.7750235795974731}, {"content": "Title: Indomethacin has a potent antiviral activity against SARS CoV-2 in vitro and canine coronavirus in vivo Content: Background The outbreak of SARS CoV-2 has caused ever-increasing attention and public panic all over the world. Currently, there is no specific treatment against the SARS CoV-2. Therefore, identifying effective antiviral agents to combat the disease is urgently needed. Previous studies found that indomethacin has the ability to inhibit the replication of several unrelated DNA and RNA viruses, including SARS-CoV. Methods SARS CoV-2 pseudovirus-infected African green monkey kidney VERO E6 cells treated with different concentrations of indomethacin or aspirin at 48 hours post infection (p.i). The level of cell infection was determined by luciferase activity. Anti-coronavirus efficacy in vivo was confirmed by evaluating the time of recovery in canine coronavirus (CCV) infected dogs treated orally with 1mg/kg body weight indomethacin. Results We found that indomethacin has a directly and potently antiviral activity against the SARS CoV-2 pseudovirus (reduce relative light unit to zero). In CCV-infected dogs, recovery occurred significantly sooner with symptomatic treatment + oral indomethacin (1 mg/kg body weight) daily treatments than with symptomatic treatment + ribavirin (10-15 mg/kg body weight) daily treatments (P =0.0031), but was not significantly different from that with symptomatic treatment + anti-canine coronavirus serum + canine hemoglobin + canine blood immunoglobulin + interferon treatments (P =0.7784). Conclusion The results identify indomethacin as a potent inhibitor of SARS CoV-2.", "qid": 5, "docid": "7joyaz7q", "rank": 28, "score": 0.7745212316513062}, {"content": "Title: Feasibility of Known RNA Polymerase Inhibitors as Anti-SARS-CoV-2 Drugs Content: Coronaviruses (CoVs) are positive-stranded RNA viruses that infect humans and animals. Infection by CoVs such as HCoV-229E, -NL63, -OC43 and -HKU1 leads to the common cold, short lasting rhinitis, cough, sore throat and fever. However, CoVs such as Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and the newest SARS-CoV-2 (the causative agent of COVID-19) lead to severe and deadly diseases with mortality rates ranging between ~1 to 35% depending on factors such as age and pre-existing conditions. Despite continuous global health threats to humans, there are no approved vaccines or drugs targeting human CoVs, and the recent outbreak of COVID-19 emphasizes an urgent need for therapeutic interventions. Using computational and bioinformatics tools, here we present the feasibility of reported broad-spectrum RNA polymerase inhibitors as anti- SARS-CoV-2 drugs targeting its main RNA polymerase, suggesting that investigational and approved nucleoside RNA polymerase inhibitors have potential as anti-SARS-CoV-2 drugs. However, we note that it is also possible for SARS-CoV-2 to evolve and acquire drug resistance mutations against these nucleoside inhibitors.", "qid": 5, "docid": "b0a0s2fs", "rank": 29, "score": 0.772653341293335}, {"content": "Title: Evaluation of 19 antiviral drugs against SARS-CoV-2 Infection Content: The global pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) has prompted multiple clinical trials to jumpstart search for anti-SARS-CoV-2 therapies from existing drugs, including those with reported in vitro efficacies as well as those ones that are not known to inhibit SARS-CoV-2, such as ritonavir/lopinavir and favilavir. Here we report that after screening 19 antiviral drugs that are either in clinical trials or with proposed activity against SARS-CoV-2, remdesivir was the most effective. Chloroquine only effectively protected virus-induced cytopathic effect at around 30 \u00b5M with a therapeutic index of 1.5. Our findings also suggest that velpatasvir, ledipasvir, ritonavir, litonavir, lopinavir, favilavir, sofosbuvir, danoprevir, and pocapavir do not have direct antiviral effect.", "qid": 5, "docid": "ai2zcke5", "rank": 30, "score": 0.7726526260375977}, {"content": "Title: Candidate drugs against SARS-CoV-2 and COVID-19 Content: Abstract Outbreak and pandemic of coronavirus SARS-CoV-2 in 2019/2020 will challenge global health for the future. Because a vaccine against the virus will not be available in the near future, we herein try to offer a pharmacological strategy to combat the virus. There exists a number of candidate drugs that may inhibit infection with and replication of SARS-CoV-2. Such drugs comprise inhibitors of TMPRSS2 serine protease and inhibitors of angiotensin-converting enzyme 2 (ACE2). Blockade of ACE2, the host cell receptor for the S protein of SARS-CoV-2 and inhibition of TMPRSS2, which is required for S protein priming may prevent cell entry of SARS-CoV-2. Further, chloroquine and hydroxychloroquine, and off-label antiviral drugs, such as the nucleotide analogue remdesivir, HIV protease inhibitors lopinavir and ritonavir, broad-spectrum antiviral drugs arbidol and favipiravir as well as antiviral phytochemicals available to date may prevent spread of SARS-CoV-2 and morbidity and mortality of COVID-19 pandemic.", "qid": 5, "docid": "n0mz098o", "rank": 31, "score": 0.772390604019165}, {"content": "Title: Repurposing old drugs as antiviral agents for coronaviruses Content: BACKGROUND: New therapeutic options to address the ongoing COVID-19 pandemic are urgently needed. One possible strategy is the repurposing of existing drugs approved for other indications as antiviral agents for SARS-CoV-2. Due to the commercial unavailability of SARS-CoV-2 drugs for treating COVID-19, we screened approximately 250 existing drugs or pharmacologically active compounds for their inhibitory activities against feline infectious peritonitis coronavirus (FIPV) and human coronavirus OC43 (HCoV-OC43), a human coronavirus in the same genus (Betacoronavirus) as SARS-CoV-2. METHODS: FIPV was proliferated in feline Fcwf-4 cells and HCoV-OC43 in human HCT-8 cells. Viral proliferation was assayed by visualization of cytopathic effects on the infected Fcwf-4 cells and immunofluorescent assay for detection of the nucleocapsid proteins of HCoV-OC43 in the HCT-8 cells. The concentrations (EC(50)) of each drug necessary to diminish viral activity to 50% of that for the untreated controls were determined. The viabilities of Fcwf-4 and HCT-8 cells were measured by crystal violet staining and MTS/PMS assay, respectively. RESULTS: Fifteen out of the 252 drugs or pharmacologically active compounds screened were found to be active against both FIPV and HCoV-OC43, with EC(50) values ranging from 11 nM to 75 \u03bcM. They are all old drugs as follows, anisomycin, antimycin A, atovaquone, chloroquine, conivaptan, emetine, gemcitabine, homoharringtonine, niclosamide, nitazoxanide, oligomycin, salinomycin, tilorone, valinomycin, vismodegib. CONCLUSION: All of the old drugs identified as having activity against FIPV and HCoV-OC43 have seen clinical use in their respective indications and are associated with known dosing schedules and adverse effect or toxicity profiles in humans. Those, when later confirmed to have an anti-viral effect on SARS-CoV-2, should be considered for immediate uses in COVID-19 patients.", "qid": 5, "docid": "fo07nxvi", "rank": 32, "score": 0.7721350193023682}, {"content": "Title: Candidate drugs against SARS-CoV-2 and COVID-19 Content: Outbreak and pandemic of coronavirus SARS-CoV-2 in 2019/2020 will challenge global health for the future. Because a vaccine against the virus will not be available in the near future, we herein try to offer a pharmacological strategy to combat the virus. There exists a number of candidate drugs that may inhibit infection with and replication of SARS-CoV-2. Such drugs comprise inhibitors of TMPRSS2 serine protease and inhibitors of angiotensin-converting enzyme 2 (ACE2). Blockade of ACE2, the host cell receptor for the S protein of SARS-CoV-2 and inhibition of TMPRSS2, which is required for S protein priming may prevent cell entry of SARS-CoV-2. Further, chloroquine and hydroxychloroquine, and off-label antiviral drugs, such as the nucleotide analogue remdesivir, HIV protease inhibitors lopinavir and ritonavir, broad-spectrum antiviral drugs arbidol and favipiravir as well as antiviral phytochemicals available to date may limit spread of SARS-CoV-2 and morbidity and mortality of COVID-19 pandemic.", "qid": 5, "docid": "xef6fr39", "rank": 33, "score": 0.7718655467033386}, {"content": "Title: Repurposing cefuroxime for treatment of COVID-19: a scoping review of in silico studies Content: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 19 (COVID-19), is a novel human Coronavirus that is responsible for about 300,000 deaths worldwide. To date, there is no confirmed treatment or vaccine prevention strategy against COVID-19. Due to the urgent need for effective treatment, drug repurposing is regarded as the immediate option. Potential drugs can often be identified via in silico drug screening experiments. Consequently, there has been an explosion of in silico experiments to find drug candidates or investigate anecdotal claims. One drug with several anecdotal accounts of benefit is Cefuroxime. The aim of this study was to identify and summarize in silico evidence for possible activity of Cefuroxime against SARS-CoV-2.To this end, we performed a scoping review of literature of in silico drug repurposing experiments for SARS-CoV-2 using PRISMA-ScR. We searched Medline, Embase, Scopus, Web of Knowledge, and Google Scholar for original studies published between 1st Feb, 2020 and 15th May, 2020 that screened drug libraries, and identified Cefuroxime as a top-ranked potential inhibitor drug against SARS-CoV-2 proteins. Six studies were identified. These studies reported Cefuroxime as a potential inhibitor of 3 key SARS-CoV-2 proteins; main protease, RNA dependent RNA polymerase, and ACE2-Spike complex. We provided a summary of the methodology and findings of the identified studies. Our scoping review identified significant in silico evidence that Cefuroxime may be a potential multi-target inhibitor of SARS-CoV-2. Further in vitro and in vivo studies are required to evaluate the potential of Cefuroxime for COVID-19. Communicated by Ramaswamy H. Sarma", "qid": 5, "docid": "aqge7xuu", "rank": 34, "score": 0.7718322277069092}, {"content": "Title: COVID\u201019 drug repurposing: Summary statistics on current clinical trials and promising untested candidates Content: Repurposing of existing antiviral drugs, immunological modulators, and supportive therapies represents a promising path toward rapidly developing new control strategies to mitigate the devastating public health consequences of the COVID\u201019 pandemic. A comprehensive text\u2010mining and manual curation approach was used to comb and summarize the most pertinent information from existing clinical trials and previous efforts to develop therapies against related betacoronaviruses, particularly SARS and MERS. In contrast to drugs in current trials, which have been derived overwhelmingly from studies on taxonomically unrelated RNA viruses, a number of untested small molecule antivirals had previously demonstrated remarkable in vitro specificity for SARS\u2010CoV or MERS\u2010CoV, with high selectivity indices, EC(50), and/or IC(50). Due to the rapid containment of the prior epidemics, however, these were generally not followed up with in vivo animal studies or clinical investigations, and thus largely overlooked as treatment prospects in the current COVID\u201019 trials. This brief review summarizes and tabulates core information on recent or ongoing drug repurposing\u2010focused clinical trials, while detailing the most promising untested candidates with prior documented success against the etiologic agents of SARS and/or MERS.", "qid": 5, "docid": "ra4uoosw", "rank": 35, "score": 0.7717617750167847}, {"content": "Title: Repurposing cefuroxime for treatment of COVID-19: a scoping review of in silico studies Content: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 19 (COVID-19), is a novel human Coronavirus that is responsible for about 300,000 deaths worldwide. To date, there is no confirmed treatment or vaccine prevention strategy against COVID-19. Due to the urgent need for effective treatment, drug repurposing is regarded as the immediate option. Potential drugs can often be identified via in silico drug screening experiments. Consequently, there has been an explosion of in silico experiments to find drug candidates or investigate anecdotal claims. One drug with several anecdotal accounts of benefit is Cefuroxime. The aim of this study was to identify and summarize in silico evidence for possible activity of Cefuroxime against SARS-CoV-2.To this end, we performed a scoping review of literature of in silico drug repurposing experiments for SARS-CoV-2 using PRISMA-ScR. We searched Medline, Embase, Scopus, Web of Knowledge, and Google Scholar for original studies published between 1st Feb, 2020 and 15th May, 2020 that screened drug libraries, and identified Cefuroxime as a top-ranked potential inhibitor drug against SARS-CoV-2 proteins. Six studies were identified. These studies reported Cefuroxime as a potential inhibitor of 3 key SARS-CoV-2 proteins; main protease, RNA dependent RNA polymerase, and ACE2-Spike complex. We provided a summary of the methodology and findings of the identified studies. Our scoping review identified significant in silico evidence that Cefuroxime may be a potential multi-target inhibitor of SARS-CoV-2. Further in vitro and in vivo studies are required to evaluate the potential of Cefuroxime for COVID-19.Communicated by Ramaswamy H. Sarma.", "qid": 5, "docid": "xui8cfzv", "rank": 36, "score": 0.7714089751243591}, {"content": "Title: The potential of drug repositioning as a short-term strategy for the control and treatment of COVID-19 (SARS-CoV-2): a systematic review Content: The novel human coronavirus (SARS-CoV-2), the causative agent of COVID-19, has quickly become a threat to the public health and economy worldwide. Despite the severity of some cases, there are no current pathogen-specific antivirals available to treat the disease. Therefore, many studies have focused on the evaluation of the anti-SARS-CoV-2 activity of clinically available drugs. Here, we conducted a systematic review to describe the drug repositioning strategy against SARS-CoV-2 and to discuss the clinical impact of this approach in the current pandemic context. The systematic review was performed on March 23, 2020, using PubMed/MEDLINE, Scopus, Cochrane Library, and Biblioteca Virtual de Sa\u00fade (BVS). The data were summarized in tables and critically analyzed. After the database search, 12 relevant studies were identified as eligible for the review. Among the drugs reported in these studies, 57 showed some evidence of antiviral activity. Antivirals, especially antiretrovirals, are the main class of therapeutic agents evaluated against COVID-19. Moreover, studies have reported the anti-SARS-CoV-2 activity of antitumor (16%; 9/57), antimalarial (7%, 4/57), and antibacterial (5%; 3/57) agents. Additionally, seven pharmacological agents (chloroquine, tetrandrine, umifenovir (arbidol), carrimycin, damageprevir, lopinavir/ritonavir) are in phase IV of clinical trials. Due to the evidence of the anti-SARS-CoV-2 activity of various clinically available agents, drug repositioning stands out as a promising strategy for a short-term response in the fight against the novel coronavirus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-020-04693-5) contains supplementary material, which is available to authorized users.", "qid": 5, "docid": "qci7khki", "rank": 37, "score": 0.7713886499404907}, {"content": "Title: Computational Models Identify Several FDA Approved or Experimental Drugs as Putative Agents Against SARS-CoV-2. Content: The outbreak of a novel human coronavirus (SARS-CoV-2) has evolved into global health emergency, infecting hundreds of thousands of people worldwide. We have identified experimental data on the inhibitory activity of compounds tested against closely related (96% sequence identity, 100% active site conservation) protease of SARS-CoV and employed this data to build QSAR models for this dataset. We employed these models for virtual screening of all drugs from DrugBank, including compounds in clinical trials. Molecular docking and similarity search approaches were explored in parallel with QSAR modeling, but molecular docking failed to correctly discriminate between experimentally active and inactive compounds. As a result of our studies, we recommended 41 approved, experimental, or investigational drugs as potential agents against SARS-CoV-2 acting as putative inhibitors of Mpro. Ten compounds with feasible prices were purchased and are awaiting the experimental validation..", "qid": 5, "docid": "hchioraj", "rank": 38, "score": 0.7709922790527344}, {"content": "Title: Repurposing old drugs as antiviral agents for coronaviruses Content: BACKGROUND: New therapeutic options to address the ongoing coronavirus disease 2019 (COVID-19) pandemic are urgently needed. One possible strategy is the repurposing of existing drugs approved for other indications as antiviral agents for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Due to the commercial unavailability of SARS-CoV-2 drugs for treating COVID-19, we screened approximately 250 existing drugs or pharmacologically active compounds for their inhibitory activities against feline infectious peritonitis coronavirus (FIPV) and human coronavirus OC43 (HCoV-OC43), a human coronavirus in the same genus (Betacoronavirus) as SARS-CoV-2. METHODS: FIPV was proliferated in feline Fcwf-4 cells and HCoV-OC43 in human HCT-8 cells. Viral proliferation was assayed by visualization of cytopathic effects on the infected Fcwf-4 cells and immunofluorescent assay for detection of the nucleocapsid proteins of HCoV-OC43 in the HCT-8 cells. The concentrations (EC50) of each drug necessary to diminish viral activity to 50% of that for the untreated controls were determined. The viabilities of Fcwf-4 and HCT-8 cells were measured by crystal violet staining and MTS/PMS assay, respectively. RESULTS: Fifteen out of the 252 drugs or pharmacologically active compounds screened were found to be active against both FIPV and HCoV-OC43, with EC50 values ranging from 11 nM to 75 \u00b5M. They are all old drugs as follows, anisomycin, antimycin A, atovaquone, chloroquine, conivaptan, emetine, gemcitabine, homoharringtonine, niclosamide, nitazoxanide, oligomycin, salinomycin, tilorone, valinomycin, and vismodegib. CONCLUSION: All of the old drugs identified as having activity against FIPV and HCoV-OC43 have seen clinical use in their respective indications and are associated with known dosing schedules and adverse effect or toxicity profiles in humans. Those, when later confirmed to have an anti-viral effect on SARS-CoV-2, should be considered for immediate uses in COVID-19 patients.", "qid": 5, "docid": "w8ta2qgh", "rank": 39, "score": 0.7706687450408936}, {"content": "Title: The potential of drug repositioning as a short-term strategy for the control and treatment of COVID-19 (SARS-CoV-2): a systematic review Content: The novel human coronavirus (SARS-CoV-2), the causative agent of COVID-19, has quickly become a threat to the public health and economy worldwide. Despite the severity of some cases, there are no current pathogen-specific antivirals available to treat the disease. Therefore, many studies have focused on the evaluation of the anti-SARS-CoV-2 activity of clinically available drugs. Here, we conducted a systematic review to describe the drug repositioning strategy against SARS-CoV-2 and to discuss the clinical impact of this approach in the current pandemic context. The systematic review was performed on March 23, 2020, using PubMed/MEDLINE, Scopus, Cochrane Library, and Biblioteca Virtual de Sa\u00fade (BVS). The data were summarized in tables and critically analyzed. After the database search, 12 relevant studies were identified as eligible for the review. Among the drugs reported in these studies, 57 showed some evidence of antiviral activity. Antivirals, especially antiretrovirals, are the main class of therapeutic agents evaluated against COVID-19. Moreover, studies have reported the anti-SARS-CoV-2 activity of antitumor (16%; 9/57), antimalarial (7%, 4/57), and antibacterial (5%; 3/57) agents. Additionally, seven pharmacological agents (chloroquine, tetrandrine, umifenovir (arbidol), carrimycin, damageprevir, lopinavir/ritonavir) are in phase IV of clinical trials. Due to the evidence of the anti-SARS-CoV-2 activity of various clinically available agents, drug repositioning stands out as a promising strategy for a short-term response in the fight against the novel coronavirus.", "qid": 5, "docid": "8gmn0tae", "rank": 40, "score": 0.7702590227127075}, {"content": "Title: COVID-19 drug repurposing: Summary statistics on current clinical trials and promising untested candidates Content: Repurposing of existing antiviral drugs, immunological modulators, and supportive therapies represents a promising path toward rapidly developing new control strategies to mitigate the devastating public health consequences of the COVID-19 pandemic. A comprehensive text-mining and manual curation approach was used to comb and summarize the most pertinent information from existing clinical trials and previous efforts to develop therapies against related betacoronaviruses, particularly SARS and MERS. In contrast to drugs in current trials, which have been derived overwhelmingly from studies on taxonomically unrelated RNA viruses, a number of untested small molecule antivirals had previously demonstrated remarkable in vitro specificity for SARS-CoV or MERS-CoV, with high selectivity indices, EC50 , and/or IC50 . Due to the rapid containment of the prior epidemics, however, these were generally not followed up with in vivo animal studies or clinical investigations, and thus largely overlooked as treatment prospects in the current COVID-19 trials. This brief review summarizes and tabulates core information on recent or ongoing drug repurposing-focused clinical trials, while detailing the most promising untested candidates with prior documented success against the etiologic agents of SARS and/or MERS.", "qid": 5, "docid": "f4xt36hf", "rank": 41, "score": 0.7696285843849182}, {"content": "Title: Machine Learning Models Identify Inhibitors of SARS-CoV-2 Content: With the ongoing SARS-CoV-2 pandemic there is an urgent need for the discovery of a treatment for the coronavirus disease (COVID-19). Drug repurposing is one of the most rapid strategies for addressing this need and numerous compounds have been selected for in vitro testing by several groups already. These have led to a growing database of molecules with in vitro activity against the virus. Machine learning models can assist drug discovery through prediction of the best compounds based on previously published data. Herein we have implemented several machine learning methods to develop predictive models from recent SARS-CoV-2 in vitro inhibition data and used them to prioritize additional FDA approved compounds for in vitro testing selected from our in-house compound library. From the compounds predicted with a Bayesian machine learning model, CPI1062 and CPI1155 showed antiviral activity in HeLa-ACE2 cell-based assays and represent potential repurposing opportunities for COVID-19. This approach can be greatly expanded to exhaustively virtually screen available molecules with predicted activity against this virus as well as a prioritization tool for SARS-CoV-2 antiviral drug discovery programs. The very latest model for SARS-CoV-2 is available at www.assaycentral.org.", "qid": 5, "docid": "vfd0su0w", "rank": 42, "score": 0.7695560455322266}, {"content": "Title: Discovery of clinically approved drugs capable of inhibiting SARS-CoV-2 in vitro infection using a phenotypic screening strategy and network-analysis to predict their potential to treat covid-19 Content: The disease caused by SARS-CoV2, covid-19, rapidly spreads worldwide, causing the greatest threat to global public health in the last 100 years. This scenario has become catastrophic as there are no approved vaccines to prevent the disease, and the main measures to contain the virus transmission are confinement and social distancing. One priority strategy is based on drug repurposing by pursuing antiviral chemotherapy that can control transmission and prevent complications associated with covid-19. With this aim, we performed a high content screening assay for the discovery of anti-SARS-CoV-2 compounds. From the 65 screened compounds, we have found four drugs capable to selectively inhibit SARS-CoV-2 in vitro infection: brequinar, abiraterone acetate, neomycin, and the extract of Hedera helix. Brequinar and abiraterone acetate had higher inhibition potency against SARS-CoV-2 than neomycin and Hedera helix extract, respectively. Drugs with reported antiviral activity and in clinical trials for covid-19, chloroquine, ivermectin, and nitazoxanide, were also included in the screening, and the last two were found to be non-selective. We used a data mining approach to build drug-host molecules-biological function-disease networks to show in a holistic way how each compound is interconnected with host node molecules and virus infection, replication, inflammatory response, and cell apoptosis. In summary, the present manuscript identified four drugs with active inhibition effect on SARS-CoV-2 in vitro infection, and by network analysis, we provided new insights and starting points for the clinical evaluation and repurposing process to treat SARS-CoV-2 infection. Summary sentence Discovery of drug repurposing candidates, inhibitors of SARS-CoV-2 infection in vitro, using a phenotypic screening strategy and network analysis.", "qid": 5, "docid": "40fz5r90", "rank": 43, "score": 0.7694664001464844}, {"content": "Title: SARS-CoV-2: Recent Reports on Antiviral Therapies Based on Lopinavir/Ritonavir, Darunavir/Umifenovir, Hydroxychloroquine, Remdesivir, Favipiravir and Other Drugs for the Treatment of the New Coronavirus Content: Here we report on the most recent updates on experimental drugs successfully em- ployed in the treatment of the disease caused by SARS-CoV-2 coronavirus, also referred to as COVID-19 (COronaVIrus Disease 19). In particular, several cases of recovered patients have been reported after being treated with lopinavir/ritonavir (which is widely used to treat human immunodeficiency virus (HIV) infection) in combination with the anti-flu drug oseltamivir. In addition, remdesivir, which has been previously administered to Ebola virus patients, has also proven effective in the U.S. against coronavirus, while antimalarial chloroquine and hydroxy- chloroquine, favipiravir and co-administered darunavir and umifenovir (in patient therapies) were also recently recorded as having anti-SARS-CoV-2 effects. Since the recoveries/deaths ratio in the last weeks significantly increased, especially in China, it is clear that the experi- mental antiviral therapy, together with the availability of intensive care unit beds in hospitals and rigorous government control measures, all play an important role in dealing with this vi- rus. This also stresses the urgent need for the scientific community to devote its efforts to the development of other more specific antiviral strategies.", "qid": 5, "docid": "fgbilulc", "rank": 44, "score": 0.7694649696350098}, {"content": "Title: Therapeutic Options for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection: How Close Are We? Content: Over 1100 cases of MERS-CoV have been reported since it was first identified in June 2012. Clinical presentation ranges from asymptomatic or mild illness to rapidly progressive disease with multi-organ failure and high mortality. Treatment has been largely supportive. A large number of compounds have been shown to have significant in vitro inhibitory activity against MERS-CoV. Until recently, macaques were the only suitable animal models for animal studies, hindering further clinical development of MERS-CoV therapy. However, the recent successful development of MERS-CoV infection model in transduced mice offers opportunities to accelerate clinical development of therapeutic agents for MERS-CoV infection. Currently available evidence supports further clinical investigation of interferon-based treatment regimens for patients with MERS-CoV. Combining interferon with mycophenolate and/or high-dose ribavirin appears especially promising. Monoclonal antibodies against various targets within MERS-CoV Spike protein have yielded encouraging in-vitro results. However, their safety and efficacy require confirmation in animal models and exploratory clinical trials.", "qid": 5, "docid": "h3980atj", "rank": 45, "score": 0.7687704563140869}, {"content": "Title: [Pharmacotherapy of severe acute respiratory syndrome (SARS)]. Content: Severe acute respiratory syndrome (SARS) constitutes the first new infectious disease of the current millennium. It is caused by the novel SARS-Coronavirus (SARS-CoV). SARS is related to a high morbidity and mortality and first appeared during an epidemic in 2002 - 2003. To date no specific therapy against the SARS-CoV is available. Due to the rapid spread of SARS during the epidemics in 2002 - 2003, randomised and controlled multicentre studies were not performed. Therefore, general guidelines have not been developed. Since the outbreak, scientists have been testing potential antiviral substances using in vitro and animal models. This study analyses the presently available in vitro and in vivo data on the pharmacotherapy of SARS.", "qid": 5, "docid": "37oidlkd", "rank": 46, "score": 0.7685492634773254}, {"content": "Title: A Review on SARS-CoV-2 Virology, Pathophysiology, Animal Models, and Anti-Viral Interventions Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of CoV disease 2019 (COVID-19) is a highly pathogenic and transmissible CoV that is presently plaguing the global human population and economy. No proven effective antiviral therapy or vaccine currently exists, and supportive care remains to be the cornerstone treatment. Through previous lessons learned from SARS-CoV-1 and MERS-CoV studies, scientific groups worldwide have rapidly expanded the knowledge pertaining to SARS-CoV-2 virology that includes in vitro and in vivo models for testing of antiviral therapies and randomized clinical trials. In the present narrative, we review SARS-CoV-2 virology, clinical features, pathophysiology, and animal models with a specific focus on the antiviral and adjunctive therapies currently being tested or that require testing in animal models and randomized clinical trials.", "qid": 5, "docid": "30tftimd", "rank": 47, "score": 0.7680723667144775}, {"content": "Title: Dermatological therapies with relevance to COVID\u201019 Content: SARS\u2010CoV\u20102 is a novel single stranded RNA virus that has gripped humanity all over. It affects primarily the respiratory system, but is not limited to it, causing widespread involvement of many organ systems. The cases are still rising at an exponential rate and manifold trials are on to test different agents with the hope for potential limitation of spread and control of symptoms. Various classes of drugs have been tried; some with moderate success while many are yet to be proven to be of definite benefit. We have observed that the drugs used in dermatology practice are featured in more than a few of such studies. Here we wish to highlight the ones that we are familiar with, which has featured at some point, in the management of this very challenging pandemic. This article is protected by copyright. All rights reserved.", "qid": 5, "docid": "fho2kble", "rank": 48, "score": 0.7677109837532043}, {"content": "Title: Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19) Content: The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signals an urgent need for an expansion in treatment options. In this study, we investigated the anti-SARS-CoV-2 activities of 22 antiviral agents with known broad-spectrum antiviral activities against coronaviruses and/or other viruses. They were first evaluated in our primary screening in VeroE6 cells and then the most potent anti-SARS-CoV-2 antiviral agents were further evaluated using viral antigen expression, viral load reduction, and plaque reduction assays. In addition to remdesivir, lopinavir, and chloroquine, our primary screening additionally identified types I and II recombinant interferons, 25-hydroxycholesterol, and AM580 as the most potent anti-SARS-CoV-2 agents among the 22 antiviral agents. Betaferon (interferon-\u00df1b) exhibited the most potent anti-SARS-CoV-2 activity in viral antigen expression, viral load reduction, and plaque reduction assays among the recombinant interferons. The lipogenesis modulators 25-hydroxycholesterol and AM580 exhibited EC50 at low micromolar levels and selectivity indices of >10.0. Combinational use of these host-based antiviral agents with virus-based antivirals to target different processes of the SARS-CoV-2 replication cycle should be evaluated in animal models and/or clinical trials.", "qid": 5, "docid": "u3ow62fn", "rank": 49, "score": 0.7675461769104004}, {"content": "Title: Natural History of COVID-19 and Current Knowledge on Treatment Therapeutic Options Content: Despite intense research there is currently no effective vaccine available against the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in the later 2019 and responsible for the COVID-19 pandemic. This infectious and communicable disease has become one of the major public health challenges in the world. The clinical management of COVID-19 has been limited to infection prevention and control measures associated with supportive care such as supplemental oxygen and mechanical ventilation. Meanwhile efforts to find an effective treatment to inhibit virus replication, mitigate the symptoms, increase survival and decrease mortality rate are ongoing. Several classes of drugs, many of them already in use for other diseases, are being evaluated based on the body of clinical knowledge obtained from infected patients regarding to the natural history and evolution of the infection. Herein we will provide an updated overview of the natural history and current knowledge on drugs and therapeutic agents being tested for the prevention and treatment of COVID-19. These include different classes of drugs such as antiviral agents (chloroquine, ivermectin, nitazoxanide, hydroxychloroquine, lopinavir, remdesivir, tocilizumab), supporting agents (Vitamin C, Vitamin D, azithromycin, corticosteroids) and promising investigational vaccines. Considering the controversies and excessive number of compounds being tested and reported in the literature we hope that this review can provide useful and updated consolidated information on potential drugs used to prevent, control and treat COVID-19 patients worldwide.", "qid": 5, "docid": "rirzes0m", "rank": 50, "score": 0.7674822807312012}, {"content": "Title: Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19). Content: The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signals an urgent need for an expansion in treatment options. In this study, we investigated the anti-SARS-CoV-2 activities of 22 antiviral agents with known broad-spectrum antiviral activities against coronaviruses and/or other viruses. They were first evaluated in our primary screening in VeroE6 cells and then the most potent anti-SARS-CoV-2 antiviral agents were further evaluated using viral antigen expression, viral load reduction, and plaque reduction assays. In addition to remdesivir, lopinavir, and chloroquine, our primary screening additionally identified types I and II recombinant interferons, 25-hydroxycholesterol, and AM580 as the most potent anti-SARS-CoV-2 agents among the 22 antiviral agents. Betaferon (interferon-\u03b21b) exhibited the most potent anti-SARS-CoV-2 activity in viral antigen expression, viral load reduction, and plaque reduction assays among the recombinant interferons. The lipogenesis modulators 25-hydroxycholesterol and AM580 exhibited EC50 at low micromolar levels and selectivity indices of >10.0. Combinational use of these host-based antiviral agents with virus-based antivirals to target different processes of the SARS-CoV-2 replication cycle should be evaluated in animal models and/or clinical trials.", "qid": 5, "docid": "tzmev77c", "rank": 51, "score": 0.767177164554596}, {"content": "Title: A Large-scale Drug Repositioning Survey for SARS-CoV-2 Antivirals Content: The emergence of novel SARS coronavirus 2 (SARS-CoV-2) in 2019 has triggered an ongoing global pandemic of severe pneumonia-like disease designated as coronavirus disease 2019 (COVID-19). To date, more than 2.1 million confirmed cases and 139,500 deaths have been reported worldwide, and there are currently no medical countermeasures available to prevent or treat the disease. As the development of a vaccine could require at least 12-18 months, and the typical timeline from hit finding to drug registration of an antiviral is >10 years, repositioning of known drugs can significantly accelerate the development and deployment of therapies for COVID-19. To identify therapeutics that can be repurposed as SARS-CoV-2 antivirals, we profiled a library of known drugs encompassing approximately 12,000 clinical-stage or FDA-approved small molecules. Here, we report the identification of 30 known drugs that inhibit viral replication. Of these, six were characterized for cellular dose-activity relationships, and showed effective concentrations likely to be commensurate with therapeutic doses in patients. These include the PIKfyve kinase inhibitor Apilimod, cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825, and ONO 5334, and the CCR1 antagonist MLN-3897. Since many of these molecules have advanced into the clinic, the known pharmacological and human safety profiles of these compounds will accelerate their preclinical and clinical evaluation for COVID-19 treatment.", "qid": 5, "docid": "1fgnfh62", "rank": 52, "score": 0.7670069932937622}, {"content": "Title: In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication Content: A novel coronavirus, named SARS-CoV-2, emerged in 2019 from Hubei region in China and rapidly spread worldwide. As no approved therapeutics exists to treat Covid-19, the disease associated to SARS-Cov-2, there is an urgent need to propose molecules that could quickly enter into clinics. Repurposing of approved drugs is a strategy that can bypass the time consuming stages of drug development. In this study, we screened the Prestwick Chemical Library\u00ae composed of 1,520 approved drugs in an infected cell-based assay. 90 compounds were identified. The robustness of the screen was assessed by the identification of drugs, such as Chloroquine derivatives and protease inhibitors, already in clinical trials. The hits were sorted according to their chemical composition and their known therapeutic effect, then EC50 and CC50 were determined for a subset of compounds. Several drugs, such as Azithromycine, Opipramol, Quinidine or Omeprazol present antiviral potency with 2<EC50<20\u00b5M. By providing new information on molecules inhibiting SARS-CoV-2 replication in vitro, this study could contribute to the short-term repurposing of drugs against Covid-19.", "qid": 5, "docid": "m7dwbheg", "rank": 53, "score": 0.7668181657791138}, {"content": "Title: Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets Content: Due to the urgent need of a therapeutic treatment for coronavirus (CoV) disease 2019 (COVID-19) patients, a number of FDA-approved/repurposed drugs have been suggested as antiviral candidates at clinics, without sufficient information. Furthermore, there have been extensive debates over antiviral candidates for their effectiveness and safety against severe acute respiratory syndrome CoV 2 (SARS-CoV-2), suggesting that rapid preclinical animal studies are required to identify potential antiviral candidates for human trials. To this end, the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir for SARS-CoV-2 infection were assessed in the ferret infection model. While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Only the emtricitabine-tenofovir-treated group showed lower virus titers in nasal washes at 8 days postinfection (dpi) than the PBS-treated control group. To further explore the effect of immune suppression on viral infection and clinical outcome, ferrets were treated with azathioprine, an immunosuppressive drug. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. Taken together, all antiviral drugs tested marginally reduced the overall clinical scores of infected ferrets but did not significantly affect in vivo virus titers. Despite the potential discrepancy of drug efficacies between animals and humans, these preclinical ferret data should be highly informative to future therapeutic treatment of COVID-19 patients.IMPORTANCE The SARS-CoV-2 pandemic continues to spread worldwide, with rapidly increasing numbers of mortalities, placing increasing strain on health care systems. Despite serious public health concerns, no effective vaccines or therapeutics have been approved by regulatory agencies. In this study, we tested the FDA-approved drugs lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir against SARS-CoV-2 infection in a highly susceptible ferret infection model. While most of the drug treatments marginally reduced clinical symptoms, they did not reduce virus titers, with the exception of emtricitabine-tenofovir treatment, which led to diminished virus titers in nasal washes at 8 dpi. Further, the azathioprine-treated immunosuppressed ferrets showed delayed virus clearance and low SN titers, resulting in a prolonged infection. As several FDA-approved or repurposed drugs are being tested as antiviral candidates at clinics without sufficient information, rapid preclinical animal studies should proceed to identify therapeutic drug candidates with strong antiviral potential and high safety prior to a human efficacy trial.", "qid": 5, "docid": "7h3rrea7", "rank": 54, "score": 0.7667115926742554}, {"content": "Title: Morphological Cell Profiling of SARS-CoV-2 Infection Identifies Drug Repurposing Candidates for COVID-19 Content: The global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the associated disease COVID-19, requires therapeutic interventions that can be rapidly translated to clinical care. Unfortunately, traditional drug discovery methods have a >90% failure rate and can take 10\u201315 years from target identification to clinical use. In contrast, drug repurposing can significantly accelerate translation. We developed a quantitative high-throughput screen to identify efficacious single agents and combination therapies against SARS-CoV-2. Quantitative high-content morphological profiling was coupled with an AI-based machine learning strategy to classify features of cells for infection and stress. This assay detected multiple antiviral mechanisms of action (MOA), including inhibition of viral entry, propagation, and modulation of host cellular responses. From a library of 1,425 FDA-approved compounds and clinical candidates, we identified 16 dose-responsive compounds with antiviral effects. In particular, we discovered that lactoferrin is an effective inhibitor of SARS-CoV-2 infection with an IC(50) of 308 nM and that it potentiates the efficacy of both remdesivir and hydroxychloroquine. Lactoferrin also stimulates an antiviral host cell response and retains inhibitory activity in iPSC-derived alveolar epithelial cells, a model for the primary site of infection. Given its safety profile in humans, these data suggest that lactoferrin is a readily translatable therapeutic adjunct for COVID-19. Additionally, several commonly prescribed drugs were found to exacerbate viral infection and warrant clinical investigation. We conclude that morphological profiling for drug repurposing is an effective strategy for the selection and optimization of drugs and drug combinations as viable therapeutic options for COVID-19 pandemic and other emerging infectious diseases.", "qid": 5, "docid": "ort27p77", "rank": 55, "score": 0.7660230398178101}, {"content": "Title: Identification of five antiviral compounds from the Pandemic Response Box targeting SARS-CoV-2 Content: With currently over 4 million confirmed cases worldwide, including more than 300\u2019000 deaths, the current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has a major impact on the economy and health care system. Currently, a limited amount of prophylactic or therapeutic intervention options are available against SARS-CoV-2. In this study, we screened 400 compounds from the antimicrobial \u2018Pandemic Response Box\u2019 library for inhibiting properties against SARS-CoV-2. We identified sixteen compounds that potently inhibited SARS-CoV-2 replication, of which five compounds displayed equal or even higher antiviral activity compared to Remdesivir. These results show that five compounds should be further investigated for their mode of action, safety and efficacy against SARS-CoV-2. Highlights 400 compounds from the pandemic response box were tested for antiviral activity against SARS-CoV-2. 5 compounds had an equal or higher antiviral efficacy towards SARS-CoV-2, compared to the nucleoside analogue Remdesivir.", "qid": 5, "docid": "sj6ts2vo", "rank": 56, "score": 0.7659837603569031}, {"content": "Title: Drug repositioning is an alternative for the treatment of coronavirus COVID-19 Content: Given the extreme importance of the current pandemic caused by COVID-19, and as scientists agree there is no identified pharmacological treatment, where possible, therapeutic alternatives are raised through drug repositioning. This paper presents a selection of studies involving drugs from different pharmaceutical classes with activity against SARS-CoV-2 and SARS-CoV, with the potential for use in the treatment of COVID-19 disease.", "qid": 5, "docid": "ij8wk06v", "rank": 57, "score": 0.7659426927566528}, {"content": "Title: Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs Content: COVID-19 is an emerging infectious disease and was recently declared as a pandemic by WHO. Currently, there is no vaccine or therapeutic available for this disease. Drug repositioning represents the only feasible option to address this global challenge and a panel of 48 FDA-approved drugs that have been pre-selected by an assay of SARS-CoV was screened to identify potential antiviral drug candidates against SARS-CoV-2 infection. We found a total of 24 drugs which exhibited antiviral efficacy (0.1 \u03bcM < IC50 < 10 \u03bcM) against SARS-CoV-2. In particular, two FDA-approved drugs - niclosamide and ciclesonide \u2013 were notable in some respects. These drugs will be tested in an appropriate animal model for their antiviral activities. In near future, these already FDA-approved drugs could be further developed following clinical trials in order to provide additional therapeutic options for patients with COVID-19.", "qid": 5, "docid": "5f95gve3", "rank": 58, "score": 0.7646853923797607}, {"content": "Title: Ivermectin as a potential COVID-19 treatment from the pharmacokinetic point of view Content: The broad-spectrum antiparasitic agent ivermectin has been very recently found to inhibit SARS-CoV-2 in vitro and proposed as a candidate for drug repurposing in COVID-19. In the present report the in vitro antiviral activity end-points are analyzed from the pharmacokinetic perspective. The available pharmacokinetic data from clinically relevant and excessive dosing studies indicate that the SARS-CoV-2 inhibitory concentrations are not likely to be attainable in humans.", "qid": 5, "docid": "3hgmuyn4", "rank": 59, "score": 0.7645633220672607}, {"content": "Title: Drug repositioning is an alternative for the treatment of coronavirus COVID-19 Content: Abstract Given the extreme importance of the current pandemic caused by COVID-19, and as scientists agree there is no identified pharmacological treatment, where possible, therapeutic alternatives are raised through drug repositioning. This paper presents a selection of studies involving drugs from different pharmaceutical classes with activity against SARS-CoV-2 and SARS-CoV, with the potential for use in the treatment of COVID-19 disease.", "qid": 5, "docid": "agc89fqv", "rank": 60, "score": 0.7644916772842407}, {"content": "Title: SARS-CoV-2 RNA polymerase as target for antiviral therapy Content: A new human coronavirus named SARS-CoV-2 was identified in several cases of acute respiratory syndrome in Wuhan, China in December 2019. On March 11 2020, WHO declared the SARS-CoV-2 infection to be a pandemic, based on the involvement of 169 nations. Specific drugs for SARS-CoV-2 are obviously not available. Currently, drugs originally developed for other viruses or parasites are currently in clinical trials based on empiric data. In the quest of an effective antiviral drug, the most specific target for an RNA virus is the RNA-dependent RNA-polymerase (RdRp) which shows significant differences between positive-sense and negative-sense RNA viruses. An accurate evaluation of RdRps from different viruses may guide the development of new drugs or the repositioning of already approved antiviral drugs as treatment of SARS-CoV-2. This can accelerate the containment of the SARS-CoV-2 pandemic and, hopefully, of future pandemics due to other emerging zoonotic RNA viruses.", "qid": 5, "docid": "c0jfa5jd", "rank": 61, "score": 0.7644338607788086}, {"content": "Title: Drug targets for COVID-19 therapeutics: Ongoing global efforts. Content: The current global pandemic COVID-19 caused by the SARS-CoV-2 virus has already inflicted insurmountable damage both to the human lives and global economy. There is an immediate need for identification of effective drugs to contain the disastrous virus outbreak. Global efforts are already underway at a war footing to identify the best drug combination to address the disease. In this review, an attempt has been made to understand the SARS-CoV-2 life cycle, and based on this information potential druggable targets against SARS-CoV-2 are summarized. Also, the strategies for ongoing and future drug discovery against the SARSCoV- 2 virus are outlined. Given the urgency to find a definitive cure, ongoing drug repurposing efforts being carried out by various organizations are also described. The unprecedented crisis requires extraordinary efforts from the scientific community to effectively address the issue and prevent further loss of human lives and health.", "qid": 5, "docid": "ovvyq18n", "rank": 62, "score": 0.7643444538116455}, {"content": "Title: Sensitivity of SARS/MERS CoV to interferons and other drugs based on achievable serum concentrations in humans. Content: A novel coronavirus (MERS-CoV) related to SARS-CoV recently emerged in the Middle East causing more than 400 deaths with a mortality rate of about 30%, much higher than SARS-CoV. Both viruses target epithelial cells in the respiratory tract, although utilizing different cellular receptors. Because of the sporadic nature of the MERS outbreak and difficulty in collecting randomized, controlled clinical data, the objective of this review was to focus on published in vitro and in vivo drug sensitivity data using both cell lines and available animal models of SARS/MERS CoV infection. Determination of drug activity was based on achievable serum levels in humans relative to in vitro IC50 (50% inhibitory concentration) or EC50 (50% effective concentration) drug concentrations. The most active drugs against SARS/MERS CoV at clinically achievable serum levels were type I interferons and a TLR3 agonist, interferon inducer/activator.", "qid": 5, "docid": "u0kyyyb7", "rank": 63, "score": 0.764190137386322}, {"content": "Title: Discovering drugs to treat coronavirus disease 2019 (COVID-19) Content: The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly to China, Japan, and South Korea. Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of coronavirus disease 2019 (COVID-19) in China; some promising results have been achieved thus far. This article summarizes agents with potential efficacy against SARS-CoV-2.", "qid": 5, "docid": "ey939w17", "rank": 64, "score": 0.7640955448150635}, {"content": "Title: Discovering drugs to treat coronavirus disease 2019 (COVID-19). Content: The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly to China, Japan, and South Korea. Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of coronavirus disease 2019 (COVID-19) in China; some promising results have been achieved thus far. This article summarizes agents with potential efficacy against SARS-CoV-2.", "qid": 5, "docid": "8ruux4sw", "rank": 65, "score": 0.7640955448150635}, {"content": "Title: In vitro evaluation of antiviral activity of single and combined repurposable drugs against SARS-CoV-2 Content: In response to the current pandemic caused by the novel SARS-CoV-2, identifying and validating effective therapeutic strategies is more than ever necessary. We evaluated the in vitro antiviral activities of a shortlist of compounds, known for their cellular broad-spectrum activities, together with drugs that are currently under evaluation in clinical trials for COVID-19 patients. We report the antiviral effect of remdesivir, lopinavir, chloroquine, umifenovir, berberine and cyclosporine A in Vero E6 cells model of SARS-CoV-2 infection, with estimated 50% inhibitory concentrations of 0.99, 5.2, 1.38, 3.5, 10.6 and 3 \u03bcM, respectively. Virus-directed plus host-directed drug combinations were also investigated. We report a strong antagonism between remdesivir and berberine, in contrast with remdesivir/diltiazem, for which we describe high levels of synergy, with mean Loewe synergy scores of 12 and peak values above 50. Combination of host-directed drugs with direct acting antivirals underscore further validation in more physiological models, yet they open up interesting avenues for the treatment of COVID-19.", "qid": 5, "docid": "vzyrcmu4", "rank": 66, "score": 0.7639899849891663}, {"content": "Title: Current pharmacological modalities for management of novel coronavirus disease 2019 (COVID\u201019) and the rationale for their utilization: A review Content: SARS\u2010CoV\u20102 has caused a pandemic which is putting strain on the health\u2010care system and global economy. There is much pressure to develop both preventative and curative therapies for SARS\u2010CoV\u20102 as there is no evidence to support therapies to improve outcomes in patients with SARS\u2010CoV\u20102. Medications that inhibit certain steps of virus life cycle that are currently used to treat other illnesses such as Malaria, Ebola, HIV and Hepatitis C are being studied for use against SARS\u2010CoV\u20102. To date, data is limited for medications that facilitate clinical improvement of COVID\u201019 infections.", "qid": 5, "docid": "ahh8or3o", "rank": 67, "score": 0.7638470530509949}, {"content": "Title: Techniques used for the discovery of therapeutic compounds: The case of SARS Content: Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS disease, which has ever severely menaced humans from the end of 2002 to June 2003. To date, great efforts have been made for the discovery of therapeutic compounds by using various technologies. In this report, we present a survey of these techniques and their applications in the development of promising anti-SARS agents. Section editors: Li-he Zhang \u2013 School of Pharmaceutical Science, Peking University, Beijing, China Kaixian Chen \u2013 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China", "qid": 5, "docid": "aa5vw5rh", "rank": 68, "score": 0.7637940645217896}, {"content": "Title: An Update on Current Therapeutic Drugs Treating COVID-19 Content: The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presented unprecedented challenges to the healthcare systems in almost every country around the world. Currently, there are no proven effective vaccines or therapeutic agents against the virus. Current clinical management includes infection prevention and control measures and supportive care including supplemental oxygen and mechanical ventilatory support. Evolving research and clinical data regarding the virologic SARS-CoV-2 suggest a potential list of repurposed drugs with appropriate pharmacological effects and therapeutic efficacies in treating COVID-19 patients. In this review, we will update and summarize the most common and plausible drugs for the treatment of COVID-19 patients. These drugs and therapeutic agents include antiviral agents (remdesivir, hydroxychloroquine, chloroquine, lopinavir, umifenovir, favipiravir, and oseltamivir), and supporting agents (Ascorbic acid, Azithromycin, Corticosteroids, Nitric oxide, IL-6 antagonists), among others. We hope that this review will provide useful and most updated therapeutic drugs to prevent, control, and treat COVID-19 patients until the approval of vaccines and specific drugs targeting SARS-CoV-2.", "qid": 5, "docid": "0jr31q5g", "rank": 69, "score": 0.7634229063987732}, {"content": "Title: A pharmacological perspective of Chloroquine in SARS-CoV-2 infection Content: The pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is having serious consequences on health and the economy worldwide. All evidence-based treatment strategies need to be considered to combat this new virus. Drugs need to be considered on scientific grounds of efficacy, safety and cost. Chloroquine (CQ) and hydroxychloroquine (HCQ) are old drugs used in the treatment of malaria; in addition, their antiviral properties have been previously studied, including in coronaviruses, where evidence of efficacy has been found. The safety of CQ and HCQ has been studied for over 50 years. In the current race against time triggered by the SARS-CoV-2 pandemic, the search for new antivirals is very important. However, consideration should be given to old drugs with known anti-coronavirus activity, such as CQ and HCQ; these could be integrated into current treatment strategies while novel treatments are awaited, also in light of the fact that they display an anticoagulant effect that facilitates the activity of low MW heparin, aimed at preventing ARDS-associated thrombotic events. The safety of CQ and HCQ has been studied for over 50 years, however, recently published data raise concerns for cardiac toxicity of CQ/HCQ in patients with COVID-19. The review that we here provide also reexamines the real information provided by some of the published alarming reports although concluding that cardiac toxicity should in any case be stringently monitored with patients with CQ/HCQ.", "qid": 5, "docid": "wgm26pla", "rank": 70, "score": 0.7634000182151794}, {"content": "Title: Elucidation on the Physicochemical Properties of Potential and Clinically Approved Antiviral Drugs: A Search for Effective Therapies against SARS-CoV-2 Infection Content: COVID-19 has been confirmed in millions of individuals worldwide, rendering it a global medical emergency In the absence of vaccines and the unavailability of effective drugs for the SARS-CoV-2 infection, vaccine development is being continuously explored and several antiviral compounds and immunotherapies are currently being investigated Given the high similarity in genetic identity between SARS-CoV and SARS-CoV-2, the present investigation identified the interaction between the physicochemical properties and the antiviral activity of different potential and clinically approved antiviral drugs against SARS-CoV using hierarchically weighted principal component analysis Representative drugs from the classes of neuraminidase inhibitors, reverse transcriptase inhibitors, protease inhibitors, nucleoside analogues, and other compounds with potential antiviral activity were examined The pharmacologic classification and the biological activity of the different antiviral drugs were described using indices, namely, rotatable bond count, molecular weight, heavy atom count, and molecular complexity (92 32% contribution rate) The physicochemical properties and inhibitory action against SARS-CoV-2 of lopinavir, chloroquine, ivermectin, and ciclesonide validated the adequacy of the current computational approach The findings of the present study provide additional information, although further investigation is warranted to identify potential targets and establish exact mechanisms, in the emergent search and design of antiviral drug candidates and their subsequent synthesis as effective therapies for COVID-19", "qid": 5, "docid": "s10iv1jg", "rank": 71, "score": 0.7631708979606628}, {"content": "Title: Indomethacin has a potent antiviral activity against SARS coronavirus. Content: UNLABELLED Severe acute respiratory syndrome (SARS) is a newly emerging, highly transmissible and fatal disease caused by a previously unknown coronavirus (SARS-CoV). Existing in non-identified animal reservoirs, SARS-CoV continues to represent a threat to humans because there is no effective specific antiviral therapy for coronavirus infections. OBJECTIVES Starting from the observation that cyclopentenone cyclooxygenase (COX) metabolites are active against several RNA viruses, we investigated the effect of the COX inhibitor indomethacin on coronavirus replication. METHODS Work involving infectious SARS-CoV was performed in biosafety level 3 facilities. SARS-CoV was grown in monkey VERO cells and human lung epithelial A549 cells, while canine coronavirus (CCoV) was grown in A72 canine cells. Antiviral activity was analysed by determining infective virus titres by TCID50, viral RNA synthesis by Northern blot analysis and real-time RT-PCR, and viral protein synthesis by SDS-PAGE analysis after 35S-methionine-labelling. Antiviral efficacy in vivo was determined by evaluating virus titres in CCoV-infected dogs treated orally with 1 mg/kg body weight indomethacin (INDO). RESULTS Unexpectedly, we found that INDO has a potent direct antiviral activity against the coronaviruses SARS-CoV and CCoV. INDO does not affect coronavirus binding or entry into host cells, but acts by blocking viral RNA synthesis at cytoprotective doses. This effect is independent of cyclooxygenase inhibition. INDO's potent antiviral activity (>1,000-fold reduction in virus yield) was confirmed in vivo in CCoV-infected dogs. CONCLUSIONS The results identify INDO as a potent inhibitor of coronavirus replication and suggest that, having both anti-inflammatory and antiviral activity, INDO could be beneficial in SARS therapy.", "qid": 5, "docid": "4ckob7b0", "rank": 72, "score": 0.763142466545105}, {"content": "Title: In silico identification of clinically approved medicines against the main protease of SARS-CoV-2, causative agent of covid-19 Content: The COVID-19 pandemic triggered by SARS-CoV-2 is a worldwide health disaster. Main protease is an attractive drug target among coronaviruses, due to its vital role in processing the polyproteins that are translated from the viral RNA. There is presently no exact drug or treatment for this diseases caused by SARS-CoV-2. In the present study, we report the potential inhibitory activity of some FDA approved drugs against SARS-CoV-2 main protease by molecular docking study to investigate their binding affinity in protease active site. Docking studies revealed that drug Oseltamivir (anti-H1N1 drug), Rifampin (anti-TB drug), Maraviroc, Etravirine, Indinavir, Rilpivirine (anti-HIV drugs) and Atovaquone, Quinidine, Halofantrine, Amodiaquine, Tetracylcine, Azithromycin, hydroxycholoroquine (anti-malarial drugs) among others binds in the active site of the protease with similar or higher affinity. However, the in-silico abilities of the drug molecules tested in this study, further needs to be validated by carrying out in vitro and in vivo studies. Moreover, this study spreads the potential use of current drugs to be considered and used to comprise the fast expanding SARS-CoV-2 infection.", "qid": 5, "docid": "w9mij6c6", "rank": 73, "score": 0.7627604603767395}, {"content": "Title: Drug Repurposing to find Inhibitors of SARS-CoV-2 Main Protease Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the strain of coronavirus that causes coronavirus disease 2019 (COVID-19), the respiratory illness responsible for the COVID-19 pandemic. Currently there is no known vaccine or specific antiviral treatment for COVID-19 and so, there is an urgent need for expedite discovery of new therapeutics to combat the disease until a vaccine will be available worldwide. Drug repurposing is a strategy for identifying new uses for approved drugs that has the advantage (over conventional approaches that attempt to develop a drug from scratch) that time frame of the overall process can be significantly reduced because of the few number of clinical trial required. In this work, a virtual screening of FDA-approved drugs was performed for repositioning as potential inhibitors of the main protease Mpro of SARS-CoV-2. As a result of this study, 12 drugs are proposed as candidates for inhibitors of the Mpro enzyme. Some of the selected compounds are antiviral drugs that are already being tested in COVID-19 clinical trials (i.e. ribavirin) or are used to alleviate symptoms of the disease (i.e. codeine). Surprisingly, the most promising candidate is the naturally occurring broad spectrum antibiotic oxytetracycline. This compound has largely outperformed the remaining selected candidates along all filtering steps of our virtual screening protocol. If the activity of any of these drugs is experimentally corroborated, they could be used directly in clinical trials without the need for pre-clinical testing or safety evaluation since they are already used as drugs for other diseases.", "qid": 5, "docid": "z17knvts", "rank": 74, "score": 0.7626930475234985}, {"content": "Title: Inhibition of SARS Coronavirus Infection In Vitro with Clinically Approved Antiviral Drugs Content: Severe acute respiratory syndrome (SARS) is an infectious disease caused by a newly identified human coronavirus (SARS-CoV). Currently, no effective drug exists to treat SARS-CoV infection. In this study, we investigated whether a panel of commercially available antiviral drugs exhibit in vitro anti\u2013SARS-CoV activity. A drug-screening assay that scores for virus-induced cytopathic effects on cultured cells was used. Tested were 19 clinically approved compounds from several major antiviral pharmacologic classes: nucleoside analogs, interferons, protease inhibitors, reverse transcriptase inhibitors, and neuraminidase inhibitors. Complete inhibition of cytopathic effects of SARS-CoV in culture was observed for interferon subtypes, \u03b2-1b, \u03b1-n1, \u03b1-n3, and human leukocyte interferon \u03b1. These findings support clinical testing of approved interferons for the treatment of SARS.", "qid": 5, "docid": "kcyao9i9", "rank": 75, "score": 0.7625918984413147}, {"content": "Title: Remdesivir, the antiviral hope against SARS-CoV-2/ Remdesivir, la esperanza antiviral frente al SARS-CoV-2 Content: On December 31, 2019 a pneumonia outbreak caused by a new coronavirus (SARS-CoV-2) was detected in the city of Wuhan (China) Due to the high capacity of diffusion and human infection it has become a new zoonotic pandemic The absence of a vaccine has determined the search for antiviral drugs with the capacity to inhibit the replication of the new virus Among them, remdesivir, an analogue of adenosine, is what seems to have a more promising future This drug has shown in vitro and in animals a high capacity to block infection and viral replication with attainable concentrations in human plasma Although all studies have been carried out with SARS-CoV and MERS-CoV, it seems that by virological and functional analogy, remdesivir is one of the few antiviral drugs with proven efficacy However, studies and clinical trials in humans are required to know the result of their application in them", "qid": 5, "docid": "puc13jf1", "rank": 76, "score": 0.7625036239624023}, {"content": "Title: What do we know about remdesivir drug interactions? Content: The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS\u2010Co\u2010V\u20102) has resulted in a critical need to rapidly develop new pharmacologic interventions and disseminate information. This has led to confusing and conflicting information on drug efficacy. Remdesivir has emerged as a promising treatment for SARS\u2010Co\u2010V\u20102 infection yet published clinical pharmacology and drug interaction studies are limited. Additional studies of the disposition of remdesivir, its active metabolite (GS\u2010441524), and its triphosphate metabolite (GS\u2010443902) are needed.", "qid": 5, "docid": "5ijdl5sl", "rank": 77, "score": 0.7623879313468933}, {"content": "Title: Available Evidence and Ongoing Clinical Trials of Remdesivir: Could It Be a Promising Therapeutic Option for COVID-19? Content: The novel coronavirus strain, severe acute respiratory syndrome coronavirus-2, the causative agent of COVID-19 emerged in Wuhan, China, in December 2019 and is skyrocketing throughout the globe and become a global public health emergency. Despite promising preventive measures being taken, there is no vaccine or drug therapy officially approved to prevent or treat the infection. Everybody is waiting the findings of ongoing clinical trials in various chemical and biological products. This review is specifically aimed to summarize the available evidence and ongoing clinical trials of remdesivir as a potential therapeutic option for COVID-19. Remdesivir is an investigational drug having broad spectrum antiviral activity with its target RNA dependent RNA polymerase. It has not yet been officially approved for Ebola and Coronaviruses. Several studies showed that remdesivir had promising in vitro and in vivo antiviral activities against SARS-CoV-1 and MERS-CoV strains. On the top of this, it exhibited a promising in vitro activity against SARS-CoV-2 strains though there are no published studies that substantiate its activity in vivo until the time of this review. There are few phase 3 randomized double-blind placebo controlled trials on the way to investigate the safety and efficacy of remdesivir. Of which, one completed double blind, placebo controlled trial showed that remdesivir showed faster time to clinical improvement in severe COVID-19 patients compared to placebo though not found statistically significant. In addition, two phase 3 randomized open label clinical trials coordinated by Gilead Sciences are being conducted. In addition, WHO Solidarity trial and INSERM DisCoVeRy trials (randomized open labels) were launched recently.", "qid": 5, "docid": "tasbdhs1", "rank": 78, "score": 0.7621922492980957}, {"content": "Title: Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets Content: Due to the urgent need of a therapeutic treatment for coronavirus (CoV) disease 2019 (COVID-19) patients, a number of FDA-approved/repurposed drugs have been suggested as antiviral candidates at clinics, without sufficient information. Furthermore, there have been extensive debates over antiviral candidates for their effectiveness and safety against severe acute respiratory syndrome CoV 2 (SARS-CoV-2), suggesting that rapid preclinical animal studies are required to identify potential antiviral candidates for human trials. To this end, the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir for SARS-CoV-2 infection were assessed in the ferret infection model. While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Only the emtricitabine-tenofovir-treated group showed lower virus titers in nasal washes at 8 days postinfection (dpi) than the PBS-treated control group. To further explore the effect of immune suppression on viral infection and clinical outcome, ferrets were treated with azathioprine, an immunosuppressive drug. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. Taken together, all antiviral drugs tested marginally reduced the overall clinical scores of infected ferrets but did not significantly affect in vivo virus titers. Despite the potential discrepancy of drug efficacies between animals and humans, these preclinical ferret data should be highly informative to future therapeutic treatment of COVID-19 patients.", "qid": 5, "docid": "l611eisi", "rank": 79, "score": 0.76198410987854}, {"content": "Title: Drug targets for COVID-19 therapeutics: Ongoing global efforts Content: The current global pandemic COVID-19 caused by the SARS-CoV-2 virus has already inflicted insurmountable damage both to the human lives and global economy. There is an immediate need for identification of effective drugs to contain the disastrous virus outbreak. Global efforts are already underway at a war footing to identify the best drug combination to address the disease. In this review, an attempt has been made to understand the SARS-CoV-2 life cycle, and based on this information potential druggable targets against SARS-CoV-2 are summarized. Also, the strategies for ongoing and future drug discovery against the SARS-CoV-2 virus are outlined. Given the urgency to find a definitive cure, ongoing drug repurposing efforts being carried out by various organizations are also described. The unprecedented crisis requires extraordinary efforts from the scientific community to effectively address the issue and prevent further loss of human lives and health.", "qid": 5, "docid": "z88imi7f", "rank": 80, "score": 0.7617605924606323}, {"content": "Title: The Rationale for Potential Pharmacotherapy of COVID-19 Content: On 11 March 2020, the coronavirus disease (COVID-19) was defined by the World Health Organization as a pandemic. Severe acute respiratory syndrome-2 (SARS-CoV-2) is the newly evolving human coronavirus infection that causes COVID-19, and it first appeared in Wuhan, China in December 2019 and spread rapidly all over the world. COVID-19 is being increasingly investigated through virology, epidemiology, and clinical management strategies. There is currently no established consensus on the standard of care in the pharmacological treatment of COVID-19 patients. However, certain medications suggested for other diseases have been shown to be potentially effective for treating this infection, though there has yet to be clear evidence. Therapies include new agents that are currently tested in several clinical trials, in addition to other medications that have been repurposed as antiviral and immune-modulating therapies. Previous high-morbidity human coronavirus epidemics such as the 2003 SARS-CoV and the 2012 Middle East respiratory syndrome coronavirus (MERS-CoV) prompted the identification of compounds that could theoretically be active against the emerging coronavirus SARS-CoV-2. Moreover, advances in molecular biology techniques and computational analysis have allowed for the better recognition of the virus structure and the quicker screening of chemical libraries to suggest potential therapies. This review aims to summarize rationalized pharmacotherapy considerations in COVID-19 patients in order to serve as a tool for health care professionals at the forefront of clinical care during this pandemic. All the reviewed therapies require either additional drug development or randomized large-scale clinical trials to be justified for clinical use.", "qid": 5, "docid": "ro1wrvf8", "rank": 81, "score": 0.7616778016090393}, {"content": "Title: Protease Inhibitors: Candidate Drugs to Inhibit Severe Acute Respiratory Syndrome Coronavirus 2 Replication. Content: The number of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly increased, although the WHO declared a pandemic. However, drugs that function against SARS-CoV-2 have not been established. SARS-CoV-2 has been suggested to bind angiotensin-converting enzyme 2, the receptor of the SARS coronavirus. SARS coronavirus and coronavirus 229E, the cause of the common cold, replicate through cell-surface and endosomal pathways using a protease, the type II transmembrane protease. To examine the effects of protease inhibitors on the replication of coronavirus 229E, we pretreated primary cultures of human nasal epithelial (HNE) cells with camostat or nafamostat, each of which has been used for the treatment of pancreatitis and/or disseminated intravascular coagulation. HNE cells were then infected with coronavirus 229E, and viral titers in the airway surface liquid of the cells were examined. Pretreatment with camostat (0.1-10 \u03bcg/mL) or nafamostat (0.01-1 \u03bcg/mL) reduced the titers of coronavirus 229E. Furthermore, a significant amount of type II transmembrane protease protein was detected in the airway surface liquid of HNE cells. Additionally, interferons have been reported to have antiviral effects against SARS coronavirus. The additive effects of interferons on the inhibitory effects of other candidate drugs to treat SARS-CoV-2 infection, such as lopinavir, ritonavir and favipiravir, have also been studied. These findings suggest that protease inhibitors of this type may inhibit coronavirus 229E replication in human airway epithelial cells at clinical concentrations. Protease inhibitors, interferons or the combination of these drugs may become candidate drugs to inhibit the replication of SARS-CoV-2.", "qid": 5, "docid": "1a6guo10", "rank": 82, "score": 0.7610454559326172}, {"content": "Title: Fight against novel coronavirus: A perspective of medicinal chemists Content: The ongoing novel coronavirus disease (COVID-19) pandemic makes us painfully perceive that our bullet shells are blank so far for fighting against severe human coronavirus (HCoV). In spite of vast research work, it is crystal clear that the evident does not warrant the commercial blossoming of anti-HCoV drugs. In this circumstance, drug repurposing and/or screening of databases are the only fastest option. This study is an initiative to recapitulate the medicinal chemistry of severe acute respiratory syndrome (SARS)-CoV-2 (SARS-CoV-2). The aim is to present an exquisite delineation of the current research from the perspective of a medicinal chemist to allow the rapid development of anti-SARS-CoV-2 agents.", "qid": 5, "docid": "50db66ru", "rank": 83, "score": 0.7609825134277344}, {"content": "Title: Potential therapeutic targets for combating SARS-CoV-2: Drug repurposing, clinical trials and recent advancements Content: The present pandemic of SARS-CoV-2 has been a tough task for the whole world to deal with. With the absence of specific drugs or vaccines against SARS-CoV-2, the situation is very difficult to control. Apart from the absence of specific therapies, the lack of knowledge about potential therapeutic targets and individual perception is adding to the complications. The present review describes the novel SARS-CoV-2 structure, surface proteins, asymptomatic and symptomatic transmission in addition to the genotype and phenotype of SARS-CoV-2 along with genetic strains and similarity between SARS, MERS and SARS-CoV-2. Therapeutic strategies such as inhibition of the endocytic pathway and suppressing RNA polymerase activity by metal ions, which could be quite beneficial for controlling COVID-19, are outlined. The drug repurposing for SARS-CoV-2 is discussed in detail along with therapeutic classes such as antivirals, antibiotics, and amino quinolones and their probable role in suppressing SARS-CoV-2 with reference to case studies. The ongoing clinical trials both with respect to drug repurposing and vaccines are summarized along with a brief description. The recent advancements and future perspective of ongoing research for therapy and detection of SARS-CoV-2 are provided. The review, in brief, summarizes epidemiology, therapy and the current scenario for combating SARS-CoV-2.", "qid": 5, "docid": "0wh7x410", "rank": 84, "score": 0.7609602808952332}, {"content": "Title: Putative Inhibitors of SARS-CoV-2 Main Protease from A Library of Marine Natural Products: A Virtual Screening and Molecular Modeling Study Content: The current emergency due to the worldwide spread of the COVID-19 caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a great concern for global public health. Already in the past, the outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle Eastern respiratory syndrome (MERS) in 2012 demonstrates the potential of coronaviruses to cross-species borders and further underlines the importance of identifying new-targeted drugs. An ideal antiviral agent should target essential proteins involved in the lifecycle of SARS-CoV. Currently, some HIV protease inhibitors (i.e., Lopinavir) are proposed for the treatment of COVID-19, although their effectiveness has not yet been assessed. The main protease (M(pro)) provides a highly validated pharmacological target for the discovery and design of inhibitors. We identified potent M(pro) inhibitors employing computational techniques that entail the screening of a Marine Natural Product (MNP) library. MNP library was screened by a hyphenated pharmacophore model, and molecular docking approaches. Molecular dynamics and re-docking further confirmed the results obtained by structure-based techniques and allowed this study to highlight some crucial aspects. Seventeen potential SARS-CoV-2 M(pro) inhibitors have been identified among the natural substances of marine origin. As these compounds were extensively validated by a consensus approach and by molecular dynamics, the likelihood that at least one of these compounds could be bioactive is excellent.", "qid": 5, "docid": "578lsck9", "rank": 85, "score": 0.7608166933059692}, {"content": "Title: Potent antiviral effect of protoporphyrin IX and verteporfin on SARS-CoV-2 infection Content: The infection of SARS-CoV-2 has spread to more than 200 countries and regions and the numbers of infected people and deaths worldwide are expected to continue to rise. Current treatment of COVID-19 is limited and mostly supportive. At present, there is no specific therapeutics against SARS-CoV-2. In this study, we discovered that protoporphyrin IX and verteporfin, two FDA-approved drugs for treatment of human diseases, had significant antiviral effect against SARS-CoV-2, with EC50 values for the reduction of viral RNA at nanomolar concentrations. Both drugs completely inhibited the cytopathic effect (CPE) produced by SARS-CoV-2 infection at lower drug concentrations than that of remdesivir. The selection indices of protoporphyrin IX and verteporfin are 952.74 and 368.93, respectively, suggesting wide safety margins. Both drugs were able to prevent SARS-CoV-2 infection as well as suppress established SARS-CoV-2 infection. The compounds share a porphyrin ring structure. Molecular docking indicates that the compounds may interact with viral receptor ACE2 and could block the cell-cell fusion mediated by ACE2 and viral S protein. Our finding suggests that protoporphyrin IX and verteporfin might be potential antivirals against SARS-CoV-2 infection and also sheds new light on the development of a novel class of small compounds against SARS-CoV-2.", "qid": 5, "docid": "l4ci8wr2", "rank": 86, "score": 0.7606863975524902}, {"content": "Title: A small molecule drug candidate targeting SARS-CoV-2 main protease Content: A new coronavirus identified as SARS-CoV-2 virus has brought the world to a state of crisis, causing a major pandemic, claiming more than 433,000 lives and instigating major financial damage to the global economy. Despite current efforts, developing safe and effective treatments remains a major challenge. Moreover, new strains of the virus are likely to emerge in the future. To prevent future pandemics, several drugs with various mechanisms of action are required. Drug discovery efforts against the virus fall into two main categories: (a) monoclonal antibodies targeting the spike protein of the virus and blocking it from entry; (b) small molecule inhibitors targeting key proteins of the virus, interfering with replication and translation of the virus. In this study, we are presenting a computational investigation of a potential drug candidate that targets SARS-CoV-2 protease, a viral protein critical for replication and translation of the virus.", "qid": 5, "docid": "2rczhxp2", "rank": 87, "score": 0.7602741718292236}, {"content": "Title: Repositioning of 8565 existing drugs for COVID-19 Content: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected near 5 million people and led to over 0.3 million deaths. Currently, there is no specific anti-SARS-CoV-2 medication. New drug discovery typically takes more than ten years. Drug repositioning becomes one of the most feasible approaches for combating COVID-19. This work curates the largest available experimental dataset for SARS-CoV-2 or SARS-CoV main protease inhibitors. Based on this dataset, we develop validated machine learning models with relatively low root mean square error to screen 1553 FDA-approved drugs as well as other 7012 investigational or off-market drugs in DrugBank. We found that many existing drugs might be potentially potent to SARS-CoV-2. The druggability of many potent SARS-CoV-2 main protease inhibitors is analyzed. This work offers a foundation for further experimental studies of COVID-19 drug repositioning.", "qid": 5, "docid": "f2e4d3bz", "rank": 88, "score": 0.7600587606430054}, {"content": "Title: The journey of remdesivir: from Ebola to COVID-19 Content: Countries around the world are currently fighting the coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a betacoronavirus, belonging to the same genus as severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV. Currently, there are no proven antiviral therapies for COVID-19. Numerous clinical trials have been initiated to identify an effective treatment. One leading candidate is remdesivir (GS-5734), a broad-spectrum antiviral that was initially developed for the treatment of Ebola virus (EBOV). Although remdesivir performed well in preclinical studies, it did not meet efficacy endpoints in a randomized trial conducted during an Ebola outbreak. Remdesivir holds promise for treating COVID-19 based on in vitro activity against SARS-CoV-2, uncontrolled clinical reports, and limited data from randomized trials. Overall, current data are insufficient to judge the efficacy of remdesivir for COVID-19, and the results of additional randomized studies are eagerly anticipated. In this narrative review, we provide an overview of Ebola and coronavirus outbreaks. We then summarize preclinical and clinical studies of remdesivir for Ebola and COVID-19.", "qid": 5, "docid": "aivub6mi", "rank": 89, "score": 0.7599807977676392}, {"content": "Title: The pharmacological development of direct acting agents for emerging needed therapy against SARS-CoV-2 Content: Recently, the SARS-CoV-2 was quickly identified as the causal pathogen leading to the outbreak of severe acute respiratory syndrome-like illness all over the world. As the SARS-CoV-2 infection pandemic proceeds, many efforts are being dedicated to the development of diverse treatment strategies. Increasing evidence showed potential therapeutic agents directly acting against SARS-CoV-2 virus, such as interferon, RNA-dependent RNA polymerase inhibitors, protease inhibitors, viral entry blockers, neuraminidase inhibitor, vaccine, antibody agent targeting the SARS-CoV-2 RNA genome, natural killer cells and nucleocytoplasmic trafficking inhibitor. To date, several direct anti-SARS-CoV-2 agents have demonstrated promising in vitro and clinical efficacy. This article reviews the current and future development of direct acting agents against SARS-CoV-2.", "qid": 5, "docid": "el7d8lck", "rank": 90, "score": 0.7598589062690735}, {"content": "Title: The pharmacological development of direct acting agents for emerging needed therapy against SARS-CoV-2. Content: Recently, the SARS-CoV-2 was quickly identified as the causal pathogen leading to the outbreak of severe acute respiratory syndrome-like illness all over the world. As the SARS-CoV-2 infection pandemic proceeds, many efforts are being dedicated to the development of diverse treatment strategies. Increasing evidence showed potential therapeutic agents directly acting against SARS-CoV-2 virus, such as interferon, RNA-dependent RNA polymerase inhibitors, protease inhibitors, viral entry blockers, neuraminidase inhibitor, vaccine, antibody agent targeting the SARS-CoV-2 RNA genome, natural killer cells and nucleocytoplasmic trafficking inhibitor. To date, several direct anti-SARS-CoV-2 agents have demonstrated promising in vitro and clinical efficacy. This article reviews the current and future development of direct acting agents against SARS-CoV-2.", "qid": 5, "docid": "7ln7p715", "rank": 91, "score": 0.7598589062690735}, {"content": "Title: Protease Inhibitors: Candidate Drugs to Inhibit Severe Acute Respiratory Syndrome Coronavirus 2 Replication Content: The number of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly increased, although the WHO declared a pandemic. However, drugs that function against SARS-CoV-2 have not been established. SARS-CoV-2 has been suggested to bind angiotensin-converting enzyme 2, the receptor of the SARS coronavirus. SARS coronavirus and coronavirus 229E, the cause of the common cold, replicate through cell-surface and endosomal pathways using a protease, the type II transmembrane protease. To examine the effects of protease inhibitors on the replication of coronavirus 229E, we pretreated primary cultures of human nasal epithelial (HNE) cells with camostat or nafamostat, each of which has been used for the treatment of pancreatitis and/or disseminated intravascular coagulation. HNE cells were then infected with coronavirus 229E, and viral titers in the airway surface liquid of the cells were examined. Pretreatment with camostat (0.1-10 \u00b5g/mL) or nafamostat (0.01-1 \u00b5g/mL) reduced the titers of coronavirus 229E. Furthermore, a significant amount of type II transmembrane protease protein was detected in the airway surface liquid of HNE cells. Additionally, interferons have been reported to have antiviral effects against SARS coronavirus. The additive effects of interferons on the inhibitory effects of other candidate drugs to treat SARS-CoV-2 infection, such as lopinavir, ritonavir and favipiravir, have also been studied. These findings suggest that protease inhibitors of this type may inhibit coronavirus 229E replication in human airway epithelial cells at clinical concentrations. Protease inhibitors, interferons or the combination of these drugs may become candidate drugs to inhibit the replication of SARS-CoV-2.", "qid": 5, "docid": "npp1y2ay", "rank": 92, "score": 0.7598361968994141}, {"content": "Title: Harnessing the power of novel animal-free test methods for the development of COVID-19 drugs and vaccines Content: The COVID-19-inducing virus, SARS-CoV2, is likely to remain a threat to human health unless efficient drugs or vaccines become available. Given the extent of the current pandemic (people in over one hundred countries infected) and its disastrous effect on world economy (associated with limitations of human rights), speedy drug discovery is critical. In this situation, past investments into the development of new (animal-free) approach methods (NAM) for drug safety, efficacy, and quality evaluation can be leveraged. For this, we provide an overview of repurposing ideas to shortcut drug development times. Animal-based testing would be too lengthy, and it largely fails, when a pathogen is species-specific or if the desired drug is based on specific features of human biology. Fortunately, industry has already largely shifted to NAM, and some public funding programs have advanced the development of animal-free technologies. For instance, NAM can predict genotoxicity (a major aspect of carcinogenicity) within days, human antibodies targeting virus epitopes can be generated in molecular biology laboratories within weeks, and various human cell-based organoids are available to test virus infectivity and the biological processes controlling them. The European Medicines Agency (EMA) has formed an expert group to pave the way for the use of such approaches for accelerated drug development. This situation illustrates the importance of diversification in drug discovery strategies and clearly shows the shortcomings of an approach that invests 95% of resources into a single technology (animal experimentation) in the face of challenges that require alternative approaches.", "qid": 5, "docid": "2mmc0llc", "rank": 93, "score": 0.7595925331115723}, {"content": "Title: Hydroxychloroquine Proves Ineffective in Hamsters and Macaques Infected with SARS-CoV-2 Content: We remain largely without effective prophylactic/therapeutic interventions for COVID-19. Although many human clinical trials are ongoing, there remains a deficiency of supportive preclinical drug efficacy studies. Here we assessed the prophylactic/therapeutic efficacy of hydroxychloroquine (HCQ), a drug of interest for COVID-19 management, in two animal models. When used for prophylaxis or treatment neither the standard human malaria dose (6.5 mg/kg) nor a high dose (50 mg/kg) of HCQ had any beneficial effect on clinical disease or SARS-CoV-2 kinetics (replication/shedding) in the Syrian hamster disease model. Similarly, HCQ prophylaxis/treatment (6.5 mg/kg) did not significantly benefit clinical outcome nor reduce SARS-CoV-2 replication/shedding in the upper and lower respiratory tract in the rhesus macaque disease model. In conclusion, our preclinical animal studies do not support the use of HCQ in prophylaxis/treatment of COVID-19.", "qid": 5, "docid": "y5cbp2yz", "rank": 94, "score": 0.759468674659729}, {"content": "Title: A systematic review protocol of the antiviral activity of chloroquine and hydroxychloroquine against COVID-19. Content: Introduction: The recent outbreak of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), or COVID-19 with no approved medicines has led to global health threat. Currently, repositioning of old medicines seems the most responsible strategy for potential cure and prevention COVID-19. Hydroxychloroquine and chloroquine have shown promising efficacy against COVID-19 related pneumonia in clinical studies. However, the mode of drug action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection is not clear. This review aims to gather evidence on antiviral activity and possible mechanism of drug action of chloroquine and hydroxychloroquine on SARS-CoV-2, including in-vitro, animal studies, and studies in humans. Method: A structured search of five bibliographic databases namely; Medline, Web of Science, PubMed, Cochrane CENTRAL, and Google Scholar will be undertaken to retrieve studies that describe the antiviral activity and possible mechanism of drug action of chloroquine and hydroxychloroquine on SARS-CoV-2. No restrictions will be placed on publication date, but studies will be limited to only publications in English. Duplication of studies will be removed using EndNote reference manager. Three authors will screen the citations independently based on inclusion criteria. Data extraction and assessment of risk of bias will be done independently. Meta-analysis of selected studies will be done wherever suitable. Ethics and dissemination: Primary data collection will not be involved in this study, hence no need for formal ethical clearance. Findings from the study will be disseminated through a peer-reviewed publication and conference meeting. Trial registration number: https://doi.org/10.17605/OSF.IO/7DJMU", "qid": 5, "docid": "em98mikz", "rank": 95, "score": 0.7594102621078491}, {"content": "Title: A SARS-CoV-2 protein interaction map reveals targets for drug repurposing Content: A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption1,2. There are no antiviral drugs with proven clinical efficacy for the treatment of COVID-19, nor are there any vaccines that prevent infection with SARS-CoV-2, and efforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells. Here we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins that physically associated with each of the SARS-CoV-2 proteins using affinity-purification mass spectrometry, identifying 332 high-confidence protein-protein interactions between SARS-CoV-2 and human proteins. Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (of which, 29 drugs are approved by the US Food and Drug Administration, 12 are in clinical trials and 28 are preclinical compounds). We screened a subset of these in multiple viral assays and found two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the sigma-1 and sigma-2 receptors. Further studies of these host-factor-targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.", "qid": 5, "docid": "7qd8z5e7", "rank": 96, "score": 0.7592475414276123}, {"content": "Title: Treatments for COVID-19: emerging drugs against the coronavirus Content: The Coronavirus disease 19 (COVID-19) outbreak has been recognized as a global threat to public health. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and no effective therapies currently exist against this novel viral agent. Along with extensive public health measures, an unprecedented global effort in identifying effective drugs for the treatment is being implemented. Potential drug targets are emerging as the result of a fast-evolving understanding of SARS-CoV-2 virology, host response to the infection, and clinical course of the disease. This brief review focuses on the latest and most promising pharmacological treatments against COVID-19 currently under investigation and discuss their potential use based on either documented efficacy in similar viral infections, or their activity against inflammatory syndromes. Ongoing clinical trials are also emphasized.", "qid": 5, "docid": "4ypv5bk5", "rank": 97, "score": 0.759059488773346}, {"content": "Title: Treatments for COVID-19: emerging drugs against the coronavirus. Content: The Coronavirus disease 19 (COVID-19) outbreak has been recognized as a global threat to public health. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and no effective therapies currently exist against this novel viral agent. Along with extensive public health measures, an unprecedented global effort in identifying effective drugs for the treatment is being implemented. Potential drug targets are emerging as the result of a fast-evolving understanding of SARS-CoV-2 virology, host response to the infection, and clinical course of the disease. This brief review focuses on the latest and most promising pharmacological treatments against COVID-19 currently under investigation and discuss their potential use based on either documented efficacy in similar viral infections, or their activity against inflammatory syndromes. Ongoing clinical trials are also emphasized.", "qid": 5, "docid": "u3enawtb", "rank": 98, "score": 0.759059488773346}, {"content": "Title: Harnessing the power of novel animal-free test methods for the development of COVID-19 drugs and vaccines Content: The COVID-19-inducing virus, SARS-CoV2, is likely to remain a threat to human health unless efficient drugs or vaccines become available. Given the extent of the current pandemic (people in over one hundred countries infected) and its disastrous effect on world economy (associated with limitations of human rights), speedy drug discovery is critical. In this situation, past investments into the development of new (animal-free) approach methods (NAM) for drug safety, efficacy, and quality evaluation can be leveraged. For this, we provide an overview of repurposing ideas to shortcut drug development times. Animal-based testing would be too lengthy, and it largely fails, when a pathogen is species-specific or if the desired drug is based on specific features of human biology. Fortunately, industry has already largely shifted to NAM, and some public funding programs have advanced the development of animal-free technologies. For instance, NAM can predict genotoxicity (a major aspect of carcinogenicity) within days, human antibodies targeting virus epitopes can be generated in molecular biology laboratories within weeks, and various human cell-based organoids are available to test virus infectivity and the biological processes controlling them. The European Medicines Agency (EMA) has formed an expert group to pave the way for the use of such approaches for accelerated drug development. This situation illustrates the importance of diversification in drug discovery strategies and clearly shows the shortcomings of an approach that invests 95% of resources into a single technology (animal experimentation) in the face of challenges that require alternative approaches. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00204-020-02787-2) contains supplementary material, which is available to authorized users.", "qid": 5, "docid": "khfrd1nk", "rank": 99, "score": 0.7585937976837158}, {"content": "Title: Animal Model Prescreening: Pre-exposure to SARS-CoV-2 impacts responses in the NHP model Content: COVID-19 presents herculean challenges to research and scientific communities for producing diagnostic and treatment solutions. Any return to normalcy requires rapid development of countermeasures, with animal models serving as a critical tool in testing vaccines and therapeutics. Animal disease status and potential COVID-19 exposure prior to study execution may severely bias efficacy testing. We developed a toolbox of immunological and molecular tests to monitor countermeasure impact on disease outcome and evaluate pre-challenge COVID-19 status. Assay application showed critical necessity for animal pre-screening. Specifically, real-time PCR results documented pre-exposure of an African Green Monkey prior to SARS-CoV-2 challenge with sequence confirmation as a community-acquired exposure. Longitudinal monitoring of nasopharyngeal swabs and serum showed pre-exposure impacted both viral disease course and resulting immunological response. This study demonstrates utility in a comprehensive pre-screening strategy for animal models, which captured the first documented case of community-acquired, non-human primate infection. One Sentence Summary Pre-exposure to SARS-CoV-2 affects biomarker responses in animal models, highlighting a need for robust pre-screening protocols prior to medical countermeasure studies.", "qid": 5, "docid": "rbt84zet", "rank": 100, "score": 0.7581793665885925}]}
{"query": "what types of rapid testing for Covid-19 have been developed?", "hits": [{"content": "Title: Point-of-Care Diagnostic Tests for Detecting SARS-CoV-2 Antibodies: A Systematic Review and Meta-Analysis of Real-World Data Content: SARS-CoV-2 is responsible for a highly contagious infection, known as COVID-19. SARS-CoV-2 was discovered in late December 2019 and, since then, has become a global pandemic. Timely and accurate COVID-19 laboratory testing is an essential step in the management of the COVID-19 outbreak. To date, assays based on the reverse-transcription polymerase chain reaction (RT-PCR) in respiratory samples are the gold standard for COVID-19 diagnosis. Unfortunately, RT-PCR has several practical limitations. Consequently, alternative diagnostic methods are urgently required, both for alleviating the pressure on laboratories and healthcare facilities and for expanding testing capacity to enable large-scale screening and ensure a timely therapeutic intervention. To date, few studies have been conducted concerning the potential utilization of rapid testing for COVID-19, with some conflicting results. Therefore, the present systematic review and meta-analysis was undertaken to explore the feasibility of rapid diagnostic tests in the management of the COVID-19 outbreak. Based on ten studies, we computed a pooled sensitivity of 64.8% (95%CI 54.5-74.0), and specificity of 98.0% (95%CI 95.8-99.0), with high heterogeneity and risk of reporting bias. We can conclude that: (1) rapid diagnostic tests for COVID-19 are necessary, but should be adequately sensitive and specific; (2) few studies have been carried out to date; (3) the studies included are characterized by low numbers and low sample power, and (4) in light of these results, the use of available tests is currently questionable for clinical purposes and cannot substitute other more reliable molecular tests, such as assays based on RT-PCR.", "qid": 6, "docid": "4ipuy7su", "rank": 1, "score": 0.7954086661338806}, {"content": "Title: Point-of-Care Diagnostic Tests for Detecting SARS-CoV-2 Antibodies: A Systematic Review and Meta-Analysis of Real-World Data Content: SARS-CoV-2 is responsible for a highly contagious infection, known as COVID-19. SARS-CoV-2 was discovered in late December 2019 and, since then, has become a global pandemic. Timely and accurate COVID-19 laboratory testing is an essential step in the management of the COVID-19 outbreak. To date, assays based on the reverse-transcription polymerase chain reaction (RT-PCR) in respiratory samples are the gold standard for COVID-19 diagnosis. Unfortunately, RT-PCR has several practical limitations. Consequently, alternative diagnostic methods are urgently required, both for alleviating the pressure on laboratories and healthcare facilities and for expanding testing capacity to enable large-scale screening and ensure a timely therapeutic intervention. To date, few studies have been conducted concerning the potential utilization of rapid testing for COVID-19, with some conflicting results. Therefore, the present systematic review and meta-analysis was undertaken to explore the feasibility of rapid diagnostic tests in the management of the COVID-19 outbreak. Based on ten studies, we computed a pooled sensitivity of 64.8% (95%CI 54.5\u201374.0), and specificity of 98.0% (95%CI 95.8\u201399.0), with high heterogeneity and risk of reporting bias. We can conclude that: (1) rapid diagnostic tests for COVID-19 are necessary, but should be adequately sensitive and specific; (2) few studies have been carried out to date; (3) the studies included are characterized by low numbers and low sample power, and (4) in light of these results, the use of available tests is currently questionable for clinical purposes and cannot substitute other more reliable molecular tests, such as assays based on RT-PCR.", "qid": 6, "docid": "tujxlve3", "rank": 2, "score": 0.795386016368866}, {"content": "Title: Optimization of the CDC Protocol of Molecular Diagnosis of COVID-19 for Timely Diagnosis Content: Coronavirus disease 2019 (COVID-19), the current uncontrolled outbreak of infectious disease, has caused significant challenges throughout the world. A reliable rapid diagnostic test for COVID-19 is demanded worldwide. The real-time reverse transcriptase polymerase chain was one of the most quickly established methods in the novel viral pandemic and was considered as the gold standard for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this report, we illustrate our experience of applying a protocol from the Taiwan CDC and achieving assay optimization in the immediate circumstances to meet the urgent medical and public health needs.", "qid": 6, "docid": "wt5o9sgm", "rank": 3, "score": 0.795154333114624}, {"content": "Title: Sensitivity and specificity of a rapid test for assessment of exposure to SARS-CoV-2 in a community-based setting in Brazil Content: Background: While the recommended laboratory diagnosis of COVID-19 is a molecular based assay, population-based studies to determine the prevalence of COVID-19 usually use serological assays. Objective: To evaluate the sensitivity and specificity of a rapid diagnostic test for COVID-19 compared to quantitative reverse transcription polymerase chain reaction (qRT-PCR). Methods: We evaluated the sensitivity using a panel of finger prick blood samples from participants >18 years of age that had been tested for COVID-19 by qRT-PCR. For assessing specificity, we used serum samples from the 1982 Pelotas (Brazil) Birth Cohort participants collected in 2012 with no exposure to SARS-CoV-2. Results: The sensitivity of the test was 77.1% (95% CI 66.6 - 85.6), based upon 83 subjects who had tested positive for qRT-PCR at least 10 days before the rapid diagnostic test (RDT). Based upon 100 sera samples, specificity was 98.0% (95% CI 92.9 - 99.8). There was substantial agreement (Kappa score 0.76) between the qRT-PCR results and the RDT. Interpretation. The validation results are well in line with previous assessments of the test, and confirm that it is sufficiently precise for epidemiological studies aimed at monitoring levels and trends of the COVID-19 pandemic.", "qid": 6, "docid": "2siuovme", "rank": 4, "score": 0.7835776805877686}, {"content": "Title: Diagnostic Performance of a Rapid Point of Care Test for SARS-CoV-2 in an Urban ED Setting Content: The ability to rapidly and accurately identify a patient's COVID-19 status has had significant impact on emergency departments (ED) and health systems globally. Since the identification of SARS-CoV-2 illness in the United States, there has been rapid development in patient testing capacity following initial challenges including sparse availability. This was made possible by increasing availability of diagnostic molecular tests in several formats, from laboratory based traditional, RT-PCR methods to near patient testing rapid point of care PCR tests.", "qid": 6, "docid": "onhiptn7", "rank": 5, "score": 0.783191442489624}, {"content": "Title: Evaluation of a COVID-19 IgM and IgG rapid test; an efficient tool for assessment of past exposure to SARS-CoV-2 Content: COVID-19 is the most rapidly growing pandemic in modern time, and the need for serological testing is most urgent. Although the diagnostics of acute patients by RT-PCR is both efficient and specific, we are also crucially in need of serological tools for investigating antibody responses and assessing individual and potential herd immunity. We evaluated a commercially available test developed for rapid (within 15 minutes) detection of SARS-CoV-2-specific IgM and IgG by 29 PCR-confirmed COVID-19 cases and 124 negative controls. The results revealed a sensitivity of 69% and 93.1% for IgM and IgG, respectively, based solely on PCR-positivity due to the absence of a serological gold standard. The assay specificities were shown to be 100% for IgM and 99.2% for IgG. This indicates that the test is suitable for assessing previous virus exposure, although negative results may be unreliable during the first weeks after infection. More detailed studies on antibody responses during and post infection are urgently needed.", "qid": 6, "docid": "knc0ruou", "rank": 6, "score": 0.7805216312408447}, {"content": "Title: Diagnostic Performance of a Rapid Point of Care Test for SARS\u2010CoV\u20102 in an Urban ED Setting Content: The ability to rapidly and accurately identify a patient's COVID\u201019 status has had significant impact on emergency departments (ED) and health systems globally. Since the identification of SARS\u2010CoV\u20102 illness in the United States, there has been rapid development in patient testing capacity following initial challenges including sparse availability. This was made possible by increasing availability of diagnostic molecular tests in several formats, from laboratory based traditional, RT\u2010PCR methods to near patient testing rapid point of care PCR tests.", "qid": 6, "docid": "30umy2ai", "rank": 7, "score": 0.7802568674087524}, {"content": "Title: \u00bfConocemos las propiedades diagn\u00f3sticas de las pruebas usadas en COVID-19? Una revisi\u00f3n r\u00e1pida de la literatura recientemente publicada./ \u00bfConocemos las propiedades diagn\u00f3sticas de las pruebas usadas en COVID-19? Una revisi\u00f3n r\u00e1pida de la literatura recientemente publicada./ Do we know the diagnostic properties of the tests used in COVID-19? A rapid review of recently published literature Content: COVID-19 has brought death and disease to large parts of the world. Governments must deploy strategies to screen the population and subsequently isolate the suspect cases. Diagnostic testing is critical for epidemiological surveillance, but the accuracy (sensitivity and specificity) and clinical utility (impact on health outcomes) of the current diagnostic methods used for SARS-CoV-2 detection are not known. I ran a quick search in PubMed/MEDLINE to find studies on laboratory diagnostic tests and rapid viral diagnosis. After running the search strategies, I found 47 eligible articles that I discuss in this review, commenting on test characteristics and limitations. I did not find any papers that report on the clinical utility of the tests currently used for COVID-19 detection, meaning that we are fighting a battle without proper knowledge of the proportion of false negatives that current testing is resulting in. This shortcoming should not be overlooked as it might hamper national efforts to contain the pandemic through testing community-based suspect cases.", "qid": 6, "docid": "gzrjca1l", "rank": 8, "score": 0.7790408134460449}, {"content": "Title: Do we know the diagnostic properties of the tests used in COVID-19? A rapid review of recently published literature. Content: COVID-19 has brought death and disease to large parts of the world. Governments must deploy strategies to screen the population and subsequently isolate the suspect cases. Diagnostic testing is critical for epidemiological surveillance, but the accuracy (sensitivity and specificity) and clinical utility (impact on health outcomes) of the current diagnostic methods used for SARS-CoV-2 detection are not known. I ran a quick search in PubMed/MEDLINE to find studies on laboratory diagnostic tests and rapid viral diagnosis. After running the search strategies, I found 47 eligible articles that I discuss in this review, commenting on test characteristics and limitations. I did not find any papers that report on the clinical utility of the tests currently used for COVID-19 detection, meaning that we are fighting a battle without proper knowledge of the proportion of false negatives that current testing is resulting in. This shortcoming should not be overlooked as it might hamper national efforts to contain the pandemic through testing community-based suspect cases.", "qid": 6, "docid": "vn0xu1cn", "rank": 9, "score": 0.7790408134460449}, {"content": "Title: Rapid Detection of Novel Coronavirus (COVID-19) by Reverse Transcription-Loop-Mediated Isothermal Amplification Content: Novel Corona virus (COVID-19 or 2019-nCoV) is an emerging global health concern that requires a rapid diagnostic test. Quantitative reverse transcription PCR (qRT-PCR) is currently the standard for COVID-19 detection; however, Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) may allow for faster and cheaper field based testing at point-of-risk. The objective of this study was to develop a rapid screening diagnostic test that could be completed in under 30 minutes. Simulated patient samples were generated by spiking serum, urine, saliva, oropharyngeal swabs, and nasopharyngeal swabs with a portion of the COVID-19 nucleic sequence. The samples were tested using RT-LAMP as well as by conventional qRT-PCR. Specificity of the RT-LAMP was evaluated by also testing against other related coronaviruses. RT-LAMP specifically detected COVID-19 in simulated patient samples. This test was performed in under 30 minutes. This approach could be used for monitoring of exposed individuals or potentially aid with screening efforts in the field and potential ports of entry.", "qid": 6, "docid": "6kpgt70s", "rank": 10, "score": 0.7782939672470093}, {"content": "Title: Overcoming the bottleneck to widespread testing: a rapid review of nucleic acid testing approaches for COVID-19 detection Content: The current COVID-19 pandemic presents a serious public health crisis, and a better understanding of the scope and spread of the virus would be aided by more widespread testing. Nucleic-acid-based tests currently offer the most sensitive and early detection of COVID-19. However, the \"gold standard\" test pioneered by the U.S. Centers for Disease Control and Prevention takes several hours to complete and requires extensive human labor, materials such as RNA extraction kits that could become in short supply, and relatively scarce qPCR machines. It is clear that a huge effort needs to be made to scale up current COVID-19 testing by orders of magnitude. There is thus a pressing need to evaluate alternative protocols, reagents, and approaches to allow nucleic-acid testing to continue in the face of these potential shortages. There has been a tremendous explosion in the number of papers written within the first weeks of the pandemic evaluating potential advances, comparable reagents, and alternatives to the \"gold-standard\" CDC RT-PCR test. Here we present a collection of these recent advances in COVID-19 nucleic acid testing, including both peer-reviewed and preprint articles. Due to the rapid developments during this crisis, we have included as many publications as possible, but many of the cited sources have not yet been peer-reviewed, so we urge researchers to further validate results in their own laboratories. We hope that this review can urgently consolidate and disseminate information to aid researchers in designing and implementing optimized COVID-19 testing protocols to increase the availability, accuracy, and speed of widespread COVID-19 testing.", "qid": 6, "docid": "opdva99w", "rank": 11, "score": 0.7777324914932251}, {"content": "Title: Diagnostic performance of COVID-19 serology assays Content: INTRODUCTION: The World Health Organization (WHO) declared COVID-19 outbreak as a world pandemic on 12th March 2020. Diagnosis of suspected cases is confirmed by nucleic acid assays with real-time PCR, using respiratory samples. Serology tests are comparatively easier to perform, but their utility may be limited by the performance and the fact that antibodies appear later during the disease course. We aimed to describe the performance data on serological assays for COVID-19. MATERIALS AND METHODS: A review of multiple reports and kit inserts on the diagnostic performance of rapid tests from various manufacturers that are commercially available were performed. Only preliminary data are available currently. RESULTS: From a total of nine rapid detection test (RDT) kits, three kits offer total antibody detection, while six kits offer combination SARS-CoV-2 IgM and IgG detection in two separate test lines. All kits are based on colloidal gold-labeled immunochromatography principle and one-step method with results obtained within 15 minutes, using whole blood, serum or plasma samples. The sensitivity for both IgM and IgG tests ranges between 72.7% and 100%, while specificity ranges between 98.7% to 100%. Two immunochromatography using nasopharyngeal or throat swab for detection of COVID-19 specific antigen are also reviewed. CONCLUSIONS: There is much to determine regarding the value of serological testing in COVID-19 diagnosis and monitoring. More comprehensive evaluations of their performance are rapidly underway. The use of serology methods requires appropriate interpretations of the results and understanding the strengths and limitations of such tests.", "qid": 6, "docid": "b7a2w4v9", "rank": 12, "score": 0.777355968952179}, {"content": "Title: Current and emerging diagnostic tests available for the novel COVID-19 global pandemic Content: On March 11, 2020 the World Health Organization (WHO) upgraded the status of the coronavirus disease 2019 (COVID-19) outbreak from epidemic to a global pandemic. This infection is caused by a novel coronavirus, SARS-CoV-2. Several rapid diagnostic tests have been developed at an astonishing pace; however, COVID-19 requires more highly specific rapid point-of-care diagnostic tests. This review describes the currently available testing approaches, as well as the available test assays including the Xpert\u00ae Xpress SARS-CoV-2 test (takes (~)45 min) and Abbott ID COVID-19 test (5 min) as easy to use point-of-care tests for diagnosis of novel COVID-19 that have so far received the US Food and Drug Administration emergency use authorizations clearance. This review is correct as of the date published and will be updated as more diagnostic tests come to light.", "qid": 6, "docid": "1dr4r3n4", "rank": 13, "score": 0.7759500741958618}, {"content": "Title: Rapid point-of-care testing for SARS-CoV-2 in a community screening setting shows low sensitivity Content: OBJECTIVE: With the current SARS-CoV2 outbreak, countless tests need to be performed on potential symptomatic individuals, contacts and travellers. The gold standard is a quantitative polymerase chain reaction (qPCR)-based system taking several hours to confirm positivity. For effective public health containment measures, this time span is too long. We therefore evaluated a rapid test in a high-prevalence community setting. STUDY DESIGN: Thirty-nine randomly selected individuals at a COVID-19 screening centre were simultaneously tested via qPCR and a rapid test. Ten previously diagnosed individuals with known SARS-CoV-2 infection were also analysed. METHODS: The evaluated rapid test is an IgG/IgM-based test for SARS-CoV-2 with a time to result of 20 min. Two drops of blood are needed for the test performance. RESULTS: Of 49 individuals, 22 tested positive by repeated qPCR. In contrast, the rapid test detected only eight of those positive correctly (sensitivity: 36.4%). Of the 27 qPCR-negative individuals, 24 were detected correctly (specificity: 88.9%). CONCLUSION: Given the low sensitivity, we recommend not to rely on an antibody-based rapid test for public health measures such as community screenings.", "qid": 6, "docid": "22kgwbz4", "rank": 14, "score": 0.7759103775024414}, {"content": "Title: Overcoming the bottleneck to widespread testing: A rapid review of nucleic acid testing approaches for COVID-19 detection. Content: The current COVID-19 pandemic presents a serious public health crisis, and a better understanding of the scope and spread of the virus would be aided by more widespread testing. Nucleic-acid based tests currently offer the most sensitive and early detection of COVID-19. However, the \"gold standard\" test pioneered by the United States Center for Disease Control & Prevention, takes several hours to complete and requires extensive human labor, materials such as RNA extraction kits that could become in short supply and relatively scarce qPCR machines. It is clear that a huge effort needs to be made to scale up current COVID-19 testing by orders of magnitude. There is thus a pressing need to evaluate alternative protocols, reagents, and approaches to allow nucleic-acid testing to continue in the face of these potential shortages. There has been a tremendous explosion in the number of papers written within the first weeks of the pandemic evaluating potential advances, comparable reagents, and alternatives to the \"gold-standard\" CDC RT-PCR test. Here we present a collection of these recent advances in COVID-19 nucleic acid testing, including both peer-reviewed and preprint articles. Due to the rapid developments during this crisis, we have included as many publications as possible, but many of the cited sources have not yet been peer-reviewed, so we urge researchers to further validate results in their own labs. We hope that this review can urgently consolidate and disseminate information to aid researchers in designing and implementing optimized COVID-19 testing protocols to increase the availability, accuracy, and speed of widespread COVID-19 testing.", "qid": 6, "docid": "b3wp314u", "rank": 15, "score": 0.7757556438446045}, {"content": "Title: Evaluation of eleven rapid tests for detection of antibodies against SARS-CoV-2 Content: Objectives SARS-CoV-2, causing COVID-19, has emerged to cause a human pandemic. Detection of SARS-CoV-2 in respiratory samples by using PCR is the standard laboratory diagnostic tool. Our aim was to perform a limited evaluation of the diagnostic performance and user-friendliness of eleven rapid tests for detection of antibodies against SARS-CoV-2. Methods All participants were tested with PCR against SARS-CoV-2 at a clinical microbiology laboratory. Comparing with results from PCR tests, we evaluated the rapid tests' performances in three arms; 1) 20 hospitalized patients with PCR-confirmed COVID-19, 2) 23 recovered outpatients with former PCR-confirmed COVID-19, and 3) 49 participants with suspected COVID-19 presenting at a primary care emergency room. Results All eleven tests detected antibodies in hospitalized COVID-19 patients, though with varying sensitivities. In former outpatients recovered from COVID-19, there were differences between tests in the immunoglobulin type G (IgG) sensitivity, with five tests having a sensitivity below 65%. In participants with suspected COVID-19 infection, the rapid tests had very low sensitivities. Most rapid tests were easy to perform and interpret. Conclusions Rapid tests were not suited as stand-alone tests to detect present infection in a Norwegian primary care emergency room population. All the rapid tests were able to detect SARS-CoV-2 antibodies, although sensitivities varied and were generally higher in the study arm of more severely affected participants. Rapid tests with high IgG sensitivity (and specificity) may be useful for confirmation of past infection. An independent evaluation should be performed in the intended population before introducing a rapid test.", "qid": 6, "docid": "xa1v5t63", "rank": 16, "score": 0.77479088306427}, {"content": "Title: Evaluation of eleven rapid tests for detection of antibodies against SARS-CoV-2. Content: Objectives SARS-CoV-2, causing COVID-19, has emerged to cause a human pandemic. Detection of SARS-CoV-2 in respiratory samples by using PCR is the standard laboratory diagnostic tool. Our aim was to perform a limited evaluation of the diagnostic performance and user-friendliness of eleven rapid tests for detection of antibodies against SARS-CoV-2. Methods All participants were tested with PCR against SARS-CoV-2 at a clinical microbiology laboratory. Comparing with results from PCR tests, we evaluated the rapid tests' performances in three arms; 1) 20 hospitalized patients with PCR-confirmed COVID-19, 2) 23 recovered outpatients with former PCR-confirmed COVID-19, and 3) 49 participants with suspected COVID-19 presenting at a primary care emergency room. Results All eleven tests detected antibodies in hospitalized COVID-19 patients, though with varying sensitivities. In former outpatients recovered from COVID-19, there were differences between tests in the immunoglobulin type G (IgG) sensitivity, with five tests having a sensitivity below 65%. In participants with suspected COVID-19 infection, the rapid tests had very low sensitivities. Most rapid tests were easy to perform and interpret. Conclusions Rapid tests were not suited as stand-alone tests to detect present infection in a Norwegian primary care emergency room population. All the rapid tests were able to detect SARS-CoV-2 antibodies, although sensitivities varied and were generally higher in the study arm of more severely affected participants. Rapid tests with high IgG sensitivity (and specificity) may be useful for confirmation of past infection. An independent evaluation should be performed in the intended population before introducing a rapid test.", "qid": 6, "docid": "7ur8hr23", "rank": 17, "score": 0.77479088306427}, {"content": "Title: Trends and Innovations in Biosensors for COVID-19 Mass Testing Content: Fast and widespread diagnosis is crucial to fighting against the outbreak of COVID-19. This work surveys the landscape of available and emerging biosensor technologies for COVID-19 testing. Molecular diagnostic assays based on quantitative reverse transcription polymerase chain reaction are used in most clinical laboratories. However, the COVID-19 pandemic has overwhelmed testing capacity and motivated the development of fast point-of-care tests and the adoption of isothermal DNA amplification. Antigenic and serological rapid tests based on lateral-flow immunoassays suffer from low sensitivity. Advanced digital systems enhance performance at the expense of speed and the need for large equipment. Emerging technologies, including CRISPR gene-editing tools, benefit from high sensitivity and specificity of molecular diagnostics and the easy use of lateral-flow assays. DNA sequencing and sample pooling strategies are highlighted to bring out the full capacity of the available biosensor technologies and accelerate mass testing.", "qid": 6, "docid": "d5d10lwr", "rank": 18, "score": 0.7736172676086426}, {"content": "Title: Trends and innovations in biosensors for COVID-19 mass testing. Content: Fast and widespread diagnosis is crucial to fight against the outbreak of COVID-19. The present work surveys the landscape of available and emerging biosensor technologies for COVID-19 testing. Molecular diagnostic assays based on quantitative Reverse Transcription Polymerase Chain Reaction are used in most clinical laboratories. The COVID-19 pandemic has overwhelmed the testing capacity and motivated the development of fast point-of-care tests and the adoption of isothermal DNA amplification. Antigenic and serological rapid tests based on lateral flow immunoassays suffer from low sensitivity. Advanced digital systems enhance the performance at the expense of speed and large equipment requirement. Emerging technologies, including CRISPR gene-editing tools, benefit from high sensitivity and selectivity of molecular diagnostics and the easy use of lateral flow assays. DNA sequencing and sample pooling strategies are highlighted to bring out the full capacity of the available biosensor technologies and accelerate mass testing.", "qid": 6, "docid": "nswmhpzf", "rank": 19, "score": 0.7722467184066772}, {"content": "Title: Fast SARS-CoV-2 detection by RT-qPCR in preheated nasopharyngeal swab samples Content: The current reference for COVID-19 diagnosis is based on the detection of SARS-CoV-2 on RNA extracts using one-step retrotranscription and quantitative PCR (RT-qPCR). Based on the urgent need for high-throughput COVID-19 screening, we tested the performance of three alternative, simple and affordable protocols to rapidly detect SARS-CoV-2, overcoming the long and tedious RNA extraction step. Although with an average increase of 6.1 ( \u00b11.6) cycles compared to standard tests with RNA extracts, we show that RT-qPCR yielded consistent results in nasopharyngeal swab samples that were subject to a direct 70\u00b0C incubation for 10 min. Our findings provide viable options to overcome any supply chain issue and help to increase the throughput of diagnostic tests by using any qPCR device, thereby complementing standard COVID-19 testing.", "qid": 6, "docid": "icpwfyss", "rank": 20, "score": 0.7719912528991699}, {"content": "Title: Diagnostic performance of COVID-19 serology assays. Content: INTRODUCTION The World Health Organization (WHO) declared COVID-19 outbreak as a world pandemic on 12th March 2020. Diagnosis of suspected cases is confirmed by nucleic acid assays with real-time PCR, using respiratory samples. Serology tests are comparatively easier to perform, but their utility may be limited by the performance and the fact that antibodies appear later during the disease course. We aimed to describe the performance data on serological assays for COVID-19. MATERIALS AND METHODS A review of multiple reports and kit inserts on the diagnostic performance of rapid tests from various manufacturers that are commercially available were performed. Only preliminary data are available currently. RESULTS From a total of nine rapid detection test (RDT) kits, three kits offer total antibody detection, while six kits offer combination SARS-CoV-2 IgM and IgG detection in two separate test lines. All kits are based on colloidal gold-labeled immunochromatography principle and one-step method with results obtained within 15 minutes, using whole blood, serum or plasma samples. The sensitivity for both IgM and IgG tests ranges between 72.7% and 100%, while specificity ranges between 98.7% to 100%. Two immunochromatography using nasopharyngeal or throat swab for detection of COVID-19 specific antigen are also reviewed. CONCLUSIONS There is much to determine regarding the value of serological testing in COVID-19 diagnosis and monitoring. More comprehensive evaluations of their performance are rapidly underway. The use of serology methods requires appropriate interpretations of the results and understanding the strengths and limitations of such tests.", "qid": 6, "docid": "ij4ibrrx", "rank": 21, "score": 0.7715284824371338}, {"content": "Title: A handheld point-of-care system for rapid detection of SARS-CoV-2 in under 20 minutes Content: The COVID-19 pandemic is a global health emergency characterized by the high rate of transmission and ongoing increase of cases globally. Rapid point-of-care (PoC) diagnostics to detect the causative virus, SARS-CoV-2, are urgently needed to identify and isolate patients, contain its spread and guide clinical management. In this work, we report the development of a rapid PoC diagnostic test (< 20 min) based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) and semiconductor technology for the detection of SARS-CoV-2 from extracted RNA samples. The developed LAMP assay was tested on a real-time benchtop instrument (RT-qLAMP) showing a lower limit of detection of 10 RNA copies per reaction. It was validated against 183 clinical samples including 127 positive samples (screened by the CDC RT-qPCR assay). Results showed 90.55% sensitivity and 100% specificity when compared to RT-qPCR and average positive detection times of 15.45 {+/-} 4.43 min. For validating the incorporation of the RT-LAMP assay onto our PoC platform (RT-eLAMP), a subset of samples was tested (n=40), showing average detection times of 12.89 {+/-} 2.59 min for positive samples (n=34), demonstrating a comparable performance to a benchtop commercial instrument. Paired with a smartphone for results visualization and geo-localization, this portable diagnostic platform with secure cloud connectivity will enable real-time case identification and epidemiological surveillance.", "qid": 6, "docid": "m9l8ntur", "rank": 22, "score": 0.7703321576118469}, {"content": "Title: Clinical meanings of rapid serological assay in patients tested for SARS-Co2 RT-PCR Content: Background RT-PCR test for identifiction of viral nucleic acid is the current standard diagnostic method for the diagnosis of COVID-19 disease but technical reasons limit the utilization of this assay on large scale screenings. Method We verified in a consecutive series of 191 symptomatic patients the clinical information that new rapid serological colorimetric test qualitatively analyzing IgM/IgG expression can provide with respect to standard assay and with respect to clinical outcome of patients. Results Rapid serological test showed a sensitivity of 30% and a specificity of 89% with respect to the standard assay but, interestingly, these performances improve after 8 days of symptoms appearance. After 10 days of symptoms the predictive value of rapid serological test is higher than that of standard assay. When the behaviour of the two immunoglobulins was evaluated with respect to time length of symptoms appearance, no significant difference in immunoglobulins behaviour was shown. Conclusions The rapid serological test analyzed in the present study is candidate to provide information on immunoreaction of the subject to COVID-19 exposure.", "qid": 6, "docid": "ilxd0ih9", "rank": 23, "score": 0.7696514129638672}, {"content": "Title: Rapid point-of-care testing for SARS-CoV-2 in a community screening setting shows low sensitivity Content: Abstract Objective With the current SARS-CoV2 outbreak, countless tests need to be performed on potential symptomatic individuals, contacts and travellers. The gold standard is a quantitative polymerase chain reaction (qPCR)\u2013based system taking several hours to confirm positivity. For effective public health containment measures, this time span is too long. We therefore evaluated a rapid test in a high-prevalence community setting. Study design Thirty-nine randomly selected individuals at a COVID-19 screening centre were simultaneously tested via qPCR and a rapid test. Ten previously diagnosed individuals with known SARS-CoV-2 infection were also analysed. Methods The evaluated rapid test is an IgG/IgM\u2013based test for SARS-CoV-2 with a time to result of 20 min. Two drops of blood are needed for the test performance. Results Of 49 individuals, 22 tested positive by repeated qPCR. In contrast, the rapid test detected only eight of those positive correctly (sensitivity: 36.4%). Of the 27 qPCR-negative individuals, 24 were detected correctly (specificity: 88.9%). Conclusion Given the low sensitivity, we recommend not to rely on an antibody-based rapid test for public health measures such as community screenings.", "qid": 6, "docid": "k1adcls8", "rank": 24, "score": 0.7682152390480042}, {"content": "Title: Multi-Tiered Screening and Diagnosis Strategy for COVID-19: A Model for Sustainable Testing Capacity in Response to Pandemic. Content: Coronavirus disease 2019 (COVID-19), caused by novel enveloped single stranded RNA coronavirus (SARS-CoV-2), is responsible for an ongoing global pandemic. While other countries deployed widespread testing as an early mitigation strategy, the U.S. experienced delays in development and deployment of organism identification assays. As such, there is uncertainty surrounding disease burden and community spread, severely hampering containment efforts. COVID-19 illuminates the need for a tiered diagnostic approach to rapidly identify clinically significant infections and reduce disease spread. Without the ability to efficiently screen patients, hospitals are overwhelmed, potentially delaying treatment for other emergencies.A multi-tiered, diagnostic strategy incorporating a rapid host immune response assay as a screening test; molecular confirmatory testing and rapid IgM/IgG testing to assess benefit from quarantine/further testing and provide information on population exposure/herd immunity would efficiently evaluate potential COVID-19 patients. Triaging patients within minutes with a fingerstick rather than hours/days after an invasive swab is critical to pandemic response as reliance on the existing strategy is limited by assay accuracy, time to results, and testing capacity. Early screening and triage is achievable from the outset of a pandemic with point-of-care host immune response testing which will improve response time to clinical and public health actions. Key MessagesDelayed testing deployment has led to uncertainty surrounding overall disease burden and community spread, severely hampering public health containment and healthcare system preparation efforts.A multi-tiered testing strategy incorporating rapid, host immune point-of-care tests can be used now and for future pandemic planning by effectively identifying patients at risk of disease thereby facilitating quarantine earlier in the progression of the outbreak during the weeks and months it can take for pathogen specific confirmatory tests to be developed, validated and manufactured in sufficient quantities.The ability to triage patients at the point of care and support the guidance of medical and therapeutic decisions, for viral isolation or confirmatory testing or for appropriate treatment of COVID-19 and/or bacterial infections, is a critical component to our national pandemic response and there is an urgent need to implement the proposed strategy to combat the current outbreak.", "qid": 6, "docid": "62v5ej3c", "rank": 25, "score": 0.767723560333252}, {"content": "Title: Testing for SARS-CoV-2 (COVID-19): a systematic review and clinical guide to molecular and serological in-vitro diagnostic assays Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated coronavirus disease 2019 (COVID-19) pandemic has demanded rapid upscaling of in-vitro diagnostic assays to enable mass screening and testing of high-risk groups, and simultaneous ascertainment of robust data on past SARS-CoV-2 exposure at an individual and a population level. To meet the exponential demand in testing, there has been an accelerated development of both molecular and serological assays across a plethora of platforms. The present review discusses the current literature on these modalities, including nucleic acid amplification tests, direct viral antigen tests and the rapidly expanding laboratory-based and point of care serological tests. This suite of complementary tests will inform crucial decisions by healthcare providers and policy makers, and understanding their strengths and limitations will be critical to their judicious application for the development of algorithmic approaches to treatment and public health strategies.", "qid": 6, "docid": "3ea1ngo2", "rank": 26, "score": 0.7675366401672363}, {"content": "Title: Multi-tiered screening and diagnosis strategy for COVID-19: a model for sustainable testing capacity in response to pandemic Content: Coronavirus disease 2019 (COVID-19), caused by novel enveloped single stranded RNA coronavirus (SARS-CoV-2), is responsible for an ongoing global pandemic. While other countries deployed widespread testing as an early mitigation strategy, the U.S. experienced delays in development and deployment of organism identification assays. As such, there is uncertainty surrounding disease burden and community spread, severely hampering containment efforts. COVID-19 illuminates the need for a tiered diagnostic approach to rapidly identify clinically significant infections and reduce disease spread. Without the ability to efficiently screen patients, hospitals are overwhelmed, potentially delaying treatment for other emergencies. A multi-tiered, diagnostic strategy incorporating a rapid host immune response assay as a screening test, molecular confirmatory testing and rapid IgM/IgG testing to assess benefit from quarantine/further testing and provide information on population exposure/herd immunity would efficiently evaluate potential COVID-19 patients. Triaging patients within minutes with a fingerstick rather than hours/days after an invasive swab is critical to pandemic response as reliance on the existing strategy is limited by assay accuracy, time to results, and testing capacity. Early screening and triage is achievable from the outset of a pandemic with point-of-care host immune response testing which will improve response time to clinical and public health actions.Key messagesDelayed testing deployment has led to uncertainty surrounding overall disease burden and community spread, severely hampering public health containment and healthcare system preparation efforts.A multi-tiered testing strategy incorporating rapid, host immune point-of-care tests can be used now and for future pandemic planning by effectively identifying patients at risk of disease thereby facilitating quarantine earlier in the progression of the outbreak during the weeks and months it can take for pathogen specific confirmatory tests to be developed, validated and manufactured in sufficient quantities.The ability to triage patients at the point of care and support the guidance of medical and therapeutic decisions, for viral isolation or confirmatory testing or for appropriate treatment of COVID-19 and/or bacterial infections, is a critical component to our national pandemic response and there is an urgent need to implement the proposed strategy to combat the current outbreak.", "qid": 6, "docid": "hpyh2dxy", "rank": 27, "score": 0.767444908618927}, {"content": "Title: Development and validation of a rapid single-step reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) system potentially to be used for reliable and high-throughput screening of COVID-19 Content: The recent pandemic of COVID-19 has involved tens of thousands of patients in numerous countries and the causative virus, SARS COV-2 is highly transmissible. Molecular diagnostic tools are central to containment of the virus and initiating proper clinical care. Rapidity, user-friendliness, and high degree of sensitivity and specificity are desirable features of diagnostic assays for screening purposes. Herein, we present a single step reverse transcriptase LAMP assay (RT-LAMP), which can detect up to 500 viral copies in 30 minutes. We challenged our assay with a large number of clinical samples collected from 47 confirmed cases and 213 negative patients. Our LAMP assay showed a high degree of sensitivity and specificity compared to two commercialized qRT-PCR assay as gold standard. We present a rapid RT-LAMP assay that could extend the capacity of laboratories to process 2.5 more clinical samples relative to qRT-PCR and potentially could be used for high-throughput screening purposes.", "qid": 6, "docid": "eo2pcgix", "rank": 28, "score": 0.7672655582427979}, {"content": "Title: Development of a rapid test kit for SARS-CoV-2: an example of product design Content: We present an example of applying 'need-driven' product design principle to the development of a rapid test kit to detect SARS-COV-2 (COVID-19). The tests are intended for use in the field and, longer term, for home use. They detect whether a subject is currently infected with the virus and is infectious. The urgent need for large numbers of tests in field setting imposes constraints such as short test time and lack of access to specialist equipment, laboratories and skilled technicians to perform the test and interpret results. To meet these needs, an antigen test based on RT-LAMP with colorimetric readout was chosen. Direct use of swab sample with no RNA extraction was explored. After extensive experimental study (reported elsewhere), a rapid test kit has been fabricated to satisfy all design criteria.", "qid": 6, "docid": "52pw2vwx", "rank": 29, "score": 0.7669360637664795}, {"content": "Title: Rapid viral diagnosis and ambulatory management of suspected COVID-19 cases presenting at the infectious diseases referral hospital in Marseille, France, - January 31st to March 1st, 2020: A respiratory virus snapshot Content: Abstract Background Rapid virological diagnosis is needed to limit the length of isolation for suspected COVID-19 cases. Method We managed the first 280 patients suspected to have COVID-19 through a rapid care circuit and virological diagnosis in our infectious disease reference hospital in Marseille, France. Rapid viral detection was performed on sputum and nasopharyngeal samples. Results Over our study period, no SARS-CoV-2 was detected. Results were obtained within approximately 3 h of the arrival of patient samples at the laboratory. Other viral infections were identified in 49% of the patients, with most common pathogens being influenza A and B viruses, rhinovirus, metapneumovirus and common coronaviruses, notably HKU1 and NL63. Conclusion Early recognition of COVID-19 is critical to isolate confirmed cases and prevent further transmission. Early rule-out of COVID-19 allows public health containment measures to be adjusted by reducing the time spent in isolation.", "qid": 6, "docid": "hfdh571v", "rank": 30, "score": 0.7666262984275818}, {"content": "Title: Testing For SARS-CoV-2: The Day the World Turned its Attention to the Clinical Laboratory Content: In the last few months, an unprecedented number of laboratory tests for coronavirus disease 2019 (COVID-19) have been developed at a remarkable speed. With the rapid adoption of these tests into clinical practice, combined with the widespread publicity they received, questions arose related to the different types of tests, their utility, performance, and regulatory approval status. The aim of this publication is to provide a general landscape of laboratory testing for COVID-19 and offer a historical and regulatory perspective associated with them. Specifically, we aim to elaborate on the regulatory complexities of diagnostic testing in the United States and its implications to the present outbreak, as well as provide a synopsis of laboratory tests that have been developed for COVID-19. We will first address the detection of severe acute respiratory syndrome-coronavirus 2 directly by either nucleic acid amplification tests or by the detection of the viral protein for active infections. Subsequently, we will provide an overview of serological tests that can aid not only in diagnosis but additionally help to identify prior infections and potential immunity.", "qid": 6, "docid": "r7glmi7p", "rank": 31, "score": 0.7665632963180542}, {"content": "Title: Loop mediated isothermal amplification (LAMP) assays as a rapid diagnostic for COVID-19 Content: Recently, a novel coronavirus (SARS-CoV-2; coronavirus disease 2019, COVID-19) has emerged, rapidly spreading and severely straining the capacity of the global health community. Many nations are employing combinations of containment and mitigation strategies, where early diagnosis of COVID-19 is vital in controlling illness progression and limiting viral spread within the population. Thus, rapid and accurate methods of early detection are vital to contain COVID-19 and prevent further spread and predicted subsequent infectious waves of viral recurrence in future. Immediately after its initial characterization, Chinese and American Centers for Disease Control and Prevention (CDCs) rapidly employed molecular assays for detection of COVID-19, mostly employing real-time polymerase chain reaction (RT-PCR) methods. However, such methods require specific expensive items of equipment and highly trained analysts, requiring upwards of 4-8 h to process. These requirements coupled with associated financial pressures may prevent effective deployment of such diagnostic tests. Loop mediated isothermal amplification(LAMP) is method of nucleic acid amplification which exhibits increased sensitivity and specificity are significantly rapid, and do not require expensive reagents or instruments, which aids in cost reduction for coronavirus detection. Studies have shown the successful application of LAMP assays in various forms to detect coronavirus RNA in patient samples, demonstrating that 1-10 copies of viral RNA template per reaction are sufficient for successful detection, ~100-fold more sensitive than conventional RT-PCR methods. Importantly, studies have also now demonstrated the effectiveness of LAMP methodology in the detection of SARS-CoV-2 RNA at significantly low levels, particularly following numerous improvements to LAMP assay protocols. We hypothesise that recent advancements in enhanced LAMP protocols assay perhaps represent the best chance for a rapid and robust assay for field diagnosis of COVID-19, without the requirement of specialized equipment and highly trained professionals to interpret results. Herein, we present our arguments with a view to disseminate such findings, to assist the combat of this virus that is proving so devastating. We hope that this strategy could be applied rapidly, and confirmed for viability with clinical samples, before being rolled out for mass-diagnostic testing in these current times.", "qid": 6, "docid": "ax8qn0ci", "rank": 32, "score": 0.7654512524604797}, {"content": "Title: A Rapid COVID-19 RT-PCR Detection Assay for Low Resource Settings Content: Quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay is the gold standard recommended to test for acute SARS-CoV-2 infection. It has been used by the Centers for Disease Control and Prevention (CDC) and several other companies in their Emergency Use Authorization (EUA) assays. RT-qPCR requires expensive equipment such as RNA isolation instruments and real-time PCR thermal cyclers, which are not available in many low resource settings and developing countries. As a pandemic, COVID-19 has quickly spread to the rest of the world. Many underdeveloped and developing counties do not have the means for fast and accurate COVID-19 detection to control this outbreak. Using COVID-19 positive clinical specimens, we demonstrated that RT-PCR assays can be performed in as little as 12 minutes using untreated samples, heat-inactivated samples, or extracted RNA templates. Rapid RT-PCR was achieved using thin-walled PCR tubes and a setup including sous vide immersion heaters/circulators. Our data suggest that rapid RT-PCR can be implemented for sensitive and specific molecular diagnosis of COVID-19 in situations where sophisticated laboratory instruments are not available.", "qid": 6, "docid": "lqio7l8k", "rank": 33, "score": 0.7653191685676575}, {"content": "Title: A comparison of group testing architectures for COVID-19 testing Content: An important component of every country's COVID-19 response is fast and efficient testing -- to identify and isolate cases, as well as for early detection of local hotspots. For many countries, producing a sufficient number of tests has been a serious limiting factor in their efforts to control COVID-19 infections. Group testing is a well-established mathematical tool, which can provide a serious and rapid improvement to this situation. In this note, we compare several well-established group testing schemes in the context of qPCR testing for COVID-19. We include example calculations, where we indicate which testing architectures yield the greatest efficiency gains in various settings. We find that for identification of individuals with COVID-19, array testing is usually the best choice, while for estimation of COVID-19 prevalence rates in the total population, Gibbs-Gower testing usually provides the most accurate estimates given a fixed and relatively small number of tests. This note is intended as a helpful handbook for labs implementing group testing methods.", "qid": 6, "docid": "rhmywn8n", "rank": 34, "score": 0.765094518661499}, {"content": "Title: Evaluation of the Practicability of a Finger-Stick Whole-Blood SARS-Cov-2 Self-Test Adapted for the General Population. Content: Background COVID-19 (COronaVIrus Disease 2019) is an infectious respiratory disease caused by the novel SARS-CoV-2 virus. Rapid Diagnostic Tests (RDTs) have been developed to detect specific antibodies, IgG and IgM, to SARS-CoV-2 virus in human whole blood and easily usable by the general population are needed in order to alleviate the lockdown that many countries have initiated in response to the growing COVID-19 pandemic. A real-life study has been conducted in order to evaluate the performance of the COVID-PRESTO RDT and the results have been submitted for publication and are currently under review. Even if this test showed very high sensitivity and specificity in a laboratory setting when used by trained professionals, it needs to be further evaluated for practicability when used by common folk in order to be approved by health authorities for in-home use Methods 142 participants were recruited between March 2020 and April 2020 among non-medical populations in central France (nuclear plants workers, individuals attending the Orleans University Hospital vaccination clinic and Orleans University Hospital non-medical staff). Instructions for use with or without a tutorial video was made available to the volunteers. Two separate objectives were pursued: evaluation of the capability of participants to obtain an interpretable result, and evaluation of the users ability to read the results. Results 88.4 % of the test users judged the instruction for use leaflet to be clear and understandable. 99.3 % of the users obtained a valid results and according to the supervisors 92.7% of the tests were properly performed by the user. Overall, 95% of the users gave positive feedback toward the COVID PRESTO as a potential self-test. No influence of age and education was observed. Conclusion COVID-PRESTO was successfully used by an overwhelming majority of participants and its utilization was judged very satisfactory, therefore showing a promising potential as a self-test to be used by the general population. This RDT can become an easy-to-use tool to help know whether individuals are protected or not, particularly in the perspective of a second wave or a mass vaccination program.", "qid": 6, "docid": "nhgc6wcg", "rank": 35, "score": 0.7645488977432251}, {"content": "Title: Challenges in Laboratory Diagnosis of the Novel Coronavirus SARS-CoV-2 Content: The recent outbreak of the Coronavirus disease 2019 (COVID-19) has quickly spread worldwide since its discovery in Wuhan city, China in December 2019. A comprehensive strategy, including surveillance, diagnostics, research, clinical treatment, and development of vaccines, is urgently needed to win the battle against COVID-19. The past three unprecedented outbreaks of emerging human coronavirus infections at the beginning of the 21st century have highlighted the importance of readily available, accurate, and rapid diagnostic technologies to contain emerging and re-emerging pandemics. Real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) based assays performed on respiratory specimens remain the gold standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging with high sensitivity and specificity as well. Even though excellent techniques are available for the diagnosis of symptomatic patients with COVID-19 in well-equipped laboratories; critical gaps still remain in screening asymptomatic people who are in the incubation phase of the virus, as well as in the accurate determination of live viral shedding during convalescence to inform decisions for ending isolation. This review article aims to discuss the currently available laboratory methods and surveillance technologies available for the detection of COVID-19, their performance characteristics and highlight the gaps in current diagnostic capacity, and finally, propose potential solutions. We also summarize the specifications of the majority of the available commercial kits (PCR, EIA, and POC) for laboratory diagnosis of COVID-19.", "qid": 6, "docid": "nm8a3jxt", "rank": 36, "score": 0.7643080949783325}, {"content": "Title: Challenges in Laboratory Diagnosis of the Novel Coronavirus SARS-CoV-2. Content: The recent outbreak of the Coronavirus disease 2019 (COVID-19) has quickly spread worldwide since its discovery in Wuhan city, China in December 2019. A comprehensive strategy, including surveillance, diagnostics, research, clinical treatment, and development of vaccines, is urgently needed to win the battle against COVID-19. The past three unprecedented outbreaks of emerging human coronavirus infections at the beginning of the 21st century have highlighted the importance of readily available, accurate, and rapid diagnostic technologies to contain emerging and re-emerging pandemics. Real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) based assays performed on respiratory specimens remain the gold standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging with high sensitivity and specificity as well. Even though excellent techniques are available for the diagnosis of symptomatic patients with COVID-19 in well-equipped laboratories; critical gaps still remain in screening asymptomatic people who are in the incubation phase of the virus, as well as in the accurate determination of live viral shedding during convalescence to inform decisions for ending isolation. This review article aims to discuss the currently available laboratory methods and surveillance technologies available for the detection of COVID-19, their performance characteristics and highlight the gaps in current diagnostic capacity, and finally, propose potential solutions. We also summarize the specifications of the majority of the available commercial kits (PCR, EIA, and POC) for laboratory diagnosis of COVID-19.", "qid": 6, "docid": "h2mloxuh", "rank": 37, "score": 0.7643080949783325}, {"content": "Title: Development of a rapid test kit for SARS-CoV-2: an example of product design Content: We present an example of applying \u2018need-driven\u2019 product design principle to the development of a rapid test kit to detect SARS-COV-2 (COVID-19). The tests are intended for use in the field and, longer term, for home use. They detect whether a subject is currently infected with the virus and is infectious. The urgent need for large numbers of tests in field setting imposes constraints such as short test time and lack of access to specialist equipment, laboratories and skilled technicians to perform the test and interpret results. To meet these needs, an antigen test based on RT-LAMP with colorimetric readout was chosen. Direct use of swab sample with no RNA extraction was explored. After extensive experimental study (reported elsewhere), a rapid test kit has been fabricated to satisfy all design criteria.", "qid": 6, "docid": "5enmq7do", "rank": 38, "score": 0.7642667293548584}, {"content": "Title: Testing for SARS-CoV-2 (COVID-19): a systematic review and clinical guide to molecular and serological in-vitro diagnostic assays Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated Coronavirus disease 2019 (COVID-19) pandemic has demanded rapid upscaling of in-vitro diagnostic assays to enable mass screening and testing of high-risk groups, and simultaneous ascertainment of robust data on past SARS-CoV-2 exposure at an individual and population level. To meet the exponential demand in testing, there has been an accelerated development of both molecular and serological assays across a plethora of platforms. In the present review, we discuss the current literature on these modalities including the nucleic acid amplification tests, direct viral antigen tests and the rapidly expanding laboratory based and point of care serological tests. This suite of complementary tests will inform crucial decisions by healthcare providers and policy makers and understanding their strengths and limitations will be critical to their judicious application for the development of algorithmic approaches to treatment and public health strategies.", "qid": 6, "docid": "8y0v6d2i", "rank": 39, "score": 0.7639265060424805}, {"content": "Title: Rapid detection of novel coronavirus/Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by reverse transcription-loop-mediated isothermal amplification Content: Novel Corona virus/Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 or 2019-nCoV), and the subsequent disease caused by the virus (coronavirus disease 2019 or COVID-19), is an emerging global health concern that requires a rapid diagnostic test. Quantitative reverse transcription PCR (qRT-PCR) is currently the standard for SARS-CoV-2 detection; however, Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) may allow for faster and cheaper field based testing at point-of-risk. The objective of this study was to develop a rapid screening diagnostic test that could be completed in 30-45 minutes. Simulated patient samples were generated by spiking serum, urine, saliva, oropharyngeal swabs, and nasopharyngeal swabs with a portion of the SARS-CoV-2 nucleic sequence. RNA isolated from nasopharyngeal swabs collected from actual COVID-19 patients was also tested. The samples were tested using RT-LAMP as well as by conventional qRT-PCR. Specificity of the RT-LAMP was evaluated by also testing against other related coronaviruses. RT-LAMP specifically detected SARS-CoV-2 in both simulated patient samples and clinical specimens. This test was performed in 30-45 minutes. This approach could be used for monitoring of exposed individuals or potentially aid with screening efforts in the field and potential ports of entry.", "qid": 6, "docid": "e54b5cbs", "rank": 40, "score": 0.7638660669326782}, {"content": "Title: SARS-CoV-2 qRT-PCR Ct value distribution in Japan and possible utility of rapid antigen testing kit Content: The exact pathology of COVID-19 remains mostly unclear, and accurate epidemiological understanding and rapid testing are crucial to overcome this disease. Several types of nucleic acid tests (NAT) have been used in Japan, but information about the viral RNA load, determined by Ct values, of the patients is limited due to the small number of patients tested in each clinical institution and lack of standardization of the testing kits. We have been performing the qRT-PCR tests established by NIID, and the mean Ct value distribution of 62 cases, which are deemed (first-visit) patients, among the total of 88 positive cases tested in a 4-day window of early April, was 24.9 with SD=5.45. Recently approved antigen testing kits were also used in the same samples (62 positives) along with 100 negative cases, and it revealed the positive predictive value of 80.6% and negative predictive value of 100%, with an overall agreement rate of 92.6%. These results indicate that a certain number of patients with lower Ct values, existed in Japan when SARS-CoV-2 virus started to spread. The newly approved rapid antigen testing kit will be a useful tool to identify such populations rapidly.", "qid": 6, "docid": "fyshred0", "rank": 41, "score": 0.7638360261917114}, {"content": "Title: Diagnostic techniques for COVID-19 and new developments Content: COVID-19 pandemic is a serious global health issue today due to the rapid human to human transmission of SARS-CoV-2, a new type of coronavirus that causes fatal pneumonia. SARS -CoV-2 has a faster rate of transmission than other coronaviruses such as SARS and MERS and until now there are no approved specific drugs or vaccines for treatment. Thus, early diagnosis is crucial to prevent the extensive spread of the disease. The reverse transcription-polymerase chain reaction (RT-PCR) is the most routinely used method until now to detect SARS-CoV-2 infections. However, several other faster and accurate assays are being developed for the diagnosis of COVID-19 aiming to control the spread of infection through the identification of patients and immediate isolation. In this review, we will discuss the various detection methods of the SARS-CoV-2 virus including the recent developments in immunological assays, amplification techniques as well as biosensors.", "qid": 6, "docid": "0oak9ggm", "rank": 42, "score": 0.763573169708252}, {"content": "Title: Rapid detection of novel coronavirus/Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by reverse transcription-loop-mediated isothermal amplification Content: Novel Corona virus/Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 or 2019-nCoV), and the subsequent disease caused by the virus (coronavirus disease 2019 or COVID-19), is an emerging global health concern that requires a rapid diagnostic test. Quantitative reverse transcription PCR (qRT-PCR) is currently the standard for SARS-CoV-2 detection; however, Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) may allow for faster and cheaper field based testing at point-of-risk. The objective of this study was to develop a rapid screening diagnostic test that could be completed in 30\u201345 minutes. Simulated patient samples were generated by spiking serum, urine, saliva, oropharyngeal swabs, and nasopharyngeal swabs with a portion of the SARS-CoV-2 nucleic sequence. RNA isolated from nasopharyngeal swabs collected from actual COVID-19 patients was also tested. The samples were tested using RT-LAMP as well as by conventional qRT-PCR. Specificity of the RT-LAMP was evaluated by also testing against other related coronaviruses. RT-LAMP specifically detected SARS-CoV-2 in both simulated patient samples and clinical specimens. This test was performed in 30\u201345 minutes. This approach could be used for monitoring of exposed individuals or potentially aid with screening efforts in the field and potential ports of entry.", "qid": 6, "docid": "dci4jbyd", "rank": 43, "score": 0.7634371519088745}, {"content": "Title: Rapid viral diagnosis and ambulatory management of suspected COVID-19 cases presenting at the infectious diseases referral hospital in Marseille, France, - January 31st to March 1st, 2020: A respiratory virus snapshot Content: BACKGROUND: Rapid virological diagnosis is needed to limit the length of isolation for suspected COVID-19 cases. METHOD: We managed the first 280 patients suspected to have COVID-19 through a rapid care circuit and virological diagnosis in our infectious disease reference hospital in Marseille, France. Rapid viral detection was performed on sputum and nasopharyngeal samples. RESULTS: Over our study period, no SARS-CoV-2 was detected. Results were obtained within approximately 3 h of the arrival of patient samples at the laboratory. Other viral infections were identified in 49% of the patients, with most common pathogens being influenza A and B viruses, rhinovirus, metapneumovirus and common coronaviruses, notably HKU1 and NL63. CONCLUSION: Early recognition of COVID-19 is critical to isolate confirmed cases and prevent further transmission. Early rule-out of COVID-19 allows public health containment measures to be adjusted by reducing the time spent in isolation.", "qid": 6, "docid": "a4dgxtff", "rank": 44, "score": 0.761346161365509}, {"content": "Title: Loop mediated isothermal amplification (LAMP) assays as a rapid diagnostic for COVID-19 Content: Abstract Recently, a novel coronavirus (SARS-CoV-2; coronavirus disease 2019, COVID-19) has emerged, rapidly spreading and severely straining the capacity of the global health community. Many nations are employing combinations of containment and mitigation strategies, where early diagnosis of COVID-19 is vital in controlling illness progression and limiting viral spread within the population. Thus, rapid and accurate methods of early detection are vital to contain COVID-19 and prevent further spread and predicted subsequent infectious waves of viral recurrence in future. Immediately after its initial characterization, Chinese and American Centers for Disease Control and Prevention (CDCs) rapidly employed molecular assays for detection of COVID-19, mostly employing real-time polymerase chain reaction (RT-PCR) methods. However, such methods require specific expensive items of equipment and highly trained analysts, requiring upwards of 4-8 hours to process. These requirements coupled with associated financial pressures may prevent effective deployment of such diagnostic tests. Loop mediated isothermal amplification(LAMP) is method of nucleic acid amplification which exhibits increased sensitivity and specificity are significantly rapid, and do not require expensive reagents or instruments, which aids in cost reduction for coronavirus detection. Studies have shown the successful application of LAMP assays in various forms to detect coronavirus RNA in patient samples, demonstrating that 1-10 copies of viral RNA template per reaction are sufficient for successful detection, \u223c100-fold more sensitive than conventional RT-PCR methods. Importantly, studies have also now demonstrated the effectiveness of LAMP methodology in the detection of SARS-CoV-2 RNA at significantly low levels, particularly following numerous improvements to LAMP assay protocols. We hypothesise that recent advancements in enhanced LAMP protocols assay perhaps represent the best chance for a rapid and robust assay for field diagnosis of COVID-19, without the requirement of specialized equipment and highly trained professionals to interpret results. Herein, we present our arguments with a view to disseminate such findings, to assist the combat of this virus that is proving so devastating. We hope that this strategy could be applied rapidly, and confirmed for viability with clinical samples, before being rolled out for mass-diagnostic testing in these current times.", "qid": 6, "docid": "wimsktta", "rank": 45, "score": 0.7606465816497803}, {"content": "Title: Real-time PCR-based SARS-CoV-2 detection in Canadian laboratories Content: With emergence of pandemic COVID-19, rapid and accurate diagnostic testing is essential. This study compared laboratory-developed tests (LDTs) used for the detection of SARS-CoV-2 in Canadian hospital and public health laboratories, and some commercially available real-time RT-PCR assays. Overall, analytical sensitivities were equivalent between LDTs and most commercially available methods.", "qid": 6, "docid": "kjol6sgh", "rank": 46, "score": 0.7603614330291748}, {"content": "Title: Real-time PCR-based SARS-CoV-2 detection in Canadian Laboratories Content: With emergence of pandemic COVID-19, rapid and accurate diagnostic testing is essential. This study compared laboratory-developed tests (LDTs) used for the detection of SARS-CoV-2 in Canadian hospital and public health laboratories, and some commercially available real-time RT-PCR assays. Overall, analytical sensitivities were equivalent between LDTs and most commercially available methods.", "qid": 6, "docid": "bqbj660w", "rank": 47, "score": 0.7603614330291748}, {"content": "Title: Laboratory Diagnosis of Coronavirus Disease-2019 (COVID-19) Content: The outbreak of Coronavirus Disease-2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has threatened health worldwide. As of the end of 2020, there were nearly 10 million confirmed cases and nearly 5 million deaths associated with COVID-19. Rapid and early laboratory diagnosis of COVID-19 is the main focus of treatment and control. Molecular tests are the basis for confirmation of COVID-19, but serological tests for SARS-CoV-2 are widely available and play an increasingly important role in understanding the epidemiology of the virus and in identifying populations at higher risk for infection. Point-of-care tests have the advantage of rapid, accurate, portable, low cost and non-specific device requirements, which provide great help for disease diagnosis and detection. This review will discuss the performance of different laboratory diagnostic tests and platforms, as well as suitable clinical samples for testing, and related biosafety protection. This review shall guide for the diagnosis of COVID-19 caused by SARS-CoV-2.", "qid": 6, "docid": "yripn8gc", "rank": 48, "score": 0.7602304220199585}, {"content": "Title: Rapid Implementation of a SARS-CoV-2 Diagnostic qRT-PCR Test with Emergency Use Authorization at a Large Academic Safety-Net Hospital Content: Summary The COVID-19 pandemic is a global public health crisis. Significant delays in the rapid development and distribution of diagnostic testing for SARS-CoV-2 infection have prevented adequate public health management of the disease, impacting the timely mapping of viral spread and the conservation of personal protective equipment. Furthermore, vulnerable populations such as those served by Boston Medical Center (BMC), the largest safety net hospital in New England, represent a high-risk group across multiple dimensions, including a higher prevalence of pre-existing conditions and substance use disorders, lower health maintenance, unstable housing, and a propensity for rapid community spread, highlighting the urgent need for expedient and reliable in-house testing. Here, we report the implementation of a SARS-CoV-2 diagnostic RT-PCR assay with rapid turnaround time enabling more informed decisions with personal and public health ramifications. This work provides a blueprint for academic centers and community hospitals lacking capital-intensive automated laboratory machinery to implement in-house testing.", "qid": 6, "docid": "kco85lqn", "rank": 49, "score": 0.7597590684890747}, {"content": "Title: Laboratory Diagnosis of Coronavirus Disease-2019 (COVID-19) Content: Abstract The outbreak of Coronavirus Disease-2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has threatened health worldwide. As of the end of 2020, there were nearly 10 million confirmed cases and nearly 5 million deaths associated with COVID-19. Rapid and early laboratory diagnosis of COVID-19 is the main focus of treatment and control. Molecular tests are the basis for confirmation of COVID-19, but serological tests for SARS-CoV-2 are widely available and play an increasingly important role in understanding the epidemiology of the virus and in identifying populations at higher risk for infection. Point-of-care tests have the advantage of rapid, accurate, portable, low cost and non-specific device requirements, which provide great help for disease diagnosis and detection. This review will discuss the performance of different laboratory diagnostic tests and platforms, as well as suitable clinical samples for testing, and related biosafety protection. This review shall guide for the diagnosis of COVID-19 caused by SARS-CoV-2.", "qid": 6, "docid": "sy91rnse", "rank": 50, "score": 0.7596390843391418}, {"content": "Title: Scarce COVID-19 Testing Capabilities at Urgent Care Centers in States with Greatest Disease Burden Content: As of March 22, 2020, the number of confirmed COVID-19 cases in the U.S. has reached nearly 30,000. While rapid and accessible diagnosis is paramount to monitoring and reducing the spread of disease, COVID-19 testing capabilities across the U.S. remain constrained. For many individuals, urgent care centers (UCCs) may offer the most accessible avenue to be tested. Through a phone survey, we describe the COVID-19 testing capabilities at UCCs and provide a snapshot highlighting the limited COVID-19 testing capabilities at UCCs in states with the greatest disease burden.", "qid": 6, "docid": "600am3mq", "rank": 51, "score": 0.7588701248168945}, {"content": "Title: Triaging moderate COVID-19 and other viral pneumonias from routine blood tests Content: The COVID-19 is sweeping the world with deadly consequences. Its contagious nature and clinical similarity to other pneumonias make separating subjects contracted with COVID-19 and non-COVID-19 viral pneumonia a priority and a challenge. However, COVID-19 testing has been greatly limited by the availability and cost of existing methods, even in developed countries like the US. Intrigued by the wide availability of routine blood tests, we propose to leverage them for COVID-19 testing using the power of machine learning. Two proven-robust machine learning model families, random forests (RFs) and support vector machines (SVMs), are employed to tackle the challenge. Trained on blood data from 208 moderate COVID-19 subjects and 86 subjects with non-COVID-19 moderate viral pneumonia, the best result is obtained in an SVM-based classifier with an accuracy of 84%, a sensitivity of 88%, a specificity of 80%, and a precision of 92%. The results are found explainable from both machine learning and medical perspectives. A privacy-protected web portal is set up to help medical personnel in their practice and the trained models are released for developers to further build other applications. We hope our results can help the world fight this pandemic and welcome clinical verification of our approach on larger populations.", "qid": 6, "docid": "qikmhoo4", "rank": 52, "score": 0.758841872215271}, {"content": "Title: Combining Point-of-Care Diagnostics and Internet of Medical Things (IoMT) to Combat the COVID-19 Pandemic Content: The current standard testing method for screening coronavirus disease 2019 (COVID-19) is through reverse real-time PCR assay (rRT-PCR), a common molecular-based assay that requires an average of four to six hours to provide results [...].", "qid": 6, "docid": "vy0x9hvr", "rank": 53, "score": 0.7581608295440674}, {"content": "Title: Combined point of care nucleic acid and antibody testing for SARS-CoV-2: a prospective cohort study in suspected moderate to severe COVID-19 disease. Content: Abstract Background Rapid COVID-19 diagnosis in hospital is essential for patient management and identification of infectious patients to limit the potential for nosocomial transmission. The diagnosis is complicated by 30-50% of COVID-19 hospital admissions with negative nose/throat swabs negative for SARS-CoV-2 nucleic acid, frequently after the first week of illness when SARS-CoV-2 antibody responses become detectable. We assessed the diagnostic accuracy of combined rapid antibody point of care (POC) and nucleic acid assays for suspected COVID-19 disease in the emergency department. Methods We developed (i) an in vitro neutralization assay using a lentivirus expressing a genome encoding luciferase and pseudotyped with spike protein and (ii) an ELISA test to detect IgG antibodies to nucleocapsid (N) and spike (S) proteins from SARS-CoV-2. We tested two promising candidate lateral flow rapid fingerprick test with bands for IgG and IgM. We then prospectively recruited participants with suspected moderate to severe COVID-19 and tested for SARS-CoV-2 nucleic acid in a combined nasal/throat swab using the standard laboratory RT-PCR and a validated rapid nucleic acid test. Additionally, serum collected at admission was retrospectively tested by in vitro neutralization, ELISA and the candidate POC antibody tests. We determined the sensitivity and specificity of the individual and combined rapid POC diagnostic tests against a composite gold standard of neutralisation and the standard laboratory RT-PCR. Results 45 participants had specimens tested for nucleic acid in nose/throat swabs as well as stored sera for antibodies. Serum neutralisation assay, SARS-CoV-2 Spike IgG ELISA and the POC antibody test results were concordant. Using the composite gold standard, prevalence of COVID-19 disease was 53.3% (24/45). Median age was 73.5 (IQR 54.0-86.5) years in those with COVID-19 disease by our gold standard and 63.0 (IQR 41.0-72.0) years in those without disease. Median duration of symptoms was 7 days (IQR 1-8) in those with infection. The overall sensitivity of rapid NAAT diagnosis was 79.2% (95CI 57.8-92.9%) and 50.0% (11.8-88.2) at days 8-28. Sensitivity and specificity of the combined rapid POC diagnostic tests reached 100% (95CI 85.8-100) and 94.7% (95CI 74.0-99.0) overall. Conclusions Dual point of care SARS-CoV-2 testing can significantly improve diagnostic sensitivity, whilst maintaining high specificity. Rapid combined tests have the potential to transform our management of COVID-19, including inflammatory manifestations where nucleic acid test results are negative. A rapid combined approach will also aid recruitment into clinical trials and in prescribing therapeutics, particularly where potentially harmful immune modulators (including steroids) are used.", "qid": 6, "docid": "2y88gzji", "rank": 54, "score": 0.7576727271080017}, {"content": "Title: COVID-19 Clinical Diagnostics and Testing Technology Content: Given the global nature of the COVID-19 pandemic, the need for disease detection and expanding testing capacity remains a critical priority. This review discusses the technological advances in testing capability and methodology that are currently employed or in development for detecting the novel coronavirus. We describe the current clinical diagnostics and technology, including molecular and serological testing approaches, for SARS-CoV-2 testing as well as address their advantages and limitations. Nucleic acid amplification technology for molecular diagnostics remains the gold standard for virus detection. We highlight alternative molecular detection techniques used for developing novel COVID-19 diagnostics on the horizon. Antibody response against SARS-CoV-2 remains poorly understood and proper validation of serology tests is necessary to demonstrate their accuracy and clinical utility. In order to bring the pandemic under control, we must speed up the development of rapid and widespread testing through improvements in clinical diagnostics and testing technology as well as access to these tools.", "qid": 6, "docid": "afcd4wc9", "rank": 55, "score": 0.75702303647995}, {"content": "Title: Testing for SARS\u2010CoV\u20102: the day the world turned its attention to the clinical laboratory Content: In the last few months, an unprecedented number of laboratory tests for COVID\u201019 have been developed at a remarkable speed. With the rapid adoption of these tests into clinical practice, combined with the widespread publicity they received, questions arose related to the different types of tests, their utility, performance, and regulatory approval status. The aim of this publication is to provide a general landscape of laboratory testing for COVID\u201019 and offer a historical and regulatory perspective associated with them. Specifically, we aim to elaborate on the regulatory complexities of diagnostic testing in the U.S. and its implications to the present outbreak, as well as provide a synopsis of laboratory tests that have been developed for COVID\u201019. We will first address the detection of Sars\u2010Cov\u20102 directly by either nucleic acid amplification tests (NAAT) or by the detection of the viral protein for active infections. Subsequently, we will provide an overview of serological tests that can aid not only in diagnosis but additionally help to identify prior infections and potential immunity.", "qid": 6, "docid": "x7v4y1ru", "rank": 56, "score": 0.7567307949066162}, {"content": "Title: FAST: a Feasible, Accurate and Speedy Test Strategy for COVID-19 Content: As the COVID-19 pandemic continues worldwide, there is an urgent need to detect infected patients as quickly and accurately as possible. Group testing proposed by Technion [2] could improve efficiency greatly. However, the false negative rate (FNR) would be doubled. Using USA as an example, group testing would have over 70,000 false negatives, compared to 35,000 false negatives by individual testing. In this paper, we propose a Flexible, Accurate and Speedy Test (FAST), which is faster and more accurate than any existing tests. FAST first forms small close contact subgroups, e.g. families and friends. It then pools subgroups to form larger groups before RT-PCR test is done. FAST needs a similar number of tests to Technion's method, but could sharply reduce the FNR to a negligible level. Again taking USA as example, FAST reduces the number of false negatives to just 2000 while it is seven times faster than individual testing.", "qid": 6, "docid": "emovh954", "rank": 57, "score": 0.7560842633247375}, {"content": "Title: Ultra-fast one-step RT-PCR protocol for the detection of SARS-CoV-2 Content: The COVID-19 pandemic resulted in lockdowns all over the world thus affecting nearly all aspects of social life and also had a huge impact on global economies. Since vaccines and therapies are still not available for the population, prevention becomes desperately needed. One important aspect for prevention is the identification and subsequent isolation of contagious specimens. The currently used methods for diagnostics are time consuming and also hindered by the limited availability of reagents and reaction costs, thus presenting a bottle neck for prevention of COVID-19 spread. Here, we present a new ultra-fast test method which is ten times faster than conventional diagnostic tests using real time quantitative PCR (RT-qPCR). In addition, this ultra-fast method is easy to handle as well as cost effective. We translated published SARS-CoV-2 testing protocols from the Centers of Disease Control and Prevention (Atlanta, Georgia, USA) and the Charite Berlin (Germany) to the NEXTGENPCR (NGPCR) machine and combined it with a fluorescence-based endpoint measurement. Fluorescence was measured with a commercial blue light scanner. We confirmed the NEXTGENPCR results with commercially available positive controls. In addition, we isolated RNA from SARS-CoV-2 infected patients and achieved similar results to clinical RT-qPCR assays. Here, we could show correlation between the results obtained by NEXTGENPCR and conventional RT-qPCR.", "qid": 6, "docid": "p8rsagx2", "rank": 58, "score": 0.7560469508171082}, {"content": "Title: Evaluation of performance of two SARS-CoV-2 Rapid whole-blood finger-stick IgM-IgGCombined Antibody Tests Content: Background The SARS-CoV-2 virus is responsible for the infectious respiratory disease called COVID-19 (COronaVIrus Disease). In response to the growing COVID-19 pandemic, Rapid Diagnostic Tests (RDTs) have been developed to detect specific antibodies, IgG and IgM, to SARS-CoV-2 virus in human whole blood. We conducted a real-life study to evaluate the performance of two RDTs, COVID-PRESTO and COVID-DUO, compared to the gold standard, RT-PCR. Methods RT-PCR testing of SARS-Cov-2 was performed from nasopharyngeal swab specimens collected in adult patients visiting the infectious disease department at the hospital (Orleans, France). Fingertip whole blood samples taken at different time points after onset of the disease were tested with RDTs. The specificity and sensitivity of the rapid test kits compared to test of reference (RT-PCR) were calculated. Results Among 381 patients with symptoms of COVID-19 who went to the hospital for a diagnostic, 143 patients were RT-PCR negative. Results of test with RDTs were all negative for these patients, indicating a specificity of 100% for both RDTs. In the RT-PCR positive subgroup (n=238), 133 patients were tested with COVID-PRESTO and 129 patients were tested with COVID-DUO (24 patients tested with both). The further the onset of symptoms was from the date of collection, the greater the sensitivity. The sensitivity of COVID-PRESTO test ranged from 10.00% for patients having experienced their 1st symptoms from 0 to 5 days ago to 100% in patients where symptoms had occurred more than 15 days before the date of tests. For COVID-DUO test, the sensitivity ranged from 35.71% [0-5 days] to 100% (> 15 days). Conclusion COVID-PRESTO and DUO RDTs turned out to be very specific (none false positive) and to be sensitive enough after 15 days from onset of symptom. These easy to use IgG/IgM combined test kits are the first ones allowing a screening with capillary blood sample, by typing from a finger prick. These rapid tests are particularly interesting for screening in low resource settings.", "qid": 6, "docid": "85b4lwh3", "rank": 59, "score": 0.755409836769104}, {"content": "Title: The Royal College of Pathologists of Australasia (RCPA) position statement on COVID-19 Content: For the detection of early COVID-19 disease, RCPA supports the use of molecular tests for SARS-CoV-2 and strongly opposes the introduction of COVID-19 IgG/IgM rapid tests for this purpose.", "qid": 6, "docid": "qyp629f6", "rank": 60, "score": 0.7542930841445923}, {"content": "Title: The Royal College of Pathologists of Australasia (RCPA) position statement on COVID-19. Content: For the detection of early COVID-19 disease, RCPA supports the use of molecular tests for SARS-CoV-2 and strongly opposes the introduction of COVID-19 IgG/IgM rapid tests for this purpose.", "qid": 6, "docid": "zzslm90b", "rank": 61, "score": 0.7542930841445923}, {"content": "Title: CONTAIN: An open-source shipping container laboratory optimised for automated COVID-19 diagnostics Content: The COVID-19 pandemic has challenged diagnostic systems globally. Expanding testing capabilities to conduct population-wide screening for COVID-19 requires innovation in diagnostic services at both the molecular and industrial scale. No report to-date has considered the complexity of laboratory infrastructure in conjunction with the available molecular assays to offer a standardised solution to testing. Here we present CONTAIN. A modular biosafety level 2+ laboratory optimised for automated RT-qPCR COVID-19 testing based on a standard 40ft shipping container. Using open-source liquid-handling robots and RNA extraction reagents we demonstrate a reproducible workflow for RT-qPCR COVID-19 testing. With five OT2 liquid handlers, a single CONTAIN unit reaches a maximum daily testing capacity of 2400 tests/day. We validate this workflow for automated RT-qPCR testing, using both synthetic SARS-CoV-2 samples and patient samples from a local NHS hospital. Finally, we discuss the suitability of CONTAIN and its flexibility in a range of diagnostic testing scenarios including high-density urban environments and mobile response units. Visual abstract", "qid": 6, "docid": "yurxs7lj", "rank": 62, "score": 0.754169225692749}, {"content": "Title: Rapid development of COVID-19 rapid diagnostics for low resource settings: accelerating delivery through transparency, responsiveness, and open collaboration Content: In January, Mologic, embarked on a product development pathway for COVID-19 diagnostics focusing on ELISA and rapid diagnostic tests (RDTs), with anticipated funding from Wellcome Trust and DFID. 755 clinical samples from known COVID-19 patients and hospital negative controls were tested on Mologics IgG ELISA. The reported sensitivity on 191 SGUL prospectively enrolled patients was 95% on day 7 or more post diagnosis, and 97% 10 days or more post-diagnosis. A specificity panel comprising 564 samples pre-December 2019 were tested to include most common respiratory pathogens, other types of coronavirus, and flaviviruses. Specificity in this panel was 97%. This is the first in a series of Mologic products for COVID-19, which will be deployed for COVID-19 diagnosis, contact tracing and sero-epidemiological studies to estimate disease burden and transmission with a focus on ensuring access, affordability, and availability to lowest resource settings.", "qid": 6, "docid": "nol2n8fo", "rank": 63, "score": 0.7540189027786255}, {"content": "Title: COVID-19 diagnostics in context Content: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for different types of diagnostics, comparative validation of new tests, faster approval by federal agencies, and rapid production of test kits to meet global demands. In this Perspective, we discuss the utility and challenges of current diagnostics for COVID-19.", "qid": 6, "docid": "rk8pract", "rank": 64, "score": 0.753959596157074}, {"content": "Title: COVID-19 diagnostics in context. Content: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for different types of diagnostics, comparative validation of new tests, faster approval by federal agencies, and rapid production of test kits to meet global demands. In this Perspective, we discuss the utility and challenges of current diagnostics for COVID-19.", "qid": 6, "docid": "n9ju3flv", "rank": 65, "score": 0.753959596157074}, {"content": "Title: A deep dive into testing and management of COVID-19 for Australian high performance and professional sport Content: The purpose of testing for any communicable disease is to support clinicians in the diagnosis and management of individual patients and to describe transmission dynamics. The novel coronavirus is formally named SARS-CoV-2 and the clinical disease state resulting from an infection is known as COVID-19. Control of the COVID-19 pandemic requires clinicians, epidemiologists, and public health officials to utilise the most comprehensive, accurate and timely information available to manage the rapidly evolving COVID-19 environment. High performance sport is a unique context that may look towards comprehensive testing as a means of risk mitigation. Characteristics of the common testing options are discussed including the circumstances where additional testing may be of benefit and considerations for the associated risks. Finally, a review of the available technology that could be considered for use by medical staff at the point of care (PoC) in a high-performance sporting context is included.", "qid": 6, "docid": "na06mkr6", "rank": 66, "score": 0.7537046670913696}, {"content": "Title: COVID-19 paraclinical diagnostic tools: Updates and future trends Content: MOTIVATION: COVID-19 is one of the most widely affecting pandemics. As for many respiratory viruses-caused diseases, diagnosis of COVID-19 relies on two main compartments: clinical and paraclinical diagnostic criteria. Rapid and accurate diagnosis is vital in such a pandemic. On one side, rapidity may enhance management effectiveness, while on the other, coupling efficiency and less costly procedures may permit more effective community-scale management. METHODOLOGY AND MAIN STRUCTURE: In this review, we shed light on the most used and the most validated diagnostic tools. Furthermore, we intend to include few under-development techniques that may be potentially useful in this context. The practical intent of our work is to provide clinicians with a realistic summarized review of the essential elements in the applied paraclinical diagnosis of COVID-19.", "qid": 6, "docid": "wn02cgsh", "rank": 67, "score": 0.7533806562423706}, {"content": "Title: A deep dive into testing and management of COVID-19 for Australian high performance and professional sport Content: Abstract The purpose of testing for any communicable disease is to support clinicians in the diagnosis and management of individual patients and to describe transmission dynamics. The novel coronavirus is formally named SARS-CoV-2 and the clinical disease state resulting from an infection is known as COVID-19. Control of the COVID-19 pandemic requires clinicians, epidemiologists, and public health officials to utilise the most comprehensive, accurate and timely information available to manage the rapidly evolving COVID-19 environment. High performance sport is a unique context that may look towards comprehensive testing as a means of risk mitigation. Characteristics of the common testing options are discussed including the circumstances where additional testing may be of benefit and considerations for the associated risks. Finally, a review of the available technology that could be considered for use by medical staff at the point of care (PoC) in a high-performance sporting context is included.", "qid": 6, "docid": "ofrcauh9", "rank": 68, "score": 0.7530531287193298}, {"content": "Title: Assay Techniques and Test Development for COVID-19 Diagnosis Content: An ongoing theme of the COVID-19 pandemic is the need for widespread availability of accurate and e\ufb03cient diagnostic testing for detection of SARS-CoV-2 and antiviral antibodies in infected individuals. This report describes various assay techniques and tests for COVID-19 diagnosis. Most tests for early detection of SARS-CoV-2 RNA rely on the reverse transcription-polymerase chain reaction, but isothermal nucleic acid ampli\ufb01cation assays, including transcription-mediated ampli\ufb01cation and CRISPR-based methodologies, are promising alternatives. Identi\ufb01cation of individuals who have developed antibodies to the SARS-CoV-2 virus requires serological tests, including enzyme-linked immunosorbent assay (ELISA) and lateral \ufb02ow immunoassay. This report also provides an overview of current development in COVID-19 diagnostic techniques and products to facilitate future improvement and innovation.", "qid": 6, "docid": "d7xq7x5g", "rank": 69, "score": 0.7529429197311401}, {"content": "Title: Analytical Validation of a COVID-19 qRT-PCR Detection Assay Using a 384-well Format and Three Extraction Methods Content: The COVID-19 global pandemic is an unprecedented health emergency. Insufficient access to testing has hampered effective public health interventions and patient care management in a number of countries. Furthermore, the availability of regulatory-cleared reagents has challenged widespread implementation of testing. We rapidly developed a qRT-PCR SARS-CoV-2 detection assay using a 384-well format and tested its analytic performance across multiple nucleic acid extraction kits. Our data shows robust analytic accuracy on residual clinical biospecimens. Limit of detection sensitivity and specificity was confirmed with currently available commercial reagents. Our methods and results provide valuable information for other high-complexity laboratories seeking to develop effective, local, laboratory-developed procedures with high-throughput capability to detect SARS-CoV-2.", "qid": 6, "docid": "ec3egn8o", "rank": 70, "score": 0.7528700828552246}, {"content": "Title: Diagnostic tests for SARS-CoV-2: Implications in head and neck oncology Content: \u2022 Screening is imperative to safeguard patients, practitioners and staff. \u2022 Various tests available for screening and diagnosing patients for SARS-CoV-2. \u2022 Rapid test can be used to screen patients before any surgical intervention. \u2022 Along with testing, clinical features should be corroborated. \u2022 Oral findings might aid in early diagnosis of COVID-19.", "qid": 6, "docid": "w55jdqcf", "rank": 71, "score": 0.7528554201126099}, {"content": "Title: Navigating the Pandemic Response Life Cycle: Molecular Diagnostics and Immunoassays in the Context of COVID-19 Management Content: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To counter COVID-19 spreading, an infrastructure to provide rapid and thorough molecular diagnostics and serology testing is the cornerstone of outbreak and pandemic management. We hereby review the clinical insights with regard to using molecular tests and immunoassays in the context of COVID-19 management life cycle: the preventive phase, the preparedness phase, the response phase and the recovery phase. The spatial and temporal distribution of viral RNA, antigens and antibodies during human infection is summarized to provide a biological foundation for accurate detection of the disease. We shared the lessons learned and the obstacles encountered during real world high-volume screening programs. Clinical needs are discussed to identify existing technology gaps in these tests. Leverage technologies, such as engineered polymerases, isothermal amplification, and direct amplification from complex matrices may improve the productivity of current infrastructure, while emerging technologies like CRISPR diagnostics, visual end point detection, and PCR free methods for nucleic acid sensing may lead to at-home tests. The lessons learned, and innovations spurred from the COVID-19 pandemic could upgrade our global public health infrastructure to better combat potential outbreaks in the future.", "qid": 6, "docid": "kawhus2f", "rank": 72, "score": 0.7518215775489807}, {"content": "Title: Navigating the Pandemic Response Life Cycle: Molecular Diagnostics and Immunoassays in the Context of COVID-19 Management. Content: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To counter COVID-19 spreading, an infrastructure to provide rapid and thorough molecular diagnostics and serology testing is the cornerstone of outbreak and pandemic management. We hereby review the clinical insights with regard to using molecular tests and immunoassays in the context of COVID-19 management life cycle: the preventive phase, the preparedness phase, the response phase and the recovery phase. The spatial and temporal distribution of viral RNA, antigens and antibodies during human infection is summarized to provide a biological foundation for accurate detection of the disease. We shared the lessons learned and the obstacles encountered during real world high-volume screening programs. Clinical needs are discussed to identify existing technology gaps in these tests. Leverage technologies, such as engineered polymerases, isothermal amplification, and direct amplification from complex matrices may improve the productivity of current infrastructure, while emerging technologies like CRISPR diagnostics, visual end point detection, and PCR free methods for nucleic acid sensing may lead to at-home tests. The lessons learned, and innovations spurred from the COVID-19 pandemic could upgrade our global public health infrastructure to better combat potential outbreaks in the future.", "qid": 6, "docid": "6wlbl0wg", "rank": 73, "score": 0.7518215179443359}, {"content": "Title: Development Optimization and Validation of RT-LAMP based COVID-19 Facility in Pakistan Content: The pandemic SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) has created a widespread panic across the globe especially in the developing countries like Pakistan. The lack of resources and technical staff are causing havoc challenges in the detection and prevention of this global outbreak. Therefore, a less expensive and massive screening of suspected individuals for COVID-19 is required. In this study, a user-friendly technique of reverse transcription-loop mediated isothermal amplification (RT-LAMP) was designed and validated to suggest a potential RT-qPCR alternate for rapid testing of COVID-19 suspected individuals. A total of 12 COVID-19 negative and 72 COVID-19 suspected individuals were analyzed. Both RT-qPCR and RT-LAMP assays were performed for all the individuals using open reading frame (ORF 1ab), nucleoprotein (N) and Spike (S) genes. All 12 specimens which were negative using RT-qPCR were also found negative using RT-LAMP assay. Overall 62 out of 72 positive samples (detected using RT-qPCR) were found COVID-19 positive using RT-LAMP assay. Interestingly all samples (45) having Ct values less than 30 showed 100% sensitivity. However, samples with weaker Ct values (i.e., => 35) showed 54% concordance, suggesting potential false negatives or false positives in RT-LAMP or RT-qPCR results, respectively. Overall comparative assessment showed that RT-LAMP assay showed strong sensitivity and specificity and can be used as an alternative strategy for rapid COVID-19 testing. Hence, based on fast processing time, minimal risk of specimens transfer and utilizing available resources, LAMP based detection of COVID-19 is strongly advocated especially for developing countries.", "qid": 6, "docid": "gtvc4c0p", "rank": 74, "score": 0.7515532374382019}, {"content": "Title: Four point-of-care lateral flow immunoassays for diagnosis of COVID-19 and for assessing dynamics of antibody responses to SARS-CoV-2 Content: OBJECTIVES: We aimed to evaluate the role of rapid serological tests in the management of coronavirus disease 2019 (COVID-19) patients. METHODS: This retrospective study enrolled 16 real-time reverse transcription polymerase chain reaction-confirmed symptomatic patients with COVID-19 and 58 COVID-19 negative patients at a medical center in Taiwan over a 3-month period. Serial serum samples were collected and tested for antibody response using four point-of-care (POC) lateral flow immunoassays (LFIA) (ALLTEST 2019-nCoV IgG/IgM Rapid Test, Dynamiker 2019-nCoV IgG/IgM Rapid Test, ASK COVID-19 IgG/IgM Rapid Test, and Wondfo SARS-CoV-2 Antibody Test). Time-dependent detection sensitivity and timeliness of seroconversion were determined and compared between the four POC rapid tests. RESULTS: The overall sensitivity and specificity of the four tests for detecting anti-SARS-CoV-2 antibodies after 3 weeks of symptom onset were 100% and 100%, respectively. There was no significant difference between the rapid tests used for detection of IgM and IgG separately and those used for detection of combined total antibody (mainly IgM/IgG). There was no significant difference between the four POC rapid tests in terms of time required for determining seroconversion of COVID-19. Patients with COVID-19 with pneumonia demonstrated shorter seroconversion time than those without pneumonia. CONCLUSION: Though the POC antibody rapid tests based on LFIA showed reliable performance in the detection of SARS-CoV-2-specific antibodies, the results of these tests should be interpreted and applied appropriately in the context of antibody dynamic of COVID-19 infection. COVID-19 patients complicated with pneumonia exhibited earlier anti-SARS-CoV-2 antibody response than COVID-19 patients without pneumonia.", "qid": 6, "docid": "gplcop2k", "rank": 75, "score": 0.7512408494949341}, {"content": "Title: COVID\u201019 Clinical Diagnostics and Testing Technology Content: Given the global nature of the COVID\u201019 pandemic, the need for disease detection and expanding testing capacity remains a critical priority. This review discusses the technological advances in testing capability and methodology that are currently employed or in development for detecting the novel coronavirus. We describe the current clinical diagnostics and technology, including molecular and serological testing approaches, for SARS\u2010CoV\u20102 testing as well as address their advantages and limitations. Nucleic acid amplification technology for molecular diagnostics remains the gold standard for virus detection. We highlight alternative molecular detection techniques used for developing novel COVID\u201019 diagnostics on the horizon. Antibody response against SARS\u2010CoV\u20102 remains poorly understood and proper validation of serology tests is necessary to demonstrate their accuracy and clinical utility. In order to bring the pandemic under control, we must speed up the development of rapid and widespread testing through improvements in clinical diagnostics and testing technology as well as access to these tools.", "qid": 6, "docid": "5mf1r24m", "rank": 76, "score": 0.7509933710098267}, {"content": "Title: Evaluating the adequacy of Prima Covid-19 IgG/IgM Rapid Test for the assessment of exposure to SARS-CoV-2 virus Content: The outbreak of the SARS-CoV-2 in early 2020 found health authorities worldwide unprepared to control the pandemic. The adoption of accurate, rapid and inexpensive methods to identify infected subjects in the general population is of paramount relevance for the control of the disease. We evaluated one of the available serological tests, the Prima Lab Covid-19 IgG/IgM Rapid Tests, on 739 volunteers. We first assessed the test's reproducibility by administering it twice on the same day on 104 subjects obtaining and overall score of 93 percent. Since the intensity of the color in the test line regions varies depending on the concentration of Covid-19 antibodies in each sample and that the determination of the positivity depends strictly on the subjective assessment by the reader, after excluding the subjects whose color intensity was too tenuous to be deemed unquestionably positive by the reader the reproducibility increased to 96%. The test would not perform properly for 6 subjects for a very limited overall technical failure of 0.83%. For 138 subjects information was available regarding a previous Real Time PCR nasopharyngeal swab test performed elsewhere. The correspondence of positive results between the two tests was 90.58% (125/138). In spite of some limitation owing especially to the choice of a self selected population sample, we conclude that Prima Lab Covid-19 IgG/IgM Rapid Test represents a low-cost, easily applicable and reproducible tool in detecting SARS-Cov-2 diffusion in the general population.", "qid": 6, "docid": "b21myin4", "rank": 77, "score": 0.7505984306335449}, {"content": "Title: Immunochromatographic test for the detection of SARS-CoV-2 in saliva Content: We evaluated the rapid immunochromatographic test for SARS-CoV-2 antigen detection using 16 saliva specimens collected from 6 COVID-19 hospitalized patients, and detected N-antigen in 4 of 7 RT-PCR positive specimens. The POCT antigen test using saliva is highly considered to be a game-changer for COVID-19 diagnosis.", "qid": 6, "docid": "ei5l6n8o", "rank": 78, "score": 0.7503526210784912}, {"content": "Title: Poolkeh Finds the Optimal Pooling Strategy for a Population-wide COVID-19 Testing (Israel, UK, and US as Test Cases) Content: The SARS-CoV-2 pandemic has changed the lifestyle of citizens of the world. In order for decision makers to manage the viral spread of COVID-19 both in the intra-national and the international frontiers, it is essential to operate based on data-driven assessments. It's crucial to do so rapidly and frequently, since the nature of the viral spread grows exponentially and can burst worldwide again. A fast and accurate health status of individuals globally during a pandemic can save many lives and bring life back to a new normal. Herein, we present a data-driven tool to allow decision-makers to assess the spread of the virus among the world population. Our framework allows health agencies to maximize the throughput of COVID-19 tests among the world population by finding the best test pooling that fits the current SIR-D status of the nation.", "qid": 6, "docid": "ecz7e3ai", "rank": 79, "score": 0.7502855062484741}, {"content": "Title: Molecular and Serological Tests for COVID-19. A Comparative Review of SARS-CoV-2 Coronavirus Laboratory and Point-of-Care Diagnostics Content: Validated and accurate laboratory testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a crucial part of the timely management of Coronavirus Disease 2019 (COVID-19) disease, supporting the clinical decision-making process for infection control at the healthcare level and detecting asymptomatic cases. This would facilitate an appropriate treatment, a prompt isolation and consequently deceleration of the pandemic. Various laboratory tests can identify the genetic material of SARS-CoV-2 that causes COVID-19 in specimens, or specific anti-viral antibodies in blood/serum. Due to the current pandemic situation, a development of point-of-care diagnostics (POCD) allows us to substantially accelerate taking clinical decisions and implement strategic planning at the national level of preventative measures. This review summarizes and compares the available POCD and those currently under development, including quantitative reverse transcription PCR (RT-qPCR), serology immunoassays (SIAs) and protein microarray method (PMM) designed for standard and rapid COVID-19 diagnosis.", "qid": 6, "docid": "tb1zsuw4", "rank": 80, "score": 0.7498354911804199}, {"content": "Title: COVID 19 diagnostic multiplicity and its role in community surveillance and control. Content: Diagnosis of persons exposed to/infected with severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is central to controlling the global pandemic of COVID-19. Currently, several diagnostic modalities are available for COVID-19, each with its own pros and cons. Although there is a global consensus to increase the testing capacity, it is also essential to prudently utilize these tests to control the pandemic. In this paper, we have reviewed the current array of diagnostics for SARS-CoV-2, highlighted the gaps in current diagnostic modalities, and their role in community surveillance and control of the pandemic. The different modalities of COVID-19 diagnosis discussed are: clinical and radiological, molecular based (laboratory based and point-of-care), Immunoassay based (ELISA, rapid antigen and antibody detection tests) and digital diagnostics (artificial intelligence based algorithms). The role of rapid antigen/antibody detection tests in community surveillance has also been described here. These tests can be used to identify asymptomatic persons exposed to the virus and in community based seroprevalence surveys to assess the epidemiology of spread of the virus. However, there are few concerns about the accuracy of these tests which needs to evaluated beforehand.", "qid": 6, "docid": "846t2t8g", "rank": 81, "score": 0.7497904300689697}, {"content": "Title: Severe underestimation of COVID-19 case numbers: effect of epidemic growth rate and test restrictions Content: To understand the scope and development of the COVID-19 pandemic, knowledge of the number of infected persons is essential. Often, the number of \"confirmed cases\", which is based on positive RT-PCR test results, is regarded as a reasonable indicator. However, limited COVID-19 test capacities in many countries are restricting the amount of testing that can be done. This can lead to the implementation of testing policies that restrict access to COVID-19 tests, and to testing backlogs and delays. As a result, confirmed case numbers can be significantly lower than the actual number of infections, especially during rapid growth phases of the epidemic. This study examines the quantitative relation between infections and reported confirmed case numbers for two different testing strategies, \"limited\" and \"inclusive\" testing, in relation to the growth rate of the epidemic. The results indicate that confirmed case numbers understate the actual number of infections substantially; during rapid growth phases where the daily growth rate can reach or exceed 30%, as has been seen in many countries, the confirmed case numbers under-report actual infections by up to 50 to 100-fold.", "qid": 6, "docid": "p0rqg7uk", "rank": 82, "score": 0.7495495080947876}, {"content": "Title: Low-Cost and High-Throughput Testing of COVID-19 Viruses and Antibodies via Compressed Sensing: System Concepts and Computational Experiments Content: Coronavirus disease 2019 (COVID-19) is an ongoing pandemic infectious disease outbreak that has significantly harmed and threatened the health and lives of millions or even billions of people. COVID-19 has also negatively impacted the social and economic activities of many countries significantly. With no approved vaccine available at this moment, extensive testing of COVID-19 viruses in people are essential for disease diagnosis, virus spread confinement, contact tracing, and determining right conditions for people to return to normal economic activities. Identifying people who have antibodies for COVID-19 can also help select persons who are suitable for undertaking certain essential activities or returning to workforce. However, the throughputs of current testing technologies for COVID-19 viruses and antibodies are often quite limited, which are not sufficient for dealing with COVID-19 viruses' anticipated fast oscillating waves of spread affecting a significant portion of the earth's population. In this paper, we propose to use compressed sensing (group testing can be seen as a special case of compressed sensing when it is applied to COVID-19 detection) to achieve high-throughput rapid testing of COVID-19 viruses and antibodies, which can potentially provide tens or even more folds of speedup compared with current testing technologies. The proposed compressed sensing system for high-throughput testing can utilize expander graph based compressed sensing matrices developed by us \\cite{Weiyuexpander2007}.", "qid": 6, "docid": "5t38x587", "rank": 83, "score": 0.7484337091445923}, {"content": "Title: Laboratory Testing Methods for Novel Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) Content: Following the first reports of coronavirus disease-19 (COVID-19) by China to the World Health Organization (WHO) on 31st December 2019, more than 4,302,774 novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) cases have been reported by authorities in 212 countries and territories by 12th May 2020. The outbreak and spread of COVID-19 worldwide, highlights the critical need for developing rapid and accurate diagnostic testing methods for emerging human coronavirus (CoV) infections. Testing is crucial to track the spread of disease during a pandemic, and to swiftly permit public health interventions including isolation, quarantine, and appropriate clinical management of afflicted individuals. The key components of viral diagnostic tests are (1) collection of the appropriate sample (blood, nasal swab, and throat swab), (2) availability of the genetic and proteomic sequences of the novel virus for analysis, and (3) rapid and accurate laboratory testing methods. The current gold standard for the molecular diagnosis of SARS-CoV-2 infection is the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for the qualitative and quantitative detection of viral nucleic acids. Other relevant laboratory methods include enzyme-linked immunoassays (EIA) for viral antibody and antigen detection, and serum viral neutralization (SVN) assays for antibody neutralization determination. The challenges faced in developing a diagnostic test for a novel pathogen are the ability to measure low viral loads for early detection, to provide low or no cross-reactivity with other viral strains and to deliver results rapidly. Several point-of-care molecular devices are currently being integrated for fast and accurate diagnosis of SARS-CoV-2 infections. This review discusses the current laboratory methods available to test for coronaviruses by focusing on the present COVID-19 outbreak.", "qid": 6, "docid": "401tisd3", "rank": 84, "score": 0.7481610774993896}, {"content": "Title: Types of Assays for SARS-CoV-2 Testing: A Review Content: Clinical laboratory testing routinely provides actionable results, which help direct patient care in the inpatient and outpatient settings. Since December 2019, a novel coronavirus (SARS-CoV-2) has been causing disease (COVID-19 [coronavirus disease 2019]) in patients, beginning in China and now extending worldwide. In this context of a novel viral pandemic, clinical laboratories have developed multiple novel assays for SARS-CoV-2 diagnosis and for managing patients afflicted with this illness. These include molecular and serologic-based tests, some with point-of-care testing capabilities. Herein, we present an overview of the types of testing available for managing patients with COVID-19, as well as for screening of potential plasma donors who have recovered from COVID-19.", "qid": 6, "docid": "qexn0nuy", "rank": 85, "score": 0.7473170757293701}, {"content": "Title: Types of Assays for SARS-CoV-2 Testing: A Review. Content: Clinical laboratory testing routinely provides actionable results, which help direct patient care in the inpatient and outpatient settings. Since December 2019, a novel coronavirus (SARS-CoV-2) has been causing disease (COVID-19 [coronavirus disease 2019]) in patients, beginning in China and now extending worldwide. In this context of a novel viral pandemic, clinical laboratories have developed multiple novel assays for SARS-CoV-2 diagnosis and for managing patients afflicted with this illness. These include molecular and serologic-based tests, some with point-of-care testing capabilities. Herein, we present an overview of the types of testing available for managing patients with COVID-19, as well as for screening of potential plasma donors who have recovered from COVID-19.", "qid": 6, "docid": "zyrzfm40", "rank": 86, "score": 0.7473170757293701}, {"content": "Title: COVID 19 diagnostic multiplicity and its role in community surveillance and control Content: Diagnosis of persons exposed to/infected with severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is central to controlling the global pandemic of COVID-19 Currently, several diagnostic modalities are available for COVID-19, each with its own pros and cons Although there is a global consensus to increase the testing capacity, it is also essential to prudently utilize these tests to control the pandemic In this paper, we have reviewed the current array of diagnostics for SARS-CoV-2, highlighted the gaps in current diagnostic modalities, and their role in community surveillance and control of the pandemic The different modalities of COVID-19 diagnosis discussed are: clinical and radiological, molecular based (laboratory based and point-of-care), Immunoassay based (ELISA, rapid antigen and antibody detection tests) and digital diagnostics (artificial intelligence based algorithms) The role of rapid antigen/antibody detection tests in community surveillance has also been described here These tests can be used to identify asymptomatic persons exposed to the virus and in community based seroprevalence surveys to assess the epidemiology of spread of the virus However, there are few concerns about the accuracy of these tests which needs to evaluated beforehand", "qid": 6, "docid": "kuk0scmr", "rank": 87, "score": 0.7469984292984009}, {"content": "Title: A mathematical study on the spread of COVID-19 considering social distancing and rapid assessment : The case of Jakarta, Indonesia Content: The aim of this study is to investigate the effects of rapid testing and social distancing in controlling the spread of COVID-19, particularly in the city of Jakarta, Indonesia. We formulate a modified susceptible exposed infectious recovered compartmental model considering asymptomatic individuals. Rapid testing is intended to trace the existence of asymptomatic infected individuals among the population. This asymptomatic class is categorized into two subclasses: detected and undetected asymptomatic individuals. Furthermore, the model considers the limitations of medical resources to treat an infected individual in a hospital. The model shows two types of equilibrium point: COVID-19 free and COVID-19 endemic. The COVID-19-free equilibrium point is locally and asymptotically stable if the basic reproduction number [Formula: see text] is less than unity. In contrast, COVID-19-endemic equilibrium always exists when [Formula: see text]. The model can also show a backward bifurcation at [Formula: see text] whenever the treatment saturation parameter, which describes the hospital capacity, is larger than a specific threshold. To justify the model parameters, we use the incidence data from the city of Jakarta, Indonesia. The data pertain to infected individuals who self-isolate in their homes and visit the hospital for further treatment. Our numerical experiments indicate that strict social distancing has the potential to succeed in reducing and delaying the time of an outbreak. However, if the strict social distancing policy is relaxed, a massive rapid-test intervention should be conducted to avoid a large-scale outbreak in the future.", "qid": 6, "docid": "srpgcy4b", "rank": 88, "score": 0.7469701766967773}, {"content": "Title: Clinical evaluation of self-collected saliva by RT-qPCR, direct RT-qPCR, RT-LAMP, and a rapid antigen test to diagnose COVID-19 Content: Background The clinical performance of six molecular diagnostic tests and a rapid antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were clinically evaluated for the diagnosis of coronavirus disease 2019 (COVID-19) in self-collected saliva. Methods Saliva samples from 103 patients with laboratory-confirmed COVID-19 (15 asymptomatic and 88 symptomatic) were collected on the day of hospital admission. SARS-CoV-2 RNA in saliva was detected using a quantitative reverse-transcription polymerase chain reaction (RT-qPCR) laboratory-developed test (LDT), a cobas SARS-CoV-2 high-throughput system, three direct RT-qPCR kits, and reverse-transcription loop mediated isothermal amplification (RT-LAMP). Viral antigen was detected by a rapid antigen immunochromatographic assay. Results Of the 103 samples, viral RNA was detected in 50.5-81.6% of the specimens by molecular diagnostic tests and an antigen was detected in 11.7% of the specimens by the rapid antigen test. Viral RNA was detected at a significantly higher percentage (65.6-93.4%) in specimens collected within 9 d of symptom onset compared to that of specimens collected after at least 10 d of symptom onset (22.2-66.7%) and that of asymptomatic patients (40.0-66.7%). Viral RNA was more frequently detected in saliva from males than females. Conclusions Self-collected saliva is an alternative specimen diagnosing COVID-19. LDT RT-qPCR, cobas SARS-CoV-2 high-throughput system, direct RT-qPCR except for one commercial kit, and RT-LAMP showed sufficient sensitivity in clinical use to be selectively used according to clinical settings and facilities. The rapid antigen test alone is not recommended for initial COVID-19 diagnosis because of its low sensitivity.", "qid": 6, "docid": "tnnhx51r", "rank": 89, "score": 0.7469548583030701}, {"content": "Title: The role of testing in infectious disease control: A case of COVID-19 in Africa Content: The dramatic increase in COVID-19 suspected cases in Africa has placed enormous burden on public and private clinical facilities. Till date, the most commonly used method for the identification and confirmation of the virus is the laboratory-based reverse transcription-polymerase chain reaction (RT-PCR) testing. Unfortunately, testing capacities have been limited in many parts of Africa because of inadequate test kits which have restricted scaling up beyond the few public health laboratories at designated locations. We present in this mini-review Africa's preparedness and readiness toward testing, why testing is crucial, the need to immediately strengthen existing facilities and what it involves as combined approaches for managing the COVID-19 crisis. The review highlights the urgent need for speedy expansion and distribution of several laboratory testing platforms to public health facilities and fully accredited private clinical laboratories, including real-time PCR and serological assays.", "qid": 6, "docid": "go8lly5h", "rank": 90, "score": 0.7468639612197876}, {"content": "Title: On Accelerated Testing for COVID-19 Using Group Testing Content: COVID-19 has resulted in a global health crisis that may become even more acute over the upcoming months. One of the main reasons behind the current rapid growth of COVID-19 in the U.S. population is the limited availability of testing kits and the relatively-high cost of screening tests. In this draft, we demonstrate the effectiveness of group testing (pooling) ideas to accelerate testing for COVID-19. This draft is semi-tutorial in nature and is written for a broad audience with interest in mathematical formulations relevant to COVID-19 testing. Therefore, ideas are presented through illustrative examples rather than through purely theoretical formulations. The focus is also on pools of size less than 64 such as what is practical with current RT-PCR technology.", "qid": 6, "docid": "m8n2p55z", "rank": 91, "score": 0.7466535568237305}, {"content": "Title: Prevalence of IgG and IgM antibodies to SARS-CoV-2 among clinic staff and patients Content: The coronavirus disease 2019 (COVID-19) is now a pandemic with devastating social and economic consequences. The extent of the spread of COVID-19 within populations is uncertain since diagnostic tests have not been carried out on all eligible persons and doing such diagnostic tests on everyone is much less feasible in developing countries such as Nigeria. Tests for antibodies to SARS-CoV-2, the virus that causes COVID-19, are more affordable, readily available, and require minimal training than current diagnostic tests. Employing a seroepidemiological strategy, serological tests were conducted on 66 volunteering staff and patients at the University of Calabar Teaching Hospital (UCTH), a Federal Government owned tertiary healthcare facility, to determine the extent of exposure to SARS-CoV-2, from 17th to 25th June 2020. Using a COVID-19 IgG/IgM Rapid Test Cassette with emergency use authorization (EUA) from the Food and Drug Administration (FDA) of the United States, it was observed that of the 66 samples tested, 5 (7.6%) were both IgG and IgM positive and 17 (26%) were IgG positive. Moreover, for 44 of the 66 participants, simultaneous tests were carried out using a rapid test kit from a different manufacturer but without FDA-EUA and all the results completely matched with the FDA-EUA kit, except one case where the FDA-EUA kit showed positive for both IgG and IgM while the other kit was positive only for IgM. The 26% positive IgG indicates a high exposure rate for the hospital staff and patients and points to community transmission where the facility is situated. Hence, immediate activation of WHO guidelines for controlling community transmission is called for. These results can further serve as a pilot study to guide public health policies in response to COVID-19 pandemic in both the general population and in healthcare settings.", "qid": 6, "docid": "3s6ytfkk", "rank": 92, "score": 0.7465640306472778}, {"content": "Title: Fighting COVID-19: Integrated Micro- and Nanosystems for Viral Infection Diagnostics Content: The pandemic of coronavirus disease 2019 (COVID-19) highlights the importance of rapid and sensitive diagnostics of viral infection that enables the efficient tracing of cases and the implementation of public health measures for disease containment. The immediate actions from both academia and industry have led to the development of many COVID-19 diagnostic systems that have secured fast-track regulatory approvals and have been serving our healthcare frontlines since the early stage of the pandemic. On diagnostic technologies, many of these clinically validated systems have significantly benefited from the recent advances in micro- and nanotechnologies in terms of platform design, analytical method, and system integration and miniaturization. The continued development of new diagnostic platforms integrating micro- and nanocomponents will address some of the shortcomings we have witnessed in the existing COVID-19 diagnostic systems. This Perspective reviews the previous and ongoing research efforts on developing integrated micro- and nanosystems for nucleic acid-based virus detection, and highlights promising technologies that could provide better solutions for the diagnosis of COVID-19 and other viral infectious diseases. With the summary and outlook of this rapidly evolving research field, we hope to inspire more research and development activities to better prepare our society for future public health crises.", "qid": 6, "docid": "7v6rj65a", "rank": 93, "score": 0.7464783191680908}, {"content": "Title: Promising methods for detection of novel coronavirus SARS\u2010CoV\u20102 Content: A very recent outbreak of the novel coronavirus, COVID\u201019, in the city of Wuhan, China, in December 2019 and its subsequent spread within and across China have resulted in several deaths and infections. Presently, nucleic acid amplification test is essential for the confirmation of COVID infection. In this report, we summarized the six promising methods, including whole\u2010genome sequencing, real\u2010time reverse transcription polymerase chain reaction, nanopore target sequencing, antibody\u2010based immunoassay techniques, use of paper\u2010based biomolecular sensors, and the clustered regularly interspaced short palindromic repeats\u2010Cas system\u2010based technology, which can also be deployed for the detection of SARS\u2010CoV\u20102. We further introduced the principles of these methods, discussed the scope and practicability of application of the available products and methods, and highlighted the potential approaches to develop additional products and techniques for early diagnosis of COVID\u201019.", "qid": 6, "docid": "c3a4bh4i", "rank": 94, "score": 0.745568037033081}, {"content": "Title: Increasing testing throughput and case detection with a pooled-sample Bayesian approach in the context of COVID-19 Content: Rapid and widespread implementation of infectious disease surveillance is a critical component in the response to novel health threats. Molecular assays are the preferred method to detect a broad range of pathogens with high sensitivity and specificity. The implementation of molecular assay testing in a rapidly evolving public health emergency can be hindered by resource availability or technical constraints. In the context of the COVID-19 pandemic, the applicability of a pooled-sample testing protocol to screen large populations more rapidly and with limited resources is discussed. A Bayesian inference analysis in which hierarchical testing stages can have different sensitivities is implemented and benchmarked against early COVID-19 testing data. Optimal pool size and increases in throughput and case detection are calculated as a function of disease prevalence. Even for moderate losses in test sensitivity upon pooling, substantial increases in testing throughput and detection efficiency are predicted, suggesting that sample pooling is a viable avenue to circumvent current testing bottlenecks for COVID-19.", "qid": 6, "docid": "si1yyg5e", "rank": 95, "score": 0.7455403804779053}, {"content": "Title: Detection of COVID-19 Infection from Routine Blood Exams with Machine Learning: a Feasibility Study Content: Background - The COVID-19 pandemia due to the SARS-CoV-2 coronavirus, in its first 4 months since its outbreak, has to date reached more than 200 countries worldwide with more than 2 million confirmed cases (probably a much higher number of infected), and almost 200,000 deaths. Amplification of viral RNA by (real time) reverse transcription polymerase chain reaction (rRT-PCR) is the current gold standard test for confirmation of infection, although it presents known shortcomings: long turnaround times (3-4 hours to generate results), potential shortage of reagents, false-negative rates as large as 15-20%, the need for certified laboratories, expensive equipment and trained personnel. Thus there is a need for alternative, faster, less expensive and more accessible tests. Material and methods - We developed two machine learning classification models using hematochemical values from routine blood exams (namely: white blood cells counts, and the platelets, CRP, AST, ALT, GGT, ALP, LDH plasma levels) drawn from 279 patients who, after being admitted to the San Raffaele Hospital (Milan, Italy) emergency-room with COVID-19 symptoms, were screened with the rRT-PCR test performed on respiratory tract specimens. Of these patients, 177 resulted positive, whereas 102 received a negative response. Results - We have developed two machine learning models, to discriminate between patients who are either positive or negative to the SARS-CoV-2: their accuracy ranges between 82% and 86%, and sensitivity between 92% e 95%, so comparably well with respect to the gold standard. We also developed an interpretable Decision Tree model as a simple decision aid for clinician interpreting blood tests (even off-line) for COVID-19 suspect cases. Discussion - This study demonstrated the feasibility and clinical soundness of using blood tests analysis and machine learning as an alternative to rRT-PCR for identifying COVID-19 positive patients. This is especially useful in those countries, like developing ones, suffering from shortages of rRT-PCR reagents and specialized laboratories. We made available a Web-based tool for clinical reference and evaluation. This tool is available at https://covid19-blood-ml.herokuapp.com.", "qid": 6, "docid": "mlitd45q", "rank": 96, "score": 0.7452171444892883}, {"content": "Title: Fast SARS-CoV-2 detection by RT-qPCR in preheated nasopharyngeal swab samples Content: OBJECTIVES: The gold-standard COVID-19 diagnosis relies on detecting SARS-CoV-2 using RNA purification and one-step retrotranscription and quantitative PCR (RT-qPCR). Based on the urgent need for high-throughput screening, we tested the performance of three alternative, simple and affordable protocols to rapidly detect SARS-CoV-2, bypassing the long and tedious RNA extraction step and reducing the time to viral detection. METHODS: We evaluated three methods based on direct nasopharyngeal swab viral transmission medium (VTM) heating before the RT-qPCR: a) direct without additives; b) in a formamide-EDTA (FAE) buffer, c) in a RNAsnapTM buffer. RESULTS: Although with a delay in cycle threshold compared to the gold-standard, we found consistent results in nasopharyngeal swab samples that were subject to a direct 70\u00b0C incubation for 10 min. CONCLUSIONS: Our findings provide valuable options to overcome any supply chain issue and help to increase the throughput of diagnostic tests, thereby complementing standard diagnosis.", "qid": 6, "docid": "uv06nfvz", "rank": 97, "score": 0.7451074123382568}, {"content": "Title: Clinical Testing For Covid-19 Content: Abstract As the novel coronavirus SARS-CoV-2 caused COVID-19 cases in the United States the initial test was developed and performed at the Center for Disease Control (CDC). As the number of cases increased the demand for tests multiplied, leading the CDC to utilize the Emergency Utilization Authorization to allow clinical and commercial laboratories to develop tests to detect the presence of the virus. Many nucleic acid tests based on reverse transcriptase-polymerase chain reaction (RT-PCR) were developed, each with different techniques, specifications and turnaround time. As the illnesses turned into a pandemic, testing became more crucial. The test supply became inadequate to meet the need that it had to be prioritized according to guidance. For surveillance, the need for serologic tests emerged. Here we review the timeline of test development, the turn-around times, the various approved tests and compare them as regards the genes they detect. We concentrate on the point-of-care tests and discuss the basis for new serologic tests. We discuss the testing guidance for prioritization and their application in a hospital setting. As SARS-CoV-2 virus arrived in the USA causing the COVID-19 illness, one of the most talked about issues in the management of the disease and the resulting pandemic has been clinical testing. A unique situation arose of a communicable and highly contagious disease necessitating the rapid diagnosis of patients and the identification of non-symptomatic infected persons. Unfortunately, the USA did not have a Food and Drug Administration (FDA) approved laboratory test for the illness. The FDA ultimately utilized its Emergency Use Authorizations (EUA) on February 4, 2020 to allow for more rapid and widespread development and implementation of in-vitro testing.1 Indeed, companies and organizations utilized the EUA to file applications for new tests based on different methodologies, amounting to 48 applications in the span of 3 months from the beginning of February to the end of April 2020. In addition, multiple other tests were put in place under a separate authorization by a Presidential memorandum in early March allowing laboratories that carry Clinical Laboratory Improvement Amendment (CLIA) certification to put tests in place without an EUA from the FDA. This created an unprecedented situation where the medical community and the public may not be familiar with the various new tests for COVID-19 that are offered to patients and hospitals. The purpose of this review is to provide information, up-to-date as of the date of submission of the manuscript to the journal, on the various tests that have been developed, their scientific basis and their interpretation. We give a real-world example demonstrating the time lag in the return of test results and review testing prioritization guidance since the supply of tests remains below the perceived need.", "qid": 6, "docid": "isswwnzn", "rank": 98, "score": 0.7449062466621399}, {"content": "Title: Testing times in Coronavirus disease (Covid-19): A tale of two nations Content: The Coronavirus Disease (Covid-19) pandemic is caused by the severe acute respiratory syndrome virus 2 and was first identified in Wuhan, China, in December 2019. The disease spread globally, leading to the World Health Organization declaring it a pandemic in March 2020. The condition is often fatal in its severe form. As it is a previously unknown virus, no treatment is identified or any vaccine available. The burden of disease control and containment, therefore, falls upon a robust and geographically appropriate testing strategy. Testing policies are modified, in turn, by the rapidly evolving patterns of the disease in various nations and by the evolving nature of tests in development. It is, therefore, helpful to study different national models to learn from the experience of different countries. This article compares testing strategies in the UK and India as the two countries travel different paths in controlling the pandemic. The UK is one of the most severely affected countries in the world. Initially restricted to hospitalised patients, the UK has broadened the scope of testing to many categories of individuals. In contrast, India appears to have a lower prevalence of the infection. However, the large Indian population and relatively insufficient testing capacities so far have led India to adopt a different testing trajectory, with the testing currently focused on high-risk groups in the community and hospitals. Owing to the rapidly changing nature of the disease, there can be no \u2018one-size-fits-all\u2019 policy but should be based on country-specific circumstances.", "qid": 6, "docid": "03z7tarm", "rank": 99, "score": 0.744617223739624}, {"content": "Title: Field-deployable, rapid diagnostic testing of saliva samples for SARS-CoV-2. Content: Abstract Rapid, scalable, point-of-need, COVID-19 diagnostic testing is necessary to safely re-open economies and prevent future outbreaks. We developed an assay that detects single copies of SARS-CoV-2 virus directly from saliva and swab samples in 30 min using a simple, one-step protocol that utilizes only a heat block and microcentrifuge tube prefilled with a mixture containing the necessary reagents and has a sensitivity and specificity of 97% and 100%, respectively.", "qid": 6, "docid": "8vp57c1o", "rank": 100, "score": 0.7444875240325928}]}
{"query": "are there serological tests that detect antibodies to coronavirus?", "hits": [{"content": "Title: Seroepidemiologic Study Designs for Determining SARS-COV-2 Transmission and Immunity Content: Serologic studies are crucial for clarifying dynamics of the coronavirus disease pandemic. Past work on serologic studies (e.g., during influenza pandemics) has made relevant contributions, but specific conditions of the current situation require adaptation. Although detection of antibodies to measure exposure, immunity, or both seems straightforward conceptually, numerous challenges exist in terms of sample collection, what the presence of antibodies actually means, and appropriate analysis and interpretation to account for test accuracy and sampling biases. Successful deployment of serologic studies depends on type and performance of serologic tests, population studied, use of adequate study designs, and appropriate analysis and interpretation of data. We highlight key questions that serologic studies can help answer at different times, review strengths and limitations of different assay types and study designs, and discuss methods for rapid sharing and analysis of serologic data to determine global transmission of severe acute respiratory syndrome coronavirus 2.", "qid": 7, "docid": "rgls0xgn", "rank": 1, "score": 0.8060368895530701}, {"content": "Title: Seroepidemiologic Study Designs for Determining SARS-COV-2 Transmission and Immunity. Content: Serologic studies are crucial for clarifying dynamics of the coronavirus disease pandemic. Past work on serologic studies (e.g., during influenza pandemics) has made relevant contributions, but specific conditions of the current situation require adaptation. Although detection of antibodies to measure exposure, immunity, or both seems straightforward conceptually, numerous challenges exist in terms of sample collection, what the presence of antibodies actually means, and appropriate analysis and interpretation to account for test accuracy and sampling biases. Successful deployment of serologic studies depends on type and performance of serologic tests, population studied, use of adequate study designs, and appropriate analysis and interpretation of data. We highlight key questions that serologic studies can help answer at different times, review strengths and limitations of different assay types and study designs, and discuss methods for rapid sharing and analysis of serologic data to determine global transmission of severe acute respiratory syndrome coronavirus 2.", "qid": 7, "docid": "91pb9nq3", "rank": 2, "score": 0.8060368895530701}, {"content": "Title: Prevalence of antibody to human coronaviruses 229E, OC43 and neonatal calf diarrhea coronavirus (NCDCV) in patients of Northern Italy Content: A seroepidemiological study for detection of antibody to human coronaviruses OC43, 229E, and neonatal calf diarrhea coronavirus (NCDCV), has been carried out using sera collected from hospitalized patients or healthy persons through routine laboratory tests in Northern Italy. Patients tested were children and adults with different pathological diseases. Antibody detection was performed by using an indirect immunoperoxidase staining technique (for all viruses) and, in the case of OC43 and NCDCV, antibody detection was obtained even with a hemagglutination inhibition test and a plaque reduction neutralization assay. Results obtained show a significant difference in the prevalence of antibody to 229E between children and adult group. Furthermore, a different titer was observed, within the two groups, between patients affected by hematological diseases (leukemia) and patients with other diseases. Finally, our data seem to confirm previous studies reporting a very high prevalence of antibody to coronavirus OC43 but a less detectable seropositivity to coronavirus 229E.", "qid": 7, "docid": "576xiuz8", "rank": 3, "score": 0.8002779483795166}, {"content": "Title: Coronavirus antibody detection in cats by computer-assisted kinetics-based enzyme-linked immunosorbent assay (KELA): field studies. Content: A total of 2238 feline serum samples submitted to the New York State Diagnostic Laboratory over a 1-year period were tested for the presence of coronavirus antibodies, using the computer-assisted, kinetics-based enzyme-linked immunosorbent assay (KELA). Cats from which sera were obtained were categorized by sex, age, breed, and disease status, and variations in mean antibody titers for different sub-classifications within each category were analyzed by computerized statistical analysis. As expected, higher mean antibody titers were recorded for cats with feline infectious peritonitis, and for cats with a recent history of possible coronavirus exposure. However, an unexpected inverse relationship between coronavirus antibody titer and age was also found. Certain cattery-oriented pure breeds appeared to have higher mean antibody titers, because their sample populations contained a higher percentage of younger cats and cats of unknown age-groups which, over-all, had higher mean titers. Taken together, the data substantiated the efficacy of the computer-assisted KELA for routine detection of serum coronavirus antibodies in cats.", "qid": 7, "docid": "il7x4l4u", "rank": 4, "score": 0.7932995557785034}, {"content": "Title: Reliability of serological tests for COVID-19: Comparison of three immunochromatography test kits for SARS-CoV-2 antibodies. Content: Background: Several immunochromatographic serological test kits have been developed to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies, but their relative performance and potential clinical utility is unclear. Methods: Three commercially available serological test kits were evaluated using 99 serum samples collected from 29 patients diagnosed with coronavirus disease 2019 (COVID-19). Results: The IgM antibody-positive rates of the three serological test kits for samples taken at the early stage of the disease (0-6 days after onset) were 19.0%, 23.8%, and 19.0%, respectively. The IgM antibody-positive rates over the entire period were 21.2%, 60.6%, and 15.2%, respectively. The IgG antibody-positive rates for samples taken after 13 days of onset were 100.0%, 97.6%, and 97.6%, respectively. Conclusion: There were large differences among the results of the three test kits. Only few cases showed positive results for IgM in the early stage of disease and the IgM antibody-positive rates over the entire period were low, suggesting that the kits used in this study were unsuitable for diagnosis of COVID-19. The IgG antibody was positive in almost all samples after 13 days of onset, suggesting that it may be useful for determining infections in the recent past.", "qid": 7, "docid": "fn9t38as", "rank": 5, "score": 0.7870568633079529}, {"content": "Title: Prevalence of coronavirus antibodies in rabbits. Content: Antibodies to coronavirus were detected by an indirect fluorescent antibody test in rabbit sera from six rabbitries. The prevalence ranged from 3 to 40% in different rabbitries and most seropositive rabbits were more than 4 months old. A rabbitry with high prevalence of antibodies and high incidence of diarrhea could serve as a source of virus and aid in studying the natural history of coronavirus infection in rabbits.", "qid": 7, "docid": "hn69l5mq", "rank": 6, "score": 0.7865350842475891}, {"content": "Title: SEROEPIDEMIOLOGIC STUDIES OF CORONAVIRUS INFECTION IN ADULTS AND CHILDREN(1) Content: McIntosh, K. A. Z. Kapikian, H. C Turner, J. W. Hartley, R. H. Parrott and R. M. Chanock. (Lab. of Infectious Diseases, NIAID, NIH, Bethesda, Md. 20014) Sero-epidemiologic studies of coronavirus infection in adults and children. Amer. J. Epid., 1970, 97: 585\u2013592-A seroepidemiologic study of infection by coronavirus strains 229E, OC38, OC43, and mouse hepatitis virus (MHV) strain A-59, is described. In adults with upper respiratory disease, two \u201coutbreaks\u201d of coronavirus infection occurred, one during the winter of 1965\u20131966 associated with complement fixing (CF) antibody responses to OC38, OC43 and MHV, and the other during the following winter associated with CF antibody responses to 229E. In hospitalized children, infection with 229E was rare; infection with OC38, OC43, and MHV occurred less often in hospitalized children with lower respiratory tract disease (3.5%) than in a control group with non-respiratory tract disease (8.2%). The limitations of the CF test using available coronavirus antigens are discussed.", "qid": 7, "docid": "dlmzcl9g", "rank": 7, "score": 0.786200761795044}, {"content": "Title: SEROEPIDEMIOLOGIC SURVEY OF CORONAVIRUS (STRAIN 229E) INFECTIONS IN A POPULATION OF CHILDREN Content: The indirect hemagglutination (IHA) test for coronavirus 229E antibodies was used for serodiagnostic and seroepidemiologic studies in a population of children. Subjects ranged in age from 5 to 19 years and lived in a home which participated in a longitudinal surveillance of respiratory illness (1960\u20131968). During this period 1477 respiratory illnesses were observed; 63 (4%) were associated with sero-response (fourfold or greater antibody rises) to 229E. An additional 105 sero-responses were associated with unreported or subclinical illness. The frequency of these infections was cyclical, and 229E and coronavirus OC 43 infections peaked in different years among the same population. Sero-responses occurred mainly in the fall, winter and spring quarters. Preexisting antibody was demonstrated in one-third of the children with 229E seroresponses. Clinical studies indicated that the most frequent complaints with 229E infections were sore throat, coryza and cough, and the most frequent findings were pharyngeal injection, coryza and fever.", "qid": 7, "docid": "5c944qki", "rank": 8, "score": 0.7851212620735168}, {"content": "Title: Review of Current Advances in Serologic Testing for COVID-19 Content: OBJECTIVES: To examine and summarize the current literature on serologic methods for the detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: A literature review was performed using searches in databases including PubMed, medRxiv, and bioRxiv. Thirty-two peer-reviewed papers and 23 preprints were examined. RESULTS: The studies included lateral flow immunoassay, enzyme-linked immunosorbent assay, chemiluminescence immunoassay, and neutralizing antibody assays. The use of all major SARS-CoV-2 antigens was demonstrated to have diagnostic value. Assays measuring total antibody reactivity had the highest sensitivity. In addition, all the methods provided opportunities to characterize the humoral immune response by isotype. The combined use of IgM and IgG detection resulted in a higher sensitivity than that observed when detecting either isotype alone. Although IgA was rarely studied, it was also demonstrated to be a sensitive marker of infection, and levels correlated with disease severity and neutralizing activity. CONCLUSIONS: The use of serologic testing, in conjunction with reverse transcription polymerase chain reaction testing, was demonstrated to significantly increase the sensitivity of detection of patients infected with SARS-CoV-2. There was conflicting evidence regarding whether antibody titers correlated with clinical severity. However, preliminary investigations indicated some immunoassays may be a surrogate for the prediction of neutralizing antibody titers and the selection of recovered patients for convalescent serum donation.", "qid": 7, "docid": "77rcr30x", "rank": 9, "score": 0.7848708629608154}, {"content": "Title: Serodiagnostics for Severe Acute Respiratory Syndrome-Related Coronavirus-2: A Narrative Review Content: Accurate serologic tests to detect host antibodies to severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) will be critical for the public health response to the coronavirus disease 2019 pandemic. Many use cases are envisaged, including complementing molecular methods for diagnosis of active disease and estimating immunity for individuals. At the population level, carefully designed seroepidemiologic studies will aid in the characterization of transmission dynamics and refinement of disease burden estimates and will provide insight into the kinetics of humoral immunity. Yet, despite an explosion in the number and availability of serologic assays to test for antibodies against SARS-CoV-2, most have undergone minimal external validation to date. This hinders assay selection and implementation, as well as interpretation of study results. In addition, critical knowledge gaps remain regarding serologic correlates of protection from infection or disease, and the degree to which these assays cross-react with antibodies against related coronaviruses. This article discusses key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies, reviews currently available assays, highlights key areas of ongoing research, and proposes potential strategies for test implementation.", "qid": 7, "docid": "01mo6yo9", "rank": 10, "score": 0.7843518853187561}, {"content": "Title: Serodiagnostics for Severe Acute Respiratory Syndrome\u2013Related Coronavirus-2: A Narrative Review Content: Accurate serologic tests to detect host antibodies to severe acute respiratory syndrome\u2013related coronavirus-2 (SARS-CoV-2) will be critical for the public health response to the coronavirus disease 2019 pandemic. Many use cases are envisaged, including complementing molecular methods for diagnosis of active disease and estimating immunity for individuals. At the population level, carefully designed seroepidemiologic studies will aid in the characterization of transmission dynamics and refinement of disease burden estimates and will provide insight into the kinetics of humoral immunity. Yet, despite an explosion in the number and availability of serologic assays to test for antibodies against SARS-CoV-2, most have undergone minimal external validation to date. This hinders assay selection and implementation, as well as interpretation of study results. In addition, critical knowledge gaps remain regarding serologic correlates of protection from infection or disease, and the degree to which these assays cross-react with antibodies against related coronaviruses. This article discusses key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies, reviews currently available assays, highlights key areas of ongoing research, and proposes potential strategies for test implementation.", "qid": 7, "docid": "ofd2ipvs", "rank": 11, "score": 0.7842063903808594}, {"content": "Title: [Acute respiratory disease caused by coronaviruses]. Content: Serological evidence of coronavirus aetiology was found in 11 patients out of 218 persons examined (5%) in the period of 1986-1987, and in 23 cases out of 311 patients (7.4%) in the period of 1987-1988. Antibody titres with a minimum of four-time elevated values in paired sera using the ELISA method were considered conclusive. Coronaviruses 229E and OC43 were employed. During the first period, more persons were infected by coronavirus 229E, while in the second period, by coronavirus OC43. The disease was equally spread over all the months of the years. For example, in the 1987-1988 period, most infections occurred in February, when out of 60 examined patients, 9 were coronavirus positive (15%).", "qid": 7, "docid": "sl1yd3ym", "rank": 12, "score": 0.7811033725738525}, {"content": "Title: Prevalence of canine coronavirus antibodies by an enzyme-linked immunosorbent assay in dogs in the south of Italy Content: Abstract An enzyme-linked immunosorbent assay (Elisa), using as antigen canine coronavirus-infected CrFK cell supernatant, was developed to detect antibodies against canine coronavirus (CCoV). Out of a total of 109 dog serum samples, 80 which were positive by routine virus neutralisation test were also Elisa positive. Seventeen samples which were negative by the virus neutralisation test, were positive by Elisa and by the confirmatory Western blotting test. The Elisa was substantially more sensitive than the virus neutralisation test in detecting antibodies to CCoV and may be used as an alternative technique to virus neutralisation.", "qid": 7, "docid": "j36vajdi", "rank": 13, "score": 0.7808399796485901}, {"content": "Title: Are antibodies tests accurate? Understanding predictive values and uncertainty of serology tests for the novel coronavirus. Content: Antibodies testing in the coronavirus era is frequently promoted, but the underlying statistics behind their validation has come under more scrutiny in recent weeks. We provide calculations, interpretations, and plots of positive and negative predictive values under a variety of scenarios. Prevalence, sensitivity, and specificity are estimated within ranges of values from researchers and antibodies manufacturers. Illustrative examples are highlighted, and interactive plots are provided in the Supplementary Material. Implications are discussed for society overall and across diverse locations with different levels of disease burden. Specifically, the proportion of positive serology tests that are false can differ drastically from up to 3% to 88% for people from different places with different proportions of infected people in the populations while the false negative rate is typically under 10%.", "qid": 7, "docid": "k54lmjxk", "rank": 14, "score": 0.778201699256897}, {"content": "Title: Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibody Responses in Coronavirus Disease Patients Content: A new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently emerged to cause a human pandemic. Although molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are needed for contact tracing, identifying the viral reservoir, and epidemiologic studies. We developed serologic assays for detection of SARS-CoV-2 neutralizing, spike protein-specific, and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed SARS-CoV-2 infections, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrated that most PCR-confirmed SARS-CoV-2-infected persons seroconverted by 2 weeks after disease onset. We found that commercial S1 IgG or IgA ELISAs were of lower specificity, and sensitivity varied between the 2 assays; the IgA ELISA showed higher sensitivity. Overall, the validated assays described can be instrumental for detection of SARS-CoV-2-specific antibodies for diagnostic, seroepidemiologic, and vaccine evaluation studies.", "qid": 7, "docid": "83odb66l", "rank": 15, "score": 0.7759929299354553}, {"content": "Title: Comparison of serologic techniques for the detection of antibodies against feline coronaviruses. Content: The seroprevalence of feline coronavirus (FCoV) antibodies was studied in cats in southern Italy. One hundred twenty sera collected from cats belonging to catteries or community shelters and to households were tested for FCoV type I and II antibodies. The virus neutralization (VN) was performed and compared with indirect fluorescent antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA). Ninety-six sera tested positive for FCoV antibodies by VN and ELISA. Interestingly, ELISA revealed 2 more positive sera than did the VN test and 3 more positive sera than did the IFAT. All results were confirmed by Western blotting. ELISA proved to be more sensitive and detected a seroprevalence of about 82%. Considering the cross-reactivity of FCoV type I and type II, ELISA was able to detect antibodies against both serotypes, allowing the use of the assay as a reference test for sera screening. The high prevalence of antibodies observed indicates that FCoVs are common in southern Italian cat populations.", "qid": 7, "docid": "xrjuma7x", "rank": 16, "score": 0.7759602069854736}, {"content": "Title: Serological Tests for SARS-CoV-2 Coronavirus by Commercially Available Point-of-Care and Laboratory Diagnostics in Pre-COVID-19 Samples in Japan Content: Serological tests for SARS-CoV-2 coronavirus in pre-COVID-19 samples in Japan showed 1.5%-1.75% positives, and previous surveys might overestimate COVID-19 seroprevalence in several population of Japan. These false negatives could be excluded by combination of different diagnostics to 0.25%.", "qid": 7, "docid": "hkvh2lc9", "rank": 17, "score": 0.7751907110214233}, {"content": "Title: Severe Acute Respiratory Syndrome Coronavirus 2\u2212Specific Antibody Responses in Coronavirus Disease Patients Content: A new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently emerged to cause a human pandemic. Although molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are needed for contact tracing, identifying the viral reservoir, and epidemiologic studies. We developed serologic assays for detection of SARS-CoV-2 neutralizing, spike protein\u2013specific, and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed SARS-CoV-2 infections, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrated that most PCR-confirmed SARS-CoV-2\u2013infected persons seroconverted by 2 weeks after disease onset. We found that commercial S1 IgG or IgA ELISAs were of lower specificity, and sensitivity varied between the 2 assays; the IgA ELISA showed higher sensitivity. Overall, the validated assays described can be instrumental for detection of SARS-CoV-2\u2013specific antibodies for diagnostic, seroepidemiologic, and vaccine evaluation studies.", "qid": 7, "docid": "mryazbnq", "rank": 18, "score": 0.7743992805480957}, {"content": "Title: Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis Content: OBJECTIVE: To determine the diagnostic accuracy of serological tests for coronavirus disease-2019 (covid-19). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, bioRxiv, and medRxiv from 1 January to 30 April 2020, using subject headings or subheadings combined with text words for the concepts of covid-19 and serological tests for covid-19. ELIGIBILITY CRITERIA AND DATA ANALYSIS: Eligible studies measured sensitivity or specificity, or both of a covid-19 serological test compared with a reference standard of viral culture or reverse transcriptase polymerase chain reaction. Studies were excluded with fewer than five participants or samples. Risk of bias was assessed using quality assessment of diagnostic accuracy studies 2 (QUADAS-2). Pooled sensitivity and specificity were estimated using random effects bivariate meta-analyses. MAIN OUTCOME MEASURES: The primary outcome was overall sensitivity and specificity, stratified by method of serological testing (enzyme linked immunosorbent assays (ELISAs), lateral flow immunoassays (LFIAs), or chemiluminescent immunoassays (CLIAs)) and immunoglobulin class (IgG, IgM, or both). Secondary outcomes were stratum specific sensitivity and specificity within subgroups defined by study or participant characteristics, including time since symptom onset. RESULTS: 5016 references were identified and 40 studies included. 49 risk of bias assessments were carried out (one for each population and method evaluated). High risk of patient selection bias was found in 98% (48/49) of assessments and high or unclear risk of bias from performance or interpretation of the serological test in 73% (36/49). Only 10% (4/40) of studies included outpatients. Only two studies evaluated tests at the point of care. For each method of testing, pooled sensitivity and specificity were not associated with the immunoglobulin class measured. The pooled sensitivity of ELISAs measuring IgG or IgM was 84.3% (95% confidence interval 75.6% to 90.9%), of LFIAs was 66.0% (49.3% to 79.3%), and of CLIAs was 97.8% (46.2% to 100%). In all analyses, pooled sensitivity was lower for LFIAs, the potential point-of-care method. Pooled specificities ranged from 96.6% to 99.7%. Of the samples used for estimating specificity, 83% (10 465/12 547) were from populations tested before the epidemic or not suspected of having covid-19. Among LFIAs, pooled sensitivity of commercial kits (65.0%, 49.0% to 78.2%) was lower than that of non-commercial tests (88.2%, 83.6% to 91.3%). Heterogeneity was seen in all analyses. Sensitivity was higher at least three weeks after symptom onset (ranging from 69.9% to 98.9%) compared with within the first week (from 13.4% to 50.3%). CONCLUSION: Higher quality clinical studies assessing the diagnostic accuracy of serological tests for covid-19 are urgently needed. Currently, available evidence does not support the continued use of existing point-of-care serological tests. STUDY REGISTRATION: PROSPERO CRD42020179452.", "qid": 7, "docid": "xw0o5ca7", "rank": 19, "score": 0.7738461494445801}, {"content": "Title: A line immunoassay utilizing recombinant nucleocapsid proteins for detection of antibodies to human coronaviruses Content: Abstract Most coronaviruses infecting humans cause mild diseases, whereas severe acute respiratory syndrome (SARS)-associated coronavirus is an extremely dangerous pathogen. Here, we report the development of a serologic assay for detection of antibodies to human coronaviruses (HCoVs) based on recombinant nucleocapsid (N) proteins of all known pathogenic strains (229E, NL63, OC43, HKU1, SARS). The novel immunoassay is highly useful for epidemiologic surveys, where use of nucleic acid diagnostics often is limited. Purified recombinant antigens were immobilized on nitrocellulose membranes and applied in a line immunoassay, which allows rapid detection of antibodies to 5 different HCoVs in a single experiment. For assay evaluation, serum samples from persons infected with 229E or OC43 (acute/convalescent), recovered SARS patients and healthy donors were analyzed. Screening for nucleocapsid (N)-specific immunoglobulin G (IgG) in convalescent sera reached 100% sensitivity. With this new technique, we found that recently identified NL63 and HKU1 contribute significantly to the overall spectrum of coronavirus infections. Possibly, cross-reactive antibody responses were observed using 229E and OC43 serum pairs. However, the potential of this assay could clearly be demonstrated employing SARS-positive serum samples, where nonspecific binding to nucleocapsids of other HCoVs was not observed. This coronavirus strain-specific line immunoassay represents a powerful tool for serologic diagnostics.", "qid": 7, "docid": "m400cal3", "rank": 20, "score": 0.7737960815429688}, {"content": "Title: Diagnosis of human coronavirus infection by immunofluorescence: Method and application to respiratory disease in hospitalized children Content: Rabbit antisera were prepared against coronavirus strains 229E and OC43 and used successfully to detect viral antigen in epithelial cells shed from the nasopharynx of symptomatic volunteers who had received coronavirus inocula three to four days before. The same serologic reagents were applied to nasopharyngeal secretion cells obtained from 106 infants and children hospitalized with respiratory tract disease and apparently not infected with conventional respiratory viruses. No coronavirus infections were detected by this method. It appears that coronavirus OC43 or 229E infections were not common in children in Tyneside hospitals during the period of study. However, fluorescence is a useful method for detection of coronavirus infections in symptomatic human subjects.", "qid": 7, "docid": "y27aa1b6", "rank": 21, "score": 0.7729564905166626}, {"content": "Title: Serologic and Molecular Biologic Methods for SARS-associated Coronavirus Infection, Taiwan Content: Severe acute respiratory syndrome (SARS) has raised a global alert since March 2003. After its causative agent, SARS-associated coronavirus (SARS-CoV), was confirmed, laboratory methods, including virus isolation, reverse transcriptase\u2013polymerase chain reaction (RT-PCR), and serologic methods, have been quickly developed. In this study, we evaluated four serologic tests ( neutralization test, enzyme-linked immunosorbent assay [ELISA], immunofluorescent assay [IFA], and immunochromatographic test [ICT]) for detecting antibodies to SARS-CoV in sera of 537 probable SARS case-patients with correlation to the RT-PCR . With the neutralization test as a reference method, the sensitivity, specificity, positive predictive value, and negative predictive value were 98.2%, 98.7%, 98.7%, and 98.4% for ELISA; 99.1%, 87.8%, 88.1% and 99.1% for IFA; 33.6%, 98.2%, 95.7%, and 56.1% for ICT, respectively. We also compared the recombinant-based western blot with the whole virus\u2013based IFA and ELISA; the data showed a high correlation between these methods, with an overall agreement of >90%. Our results provide a systematic analysis of serologic and molecular methods for evaluating SARS-CoV infection.", "qid": 7, "docid": "zo9uzk52", "rank": 22, "score": 0.7704366445541382}, {"content": "Title: A serological assay to detect SARS-CoV-2 seroconversion in humans Content: SARS-Cov-2 (severe acute respiratory disease coronavirus 2), which causes Coronavirus Disease 2019 (COVID19) was first detected in China in late 2019 and has since then caused a global pandemic. While molecular assays to directly detect the viral genetic material are available for the diagnosis of acute infection, we currently lack serological assays suitable to specifically detect SARS-CoV-2 antibodies. Here we describe serological enzyme-linked immunosorbent assays (ELISA) that we developed using recombinant antigens derived from the spike protein of SARS-CoV-2. Using negative control samples representing pre-COVID 19 background immunity in the general adult population as well as samples from COVID19 patients, we demonstrate that these assays are sensitive and specific, allowing for screening and identification of COVID19 seroconverters using human plasma/serum as early as two days post COVID19 symptoms onset. Importantly, these assays do not require handling of infectious virus, can be adjusted to detect different antibody types and are amendable to scaling. Such serological assays are of critical importance to determine seroprevalence in a given population, define previous exposure and identify highly reactive human donors for the generation of convalescent serum as therapeutic. Sensitive and specific identification of coronavirus SARS-Cov-2 antibody titers may, in the future, also support screening of health care workers to identify those who are already immune and can be deployed to care for infected patients minimizing the risk of viral spread to colleagues and other patients.", "qid": 7, "docid": "ntra3jhs", "rank": 23, "score": 0.7696071267127991}, {"content": "Title: Prevalence of feline coronavirus antibodies in cats in Bursa province, Turkey, by an enzyme-linked immunosorbent assay Content: Feline sera from Bursa province (Turkey) were assayed for coronavirus antibody using an enzyme-linked immunosorbent assay (ELISA). The study was performed on 100 sera collected from cats belonging to catteries or community shelters and to households. The serum samples were initially tested with the virus neutralisation (VN) test and the results were then compared with the ELISA. The VN yielded 79 negative and 21 positive sera but the ELISA confirmed only 74 as negative. The ELISA-negative sera were also found to be free of feline coronoviruses-specific antibodies by Western blotting. Using the VN as the gold standard test, ELISA had a sensitivity of 100% and a specificity of 93.6%, with an overall agreement of 95%. The Kappa (\u03ba) test indicated high association between the two tests (\u03ba =0.86, 95% confidence interval (CI) 0.743\u20130.980). The positive predictive value (PPV) was 0.8, and the negative predictive value (NPV) was 0.93. The prevalence of FCoV II antibodies in the sampled population based on the gold standard was 62% (95% CI 0.44\u20130.77) among multi-cat environments, and 4% (95% CI 0.01\u20130.11) among single cat households.", "qid": 7, "docid": "se27uebt", "rank": 24, "score": 0.7692564725875854}, {"content": "Title: Diagnosis of human coronavirus infections in children using enzyme\u2010linked immunosorbent assay Content: An enzyme\u2010linked immunosorbent assay (ELISA) was developed for diagnosing human coronavirus (HCV) infections in children. One hundred and seventy seven nose swabs, throat swabs, and nasopharyngeal aspirates were collected from 30 children suffering from acute respiratory infections. These samples were tested for HCV antigens by ELISA and 28.2% of the samples were shown to be HCV positive. These results indicate that our ELISA should prove useful in the diagnosis of HCV infections in children. Further studies are in progress to extend the ELISA to detect HCVs in experimentally and naturally acquired infections in adults.", "qid": 7, "docid": "qtz3r5di", "rank": 25, "score": 0.7690579891204834}, {"content": "Title: Characteristics and assessment of the usefulness of serological tests in the diagnostic of infections caused by coronavirus SARS-CoV-2 on the basis of available manufacturer's data and literature review. Content: Recognized in 2019 in Wuhan, China, the new SARS-CoV-2 coronavirus is responsible for the occurrence of a global pandemic disease called COVID-19. So far, confirmation of infection is based on the detection of virus RNA in a sample taken from a person meeting the suspected case definition. However, in the laboratory diagnosis of SARS-CoV-2 infections, in addition to genetic tests, serological methods can also be used to detect specific antibodies of the IgM, IgG and IgA class produced after contact with antigens or to detect viral antigen. Currently, a number of rapid immunochromatographic, chemiluminescent and ELISA immunoassay tests developed by different manufacturers for the diagnosis of COVID-19 are available on the market. Despite this fact, so far there is no WHO or ECDC recommendations or even reliable research regarding the usefulness of serological investigations in the laboratory diagnosis of infections caused by SARS-CoV-2.", "qid": 7, "docid": "82iy2prw", "rank": 26, "score": 0.7677780389785767}, {"content": "Title: Characteristics and assessment of the usefulness of serological tests in the diagnostic of infections caused by coronavirus SARS-CoV-2 on the basis of available manufacturer's data and literature review Content: Recognized in 2019 in Wuhan, China, the new SARS-CoV-2 coronavirus is responsible for the occurrence of a global pandemic disease called COVID-19. So far, confirmation of infection is based on the detection of virus RNA in a sample taken from a person meeting the suspected case definition. However, in the laboratory diagnosis of SARS-CoV-2 infections, in addition to genetic tests, serological methods can also be used to detect specific antibodies of the IgM, IgG and IgA class produced after contact with antigens or to detect viral antigen. Currently, a number of rapid immunochromatographic, chemiluminescent and ELISA immunoassay tests developed by different manufacturers for the diagnosis of COVID-19 are available on the market. Despite this fact, so far there is no WHO or ECDC recommendations or even reliable research regarding the usefulness of serological investigations in the laboratory diagnosis of infections caused by SARS-CoV-2.", "qid": 7, "docid": "84yjdlab", "rank": 27, "score": 0.7677779197692871}, {"content": "Title: Laboratory Tests for COVID-19: A Review of Peer-Reviewed Publications and Implications for Clinical UIse. Content: Diagnostic tests for the coronavirus infection 2019 (COVID-19) are critical for prompt diagnosis, treatment and isolation to break the cycle of transmission. A positive real-time reverse-transcriptase polymerase chain reaction (RT-PCR), in conjunction with clinical and epidemiologic data, is the current standard for diagnosis, but several challenges still exist. Serological assays help to understand epidemiology better and to evaluate vaccine responses but they are unreliable for diagnosis in the acute phase of illness or assuming protective immunity. Serology is gaining attention, mainly because of convalescent plasma gaining importance as treatment for clinically worsening COVID-19 patients. We provide a narrative review of peer-reviewed research studies on RT-PCR, serology and antigen immune-assays for COVID-19, briefly describe their lab methods and discuss their limitations for clinical practice.", "qid": 7, "docid": "ey34e59f", "rank": 28, "score": 0.7676877379417419}, {"content": "Title: Enzyme-linked immunosorbent assay for the detection of the coronavirus-like agent and its antibodies in pigs with porcine epidemic diarrhea Content: Abstract An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of the coronavirus-like agent in feces of pigs naturally affected with porcine epidemic diarrhea (PED) or experimentally infected with the CV777 isolate. The assay was specific and more sensitive than electron microscopy. An ELISA blocking assay is described for the detection and titration of antibodies. Specific antibody formation was demonstrated in pigs experimentally infected with CV777 and in swine naturally affected with PED.", "qid": 7, "docid": "mgegswvn", "rank": 29, "score": 0.7671697735786438}, {"content": "Title: Seroprevalence of Antibodies to SARS-CoV-2 in Healthcare Workers in Non-epidemic Region: A Report from Iwate Prefecture in Japan Content: Background: As of June 8, 2020, Iwate is the only one of 47 prefectures in Japan with no confirmed coronavirus disease 2019 (COVID-19) cases. Serological survey for COVID-19 antibodies is crucial in area with low prevalence as well as epidemic area when addressing health and social issues caused by COVID-19. Rapid, accurate and easy-to-use antibody tests as well laboratory-based antibody tests are necessary for confirming immunity in a given community. Methods:Serum samples from healthcare workers (n = 1,000, mean 40 {+/-} 11 years) of Iwate Prefectural Central Hospital, Iwate, Japan were tested for the prevalence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Two laboratory-based quantitative tests (Abbott Architect SARS-CoV-2 IgG and Roche Elecsys Anti-SARS-CoV-2 assays) and one point-of-care (POC) qualitative test (Alfa Instant-view plus COVID-19 Test) were performed simultaneously. Sensitivity and specificity were 100%, 99.6% in Abbott assay; 100%, 99.8% in Roche assay; 97.8%, 94.6% in Alfa POC test, respectively. Results:The laboratory-based quantitative tests showed positive in 4 of 1,000 samples (0.4%) (95% CI: 0.01 to 0.79): 4/1,000 (0.4%) (95% CI: 0.01 to 0.79) in Abbott; 0/1,000 (0%) in Roche. Positive samples were not detected for both Abbott and Roche assays. The POC qualitative test showed positive in 33 of 1,000 samples (3.3%) (95% CI: 2.19 to 4.41), showing higher rates than those of the laboratory-based quantitative tests. There were no samples with simultaneous positive reaction for two quantitative tests and a POC test. Conclusions: Infected COVID-2 cases were not confirmed by a retrospective serological study in healthcare workers of our hospital. The POC qualitative tests with lower specificity have the potential for higher false positive reactions than the laboratory-based quantitative tests in areas with very low prevalence of COVID-19.", "qid": 7, "docid": "bj8wn9dh", "rank": 30, "score": 0.7664816379547119}, {"content": "Title: Antigenic relationships amongst coronaviruses Content: Several serological interrelationships between various members of the corona-virus group have been revealed in neutralization, complement fixation, and gel-diffusion tests, using human and hyperimmune animal sera. Several members of this group of human and animal pathogens are shown to cross-react in one or more type of test, but one member, avian infectious bronchitis virus, was shown to be unrelated. Mouse hepatitis virus (MHV(3)) was found to be antigenically related to a number of human types of coronavirus. Difficulties were encountered in the investigation of paired human sera in demonstrating the specificity of antibody rises, placing doubt on the values of some serological studies. The significance of these interrelationships is discussed in the light of other investigations.", "qid": 7, "docid": "cxt9oq0j", "rank": 31, "score": 0.7659958600997925}, {"content": "Title: Detection of human coronavirus 229E-specific antibodies using recombinant fusion proteins Content: Abstract Human coronaviruses are known to be a common cause of respiratory infections in man. However, the diagnosis of human coronavirus infections is not carried out routinely, primarily because the isolation and propagation of these viruses in tissue culture is difficult and time consuming. The aim of this study was to evaluate the use of recombinant, bacterial expressed proteins in the serodiagnosis of coronavirus infections. Two proteins were examined: the human coronavirus 229E nucleocapsid protein (N), expressed as a fusion protein in the vector pUR and the coronavirus 229E surface glycoprotein (S), expressed as a fusion protein in the vector pROS. The recombinant proteins were used as antigens in Western blot (WB) assays to detect the 229E-specific IgG antibodies and the results were compared with a standard serological method, indirect immunofluorescence. Serum samples of 51 paediatric patients, suffering from acute respiratory illness, and 10 adults, voluntarily infected with human coronavirus, were tested. The serum samples of the adult group had coronavirus-specific IgG antibodies in both test systems. In contrast, only 8 51 sera of the paediatric group were positive for coronavirus-specific IgG by both WB and IF and 20 51 sera were positive by WB, but not by IF. The overall incidence of human coronavirus infections in the paediatric age group was 55% evaluated by WB analysis and 16% evaluated by IF. This study shows that recombinant human coronavirus 229E proteins are suitable reagents for the epidemiological screening of coronavirus 229E infections.", "qid": 7, "docid": "gbyyehbu", "rank": 32, "score": 0.7659540772438049}, {"content": "Title: Coronative antibody tires in sera of healthy adults and experimentally infected volunteers. Content: Six coronaviruses isolated in the U.S.A. have been inoculated into volunteers and all produced colds. Between 10 and 20% of infected volunteers developed heterologous antibody responses after these and other experimental infections with coronaviruses. The haemagglutination-inhibition test with the OC43 virus strain was found to detect antibody rises after infection with a variety of strains.Studies on normal adult sera taken between 1965 and 1970 revealed a high frequency of neutralizing antibody to one strain (229 E) and a frequency of HI antibody to strain OC43 which fluctuated from year to year. Complement-fixing antibodies to these two viruses were also found, revealing an apparent increase in the activity of coronaviruses in the general population of the U.K., during the winter of 1968-9.", "qid": 7, "docid": "utnqvdvl", "rank": 33, "score": 0.7658407688140869}, {"content": "Title: Development of a nucleocapsid-based human coronavirus immunoassay and estimates of individuals exposed to coronavirus in a U.S. metropolitan population. Content: Coronaviruses cause respiratory infections ranging from common colds to severe acute respiratory syndrome (SARS) in humans. Estimates for exposure to non-SARS coronaviruses are high, particularly for 229E and OC43; however, less information regarding seroprevalence is available for HKU1 and NL63. To measure exposure rates to these four coronavirus strains (229E, HKU1, NL63, and OC43), we devised an immunoassay based on amino- and carboxy-terminally tagged recombinant coronavirus nucleocapsid antigens. Four human and one feline coronavirus antigen were cloned into baculoviruses expressed in insect cells and recovered proteins bound in the solid phase of an enzyme-linked immunosorbent assay-based system. We screened sera from 10 children and 196 adults and established primary cutoff points based on immunoglobulin G (IgG) antibody levels of the predominantly seronegative children. The proportion of seropositive adults for each coronavirus was as follows: 229E, 91.3%; HKU1, 59.2%; NL63, 91.8%; and OC43, 90.8%. No evidence of a significant serological response to the feline coronavirus was observed. Significant associations of coronavirus seropositivity and antibody levels with age, gender, race, socioeconomic status, smoking status, and season of the blood draw were tested with chi-square and regression analyses. The group II coronaviruses (OC43 and HKU1) were significantly associated with race (P<or=0.009 and P<or=0.03, respectively). Elevated OC43 IgG levels were further significantly associated with smoking status (P<or=0.03), as were high NL63 titers with socioeconomic status (P<or=0.04). The high-level immunoreactivity of each coronavirus was significantly associated with the summer season (P<or=0.01 to 0.0001). In summary, high rates of exposure to 229E, NL63, and OC43 and a moderate rate of exposure to HKU1 characterized the seroprevalence among individuals in this population. Demographic factors, such as race, smoking status, and socioeconomic status, may confer an increased risk of susceptibility to these viruses.", "qid": 7, "docid": "1m6hvgla", "rank": 34, "score": 0.7658407092094421}, {"content": "Title: Singapore claims first use of antibody test to track coronavirus infections ;Science ;AAAS Content: In what appears to be a first, disease trackers in Singapore have used an experimental antibody test for COVID-19 to confirm that a suspected patient was infected with the coronavirus The patient was one of two people who together formed a missing link between two clusters of cases that each occurred in a Singaporean church Researchers around the world are racing to develop antibody tests, also called serological tests, that can confirm whether someone was infected even after their immune system has cleared the virus that causes COVID-19 The group that developed the test, at Duke-NUS Medical School in Singapore, is among the front-runners, although its assay has to be validated before it is taken into production and deployed widely", "qid": 7, "docid": "g693adjd", "rank": 35, "score": 0.7653262615203857}, {"content": "Title: Enzyme-linked immunosorbent assay for detection of antibody in volunteers experimentally infected with human coronavirus strain 229 E. Content: An enzyme-linked immunosorbent assay was developed for detecting antibody rises to human coronavirus strain 229E and related strains in paired sera from infected volunteers. There was a close correlation between development of colds infected volunteers. There was a close correlation between development of colds and significant antibody rises detected by the enzyme-linked immunosorbent assay. Furthermore, the assay was more sensitive than a neutralization assay. This enzyme-linked immunosorbent assay is an easy, accurate, and sensitive assay for measuring significant antibody rises to human coronavirus strain 229E group viruses, and it could be useful in the clinical diagnosis of these infections.", "qid": 7, "docid": "hoh3z39d", "rank": 36, "score": 0.7649805545806885}, {"content": "Title: SARS-CoV-2 specific antibody responses in COVID-19 patients Content: A new coronavirus, SARS-CoV-2, has recently emerged to cause a human pandemic. Whereas molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are important for contact tracing, identifying the viral reservoir and epidemiological studies. Here, we developed serological assays for the detection of SARS-CoV-2 neutralizing, spike- and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed infections of SARS-CoV-2, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrate that most PCR-confirmed SARS-CoV-2 infected individuals seroconverted, as revealed by sensitive and specific in-house ELISAs. We found that commercial S1 IgG or IgA ELISAs were of lower specificity while sensitivity varied between the two, with IgA showing higher sensitivity. Overall, the validated assays described here can be instrumental for the detection of SARS-CoV-2-specific antibodies for diagnostic, seroepidemiological and vaccine evaluation studies.", "qid": 7, "docid": "9595vm0k", "rank": 37, "score": 0.7648280262947083}, {"content": "Title: [Seasonal patterns of coronavirus infections in Hamburg]. Content: During a serological surveillance programme between October 1974 and September 1975 in Hamburg, 1624 sera from all age groups of the population were examined for the presence of coronavirus antibodies (OC 43 agent). 61,51% of the sera showed HI-titres between 1:8 and 1:128. The geometric mean antiboty titre (GMT) for the whole group was 1:12,2. The serological seasonal pattern suggests that coronaviruses are circulating the whole year in the urban population with a prevalence in the cold and a decrease in the warm season (June). The highest incidence of seropositive reactions (82,9%) was found in the 15-24 years old individuals (GMT 1:13,8). These data indicate an increased spread of coronaviruses in this segment of the population and a marked susceptibility of the group.", "qid": 7, "docid": "gpprz8a1", "rank": 38, "score": 0.7641779780387878}, {"content": "Title: Prevalence of human coronavirus antibody in the population of southern iraq Content: Sera from adults in Southern Iraq were collected during winter and screened by an enzyme\u2013linked immunosorbent assay for the presence of antibodies to the two antigenic groups of human coronaviruses, the 229E and the OC43 groups: 91% of the sera had antibodies to at least one of the groups, whereas 4 and 5% of the sera had antibodies to only the 229E or OC43 groups, respectively. There was significant correlation between the levels of antibody to the 229E and OC43 group coronaviruses in these sera.", "qid": 7, "docid": "5xisw9au", "rank": 39, "score": 0.7640831470489502}, {"content": "Title: Nonspecific inhibitors of coronavirus OC43 haemagglutination in human sera Content: Antibodies against the human coronavirus OC43 in human sera were measured by haemagglutination inhibition (HI), complement fixation (CF), and radial diffusion-haemolysis in gel (HIG) techniques. The apparent HI titres in a fraction of sera with no antibodies detectable by the two other methods were found to be reduced considerably after treating the sera with phospholipase C (PLC). The PLC treatment also reduced the apparent HI titres in some sera containing variable amounts of CF and/or HIG antibodies, but did not affect antibody determinations by the two latter methods. These results suggest that false positive results can be obtained in the OC43 HI test unless the sera are treated with phospholipase C before the assay.", "qid": 7, "docid": "0s2rx3gc", "rank": 40, "score": 0.76383376121521}, {"content": "Title: Feline infectious peritonitis: a worldwide serosurvey. Content: Feline sera from 13 countries were assayed for coronavirus antibody, using a heterologous indirect immunofluorescence test. Significantly higher percentages of antibody carriers were obtained during testing randomly collected sera from mature males (greater than 1 year old) than in testing females of the same age. Antibodies were infrequently found in immature cats (less than 6 months old); at 1 year of age or older, a plateau was reached and little change in the percentage of seroconverted animals was observed. Differences were not detected between purebred cats vs mixed-breed cats or household vs stray cats. In animals showing clinical signs of feline infection peritonitis (FIP), antibodies were encountered with higher frequency than in clinically healthy cats. Significant differences in antibody incidence were found between countries, with a range between less than 10% and greater than 50% of seropositive individuals. Antibodies were detected in sera from an isolated cat population (Marion Island) and from wild-caught cheetahs (Acinonyx jubatus). The antibody specificity for FIP virus was confirmed by neutralization tests. The antibody pattern in randomly collected solitary cats, in catteries, and cats with clinical FIP showed characteristic differences in titer and incidence. The implications of these results for the epizootiology of FIP are discussed.", "qid": 7, "docid": "dfyq0szh", "rank": 41, "score": 0.7634515762329102}, {"content": "Title: A two year serological surveillance of coronavirus infections in Hamburg Content: The occurrence of OC-43 coronavirus-like infections in the population of Hamburg was determined by a monthly serological survey (hemagglutination inhibition test [HI]) undertaken between October 1974 and October 1976. Studies of 3,016 sera revealed a high incidence of HI antibodies (58.2%). The frequency of seropositive reactions (=1:8) and the geometric mean titer were higher in individuals 15 to 24 years old. Treatment of 50 positive sera (titer 1:16 \u2013 1:64) with receptor destroying enzyme, kaolin and ethacridin for elimination of nonspecific inhibitors did not modify the HI-titer of the investigated sera. The serological seasonal pattern suggests that coronaviruses are circulating the whole year in the urban population with a prevalence in the fall-winter period. Of the 331 paired sera examined, 6.6% presented a four- to eightfold rise in titer within eight weeks.", "qid": 7, "docid": "s0qpiovr", "rank": 42, "score": 0.7634115219116211}, {"content": "Title: SEROEPIDEMIOLOGIC SURVEY OF CORONAVIRUS (STRAIN OC 43) RELATED INFECTIONS IN A CHILDREN'S POPULATION Content: Kaye, H. S. (CDC, Atlanta, Ga. 30333), H. B. Marsh and W. R. Dowdle. Sero-epidemiologic survey of coronavirus (strain OC 43) related infections in a children's population. Amer J Epid 94: 43\u201349, 1971.\u2014Acute and convalescent serum pairs and control sera collected from subjects living in a children's home over a 7-year period (1960\u20131967) were examined by hemagglutination-inhibition (HI) test with coronavirus strain OC 43. Ninety-three serologic conversions were observed; 44 were associated with reported illnesses and 49 with no reported illnesses. In three distinct outbreaks during the winter and spring quarter of 1960\u20131961, 1964\u20131965, and 1966\u20131967, 67 conversions occurred. Seroconversions to strain OC 43 were associated with as much as 19% of the respiratory diseases in a single season. Over the 7-year period coronavirus strain OC 43 accounted for 3% of the total 1328 respiratory illnesses. Evidence of preexisting antibody was apparent in one-third of the children showing seroconversions. The HI test was more sensitive for serodiagnosis than the complement-fixaticn test. The major presenting complaints of the children with respiratory disease associated with coronavirus strain OC 43 were sore throat, cough and coryza; the predominating symptoms were pharyngitis, coryza, fever and cervical adenitis.", "qid": 7, "docid": "tqruna9t", "rank": 43, "score": 0.763256311416626}, {"content": "Title: Monoclonal antibody capture enzyme-linked immunosorbent assay for detection of bovine enteric coronavirus. Content: Monoclonal antibodies reactive with three different viral polypeptides were evaluated singly and in combination as the capture antibody(s) in an enzyme-linked immunosorbent assay system for the detection of bovine enteric coronavirus. Similar levels of sensitivity were found for all combinations tested. A sensitive, highly specific, and reproducible assay for the detection of bovine enteric coronavirus was developed, using a mixture of two of these monoclonal antibodies reactive with antigenic components either external or internal to the virion. These monoclonal antibodies were bound indirectly to 96-well plates via rabbit anti-mouse immunoglobulin. After sample application and incubation, virus was detected by using rabbit anti-coronavirus peroxidase conjugate followed by enzyme substrate and chromagen. Fecal samples from a single herd of cows were screened for the presence of coronavirus by this assay. Five percent of clinically normal cows were found to be shedding coronavirus.", "qid": 7, "docid": "4cllq5ts", "rank": 44, "score": 0.761016845703125}, {"content": "Title: Evaluation of nine commercial SARS-CoV-2 immunoassays Content: Due to urgency and demand, numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoassays are rapidly being developed and placed on the market with limited validation on clinical samples. Thorough validation of serological tests are required to facilitate their use in the accurate diagnosis of SARS-CoV-2 infection, confirmation of molecular results, contact tracing, and epidemiological studies. This study evaluated the sensitivity and specificity of nine commercially available serological tests. These included three enzyme-linked immunosorbent assays (ELISAs) and six point-of-care (POC) lateral flow tests. The assays were validated using serum samples from: i) SARS-CoV-2 PCR-positive patients with a documented first day of disease; ii) archived sera obtained from healthy individuals before the emergence of SARS-CoV-2 in China; iii) sera from patients with acute viral respiratory tract infections caused by other coronaviruses or non-coronaviruses; and iv) sera from patients positive for dengue virus, cytomegalovirus and Epstein Barr virus. The results showed 100% specificity for the Wantai SARS-CoV-2 Total Antibody ELISA, 93% for the Euroimmun IgA ELISA, and 96% for the Euroimmun IgG ELISA with sensitivities of 90%, 90%, and 65%, respectively. The overall performance of the POC tests according to manufacturer were in the rank order of AutoBio Diagnostics > Dynamiker Biotechnology = CTK Biotech > Artron Laboratories > Acro Biotech \u2265 Hangzhou Alltest Biotech. Overall, these findings will facilitate selection of serological assays for the detection SARS-CoV-2-specific antibodies towards diagnosis as well as sero-epidemiological and vaccine development studies.", "qid": 7, "docid": "8cg5yj20", "rank": 45, "score": 0.7608472108840942}, {"content": "Title: Determination of coronavirus 229E antibody by an immune\u2010adherence hemagglutination method Content: An immune\u2010adherence hemagglutination (IAHA) method for coronavirus 229E antibody determination has been developed both for diagnosis of recent infections and for detection of long\u2010past infections. Results have been compared with those obtained by complement fixation (CF), neutralization (Nt), and indirect hemagglutination (IHA) tests. The IAHA method has been shown to be as sensitive as the CF, Nt, and IHA tests in detecting cases of acute 229E infection. However, in a seroepidemiological survey of 343 healthy people of all ages, IAHA detected 229E antibody in 254 individuals (74.0%), Nt in 166 (48.3%), IHA in 89 (25.9%), and CF in 30 (8.7%). A study of the prevalence of coronavirus 229E IAHA antibody in the different age groups has shown that during the second decade of life nearly 100% of the population acquire this type of antibody, whereas only 50% are positive at the end of the first decade. In the older age groups, the high frequency of CF antibody (\u201cmarker\u201d of recent infection) indirectly confirms the high rate of 229E reinfections and the nonprotective nature of IAHA antibody. CF titer \u2a7e 1:8 in 90% of cases corresponded to IAHA titers \u2a7e 1:64. However, sera with IAHA titers of \u2a7e 1:128 were often CF\u2010negative. Recent 229E infections (or reinfections), as determined by the presence of CF antibody, were more frequent in April\u2010May than in October\u2010November. Three cases of acute infection showing 229E seroconversion (two adults and one child) were observed during the winter\u2010spring season. IAHA appears to be the test of choice for seroepidemiological surveys.", "qid": 7, "docid": "yaiadylf", "rank": 46, "score": 0.7607417106628418}, {"content": "Title: Detection of turkey enteric coronavirus by enzyme-linked immunosorbent assay and differentiation from other coronaviruses. Content: A double-antibody ELISA for the detection of coronaviruses in intestinal contents from turkey poults with diarrhea was developed. Antibodies were raised in rabbits and guinea pigs against a Minnesota isolate of turkey enteric coronavirus (TCV) propagated in embryonating turkey eggs and were purified by density-gradient centrifugation. The specificity of antisera was confirmed by hemagglutination-inhibition and immunoelectron microscopy. Absorption of anti-TCV hyperimmune sera with egg extracts or egg ovalbumin and the use of different dilution and blocking buffers influenced the sensitivity and specificity of the ELISA. Reciprocal cross-reactivity was detected among turkey, chicken, bovine, and murine coronaviruses. Antisera to the transmissible gastroenteritis virus of swine, the rabbit enteric coronavirus, or the human coronavirus strain 299E failed to react with TCV. The TCV cross-reacted only moderately with the avian infectious bronchitis virus and the hemagglutinating encephalomyelitis virus of swine. Investigations with samples from 47 commercial turkey flocks in Quebec with episodes of transmissible enteritis revealed that the ELISA was more sensitive than was electron microscopy for detection of TCV.", "qid": 7, "docid": "mh6z976r", "rank": 47, "score": 0.7602723836898804}, {"content": "Title: Evaluation of a computer-assisted, kinetics-based enzyme-linked immunosorbent assay for detection of coronavirus antibodies in cats. Content: A computer-assisted, kinetics-based enzyme-linked immunosorbent assay was adapted for the detection of coronavirus antibodies in feline serum. An alkaline antigen diluent (carbonate-bicarbonate buffer, pH 9.6) used in initial experiments produced diffuse, nonspecific color reactions in both viral and control antigen cuvettes which were correlated, paradoxically, with coronavirus antibody levels in test sera. These interfering reactions were minimized by use of lower-pH antigen diluents such as water and phosphate-buffered saline. Background kinetics-based enzyme-linked immunosorbent assay reactivity directed against a noncoronaviral component of antigen tissue culture fluids could then detected in numerous sera, particularly in samples with lower titers. Much of this reactivity was shown to be associated with bovine gamma globulins in cell culture fluid. It was not serum lot or species specific, since a variety of bovine serum lots as well as individual lots of serum from other mammalian and avian species reacted. Reactivity was markedly reduced when cells for antigen preparation were grown in gamma globulin-free bovine serum. Generation of corrected slope values from the kinetics-based enzyme-linked immunosorbent assay made it possible to correct for residual background reactivity in individual test sera and thus eliminate a potentially major source of false-positive reactions. Collectively, these studies indicated that the control of nonspecific reactivity in feline coronavirus serology is absolutely essential to obtain useful estimates of specific antibody responses.", "qid": 7, "docid": "ku45p8f2", "rank": 48, "score": 0.7602009773254395}, {"content": "Title: Two enzyme immunoassays for the detection of antibody to rodent coronaviruses Content: Abstract Two enzyme immunoassays for detection of antibody to rodent coronaviruses were compared. Mouse hepatitis virus (MHV), strain JHM, antigen was in the form of formalin-fixed, infected 17 C1 1 cells. This antigen detected antibody to the homologous strain of MHV as well as to two heterologous MHV strains and a serologically related rat coronavirus, sialodacryodenititis virus. Antibody titers in assays using horseradish peroxidase (HRP)-conjugated or ureiase-conjugated anti-mouse IgG were substantially higher than in an indirect immunofluorescence assay. The ureiase assay was somewhat more sensitive than the HRP assay. MHV-JHM antigen was stable under a variety of storage conditions for at least two months.", "qid": 7, "docid": "xob8d5nz", "rank": 49, "score": 0.7592953443527222}, {"content": "Title: Evaluation of commercial and automated SARS-CoV-2 IgG and IgA ELISAs using coronavirus disease (COVID-19) patient samples Content: Antibody-screening methods to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) need to be validated. We evaluated SARS-CoV-2 IgG and IgA ELISAs in conjunction with the EUROLabworkstation (Euroimmun, L\u00fcbeck, Germany). Overall specificities were 91.9% and 73.0% for IgG and IgA ELISAs, respectively. Of 39 coronavirus disease patients, 13 were IgG and IgA positive and 11 IgA alone at sampling. IgGs and IgAs were respectively detected at a median of 12 and 11 days after symptom onset.", "qid": 7, "docid": "5najee33", "rank": 50, "score": 0.7592501044273376}, {"content": "Title: OC43 strain\u2010related coronavirus antibodies in different age groups Content: Serum antibodies against human coronavirus OC43 in different age groups were measured by complement fixation (CF), haemagglutination inhibition (HI), radial diffusion haemolysis\u2010in\u2010gel (HIG), and solid\u2010phase radioimmunoassay (RIA) methods. Antigen grown in suckling mouse brain was used in all tests. Results obtained by the CF and HIG tests, and the RIA, were in good agreement with regard to the presence or absence of antibodies. Similar results were also obtained with the HI test if nonspecific haemagglutination inhibitors were first removed by treatment with phospholipase C and only titers of 1:20 or greater were considered positive. Children 6\u201323 months of age (n = 45) were without measurable coronavirus antibodies in all four assays. A rapid increase in the prevalence of antibodies then occurred in subsequent age groups, and practically all persons 6 years of age or older were found to have OC43 antibodies as measured by the HIG test or the RIA. The mean antibody levels determined by these two methods continued to increase, however, up to the age group of 10\u201314 years. This increase in antibody levels after the initial antibody incidence plateau may be due to boosting effects caused by related coronavirus strains, since OC43 antigens are known to cross\u2010react with antibodies induced by other human coronaviruses. Taken together, these data suggest that OC43 virus, or an antigenically related coronavirus strain, is very common in Finland.", "qid": 7, "docid": "1e3n1bfy", "rank": 51, "score": 0.7590233683586121}, {"content": "Title: Development and application of an enzyme immunoassay for coronavirus OC43 antibody in acute respiratory illness. Content: Study of coronavirus OC43 infections has been limited because of the lack of sensitive cell culture systems and serologic assays. To improve this circumstance, we developed an indirect enzyme immunoassay (EIA) to detect serum antibody to OC43. Antigen (100 ng) prepared by polyethylene glycol precipitation provided optimal results without a postcoat procedure. Evaluation of intraplate variation indicated that a > or = 2.5-fold increase in serum titer was significant. Sixteen of 18 (89%) paired serum samples with previously identified, reproducible increases in the level of hemagglutination inhibition (HAI) antibody to OC43 also showed significant increases as detected by EIA. Specificity for the EIA was established with paired sera obtained from persons given influenza immunizations or experiencing a respiratory infection. No rise in antibody titers occurred among 33 persons with documented coronavirus 229E infection. EIA was then performed on each of 419 paired serum samples from ambulatory chronic obstructive pulmonary disease patients and healthy older adults, from asthmatic adults presenting for emergency room treatment, and from persons hospitalized with acute respiratory symptoms. Twenty-three antibody rises to OC43 were detected; only nine of these were detected by the HAI test, and the HAI test did not detect any increases in antibody titers that were not detected by EIA. Nineteen of 25 coronavirus OC43 infections for which a month of infection could be assigned occurred between November and February. Overall, 4.4% of acute respiratory illnesses in the studied populations were associated with a coronavirus OC43 infection.", "qid": 7, "docid": "gzf2b2y0", "rank": 52, "score": 0.7586891651153564}, {"content": "Title: Serologic evidence of coronavirus infection in New York and New England dairy cattle with winter dysentery. Content: Acute and convalescent sera were collected from 8 dairy herds with classic clinical features of winter dysentery. An enzyme-linked immunosorbent assay was used to measure coronavirus antibody titers, employing calf diarrhea coronavirus as antigen. Twenty-two of the 35 animals tested (63%) showed a greater than or equal to 4-fold seroconversion. Adult cattle in all 8 herds seroconverted. These findings complement previously reported immunoperoxidase and electron microscopic evidence, suggesting an etiologic role for an enteric coronavirus in this disease.", "qid": 7, "docid": "sqxeyae0", "rank": 53, "score": 0.758552074432373}, {"content": "Title: Coronavirus infections of man associated with diseases other than the common cold Content: About 14,000 paired sera, from patients with various types of acute infectious diseases with suspected viral origin, were screened by complement fixation against a wide set of viral antigens, including coronavirus OC43. A significant change in OC43 antibodies was recorded in 33 cases and a constant high titre, defined as a titre occurring in the respective age group in less than 1 % of all sera examined, was found in 45 cases. On the basis of careful retrospective analysis of hospital case records it was concluded that in 28 cases with an increase of OC43 antibody litres, and in two with titre decrease, a disease could be associated with an acute coronavirus infection. In 16 cases the disease was dominated by respiratory symptoms. Eight of these patients, four children and four adults, had pneumonia. Three of the eight pneumonia patients had, however, another concomitant infection, too. Four patients had neurological symptoms, one had severe perimyocarditis, and in five cases fever was the only symptom recorded. Among the patients with a statistically significant high titre of OC43 antibodies, there were 14 cases where a suggestive association with a disease could be envisaged on the basis of hospital records. Five of these patients had pneumonia. These results suggest that human coronaviruses, so far considered only as one group of causative agents of the common cold, may also be associated with other and more severe diseases in all age groups.", "qid": 7, "docid": "tsb6gul8", "rank": 54, "score": 0.7583032846450806}, {"content": "Title: Seroepidemiology of group I human coronaviruses in children Content: BACKGROUND: Recently, several new human coronaviruses have been identified. OBJECTIVES: To define the seroepidemiology of group I human coronaviruses STUDY DESIGN: A recombinant protein enzyme linked immunosorbent assay (ELISA) based on portions of the nucleocapsid protein of group I human coronaviruses was developed and was used to screen serum from 243 children and young adults. RESULTS: For HCoV-229E, the percentages of seropositive individuals were 57.1% for infants < 2 months old; 38.9% for infants 2\u20133 months old; 4.7% for infants 4\u20135 months old; 42.9\u201350.0% for infants 6\u201312 months old; and 34.8\u201362.5% for individuals 1\u201320 years old. For HCoV-NL63, the percentages of seropositive individuals were 45.2% for infants < 2 months old; 11.1% for infants 2\u20133 months old; 4.7% for infants 4\u20135 months old; 28.6\u201340.0% for infants 6\u201312 months old; and 25.0\u201370.3% for individuals 1\u201320 years old. CONCLUSIONS: Infection with these viruses is common in childhood though the prevalence of these viruses may vary from year to year.", "qid": 7, "docid": "s6x8tblx", "rank": 55, "score": 0.7581027746200562}, {"content": "Title: Analysis of SARS-CoV-2 Antibodies in COVID-19 Convalescent Plasma using a Coronavirus Antigen Microarray Content: The current practice for diagnosis of COVID-19, based on SARS-CoV-2 PCR testing of pharyngeal or respiratory specimens in a symptomatic patient at high epidemiologic risk, likely underestimates the true prevalence of infection. Serologic methods can more accurately estimate the disease burden by detecting infections missed by the limited testing performed to date. Here, we describe the validation of a coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2, in addition to SARS-CoV, MERS-CoV, common human coronavirus strains, and other common respiratory viruses. A comparison of antibody profiles detected on the array from control sera collected prior to the SARS-CoV-2 pandemic versus convalescent blood specimens from virologically confirmed COVID-19 cases demonstrates complete discrimination of these two groups. This array can be used as a diagnostic tool, as an epidemiologic tool to more accurately estimate the disease burden of COVID-19, and as a research tool to correlate antibody responses with clinical outcomes.", "qid": 7, "docid": "ax9btc74", "rank": 56, "score": 0.757627546787262}, {"content": "Title: Cats, coronaviruses and coronavirus antibody tests Content: Feline infectious peritonitis and other coronavirus infections of cats are briefly reviewed. Interpretation and applications of feline coronavirus antibody tests are described, and general recommendations are provided for practitioners. Some of the major unresolved questions regarding coronavirus infections of cats are delineated.", "qid": 7, "docid": "j061ywrl", "rank": 57, "score": 0.7571066617965698}, {"content": "Title: Testing For SARS-CoV-2: The Day the World Turned its Attention to the Clinical Laboratory Content: In the last few months, an unprecedented number of laboratory tests for coronavirus disease 2019 (COVID-19) have been developed at a remarkable speed. With the rapid adoption of these tests into clinical practice, combined with the widespread publicity they received, questions arose related to the different types of tests, their utility, performance, and regulatory approval status. The aim of this publication is to provide a general landscape of laboratory testing for COVID-19 and offer a historical and regulatory perspective associated with them. Specifically, we aim to elaborate on the regulatory complexities of diagnostic testing in the United States and its implications to the present outbreak, as well as provide a synopsis of laboratory tests that have been developed for COVID-19. We will first address the detection of severe acute respiratory syndrome-coronavirus 2 directly by either nucleic acid amplification tests or by the detection of the viral protein for active infections. Subsequently, we will provide an overview of serological tests that can aid not only in diagnosis but additionally help to identify prior infections and potential immunity.", "qid": 7, "docid": "r7glmi7p", "rank": 58, "score": 0.7568690180778503}, {"content": "Title: Performance of Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Assays in Different Stages of Infection: Comparison of Commercial Enzyme-Linked Immunosorbent Assays and Rapid Tests Content: We comparatively assessed sensitivities and specificities of 4 commercial enzyme-linked immunosorbent assays (ELISAs) and 2 rapid tests in 77 patients with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection, grouped by interval since symptom onset. Although test sensitivities were low (<40%) within the first 5 days after disease onset, immunoglobulin (Ig) M, IgA, and total antibody ELISAs increased in sensitivity to >80% between days 6 and 10 after symptom onset. The evaluated tests (including IgG and rapid tests) provided positive results in all patients at or after the 11th day after onset of disease. The specificities of the ELISAs were 83% (IgA), 98% (IgG), and 97% (IgM and total antibody).", "qid": 7, "docid": "ub1t0wwq", "rank": 59, "score": 0.7566680312156677}, {"content": "Title: Specific serology for emerging human coronaviruses by protein microarray. Content: We present a serological assay for the specific detection of IgM and IgG antibodies against the emerging human coronavirus hCoV-EMC and the SARS-CoV based on protein microarray technology. The assay uses the S1 receptor-binding subunit of the spike protein of hCoV-EMC and SARS-CoV as antigens. The assay has been validated extensively using putative cross-reacting sera of patient cohorts exposed to the four common hCoVs and sera from convalescent patients infected with hCoV-EMC or SARS-CoV.", "qid": 7, "docid": "79bzd4nl", "rank": 60, "score": 0.7564783692359924}, {"content": "Title: Evolving status of the 2019 novel coronavirus infection: Proposal of conventional serologic assays for disease diagnosis and infection monitoring Content: The novel coronavirus (nCoV-2019) outbreak in Wuhan, China has spread rapidly nationwide, with some cases occurring in other parts of the world. Although most patients present with mild febrile illness with patchy pulmonary inflammation, a significant portion develop severe acute respiratory distress syndrome (ARDS), with a current case fatality of 2.3-3%. Diagnosis is based on clinical history and laboratory and chest radiographic findings, but confirmation currently relies on nucleic acid-based assays. The latter are playing an important role in facilitating patient isolation, treatment and assessment of infectious activities. However, due to their limited capacity to handle an epidemic of the current scale and insufficient supply of assay kits, only a portion of suspected cases can be tested, leading to incompleteness and inaccuracy in updating new cases, as well as delayed diagnosis. Furthermore, there has not been enough time to assess specificity and sensitivity. Conventional serological assays, such as enzyme-linked immunoassay (ELISA) for specific IgM and IgG antibodies, should offer a high-throughput alternative, which allows for uniform tests for all suspected patients, and can facilitate more complete identification of infected cases and avoidance of unnecessary cross infection among unselected patients. This article is protected by copyright. All rights reserved.", "qid": 7, "docid": "ewcv8m06", "rank": 61, "score": 0.7564666271209717}, {"content": "Title: Development and applications of a bovine coronavirus antigen detection enzyme-linked immunosorbent assay. Content: We developed a monoclonal antibody-based, antigen capture sandwich enzyme-linked immunosorbent assay (ELISA) for bovine coronavirus. We compared the ELISA with electron microscopy and the hemagglutination test and found a close correlation between them. The sensitivity of the ELISA was 10(4) bovine coronavirus particles per ml of 10% fecal suspension. Compared with electron microscopy, bovine coronavirus ELISA had 96% specificity.", "qid": 7, "docid": "6r0gfdma", "rank": 62, "score": 0.7561048269271851}, {"content": "Title: Detection by radioimmunoassay and enzyme-linked immunosorbent assay of coronavirus antibodies in bovine serum and lacteal secretions. Content: The sensitivity of a radioimmunoassay (RIA), an enzyme-linked immunosorbent assay (ELISA), and a serum neutralization assay (SN) for detecting antibodies to bovine coronavirus in serum and colostrum were compared. Although there proved to be a good correlation among all three assays (r = 0.915 and 0.964 for RIA with SN and ELISA, respectively), RIA and ELISA proved to be at least 10 times more sensitive than neutralization tests. By using these techniques, it was possible to detect a time-dependent decrease in antibody levels in bovine colostrum after parturition. Using ELISA, we demonstrated that 12 of 12 herds in Saskatchewan, and 109 of 110 animals tested, and antibody to bovine coronavirus. There was no elevated antibody response in serum or lacteal secretions of cows vaccinated once or twice with a commercially available modified live rota-coronavirus vaccine. In addition to being more sensitive than SN, ELISA and RIA proved to have other advantages for measuring antibody levels to bovine coronavirus and therefore warrant wider use as tools in diagnostic virology.", "qid": 7, "docid": "grahy9up", "rank": 63, "score": 0.7558138370513916}, {"content": "Title: Coronavirus antibodies in sera from patients with multiple sclerosis and matched controls. Content: Sera from patients with multiple sclerosis and carefully matched controls were tested for antibodies to three strains of coronavirus. There was no significant difference in the levels of antibody in the patients vs the controls. We conclude that unless the strains of coronaviruses recently reported to have been isolated from patients with multiple sclerosis express important serological differences from those used in these studies, coronaviruses are not associated with the cause of multiple sclerosis.", "qid": 7, "docid": "o0y0xiq6", "rank": 64, "score": 0.7554759383201599}, {"content": "Title: The spectrum of severe acute respiratory syndrome-associated coronavirus infection. Content: BACKGROUND Whether subclinical or atypical presentations of severe acute respiratory syndrome (SARS) occur and whether clinical judgment is accurate in detecting SARS are unknown. OBJECTIVES To describe the spectrum of SARS coronavirus infection in a large outbreak and to compare diagnoses based on clinical judgment with the SARS coronavirus test. DESIGN Secondary analysis of prospectively collected clinical data and archived serum. SETTING A SARS screening clinic of a university hospital in the New Territories of Hong Kong. PATIENTS 1221 patients attending the clinic between 12 March 2003 and 12 May 2003. MEASUREMENTS SARS coronavirus serology. RESULTS 145 of 553 (26%) patients had serologic evidence of SARS coronavirus infection. Of 910 patients who were managed without hospitalization, only 6 had serologic evidence of SARS. Five of the six patients had normal chest radiographs, and four had symptoms such as myalgia, chills, coughing, and feeling feverish. With the SARS coronavirus serologic test as the gold standard, the clinical diagnosis of probable SARS at hospitalization had a sensitivity of 0.96 (95% CI, 0.91 to 0.98) and a specificity of 0.96 (CI, 0.92 to 0.97). LIMITATIONS Follow-up serologic samples were not obtained from almost half of the patients because they declined further testing. Some people living in the community who were infected but who had minor or no symptoms might not have visited the clinic. CONCLUSIONS There is little evidence of widespread subclinical or mild forms of SARS coronavirus infection. Clinical diagnoses during the outbreak were reasonable and resulted in appropriate triaging.", "qid": 7, "docid": "gu66wmjb", "rank": 65, "score": 0.7551873326301575}, {"content": "Title: The Tecumseh Study of Respiratory Illness. VI. Frequency of and Relationship between Outbreaks of Coronavims Infection Content: Specimens of blood collected in Tecumseh, Michigan over a four-year period were studied for rise in antibody titer against coronavirus OC43. Peaks of infection were found in the winter and spring of 1966, 1968, and 1969; at other times, infections occurred sporadically. All age groups were involved, especially the very young. Rises in titer by CF and by HAI tests frequently did not occur together in the same individual. Agreement between the two tests was better in 1966 and 1969 than in the other years. A portion of the paired specimens showing rises in CF and/ or HAI titer was tested by neutralization. Rises in neutralizing antibody were usually found in pairs collected in 1966 and 1969 but not in those collected in 1967 and 1968. The infecting viruses in 1966 and 1969 thus appeared more closely related to OC43 than did those in 1967 and 1968.", "qid": 7, "docid": "42sx52tn", "rank": 66, "score": 0.7542300820350647}, {"content": "Title: First external quality assurance of antibody diagnostic for SARS-new coronavirus Content: Abstract To confirm an infection with the new coronavirus (SARS-CoV) causing the severe acute respiratory syndrome (SARS) diagnostic assays for detection of SARS-CoV specific antibody are necessary. To evaluate the diagnostic performance of laboratories an external quality assurance (EQA) study was performed in 2004. Participating laboratories (9/20) correctly detected anti-SARS antibodies in serum samples without false positive results in an immunofluorescence assay. In contrast, only 4/13 laboratories detected most of the anti-SARS antibody positive samples without false positive results using enzyme immunoassays (EIA) and/or immunoblot. The overall results clearly demonstrate that serological diagnosis of SARS-CoV remains at an early stage of development, with further technical improvements required, particularly with respect to the use of SARS specific EIAs.", "qid": 7, "docid": "bt4oi1xf", "rank": 67, "score": 0.7540801763534546}, {"content": "Title: [Serological diagnostic studies of the occurrence of coronavirus infections in cattle with respiratory diseases]. Content: Of paired serum samples of 196 cattle with respiratory disease from 37 herds which were tested for hemagglutination inhibiting antibodies against coronavirus (BCV) 185 of the first specimens and 190 of the second ones gave positive results. This difference was due to five animals of five different farms showing seroconversions between the time of the blood collections. A significant rise in antibody titer (no less than 4-fold) was evident in 28 cattle from 3 of the above mentioned and 12 other farms. Altogether serological indication of acute coronavirus infections were gained in 33 (16.8%) of animals with respiratory diseases which derived from 17 of 37 herds. Most of these infections (about 35%) occurred in animals older than 6 months while calves up to 3 or 6 months were only affected in a ratio of ca. 10%, respectively.", "qid": 7, "docid": "vsy97xb3", "rank": 68, "score": 0.7537621855735779}, {"content": "Title: Enqu\u00eate s\u00e9rologique par immunofluorescence indirecte, sur les infections \u00e0 coronavirus OC43 Content: Summary Four-hundred seventy-two sera were examined by the indirect immunofluorescence test against Coronavirus strain OC43 adapted to the HRT18 cell culture. Sera were from children and adults hospitalized over a 4-year period, from 1979 to 1982, at the CHRU of Clermont-Ferrand (France) for different clinical reasons. Of the 446 sera tested, 61 % showed antibodies against OC43; 90 % of adult sera were positive. Coronavirus infections are very common in France. Immunity appears early in life, and infection is frequent in children from 12\u201336 months of age.", "qid": 7, "docid": "olhh6pjg", "rank": 69, "score": 0.7534849047660828}, {"content": "Title: Evaluation of the EUROIMMUN Anti-SARS-CoV-2 ELISA Assay for detection of IgA and IgG antibodies Content: As the Coronavirus 2019 (COVID-19) pandemic evolves, the development of immunoassays to help determine exposure and potentially predict immunity has become a pressing priority. In this report we present the performance of the EUROIMMUN enzyme-linked immunosorbent assay (ELISA) for semi-quantitative detection of IgA and IgG antibodies in serum and plasma samples using recombinant S1 domain of the SARS-CoV-2 spike protein as antigen. Specimens from patients, with and without COVID-19 infection, were tested at the University of Chicago Clinical Microbiology and Immunology Laboratory. Of 57 samples from COVID-19 PCR-negative patients, including 28 samples positive for common human coronavirus strains, 53 tested negative and 4 tested positive for IgA (93.0% agreement) while 56 tested negative and 1 tested positive for IgG (98.2% agreement). For COVID-19 PCR-positive patients, 29 of 30 (96.7%) samples collected \u22653 days after positive PCR were positive for IgA, and 28 of 28 samples collected \u22654 days after positive PCR were positive for IgG. The EUROIMMUN Anti-SARS-CoV-2 ELISA Assay demonstrates excellent sensitivity for detection of IgA and IgG antibodies from samples collected \u22653 days and \u22654 days, respectively, after COVID-19 diagnosis by PCR. This assay did not demonstrate cross reaction in any of the 28 samples from patients with common human coronaviruses, including types HKU1, NL63, CV229E, and OC43.", "qid": 7, "docid": "jzpwo5un", "rank": 70, "score": 0.7534738779067993}, {"content": "Title: Dynamic profile for the detection of anti-SARS-CoV-2 antibodies using four immunochromatographic assays Content: In order to fight the SARS-CoV-2 pandemic infection, there is a growing need and demand for diagnostic tools that are complementary and different from the RT-PCR currently in use. Multiple serological tests are or will be very soon available but need to be evaluated and validated. We have thus tested 4 immunochromatographic tests for the detection of antibodies to SARS-CoV-2. In addition, we assessed the kinetics of antibody appearance using these assays in 22 patients after they were tested positive by RT-PCR. We observed great heterogeneity in antibody detection post-symptom onset. The median antibody detection time was between 8 and 10 days according to the manufacturers. All the tests showed a sensitivity of 60 to 80% on day 10 and 100% on day 15. In addition, a single cross-reaction was observed with other human coronavirus infections. Thus, immunochromatographic tests for the detection of anti-SARS-CoV-2 antibodies may have their place for the diagnostic panel of COVID-19.", "qid": 7, "docid": "wf5cozst", "rank": 71, "score": 0.7532278895378113}, {"content": "Title: Antibody tests for identification of current and past infection with SARS-CoV-2. Content: BACKGROUND The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and resulting COVID-19 pandemic present important diagnostic challenges. Several diagnostic strategies are available to identify current infection, rule out infection, identify people in need of care escalation, or to test for past infection and immune response. Serology tests to detect the presence of antibodies to SARS-CoV-2 aim to identify previous SARS-CoV-2 infection, and may help to confirm the presence of current infection. OBJECTIVES To assess the diagnostic accuracy of antibody tests to determine if a person presenting in the community or in primary or secondary care has SARS-CoV-2 infection, or has previously had SARS-CoV-2 infection, and the accuracy of antibody tests for use in seroprevalence surveys. SEARCH METHODS We undertook electronic searches in the Cochrane COVID-19 Study Register and the COVID-19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. We conducted searches for this review iteration up to 27 April 2020. SELECTION CRITERIA We included test accuracy studies of any design that evaluated antibody tests (including enzyme-linked immunosorbent assays, chemiluminescence immunoassays, and lateral flow assays) in people suspected of current or previous SARS-CoV-2 infection, or where tests were used to screen for infection. We also included studies of people either known to have, or not to have SARS-CoV-2 infection. We included all reference standards to define the presence or absence of SARS-CoV-2 (including reverse transcription polymerase chain reaction tests (RT-PCR) and clinical diagnostic criteria). DATA COLLECTION AND ANALYSIS We assessed possible bias and applicability of the studies using the QUADAS-2 tool. We extracted 2x2 contingency table data and present sensitivity and specificity for each antibody (or combination of antibodies) using paired forest plots. We pooled data using random-effects logistic regression where appropriate, stratifying by time since post-symptom onset. We tabulated available data by test manufacturer. We have presented uncertainty in estimates of sensitivity and specificity using 95% confidence intervals (CIs). MAIN RESULTS We included 57 publications reporting on a total of 54 study cohorts with 15,976 samples, of which 8526 were from cases of SARS-CoV-2 infection. Studies were conducted in Asia (n = 38), Europe (n = 15), and the USA and China (n = 1). We identified data from 25 commercial tests and numerous in-house assays, a small fraction of the 279 antibody assays listed by the Foundation for Innovative Diagnostics. More than half (n = 28) of the studies included were only available as preprints. We had concerns about risk of bias and applicability. Common issues were use of multi-group designs (n = 29), inclusion of only COVID-19 cases (n = 19), lack of blinding of the index test (n = 49) and reference standard (n = 29), differential verification (n = 22), and the lack of clarity about participant numbers, characteristics and study exclusions (n = 47). Most studies (n = 44) only included people hospitalised due to suspected or confirmed COVID-19 infection. There were no studies exclusively in asymptomatic participants. Two-thirds of the studies (n = 33) defined COVID-19 cases based on RT-PCR results alone, ignoring the potential for false-negative RT-PCR results. We observed evidence of selective publication of study findings through omission of the identity of tests (n = 5). We observed substantial heterogeneity in sensitivities of IgA, IgM and IgG antibodies, or combinations thereof, for results aggregated across different time periods post-symptom onset (range 0% to 100% for all target antibodies). We thus based the main results of the review on the 38 studies that stratified results by time since symptom onset. The numbers of individuals contributing data within each study each week are small and are usually not based on tracking the same groups of patients over time. Pooled results for IgG, IgM, IgA, total antibodies and IgG/IgM all showed low sensitivity during the first week since onset of symptoms (all less than 30.1%), rising in the second week and reaching their highest values in the third week. The combination of IgG/IgM had a sensitivity of 30.1% (95% CI 21.4 to 40.7) for 1 to 7 days, 72.2% (95% CI 63.5 to 79.5) for 8 to 14 days, 91.4% (95% CI 87.0 to 94.4) for 15 to 21 days. Estimates of accuracy beyond three weeks are based on smaller sample sizes and fewer studies. For 21 to 35 days, pooled sensitivities for IgG/IgM were 96.0% (95% CI 90.6 to 98.3). There are insufficient studies to estimate sensitivity of tests beyond 35 days post-symptom onset. Summary specificities (provided in 35 studies) exceeded 98% for all target antibodies with confidence intervals no more than 2 percentage points wide. False-positive results were more common where COVID-19 had been suspected and ruled out, but numbers were small and the difference was within the range expected by chance. Assuming a prevalence of 50%, a value considered possible in healthcare workers who have suffered respiratory symptoms, we would anticipate that 43 (28 to 65) would be missed and 7 (3 to 14) would be falsely positive in 1000 people undergoing IgG/IgM testing at days 15 to 21 post-symptom onset. At a prevalence of 20%, a likely value in surveys in high-risk settings, 17 (11 to 26) would be missed per 1000 people tested and 10 (5 to 22) would be falsely positive. At a lower prevalence of 5%, a likely value in national surveys, 4 (3 to 7) would be missed per 1000 tested, and 12 (6 to 27) would be falsely positive. Analyses showed small differences in sensitivity between assay type, but methodological concerns and sparse data prevent comparisons between test brands. AUTHORS' CONCLUSIONS The sensitivity of antibody tests is too low in the first week since symptom onset to have a primary role for the diagnosis of COVID-19, but they may still have a role complementing other testing in individuals presenting later, when RT-PCR tests are negative, or are not done. Antibody tests are likely to have a useful role for detecting previous SARS-CoV-2 infection if used 15 or more days after the onset of symptoms. However, the duration of antibody rises is currently unknown, and we found very little data beyond 35 days post-symptom onset. We are therefore uncertain about the utility of these tests for seroprevalence surveys for public health management purposes. Concerns about high risk of bias and applicability make it likely that the accuracy of tests when used in clinical care will be lower than reported in the included studies. Sensitivity has mainly been evaluated in hospitalised patients, so it is unclear whether the tests are able to detect lower antibody levels likely seen with milder and asymptomatic COVID-19 disease. The design, execution and reporting of studies of the accuracy of COVID-19 tests requires considerable improvement. Studies must report data on sensitivity disaggregated by time since onset of symptoms. COVID-19-positive cases who are RT-PCR-negative should be included as well as those confirmed RT-PCR, in accordance with the World Health Organization (WHO) and China National Health Commission of the People's Republic of China (CDC) case definitions. We were only able to obtain data from a small proportion of available tests, and action is needed to ensure that all results of test evaluations are available in the public domain to prevent selective reporting. This is a fast-moving field and we plan ongoing updates of this living systematic review.", "qid": 7, "docid": "4cbjbo7t", "rank": 72, "score": 0.75300133228302}, {"content": "Title: Evaluating the serological status of COVID-19 patients using an indirect immunofluorescent assay, France. Content: An indirect immunofluorescent assay was developed in order to assess the serological status of 888 RT-PCR-confirmed COVID-19 patients (1,302 serum samples) and controls in Marseille, France. Incorporating an inactivated clinical SARS CoV-2 isolate as the antigen, the specificity of the assay was measured as 100% for IgA titre [\u2265] 1:200; 98.6% for IgM titre [\u2265] 1:200; and 96.3% for IgG titre [\u2265] 1:100 after testing a series of negative controls as well as 150 serums collected from patients with non-SARS-CoV-2 Coronavirus infection, non-Coronavirus pneumonia and infections known to elicit false-positive serology. Seroprevalence was then measured at 3% before a five-day evolution up to 47% after more than 15 days of evolution. We observed that the seroprevalence as well as the titre of specific antibodies were both significantly higher in patients with a poor clinical outcome than in patients with a favourable evolution. These data, which have to be integrated into the ongoing understanding of the immunological phase of the infection, suggest that serotherapy may not be a therapeutic option in patients with severe COVID-19 infection. The IFA assay reported here is useful for monitoring SARS-CoV-2 exposure at the individual and population levels.", "qid": 7, "docid": "vd2ti1l8", "rank": 73, "score": 0.7520589828491211}, {"content": "Title: [Development of a SPA-ELISA method for detecting anti-coronavirus IgG antibodies in serum samples from fulvous fruit bats]. Content: OBJECTIVE To develop an simple and sensitive method for detecting anti-coronavirus IgG antibodies in bat sera based on enzyme-linked immunosorbent assay (ELISA). METHODS A commercial ELISA kit for detecting SARS-CoV antibody was modified for detecting coronavirus antibodies in bat serum samples. The second antibody in the kit was replaced with horseradish peroxidase-conjugated protein-A (HRP-SPA) based on the characteristics of binding between Staphylococcus aureus protein A (SPA) and mammal IgG Fc fragment. The sera of 55 fulvous fruit bats (Rousettus dasymallus) were tested using the SPA-ELISA. RESULTS The test results of the positive and negative controls in the kit and the serum samples from convalescent ;patient were consistent with expectation. Coronavirus antibody was detected in 2 out of the 55 bat serum samples. Serum neutralization test confirmed the validity of the SPA-ELISA method. CONCLUSION This SPA-ELISA method is applicable for detecting coronavirus antibody in bat sera.", "qid": 7, "docid": "vwy25qah", "rank": 74, "score": 0.7517439126968384}, {"content": "Title: Serological differentiation between COVID-19 and SARS infections Content: In response to the coronavirus disease 2019 (COVID-19) outbreak, caused by the SARS-CoV-2 virus, multiple diagnostic tests are required globally for acute disease diagnosis, contact tracing, monitoring of asymptomatic infection rates and assessing herd immunity. While PCR remains the frontline test of choice in the acute diagnostic setting, serological tests are urgently needed to fulfil the other requirements. Unlike PCR tests which are highly specific for each virus, cross-reactivity could potentially be a major challenge for COVID-19 antibody tests considering there are six other coronaviruses known to infect humans. Among the human pathogens, SARS-CoV is genetically most related to SARS-CoV-2 sharing approximately 80% sequence identity and both belong to the species SARS related coronavirus (SARSr-CoV) in the genus Betacoronavirus of family Coronaviridae. In this study, we developed and compared the performance of four different serological tests to comprehensively assess the cross-reactivity between COVID-19 and SARS patient sera. Our results indicate that there is a significant cross-reactivity when N protein of either SARS-CoV or SARS-CoV-2 is used. The S1 or RBD derived the spike (S) protein offers better specificity. Amongst the different platforms, capture ELISA performed best. Finally, we found that SARS survivors all have significant level of antibodies remaining in their blood 17 years after infection. We discovered that anti-N antibodies waned more than anti-RBD antibodies, and the latter is known to play a more important role in providing protective immunity.", "qid": 7, "docid": "0yj3xp9s", "rank": 75, "score": 0.7516833543777466}, {"content": "Title: Serological differentiation between COVID-19 and SARS infections. Content: In response to the coronavirus disease 2019 (COVID-19) outbreak, caused by the SARS-CoV-2 virus, multiple diagnostic tests are required globally for acute disease diagnosis, contact tracing, monitoring of asymptomatic infection rates and assessing herd immunity. While PCR remains the frontline test of choice in the acute diagnostic setting, serological tests are urgently needed to fulfil the other requirements. Unlike PCR tests which are highly specific for each virus, cross-reactivity could potentially be a major challenge for COVID-19 antibody tests considering there are six other coronaviruses known to infect humans. Among the human pathogens, SARS-CoV is genetically most related to SARS-CoV-2 sharing approximately 80% sequence identity and both belong to the species SARS related coronavirus (SARSr-CoV) in the genus Betacoronavirus of family Coronaviridae. In this study, we developed and compared the performance of four different serological tests to comprehensively assess the cross-reactivity between COVID-19 and SARS patient sera. Our results indicate that there is a significant cross-reactivity when N protein of either SARS-CoV or SARS-CoV-2 is used. The S1 or RBD derived the spike (S) protein offers better specificity. Amongst the different platforms, capture ELISA performed best. Finally, we found that SARS survivors all have significant level of antibodies remaining in their blood 17 years after infection. We discovered that anti-N antibodies waned more than anti-RBD antibodies, and the latter is known to play a more important role in providing protective immunity.", "qid": 7, "docid": "0jl6qu0i", "rank": 76, "score": 0.7516833543777466}, {"content": "Title: Prevalence of subclinical infection by the SARS coronavirus among general practitioners in Hong Kong. Content: Eight general practitioners had severe acute respiratory distress syndrome (SARS) in Hong Kong during the epidemic, and others may have been infected by the SARS coronavirus without developing the full syndrome. We conducted a serological and questionnaire survey to determine the prevalence of subclinical infection by SARS coronavirus among general practitioners in Hong Kong. Participants had to be doctors actively practising in family medicine and who did not have SARS. Approximately 3200 general practitioners were invited to participate and the results of 574 were eligible for analysis. 29 samples were tested positive by enzyme-linked immunosorbent assay, but all these samples had titre < 25 by immunoflorescence assay. The prevalence for seropositivity was thus 0% (95% CI, 0.0%-0.6%). This finding documents the lack of subclinical infection by SARS coronavirus in an at-risk group in the community.", "qid": 7, "docid": "2dkn2udm", "rank": 77, "score": 0.7515672445297241}, {"content": "Title: Efficacy of Serology Testing in Predicting Reinfection in Patients with SARS-CoV-2. Content: In many parts of the United States, SARS-CoV-2 cases have reached peak infection rates, prompting administrators to create protocols to resume elective cases. As elective procedures and surgeries get scheduled, ASCs must implement some form of widespread testing in order to ensure the safety of both the ASC staff as well as the patients being seen. The CDC recently announced the approval of new serological testing for SARS-CoV-2, a test that can indicate the presence of IgM and IgG antibodies in the serum against viral particles. However, the possibility for reinfection raises questions about the utility of this new serological test, as the presence of IgG may not correspond to long-term immunity. The coronavirus has been known to form escape mutations, which may correspond to reduction in immunoglobulin binding capacity. Patients who develop more robust immune responses with formation of memory CD8+ T-cells and helper CD4+ T-cells will be the most equipped if exposed to the virus, but unfortunately the serology test will not help us in distinguishing those individuals. Given the inherent disadvantages of serological testing, antibody testing alone should not be used when deciding patient care and should be combined with PCR testing.", "qid": 7, "docid": "g1dij8ty", "rank": 78, "score": 0.7513519525527954}, {"content": "Title: Efficacy of Serology Testing in Predicting Reinfection in Patients with SARS-CoV-2 Content: In many parts of the United States, SARS-CoV-2 cases have reached peak infection rates, prompting administrators to create protocols to resume elective cases. As elective procedures and surgeries get scheduled, ASCs must implement some form of widespread testing in order to ensure the safety of both the ASC staff as well as the patients being seen. The CDC recently announced the approval of new serological testing for SARS-CoV-2, a test that can indicate the presence of IgM and IgG antibodies in the serum against viral particles. However, the possibility for reinfection raises questions about the utility of this new serological test, as the presence of IgG may not correspond to long-term immunity. The coronavirus has been known to form escape mutations, which may correspond to reduction in immunoglobulin binding capacity. Patients who develop more robust immune responses with formation of memory CD8+ T-cells and helper CD4+ T-cells will be the most equipped if exposed to the virus, but unfortunately the serology test will not help us in distinguishing those individuals. Given the inherent disadvantages of serological testing, antibody testing alone should not be used when deciding patient care and should be combined with PCR testing.", "qid": 7, "docid": "m71ut1sd", "rank": 79, "score": 0.7513518929481506}, {"content": "Title: Preliminary Results of Seroprevalence of SARS-CoV-2 at Community Clinics in Tokyo Content: Serological evaluation with SARS-CoV-2 specific IgG antibody will be an alternative way to know the pandemic of novel coronavirus disease (COVID-19) if the capacity for diagnostic PCR test is limited. The point-of-care test to detect SARS-CoV-2 specific IgG antibody in peripheral blood (n =202) was performed in two community clinics in Tokyo, Japan. The overall positive rate of SRAS-CoV-2 IgG antibody was 5.9% (95% confidence interval[CI]: 3.1-10.1). Higher rate was observed for healthcare workers (n =55, 9.1 [3.0-20.0]). The limitation on antibody tests includes low sensitivity and potent cross-reactivity with the previous coronavirus. Robust healthcare policy to efficiently monitor COVID-19 spread is warranted in Tokyo.", "qid": 7, "docid": "vchnxw27", "rank": 80, "score": 0.7511273622512817}, {"content": "Title: SARS-CoV-2 antibody testing-questions to be asked Content: Severe acute respiratory syndrome coronavirus 2 infection and development of coronavirus disease 2019 presents a major health care challenge of global dimensions. Laboratory diagnostics of infected patients, and the assessment of immunity against severe acute respiratory syndrome coronavirus 2, presents a major cornerstone in handling the pandemic. Currently, there is an increase in demand for antibody testing and a large number of tests are already marketed or are in the late stage of development. However, the interpretation of test results depends on many variables and factors, including sensitivity, specificity, potential cross-reactivity and cross-protectivity, the diagnostic value of antibodies of different isotypes, and the use of antibody testing in identification of acutely ill patients or in epidemiological settings. In this article, the recently established COVID-19 Task Force of the German Society for Clinical Chemistry and Laboratory Medicine (DGKL) addresses these issues on the basis of currently available data sets in this rapidly moving field.", "qid": 7, "docid": "laobflfb", "rank": 81, "score": 0.7510682940483093}, {"content": "Title: Identification of antibody against porcine coronavirus in human milk. Content: A total of 239 human milk samples collected from mothers in Chiba City, Japan during 1994-1997 were tested for the presence of anti-coronavirus antibody. Interestingly, twelve human milk samples were positive for IgA against porcine transmissible gastroenteritis coronavirus, and this represented 5%. These findings provided evidence that the interspecies transmission of coronavirus between human and porcine might occur in nature. This report is noteworthy because it is the first, to the best of our knowledge, demonstrating the presence of antibody against porcine transmissible gastroenteritis coronavirus in human milk.", "qid": 7, "docid": "d0ck3fg7", "rank": 82, "score": 0.7506386637687683}, {"content": "Title: Antibodies to coronaviruses are higher in older compared with younger adults and binding antibodies are more sensitive than neutralizing antibodies in identifying coronavirus\u2010associated illnesses Content: Human coronaviruses (HCoV) are common causes of respiratory illnesses (RI) despite preexisting humoral immunity. Sera were obtained near the onset of RI and 3 to 4 weeks later as part of a prospective study of 200 subjects evaluated for RI from 2009 to 2013. Antibodies against common HCoV strains were measured by enzyme\u2010linked immunosorbent assay and neutralization assay comparing older adults with cardiopulmonary diseases (99 subjects) to younger, healthy adults (101 subjects). Virus shedding was detected in respiratory secretions by polymerase chain reaction. Of 43 HCoV\u2010associated illnesses, 15 (35%) occurred in 14 older adults (aged \u226560 years) and 28 (65%) in 28 younger adults (aged 21\u201040 years). Binding and neutralizing antibodies were higher in older adults. Only 16 (35.7%) of RI with increases in binding antibodies also had increases in neutralizing antibodies to HCoV. Increases in binding antibodies with RI were more frequent than increased neutralizing antibodies and virus shedding, and more frequent in younger compared to older adults. Functional neutralizing antibodies were not stimulated as often as binding antibodies, explaining in part a susceptibility to reinfection with HCoV. Monitoring binding antibodies may be more sensitive for the serologic detection of HCoV infections.", "qid": 7, "docid": "o0xwhm57", "rank": 83, "score": 0.7504415512084961}, {"content": "Title: Evaluation of the performance of SARS-CoV-2 serological tools and their positioning in COVID-19 diagnostic strategies Content: Rapid and accurate diagnosis is crucial for successful outbreak containment. During the current coronavirus disease 2019 (COVID-19) public health emergency, the gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosis is the detection of viral RNA by reverse transcription (RT)-PCR. Additional diagnostic methods enabling the detection of current or past SARS-CoV-2 infection would be highly beneficial to ensure the timely diagnosis of all infected and recovered patients. Here, we investigated several serological tools, i.e., two immunochromatographic lateral flow assays (LFA-1 (Biosynex COVID-19 BSS) and LFA-2 (COVID-19 Sign IgM/IgG)) and two enzyme-linked immunosorbent assays (ELISAs) detecting IgA (ELISA-1 Euroimmun), IgM (ELISA-2 EDI) and/or IgG (ELISA-1 and ELISA-2) based on well-characterized panels of serum samples from patients and healthcare workers with PCR-confirmed COVID-19 and from SARS-CoV-2-negative patients. A total of 272 serum samples were used, including 62 serum samples from hospitalized patients (panel 1 and panel 3), 143 serum samples from healthcare workers (panel 2) diagnosed with COVID-19 and 67 serum samples from negative controls. Diagnostic performances of each assay were assessed according to days after symptom onset (dso) and the antigenic format used by manufacturers. We found overall sensitivities ranging from 69% to 93% on panels 1 and 2 and specificities ranging from 83% to 98%. The clinical sensitivity varied greatly according to the panel tested and the dso. The assays we tested showed poor mutual agreement. A thorough selection of serological assays for the detection of ongoing or past infections is advisable.", "qid": 7, "docid": "chuaqnl2", "rank": 84, "score": 0.7504007816314697}, {"content": "Title: Detection of specific antibodies to severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein for serodiagnosis of SARS coronavirus pneumonia. Content: We report the evaluation of recombinant severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) nucleocapsid protein enzyme-linked immunosorbent assay (ELISA)-based antibody tests for serodiagnosis of SARS-CoV pneumonia and compare the sensitivities and specificities of this ELISA for detection of immunoglobulin G (IgG), IgM, IgA, and their combinations with serum samples from 149 healthy blood donors who donated blood 3 years ago as controls and 106 SARS-CoV pneumonia patients in Hong Kong. The specificities of the ELISA for IgG, IgM, and IgA detection were 95.3, 96.6, and 96.6%, respectively, with corresponding sensitivities of 94.3, 59.4, and 60.4%, respectively. The present ELISA appears to be a sensitive test for serodiagnosis of SARS-CoV pneumonia, is much more economical and less labor-intensive than the indirect immunofluorescence assay, and does not require cultivation of SARS-CoV.", "qid": 7, "docid": "b1qnfl41", "rank": 85, "score": 0.7503347992897034}, {"content": "Title: An enzyme-linked immunosorbent assay using canine coronavirus-infected CRFK cells as antigen for detection of anti-coronavirus antibody in cat Content: Abstract From the reasons that canine coronavirus (CCV) grows more efficiently than feline coronavirus in a cell culture and they are mutually related in their antigenicities, an enzyme-linked immunosorbent assay (ELISA) using CCV-infected feline kidney (CRFK) cells as substrate antigens was developed for detection of anti-coronavirus antibodies in cats. It was indispensable for generating coronavirus-specific ELISA antibody activities that the sample was applied to the mock-infected, normal CRFK cells in parallel with the CCV-infected cells and then the optical density values given by the mock-infected cell antigen were subtracted from those given by the virus-infected cell antigen. On the basis of ELISA antibody titers obtained in sera from the cats experimentally infected with CCV and from the spontaneous feline infectious peritonitis (FIP) cases, the ELISA described in the present study was found to be applicable as a simple and easy serologic test which was able to detect anti-coronavirus antibodies as efficiently as the indirect immunofluorescence assay with homologous FIP virus.", "qid": 7, "docid": "uyqqalyv", "rank": 86, "score": 0.7501816749572754}, {"content": "Title: Antigenic assessment of coronaviruses isolated from patients with multiple sclerosis. Content: Many studies have either supported or discounted the role of coronaviruses as etiologic agents in multiple sclerosis (MS). Two new approaches were applied to investigate this controversy. First, monoclonal antibodies specific for either murine coronaviruses (mouse hepatitis viruses) or human coronaviruses were used to characterize the antigenic features of MS-derived coronaviruses SK and SD. Both isolates were found to have a mouse hepatitis virus-type profile. Second, serum and cerebrospinal fluid antibodies to different coronaviruses, including SD, were measured in MS and control groups. No significant difference in antibody level to coronaviruses was found between MS and control samples. The results of these antigenic studies do not support a specific association between MS and coronaviruses.", "qid": 7, "docid": "xo7vyahe", "rank": 87, "score": 0.7498295307159424}, {"content": "Title: Double-antigen sandwich ELISA for detection of antibodies to SARS-associated coronavirus in human serum Content: The study presented here was conducted to evaluate the performance of a double-antigen sandwich ELISA to detect antibodies in human serum against the coronavirus associated with severe acute respiratory syndrome (SARS). A recombinant partial nucleocapsid protein of SARS-associated coronavirus was used as a serodiagnostic antigen in the ELISA. A total of 2892 clinical serum samples were tested with the ELISA kit, which positively identified 25 of 35 (71.4%) samples of patients with confirmed SARS infection, 286 of 407 (70%) samples of patients suspected of having SARS, 229 of 302 (75.8%) samples of convalescent SARS patients, and 0 of 544 samples obtained from healthcare workers; only 1 of 1604 clinical samples obtained from patients with other diseases demonstrated a weakly positive result. These results indicate that the double-antigen sandwich ELISA is an effective screening method for the serodiagnosis of SARS-associated coronavirus.", "qid": 7, "docid": "epd1zeif", "rank": 88, "score": 0.7497344017028809}, {"content": "Title: Serology characteristics of SARS-CoV-2 infection since exposure and post symptom onset. Content: BACKGROUND Timely diagnosis of SARS-CoV-2 infection is a prerequisite for treatment and prevention. The serology characteristics and complement diagnosis value of the antibody test to RNA test need to be demonstrated. METHOD Serial sera of 80 patients with PCR-confirmed COVID-19 were collected at the First Affiliated Hospital of Zhejiang University, China. Total antibody (Ab), IgM and IgG antibodies against SARS-CoV-2 were detected, and the antibody dynamics during the infection were described. RESULTS The seroconversion rates for Ab, IgM and IgG were 98.8%, 93.8% and 93.8%, respectively. The first detectible serology marker was Ab, followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 days post exposure (d.p.e) or 9, 10 and 12 days post onset (d.p.o), respectively. The antibody levels increased rapidly beginning at 6 d.p.o. and were accompanied by a decline in viral load. For patients in the early stage of illness (0-7 d.p.o), Ab showed the highest sensitivity (64.1%) compared to IgM and IgG (33.3% for both, p<0.001). The sensitivities of Ab, IgM and IgG increased to 100%, 96.7% and 93.3% 2 weeks later, respectively. When the same antibody type was detected, no significant difference was observed between enzyme-linked immunosorbent assays and other forms of immunoassays. CONCLUSIONS A typical acute antibody response is induced during SARS-CoV-2 infection. Serology testing provides an important complement to RNA testing in the later stages of illness for pathogenic specific diagnosis and helpful information to evaluate the adapted immunity status of patients.", "qid": 7, "docid": "hnbxfbeo", "rank": 89, "score": 0.7496959567070007}, {"content": "Title: Serological studies of transmissible gastroenteritis in Great Britain, using a competitive ELISA. Content: A competitive ELISA which differentiates between transmissible gastroenteritis virus (TGEV) and porcine respiratory coronavirus (PRCV) was used to detect non-neutralising antibodies to the peplomer protein of TGEV in porcine sera. The test was shown to be TGEV specific, having a relative specificity of 100 per cent, and to have a relative sensitivity of 94.9 per cent when compared with the virus neutralisation test. The prevalence of TGEV in Great Britain is low; only 0.6 per cent of sows sampled in 1990 were seropositive to TGEV. Seroconversion to the virus neutralisation test occurred in a closed herd in 1984, with no apparent spread, but later testing by the ELISA did not detect any blocking antibodies. The possibility of the existence of a less contagious strain of PRCV is discussed. All British isolates of TGEV tested by the indirect fluorescent antibody test were recognised by the monoclonal antibody 1D.B12, the indicator antibody in the ELISA.", "qid": 7, "docid": "2n2toniv", "rank": 90, "score": 0.7492015361785889}, {"content": "Title: Diagnostic value and dynamic variance of serum antibody in coronavirus disease 2019 Content: OBJECTIVE: To investigate the diagnostic value of serological testing and dynamic variance of serum antibody in coronavirus disease 2019 (COVID-19). METHODS: This study retrospectively included 43 patients with a laboratory-confirmed infection and 33 patients with a suspected infection, in whom the disease was eventually excluded. The IgM/IgG titer of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was measured by chemiluminescence immunoassay analysis. RESULTS: Compared to molecular detection, the sensitivities of serum IgM and IgG antibodies to diagnose COVID-19 were 48.1% and 88.9%, and the specificities were 100% and 90.9%, respectively.In the COVID-19 group, the IgM-positive rate increased slightly at first and then decreased over time; in contrast, the IgG-positive rate increased to 100% and was higher than IgM at all times. The IgM-positive rate and titer were not significantly different before and after conversion to virus-negative. The IgG-positive rate was up to 90% and not significantly different before and after conversion to virus-negative. However, the median IgG titer after conversion to virus-negative was double that before, and the difference was significant. CONCLUSIONS: Viral serological testing is an effective means of diagnosis for SARS-CoV-2 infection. The positive rate and titer variance of IgG are higher than those of IgM in COVID-19.", "qid": 7, "docid": "5ig5upot", "rank": 91, "score": 0.7492014169692993}, {"content": "Title: Serology characteristics of SARS-CoV-2 infection since exposure and post symptom onset Content: BACKGROUND: Timely diagnosis of SARS-CoV-2 infection is a prerequisite for treatment and prevention. The serology characteristics and complement diagnosis value of the antibody test to RNA test need to be demonstrated. METHOD: Serial sera of 80 patients with PCR-confirmed COVID-19 were collected at the First Affiliated Hospital of Zhejiang University, China. Total antibody (Ab), IgM and IgG antibodies against SARS-CoV-2 were detected, and the antibody dynamics during the infection were described. RESULTS: The seroconversion rates for Ab, IgM and IgG were 98.8%, 93.8% and 93.8%, respectively. The first detectible serology marker was Ab, followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20\u00e2\u0080 days post exposure (d.p.e) or 9, 10 and 12\u00e2\u0080 days post onset (d.p.o), respectively. The antibody levels increased rapidly beginning at 6\u00e2\u0080 d.p.o. and were accompanied by a decline in viral load. For patients in the early stage of illness (0-7\u00e2\u0080 d.p.o), Ab showed the highest sensitivity (64.1%) compared to IgM and IgG (33.3% for both, p<0.001). The sensitivities of Ab, IgM and IgG increased to 100%, 96.7% and 93.3% 2\u00e2\u0080 weeks later, respectively. When the same antibody type was detected, no significant difference was observed between enzyme-linked immunosorbent assays and other forms of immunoassays. CONCLUSIONS: A typical acute antibody response is induced during SARS-CoV-2 infection. Serology testing provides an important complement to RNA testing in the later stages of illness for pathogenic specific diagnosis and helpful information to evaluate the adapted immunity status of patients.", "qid": 7, "docid": "j5ag12zr", "rank": 92, "score": 0.7491264343261719}, {"content": "Title: Test, test, test for COVID-19 antibodies: the importance of sensitivity, specificity and predictive powers Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests of varying specificity and sensitivity are now available. For informing individuals whether they have had coronavirus disease 2019 (COVID-19), they need to be very accurate. For measuring population prevalence of past infection, the numbers of false positives and negatives need to be roughly equal. With a series of worked examples for a notional population of 100,000 people, we show that even test systems with a high specificity can yield a large number of false positive results, especially where the population prevalence is low. For example, at a true population prevalence of 5%, using a test with 99% sensitivity and specificity, 16% of positive results will be false and thus 950 people will be incorrectly informed they have had the infection. Further confirmatory testing may be needed. Giving false reassurance on which personal or societal decisions might be based could be harmful for individuals, undermine public confidence and foster further outbreaks.", "qid": 7, "docid": "hzi3kvw5", "rank": 93, "score": 0.7490869760513306}, {"content": "Title: In vitro diagnostics of coronavirus disease 2019: Technologies and application Content: Laboratory-based diagnostic measures including virological and serological tests are essential for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Real-time reverse transcription-polymerase chain reactions (rRT-PCR) can detect SARS-COV-2 by targeting open reading frame-1 antibodies (ORF1ab), envelope protein, nucleocapsid protein, RNA-dependent RNA polymerase genes, and the N1, N2, and N3 (3N) target genes. Therefore, rRT-PCR remains the primary method of diagnosing SARS-CoV-2 despite being limited by false-negative results, long turnaround, complex protocols, and a need for skilled personnel. Serological diagnosis of coronavirus disease 2019 (COVID-19) is simple and does not require complex techniques and equipment, rendering it suitable for rapid detection and massive screening. However, serological tests cannot confirm SARS-CoV-2, and results will be false-negative when antibody concentrations fall below detection limits. Balancing the increased use of laboratory tests, risk of testing errors, need for tests, burden on healthcare systems, benefits of early diagnosis, and risk of unnecessary exposure is a significant and persistent challenge in diagnosing COVID-19.", "qid": 7, "docid": "r1yf75bo", "rank": 94, "score": 0.7488898634910583}, {"content": "Title: A serological assay to detect SARS-CoV-2 seroconversion in humans Content: Here, we describe a serological enzyme-linked immunosorbent assay for the screening and identification of human SARS-CoV-2 seroconverters. This assay does not require the handling of infectious virus, can be adjusted to detect different antibody types in serum and plasma and is amenable to scaling. Serological assays are of critical importance to help define previous exposure to SARS-CoV-2 in populations, identify highly reactive human donors for convalescent plasma therapy and investigate correlates of protection.", "qid": 7, "docid": "1vd4zcad", "rank": 95, "score": 0.7486347556114197}, {"content": "Title: A serological assay to detect SARS-CoV-2 seroconversion in humans. Content: Here, we describe a serological enzyme-linked immunosorbent assay for the screening and identification of human SARS-CoV-2 seroconverters. This assay does not require the handling of infectious virus, can be adjusted to detect different antibody types in serum and plasma and is amenable to scaling. Serological assays are of critical importance to help define previous exposure to SARS-CoV-2 in populations, identify highly reactive human donors for convalescent plasma therapy and investigate correlates of protection.", "qid": 7, "docid": "u79trvqf", "rank": 96, "score": 0.7486347556114197}, {"content": "Title: Detection of bovine coronavirus by enzyme-linked immunosorbent assay using monoclonal antibodies. Content: A sensitive and highly specific enzyme-linked immunosorbent assay (ELISA) system for detection of bovine coronavirus was developed using monoclonal antibodies, which showed both neutralization and hemagglutination inhibition activities. A monoclonal antibody was coated onto microplates for capturing antigen and a mixture of two monoclonal antibodies served as detecting antibodies. Using this assay, 40 of 202 fecal specimens from 29 herds were shown to be positive for viral antigen. From 10 ELISA positive specimens from 5 herds, the virus was isolated after several passages on human rectal adenocarcinoma (HRT-18) cell culture.", "qid": 7, "docid": "sza605p7", "rank": 97, "score": 0.7484945058822632}, {"content": "Title: Enzyme-linked immunosorbent assay for the detection of canine coronavirus and its antibody in dogs Content: Abstract Two methods of enzyme-linked immunosorbent assay (ELISA) were developed for the diagnosis of canine coronavirus (CCV) infection in dogs. One ELISA, in which CCV-infected CRFK cell lysate is used as antigen, is for the detection and titration of antibody against CCV, and the other ELISA uses the double antibody sandwich method for the detection of CCV antigen. The first ELISA procedure demonstrated antibody responses in dogs inoculated with CCV, as did the virus neutralization test; the second ELISA detected specific CCV antigen in feces and organ homogenates of inoculated dogs.", "qid": 7, "docid": "ldeylpne", "rank": 98, "score": 0.7483072876930237}, {"content": "Title: Antibody Detection and Dynamic Characteristics in Patients with COVID-19 Content: BACKGROUND: The corona virus disease 2019 (COVID-19) caused by the corona virus 2 (SARS-CoV-2) has been rapidly spreading nationwide and abroad. A serologic test to identify antibody dynamics and response to SARS-CoV-2 was developed. METHODS: The antibodies against SARS-CoV-2 were detected by an enzyme-linked immunosorbent assay (ELISA) based on the recombinant nucleocapsid protein of SARS-CoV-2 in patients with confirmed or suspected COVID-19 at 3-40 days after symptom onset. The gold standard for COVID-19 diagnosis was nucleic acid testing for SARS-CoV-2 by RT-PCR. The serodiagnostic power of the specific IgM and IgG antibodies against SARS-CoV-2 was investigated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and consistency rate. RESULTS: The seroconversion of specific IgM and IgG antibodies were observed as early as the 4(th) day after symptom onset. In the confirmed patients with COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 77.3% (51/66), 100%, 100%, 80.0%, and 88.1%, and those of IgG were 83.3.3% (55/66), 95.0%, 94.8%, 83.8%, and 88.9 %. In patients with suspected COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 87.5% (21/24), 100%, 100%, 95.2%, and 96.4%, and those of IgG were 70.8% (17/24), 96.6%, 85.0%, 89.1%, and 88.1%. Both antibodies performed well in serodiagnosis for COVID-19 rely on great specificity. CONCLUSIONS: The antibodies against SARS-CoV-2 can be detected in the middle and later stage of the illness. Antibody detection may play an important role in the diagnosis of COVID-19 as complement approach for viral nucleid acid assays.", "qid": 7, "docid": "uhh3owcx", "rank": 99, "score": 0.7482755780220032}, {"content": "Title: Development of a competitive enzyme-linked immunosorbent assay for detection of turkey coronavirus antibodies. Content: A competitive enzyme-linked immunosorbent assay (cELISA) was developed for detection of turkey coronavirus (TCV) antibodies. The cELISA utilized a recombinant baculovirus (Autographa californica nuclear polyhedrosis virus)-expressed TCV nucleocapsid (N) protein and biotin-labeled TCV N protein-specific monoclonal antibody. Sensitivity and specificity of the cELISA for detection of TCV antibodies were determined by comparison with the indirect fluorescent antibody test (IFAT) with 1269 reference, experimentally derived, and field-origin sera. Sera with discordant cELISA and IFAT results were further evaluated by western immunoblot analyses. The cELISA detected antibodies specific for TCV and infectious bronchitis virus, a closely related coronavirus, but did not detect antibodies specific for other avian viruses. A high degree of concordance was observed between the cELISA and IFAT; sensitivity and specificity of the cELISA relative to IFAT were 92.9% and 96.2%, respectively. Western immunoblot analyses provided additional evidence of cELISA specificity. The findings indicate that the cELISA is a rapid, sensitive, and specific serologic test for detection of TCV antibodies in turkeys.", "qid": 7, "docid": "wlqk3hht", "rank": 100, "score": 0.7482342720031738}]}
{"query": "how has lack of testing availability led to underreporting of true incidence of Covid-19?", "hits": [{"content": "Title: Adjusting Coronavirus prevalence estimates for laboratory test kit error Content: Testing representative populations to determine the prevalence or percent of the population with active SARS-Cov-2 (COVID-19) infection and/or antibodies to infection is being recommended as essential for making public policy decisions to open-up or to continue enforcing national, state and local government rules to shelter-in-place. However, all laboratory tests are imperfect and have estimates of sensitivity and specificity less than 100% - in some cases considerably less than 100%. That error will lead to biased prevalence estimates. If the true prevalence of COVID-19 is low, possibly in the range of 1-5%, then testing error will lead to a constant background of bias that will most likely be larger and possibly much larger than the true prevalence itself. As a result, what is needed is a method for adjusting prevalence estimates for testing error. In this paper we outline methods for adjusting prevalence estimates for testing error both prospectively in studies being planned and retrospectively in studies that have been conducted. The methods if employed would also help to harmonize study results within countries and around the world. Adjustment can lead to more accurate prevalence estimates and to better policy decisions.", "qid": 8, "docid": "1xjgtj0t", "rank": 1, "score": 0.7958704233169556}, {"content": "Title: Severe underestimation of COVID-19 case numbers: effect of epidemic growth rate and test restrictions Content: To understand the scope and development of the COVID-19 pandemic, knowledge of the number of infected persons is essential. Often, the number of \"confirmed cases\", which is based on positive RT-PCR test results, is regarded as a reasonable indicator. However, limited COVID-19 test capacities in many countries are restricting the amount of testing that can be done. This can lead to the implementation of testing policies that restrict access to COVID-19 tests, and to testing backlogs and delays. As a result, confirmed case numbers can be significantly lower than the actual number of infections, especially during rapid growth phases of the epidemic. This study examines the quantitative relation between infections and reported confirmed case numbers for two different testing strategies, \"limited\" and \"inclusive\" testing, in relation to the growth rate of the epidemic. The results indicate that confirmed case numbers understate the actual number of infections substantially; during rapid growth phases where the daily growth rate can reach or exceed 30%, as has been seen in many countries, the confirmed case numbers under-report actual infections by up to 50 to 100-fold.", "qid": 8, "docid": "p0rqg7uk", "rank": 2, "score": 0.7916514277458191}, {"content": "Title: Estimating the true (population) infection rate for COVID-19: A Backcasting Approach with Monte Carlo Methods Content: Differences in COVID-19 testing and tracing across countries, as well as changes in testing within each country over time, make it difficult to estimate the true (population) infection rate based on the confirmed number of cases obtained through RNA viral testing. We applied a backcasting approach, coupled with Monte Carlo methods, to estimate a distribution for the true (population) cumulative number of infections (infected and recovered) for 15 countries where reliable data are available. We find a positive relationship between the testing rate per 1,000 people and the implied true detection rate of COVID-19, and a negative relationship between the proportion who test positive and the implied true detection rate. Our estimates suggest that the true number of people infected across our sample of 15 developed countries is 18.2 (5-95% CI: 11.9-39.0) times greater than the reported number of cases. In individual countries, the true number of cases exceeds the reported figure by factors that range from 1.7 (5-95% CI: 1.1-3.6) for Australia to 35.6 (5-95% CI: 23.2-76.3) for Belgium.", "qid": 8, "docid": "vq7k0gma", "rank": 3, "score": 0.7893612384796143}, {"content": "Title: Covid-19 prevalence estimation by random sampling in the wider population - Optimal sample pooling under varying assumptions about true prevalence Content: The number of confirmed Covid-19 cases in a population is used as a coarse measurement for the burden of disease. However, this number depends heavily on the sampling intensity and the various test criteria used in different jurisdictions. A wide range of sources indicate that a large fraction of cases go undetected. Estimates of the true prevalence of Covid-19 can be made by random sampling in the wider population. Here we use simulations to explore confidence intervals of prevalence estimates under different sampling intensities and degrees of sample pooling.", "qid": 8, "docid": "zbax2vk7", "rank": 4, "score": 0.788981020450592}, {"content": "Title: Disentangling Increased Testing From Covid-19 Epidemic Spread Content: To design effective disease control strategies, it is critical to understand the incidence of diseases. In the Covid-19 epidemic in the United States (caused by outbreak of the SARS-CoV-2 virus), testing capacity was initially very limited and has been increasing at the same time as the virus has been spreading. When estimating the incidence, it can be difficult to distinguish whether increased numbers of positive tests stem from increases in the spread of the virus or increases in testing. This has made it very difficult to identify locations in which the epidemic poses the largest public health risks. Here, we use a probabilistic model to quantify beliefs about testing strategies and understand implications regarding incidence. We apply this model to estimate the incidence in each state of the United States, and find that: (1) the Covid-19 epidemic is likely to be more widespread than reported by limited testing, (2) the Covid-19 epidemic growth in the summer months is likely smaller than it was during the spring months, and (3) the regions which are at highest risk of Covid-19 epidemic outbreaks are not always those with the largest number of positive test results.", "qid": 8, "docid": "l7jme343", "rank": 5, "score": 0.7877130508422852}, {"content": "Title: Evaluating the massive underreporting and undertesting of COVID-19 cases in multiple global epicenters Content: BACKGROUND: With continuous global COVID-19 outbreak, differing case numbers and mortality rates are observed. While actual case numbers appear vague, mortality numbers related to COVID-19 seem more precise. In this study, we used the mortality rate as the main indicator to evaluate the extent of underreporting and underdetection of COVID-19 cases. METHODS: We have analyzed all available data provided by the World Health Organization on the development of international COVID-19 cases and mortality numbers on March 17th, 2020. A crude case-fatality risk (cCFR) and adjusted case-fatality risk (aCFR) was calculated for China, South Korea, Japan, Italy, France, Spain, Germany, Iran and the United States. Additionally, a fold-change (FC) was derived for each country. RESULTS: The highest aCFR and FC were detected for Spain. Based on their FC values, an extremely high number of undetected COVID-19 cases was displayed in France, the United States, Italy and Spain. For these countries, our findings indicate a detection rate of only 1-2% of total actual COVID-19 cases. CONCLUSIONS: Due to limited testing capacities, mortality numbers may serve as a better indicator for COVID-19 case spread in many countries. Our data indicate that countries like France, Italy, the United States, Iran and Spain have extremely high numbers of undetected and underreported cases. Differences in testing availability and capacity, containment as well as overall health care and medical infrastructure result in significantly different mortality rates and COVID-19 case numbers for each respective country.", "qid": 8, "docid": "hnbatlj0", "rank": 6, "score": 0.7853137254714966}, {"content": "Title: Evaluating the massive underreporting and undertesting of COVID-19 cases in multiple global epicenters Content: Abstract Background With continuous global COVID-19 outbreak, differing case numbers and mortality rates are observed. While actual case numbers appear vague, mortality numbers related to COVID-19 seem more precise. In this study, we used the mortality rate as the main indicator to evaluate the extent of underreporting and underdetection of COVID-19 cases. Methods We have analyzed all available data provided by the World Health Organization on the development of international COVID-19 cases and mortality numbers on March 17th, 2020. A crude case-fatality risk (cCFR) and adjusted case-fatality risk (aCFR) was calculated for China, South Korea, Japan, Italy, France, Spain, Germany, Iran and the United States. Additionally, a fold-change (FC) was derived for each country. Results The highest aCFR and FC were detected for Spain. Based on their FC values, an extremely high number of undetected COVID-19 cases was displayed in France, the United States, Italy and Spain. For these countries, our findings indicate a detection rate of only 1-2% of total actual COVID-19 cases. Conclusions Due to limited testing capacities, mortality numbers may serve as a better indicator for COVID-19 case spread in many countries. Our data indicate that countries like France, Italy, the United States, Iran and Spain have extremely high numbers of undetected and underreported cases. Differences in testing availability and capacity, containment as well as overall health care and medical infrastructure result in significantly different mortality rates and COVID-19 case numbers for each respective country.", "qid": 8, "docid": "ckecol7i", "rank": 7, "score": 0.7840837240219116}, {"content": "Title: Estimating the undetected infections in the Covid-19 outbreak by harnessing capture-recapture methods Content: OBJECTIVES: A major open question, affecting the decisions of policy makers, is the estimation of the true number of Covid-19 infections. Most of them are undetected, because of a large number of asymptomatic cases. We provide an efficient, easy to compute and robust lower bound estimator for the number of undetected cases. METHODS: A modified version of the Chao estimator is proposed, based on the cumulative time-series distributions of cases and deaths. Heterogeneity has been addressed by assuming a geometrical distribution underlying the data generation process. An (approximated) analytical variance of the estimator has been derived to compute reliable confidence intervals at 95% level. RESULTS: A motivating application to the Austrian situation is provided and compared with an independent and representative study on prevalence of Covid-19 infection. Our estimates match well with the results from the independent prevalence study, but the capture-recapture estimate has less uncertainty involved as it is based on a larger sample size. Results from other European countries are mentioned in the discussion. The estimated ratio of the total estimated cases to the observed cases is around the value of 2.3 for all the analyzed countries. CONCLUSIONS: The proposed method answers to a fundamental open question: \"How many undetected cases are going around?\". CR methods provide a straightforward solution to shed light on undetected cases, incorporating heterogeneity that may arise in the probability of being detected.", "qid": 8, "docid": "8jtbj10k", "rank": 8, "score": 0.7837494611740112}, {"content": "Title: Correcting under-reported COVID-19 case numbers: estimating the true scale of the pandemic Content: The COVID-19 virus has spread worldwide in a matter of a few months, while healthcare systems struggle to monitor and report current cases. Testing results have struggled with the relative capabilities, testing policies and preparedness of each affected country, making their comparison a non-trivial task. Since severe cases, which more likely lead to fatal outcomes, are detected at a higher rate than mild cases, the reported virus mortality is likely inflated in most countries. Lockdowns and changes in human behavior modulate the underlying growth rate of the virus. Under-sampling of infection cases may lead to the under-estimation of total cases, resulting in systematic mortality estimation biases. For healthcare systems worldwide it is important to know the expected number of cases that will need treatment. In this manuscript, we identify a generalizable growth rate decay reflecting behavioral change. We propose a method to correct the reported COVID-19 cases and death numbers by using a benchmark country (South Korea) with near-optimal testing coverage, with considerations on population demographics. We extrapolate expected deaths and hospitalizations with respect to observations in countries that passed the exponential growth curve. By applying our correction, we predict that the number of cases is highly under-reported in most countries and a significant burden on worldwide hospital capacity.", "qid": 8, "docid": "gttuxtw6", "rank": 9, "score": 0.7809998393058777}, {"content": "Title: Estimating the undetected infections in the Covid-19 outbreak by harnessing capture-recapture methods Content: OBJECTIVES: A major open question, affecting the decisions of policy makers, is the estimation of the true number of Covid-19 infections. Most of them are undetected, because of a large number of asymptomatic cases. We provide an efficient, easy to compute and robust lower bound estimator for the number of undetected cases. METHODS: A modified version of the Chao estimator is proposed, based on the cumulative time-series distributions of cases and deaths. Heterogeneity has been addressed by assuming a geometrical distribution underlying the data generation process. An (approximated) analytical variance of the estimator has been derived to compute reliable confidence intervals at 95% level. RESULTS: A motivating application to the Austrian situation is provided and compared with an independent and representative study on prevalence of Covid-19 infection. Our estimates match well with the results from the independent prevalence study, but the capture-recapture estimate has less uncertainty involved as it is based on a larger sample size. Results from other European countries are mentioned in the discussion. The estimated ratio of the total estimated cases to the observed cases is around the value of 2.3 for all the analyzed countries. CONCLUSIONS: The proposed method answers to a fundamental open question: \u201cHow many undetected cases are going around?\u201d. CR methods provide a straightforward solution to shed light on undetected cases, incorporating heterogeneity that may arise in the probability of being detected.", "qid": 8, "docid": "wv7c8938", "rank": 10, "score": 0.7809334993362427}, {"content": "Title: Epidemic Surveillance of Covid-19: Considering Uncertainty and Under-Ascertainment Content: Epidemic surveillance is a fundamental part of public health practice. Addressing under-ascertainment of cases is relevant in most surveillance systems, especially in pandemics of new diseases with a large spectrum of clinical presentations as it may influence timings of policy implementation and public risk perception. From this perspective, this article presents and discusses early evidence on under-ascertainment of COVID-19 and its motifs, options for surveillance, and reflections around their importance to tailor public health measures. In the case of COVID-19, systematically addressing and estimating under-ascertainment of cases is essential to tailor timely public health measures, and communicating these findings is of the utmost importance for policy making and public perception.", "qid": 8, "docid": "ff5ex004", "rank": 11, "score": 0.7787232398986816}, {"content": "Title: The Hypothesis of Testing: Paradoxes arising out of reported coronavirus case-counts Content: Many statisticians, epidemiologists, economists and data scientists have registered serious reservations regarding the reported coronavirus case-counts. Limited testing capacity across the country has been widely identified as a key driver of suppressed coronavirus case-counts. The calls to increase testing capacity are well-justified as they become a more frequent point of discussion in the public sphere. While expanded testing is a laudable goal, selection bias will impact estimates of disease prevalence and the effective reproduction number until the entire population is sampled. Moreover, tests are imperfect as false positive/negative rates interact in complex ways with selection bias. In this paper, we attempt to clarify this interaction. Through simple calculations, we demonstrate pitfalls and paradoxes that can arise when considering case-count data in the presence of selection bias and measurement error. The discussion guides several suggestions on how to improve current case-count reporting.", "qid": 8, "docid": "u5s5heqm", "rank": 12, "score": 0.7751131653785706}, {"content": "Title: The usefulness of SARS-CoV-2 test positive proportion as a surveillance tool Content: Comparison of COVID-19 case numbers over time and between locations is complicated by limits to virologic testing confirm SARS-CoV-2 infection, leading to under-reporting of incidence, and by variations in testing capacity between locations and over time. The proportion of tested individuals who have tested positive (test positive proportion, TPP) can potentially be used to qualitatively assess the testing capacity of a location; a high TPP could provide evidence that too few people are tested, leading to more under-reporting. In this study we propose a simple model for testing in a population experiencing an epidemic of COVID-19, and derive an expression for TPP in terms of well-defined parameters in the model, related to testing and presence of other pathogens causing COVID-19 like symptoms. We use simulations to show situations in which the TPP is higher or lower than we expect based on these parameters, and the effect of testing strategies on the TPP. In our simulations, we find in the absence of dramatic shifts of testing practices in time or between spatial locations, the TPP is positively correlated with the incidence of infection. As a corollary, the TPP can be used to distinguish between a decline in confirmed cases due to decline in incidence (in which case TPP should decline) and a decline in confirmed cases due to testing constraints (in which case TPP should remain constant). We show that the proportion of tested individuals who present COVID-19 like symptoms (test symptomatic proportion, TSP) encodes similar information to the TPP but has different relationships with the testing parameters, and can thus provide additional information regarding dynamic changes in TPP and incidence. Finally, we compare data on confirmed cases and TPP from US states. We conjecture why states may have higher or lower TPP than average. We suggest that collection of symptom status and age/risk category of tested individuals can aid interpretation of changes in TPP and increase the utility of TPP in assessing the state of the pandemic in different locations and times.", "qid": 8, "docid": "ole70vk0", "rank": 13, "score": 0.7739976644515991}, {"content": "Title: \"No test is better than a bad test\": Impact of diagnostic uncertainty in mass testing on the spread of Covid-19 Content: Background: The cessation of lock-down measures will require an effective testing strategy. Much focus at the beginning of the UK's Covid-19 epidemic was directed to deficiencies in the national testing capacity. The quantity of tests may seem an important focus, but other characteristics are likely more germane. False positive tests are more probable than positive tests when the overall population has a low prevalence of the disease, even with highly accurate tests. Methods: We modify an SIR model to include quarantines states and test performance using publicly accessible estimates for the current situation. Three scenarios for cessation of lock-down measures are explored: (1) immediate end of lock-down measures, (2) continued lock-down with antibody testing based immunity passports, and (3) incremental relaxation of lock-down measures with active viral testing. Sensitivity, specifcity, prevalence and test capacity are modified for both active viral and antibody testing to determine their population level effect on the continuing epidemic. Findings: Diagnostic uncertainty can have a large effect on the epidemic dynamics of Covid-19 within the UK. The dynamics of the epidemic are more sensitive to test performance and targeting than test capacity. The quantity of tests is not a substitute for an effective strategy. Poorly targeted testing has the propensity to exacerbate the peak in infections. Interpretation: The assessment that 'no test is better than a bad test' is broadly supported by the present analysis. Antibody testing is unlikely to be a solution to the lock-down, regardless of test quality or capacity. A well designed active viral testing strategy combined with incremental relaxation of the lock-down measures is shown to be a potential strategy to restore some social activity whilst continuing to keep infections low.", "qid": 8, "docid": "2jwuzfan", "rank": 14, "score": 0.773356556892395}, {"content": "Title: Testing Asymptomatic Emergency Department Patients for Coronavirus of 2019 (COVID\u201019) in a Low Prevalence Region Content: The first cases of Coronavirus of 2019 (COVID\u201019) were reported in Wuhan, China in December 2019(1). The literature demonstrates geographical variation with regards to estimates of infection incidence, suggesting that COVID\u201019 has been underdiagnosed in certain regions(2,3). The rate of asymptomatic infection has been estimated to be as high as 30.8%, which may help explain variation in incidence, particularly in regions with differing screening practices (3). Transmission of COVID\u201019 by asymptomatic carriers has been reported in multiple family units, indicating that this mode of infection is important in understanding disease epidemiology and population risk(4,5).", "qid": 8, "docid": "wzb6qv7y", "rank": 15, "score": 0.7728508710861206}, {"content": "Title: COVID-19: Should We Test Everyone? Content: Since the beginning of 2020, the coronavirus disease 2019 (COVID-19) has spread rapidly in the city of Wuhan, P.R. China, and subsequently, across the world. The swift spread of the virus is largely attributed to its stealth transmissions in which infected patients may be asymptomatic. Undetected transmissions present a remarkable challenge for the containment of the virus and pose an appalling threat to the public. An urgent question that has been asked by the public is\"Should I be tested for COVID-19 if I am sick?\". While different regions established their own criteria for screening infected cases, the screening criteria have been modified based on new evidence and understanding of the virus as well as the availability of resources. The shortage of test kits and medical personnel has considerably limited our ability to do as many tests as possible. Public health officials and clinicians are facing a dilemma of balancing the limited resources and unlimited demands. On one hand, they are striving to achieve the best outcome by optimizing the usage of the scant resources. On the other hand, they are challenged by the patients' frustrations and anxieties, stemming from the concerns of not being tested for COVID-19 for not meeting the definition of PUI (person under investigation). In this paper, we evaluate the situation from the statistical viewpoint by factoring into the considerations of the uncertainty and inaccuracy of the test, an issue that is often overlooked by the general public. We aim to shed light on the tough situation by providing evidence-based reasoning from the statistical angle, and we expect this examination will help the general public understand and assess the situation rationally. Most importantly, the development offers recommendations for physicians to make sensible evaluations to optimally use the limited resources for the best medical outcome.", "qid": 8, "docid": "1mfize6h", "rank": 16, "score": 0.7726806998252869}, {"content": "Title: Estimating the Early Outbreak Cumulative Incidence of COVID-19 in the United States: Three Complementary Approaches Content: Effectively designing and evaluating public health responses to the ongoing COVID-19 pandemic requires accurate estimation of the weekly incidence of COVID-19. Unfortunately, a lack of systematic testing across the United States (US) due to equipment shortages and varying testing strategies has hindered the usefulness of the reported positive COVID-19 case counts. We introduce three complementary approaches to estimate the cumulative incidence of symptomatic COVID-19 during the early outbreak in each state in the US as well as in New York City, using a combination of excess influenza-like illness reports, COVID-19 test statistics, and COVID-19 mortality reports. Instead of relying on an estimate from a single data source or method that may be biased, we provide multiple estimates, each relying on different assumptions and data sources. Across our three approaches, there is a consistent conclusion that estimated state-level COVID-19 symptomatic case counts from March 1 to April 4, 2020 varied from 5 to 50 times greater than the official positive test counts. Nationally, our estimates of COVID-19 symptomatic cases in the US as of April 4 have a likely range of 2.2 to 5.1 million cases, with possibly as high as 8.1 million cases, up to 26 times greater than the cumulative confirmed cases of about 311,000. Extending our method to May 16, 2020, we estimate that cumulative symptomatic incidence ranges from 6.0 to 12.2 million, which compares with 1.5 million positive test counts. Our approaches demonstrate the value of leveraging existing influenza-like-illness surveillance systems during the flu season for measuring the burden of new diseases that share symptoms with influenza-like-illnesses. Our methods may prove useful in assessing the burden of COVID-19 during upcoming flu seasons in the US and other countries with comparable influenza surveillance systems.", "qid": 8, "docid": "4i0gici7", "rank": 17, "score": 0.7722254395484924}, {"content": "Title: Application of pooled testing in screening and estimating the prevalence of Covid-19 Content: The recent emergence of the COVID-19 pandemic has posed an unprecedented healthcare challenge and catastrophic economic and social consequences to the countries across the world. The situation is even worse for emerging economies like India. WHO recommends mass scale testing as one of the most effective ways to contain its spread and fight the pandemic. But, due to the high cost and shortage of test kits, specifically in India, the testing is restricted to only those who are symptomatic. In this context, pooled testing is recommended by some experts as a partial solution to overcome this problem. In this article, we explain the basic statistical theory behind the pooled testing procedure for screening as well as prevalence estimation. In real world situations, the tests are imperfect, and lead to false positive and false negative results. We provide theoretical explanation of the impact of these diagnostic errors on the performances of individual testing and pooled testing procedures. Finally, we study the effect of misspecification of sensitivity and specificity of tests on the estimate of prevalence, an issue, which is debated a lot among the scientists in the context of COVID-19. Our theoretical investigations lead to some interesting and precise understanding of some of these issues.", "qid": 8, "docid": "dbzpcy5v", "rank": 18, "score": 0.7721208930015564}, {"content": "Title: Estimating the COVID-19 Infection Rate: Anatomy of an Inference Problem Content: As a consequence of missing data on tests for infection and imperfect accuracy of tests, reported rates of population infection by the SARS CoV-2 virus are lower than actual rates of infection. Hence, reported rates of severe illness conditional on infection are higher than actual rates. Understanding the time path of the COVID-19 pandemic has been hampered by the absence of bounds on infection rates that are credible and informative. This paper explains the logical problem of bounding these rates and reports illustrative findings, using data from Illinois, New York, and Italy. We combine the data with assumptions on the infection rate in the untested population and on the accuracy of the tests that appear credible in the current context. We find that the infection rate might be substantially higher than reported. We also find that the infection fatality rate in Italy is substantially lower than reported.", "qid": 8, "docid": "4kkzi70v", "rank": 19, "score": 0.7705051898956299}, {"content": "Title: The impact of changes in diagnostic testing practices on estimates of COVID-19 transmission in the United States Content: Estimates of the reproductive number for novel pathogens such as SARS-CoV-2 are essential for understanding the potential trajectory of the epidemic and the level of intervention that is needed to bring the epidemic under control. However, most methods for estimating the basic reproductive number (R(0)) and time-varying effective reproductive number (R(t)) assume that the fraction of cases detected and reported is constant through time. We explore the impact of secular changes in diagnostic testing and reporting on estimates of R(0) and R(t) using simulated data. We then compare these patterns to data on reported cases of COVID-19 and testing practices from different United States (US) states. We find that changes in testing practices and delays in reporting can result in biased estimates of R(0) and R(t). Examination of changes in the daily number of tests conducted and the percent of patients testing positive may be helpful for identifying the potential direction of bias. Changes in diagnostic testing and reporting processes should be monitored and taken into consideration when interpreting estimates of the reproductive number of COVID-19.", "qid": 8, "docid": "e5q27vpw", "rank": 20, "score": 0.770204484462738}, {"content": "Title: Adjusting confirmed COVID-19 case counts for testing volume Content: When assessing the relative prevalence of the novel coronavirus (COVID-19), observers often point to the number of COVID-19 cases that have been confirmed through viral testing. However, comparisons based on confirmed case counts alone can be misleading since a higher case count may reflect either a higher disease prevalence or a better rate of disease detection. Using weekly records of viral test results for each state in the US, I demonstrate how confirmed case counts can be adjusted based on the percentage of COVID-19 tests that come back positive. A regression analysis indicates that case counts track better with future hospitalizations and deaths when employing this simple adjustment for testing coverage. Viral testing results can be used as a leading indicator of COVID-19 prevalence, but data reporting standards should be improved, and care should be taken to account for testing coverage when comparing confirmed case counts.", "qid": 8, "docid": "g096k79u", "rank": 21, "score": 0.7690736055374146}, {"content": "Title: Coronavirus-19 disease (COVID-19): A case series of early suspected cases reported and the implications towards the response to the pandemic in Zimbabwe Content: Zimbabwe is among the countries that have been identified to be at risk of the COVID-19 pandemic. As of the 15th of March 2020, there was no confirmed case of the virus. Official reports of suspected cases were used to appraise the general screening, case management, and the emergency preparedness and response of the country towards the COVID-19 pandemic. In terms of the surveillance and capacity to screen at the ports of entry, the country seems to be faring well. The country might not be screening optimally, considering the number of COVID-19 tests conducted to date and the suspected cases who missed testing. Three of the suspected cases faced mental, social, and psychological consequences due to them being suspected cases of COVID-19. There is a need to enhance the screening process and infrastructure at all the ports of entry. More COVID-19 diagnostic tests should be procured to increase the testing capacity. Training and awareness on mental, social, and psychological consequences of COVID-19 should be offered to the health care workers and the general public. More financial resources should be sourced to enable the country control the pandemic.", "qid": 8, "docid": "exgppsx7", "rank": 22, "score": 0.768703818321228}, {"content": "Title: Substantial underestimation of SARS-CoV-2 infection in the United States due to incomplete testing and imperfect test accuracy Content: Accurate estimates of the burden of SARS-CoV-2 infection are critical to informing pandemic response. Current confirmed COVID-19 case counts in the U.S. do not capture the total burden of the pandemic because testing has been primarily restricted to individuals with moderate to severe symptoms due to limited test availability. Using a semi-Bayesian probabilistic bias analysis to account for incomplete testing and imperfect diagnostic accuracy, we estimated 6,275,072 cumulative infections compared to 721,245 confirmed cases (1.9% vs. 0.2% of the population) as of April 18, 2020. Accounting for uncertainty, the number of infections was 3 to 20 times higher than the number of confirmed cases. 86% (simulation interval: 64-99%) of this difference was due to incomplete testing, while 14% (0.3-36%) was due to imperfect test accuracy. Estimates of SARS-CoV-2 infections that transparently account for testing practices and diagnostic accuracy reveal that the pandemic is larger than confirmed case counts suggest.", "qid": 8, "docid": "ehcikhnw", "rank": 23, "score": 0.7675284147262573}, {"content": "Title: Estimating the COVID-19 infection rate: Anatomy of an inference problem Content: As a consequence of missing data on tests for infection and imperfect accuracy of tests, reported rates of cumulative population infection by the SARS CoV-2 virus are lower than actual rates of infection. Hence, reported rates of severe illness conditional on infection are higher than actual rates. Understanding the time path of the COVID-19 pandemic has been hampered by the absence of bounds on infection rates that are credible and informative. This paper explains the logical problem of bounding these rates and reports illustrative findings, using data from Illinois, New York, and Italy. We combine the data with assumptions on the infection rate in the untested population and on the accuracy of the tests that appear credible in the current context. We find that the infection rate might be substantially higher than reported. We also find that the infection fatality rate in Illinois, New York, and Italy is substantially lower than reported.", "qid": 8, "docid": "8wg27hcu", "rank": 24, "score": 0.7661349773406982}, {"content": "Title: Associations between psychiatric disorders, COVID-19 testing probability and COVID-19 testing results: Findings from a population-based study Content: Background The novel COVID-19 pandemic has affected over 2.4 million people worldwide. Little is known about COVID-19 testing rates and COVID-19 test outcomes in people with mental illness. We hypothesized that people with psychiatric disorders are less likely to undergo COVID-19 testing and more likely to test positive. Methods We used data on COVID-19 testing in the UK Biobank (UKB) cohort to compare the prevalence of COVID-19 testing and test outcomes among individuals with psychiatric disorders to those without such diagnoses. We further investigated associations of testing probability and outcome with psychiatric diagnostic categories. Outcomes Individuals with psychiatric disorders were overrepresented among the 1 474 UKB participants with test data: 23% of the COVID-19 test sample had a psychiatric diagnosis compared to 10% in the full cohort (p<0.0001). This overrepresentation persisted for each of the specific psychiatric disorders tested. Furthermore, individuals with a psychiatric disorder (p=0.01), particularly with substance use disorder (p<0.005), had negative test results significantly more often than individuals without psychiatric disorders. Sensitivity analyses confirmed our results. Interpretation In contrast with our hypotheses, UKB participants with psychiatric disorders have been tested for COVID-19 more frequently than individuals without a psychiatric history, pleading against the notion that limited health care access is preventing them from undergoing testing. Among those tested, test outcomes were more frequently negative for UKB participants with psychiatric disorders than in others, countering arguments that people with mental illness are more prone to contract the virus. Funding No external funding sources participated in any stage of the present study.", "qid": 8, "docid": "exjsq3up", "rank": 25, "score": 0.765129566192627}, {"content": "Title: Estimation of testing bias in covid-19 Content: COVID-19 testing studies have become a standard approach for estimating prevalence and fatality rates which then assist in public health decision making to contain and mitigate the spread of the disease. The sampling designs used are often biased in that they do not reflect the true underlying populations. For instance, individuals with strong symptoms are more likely to be tested than those with no symptoms. This results in biased estimates of prevalence (too high) and over-estimation of fatality rates. Typical post-sampling corrections are not always possible. Here we present a simple bias correction methodology derived and adapted from a correction for publication bias in meta analysis studies. The methodology is general enough to allow a wide variety of customization making it more useful in practice. Implementation is easily done using already collected information. We show via an example that the bias corrections can provide dramatic reductions in estimation error.", "qid": 8, "docid": "ee22gcx1", "rank": 26, "score": 0.7634595036506653}, {"content": "Title: Estimation of Excess Deaths Associated With the COVID-19 Pandemic in the United States, March to May 2020. Content: Importance Efforts to track the severity and public health impact of coronavirus disease 2019 (COVID-19) in the United States have been hampered by state-level differences in diagnostic test availability, differing strategies for prioritization of individuals for testing, and delays between testing and reporting. Evaluating unexplained increases in deaths due to all causes or attributed to nonspecific outcomes, such as pneumonia and influenza, can provide a more complete picture of the burden of COVID-19. Objective To estimate the burden of all deaths related to COVID-19 in the United States from March to May 2020. Design, Setting, and Population This observational study evaluated the numbers of US deaths from any cause and deaths from pneumonia, influenza, and/or COVID-19 from March 1 through May 30, 2020, using public data of the entire US population from the National Center for Health Statistics (NCHS). These numbers were compared with those from the same period of previous years. All data analyzed were accessed on June 12, 2020. Main Outcomes and Measures Increases in weekly deaths due to any cause or deaths due to pneumonia/influenza/COVID-19 above a baseline, which was adjusted for time of year, influenza activity, and reporting delays. These estimates were compared with reported deaths attributed to COVID-19 and with testing data. Results There were approximately 781 000 total deaths in the United States from March 1 to May 30, 2020, representing 122 300 (95% prediction interval, 116 800-127 000) more deaths than would typically be expected at that time of year. There were 95 235 reported deaths officially attributed to COVID-19 from March 1 to May 30, 2020. The number of excess all-cause deaths was 28% higher than the official tally of COVID-19-reported deaths during that period. In several states, these deaths occurred before increases in the availability of COVID-19 diagnostic tests and were not counted in official COVID-19 death records. There was substantial variability between states in the difference between official COVID-19 deaths and the estimated burden of excess deaths. Conclusions and Relevance Excess deaths provide an estimate of the full COVID-19 burden and indicate that official tallies likely undercount deaths due to the virus. The mortality burden and the completeness of the tallies vary markedly between states.", "qid": 8, "docid": "92tvskxw", "rank": 27, "score": 0.7630413770675659}, {"content": "Title: Coronavirus-19 Disease (COVID-19): A case series of early suspects reported and the implications towards the response to the pandemic in Zimbabwe Content: Abstract Zimbabwe is among the countries that have been identified to be at risk of the COVID-19 pandemic. As of the 15th of March 2020, there has been no confirmed case of the virus. Official reports of suspect cases were used to appraise the general screening, case management, and preparedness of the country towards the COVID-19 pandemic. In terms of the surveillance and capacity to screen at ports of entry, the country seems to be faring well. The country might not be screening optimally, considering the number of COVID-19 tests conducted to date and suspected cases who missed testing. Three of the suspected cases faced mental, social, and psychological consequences due to them being suspects of COVID-19. There is a need to enhance the screening process and infrastructure at all ports of entry. More COVID-19 diagnostic tests should be procured to increase the testing capacity. Training and awareness of mental, social, and psychological consequences of COVID-19 should be offered to health care workers and the public. More financial resources should be sourced to enable the country to control the pandemic.", "qid": 8, "docid": "2z0ftel0", "rank": 28, "score": 0.7624744176864624}, {"content": "Title: The Challenge of Using Epidemiological Case Count Data: The Example of Confirmed COVID-19 Cases and the Weather Content: The publicly available data on COVID-19 cases provides an opportunity to better understand this new disease. However, strong attention needs to be paid to the limitations of the data to avoid making inaccurate conclusions. This article, which focuses on the relationship between the weather and COVID-19, raises the concern that the same factors influencing the spread of the disease might also affect the number of tests performed and who gets tested. For example, weather conditions impact the prevalence of respiratory diseases with symptoms similar to COVID-19, and this will likely influence the number of tests performed. This general limitation could severely undermine any similar analysis using existing COVID-19 data or similar epidemiological data, which could, therefore, mislead decision-makers on questions of great policy relevance.", "qid": 8, "docid": "0jm73t0s", "rank": 29, "score": 0.7624301910400391}, {"content": "Title: Beyond predicting the number of infections: predicting who is likely to be COVID negative or positive Content: This study provides the first attempt to identify people at greater risk of COVID-19 infection, enabling more targeted infectious disease prevention and control, which are especially important in the ongoing shortage of COVID-19 testing. We conducted a primary survey of 521 adults on April 1-10, 2020 in Iran, where the official infection rate was 0.08%. In our sample, 3% reported being COVID-19 positive and 15% were unsure of their status. This relatively high positive rate enabled us to conduct the analysis at the 5% significance level. At the time of the survey, 44% of the adults worked from home; 26% still went to work in their workplaces; 27% had stopped working due to the COVID-19 pandemic; and 3% were unemployed. Adults who exercised more were more likely to be COVID-19 negative. Each additional hour of exercise per day predicted a 78% increase in the likelihood of being COVID-19 negative. Adults with chronic medical illnesses were 48% more likely to be COVID-19 negative. In terms of work situation, those who worked from home were the most likely to be COVID-19 negative, and those who had stopped working were the most likely to be COVID-19 positive. Individuals in larger organizations were less likely to be COVID-19 positive. Given the testing shortage in many countries, we identify a novel approach to predict the likelihood of COVID-19 infection by a set of personal and work situation characteristics, in order to help to identify individuals with more or less risk of contracting the virus. We hope this research opens a new research avenue to identify the individual risk factors of COVID-19 infection to enable more targeted infectious disease prevention, communication, testing, and control to complement the effort to expand testing capacity.", "qid": 8, "docid": "2jhrd9ex", "rank": 30, "score": 0.7621222734451294}, {"content": "Title: Intensive COVID-19 testing associated with reduced mortality - an ecological analysis of 108 countries Content: Background Intensive screening and testing for COVID-19 could facilitate early detection and isolation of infected persons and thereby control the size of the epidemic. It could also facilitate earlier and more targeted therapy. These factors could plausibly reduce attributable mortality which was the hypothesis tested in this study. Methods Linear regression was used to assess the country-level association between COVID-19 attributable mortality per 100 000 inhabitants (mortality/capita) and COVID-19 tests/capita (number of tests/100 000 inhabitants) controlling for the cumulative number of COVID-19 infections/100 000 inhabitants (cases/capita), the age of the epidemic (number of days between first case reported and 8 April), national health expenditure per capita and WHO world region. Results The COVID-19 mortality rate varied between 0.3 and 3110 deaths/100 000 inhabitants (median 30, IQR 8-105). The intensity of testing per 100 000 also varied considerably (median 21,970, IQR 2,735-89,095) as did the number of COVID-19 cases per 100 000 (median 1,600, IQR 340-4,760 cases/100 000). In the multivariate model, the COVID-19 mortality rate was negatively associated with tests/capita (Coef. -0.036, 95% CI -0.047- -0.025) and positively associated with cases/capita (Coef. 0.093, 95% CI 0.819- 1.034). Conclusions The results are compatible with the hypothesis that intensive testing and isolation could play a role in reducing COVID-10 mortality rates.", "qid": 8, "docid": "pps56i3b", "rank": 31, "score": 0.7621141672134399}, {"content": "Title: Using Machine Learning to Estimate Unobserved COVID-19 Infections in North America. Content: BACKGROUND The detection of coronavirus disease 2019 (COVID-19) cases remains a huge challenge. As of April 22, 2020, the COVID-19 pandemic continues to take its toll, with >2.6 million confirmed infections and >183,000 deaths. Dire projections are surfacing almost every day, and policymakers worldwide are using projections for critical decisions. Given this background, we modeled unobserved infections to examine the extent to which we might be grossly underestimating COVID-19 infections in North America. METHODS We developed a machine-learning model to uncover hidden patterns based on reported cases and to predict potential infections. First, our model relied on dimensionality reduction to identify parameters that were key to uncovering hidden patterns. Next, our predictive analysis used an unbiased hierarchical Bayesian estimator approach to infer past infections from current fatalities. RESULTS Our analysis indicates that, when we assumed a 13-day lag time from infection to death, the United States, as of April 22, 2020, likely had at least 1.3 million undetected infections. With a longer lag time-for example, 23 days-there could have been at least 1.7 million undetected infections. Given these assumptions, the number of undetected infections in Canada could have ranged from 60,000 to 80,000. Duarte's elegant unbiased estimator approach suggested that, as of April 22, 2020, the United States had up to >1.6 million undetected infections and Canada had at least 60,000 to 86,000 undetected infections. However, the Johns Hopkins University Center for Systems Science and Engineering data feed on April 22, 2020, reported only 840,476 and 41,650 confirmed cases for the United States and Canada, respectively. CONCLUSIONS We have identified 2 key findings: (1) as of April 22, 2020, the United States may have had 1.5 to 2.029 times the number of reported infections and Canada may have had 1.44 to 2.06 times the number of reported infections and (2) even if we assume that the fatality and growth rates in the unobservable population (undetected infections) are similar to those in the observable population (confirmed infections), the number of undetected infections may be within ranges similar to those described above. In summary, 2 different approaches indicated similar ranges of undetected infections in North America. LEVEL OF EVIDENCE Prognostic Level V. See Instructions for Authors for a complete description of levels of evidence.", "qid": 8, "docid": "v93mde6l", "rank": 32, "score": 0.7592883110046387}, {"content": "Title: Using Machine Learning to Estimate Unobserved COVID-19 Infections in North America Content: BACKGROUND: The detection of coronavirus disease 2019 (COVID-19) cases remains a huge challenge. As of April 22, 2020, the COVID-19 pandemic continues to take its toll, with >2.6 million confirmed infections and >183,000 deaths. Dire projections are surfacing almost every day, and policymakers worldwide are using projections for critical decisions. Given this background, we modeled unobserved infections to examine the extent to which we might be grossly underestimating COVID-19 infections in North America. METHODS: We developed a machine-learning model to uncover hidden patterns based on reported cases and to predict potential infections. First, our model relied on dimensionality reduction to identify parameters that were key to uncovering hidden patterns. Next, our predictive analysis used an unbiased hierarchical Bayesian estimator approach to infer past infections from current fatalities. RESULTS: Our analysis indicates that, when we assumed a 13-day lag time from infection to death, the United States, as of April 22, 2020, likely had at least 1.3 million undetected infections. With a longer lag time-for example, 23 days-there could have been at least 1.7 million undetected infections. Given these assumptions, the number of undetected infections in Canada could have ranged from 60,000 to 80,000. Duarte's elegant unbiased estimator approach suggested that, as of April 22, 2020, the United States had up to >1.6 million undetected infections and Canada had at least 60,000 to 86,000 undetected infections. However, the Johns Hopkins University Center for Systems Science and Engineering data feed on April 22, 2020, reported only 840,476 and 41,650 confirmed cases for the United States and Canada, respectively. CONCLUSIONS: We have identified 2 key findings: (1) as of April 22, 2020, the United States may have had 1.5 to 2.029 times the number of reported infections and Canada may have had 1.44 to 2.06 times the number of reported infections and (2) even if we assume that the fatality and growth rates in the unobservable population (undetected infections) are similar to those in the observable population (confirmed infections), the number of undetected infections may be within ranges similar to those described above. In summary, 2 different approaches indicated similar ranges of undetected infections in North America. LEVEL OF EVIDENCE: Prognostic Level V. See Instructions for Authors for a complete description of levels of evidence.", "qid": 8, "docid": "mdt11ba5", "rank": 33, "score": 0.759105920791626}, {"content": "Title: CoronaSurveys: Using Surveys with Indirect Reporting to Estimate the Incidence and Evolution of Epidemics Content: The world is suffering from a pandemic called COVID-19, caused by the SARS-CoV-2 virus. National governments have problems evaluating the reach of the epidemic, due to having limited resources and tests at their disposal. This problem is especially acute in low and middle-income countries (LMICs). Hence, any simple, cheap and flexible means of evaluating the incidence and evolution of the epidemic in a given country with a reasonable level of accuracy is useful. In this paper, we propose a technique based on (anonymous) surveys in which participants report on the health status of their contacts. This indirect reporting technique, known in the literature as network scale-up method, preserves the privacy of the participants and their contacts, and collects information from a larger fraction of the population (as compared to individual surveys). This technique has been deployed in the CoronaSurveys project, which has been collecting reports for the COVID-19 pandemic for more than two months. Results obtained by CoronaSurveys show the power and flexibility of the approach, suggesting that it could be an inexpensive and powerful tool for LMICs.", "qid": 8, "docid": "e1ovtngw", "rank": 34, "score": 0.7588344216346741}, {"content": "Title: How much of SARS-CoV-2 Infections is India detecting? A model-based estimation Content: Background and Rationale: Amid SARS-CoV-2 outbreak, the low number of infections for a population size of 1.38 billion is widely discussed, but with no definite answers. Methods: We used the model proposed by Bommer and Vollmer to assess the quality of official case records. The infection fatality rates were taken from Verity et al (2020). Age distribution of the population for India and states are taken from the Census of India (2011). Reported number of deaths and SARS-CoV-2 confirmed cases from https://www.covid19india.org. The reported numbers of samples tests were collected from the reports of the Indian Council for Medical Research (ICMR). Results: The findings suggest that India is detecting just 3.6% of the total number of infections with a huge variation across its states. Among 13 states which have more than 100 COVID-19 cases, the detection rate varies from 81.9% (of 410 estimated infections) in Kerala to 0.8% (of 35487 estimated infections) in Madhya Pradesh and 2.4% (of 7431 estimated infections) in Gujarat. Conclusion: As the study reports a lower number of deaths and higher recovery rates in the states with a high detection rate, thus suggest that India must enhance its testing capacity and go for widespread testing. Late detection puts patients in greater need of mechanical ventilation and ICU care, which imposes greater costs on the health system. The country should also adopt population-level random testing to assess the prevalence of the infection.", "qid": 8, "docid": "c9bp9euw", "rank": 35, "score": 0.758223831653595}, {"content": "Title: Correlation of population mortality of COVID-19 and testing coverage: a comparison among 36 OECD countries and Taiwan Content: Although testing is widely regarded as critical to fighting the Covid-19 pandemic, what measure and level of testing best reflects successful infection control remains unresolved. Our aim was to compare the sensitivity of two testing metrics--population testing number and testing coverage--to population mortality outcomes and identify a benchmark for testing adequacy with respect to population mortality and capture of potential disease burden. This ecological study aggregated publicly available data through April 12 on testing and outcomes related to COVID-19 across 36 OECD (Organization for Economic Development) countries and Taiwan. All OECD countries and Taiwan were included in this population-based study as a proxy for countries with highly developed economic and healthcare infrastructure. Spearman correlation coefficients were calculated between the aforementioned metrics and following outcome measures: deaths per 1 million people, case fatality rate, and case proportion of critical illness. Fractional polynomials were used to generate scatter plots to model the relationship between the testing metrics and outcomes. Testing coverage, but not population testing number, was highly correlated with population mortality (rs= -0.79, P=5.975e-09 vs rs =- 0.3, P=0.05) and case fatality rate (rs= -0.67, P=9.067e-06 vs rs = -0.21, P=0.20). A testing coverage threshold of 15-45 signified adequate testing: below 15, testing coverage was associated with exponentially increasing population mortality, whereas above 45, increased testing did not yield significant incremental mortality benefit. Testing coverage was better than population testing number in explaining country performance and can be used as an early and sensitive indicator of testing adequacy and disease burden. This may be particularly useful as countries consider re-opening their economies.", "qid": 8, "docid": "3jmxamtj", "rank": 36, "score": 0.7576178312301636}, {"content": "Title: Major testing issues in US Content: Delays and restrictions on who can be tested for the covid-19 virus in the US have raised the risk that it is spreading undetected, reports Colin Barras", "qid": 8, "docid": "dftnv7ez", "rank": 37, "score": 0.7571402788162231}, {"content": "Title: The role of testing in infectious disease control: A case of COVID-19 in Africa Content: The dramatic increase in COVID-19 suspected cases in Africa has placed enormous burden on public and private clinical facilities. Till date, the most commonly used method for the identification and confirmation of the virus is the laboratory-based reverse transcription-polymerase chain reaction (RT-PCR) testing. Unfortunately, testing capacities have been limited in many parts of Africa because of inadequate test kits which have restricted scaling up beyond the few public health laboratories at designated locations. We present in this mini-review Africa's preparedness and readiness toward testing, why testing is crucial, the need to immediately strengthen existing facilities and what it involves as combined approaches for managing the COVID-19 crisis. The review highlights the urgent need for speedy expansion and distribution of several laboratory testing platforms to public health facilities and fully accredited private clinical laboratories, including real-time PCR and serological assays.", "qid": 8, "docid": "go8lly5h", "rank": 38, "score": 0.7568749189376831}, {"content": "Title: Controlling the Hidden Growth of COVID-19 Content: The COVID-19 pandemic has plagued the world for months. The U.S. has taken measures to counter it. On a daily basis, newly confirmed cases have been reported. In the early days, these numbers showed an increasing trend. Recently, the numbers have been generally flattened out. This report tries to estimate the hidden number of currently alive infections in the population by using the confirmed cases. A major result indicates an existing infections estimate at about 10-50 times the daily confirmed new cases, with the stringent social distancing policy tipping to the upper end of this range. It clarifies the relationship between the infection rate and the test rate to put the epidemic under control, which says that the test rate shall keep up at the same pace as infection rate to prevent an outbreak. This relationship is meaningful in the wake of business re-opening in the U.S. and the world. The report also reveals the connections of all the measures taken to the epidemic spread. A stratified sampling method is proposed to add to the current tool kits of epidemic control. Again, this report is a summary of some straight observations and thoughts, not through a thorough study backed with field data. The results appear obvious and suitable for general education to interested policymakers and the public.", "qid": 8, "docid": "z0lvcb3z", "rank": 39, "score": 0.7568297982215881}, {"content": "Title: A novel comprehensive metric to assess COVID-19 testing outcomes: Effects of geography, government, and policy response Content: Testing and case identification are key strategies in controlling the COVID-19 pandemic. Contact tracing and isolation are only possible if cases have been identified. The effectiveness of testing must be tracked, but a single comprehensive metric is not available to assess testing effectiveness, and no timely estimates of case detection rate are available globally, making inter-country comparisons difficult. The purpose of this paper was to propose a single, comprehensive metric, called the COVID-19 Testing Index (CovTI) scaled from 0 to 100, that incorporated several testing metrics. The index was based on case-fatality rate, test positivity rate, active cases, and an estimate of the detection rate. It used parsimonious modeling to estimate the true total number of COVID-19 cases based on deaths, testing, health system capacity, and government transparency. Publicly reported data from 188 countries and territories were included in the index. Estimates of detection rates aligned with previous estimates in literature (R2=0.97). As of June 3, 2020, the states with the highest CovTI included Iceland, Australia, New Zealand, Hong Kong, and Thailand, and some island nations. Globally, CovTI increased from April 20 ([x]=43.2) to June 3 ([x]=52.2) but declined in ca. 10% of countries. Bivariate analyses showed the average in countries with open public testing policies (59.7, 95% CI 55.6-63.8) were significantly higher than countries with no testing policy (30.2, 95% CI 18.1-42.3) (p<0.0001). A multiple linear regression model assessed the association of independent grouping variables with CovTI. Open public testing and extensive contact tracing were shown to significantly increase CovTI, after adjusting for extrinsic factors, including geographic isolation and centralized forms of government. This tool may be useful for policymakers to assess testing effectiveness, inform decisions, and identify model countries. It may also serve as a tool for researchers in analyses by combining it with other databases.", "qid": 8, "docid": "6ed3two6", "rank": 40, "score": 0.7568182945251465}, {"content": "Title: Testing COVID-19 tests faces methodological challenges Content: In battling the COVID-19 pandemic, testing is essential. The detection of viral RNA allows the identification of infected persons, while the detection of antibodies may reveal a response to a previous infection. Tests for coronavirus should be rigorously evaluated in terms of their analytical and clinical performance. This poses not only logistic challenges, but also methodological ones. Some of these are generic for the diagnostic accuracy paradigm, while others are more specific for tests for viruses. Problematic for evaluations of the clinical performance of tests for viral RNA is the absence of an independent reference standard. Many studies lack rigor in terms of the recruitment of study participants. Study reports are often insufficiently informative, which makes it difficult to assess the applicability of study findings. Attempts to summarize the performance of these tests in terms of a single estimate of the clinical sensitivity fails to do justice to the identifiable sources of the large heterogeneity in mechanisms for generating false negative results.", "qid": 8, "docid": "6n35qvi8", "rank": 41, "score": 0.7563212513923645}, {"content": "Title: The Mathematics of Testing with Application to Prevalence of COVID-19 Content: We formulate three basic assumptions that should ideally guide any well-designed COVID-19 prevalence study. We provide, on the basis of these assumptions alone, a full derivation of mathematical formulas required for statistical analysis of testing data. In particular, we express the disease prevalence in a population through those for its homogeneous subpopulations. Although some of these formulas are routinely employed in prevalence studies, the study design often contravenes the assumptions upon which these formulas vitally depend. We also designed a natural prevalence estimator from the testing data and studied some of its properties. The results are equally valid for diseases other than COVID-19 as well as in non-epidemiological settings.", "qid": 8, "docid": "39jcr69r", "rank": 42, "score": 0.7559598684310913}, {"content": "Title: Suboptimal biological sampling as a probable cause of false-negative COVID-19 diagnostic test results Content: Improper nasopharyngeal swab collection could contribute to false-negative COVID-19 results. In support of this, specimens from confirmed or suspected COVID-19 cases that tested negative or indeterminate (i.e. suspected false-negatives) contained less human DNA (a stable molecular marker of sampling quality) compared to a representative pool of specimens submitted for testing.", "qid": 8, "docid": "5k55lmfm", "rank": 43, "score": 0.7548514008522034}, {"content": "Title: How to Best Predict the Daily Number of New Infections of Covid-19 Content: Knowledge about the daily number of new infections of Covid-19 is important because it is the basis for political decisions resulting in lockdowns and urgent health care measures. We use Germany as an example to illustrate shortcomings of official numbers, which are, at least in Germany, disclosed only with several days of delay and severely underreported on weekends (more than 40%). These shortcomings outline an urgent need for alternative data sources. The other widely cited source provided by the Center for Systems Science and Engineering at Johns Hopkins University (JHU) also deviates for Germany on average by 79% from the official numbers. We argue that Google Search and Twitter data should complement official numbers. They predict even better than the original values from Johns Hopkins University and do so several days ahead. These two data sources could also be used in parts of the world where official numbers do not exist or are perceived to be unreliable.", "qid": 8, "docid": "ojhc7peo", "rank": 44, "score": 0.7542946338653564}, {"content": "Title: Explaining national differences in the mortality of Covid-19: individual patient simulation model to investigate the effects of testing policy and other factors on apparent mortality. Content: There has been extensive speculation on the apparent differences in mortality between countries reporting on the confirmed cases and deaths due to Covid-19. A number of explanations have been suggested, but there is no clear evidence about how apparent fatality rates may be expected to vary with the different testing regimes, admission policies and other variables. An individual patient simulation model was developed to address this question. Parameters and sensitivity analysis based upon recent international data sources for Covid-19 and results were averaged over 100 iterations for a simulated cohort of over 500,000 patients. Different testing regimes for Covid-19 were considered; testing admitted patients only, various rates of community testing of symptomatic cases and active contact-tracing and screening. In the base case analysis, apparent mortality ranged from 10.5% under a policy of testing only admitted patients to 0.4% with intensive contact tracing and community testing. These findings were sensitive to assumptions regarding admission rates and the rate of spread, with more selective admission policies and suppression of spread increasing the apparent mortality and the potential for apparent mortality rates to exceed 18% under some circumstances. Under all scenarios the proportion of patients tested in the community had the greatest impact on apparent mortality. Whilst differences in mortality due to health service and demographic factors cannot be excluded, the current international differences in reported mortality are all consistent with differences in practice regarding screening, community testing and admission policies.", "qid": 8, "docid": "gkd1h8yi", "rank": 45, "score": 0.7538760900497437}, {"content": "Title: Testing COVID-19 tests faces methodological challenges Content: Abstract In battling the COVID-19 pandemic, testing is essential. The detection of viral RNA allows the identification of infected persons, while the detection of antibodies may reveal a response to a previous infection. Tests for coronavirus should be rigorously evaluated in terms of their analytical and clinical performance. This poses not only logistic challenges, but also methodological ones. Some of these are generic for the diagnostic accuracy paradigm, while others are more specific for tests for viruses. Problematic for evaluations of the clinical performance of tests for viral RNA is the absence of an independent reference standard. Many studies lack rigor in terms of the recruitment of study participants. Study reports are often insufficiently informative, which makes it difficult to assess the applicability of study findings. Attempts to summarize the performance of these tests in terms of a single estimate of the clinical sensitivity fails to do justice to the identifiable sources of the large heterogeneity in mechanisms for generating false negative results.", "qid": 8, "docid": "d4mqgesb", "rank": 46, "score": 0.7538133263587952}, {"content": "Title: Trends in excess cancer and cardiovascular deaths in Scotland during the COVID-19 pandemic 30 December 2019 to 20 April 2020 Content: Understanding the trends in causes of death for different diseases during the current COVID-19 pandemic is important to determine whether there are excess deaths beyond what is normally expected. Using the most recent report from National Records Scotland (NRS) on 29 April 2020, we examined the percentage difference in crude numbers of deaths in 2020 compared to the average for 2015-2019 by week of death within calendar year. To determine if trends were similar, suggesting underreporting/underdiagnosed COVID-19 related deaths, we also looked at the trends in % differences for cardiovascular disease deaths. From the first 17 weeks' of data, we found a peak in excess deaths between weeks 14 of 2020, about four weeks after the first case in Scotland was detected on 1 March 2020-- but by week 17 these excesses had diminished around the time lockdown in the UK began. Similar observations were seen for cardiovascular disease-related deaths. These observations suggest that the short-term increase in excess cancer and cardiovascular deaths might be associated with undetected/unconfirmed deaths related to COVID-19. Both of these conditions make patients more susceptible to infection and lack of widespread access to testing for COVID-19 are likely to have resulted in under-estimation of COVID-19 mortality. These data further suggest that the cumulative toll of COVID-19 on mortality is likely undercounted. More detailed analysis is needed to determine if these excesses were directly or indirectly related to COVID-19. Disease specific mortality will need constant monitoring for the foreseeable future as changes occur in increasing capacity and access to testing, reporting criteria, changes to health services and different measures are implemented to control the spread of the COVID-19. Multidisciplinary, multi-institutional, national and international collaborations for complementary and population specific data analysis is required to respond and mitigate adverse effects of the COVID-19 pandemic and to inform planning for future pandemics.", "qid": 8, "docid": "223v2obv", "rank": 47, "score": 0.7536493539810181}, {"content": "Title: Estimating the undetected infections in the Covid-19 outbreak by harnessing capture-recapture methods Content: A major open question, affecting the policy makers decisions, is the estimation of the true size of COVID-19 infections. Most of them are undetected, because of a large number of asymptomatic cases. We provide an efficient, easy to compute and robust lower bound estimator for the number of undetected cases. A \"modified\" version of the Chao estimator is proposed, based on the cumulative time-series distribution of cases and deaths. Heterogeneity has been accounted for by assuming a geometrical distribution underlying the data generation process. An (approximated) analytical variance formula has been properly derived to compute reliable confidence intervals at 95%. An application to Austrian situation is provided and results from other European Countries are mentioned in the discussion.", "qid": 8, "docid": "kq903zbo", "rank": 48, "score": 0.7534006834030151}, {"content": "Title: Estimation of COVID-19 under-reporting in Brazilian States through SARI Content: Due to its impact, COVID-19 has been stressing the academy to search for curing, mitigating, or controlling it. However, when it comes to controlling, there are still few studies focused on under-reporting estimates. It is believed that under-reporting is a relevant factor in determining the actual mortality rate and, if not considered, can cause significant misinformation. Therefore, the objective of this work is to estimate the under-reporting of cases and deaths of COVID-19 in Brazilian states using data from the Infogripe on notification of Severe Acute Respiratory Infection (SARI). The methodology is based on the concepts of inertia and the use of event detection techniques to study the time series of hospitalized SARI cases. The estimate of real cases of the disease, called novelty, is calculated by comparing the difference in SARI cases in 2020 (after COVID-19) with the total expected cases in recent years (2016 to 2019) derived from a seasonal exponential moving average. The results show that under-reporting rates vary significantly between states and that there are no general patterns for states in the same region in Brazil.", "qid": 8, "docid": "7dq28q1x", "rank": 49, "score": 0.7533963918685913}, {"content": "Title: COVID-19 Waves: Importance of Accumulative Mortality per Million Inhabitants Content: The reported number of new cases underestimates the real spread of COVID-19 pandemic because of non-tested asymptomatic people and limited global access to reliable diagnostic tests. In this context, COVID-19 mortality with confirmed diagnosis becomes an attractive source of information to be included in the analysis of perspectives and proposals. Objective data are required to calculate the capacity of resources provided by health systems. New strategies are needed to stabilize or minimize the mortality surge. However, we will not afford this goal until more alternatives were available. We still need an effective treatment, an affordable vaccine, or a collective achievement of sufficient immunity (reaching up to 70% of the whole population). At any time, the arriving waves of the pandemic are testing the capacity of governments. The health services struggle to keep the plateau in a steady-state below 100 deaths per million inhabitants. Therefore, it is necessary to increase the alternatives and supplies based on the current and near-future expected demands imposed by the number of deaths by COVID-19. Estimating COVID-19 mortality in various scenarios with the gradual release of social constraints will help predict the magnitude of those arriving waves.", "qid": 8, "docid": "acceu3l5", "rank": 50, "score": 0.753177285194397}, {"content": "Title: COVID-19 Waves: Importance of Accumulative Mortality per Million Inhabitants. Content: The reported number of new cases underestimates the real spread of COVID-19 pandemic because of non-tested asymptomatic people and limited global access to reliable diagnostic tests. In this context, COVID-19 mortality with confirmed diagnosis becomes an attractive source of information to be included in the analysis of perspectives and proposals. Objective data are required to calculate the capacity of resources provided by health systems. New strategies are needed to stabilize or minimize the mortality surge. However, we will not afford this goal until more alternatives were available. We still need an effective treatment, an affordable vaccine, or a collective achievement of sufficient immunity (reaching up to 70% of the whole population). At any time, the arriving waves of the pandemic are testing the capacity of governments. The health services struggle to keep the plateau in a steady-state below 100 deaths per million inhabitants. Therefore, it is necessary to increase the alternatives and supplies based on the current and near-future expected demands imposed by the number of deaths by COVID-19. Estimating COVID-19 mortality in various scenarios with the gradual release of social constraints will help predict the magnitude of those arriving waves.", "qid": 8, "docid": "qdxccgea", "rank": 51, "score": 0.753177285194397}, {"content": "Title: Estimation of Excess Deaths Associated With the COVID-19 Pandemic in the United States, March to May 2020 Content: Importance: Efforts to track the severity and public health impact of coronavirus disease 2019 (COVID-19) in the United States have been hampered by state-level differences in diagnostic test availability, differing strategies for prioritization of individuals for testing, and delays between testing and reporting. Evaluating unexplained increases in deaths due to all causes or attributed to nonspecific outcomes, such as pneumonia and influenza, can provide a more complete picture of the burden of COVID-19. Objective: To estimate the burden of all deaths related to COVID-19 in the United States from March to May 2020. Design, Setting, and Population: This observational study evaluated the numbers of US deaths from any cause and deaths from pneumonia, influenza, and/or COVID-19 from March 1 through May 30, 2020, using public data of the entire US population from the National Center for Health Statistics (NCHS). These numbers were compared with those from the same period of previous years. All data analyzed were accessed on June 12, 2020. Main Outcomes and Measures: Increases in weekly deaths due to any cause or deaths due to pneumonia/influenza/COVID-19 above a baseline, which was adjusted for time of year, influenza activity, and reporting delays. These estimates were compared with reported deaths attributed to COVID-19 and with testing data. Results: There were approximately 781\u00e2\u0080\u00af000 total deaths in the United States from March 1 to May 30, 2020, representing 122\u00e2\u0080\u00af300 (95% prediction interval, 116\u00e2\u0080\u00af800-127\u00e2\u0080\u00af000) more deaths than would typically be expected at that time of year. There were 95\u00e2\u0080\u00af235 reported deaths officially attributed to COVID-19 from March 1 to May 30, 2020. The number of excess all-cause deaths was 28% higher than the official tally of COVID-19-reported deaths during that period. In several states, these deaths occurred before increases in the availability of COVID-19 diagnostic tests and were not counted in official COVID-19 death records. There was substantial variability between states in the difference between official COVID-19 deaths and the estimated burden of excess deaths. Conclusions and Relevance: Excess deaths provide an estimate of the full COVID-19 burden and indicate that official tallies likely undercount deaths due to the virus. The mortality burden and the completeness of the tallies vary markedly between states.", "qid": 8, "docid": "f74q6nwj", "rank": 52, "score": 0.7529337406158447}, {"content": "Title: COVID-19 and US Health Financing: Perils and Possibilities Content: While the COVID-19 pandemic presents every nation with challenges, the United States' underfunded public health infrastructure, fragmented medical care system, and inadequate social protections impose particular impediments to mitigating and managing the outbreak. Years of inadequate funding of the nation's federal, state, and local public health agencies, together with mismanagement by the Trump administration, hampered the early response to the epidemic. Meanwhile, barriers to care faced by uninsured and underinsured individuals in the United States could deter COVID-19 care and hamper containment efforts, and lead to adverse medical and financial outcomes for infected individuals and their families, particularly those from disadvantaged groups. While the United States has a relatively generous supply of Intensive Care Unit beds and most other health care infrastructure, such medical resources are often unevenly distributed or deployed, leaving some areas ill-prepared for a severe respiratory epidemic. These deficiencies and shortfalls have stimulated a debate about policy solutions. Recent legislation, for instance, expanded coverage for testing for COVID-19 for the uninsured and underinsured, and additional reforms have been proposed. However comprehensive health care reform - for example, via national health insurance - is needed to provide full protection to American families during the COVID-19 outbreak and in its aftermath.", "qid": 8, "docid": "gt3nzokj", "rank": 53, "score": 0.7528558373451233}, {"content": "Title: COVID-19 and US Health Financing: Perils and Possibilities. Content: While the COVID-19 pandemic presents every nation with challenges, the United States' underfunded public health infrastructure, fragmented medical care system, and inadequate social protections impose particular impediments to mitigating and managing the outbreak. Years of inadequate funding of the nation's federal, state, and local public health agencies, together with mismanagement by the Trump administration, hampered the early response to the epidemic. Meanwhile, barriers to care faced by uninsured and underinsured individuals in the United States could deter COVID-19 care and hamper containment efforts, and lead to adverse medical and financial outcomes for infected individuals and their families, particularly those from disadvantaged groups. While the United States has a relatively generous supply of Intensive Care Unit beds and most other health care infrastructure, such medical resources are often unevenly distributed or deployed, leaving some areas ill-prepared for a severe respiratory epidemic. These deficiencies and shortfalls have stimulated a debate about policy solutions. Recent legislation, for instance, expanded coverage for testing for COVID-19 for the uninsured and underinsured, and additional reforms have been proposed. However comprehensive health care reform - for example, via national health insurance - is needed to provide full protection to American families during the COVID-19 outbreak and in its aftermath.", "qid": 8, "docid": "e841wdeu", "rank": 54, "score": 0.7528558373451233}, {"content": "Title: It can be dangerous to take epidemic curves of COVID-19 at face value Content: During an epidemic with a new virus, we depend on modelling to plan the response: but how good are the data? The aim of our work was to better understand the impact of misclassification errors in identification of true cases of COVID-19 on epidemic curves. Data originated from Alberta, Canada (available on 28 May 2020). There is presently no information of sensitivity (Sn) and specificity (Sp) of laboratory tests used in Canada for the causal agent for COVID-19. Therefore, we examined best attainable performance in other jurisdictions and similar viruses. This suggested perfect Sp and Sn 60-95%. We used these values to re-calculate epidemic curves to visualize the potential bias due to imperfect testing. If the sensitivity improved, the observed and adjusted epidemic curves likely fall within 95% confidence intervals of the observed counts. However, bias in shape and peak of the epidemic curves can be pronounced, if sensitivity either degrades or remains poor in the 60-70% range. These issues are minor early in the epidemic, but hundreds of undiagnosed cases are likely later on. It is therefore hazardous to judge progress of the epidemic based on observed epidemic curves unless quality of testing is better understood.", "qid": 8, "docid": "hsr2ue28", "rank": 55, "score": 0.7525920271873474}, {"content": "Title: Evolu\u00e7\u00e3o da preval\u00eancia de infec\u00e7\u00e3o por COVID-19 no Rio Grande do Sul, Brasil: inqu\u00e9ritos sorol\u00f3gicos seriados./ Evolu\u00e7\u00e3o da preval\u00eancia de infec\u00e7\u00e3o por COVID-19 no Rio Grande do Sul, Brasil: inqu\u00e9ritos sorol\u00f3gicos seriados./ Trends in the prevalence of COVID-19 infection in Rio Grande do Sul, Brazil: repeated serological surveys Content: COVID-19, the disease produced by the virus SARS-CoV-2, has spread quickly throughout the world, leading the World Health Organization to first classify it as an international health emergency and, subsequently, declaring it pandemic. The number of confirmed cases, as April 11, surpassed 1,700,000, but this figure does not reflect the prevalence of COVID-19 in the population as, in many countries, tests are almost exclusively performed in people with symptoms, particularly severe cases. To properly assess the magnitude of the problem and to contribute to the design of evidence-based policies for fighting COVID-19, one must accurately estimate the population prevalence of infection. Our study is aimed at estimating the prevalence of infected individuals in the state of Rio Grande do Sul, Brazil, to document how fast the infection spreads, and to estimate the proportion of infected persons who present or presented symptoms, as well as the proportion of asymptomatic infections. Four repeated serological surveys will be conducted in probability samples of nine sentinel cities every two weeks. Tests will be performed in 4,500 participants in each survey, totaling18,000 interviews. Interviews and tests will be conducted at the participants' household. A rapid test for the detection of antibodies will be used; the test was validated prior to the beginning of the fieldwork.", "qid": 8, "docid": "73a9yes1", "rank": 56, "score": 0.7525713443756104}, {"content": "Title: Trends in the prevalence of COVID-19 infection in Rio Grande do Sul, Brazil: repeated serological surveys. Content: COVID-19, the disease produced by the virus SARS-CoV-2, has spread quickly throughout the world, leading the World Health Organization to first classify it as an international health emergency and, subsequently, declaring it pandemic. The number of confirmed cases, as April 11, surpassed 1,700,000, but this figure does not reflect the prevalence of COVID-19 in the population as, in many countries, tests are almost exclusively performed in people with symptoms, particularly severe cases. To properly assess the magnitude of the problem and to contribute to the design of evidence-based policies for fighting COVID-19, one must accurately estimate the population prevalence of infection. Our study is aimed at estimating the prevalence of infected individuals in the state of Rio Grande do Sul, Brazil, to document how fast the infection spreads, and to estimate the proportion of infected persons who present or presented symptoms, as well as the proportion of asymptomatic infections. Four repeated serological surveys will be conducted in probability samples of nine sentinel cities every two weeks. Tests will be performed in 4,500 participants in each survey, totaling18,000 interviews. Interviews and tests will be conducted at the participants' household. A rapid test for the detection of antibodies will be used; the test was validated prior to the beginning of the fieldwork.", "qid": 8, "docid": "1cdmsxu1", "rank": 57, "score": 0.7525713443756104}, {"content": "Title: Hemogram data as a tool for decision-making in COVID-19 management: applications to resource scarcity scenarios Content: BACKGROUND: COVID-19 pandemics has challenged emergency response systems worldwide, with widespread reports of essential services breakdown and collapse of health care structure. A critical element involves essential workforce management since current protocols recommend release from duty for symptomatic individuals, including essential personnel. Testing capacity is also problematic in several countries, where diagnosis demand outnumbers available local testing capacity. PURPOSE: This work describes a machine learning model derived from hemogram exam data performed in symptomatic patients and how they can be used to predict qRT-PCR test results. METHODS: Hemogram exams data from 510 symptomatic patients (73 positives and 437 negatives) were used to model and predict qRT-PCR results through Na\u00efve-Bayes algorithms. Different scarcity scenarios were simulated, including symptomatic essential workforce management and absence of diagnostic tests. Adjusts in assumed prior probabilities allow fine-tuning of the model, according to actual prediction context. RESULTS: Proposed models can predict COVID-19 qRT-PCR results in symptomatic individuals with high accuracy, sensitivity and specificity, yielding a 100% sensitivity and 22.6% specificity with a prior of 0.9999; 76.7% for both sensitivity and specificity with a prior of 0.2933; and 0% sensitivity and 100% specificity with a prior of 0.001. Regarding background scarcity context, resources allocation can be significantly improved when model-based patient selection is observed, compared to random choice. CONCLUSIONS: Machine learning models can be derived from widely available, quick, and inexpensive exam data in order to predict qRT-PCR results used in COVID-19 diagnosis. These models can be used to assist strategic decision-making in resource scarcity scenarios, including personnel shortage, lack of medical resources, and testing insufficiency.", "qid": 8, "docid": "jcyq8qve", "rank": 58, "score": 0.7522283792495728}, {"content": "Title: Who should we test for COVID-19?A triage model built from national symptom surveys Content: The gold standard for COVID-19 diagnosis is detection of viral RNA in a reverse transcription PCR test. Due to global limitations in testing capacity, effective prioritization of individuals for testing is essential. Here, we devised a model that estimates the probability of an individual to test positive for COVID-19 based on answers to 9 simple questions regarding age, gender, presence of prior medical conditions, general feeling, and the symptoms fever, cough, shortness of breath, sore throat and loss of taste or smell, all of which have been associated with COVID-19 infection. Our model was devised from a subsample of a national symptom survey that was answered over 2 million times in Israel over the past 2 months and a targeted survey distributed to all residents of several cities in Israel. Overall, 43,752 adults were included, from which 498 self-reported as being COVID-19 positive. The model provides statistically significant predictions on held-out individuals and achieves a positive predictive value (PPV) of 46.3% at a 10% sensitivity. As our tool can be used online and without the need of exposure to suspected patients, it may have worldwide utility in combating COVID-19 by better directing the limited testing resources through prioritization of individuals for testing, thereby increasing the rate at which positive individuals can be identified and isolated.", "qid": 8, "docid": "ryibszjm", "rank": 59, "score": 0.7520049810409546}, {"content": "Title: Radiologist Reporting and Operational Management for Patients with Suspected COVID-19 Content: Abstract Objective Evaluate adoption and outcomes of locally-designed reporting guidelines for patients with possible COVID-19. Methods We developed a departmental guideline for radiologists that specified reporting terminology and required communication for patients with imaging findings suggestive of COVID-19, based on patient test status and imaging indication. In this retrospective study, radiology reports completed 3/1/2020-5/3/2020 that mentioned COVID-19 were reviewed. Reports were divided into patients with known COVID-19, patients with \u201csuspected\u201d COVID-19 (having an order indication of respiratory or infectious signs or symptoms), and \u201cunsuspected patients\u201d (other order indications, e.g., trauma or non-chest pain). Primary outcome was percentage of COVID-19 reports using recommended terminology; secondary outcome was percentages of suspected and unsuspected patients diagnosed with COVID-19. Relationships between categorical variables were assessed with Fisher\u2019s exact test. Results Among 77,400 total reports, 1,083 suggested COVID-19 based on imaging findings; 774 (71%) of COVID-19 reports used recommended terminology. Of 574 patients without known COVID-19 at time of interpretation, 345 (60%) were eventually diagnosed with COVID-19, including 61% (315/516) of suspected and 52% (30/58) of unsuspected patients. Nearly all (46/58) unsuspected patients were identified at CT. Discussion Radiologists rapidly adopted recommended reporting terminology for patients with suspected COVID-19. The majority of patients for whom radiologists raised concern for COVID-19 were subsequently diagnosed with the disease, including the majority of clinically unsuspected patients. Using unambiguous terminology and timely notification about previously unsuspected patients will become increasingly critical to facilitate COVID-19 testing and contact tracing as states begin to lift restrictions.", "qid": 8, "docid": "ry1diso2", "rank": 60, "score": 0.7519127130508423}, {"content": "Title: The role of testing in infectious disease control: A case of COVID-19 in Africa Content: Abstract The dramatic increase in COVID-19 suspected cases in Africa has placed enormous burden on public and private clinical facilities. Till date, the most commonly used method for the identification and confirmation of the virus is the laboratory-based reverse transcription-polymerase chain reaction (RT-PCR) testing. Unfortunately, testing capacities have been limited in many parts of Africa because of inadequate test kits which have restricted scaling up beyond the few public health laboratories at designated locations. We present in this mini-review Africa\u2019s preparedness and readiness toward testing, why testing is crucial, the need to immediately strengthen existing facilities and what it involves as combined approaches for managing the COVID-19 crisis. The review highlights the urgent need for speedy expansion and distribution of several laboratory testing platforms to public health facilities and fully accredited private clinical laboratories, including real-time PCR and serological assays.", "qid": 8, "docid": "cn9ukws9", "rank": 61, "score": 0.7515069842338562}, {"content": "Title: Visualization of Countermeasures against COVID-19 Infections in Japan by Systems Thinking : The reason why the Japanese government and its Council of Experts couldn't increase PCR tests Content: Many people in Japan and around the world have questioned whether Japan's \"number of tests\" for COVID-19 infection control is sufficient Because the scope of influence caused by infection is broad and complex, it is difficult to see the whole picture by only cutting one aspect of the situation, and there are differences among the sectors involved This misunderstanding can be seen as a communication failure in Japan's countermeasures against COVID-19 infection, and it is important for science and technology to clarify the reasons for the failure Why has the number of tests been narrowed down? The problem is not limited to the government's ability to execute, but there are also systemic impediments and overlooked issues in the effective implementation of countermeasures against new coronavirus infection In this paper, we first used a systems thinking technique (causal loop diagram) to visualize the situation related to COVID-19 infection, and confirmed its characteristics as a system Our causal loop diagram consists of an \"infection model\" and an \"incidence response model\" The government and the Council of Experts) have separated the \"infection model\" from the \"incidence model\" with the goal of reducing the number of deaths and, by extension, serious illnesses as much as possible In the process, attention has been paid to avoiding the depletion of medical resources, which is probably one of the reasons why the number of tests has not been able to increase so far However, while this approach is reasonable when each model is taken separately, it turns out that there are serious systemic weaknesses that occur at the interface between the two models For example, raising the testing hurdle will increase the number of mild cases that are active in the city without being tested, increasing the chance of infection and increasing the number of new cases This will create a new spread of infection Considering this, the following two measures need to be implemented It is necessary to implement blockades or other measures to reduce the number of opportunities for infection as soon as possible, or equivalent measures to reduce the number of opportunities for infection (e g , school closures, refraining from going outside, cancellation of events, city blockades, etc ) In order to expand inspections, it is necessary to introduce an inspection system that minimizes the connection with medical resources, such as the combination of drive-through inspections and walk-through inspections, which are famous in Korea, with Internet interviews However, in the current situation where infection is spreading to a certain extent and medical resources are tight, a two-sided strategy, such as increasing the number of tests, is necessary to control the spread of infection by lightly infected people (and subclinical infected people) who spread infection in the city in order to deal with the serious systemic problems at the interface between the two models The causal loop diagram shows that citizens are also required to take measures to prevent infection, such as masks and hand washing, and to change their behavior in order to reduce the chance of infection This case is an example of the importance of system-wide understanding of the situation for both citizens and experts, and of sharing that understanding Translated with www DeepL com/Translator (free version)", "qid": 8, "docid": "vxjfgdbi", "rank": 62, "score": 0.7513949871063232}, {"content": "Title: Internationally lost COVID-19 cases Content: Abstract Background With its epicenter in Wuhan, China, the COVID-19 outbreak was declared a pandemic by the World Health Organization (WHO). While many countries have implemented flight restrictions to China, an increasing number of cases with or without travel background to China are confirmed daily. These developments support concerns on possible unidentified and unreported international COVID-19 cases, which could lead to new local disease epicenters. Methods We have analyzed all available data on the development of international COVID-19 cases from January 20th, 2020 until February 18th, 2020. COVID-19 cases with and without travel history to China were divided into cohorts according to the Healthcare Access and Quality Index (HAQ-Index) of each country. Chi-square and Post-hoc testing were performed. Results While COVID-19 cases with travel history to China seem to peak for each HAQ-cohort, the number of non-travel related COVID-19 cases seem to continuously increase in the HAQ-cohort of countries with higher medical standards. Further analyses demonstrate a significantly lower proportion of reported COVID-19 cases without travel history to China in countries with lower HAQ (HAQ I vs. HAQ II, posthoc p < 0.01). Conclusions Our data indicate that countries with lower HAQ-index may either underreport COVID-19 cases or are unable to adequately detect them. Although our data may be incomplete and must be interpreted with caution, inconsistencies in reporting COVID-19 cases is a serious problem which might sabotage efforts to contain the virus.", "qid": 8, "docid": "l0zv0xuw", "rank": 63, "score": 0.7503705024719238}, {"content": "Title: Network structure of COVID-19 spread and the lacuna in India's testing strategy Content: We characterize the network of COVID-19 spread in India and find that the transmission rate is 0.43, with daily case growth driven by individuals who contracted the virus abroad. We explore the question of whether this represents exponentially decaying dynamics or is simply an artefact of India's testing strategy. Testing has largely been limited to individuals travelling from high-risk countries and their immediate contacts, meaning that the network reflects positive identifications from a biased testing sample. Given generally low levels of testing and an almost complete absence of testing for community spread, there is significant risk that we may be missing out on the actual nature of outbreak. India still has an apparently low current caseload, with possibly a small window of time to act, and should therefore aggressively and systematically expand random testing for community spread, including for asymptomatic cases. This will help understand true transmission characteristics and plan appropriately for the immediate future.", "qid": 8, "docid": "deuvq0wf", "rank": 64, "score": 0.7503540515899658}, {"content": "Title: Testing for SARS-CoV-2: Can We Stop at Two? Content: The COVID-19 epidemic requires accurate identification and isolation of confirmed cases for effective control. This report describes the effectiveness of our testing strategy and highlights the importance of repeat testing in suspect cases in our cohort.", "qid": 8, "docid": "vrpms6yz", "rank": 65, "score": 0.7503352165222168}, {"content": "Title: Accounting for underreporting in mathematical modelling of transmission and control of COVID-19 in Iran Content: BACKGROUND: Iran has been the hardest hit country by the outbreak of SARS-CoV-2 in the Middle East with 74,877 confirmed cases and 4,683 deaths as of 15 April 2020. With a relatively high case fatality ratio and limited testing capacity, the number of confirmed cases reported is suspected to suffer from significant under-reporting. Therefore, understanding the transmission dynamics of COVID-19 and assessing the effectiveness of the interventions that have taken place in Iran while accounting for the uncertain level of underreporting is of critical importance. We use a mathematical epidemic model utilizing official confirmed data and estimates of underreporting to understand how transmission in Iran has been changing between February and April 2020. METHODS: We developed a compartmental transmission model to estimate the effective reproduction number and its fluctuations since the beginning of the outbreak in Iran. We associate the variations in the effective reproduction number with a timeline of interventions and national events. The estimation method also accounts for the underreporting due to low case ascertainment by estimating the percentage of symptomatic cases using delay adjusted case fatality ratio based on the distribution of the delay from hospitalization to death. FINDINGS: Our estimates of the effective reproduction number ranged from 0.66 to 1.73 between February and April 2020, with a median of 1.16. We estimate a reduction in the effective reproduction number during this period, from 1.73 (95% CI 1.60-1.87) on 1 March 2020 to 0.69 (95% CI 0.68-0.70) on 15 April 2020, due to various non-pharmaceutical interventions including school closures, a ban on public gatherings including sports and religious events, and full or partial closure of non-essential businesses. Based on these estimates and given that a near complete containment is no longer feasible, it is likely that the outbreak may continue until the end of the 2020 if the current level of physical distancing and interventions continue and no effective vaccination or therapeutic are developed and made widely available. INTERPRETATION: The series of non-pharmaceutical interventions and the public compliance that took place in Iran are found to be effective in slowing down the speed of the spread of COVID-19 within the studied time period. However, we argue that if the impact of underreporting is overlooked, the estimated transmission and control dynamics could mislead the public health decisions, policy makers, and general public especially in the earlier stages of the outbreak. FUNDING: Nil.", "qid": 8, "docid": "ll2pnl81", "rank": 66, "score": 0.7503032684326172}, {"content": "Title: Spatial Analysis of COVID-19 Clusters and Contextual Factors in New York City Content: Identifying areas with low access to testing and high case burden is necessary to understand risk and allocate resources in the COVID-19 pandemic. Using zip code level data for New York City, we analyzed testing rates, positivity rates, and proportion positive. A spatial scan statistic identified clusters of high and low testing rates, high positivity rates, and high proportion positive. Boxplots and Pearson correlations determined associations between outcomes, clusters, and contextual factors. Clusters with less testing and low proportion positive tests had higher income, education, and white population, whereas clusters with high testing rates and high proportion positive tests were disproportionately black and without health insurance. Correlations showed inverse associations of white race, education, and income with proportion positive tests, and positive associations with black race, Hispanic ethnicity, and poverty. We recommend testing and health care resources be directed to eastern Brooklyn, which has low testing and high proportion positives.", "qid": 8, "docid": "yafkd0sf", "rank": 67, "score": 0.7502375245094299}, {"content": "Title: Bayesian modeling of COVID-19 cases with a correction to account for under-reported cases Content: The novel of COVID-19 disease started in late 2019 making the worldwide governments came across a high number of critical and death cases, beyond constant fear of the collapse in their health systems. Since the beginning of the pandemic, researchers and authorities are mainly concerned with carrying out quantitative studies (modeling and predictions) overcoming the scarcity of tests that lead us to under- reporting cases. To address these issues, we introduce a Bayesian approach to the SIR model with correction for under-reporting in the analysis of COVID-19 cases in Brazil. The proposed model was enforced to obtain estimates of important quantities such as the reproductive rate and the average infection period, along with the more likely date when the pandemic peak may occur. Several under-reporting scenarios were considered in the simulation study, showing how impacting is the lack of information in the modeling.", "qid": 8, "docid": "orh8fd1c", "rank": 68, "score": 0.7502086758613586}, {"content": "Title: COVID-19: Recovering estimates of the infected fatality rate during an ongoing pandemic through partial data Content: In an ongoing epidemic, the case fatality rate is not a reliable estimate of a disease's severity. This is particularly so when a large share of asymptomatic or pauci-symptomatic patients escape testing, or when overwhelmed healthcare systems are forced to limit testing further to severe cases only. By leveraging data on COVID-19, we propose a novel way to estimate a disease's infected fatality rate, the true lethality of the disease, in the presence of sparse and partial information. We show that this is feasible when the disease has turned into a pandemic and data comes from a large number of countries, or regions within countries, as long as testing strategies vary sufficiently. For Italy, our method estimates an IFR of 1.1% (95% CI: 0.2% - 2.1%), which is strongly in line with other methods. At the global level, our method estimates an IFR of 1.6% (95% CI: 1.1% - 2.1%). This method also allows us to show that the IFR varies according to each country's age structure and healthcare capacity.", "qid": 8, "docid": "a1c7bfr4", "rank": 69, "score": 0.750137448310852}, {"content": "Title: Towards reduction in bias in epidemic curves due to outcome misclassification through Bayesian analysis of time-series of laboratory test results: case study of COVID-19 in Alberta, Canada and Philadelphia, USA Content: BACKGROUND: Despite widespread use, the accuracy of the diagnostic test for SARS-CoV-2 infection is poorly understood. The aim of our work was to better quantify misclassification errors in identification of true cases of COVID-19 and to study the impact of these errors in epidemic curves using publicly available surveillance data from Alberta, Canada and Philadelphia, USA. METHODS: We examined time-series data of laboratory tests for SARS-CoV-2 viral infection, the causal agent for COVID-19, to try to explore, using a Bayesian approach, the sensitivity and specificity of the diagnostic test. RESULTS: Our analysis revealed that the data were compatible with near-perfect specificity, but it was challenging to gain information about sensitivity. We applied these insights to uncertainty/bias analysis of epidemic curves under the assumptions of both improving and degrading sensitivity. If the sensitivity improved from 60 to 95%, the adjusted epidemic curves likely falls within the 95% confidence intervals of the observed counts. However, bias in the shape and peak of the epidemic curves can be pronounced, if sensitivity either degrades or remains poor in the 60\u201370% range. In the extreme scenario, hundreds of undiagnosed cases, even among the tested, are possible, potentially leading to further unchecked contagion should these cases not self-isolate. CONCLUSION: The best way to better understand bias in the epidemic curves of COVID-19 due to errors in testing is to empirically evaluate misclassification of diagnosis in clinical settings and apply this knowledge to adjustment of epidemic curves.", "qid": 8, "docid": "vvm1gfku", "rank": 70, "score": 0.7498646974563599}, {"content": "Title: Towards reduction in bias in epidemic curves due to outcome misclassification through Bayesian analysis of time-series of laboratory test results: case study of COVID-19 in Alberta, Canada and Philadelphia, USA Content: BACKGROUND: Despite widespread use, the accuracy of the diagnostic test for SARS-CoV-2 infection is poorly understood. The aim of our work was to better quantify misclassification errors in identification of true cases of COVID-19 and to study the impact of these errors in epidemic curves using publicly available surveillance data from Alberta, Canada and Philadelphia, USA. METHODS: We examined time-series data of laboratory tests for SARS-CoV-2 viral infection, the causal agent for COVID-19, to try to explore, using a Bayesian approach, the sensitivity and specificity of the diagnostic test. RESULTS: Our analysis revealed that the data were compatible with near-perfect specificity, but it was challenging to gain information about sensitivity. We applied these insights to uncertainty/bias analysis of epidemic curves under the assumptions of both improving and degrading sensitivity. If the sensitivity improved from 60 to 95%, the adjusted epidemic curves likely falls within the 95% confidence intervals of the observed counts. However, bias in the shape and peak of the epidemic curves can be pronounced, if sensitivity either degrades or remains poor in the 60-70% range. In the extreme scenario, hundreds of undiagnosed cases, even among the tested, are possible, potentially leading to further unchecked contagion should these cases not self-isolate. CONCLUSION: The best way to better understand bias in the epidemic curves of COVID-19 due to errors in testing is to empirically evaluate misclassification of diagnosis in clinical settings and apply this knowledge to adjustment of epidemic curves.", "qid": 8, "docid": "t2utj1a6", "rank": 71, "score": 0.7498581409454346}, {"content": "Title: Higher testing coverage is associated with lower COVID-19 mortality rate: insights from Italian regions. Content: Different COVID-19 testing approaches have been implemented among Italian regions, reflected in heterogeneous testing rates. We analysed the number COVID-19-related deaths in relation to the number of tests performed among the most hit Italian regions. We showed that regions with the highest number of tests performed (Veneto and Toscana) had the lowest 30-day crude mortality rate per 100,000 inhabitants. In addition, an inverse association between crude mortality rates and tests performed (mortality rate ratio for unit increase in tests per 1,000 inhabitants: 0.92; 95% CI 0.89-0.94) was observed. Early identification and isolation of active cases (including asymptomatic or mildly symptomatic subjects) could have had an important effect in lowering COVID-19 mortality.", "qid": 8, "docid": "th2byzpj", "rank": 72, "score": 0.7497833967208862}, {"content": "Title: A demographic scaling model for estimating the total number of COVID-19 infections Content: Understanding how widely COVID-19 has spread is critical for examining the pandemic's progression. Despite efforts to carefully monitor the pandemic, the number of confirmed cases may underestimate the total number of infections. We introduce a demographic scaling model to estimate COVID-19 infections using an broadly applicable approach that is based on minimal data requirements: COVID-19 related deaths, infection fatality rates (IFRs), and life tables. As many countries lack reliable estimates of age-specific IFRs, we scale IFRs between countries using remaining life expectancy as a marker to account for differences in age structures, health conditions, and medical services. Across 10 countries with most COVID-19 deaths as of May 13, 2020, the number of infections is estimated to be four [95% prediction interval: 2-11] times higher than the number of confirmed cases. Cross-country variation is high. The estimated number of infections is 1.4 million (six times the number of confirmed cases) for Italy; 3.1 million (2.2 times the number of confirmed cases) for the U.S.; and 1.8 times the number of confirmed cases for Germany, where testing has been comparatively extensive. Our prevalence estimates, however, are markedly lower than most others based on local seroprevalence studies. We introduce formulas for quantifying the bias that is required in our data on deaths in order to reproduce estimates published elsewhere. This bias analysis shows that either COVID-19 deaths are severely underestimated, by a factor of two or more; or alternatively, the seroprevalence based results are overestimates and not representative for the total population.", "qid": 8, "docid": "vjpscyjf", "rank": 73, "score": 0.7495560646057129}, {"content": "Title: Bayesian adjustment for preferential testing in estimating the COVID-19 infection fatality rate: Theory and methods Content: A key challenge in estimating the infection fatality rate (IFR) of COVID-19 is determining the total number of cases. The total number of cases is not known because not everyone is tested but also, more importantly, because tested individuals are not representative of the population at large. We refer to the phenomenon whereby infected individuals are more likely to be tested than non-infected individuals, as\"preferential testing.\"An open question is whether or not it is possible to reliably estimate the IFR without any specific knowledge about the degree to which the data are biased by preferential testing. In this paper we take a partial identifiability approach, formulating clearly where deliberate prior assumptions can be made and presenting a Bayesian model, which pools information from different samples. Results suggest that when limited knowledge is available about the magnitude of preferential testing, reliable estimation of the IFR is still possible so long as there is sufficient\"heterogeneity of bias\"across samples.", "qid": 8, "docid": "tnr625zk", "rank": 74, "score": 0.7494199872016907}, {"content": "Title: Making sense of the Global Coronavirus Data: The role of testing rates in understanding the pandemic and our exit strategy Content: The Coronavirus disease 2019(COVID-19) outbreak has caused havoc across the world. Subsequently, research on COVID-19 has focused on number of cases and deaths and predicted projections have focused on these parameters. We propose that the number of tests performed is a very important denominator in understanding the COVID-19 data. We analysed the number of diagnostic tests performed in proportion to the number of cases and subsequently deaths across different countries and projected pandemic outcomes. We obtained real time COVID-19 data from the reference website Worldometer at 0900 BST on Saturday 4th April, 2020 and collated the information obtained on the top 50 countries with the highest number of COVID 19 cases. We analysed this data according to the number of tests performed as the main denominator. Country wise population level pandemic projections were extrapolated utilising three models - 1) inherent case per test and death per test rates at the time of obtaining the data (4/4/2020 0900 BST) for each country; 2) rates adjusted according to the countries who conducted at least 100000 tests and 3) rates adjusted according to South Korea. We showed that testing rates impact on the number of cases and deaths and ultimately on future projections for the pandemic across different countries. We found that countries with the highest testing rates per population have the lowest death rates and give us an early indication of an eventual COVID-19 mortality rate. It is only by continued testing on a large scale that will enable us to know if the increasing number of patients who are seriously unwell in hospitals across the world are the tip of the iceberg or not. Accordingly, obtaining this information through a rapid increase in testing globally is the only way which will enable us to exit the COVID-19 pandemic and reduce economic and social instability.", "qid": 8, "docid": "1kxxg0s9", "rank": 75, "score": 0.7493647336959839}, {"content": "Title: Hemogram Data as a Tool for Decision-making in COVID-19 Management: Applications to Resource Scarcity Scenarios Content: COVID-19 pandemics has challenged emergency response systems worldwide, with widespread reports of essential services breakdown and collapse of health care structure. A critical element involves essential workforce management since current protocols recommend release from duty for symptomatic individuals, including essential personnel. Testing capacity is also problematic in several countries, where diagnosis demand outnumbers available local testing capacity. This work describes a machine learning model derived from hemogram exam data performed in symptomatic patients and how they can be used to predict qRT-PCR test results. Methods: A Naive-Bayes model for machine learning is proposed for handling different scarcity scenarios, including managing symptomatic essential workforce and absence of diagnostic tests. Hemogram result data was used to predict qRT-PCR results in situations where the latter was not performed, or results are not yet available. Adjusts in assumed prior probabilities allow fine-tuning of the model, according to actual prediction context. Proposed models can predict COVID-19 qRT-PCR results in symptomatic individuals with high accuracy, sensitivity and specificity. Data assessment can be performed in an individual or simultaneous basis, according to desired outcome. Based on hemogram data and background scarcity context, resource distribution is significantly optimized when model-based patient selection is observed, compared to random choice. The model can help manage testing deficiency and other critical circumstances. Machine learning models can be derived from widely available, quick, and inexpensive exam data in order to predict qRT-PCR results used in COVID-19 diagnosis. These models can be used to assist strategic decision-making in resource scarcity scenarios, including personnel shortage, lack of medical resources, and testing insufficiency.", "qid": 8, "docid": "v7b6z86y", "rank": 76, "score": 0.7488490343093872}, {"content": "Title: False positives in reverse transcription PCR testing for SARS-CoV-2 Content: Background: Large-scale testing for SARS-CoV-2 by RT-PCR is a key element of the response to COVID-19, but little attention has been paid to the potential frequency and impacts of false positives. Method: From a meta-analysis of external quality assessments of RT-PCR assays of RNA viruses, we derived a conservative estimate of the range of false positive rates that can reasonably be expected in SARS-CoV-2 testing, and analyzed the effect of such rates on analyses of regional test data and estimates of population prevalence and asymptomatic ratio. Findings: Review of external quality assessments revealed false positive rates of 0-16.7%, with an interquartile range of 0.8-4.0%. Such rates would have large impacts on test data when prevalence is low. Inclusion of such rates significantly alters four published analyses of population prevalence and asymptomatic ratio. Interpretation: The high false discovery rate that results, when prevalence is low, from false positive rates typical of RT-PCR assays of RNA viruses raises questions about the usefulness of mass testing; and indicates that across a broad range of likely prevalences, positive test results are more likely to be wrong than are negative results, contrary to public health advice about SARS-CoV-2 testing. There are myriad clinical and case management implications. Failure to appreciate the potential frequency of false positives and the consequent unreliability of positive test results across a range of scenarios could unnecessarily remove critical workers from service, expose uninfected individuals to greater risk of infection, delay or impede appropriate medical treatment, lead to inappropriate treatment, degrade patient care, waste personal protective equipment, waste human resources in unnecessary contact tracing, hinder the development of clinical improvements, and weaken clinical trials. Measures to raise awareness of false positives, reduce their frequency, and mitigate their effects should be considered.", "qid": 8, "docid": "ywvk6gu6", "rank": 77, "score": 0.7487342953681946}, {"content": "Title: Forecasting undetected COVID-19 cases in Small Island Developing States using Bayesian approach Content: In dealing with the COVID-19, the fundamental question is how many actually undetected cases are going around regarding the capabilities of current health systems to contain the virus?. Due to a large number of asymptomatic cases, most COVID-19 cases are possibly undetected. For that reason, this study aims to provide an e[ff]icient, versatile, easy to compute, and robust estimator for the number of undetected cases using Bayes theorem based on the actual COVID-19 cases. This theorem is applied to 25 Small Island Developing States (SIDS) due to SIDS vulnerability. The results in this study forecast that possibly undetected COVID-19 cases are approximately 4 times larger than the numbers of actual COVID-19 cases as observed. This finding highlights the importance of using modeling tool to get the better and comprehensive of current COVID-19 cases and to take immediately precaution approaches to mitigate the growing numbers of COVID-19 cases as well.", "qid": 8, "docid": "6vlgsomg", "rank": 78, "score": 0.7485636472702026}, {"content": "Title: The need for COVID-19 research in low- and middle-income countries Content: In the early months of the pandemic, most reported cases and deaths due to COVID-19 occurred in high-income countries. However, insufficient testing could have led to an underestimation of true infections in many low- and middle-income countries. As confirmed cases increase, the ultimate impact of the pandemic on individuals and communities in low- and middle-income countries is uncertain. We therefore propose research in three broad areas as urgently needed to inform responses in low- and middle-income countries: transmission patterns of SARS-CoV-2, the clinical characteristics of the disease, and the impact of pandemic prevention and response measures. Answering these questions will require a multidisciplinary approach led by local investigators and in some cases additional resources. Targeted research activities should be done to help mitigate the potential burden of COVID-19 in low- and middle-income countries without diverting the limited human resources, funding, or medical supplies from response activities.", "qid": 8, "docid": "uzrxtgrg", "rank": 79, "score": 0.7484411001205444}, {"content": "Title: Statistically-based methodology for revealing real contagion trends and correcting delay-induced errors in the assessment of COVID-19 pandemic Content: COVID-19 pandemic has reshaped our world in a timescale much shorter than what we can understand. Particularities of SARS-CoV-2, such as its persistence in surfaces and the lack of a curative treatment or vaccine against COVID-19, have pushed authorities to apply restrictive policies to control its spreading. As data drove most of the decisions made in this global contingency, their quality is a critical variable for decision-making actors, and therefore should be carefully curated. In this work, we analyze the sources of error in typically reported epidemiological variables and usual tests used for diagnosis, and their impact on our understanding of COVID-19 spreading dynamics. We address the existence of different delays in the report of new cases, induced by the incubation time of the virus and testing-diagnosis time gaps, and other error sources related to the sensitivity/specificity of the tests used to diagnose COVID-19. Using a statistically-based algorithm, we perform a temporal reclassification of cases to avoid delay-induced errors, building up new epidemiologic curves centered in the day where the contagion effectively occurred. We also statistically enhance the robustness behind the discharge/recovery clinical criteria in the absence of a direct test, which is typically the case of non-first world countries, where the limited testing capabilities are fully dedicated to the evaluation of new cases. Finally, we applied our methodology to assess the evolution of the pandemic in Chile through the Effective Reproduction Number R(t), identifying different moments in which data was misleading governmental actions. In doing so, we aim to raise public awareness of the need for proper data reporting and processing protocols for epidemiological modelling and predictions.", "qid": 8, "docid": "iydjrmhh", "rank": 80, "score": 0.7484203577041626}, {"content": "Title: Swab Tests and COVID 19, Italy case studied using Artificial Intelligence, Statistical Analysis and MLR Content: Abstract: Objectives: The outbreak of the new Coronavirus (COVID-19) pandemic has prompted investigations on various aspects. This research aims to study the possible correlation between the numbers of swab tests and confirmed cases of infection, with special attention to the sickness level. Study Design: The study is carried out with reference to the Italian case, but the result is of more general importance, in particular for countries with limited availability of ICUs (intensive care units). Methods: The statistical analysis shows correlation between the number of swab tests and those of daily positive cases, mild cases admitted to hospital, intensive care cases, recovery, and death rate, and provides a basis to carry on an AI study. The results were validated using a multivariate linear regression (MLR) approach. Results: Our main result is the identification of a significant statistical effect of reduction of the pressure on the Health system as result of the increase of the tests. The relevance of this result is not confined to the COVID-19 outbreak, because the high demand of hospitalizations and ICU treatments due to this pandemic has an indirect effect on the possibility of guaranteeing an adequate treatment for other high-fatality disease, such as e.g. cardiological, and oncological. Conclusions: Our results show that swab testing may play a major role to decrease the stress on the Health system of a country. Therefore, this case study is relevant in particular for the planning of the control of the pandemic in countries with a limited capacity of admission to ICU s units.", "qid": 8, "docid": "zyn8p6w9", "rank": 81, "score": 0.747967541217804}, {"content": "Title: A population-based study of the prevalence of COVID-19 infection in Espirito Santo, Brazil: methodology and results of the first stage Content: BACKGROUND: COVID-19 is affecting almost the entire world, causing more than four hundred thousand deaths and undermining the health care systems, as much as the economy, of the afflicted countries. The strategies for prevention depend on largely lacking information, as infection prevalence and virus pathogenicity. This study aimed to determine the prevalence, the pathogenicity, and the speed of infection spreading in a large population in Brazil. MATERIALS AND METHODS: This is a serial cross-sectional study designed on a population basis and structured over houses as the sampling units. The sampling consisted of four visits at 15 days intervals in randomly selected census-designated sectors of the State major municipalities (reference municipalities) and two visits at 30 days intervals in smaller municipalities of the same regions of those of reference. At each visit, the investigators sampled houses and sampled one individual in each house for data collection. After the informed consent, the investigators performed a rapid antibody detection test (Celer Technology, Inc) and applied a questionnaire containing clinical and demographic questions. RESULTS: From May 13th to 15th, the investigators performed 6,393 rapid tests in 4,612 individuals of the reference municipalities, 1,163 individuals of the smaller municipalities, and 166 contacts of the positive individuals. Ninety-seven dwellers were positive in the reference municipalities, giving a prevalence of 2.1% (CI 95%: 1.67-2.52%). In the smaller municipalities, the figure was 0.26% (CI 95%: 0.05%-0.75%) (three positives). There was an association of the positive result with female sex (p = 0.013) and houses with five dwellers or more (p = 0.003). Seventy-eight positive individuals reported symptoms in the previous 15 days (80.4%), being anosmia (45.4%), cough (40.2%), and myalgia (38.1%) the more frequent. About one-third of them reported fever (28.9%). CONCLUSIONS: The results reveal a still small prevalence of infection in the study area, despite the significant number of sick people overloading the health system. The figures indicate an important underreporting in the area and a frequency that still can grow, making necessary public health actions for the containment of the transmission.", "qid": 8, "docid": "tkzfjth1", "rank": 82, "score": 0.7479578256607056}, {"content": "Title: COVID-19 incidence and R decreased on the Isle of Wight after the launch of the Test, Trace, Isolate programme Content: In May 2020 the UK introduced a Test, Trace, Isolate programme in response to the COVID-19 pandemic. The programme was first rolled out on the Isle of Wight and included Version 1 of the NHS contact tracing app. We used COVID-19 daily case data to infer incidence of new infections and estimate the reproduction number R for each of 150 Upper Tier Local Authorities in England, and at the National level, before and after the launch of the programme on the Isle of Wight. We used Bayesian and Maximum-Likelihood methods to estimate R, and compared the Isle of Wight to other areas using a synthetic control method. We observed significant decreases in incidence and R on the Isle of Wight immediately after the launch. These results are robust across each of our approaches. Our results show that the sub-epidemic on the Isle of Wight was controlled significantly more effectively than the sub-epidemics of most other Upper Tier Local Authorities, changing from having the third highest reproduction number R (of 150) before the intervention to the tenth lowest afterwards. The data is not yet available to establish a causal link. However, the findings highlight the need for further research to determine the causes of this reduction, as these might translate into local and national non-pharmaceutical intervention strategies in the period before a treatment or vaccination becomes available.", "qid": 8, "docid": "hf54ic40", "rank": 83, "score": 0.747083306312561}, {"content": "Title: It can be dangerous to take epidemic curves of COVID-19 at face value Content: During an epidemic with a new virus, we depend on modelling to plan the response: but how good are the data? The aim of our work was to better understand the impact of misclassification errors in identification of true cases of COVID-19 on epidemic curves. Data originated from Alberta, Canada (available on 28 May 2020). There is presently no information of sensitivity (Sn) and specificity (Sp) of laboratory tests used in Canada for the causal agent for COVID-19. Therefore, we examined best attainable performance in other jurisdictions and similar viruses. This suggested perfect Sp and Sn 60\u201395%. We used these values to re-calculate epidemic curves to visualize the potential bias due to imperfect testing. If the sensitivity improved, the observed and adjusted epidemic curves likely fall within 95% confidence intervals of the observed counts. However, bias in shape and peak of the epidemic curves can be pronounced, if sensitivity either degrades or remains poor in the 60\u201370% range. These issues are minor early in the epidemic, but hundreds of undiagnosed cases are likely later on. It is therefore hazardous to judge progress of the epidemic based on observed epidemic curves unless quality of testing is better understood. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.17269/s41997-020-00367-6) contains supplementary material, which is available to authorized users.", "qid": 8, "docid": "3p9yc6ti", "rank": 84, "score": 0.746524453163147}, {"content": "Title: COVID-19 in Italy: considerations on official data Content: Abstract COVID-19 represents a major public health issue in Italy; estimating the size of the outbreak could direct public health policies and inform us on the extent of the reorganization needed in the healthcare system, on the efficacy of quarantine measures and eventually on the achievement of herd immunity. In order to chart the real extent of COVID-19 infection in Italy, official data need to be interpreted considering various aspects such the \u201csuspected-case\u201d definition, that changed during the past months, the management of asymptomatic and untested symptomatic cases, the deaths reporting system and short-term fluctuations. All these aspects should be taken into consideration when reflecting about the meaning of the official COVID-19 figures in Italy. Regionalization of the healthcare system and fragmentation of data represent real challenges in the management of the COVID-19 outbreak in Italy. Authors\u2019 opinion is that a transparent and accurate reporting could guide policymaking and help reorganize health services.", "qid": 8, "docid": "u2c5xfos", "rank": 85, "score": 0.7464723587036133}, {"content": "Title: Assessing risk factors for SARS-CoV-2 infection in patients presenting with symptoms in Shanghai, China: a multicentre, observational cohort study Content: Background: The outbreak of COVID-19 has led to international concern. We aimed to establish an effective screening strategy in Shanghai, China, to aid early identification of patients with COVID-19. Methods: We did a multicentre, observational cohort study in fever clinics of 25 hospitals in 16 districts of Shanghai. All patients visiting the clinics within the study period were included. A strategy for COVID-19 screening was presented and then suspected cases were monitored and analysed until they were confirmed as cases or excluded. Logistic regression was used to determine the risk factors of COVID-19. Findings: We enrolled patients visiting fever clinics from Jan 17 to Feb 16, 2020. Among 53\u00e2\u0080\u0088617 patients visiting fever clinics, 1004 (1\u00b79%) were considered as suspected cases, with 188 (0\u00b74% of all patients, 18\u00b77% of suspected cases) eventually diagnosed as confirmed cases. 154 patients with missing data were excluded from the analysis. Exposure history (odds ratio [OR] 4\u00b716, 95% CI 2\u00b774-6\u00b733; p<0\u00b70001), fatigue (OR 1\u00b756, 1\u00b701-2\u00b741; p=0\u00b7043), white blood cell count less than 4\u00e2\u0080\u0088\u00d7\u00e2\u0080\u0088109 per L (OR 2\u00b744, 1\u00b728-4\u00b764; p=0\u00b70066), lymphocyte count less than 0\u00b78\u00e2\u0080\u0088\u00d7\u00e2\u0080\u0088109 per L (OR 1\u00b782, 1\u00b700-3\u00b731; p=0\u00b7049), ground glass opacity (OR 1\u00b795, 1\u00b732-2\u00b789; p=0\u00b70009), and having both lungs affected (OR 1\u00b754, 1\u00b704-2\u00b728; p=0\u00b7032) were independent risk factors for confirmed COVID-19. Interpretation: The screening strategy was effective for confirming or excluding COVID-19 during the spread of this contagious disease. Relevant independent risk factors identified in this study might be helpful for early recognition of the disease. Funding: National Natural Science Foundation of China.", "qid": 8, "docid": "ttl8tu7b", "rank": 86, "score": 0.7462707757949829}, {"content": "Title: Impact of the accuracy of case-based surveillance data on the estimation of time-varying reproduction numbers Content: Studies aimed at characterizing the evolution of COVID-19 disease often rely on case-based surveillance data publicly released by health authorities, that can be incomplete and prone to errors. Here, we quantify the biases caused by the use of inaccurate data in the estimation of the Time-Varying Reproduction Number R(t). By focusing on Italy and Spain, two of the hardest-hit countries in Europe and worldwide, we show that if the symptoms' onset time-series is inferred from the notification date series, the R(t) curve cannot capture nor describe accurately the early dynamics of the epidemic. Furthermore, the effectiveness of the containment measures that were implemented, such as national lockdowns, can be properly evaluated only when R(t) is estimated using the real time-series of dates of symptoms' onset. Our findings show that extreme care should be taken when a pivotal quantity like R(t) is used to make decisions and to evaluate different alternatives.", "qid": 8, "docid": "chbdqxk8", "rank": 87, "score": 0.7461020946502686}, {"content": "Title: Seeding COVID-19 across sub-Saharan Africa: an analysis of reported importation events across 40 countries Content: Background: The first case of COVID-19 in sub-Saharan Africa (SSA) was reported by Nigeria on February 27, 2020. While case counts in the entire region remain considerably less than those being reported by individual countries in Europe, Asia, and the Americas, SSA countries remain vulnerable to significant COVID morbidity and mortality due to systemic healthcare weaknesses, less financial resources and infrastructure to address the new crisis, and untreated comorbidities. Variation in preparedness and response capacity as well as in data availability has raised concerns about undetected transmission events. Methods: Confirmed cases reported by SSA countries were line-listed to capture epidemiological details related to early transmission events into and within countries. Data were retrieved from publicly available sources, including institutional websites, situation reports, press releases, and social media accounts, with supplementary details obtained from news articles. A data availability score was calculated for each imported case in terms of how many indicators (sex, age, travel history, date of arrival in country, reporting date of confirmation, and how detected) could be identified. We assessed the relationship between time to first importation and overall Global Health Security Index (GHSI) using Cox regression. K-means clustering grouped countries according to healthcare capacity and health and demographic risk factors. Results: A total of 2417 confirmed cases of COVID-19 were reported by 40 countries in sub-Saharan Africa during the 30 days after the first known introduction to the region. Out of the 876 cases for which information was publicly available, 677 (77.3%) were considered importation events. At the regional level, imported cases tended to be male (67.3%), were a median 43.0 years old (Range: 6 weeks - 88 years), and most frequently had recent travel history from Europe (43.3%). The median time to reporting an introduction was 19 days; a country's time to report its first importation was not related to GHSI. Mean data availability scores were lowest for countries that had, on average, the highest case fatality rates, lowest healthcare capacity, and highest probability of premature death due to non-communicable diseases. Conclusion: Countries with systemic, demographic, and pre-existing health vulnerabilities to severe COVID-related morbidity and mortality are less likely to report any cases or are reporting with limited public availability of information. Reporting of information on COVID detection and response efforts, as well as on trends in non-COVID illness and care-seeking behavior, is critical to assessing direct and indirect consequences and capacity needs in resource-constrained settings. Such assessments aid in the ability to make data-driven decisions about interventions, country priorities, and risk assessment.", "qid": 8, "docid": "vtuljhcp", "rank": 88, "score": 0.7460125684738159}, {"content": "Title: COVID-19 in pregnancy with comorbidities: More liberal testing strategy is needed. Content: Despite a global pandemic, reports on pregnant women with Coronavirus disease 2019 (COVID-19) are few so far, testing strategies vary substantially and management guidelines are not uniform.", "qid": 8, "docid": "5ns5d4kv", "rank": 89, "score": 0.7456929683685303}, {"content": "Title: Accounting for incomplete testing in the estimation of epidemic parameters Content: As the COVID-19 pandemic spreads across the world, it is important to understand its features and responses to public health interventions in real-time. The field of infectious diseases epidemiology has highly advanced modeling strategies that yield relevant estimates. These include the doubling time of the epidemic and various other representations of the numbers of cases identified over time. Crude estimates of these quantities suffer from dependence on the underlying testing strategies within communities. We clarify the functional relationship between testing and the epidemic parameters, and thereby derive sensitivity analyses that explore the range of possible truths under various testing dynamics. We derive the required adjustment to the estimates of interest for New York City. We demonstrate that crude estimates that assume stable testing or complete testing can be biased.", "qid": 8, "docid": "u0prnwk6", "rank": 90, "score": 0.7456862926483154}, {"content": "Title: A spatial model to optimise predictions of COVID-19 incidence risk in Belgium using symptoms as reported in a large-scale online survey Content: Although COVID-19 has been spreading throughout Belgium since February, 2020, its spatial dynamics in Belgium remain poorly understood, due to the limited testing of suspected cases. We analyse data of COVID-19 symptoms, as self-reported in a weekly online survey, which is open to all Belgian citizens. We predict symptoms' incidence using binomial models for spatially discrete data, and we introduce these as a covariate in the spatial analysis of COVID-19 incidence, as reported by the Belgian government during the days following a survey round. The symptoms' incidence predictions explain a significant proportion of the variation in the relative risks based on the confirmed cases, and exceedance probability maps of the symptoms' incidence and the confirmed cases' relative risks pinpoint the same high-risk region. We conclude that these results can be used to develop public monitoring tools in scenarios with limited lab testing capacity, and to supplement test-based information otherwise.", "qid": 8, "docid": "k4rdzlph", "rank": 91, "score": 0.7456517219543457}, {"content": "Title: Inferring the number of COVID-19 cases from recently reported deaths Content: We estimate the number of COVID-19 cases from newly reported deaths in a population without previous reports. Our results suggest that by the time a single death occurs, hundreds to thousands of cases are likely to be present in that population. This suggests containment via contact tracing will be challenging at this point, and other response strategies should be considered. Our approach is implemented in a publicly available, user-friendly, online tool.", "qid": 8, "docid": "zklwovba", "rank": 92, "score": 0.7456337213516235}, {"content": "Title: [Covid-19 diagnosis : clinical recommendations and performance of nasopharyngeal swab-PCR]. Content: The Covid-19 pandemic imposes new diagnostic strategies in order to optimize the medical care of our patients. The current biblio-graphy, although of low quality, shows a sensitivity of 56 to 83 % for the Covid-19 PCR. Even though one negative test can exclude a Covid-19 in the majority of cases, the NPV (Negative Predictive Value) decreases with increasing prevalence (pre-test probability). This finding suggests the need for strict auto-isolation of patients until the resolution of their symptoms. For patients that present with typical symptoms, who have a presumed Covid-19 prevalence of -40-50 %, a negative test should be interpreted with caution and a repeat test may be needed.", "qid": 8, "docid": "1mcmwe7f", "rank": 93, "score": 0.7455853223800659}, {"content": "Title: Undersampling in action and at scale: application to the COVID-19 pandemic Content: It is the purpose of this short communication to analyze the possible caveats in the statistical interpretation of collected data, particularly in the light of decision-making concerning the current COVID-19 coronavirus pandemic. A mitigation of undersampling is proposed, based on re-scaling of statistics that can be considered reliable, such as deaths, and epidemic properties like mortality, that may be considered comparable between countries with similar levels of health care, which would not have reached a saturation level.", "qid": 8, "docid": "tl3hskew", "rank": 94, "score": 0.7452867031097412}, {"content": "Title: ESTIMATING UNDERDIAGNOSIS OF COVID-19 WITH NOWCASTING AND MACHINE LEARNING: EXPERIENCE FROM BRAZIL Content: Background: Brazil has the second largest COVID-19 number of cases, worldly. Even so, underdiagnosis in the country is massive. Nowcasting techniques have helped to overcome the underdiagnosis. Recent advances in machine learning techniques offer opportunities to refine the nowcasting. This study aimed to analyze the underdiagnosis of COVID-19, through nowcasting with machine learning, in a South of Brazil capital. Methods: The study has an observational ecological design. It used data from 3916 notified cases of COVID-19, from April 14th to June 02nd, 2020, in Florianopolis, Santa Catarina, Brazil. We used machine-learning algorithm to classify cases which had no diagnosis yet, producing the nowcast. To analyze the underdiagnosis, we compared the difference between the data without nowcasting and the median of the nowcasted projections for the entire period and for the six days from the date of onset of symptoms to diagnosis at the moment of data extraction. Results: The number of new cases throughout the entire period, without nowcasting, was 389. With nowcasting, it was 694 (UI95 496-897,025). At the six days period, the number without nowcasting was 19 and 104 (95% UI 60-142) with. The underdiagnosis was 37.29% in the entire period and 81.73% at the six days period. Conclusions: The underdiagnosis was more critical in six days from the date of onset of symptoms to diagnosis before the data collection than in the entire period. The use of nowcasting with machine learning techniques can help to estimate the number of new cases of the disease.", "qid": 8, "docid": "u3bs5sj0", "rank": 95, "score": 0.7447227835655212}, {"content": "Title: Testing for COVID-19: willful ignorance or selfless behavior? Content: Widespread testing is key to controlling the spread of COVID-19. But should we worry about self-selection bias in the testing? The recent literature on willful ignorance says we should \u2013 people often avoid health information. In the context of COVID-19, such willful ignorance can bias testing data. Furthermore, willful ignorance often arises when selfish wants conflict with social benefits, which might be particularly likely for potential \u2018super-spreaders\u2019 \u2013 people with many social interactions \u2013 given people who test positive are urged to self-isolate for two weeks. We design a survey in which participants (n = 897) choose whether to take a costless COVID-19 test. We find that 70% would take a test. Surprisingly, the people most likely to widely spread COVID-19 \u2013 the extraverts, others who meet more people in their daily lives and younger people \u2013 are the most willing to take a test. People's ability to financially or emotionally sustain self-isolation does not matter to their decision. We conclude that people are selfless in their decision to test for COVID-19. Our results are encouraging \u2013 they imply that COVOD-19 testing may succeed in targeting those who generate the largest social benefits from self-isolation if infected, which strengthens the case for widespread testing.", "qid": 8, "docid": "oyfx3ij5", "rank": 96, "score": 0.7446483969688416}, {"content": "Title: The COVID-19 (SARS-CoV-2) Uncertainty Tripod in Brazil: Assessments on model-based predictions with large under-reporting Content: The COVID-19 pandemic (SARS-CoV-2 virus) is the defying global health crisis of our time. The absence of mass testing and the relevant presence of asymptomatic individuals causes the available data of the COVID-19 pandemic in Brazil to be largely under-reported regarding the number of infected individuals and deaths. We propose an adapted Susceptible-Infected-Recovered (SIR) model which explicitly incorporates the under-reporting and the response of the population to public policies (such as confinement measures, widespread use of masks, etc) to cast short-term and long-term predictions. Large amounts of uncertainty could provide misleading models and predictions. In this paper, we discuss the role of uncertainty in these prediction, which is illustrated regarding three key aspects. First, assuming that the number of infected individuals is under-reported, we demonstrate an anticipation regarding the peak of infection. Furthermore, while a model with a single class of infected individuals yields forecasts with increased peaks, a model that considers both symptomatic and asymptomatic infected individuals suggests a decrease of the peak of symptomatic. Second, considering that the actual amount of deaths is larger than what is being register, then demonstrate the increase of the mortality rates. Third, when consider generally under-reported data, we demonstrate how the transmission and recovery rate model parameters change qualitatively and quantitatively. We also investigate the effect of the\"COVID-19 under-reporting tripod\", i.e. the under-reporting in terms of infected individuals, of deaths and the true mortality rate. If two of these factors are known, the remainder can be inferred, as long as proportions are kept constant. The proposed approach allows one to determine the margins of uncertainty by assessments on the observed and true mortality rates.", "qid": 8, "docid": "8cw3bjxh", "rank": 97, "score": 0.7445992231369019}, {"content": "Title: Burden of COVID-19 pandemic in India: Perspectives from Health Infrastructure Content: The coronavirus (COVID-19) is spreading rapidly across the country but testing regime of India is far from the global standards. It is important to identify the states where testing needs expansion and the magnitudes of active COVID cases are higher focusing on current health infrastructure to meet the pandemic. The data on COVID-19 was extracted from the Application Programming Interface. Test positive rate, test per confirmed case, recovery rate, case fatality rate, and percent distribution of active cases were computed. Availability of hospitals, hospital beds, intensive care unit and ventilators per lakh population was also computed by public and private sector. The result revealed that, Maharashtra constitutes more than one-third positive cases in the country. More than a quarter of the active cases in India belonged to the Mumbai district of Maharashtra, followed by the Chennai district (9.4%) and Ahmedabad district (9.1%). Further, about 40 percent of the active cases in India belonged to the 11 districts of Maharashtra. The increased test positive rate in Maharashtra and Gujarat to almost double in last one month is a concern. In order to bring the states and the country in right track, the test positive rate need to be brought down to below 2 percent. The procurement of higher number of high throughput machine, the Cobas 6800 testing machine, is need of the hour. Only few states have adequate health infrastructure. The priority should be the laid on expansion of more laboratories and hospitals, storage of PPE kit, testing kit, and indigenously developed vaccines.", "qid": 8, "docid": "7t31dkjj", "rank": 98, "score": 0.7445051074028015}, {"content": "Title: Racial segregation, testing sites access, and COVID-19 incidence rate in Massachusetts, USA Content: The U.S. has merely 4% of the world population but 25% of the world's COVID-19 cases. Massachusetts has been in the leading position of total cases since the outbreak in the U.S. Racial residential segregation is a fundamental cause of racial disparities in health. Moreover, disparities of access to health care have a large impact on COVID-19 cases. Thus, this study estimates racial segregation and disparities in testing sites access and employs economic, demographic, and transportation variables at the city/town level in Massachusetts. Spatial regression models are applied to evaluate the relationships between COVID-19 incidence rate and related variables. This is the first study to apply spatial analysis methods across neighborhoods in the U.S. to examine the COVID-19 incidence rate. The findings are: 1) residential segregations of Hispanic and Non-Hispanic Black/African Americans have a significantly positive association with COVID-19 incidence rate, indicating the higher susceptibility of COIVD-19 infections among minority; 2) The Black has the shortest drive time to testing sites, followed by Hispanic, Asian, and Whites. The drive time to testing sites is significantly negatively associated with the COVID-19 incidence rate, implying the importance of testing location being accessed by all populations; 3) Poverty rate and road density are significant explanatory variables. Importantly, overcrowding represented by more than one person per room is a significant variable found to be positively associated with COVID-19 incidence rate, suggesting the effectiveness of social distancing for reducing infection; 4) Different from previous studies, elderly population rate is not statistically significant with incidence rate because the elderly population in Massachusetts is less distributed in the hot spot regions of COVID-19 infections. The findings in this study provide useful insights for policymakers to propose new strategies to contain the COVID-19 transmissions in Massachusetts.", "qid": 8, "docid": "gxjsv896", "rank": 99, "score": 0.7442835569381714}, {"content": "Title: Assessing risk factors for SARS-CoV-2 infection in patients presenting with symptoms in Shanghai, China: a multicentre, observational cohort study Content: BACKGROUND: The outbreak of COVID-19 has led to international concern. We aimed to establish an effective screening strategy in Shanghai, China, to aid early identification of patients with COVID-19. METHODS: We did a multicentre, observational cohort study in fever clinics of 25 hospitals in 16 districts of Shanghai. All patients visiting the clinics within the study period were included. A strategy for COVID-19 screening was presented and then suspected cases were monitored and analysed until they were confirmed as cases or excluded. Logistic regression was used to determine the risk factors of COVID-19. FINDINGS: We enrolled patients visiting fever clinics from Jan 17 to Feb 16, 2020. Among 53 617 patients visiting fever clinics, 1004 (1\u00b79%) were considered as suspected cases, with 188 (0\u00b74% of all patients, 18\u00b77% of suspected cases) eventually diagnosed as confirmed cases. 154 patients with missing data were excluded from the analysis. Exposure history (odds ratio [OR] 4\u00b716, 95% CI 2\u00b774\u20136\u00b733; p<0\u00b70001), fatigue (OR 1\u00b756, 1\u00b701\u20132\u00b741; p=0\u00b7043), white blood cell count less than 4 \u00d7 10(9) per L (OR 2\u00b744, 1\u00b728\u20134\u00b764; p=0\u00b70066), lymphocyte count less than 0\u00b78 \u00d7 10(9) per L (OR 1\u00b782, 1\u00b700\u20133\u00b731; p=0\u00b7049), ground glass opacity (OR 1\u00b795, 1\u00b732\u20132\u00b789; p=0\u00b70009), and having both lungs affected (OR 1\u00b754, 1\u00b704\u20132\u00b728; p=0\u00b7032) were independent risk factors for confirmed COVID-19. INTERPRETATION: The screening strategy was effective for confirming or excluding COVID-19 during the spread of this contagious disease. Relevant independent risk factors identified in this study might be helpful for early recognition of the disease. FUNDING: National Natural Science Foundation of China.", "qid": 8, "docid": "e2xh6s42", "rank": 100, "score": 0.7442629337310791}]}
{"query": "how has COVID-19 affected Canada", "hits": [{"content": "Title: Understanding the Perceived Mental Health of Canadians During the COVID-19 Pandemic. Content: BACKGROUND While the physical health implications of the COVID-19 pandemic are regularly publicly available, the mental health toll on Canadians is unknown. This article examines the self-perceived mental health of Canadians during the COVID-19 pandemic and explores associations with various concerns after accounting for socioeconomic and health factors. DATA The cross-sectional Canadian Perspectives Survey Series 1 collected information related to COVID-19 in late March and early April 2020 concerning labour market participation, behaviours, and health for the Canadian population 15 years and older living in the 10 provinces. METHODS Socioeconomic and health characteristics of respondents as well as concerns about the impact of COVID-19 were examined to determine differences in experiencing excellent or very good compared to good, fair or poor perceived mental health. RESULTS Just over half of Canadians aged 15 and older (54%) reported excellent or very good mental health during the COVID-19 pandemic. Several concerns were also associated with mental health. Notably, after considering the effects of socioeconomic and health characteristics, women, youth, individuals with a physical health condition and those who were very or extremely concerned with family stress from confinement were less likely to report excellent or very good mental health. DISCUSSION These findings point to particular risks for lower perceived mental health during the COVID-19 pandemic. Results highlight various concerns of Canadians which may be associated with mental health, in particular, family stress in the home.", "qid": 9, "docid": "lf5xg8p3", "rank": 1, "score": 0.8211932182312012}, {"content": "Title: Understanding the Perceived Mental Health of Canadians During the COVID-19 Pandemic Content: BACKGROUND: While the physical health implications of the COVID-19 pandemic are regularly publicly available, the mental health toll on Canadians is unknown. This article examines the self-perceived mental health of Canadians during the COVID-19 pandemic and explores associations with various concerns after accounting for socioeconomic and health factors. DATA: The cross-sectional Canadian Perspectives Survey Series 1 collected information related to COVID-19 in late March and early April 2020 concerning labour market participation, behaviours, and health for the Canadian population 15 years and older living in the 10 provinces. METHODS: Socioeconomic and health characteristics of respondents as well as concerns about the impact of COVID-19 were examined to determine differences in experiencing excellent or very good compared to good, fair or poor perceived mental health. RESULTS: Just over half of Canadians aged 15 and older (54%) reported excellent or very good mental health during the COVID-19 pandemic. Several concerns were also associated with mental health. Notably, after considering the effects of socioeconomic and health characteristics, women, youth, individuals with a physical health condition and those who were very or extremely concerned with family stress from confinement were less likely to report excellent or very good mental health. DISCUSSION: These findings point to particular risks for lower perceived mental health during the COVID-19 pandemic. Results highlight various concerns of Canadians which may be associated with mental health, in particular, family stress in the home.", "qid": 9, "docid": "90t0jmwf", "rank": 2, "score": 0.8185496926307678}, {"content": "Title: Health-related concerns and precautions during the COVID-19 pandemic: A comparison of Canadians with and without underlying health conditions Content: BACKGROUND: The risk of experiencing adverse outcomes from the coronavirus disease 2019 (COVID-19), such as hospitalization, admission to intensive care units and death, is elevated for older individuals and those with certain underlying health conditions including diabetes, chronic conditions affecting lungs, heart or kidneys, and a compromised immune system. DATA AND METHODS: Data collected between March 29 and April 3, 2020 from the Canadian Perspectives Survey Series 1: Impacts of COVID-19 (n=4,627) were used to estimate the prevalence of underlying health conditions, health concerns and precautionary behaviours among Canadians aged 15 or older living in the provinces. Multivariate analyses examined associations between these variables after accounting for age, sex and education. RESULTS: Close to 1 in 4 Canadians (24%) had an underlying health condition that increased their risk of adverse outcomes from COVID-19. Overall, 36% of the population were very or extremely concerned about the impact of COVID-19 on their own health. Individuals with underlying health conditions had higher odds (odds ratio: 2.0, 95% confidence interval: 1.6 to 2.5) of being highly concerned than those without these conditions, after adjustment for demographic characteristics. High percentages of Canadians took precautions to reduce the risk of infection regardless of whether or not they had underlying health conditions. DISCUSSION: Health status was associated with higher levels of concern for one's own health in the early period of the COVID-19 pandemic. Most Canadians were taking precautions recommended by public health authorities to protect themselves and others.", "qid": 9, "docid": "in2edn29", "rank": 3, "score": 0.8080804347991943}, {"content": "Title: Health-related concerns and precautions during the COVID-19 pandemic: A comparison of Canadians with and without underlying health conditions. Content: BACKGROUND The risk of experiencing adverse outcomes from the coronavirus disease 2019 (COVID-19), such as hospitalization, admission to intensive care units and death, is elevated for older individuals and those with certain underlying health conditions including diabetes, chronic conditions affecting lungs, heart or kidneys, and a compromised immune system. DATA AND METHODS Data collected between March 29 and April 3, 2020 from the Canadian Perspectives Survey Series 1: Impacts of COVID-19 (n=4,627) were used to estimate the prevalence of underlying health conditions, health concerns and precautionary behaviours among Canadians aged 15 or older living in the provinces. Multivariate analyses examined associations between these variables after accounting for age, sex and education. RESULTS Close to 1 in 4 Canadians (24%) had an underlying health condition that increased their risk of adverse outcomes from COVID-19. Overall, 36% of the population were very or extremely concerned about the impact of COVID-19 on their own health. Individuals with underlying health conditions had higher odds (odds ratio: 2.0, 95% confidence interval: 1.6 to 2.5) of being highly concerned than those without these conditions, after adjustment for demographic characteristics. High percentages of Canadians took precautions to reduce the risk of infection regardless of whether or not they had underlying health conditions. DISCUSSION Health status was associated with higher levels of concern for one's own health in the early period of the COVID-19 pandemic. Most Canadians were taking precautions recommended by public health authorities to protect themselves and others.", "qid": 9, "docid": "06v5bf01", "rank": 4, "score": 0.8066874742507935}, {"content": "Title: Impact of COVID-19 on Canadian medical oncologists and cancer care: Canadian Association of Medical Oncologists survey report. Content: Background The covid-19 pandemic has presented unprecedented professional and personal challenges for the oncology community. Under the auspices of the Canadian Association of Medical Oncologists, we conducted an online national survey to better understand the impact of the pandemic on the medical oncology community in Canada. Methods An English-language multiple-choice survey, including questions about demographics, covid-19 risk, use of personal protective equipment (ppe), personal challenges, and chemotherapy management was distributed to Canadian medical oncologists. The survey was open from 30 March to 4 April 2020, and attracted 159 responses. Results More than 70% of medical oncologists expressed moderate-to-extreme concern about personally contracting covid-19 and about family members or patients (or both) contracting covid-19 from them. Despite that high level of concern, considerable variability in the use of ppe in direct cancer care was reported at the time of this survey, with 33% of respondents indicating no routine ppe use at their institutions and 69% indicating uncertainty about access to adequate ppe. Of the respondents, 54% were experiencing feelings of nervousness or anxiety on most days, and 52% were having feelings of depression or hopelessness on at least some days. Concern about aging parents or family and individual wellness represented the top personal challenges identified. The management of cancer patients has been affected, with adoption of telemedicine reported by 82% of respondents, and cessation of clinical trial accrual reported by 54%. The 3 factors deemed most important for treatment decision-making were\u25a0 cancer prognosis and anticipated benefit from treatment,\u25a0 risk of treatment toxicity during scarce health care access, and\u25a0 patient risk of contracting covid-19. Conclusions This report describes the results of the first national survey assessing the impact of the covid-19 on Canadian medical oncologists and how they deliver systemic anticancer therapies. We hope that these data will provide a framework to address the challenges identified.", "qid": 9, "docid": "ux0kjt9l", "rank": 5, "score": 0.7973631620407104}, {"content": "Title: A population mental health perspective on the impact of COVID-19 Content: The global pandemic of coronavirus disease 2019 (COVID-19) has resulted in massive societal, economic, and environmental impacts that have both short- and long-term mental health influences. This commentary serves to tie existing literature on mental health and COVID-19 to the clinical experiences of a psychologist working in the Canadian hospital sector. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 9, "docid": "6ngsyo8o", "rank": 6, "score": 0.7933013439178467}, {"content": "Title: A population mental health perspective on the impact of COVID-19. Content: The global pandemic of coronavirus disease 2019 (COVID-19) has resulted in massive societal, economic, and environmental impacts that have both short- and long-term mental health influences. This commentary serves to tie existing literature on mental health and COVID-19 to the clinical experiences of a psychologist working in the Canadian hospital sector. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 9, "docid": "4q1j6g44", "rank": 7, "score": 0.7933013439178467}, {"content": "Title: The Coronavirus 2019 pandemic in Canada: the impact of public health interventions on the course of the outbreak in Alberta and other provinces Content: Background: The SARS-CoV-2 disease 2019 (COVID-19) pandemic has spread across the world with varying impact on health systems and outcomes. We assessed how the type and timing of public- health interventions impacted the course of the outbreak in Alberta and other Canadian provinces. Methods: We used publicly-available data to summarize rates of laboratory data and mortality in relation to measures implemented to contain the outbreak and testing strategy. We estimated the transmission potential of SARS-CoV-2 before the state of emergency declaration for each province (R0) and at the study end date (Rt). Results: The first cases were confirmed in Ontario (January 25) and British Columbia (January 28). All provinces implemented the same health-policy measures between March 12 and March 30. Alberta had a higher percentage of the population tested (3.8%) and a lower mortality rate (3/100,000) than Ontario (2.6%; 11/100,000) or Quebec (3.1%; 31/100,000). British Columbia tested fewer people (1.7%) and had similar mortality as Alberta. Data on provincial testing strategies were insufficient to inform further analyses. Mortality rates increased with increasing rates of lab- confirmed cases in Ontario and Quebec, but not in Alberta. R0 was similar across all provinces, but varied widely from 2.6 (95% confidence intervals 1.9-3.4) to 6.4 (4.3-8.5), depending on the assumed time interval between onset of symptoms in a primary and a secondary case (serial interval). The outbreak is currently under control in Alberta, British Columbia and Nova Scotia (Rt <1). Interpretation: COVID-19-related health outcomes varied by province despite rapid implementation of similar health-policy interventions across Canada. Insufficient information about provincial testing strategies and a lack of primary data on serial interval are major limitations of existing data on the Canadian COVID-19 outbreak.", "qid": 9, "docid": "v346cpkl", "rank": 8, "score": 0.7910109758377075}, {"content": "Title: Assessing the burden of COVID-19 in Canada Content: Background: The burden of COVID-19 in Canada is unequally distributed geographically, with the largest number of cases and fatalities recorded in Quebec and Ontario while other provinces experienced limited outbreaks. To date, however, no study has assessed how provincial epidemics have unfolded in a comparative perspective. This is essential to calibrate projections of the future course of the epidemic and plan health care resources for the second wave of infections. Methods: Using newly released individual-level data collected by the Public Health Agency of Canada, we assess COVID-19-related morbidity and mortality across age and gender groups at the provincial level through a combination of demographic and survival analyses. Results: Quebec has the highest absolute and per capita number of COVID-19 confirmed positive cases, hospitalizations and fatalities in all age groups. In each province, a higher number of women than men test positive for the disease, especially above age 80. Yet consistently across age groups, infected men are more likely to be hospitalized and enter intensive care than women do. These gender differences in hospitalisation rates account for the higher case fatality risk due to COVID-19 among men compared to women. Interpretation: Although health care capacity across provinces has been sufficient to treat severe cases, we find that the main factor accounting for gender differences in COVID-19-related mortality is the need for hospitalization and intensive care, especially above age 80. This suggests a selection effect of severe cases requiring to be treated in a hospital setting that needs to be further investigated.", "qid": 9, "docid": "54obt430", "rank": 9, "score": 0.7908949851989746}, {"content": "Title: Impact of COVID-19 on Canadian medical oncologists and cancer care: Canadian Association of Medical Oncologists survey report Content: Background: The covid-19 pandemic has presented unprecedented professional and personal challenges for the oncology community. Under the auspices of the Canadian Association of Medical Oncologists, we conducted an online national survey to better understand the impact of the pandemic on the medical oncology community in Canada. Methods: An English-language multiple-choice survey, including questions about demographics, covid-19 risk, use of personal protective equipment (ppe), personal challenges, and chemotherapy management was distributed to Canadian medical oncologists. The survey was open from 30 March to 4 April 2020, and attracted 159 responses. Results: More than 70% of medical oncologists expressed moderate-to-extreme concern about personally contracting covid-19 and about family members or patients (or both) contracting covid-19 from them. Despite that high level of concern, considerable variability in the use of ppe in direct cancer care was reported at the time of this survey, with 33% of respondents indicating no routine ppe use at their institutions and 69% indicating uncertainty about access to adequate ppe. Of the respondents, 54% were experiencing feelings of nervousness or anxiety on most days, and 52% were having feelings of depression or hopelessness on at least some days. Concern about aging parents or family and individual wellness represented the top personal challenges identified. The management of cancer patients has been affected, with adoption of telemedicine reported by 82% of respondents, and cessation of clinical trial accrual reported by 54%. The 3 factors deemed most important for treatment decision-making were\u00e2\u0096 cancer prognosis and anticipated benefit from treatment,\u00e2\u0096 risk of treatment toxicity during scarce health care access, and\u00e2\u0096 patient risk of contracting covid-19. Conclusions: This report describes the results of the first national survey assessing the impact of the covid-19 on Canadian medical oncologists and how they deliver systemic anticancer therapies. We hope that these data will provide a framework to address the challenges identified.", "qid": 9, "docid": "y8ntig41", "rank": 10, "score": 0.7904946208000183}, {"content": "Title: Cardiac Surgery in Canada During the COVID-19 Pandemic: A Guidance Statement From the Canadian Society of Cardiac Surgeons Content: On March 11, 2020, the World Health Organization declared that COVID-19 was a pandemic.1 At that time, only 118,000 cases had been reported globally, 90% of which had occurred in 4 countries.1 Since then, the world landscape has changed dramatically. As of March 31, 2020, there are now nearly 800,000 cases, with truly global involvement.2 Countries that were previously unaffected are currently experiencing mounting rates of the novel coronavirus infection with associated increases in COVID-19-related deaths. At present, Canada has more than 8000 cases of COVID-19, with considerable variation in rates of infection among provinces and territories.3 Amid concerns over growing resource constraints, cardiac surgeons from across Canada have been forced to make drastic changes to their clinical practices. From prioritizing and delaying elective cases to altering therapeutic strategies in high-risk patients, cardiac surgeons, along with their heart teams, are having to reconsider how best to manage their patients. It is with this in mind that the Canadian Society of Cardiac Surgeons (CSCS) and its Board of Directors have come together to formulate a series of guiding statements. With strong representation from across the country and the support of the Canadian Cardiovascular Society, the authors have attempted to provide guidance to their colleagues on the subjects of leadership roles that cardiac surgeons may assume during this pandemic: patient assessment and triage, risk reduction, and real-time sharing of expertise and experiences.", "qid": 9, "docid": "mzaxgbtc", "rank": 11, "score": 0.7887367606163025}, {"content": "Title: COVID-19 and Long-Term Care Policy for Older People in Canada Content: Older people are especially vulnerable to COVID-19, including and especially people living in long-term care facilities. In this Perspective, we discuss the impact of the COVID-19 pandemic on long-term care policy in Canada. More specifically, we use the example of recent developments in Quebec, where a tragedy in a specific facility is acting as a dramatic \"focusing event\". It draws attention to the problems facing long-term care facilities, considering existing policy legacies and the opening of a \"policy window\" that may facilitate comprehensive reforms in the wake of the COVID-19 pandemic.", "qid": 9, "docid": "ulav1vcf", "rank": 12, "score": 0.7878285646438599}, {"content": "Title: COVOID-19 and Long-Term Care Policy for Older People in Canada. Content: Older people are especially vulnerable to COVID-19, including and especially people living in long-term care facilities. In this Perspective, we discuss the impact of the COVID-19 pandemic on long-term care policy in Canada. More specifically, we use the example of recent developments in Quebec, where a tragedy in a specific facility is acting as a dramatic \"focusing event\". It draws attention to the problems facing long-term care facilities, considering existing policy legacies and the opening of a \"policy window\" that may facilitate comprehensive reforms in the wake of the COVID-19 pandemic.", "qid": 9, "docid": "scjui91o", "rank": 13, "score": 0.7878285646438599}, {"content": "Title: Post-Discharge Cardiac Care in the Era of Coronavirus 2019: How Should We Prepare? Content: The novel coronavirus 2019 disease (COVID-19) pandemic has placed intense pressure on health care organizations around the world. Among other concerns, there has been an increasing recognition of common and deleterious cardiovascular effects of COVID-19 based on preliminary studies. Furthermore, patients with preexisting cardiac disease are likely to experience a more severe disease course with COVID-19. As case numbers continue to increase exponentially, a surge in the number of patients with new or comorbid cardiovascular disease will translate into more frequent and, in some cases, prolonged rehabilitation needs after acute hospitalization. This report describes the current status of post-discharge cardiac care in Canada and provides suggestions regarding steps that policymakers and health care organizations can take to prepare for the COVID-19 pandemic.", "qid": 9, "docid": "8508n0ex", "rank": 14, "score": 0.787259042263031}, {"content": "Title: Ramping Up the Delivery of Cardiac Surgery During the COVID-19 Pandemic: A Guidance Statement from the Canadian Society of Cardiac Surgeons Content: Abstract The coronavirus disease 2019 (COVID-19) has had a profound global impact. Its rapid transmissibility has forced whole countries to adopt strict measures to contain its spread. As part of necessary pandemic planning, the majority of Canadian cardiac surgical programs have prioritized and delayed elective procedures in an effort to reduce the burden on the health care system and to mobilize resources in the event of a pandemic surge. While the number of COVID-19 cases continue to increase worldwide, new cases have begun to decline in many jurisdictions. This \u201cflattening of the curve\u201d has inevitably prompted discussions around re-opening of the economy, relaxing some public health restrictions and resuming non-urgent health care delivery.", "qid": 9, "docid": "xtudcufl", "rank": 15, "score": 0.7859123945236206}, {"content": "Title: Life, Interrupted Content: The effects of COVID-19 are still unfolding.", "qid": 9, "docid": "dg6o8hz7", "rank": 16, "score": 0.7845077514648438}, {"content": "Title: Life, Interrupted. Content: The effects of COVID-19 are still unfolding.", "qid": 9, "docid": "cn6e4vjg", "rank": 17, "score": 0.7845077514648438}, {"content": "Title: Post-Discharge Cardiac Care in the Era of Coronavirus 2019: How Should We Prepare? Content: Abstract The novel coronavirus 2019 (COVID-19) pandemic has placed intense pressure on healthcare organizations around the world. Amongst others, there has been an increasing recognition of common and deleterious cardiovascular effects of COVID-19 based on preliminary studies. Furthermore, patients with pre-existing cardiac disease are likely to experience a more severe disease course with COVID-19. As case numbers continue to increase exponentially, a surge in the number of patients with new or comorbid cardiovascular disease will translate into more frequent, and in some cases, prolonged rehabilitation needs following acute hospitalization. This manuscript describes the current status of post-discharge cardiac care in Canada and provides suggestions with regards to steps that policymakers and healthcare organizations can take to prepare for the COVID-19 pandemic.", "qid": 9, "docid": "8obqdbh9", "rank": 18, "score": 0.7839357852935791}, {"content": "Title: Economic thoughts on COVID\u201019 for Canadian food processors Content: In this paper, I explore the potential effects of the COVID\u201019 pandemic on Canadian food processors. First, COVID\u201019 may have an impact on food processing economic activities because of supply and demand shocks. Second, the impact of COVID\u201019 on food processing may depend on the type of products and the size of the processors. The effects of measures taken by the government to flatten the epidemiological curve on the economic activities of the food processing sector are uncertain.", "qid": 9, "docid": "qunw5hhy", "rank": 19, "score": 0.7835147380828857}, {"content": "Title: Cardiac Surgery in Canada During the COVID-19 Pandemic: A Guidance Statement From the Canadian Society of Cardiac Surgeons Content: Abstract On March 11, 2020, the World Health Organization declared that COVID-19 was a pandemic. 1 At that time, only 118,000 cases had been reported globally, 90% of which had occurred in 4 countries. 1 Since then, the world landscape has changed dramatically. As of March 31, 2020, there are now nearly 800,000 cases, with truly global involvement. 2 Countries that were previously unaffected are currently experiencing mounting rates of the novel coronavirus infection with associated increases in COVID-19\u2013related deaths. At present, Canada has more than 8000 cases of COVID-19, with considerable variation in rates of infection among provinces and territories. 3 Amid concerns over growing resource constraints, cardiac surgeons from across Canada have been forced to make drastic changes to their clinical practices. From prioritizing and delaying elective cases to altering therapeutic strategies in high-risk patients, cardiac surgeons, along with their heart teams, are having to reconsider how best to manage their patients. It is with this in mind that the Canadian Society of Cardiac Surgeons (CSCS) and its Board of Directors have come together to formulate a series of guiding statements. With strong representation from across the country and the support of the Canadian Cardiovascular Society, the authors have attempted to provide guidance to their colleagues on the subjects of leadership roles that cardiac surgeons may assume during this pandemic: patient assessment and triage, risk reduction, and real-time sharing of expertise and experiences. A visual abstract of the main principles underlying our recommended approach is provided in Figure 1.", "qid": 9, "docid": "n8omnki4", "rank": 20, "score": 0.7778403759002686}, {"content": "Title: It\u2019s a small world after all: A Canadian resident\u2019s perspective on COVID-19 Content: COVID-19 has infected millions of people, with an estimated total dead in the hundreds of thousands. This has significantly impacted health care, including who is delivering it, how it is delivered, and how it is taught. This article describes challenges of the COVID-19 pandemic from the perspective of a Canadian nuclear medicine resident, including new risks with nuclear imaging, navigating new and sometimes challenging guidelines, as well as working and living within the confines of social distancing.", "qid": 9, "docid": "4crdebgq", "rank": 21, "score": 0.7778046727180481}, {"content": "Title: It's a small world after all: A Canadian resident's perspective on COVID-19 Content: COVID-19 has infected millions of people, with an estimated total dead in the hundreds of thousands. This has significantly impacted health care, including who is delivering it, how it is delivered, and how it is taught. This article describes challenges of the COVID-19 pandemic from the perspective of a Canadian nuclear medicine resident, including new risks with nuclear imaging, navigating new and sometimes challenging guidelines, as well as working and living within the confines of social distancing.", "qid": 9, "docid": "js77ymx4", "rank": 22, "score": 0.7778046727180481}, {"content": "Title: Determinants of self-reported symptoms and testing for COVID-19 in Canada using a nationally representative survey Content: In April 2020, a nationally representative sample of 4, 240 Canadians age 18 years and older were polled about COVID experience in March, early in the epidemic. We examined determinants of COVID symptoms, defined as fever plus difficulty breathing/shortness of breath, dry cough so severe that it disrupts sleep, and/or loss of sense of smell; and testing for SARS-CoV-2 by respondents and/or household members. About 8% of Canadians reported that they and/or one or more household members experienced COVID symptoms. Symptoms were more common in younger than older adults, and among visible minorities. Overall, 3% of respondents and/or household members had been tested for SARS-CoV-2. Being tested was associated with having COVID symptoms, being of Indigenous identity, and living in Quebec. Periodic nationally representative surveys, including high-risk older populations, of symptoms, as well as SARS-CoV-2 antibodies, are needed to understand the course of the Canadian epidemic and prepare for the future.", "qid": 9, "docid": "u54kja4g", "rank": 23, "score": 0.7775646448135376}, {"content": "Title: Canada\u2019s role in strengthening global health security during the COVID-19 pandemic Content: The world is confronted by the current pandemic of Corona Virus Disease (COVID-19), which is a wake-up call for all nations irrespective of their development status or geographical location. Since the start of the century we have seen five big infectious outbreaks which proved that epidemics are no more regarded as historic and geographically confined threats. The Canadian government underlined that these infectious disease outbreaks are threats to global health security and disrupt societal wellbeing and development. In this context, the Public Health Agency of Canada is proactive and has shown its preparedness for outbreaks of emerging and epidemic-prone diseases, and in dealing with these pathogens. Even before the declaration of pandemic, Canada has proved its global health leadership by ensuring collective action and multisectoral coordination which still remains a serious challenge especially for low and middle- income countries with existing poor health systems. In this article we discuss how Canada is addressing the global challenges posed by the COVID-19 pandemic through its leadership and practice of global health diplomacy.", "qid": 9, "docid": "qy66ih4m", "rank": 24, "score": 0.7773122191429138}, {"content": "Title: COVID-19: Pandemic Risk, Resilience and Possibilities for Aging Research Content: The COVID-19 global crisis is reshaping Canadian society in unexpected and profound ways. The significantly higher morbidity and mortality risks by age suggest that this is largely a \u201cgero-pandemic,\u201d which has thrust the field of aging onto center stage. This editorial emphasizes that vulnerable older adults are also those most affected by COVID-19 in terms of infection risk, negative health effects, and the potential deleterious outcomes on a range of social, psychological, and economic contexts \u2013 from ageism to social isolation. We also contend that the pathogenic analysis of this pandemic needs to be balanced with a salutogenic approach that examines the positive adaptation of people, systems and society, termed COVID-19 resilience. This begs the question: how and why do some older adults and communities adapt and thrive better than others? This examination will lead to the identification and response to research and data gaps, challenges, and innovative opportunities as we plan for a future in which COVID-19 has become another endemic infection in the growing list of emerging and re-emerging pathogens.", "qid": 9, "docid": "no8y1ior", "rank": 25, "score": 0.7765606641769409}, {"content": "Title: Interdisciplinary and Collaborative Approaches Needed to Determine Impact of COVID-19 on Older Adults and Aging: CAG/ACG and CJA/RCV Joint Statement Content: The COVID-19 pandemic and subsequent state of public emergency have significantly affected older adults in Canada and worldwide. It is imperative that the gerontological response be efficient and effective. In this statement, the board members of the Canadian Association on Gerontology/L\u2019Association canadienne de g\u00e9rontologie (CAG/ACG) and the Canadian Journal on Aging/La revue canadienne du vieillissement (CJA/RCV) acknowledge the contributions of CAG/ACG members and CJA/RCV readers. We also profile the complex ways that COVID-19 is affecting older adults, from individual to population levels, and advocate for the adoption of multidisciplinary collaborative teams to bring together different perspectives, areas of expertise, and methods of evaluation in the COVID-19 response.", "qid": 9, "docid": "4kojv5pv", "rank": 26, "score": 0.7756562232971191}, {"content": "Title: Interdisciplinary and Collaborative Approaches Needed to Determine Impact of COVID-19 on Older Adults and Aging: CAG/ACG and CJA/RCV Joint Statement Content: The COVID-19 pandemic and subsequent state of public emergency have significantly affected older adults in Canada and worldwide. It is imperative that the gerontological response be efficient and effective. In this statement, the board members of the Canadian Association on Gerontology/L'Association canadienne de g\u00e9rontologie (CAG/ACG) and the Canadian Journal on Aging/La revue canadienne du vieillissement (CJA/RCV) acknowledge the contributions of CAG/ACG members and CJA/RCV readers. We also profile the complex ways that COVID-19 is affecting older adults, from individual to population levels, and advocate for the adoption of multidisciplinary collaborative teams to bring together different perspectives, areas of expertise, and methods of evaluation in the COVID-19 response.", "qid": 9, "docid": "fbq90100", "rank": 27, "score": 0.7756429314613342}, {"content": "Title: Impact of COVID-19 on Canadian Radiology Residency Training Programs Content: PURPOSE: The novel coronavirus disease (COVID-19) pandemic has swept the globe, with a domino effect on medical education and training. In this study, we surveyed Canadian radiology residents to understand the impact of the pandemic on their residency training, strategies utilized by the residency programs in mitigating those impacts, and factors important to residents in the selection of educational resources on COVID-19. METHODS: A 10-item questionnaire was distributed to 460 resident members of the Canadian Association of Radiologists. The survey was open for 2 weeks, with a reminder sent at half-way mark. RESULTS: We received 96 responses (response rate: 20.9%). The 4 highest affected domains of training were daytime case volumes (92.4%), daytime schedules (87.4%), internal and external assessments (86.5%), and vacation/travel (83.3%). Virtual teaching rounds (91.7%), change in schedules to allow staying home (78.1%), and virtual/phone readouts (72.9%) were the most utilized strategies by the Canadian radiology residency programs. Overall stress of exposure to the disease was moderate to low (86.5%). A minority of the residents were redeployed (6.2%), although most (68.8%) were on standby for redeployment. Residents preferred published society guidelines (92.3%), review papers (79.3%), video lectures (79.3%), and web tools (76.9%) for learning about COVID-19 imaging manifestations. CONCLUSION: The COVID-19 pandemic has had a significant impact on various domains of the Canadian radiology residency programs, which has been mitigated by several strategies employed by the training programs.", "qid": 9, "docid": "12eny1vl", "rank": 28, "score": 0.7750486731529236}, {"content": "Title: Potential magnitude of COVID-19-induced healthcare resource depletion in Ontario, Canada Content: Background: The global spread of coronavirus disease 2019 (COVID-19) continues in several jurisdictions, causing significant strain to healthcare systems. The purpose of our study is to predict the impact of the COVID-19 pandemic on patient outcomes and the healthcare system in Ontario, Canada. Methods: We developed an individual-level simulation to model the flow of COVID-19 patients through the Ontario healthcare system. We simulated different combined scenarios of epidemic trajectory and healthcare capacity. Outcomes include numbers of patients needing admission to the ward, Intensive Care Unit (ICU), and requiring ventilation; days to resource depletion; and numbers of patients awaiting resources and deaths associated with limited access to resources. Findings: We demonstrate that with effective early public health measures system resources need not be depleted. For scenarios considering late or ineffective implementation of physical distancing, health system resources would be depleted within 14-26 days. Resource depletion was also avoided or delayed with aggressive measures to rapidly increase ICU, ventilator, and acute care hospital capacity. Interpretation: We found that without aggressive physical distancing measures the Ontario healthcare system would have been inadequately equipped to manage the expected number of patients with COVID-19, despite the rapid capacity increase. This overall lack of resources would have led to an increase in mortality. By slowing the spread of the disease via ongoing public health measures and having increased healthcare capacity, Ontario may have avoided catastrophic stresses to its health care system.", "qid": 9, "docid": "u2upcaod", "rank": 29, "score": 0.7749186754226685}, {"content": "Title: COVID-19: Pandemic Risk, Resilience and Possibilities for Aging Research Content: The COVID-19 global crisis is reshaping Canadian society in unexpected and profound ways. The significantly higher morbidity and mortality risks by age suggest that this is largely a \"gero-pandemic,\" which has thrust the field of aging onto center stage. This editorial emphasizes that vulnerable older adults are also those most affected by COVID-19 in terms of infection risk, negative health effects, and the potential deleterious outcomes on a range of social, psychological, and economic contexts - from ageism to social isolation. We also contend that the pathogenic analysis of this pandemic needs to be balanced with a salutogenic approach that examines the positive adaptation of people, systems and society, termed COVID-19 resilience. This begs the question: how and why do some older adults and communities adapt and thrive better than others? This examination will lead to the identification and response to research and data gaps, challenges, and innovative opportunities as we plan for a future in which COVID-19 has become another endemic infection in the growing list of emerging and re-emerging pathogens.", "qid": 9, "docid": "kshgjhzh", "rank": 30, "score": 0.7739884853363037}, {"content": "Title: Food security and Canada's agricultural system challenged by COVID\u201019 Content: The effect of COVID\u201019 on Canadian food security is examined from two different perspectives. COVID\u201019 creates a unique \u201cincome shock\u201d that is expected to increase the prevalence of household food insecurity. This food insecurity can be measured by utilizing the Canadian Community Health Survey (CCHS). More fundamentally, COVID\u201019 heightens household concern about the capacity of the Canadian food system to ensure food availability. Despite surges in demand and supply chain disruptions, we currently do not observe broad, rapid appreciation in food prices. This suggests that there is an adequate supply of food for the near term. There is less certainty over intermediate and longer time periods because so many factors are in flux, particularly the rate of increases in sicknesses and deaths across the country and globally. Data on these health factors and elements of the food supply chain are needed to predict beyond a short time frame. In this regard, we discuss three ongoing considerations\u2014ease of capital flows, international exchange, and maintaining transportation\u2014that will help ensure food availability in the longer run.", "qid": 9, "docid": "tz5jajeb", "rank": 31, "score": 0.7693769335746765}, {"content": "Title: Precautions and Procedures for Coronary and Structural Cardiac Interventions During the COVID-19 Pandemic: Guidance from Canadian Association of Interventional Cardiology Content: The globe is currently in the midst of a COVID-19 pandemic, resulting in significant morbidity and mortality. This pandemic has placed considerable stress on health care resources and providers. This document from the Canadian Association of Interventional Cardiology- Association Canadienne de Cardiologie d'intervention, specifically addresses the implications for the care of patients in the cardiac catheterization laboratory (CCL) in Canada during the COVID-19 pandemic. The key principles of this document are to maintain essential interventional cardiovascular care while minimizing risks of COVID-19 to patients and staff and maintaining the overall health care resources. As the COVID-19 pandemic evolves, procedures will be increased or reduced based on the current level of restriction to health care services. Although some consistency across the country is desirable, provincial and regional considerations will influence how these recommendations are implemented. We believe the framework and recommendations in this document will provide crucial guidance for clinicians and policy makers on the management of coronary and structural procedures in the CCL as the COVID-19 pandemic escalates and eventually abates.", "qid": 9, "docid": "v31uzr68", "rank": 32, "score": 0.7685496807098389}, {"content": "Title: COVID-19 Pandemic: Global Impact and Potential Implications for Cardiovascular Disease in Canada Content: BACKGROUND: Literature indicates that cardiovascular disease (CVD, including stroke), older age, and availability of healthcare resources impact COVID-19 case fatality rates (CFR). The cumulative effect of COVID-19 CFR in global CVD populations and the extrapolated impact on access to healthcare services in the CVD population in Canada are not fully known. This study explored the relationships of factors that may impact COVID-19 CFR and estimated the potential indirect impact of COVID-19 on Canadian healthcare resources. METHODS: Country-level epidemiological data were analyzed to study the correlation, main effect, and interaction between COVID-19 CFR and: a) proportion of the population with CVD, b) proportion of the population \u2265 65 years, and c) availability of essential health services as defined by the World Health Organization Universal Health Coverage (UHC) index. For indirect implications on healthcare resources, estimates of the volume of postponed coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) and valve surgeries in Ontario were calculated. RESULTS: Positive correlations were found between COVID-19 CFR and a) proportion of the population with CVD (\u03c1=0.40, p=0.001), b) proportion of the population \u2265 65 years (\u03c1=0.43, p=0.0005) and c) UHC index (\u03c1=0.27, p=0.03). For every 1% increase in proportion of the population \u2265 65 years or proportion of the population with CVD, COVID-19 CFR was 9% and 19% higher, respectively. Approximately 1,252 procedures would be postponed monthly in Ontario due to current public health measures. CONCLUSIONS: Countries with more prevalent CVD reported higher COVID-19 CFR. Strain on healthcare resources is likely in Canada.", "qid": 9, "docid": "el11o2cg", "rank": 33, "score": 0.7676355242729187}, {"content": "Title: Economic Consequences of the COVID-19 Outbreak: the Need for Epidemic Preparedness Content: COVID-19 is not only a global pandemic and public health crisis; it has also severely affected the global economy and financial markets. Significant reductions in income, a rise in unemployment, and disruptions in the transportation, service, and manufacturing industries are among the consequences of the disease mitigation measures that have been implemented in many countries. It has become clear that most governments in the world underestimated the risks of rapid COVID-19 spread and were mostly reactive in their crisis response. As disease outbreaks are not likely to disappear in the near future, proactive international actions are required to not only save lives but also protect economic prosperity.", "qid": 9, "docid": "1ts0734u", "rank": 34, "score": 0.7669380903244019}, {"content": "Title: \u2018What is Inconvenient for You is Life-saving for Me\u2019: How Health Inequities are playing out during the COVID-19 Pandemic Content: The COVID-19 pandemic has had a significant impact globally. Most affected, however, are those individuals and groups routinely disadvantaged by the social injustice created by the misdistribution of power, money, and resources. Simple measures that prevent the spread of COVID-19, such as frequent hand washing and social distancing, are unavailable to millions of people in the wealthiest of nations and in the poorest of nations. Disadvantaged groups are impacted more directly and in disproportionately higher numbers due to existing poor health, and the disruption of services central to securing an income and an education will have lasting consequences for their futures. The unintended effect of exclusionary government policies is that privileged citizens and healthcare systems are also at greater risk. This paper seeks to highlight the impact of COVID-19 on those already suffering health inequities through consideration of some of the social determinants of health on groups in affluent and poorer nations. It also highlights some of the factors that may assist in tackling health inequities as we emerge from this pandemic.", "qid": 9, "docid": "3ly4f8dy", "rank": 35, "score": 0.7656675577163696}, {"content": "Title: 'What is Inconvenient for You is Life-saving for Me': How Health Inequities are playing out during the COVID-19 Pandemic Content: The COVID-19 pandemic has had a significant impact globally. Most affected, however, are those individuals and groups routinely disadvantaged by the social injustice created by the misdistribution of power, money, and resources. Simple measures that prevent the spread of COVID-19, such as frequent hand washing and social distancing, are unavailable to millions of people in the wealthiest of nations and in the poorest of nations. Disadvantaged groups are impacted more directly and in disproportionately higher numbers due to existing poor health, and the disruption of services central to securing an income and an education will have lasting consequences for their futures. The unintended effect of exclusionary government policies is that privileged citizens and healthcare systems are also at greater risk. This paper seeks to highlight the impact of COVID-19 on those already suffering health inequities through consideration of some of the social determinants of health on groups in affluent and poorer nations. It also highlights some of the factors that may assist in tackling health inequities as we emerge from this pandemic.", "qid": 9, "docid": "hwlr3qfz", "rank": 36, "score": 0.7656675577163696}, {"content": "Title: Tracking the origin of early COVID-19 cases in Canada Content: Abstract The original coronavirus disease (COVID-19) outbreak in Wuhan, China has become a global pandemic. By tracking the earliest 118 COVID-19 cases in Canada, we produced a Voronoi treemap to show the travel origins of the country\u2019s earliest COVID-19 cases. By March 11, 2020, even though the majority (64.1%) of the world\u2019s COVID-19 confirmed cases still had their origin in China, only 7.6% of Canada\u2019s first 118 COVID-19 cases arose due in travelers to China. The most commonly reported travel history among the 118 cases originated from the Middle East, the United States, and Europe. Thus, in retrospect, broadening of early screening tools and travel restrictions to countries and regions outside China may help control global COVID-19 spread.", "qid": 9, "docid": "wmfcey6f", "rank": 37, "score": 0.7653477191925049}, {"content": "Title: Atypical skin manifestations during immune checkpoint blockage in COVID19-infected lung cancer patients Content: A new coronavirus, named SARS-CoV-2 by the World Health Organization (WHO), has rapidly spread around the world since its first reported case in late December of 2019 from Wuhan, China. As of mid-April 2020, this virus has affected more than 180 countries and territories, infecting more than 1,650,000 individuals and causing over 100.000 deaths. With &#8776;20 million new cases per year globally, cancer affects a significant portion of the population. Individuals affected by cancer are more susceptible to infections due to coexisting chronic diseases (cardiovascular, pulmonary and diabetes), overall poor health status, and systemic immunosuppressive states caused by both cancer and anticancer treatments. As a consequence, patients with malignancies, and especially with lung cancer who develop COVID19 experience more difficult outcomes. A recent multicenter study developed by the Hubei Anti-Cancer Association also documented that lung cancer patients had an increased risk of death, ICU requirement, risk of presenting severe or critical symptoms, and use of invasive mechanical ventilation. Here we present two representative cases of patients with lung cancer and COVID19 without respiratory compromise and with atypical and severe skin manifestations, findings that could be influenced by the chronic use of anti-PD1 antibodies.", "qid": 9, "docid": "924xcntx", "rank": 38, "score": 0.7634902000427246}, {"content": "Title: Exploratory Analysis of COVID-19 Related Tweets in North America to Inform Public Health Institutes Content: Social media is a rich source where we can learn about people's reactions to social issues. As COVID-19 has significantly impacted on people's lives, it is essential to capture how people react to public health interventions and understand their concerns. In this paper, we aim to investigate people's reactions and concerns about COVID-19 in North America, especially focusing on Canada. We analyze COVID-19 related tweets using topic modeling and aspect-based sentiment analysis, and interpret the results with public health experts. We compare timeline of topics discussed with timing of implementation of public health interventions for COVID-19. We also examine people's sentiment about COVID-19 related issues. We discuss how the results can be helpful for public health agencies when designing a policy for new interventions. Our work shows how Natural Language Processing (NLP) techniques could be applied to public health questions with domain expert involvement.", "qid": 9, "docid": "yuv2ki4o", "rank": 39, "score": 0.763297438621521}, {"content": "Title: Pharmacist intervention amid the coronavirus disease 2019 (COVID-19) pandemic: from direct patient care to telemedicine Content: The coronavirus disease (COVID-19) pandemic has placed enormous pressures on the Canadian healthcare system. Patients are expected to stay home in order to contain the spread of the virus, but understandably have numerous questions and concerns about their health. With physical distancing being of utmost importance during the pandemic, much of healthcare has been forced to move online or over the telephone. Virtual healthcare, in the form of video calls, email, or telephone calls with patients, can significantly enhance access to healthcare. Many clinics have moved their appointments online, and physicians are seeing their patients by means of online video calls. Similarly, patients are refilling their prescriptions online and calling pharmacists whenever they have questions about their medications or medical conditions. Pharmacists are considered the most accessible primary care providers, so it is crucial for patients to know that pharmacists are there to support them throughout the pandemic.", "qid": 9, "docid": "9mvn6bqu", "rank": 40, "score": 0.7632383704185486}, {"content": "Title: Tracking the origin of early COVID-19 cases in Canada Content: The original coronavirus disease (COVID-19) outbreak in Wuhan, China has become a global pandemic. By tracking the earliest 118 COVID-19 cases in Canada, we produced a Voronoi treemap to show the travel origins of the country's earliest COVID-19 cases. By March 11, 2020, even though the majority (64.1%) of the world's COVID-19 confirmed cases still had their origin in China, only 7.6% of Canada's first 118 COVID-19 cases arose due in travelers to China. The most commonly reported travel history among the 118 cases originated from the Middle East, the United States, and Europe. Thus, in retrospect, broadening of early screening tools and travel restrictions to countries and regions outside China may help control global COVID-19 spread.", "qid": 9, "docid": "kgifmjvb", "rank": 41, "score": 0.7624189257621765}, {"content": "Title: Hasty Reduction of COVID-19 Lockdown Measures Leads to the Second Wave of Infection Content: The outbreak of COVID-19 has an undeniable global impact, both socially and economically. March 11th, 2020, COVID-19 was declared as a pandemic worldwide. Many governments, worldwide, have imposed strict lockdown measures to minimize the spread of COVID-19. However, these measures cannot last forever; therefore, many countries are already considering relaxing the lockdown measures. This study, quantitatively, investigated the impact of this relaxation in the United States, Germany, the United Kingdom, Italy, Spain, and Canada. A modified version of the SIR model is used to model the reduction in lockdown based on the already available data. The results showed an inevitable second wave of COVID-19 infection following loosening the current measures. The study tries to reveal the predicted number of infected cases for different reopening dates. Additionally, the predicted number of infected cases for different reopening dates is reported.", "qid": 9, "docid": "wqkphg2e", "rank": 42, "score": 0.7624073028564453}, {"content": "Title: COVID-19: Stroke Admissions, Emergency Department Visits, and Prevention Clinic Referrals Content: We assessed the impact of the coronavirus disease 19 (COVID-19) pandemic on code stroke activations in the emergency department, stroke unit admissions, and referrals to the stroke prevention clinic at London\u2019s regional stroke center, serving a population of 1.8 million in Ontario, Canada. We found a 20% drop in the number of code strokes in 2020 compared to 2019, immediately after the first cases of COVID-19 were officially confirmed. There were no changes in the number of stroke admissions and there was a 22% decrease in the number of clinic referrals, only after the provincial lockdown. Our findings suggest that the decrease in code strokes was mainly driven by patient-related factors such as fear to be exposed to the SARS-CoV-2, while the reduction in clinic referrals was largely explained by hospital policies and the Government lockdown.", "qid": 9, "docid": "7g2kg2tz", "rank": 43, "score": 0.7616575360298157}, {"content": "Title: COVID-19: Stroke Admissions, Emergency Department Visits, and Prevention Clinic Referrals Content: We assessed the impact of the coronavirus disease 19 (COVID-19) pandemic on code stroke activations in the emergency department, stroke unit admissions, and referrals to the stroke prevention clinic at London's regional stroke center, serving a population of 1.8 million in Ontario, Canada. We found a 20% drop in the number of code strokes in 2020 compared to 2019, immediately after the first cases of COVID-19 were officially confirmed. There were no changes in the number of stroke admissions and there was a 22% decrease in the number of clinic referrals, only after the provincial lockdown. Our findings suggest that the decrease in code strokes was mainly driven by patient-related factors such as fear to be exposed to the SARS-CoV-2, while the reduction in clinic referrals was largely explained by hospital policies and the Government lockdown.", "qid": 9, "docid": "oek9ud99", "rank": 44, "score": 0.7613080739974976}, {"content": "Title: The Australian response to the COVID-19 pandemic and diabetes \u2013 lessons learned Content: The COVID-19 pandemic has had a significant impact on the economy and health system of most countries in the world and this is also true of Australia. Australia has not seen the huge surge of COVID-19 positive cases and subsequent hospitalisations and deaths experienced in other parts of the world. However there have been important social and health strategies to \u201cflatten\u201d the curve, to reduce infections and to manage those infected. These have included closure of international and interstate borders, local lockdown measures, physical distancing, shift to work from home, closure of non-essential businesses and full or partial closure of all schools and tertiary education facilities. From the diabetes care perspective, there was a significant and concerted diversion of hospital resources and staff to COVID-19 specific activities. Reduced access to primary care, diagnostic and hospital services for diabetes, combined with fear of exposure to the virus in these settings, led to a significant drop in access to usual diabetes care. Provision of outpatient and private sector diabetes services via telehealth was encouraged and supported by expanded and new government subsidies. Importantly, for the first time, there was government funded subsidy for care delivered via the telephone and inclusion of credentialled diabetes educators in funded telephone/telehealth support. The Australian health professional and consumer organisations worked cooperatively producing guidelines, position statements and other educational resources specific for the COVID-19 setting. Once the COVID-19 pandemic is over, review of all the changes will be important, determining which should be permanently implemented. The learnings from COVID-19 should help prepare Australia for future pandemics or other major health crises.", "qid": 9, "docid": "j2jvdpbg", "rank": 45, "score": 0.7612260580062866}, {"content": "Title: Estimation of COVID-19-induced depletion of hospital resources in Ontario, Canada. Content: BACKGROUND The global spread of coronavirus disease 2019 (COVID-19) continues in several jurisdictions, causing substantial strain to health care systems. The purpose of our study was to predict the effect of the COVID-19 pandemic on patient outcomes and use of hospital resources in Ontario, Canada. METHODS We developed an individuallevel simulation to model the flow of patients with COVID-19 through the hospital system in Ontario. We simulated different combined scenarios of epidemic trajectory and hospital health care capacity. Our outcomes included the number of patients who needed admission to the ward or to the intensive care unit (ICU) with or without the need for mechanical ventilation, number of days to resource depletion, number of patients awaiting resources and number of deaths. RESULTS We found that with effective early public health measures, hospital system resources would not be depleted. For scenarios with late or ineffective implementation of physical distancing, hospital resources would be depleted within 14-26 days, and in the worst case scenario, 13 321 patients would die while waiting for needed resources. Resource depletion would be avoided or delayed with aggressive measures to increase ICU, ventilator and acute care hospital capacities. INTERPRETATION We found that without aggressive physical distancing measures, the Ontario hospital system would have been inadequately equipped to manage the expected number of patients with COVID-19 despite a rapid increase in capacity. This lack of hospital resources would have led to an increase in mortality. By slowing the spread of the disease using public health measures and by increasing hospital capacity, Ontario may have avoided catastrophic stresses to its hospitals.", "qid": 9, "docid": "gpxxdebo", "rank": 46, "score": 0.7611418962478638}, {"content": "Title: Precautions and Procedures for Coronary and Structural Cardiac Interventions during the COVID-19 Pandemic: Guidance from Canadian Association of Interventional Cardiology Content: Abstract The globe is currently in the midst of a COVID-19 pandemic resulting in significant morbidity and mortality. This pandemic has placed considerable stress on health care resources and providers. This document from the Canadian Association of Interventional Cardiology - Association Canadienne de Cardiologie d'intervention, specifically addresses the implications for the care of patients in the Cardiac Catheterization Laboratory (CCL) in Canada during the COVID-19 pandemic. The key principles of this document are to maintain essential interventional cardiovascular care while minimizing risks of COVID-19 to patients/staff and maintaining the overall healthcare resources. As the COVID-19 pandemic evolves, procedures will be increased or reduced based on the current level of restriction to health care services. While some consistency across the country is desirable, provincial and regional considerations will influence how these recommendations are implemented. We believe the framework and recommendations in this document will provide crucial guidance for clinicians and policy makers on the management of coronary and structural procedures in the CCL as the COVID-19 pandemic escalates and eventually abates.", "qid": 9, "docid": "hn1z0817", "rank": 47, "score": 0.7610390186309814}, {"content": "Title: Special considerations in the management of adult patients with acute leukaemias and myeloid neoplasms in the COVID-19 era: recommendations from a panel of international experts Content: The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 is a global public health crisis. Multiple observations indicate poorer post-infection outcomes for patients with cancer than for the general population. Herein, we highlight the challenges in caring for patients with acute leukaemias and myeloid neoplasms amid the COVID-19 pandemic. We summarise key changes related to service allocation, clinical and supportive care, clinical trial participation, and ethical considerations regarding the use of lifesaving measures for these patients. We recognise that these recommendations might be more applicable to high-income countries and might not be generalisable because of regional differences in health-care infrastructure, individual circumstances, and a complex and highly fluid health-care environment. Despite these limitations, we aim to provide a general framework for the care of patients with acute leukaemias and myeloid neoplasms during the COVID-19 pandemic on the basis of recommendations from international experts.", "qid": 9, "docid": "ec27ech5", "rank": 48, "score": 0.7606816291809082}, {"content": "Title: How Simulations May Help Us to Understand the Dynamics of COVID\u201019 Spread. \u2013 Visualizing Non\u2010Intuitive Behaviors of a Pandemic (pansim.uni\u2010jena.de) Content: The new coronavirus SARS\u2010COV\u20102 is currently impacting life around the globe (1). The rapid spread of this viral disease might be highly challenging for health care systems. This was seen in Northern Italy and in New York City for example(2). Governments reacted with different measures such as shutdown of all schools, universities and up to a general curfew. All of those measures have a huge impact on the economy. The United Nations secretary general has stated recently: \u201cThe COVID\u201019 pandemic is one of the most dangerous challenges this world has faced in our lifetime.", "qid": 9, "docid": "refvewcm", "rank": 49, "score": 0.7605895400047302}, {"content": "Title: Estimation of COVID-19-induced depletion of hospital resources in Ontario, Canada Content: BACKGROUND: The global spread of coronavirus disease 2019 (COVID-19) continues in several jurisdictions, causing substantial strain to health care systems. The purpose of our study was to predict the effect of the COVID-19 pandemic on patient outcomes and use of hospital resources in Ontario, Canada. METHODS: We developed an individual-level simulation to model the flow of patients with COVID-19 through the hospital system in Ontario. We simulated different combined scenarios of epidemic trajectory and hospital health care capacity. Our outcomes included the number of patients who needed admission to the ward or to the intensive care unit (ICU) with or without the need for mechanical ventilation, number of days to resource depletion, number of patients awaiting resources and number of deaths. RESULTS: We found that with effective early public health measures, hospital system resources would not be depleted. For scenarios with late or ineffective implementation of physical distancing, hospital resources would be depleted within 14-26 days, and in the worst case scenario, 13 321 patients would die while waiting for needed resources. Resource depletion would be avoided or delayed with aggressive measures to increase ICU, ventilator and acute care hospital capacities. INTERPRETATION: We found that without aggressive physical distancing measures, the Ontario hospital system would have been inadequately equipped to manage the expected number of patients with COVID-19 despite a rapid increase in capacity. This lack of hospital resources would have led to an increase in mortality. By slowing the spread of the disease using public health measures and by increasing hospital capacity, Ontario may have avoided catastrophic stresses to its hospitals.", "qid": 9, "docid": "h6g65f9w", "rank": 50, "score": 0.7605262994766235}, {"content": "Title: Coronavirus Disease 2019 (COVID-19) in Children: Vulnerable or Spared? A Systematic Review Content: The ongoing pandemic of coronavirus disease 2019 (COVID-19) has affected people from all cultures, religions, gender, and age groups around the world. In the last few months, several studies have been conducted on various aspects of COVID-19. Our goal was to see if the pediatric population is vulnerable to this infection. In this review, we conducted extensive research mainly by using the PubMed database. We used Medical Subject Headings (MeSH) and associated keywords to engage in an extensive search focussing on COVID-19 in the pediatric population. We discovered that most of the studies were from China, and some of them were in the Chinese language. However, English translations of many of the studies were available. For accessing the relevant statistical data, we relied on the World Health Organization (WHO) resources and the official website of the Ontario Government (ontario.ca). Most of the studies showed that the virus has affected the pediatric population. However, we found some differences among these studies regarding the severity of symptoms in children affected by COVID-19. While a few studies stated that the virus has presented with milder symptoms in the pediatric population, some studies have presented data of children who have suffered life-threatening complications due to COVID-19. Although the data is limited, we have been able to conclude from the studies we reviewed that COVID-19 does indeed affect children the same way as any other age group. Moreover, children can act as carriers of the virus and can endanger the lives of other individuals. Besides, neonates and infants can easily acquire the infection from family members without having any exposure to the outside world. Hence, utmost care should be taken while handling this population. More trials and studies should be conducted to analyze the impact of early diagnosis of infection in children and its management.", "qid": 9, "docid": "62cyo5kj", "rank": 51, "score": 0.7602411508560181}, {"content": "Title: COVID-19 related concerns of people with long-term respiratory conditions: A qualitative study Content: BACKGROUND The COVID-19 pandemic is having profound psychological impacts on populations globally, with increasing levels of stress, anxiety, and depression being reported, especially in people with pre-existing medical conditions who appear to be particularly vulnerable. There are limited data on the specific concerns people have about COVID-19 and what these are based on. METHODS The aim of this study was to identify and explore the concerns of people with long-term respiratory conditions in the UK regarding the impact of the COVID-19 pandemic and how these concerns were affecting them. We conducted a thematic analysis of free text responses to the question 'What are your main concerns about getting coronavirus?', which was included in the British Lung Foundation/Asthma UK (BLF-AUK) partnership COVID-19 survey, conducted between the 1st and 8th of April. This was during the 3rd week of the UK's initial social distancing measures. RESULTS 7,039 responses were analysed, with respondents from a wide range of ages, gender, and all UK nations. Respondents reported having asthma (85%), COPD (9%), bronchiectasis (4%), interstitial lung disease (2%), or 'other' lung diseases (e.g. lung cancer) (1%). Four main themes were identified: 1) vulnerability to COVID-19; 2) anticipated experience of contracting COVID-19; 3) wide-reaching uncertainty; and 4) inadequate national response. CONCLUSIONS The COVID-19 pandemic is having profound psychological impacts. The concerns we identified largely reflect objective, as well as subjective, aspects of the current situation. Hence, key approaches to reducing these concerns require changes to the reality of their situation, and are likely to include i) helping people optimise their health, limit risk of infection, and access necessities; ii) minimising the negative experience of disease where possible, iii) providing up-to-date, accurate and consistent information, iv) improving the government and healthcare response.", "qid": 9, "docid": "pwoe3p1p", "rank": 52, "score": 0.7601957321166992}, {"content": "Title: Has the COVID-19 Pandemic Affected MPs\u2019 Representational Activities? Content: The COVID-19 pandemic has necessarily affected the operation of Canada's Parliament and, thus, the activities of Members of Parliament (MPs) (Malloy, 2020; Rayment and VandenBeukel, 2020). Here, we explore how the pandemic has affected the representational activities of individual MPs.", "qid": 9, "docid": "u8hogdyf", "rank": 53, "score": 0.7599997520446777}, {"content": "Title: Laboratory-confirmed COVID-19 in children and youth in Canada, January 15-April 27, 2020 Content: Understanding the epidemiology of COVID-19 among children and youth in Canada will help to inform public health measures in settings where children gather. As of April 27, 2020, provinces and territories provided the Public Health Agency of Canada with detailed information on 24,079 cases, of which 3.9% (n=938) were younger than 20 years of age. The detection rate per 100,000 population was lower in this age group (11.9 per 100,000), compared with those aged 20-59 years (72.4 per 100,000) and 60 and older (113.6 per 100,000). The median age among those younger than 20 years of age was 13 years, and cases were distributed equally across male and female genders. Among provinces and territories with more than 100 cases, 1.6% to 9.8% of cases were younger than 20 years of age. Cases in this age group were more likely to be asymptomatic: 10.7% compared with 2.4% in those aged 20-59 years and 4.1% in those aged 60 and older. Children and youth experienced severe outcomes less often, but 2.2% (n=15/672) of cases within this age group were severe enough to require hospitalization. Based on available exposure information, 11.3% (n=59/520) of cases aged younger than 20 years had no known contact with a case. Canadian findings align with those of other countries.", "qid": 9, "docid": "bvujapf5", "rank": 54, "score": 0.7598890066146851}, {"content": "Title: Laboratory-confirmed COVID-19 in children and youth in Canada, January 15-April 27, 2020. Content: Understanding the epidemiology of COVID-19 among children and youth in Canada will help to inform public health measures in settings where children gather. As of April 27, 2020, provinces and territories provided the Public Health Agency of Canada with detailed information on 24,079 cases, of which 3.9% (n=938) were younger than 20 years of age. The detection rate per 100,000 population was lower in this age group (11.9 per 100,000), compared with those aged 20-59 years (72.4 per 100,000) and 60 and older (113.6 per 100,000). The median age among those younger than 20 years of age was 13 years, and cases were distributed equally across male and female genders. Among provinces and territories with more than 100 cases, 1.6% to 9.8% of cases were younger than 20 years of age. Cases in this age group were more likely to be asymptomatic: 10.7% compared with 2.4% in those aged 20-59 years and 4.1% in those aged 60 and older. Children and youth experienced severe outcomes less often, but 2.2% (n=15/672) of cases within this age group were severe enough to require hospitalization. Based on available exposure information, 11.3% (n=59/520) of cases aged younger than 20 years had no known contact with a case. Canadian findings align with those of other countries.", "qid": 9, "docid": "xzoleks8", "rank": 55, "score": 0.7598890066146851}, {"content": "Title: The coronavirus (COVID-19) pandemic's impact on mental health Content: Throughout the world, the public is being informed about the physical effects of SARS-CoV-2 infection and steps to take to prevent exposure to the coronavirus and manage symptoms of COVID-19 if they appear. However, the effects of this pandemic on one's mental health have not been studied at length and are still not known. As all efforts are focused on understanding the epidemiology, clinical features, transmission patterns, and management of the COVID-19 outbreak, there has been very little concern expressed over the effects on one's mental health and on strategies to prevent stigmatization. People's behavior may greatly affect the pandemic's dynamic by altering the severity, transmission, disease flow, and repercussions. The present situation requires raising awareness in public, which can be helpful to deal with this calamity. This perspective article provides a detailed overview of the effects of the COVID-19 outbreak on the mental health of people.", "qid": 9, "docid": "5cmcri6u", "rank": 56, "score": 0.7598526477813721}, {"content": "Title: Lack of coordination and medical disinformation in Canadian self-assessment tools for COVID-19 Content: As SARS-CoV-2 threatens to overwhelm health systems in Canada, it is imperative that provinces are able to plan and manage an effective and reduced risk response. For this response to be most effective, it must reflect an evidence-based, pan-Canadian response. We designed four different prototypical patients with a combination of common COVID-19 symptoms and opportunities for exposure who were made to self-assess using the 10 provincial COVID-19 self-assessment tools on 1 April. These tools were developed to allow individuals to self-triage, allowing health systems direct capacity to testing and care. We assessed the consistency of the self-assessment tools and of the guidance provided to the patients. While the tools generally screen in three areas, the scope of included COVID-19 associated symptoms as well as the opportunities for exposure, and therefore transmission, vary between provinces such that no two provinces screened in the same way. This was, in turn, reflected in the inconsistency in guidance found. A patient with cough who had travelled abroad or had close contact with a confirmed case within 14 days received the most consistent guidance, with remaining patients receiving guidance ranging from mandatory quarantine or self-isolation to being told they did not have COVID-19 symptoms, guidance at odds with medical evidence. Thus, there is not a single, evidence-based Canadian standard of care simply for self-assessment. Without consistency in public health guidance, Canadians cannot appropriately self-isolate to mitigate community transmission, nor can the necessary valid and reliable data be collected to inform critical epidemiological models that help guide pandemic response. If federal and provincial governments are unable to coordinate a response, Parliament must use its available jurisdiction to legislate a duty on both to follow national standards, so as to improve coordination on COVID-19 in coming months.", "qid": 9, "docid": "idg60ids", "rank": 57, "score": 0.7593573331832886}, {"content": "Title: How Does COVID-19 impact Students with Disabilities/Health Concerns? Content: The impact of COVID-19 on students has been enormous, with an increase in worries about fiscal and physical health, a rapid shift to online learning, and increased isolation. In addition to these changes, students with disabilities/health concerns may face accessibility problems with online learning or communication tools, and their stress may be compounded by additional risks such as financial stress or pre-existing conditions. To our knowledge, no one has looked specifically at the impact of COVID-19 on students with disabilities/health concerns. In this paper, we present data from a survey of 147 students with and without disabilities collected in late March to early April of 2020 to assess the impact of COVID-19 on these students' education and mental health. Our findings show that students with disabilities/health concerns were more concerned about classes going online than their peers without disabilities. In addition, students with disabilities/health concerns also reported that they have experienced more COVID-19 related adversities compared to their peers without disabilities/health concerns. We argue that students with disabilities/health concerns in higher education need confidence in the accessibility of the online learning tools that are becoming increasingly prevalent in higher education not only because of COVID-19 but also more generally. In addition, educational technologies will be more accessible if they consider the learning context, and are designed to provide a supportive, calm, and connecting learning environment.", "qid": 9, "docid": "4ni1vv4l", "rank": 58, "score": 0.7583844065666199}, {"content": "Title: COVID-19 and diabetes: What have we learned so far? Content: COVID-19 and diabetes are both pandemics with major impacts on global public health. While the response to COVID-19 has been rapid and progressive to reduce risk of harm, the response to the diabetes pandemic has been somewhat more muted. People with diabetes have been disproportionately affected by COVID-19, with growing evidence of higher mortality and morbidity. In this article, we discuss the impact of COVID-19 on our diabetes service in an urban area in the UK. We discuss the impact on our patients and ourselves, and the possible lessons we can carry into the future.", "qid": 9, "docid": "dbclnrwr", "rank": 59, "score": 0.7580667734146118}, {"content": "Title: COVID-19 and finance: Agendas for future research Content: This paper highlights the enormous economic and social impact of COVID-19 with respect to articles that have either prognosticated such a large-scale event, and its economic consequences, or have assessed the impacts of other epidemics and pandemics. A consideration of possible impacts of COVID-19 on financial markets and institutions, either directly or indirectly, is briefly outlined by drawing on a variety of literatures. A consideration of the characteristics of COVID-19, along with what research suggests have been the impacts of other past events that in some ways roughly parallel COVID-19, points toward avenues of future investigation.", "qid": 9, "docid": "3sem1q9e", "rank": 60, "score": 0.7574557065963745}, {"content": "Title: A Comprehensive Review of the COVID-19 Pandemic and the Role of IoT, Drones, AI, Blockchain, and 5G in Managing its Impact Content: The unprecedented outbreak of the 2019 novel coronavirus, termed as COVID-19 by the World Health Organization (WHO), has placed numerous governments around the world in a precarious position. The impact of the COVID-19 outbreak, earlier witnessed by the citizens of China alone, has now become a matter of grave concern for virtually every country in the world. The scarcity of resources to endure the COVID-19 outbreak combined with the fear of overburdened healthcare systems has forced a majority of these countries into a state of partial or complete lockdown. The number of laboratory-confirmed coronavirus cases has been increasing at an alarming rate throughout the world, with reportedly more than 3 million confirmed cases as of 30 April 2020. Adding to these woes, numerous false reports, misinformation, and unsolicited fears in regards to coronavirus, are being circulated regularly since the outbreak of the COVID-19. In response to such acts, we draw on various reliable sources to present a detailed review of all the major aspects associated with the COVID-19 pandemic. In addition to the direct health implications associated with the outbreak of COVID-19, this study highlights its impact on the global economy. In drawing things to a close, we explore the use of technologies such as the Internet of Things (IoT), Unmanned Aerial Vehicles (UAVs), blockchain, Artificial Intelligence (AI), and 5G, among others, to help mitigate the impact of COVID-19 outbreak.", "qid": 9, "docid": "loishurx", "rank": 61, "score": 0.7569355964660645}, {"content": "Title: The impact of COVID-19 on the provision of cardiac surgical services Content: The global pandemic caused by COVID-19 has had a significant global impact on healthcare systems. One implication of this pandemic is the cancellation of elective cardiac surgeries and the centralization of services. As a result, hospitals in Europe, North America, and the United Kingdom have had to alter the services offered to patients to be able to cope with service provision for COVID infected patients. Data should be collected during this period to provide a good insight following the lockdown period to understand the implication of such service alteration. Future research should also focus on the effects on long-term mortality and morbidity as well as financial implications on hospitals as a result of these changes.", "qid": 9, "docid": "najlyli3", "rank": 62, "score": 0.7569244503974915}, {"content": "Title: Managing the COVID-19 Pandemic as a National Radiation Oncology Centre in Singapore Content: COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a global pandemic in March 2020. It has impacted the world medically, financially, politically and socially, with countries such as China and Italy adopting a full lockdown of their cities to mitigate the transmission. The current mortality rate is 5.4%, with 1 056 159 people infected worldwide. The disease is reminiscent of SARS in 2002, from which the healthcare system of Singapore has garnered many lessons and applied them in the current climate. As a result of the high transmissibility of the virus, hospitals in Singapore have reduced clinic loads and elective treatments to halt propagation of the virus and also to allow redistribution of healthcare workforce to the frontline. Cancer patients, who are often immunocompromised, are at risk of contracting the disease and becoming seriously ill. At the same time, delaying treatment such as radiotherapy in cancer patients can be detrimental. Here, we describe our experience as a large radiation oncology department in Singapore, including the challenges we encountered and how we managed our patient flow.", "qid": 9, "docid": "cw48tg50", "rank": 63, "score": 0.7567942142486572}, {"content": "Title: Real-time observations of the impact of COVID-19 on underwater noise. Content: A slowdown in global trade activity due to COVID-19 has led to a reduction in commercial shipping traffic into the Port of Vancouver. The Ocean Networks Canada observatory system provides researchers real-time access to oceanographic data from a wide range of instruments including hydrophones located along the offshore and inshore approaches to Vancouver. Measurements of power spectral density at 100 Hz from four of these bottom mounted hydrophones are presented, along with AIS data and shipping and trade statistics to assess to what extent the economic impact of COVID-19 can be observed acoustically and in near real-time. The quarterly trend in median weekly noise power in the shipping band of frequencies shows that a reduction in noise commensurate with the economic slowdown has been observed at three of the four hydrophone stations.", "qid": 9, "docid": "vj5mufav", "rank": 64, "score": 0.756091833114624}, {"content": "Title: Environmental impact of the COVID-19 pandemic\u2013a lesson for the future Content: The environment is an integral component of human and animal health. COVID-19 is a global health challenge in the twenty-first century. The emergence of SARS-CoV-2 in Wuhan, China in December 2019, and its spread to regional countries and nowadays affecting more than 210 countries worldwide represents the first pandemic in history to be caused by a coronavirus. The COVID-19 pandemic has huge impacts on most aspects of human activities, as well as on the economy and health care systems. Lock-downs, quarantines and border closures in the wake of the pandemic have led to reductions in air pollution through decreased travel and production. These positive environmental effects are likely mostly temporary, but may serve as an example that changes in our way of life can have prompt positive effects for the environment and demonstrate the usefulness of travel-reducing measures such as teleconferencing. Thus, acknowledging that COVID-19 is first and foremost a global disaster, the pandemic may inspire to future behavioral changes with positive environmental effects.", "qid": 9, "docid": "ulbuy16y", "rank": 65, "score": 0.7560192346572876}, {"content": "Title: COVID-19 and water Content: The 2019 coronavirus disease, called COVID-19, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since it was first identified in China in December 2019, COVID-19 has spread to almost all countries and territories and caused over 310,000 deaths, as on May 16, 2020. The impacts of the COVID-19 pandemic are now seen in almost every sector of our society. In this article, I discuss the impacts of COVID-19 on the water sector. I point out that our efforts to control the spread of COVID-19 will increase the water demand and worsen the water quality, leading to additional challenges in water planning and management. In view of the impacts of COVID-19 and other global-scale phenomena influencing water resources (e.g., global climate change), I highlight the urgent need for interdisciplinary collaborations among researchers studying water and new strategies to address water issues.", "qid": 9, "docid": "7rrq3o7n", "rank": 66, "score": 0.7559078931808472}, {"content": "Title: The Impact of COVID-19 on HIV Treatment and Research: A Call to Action Content: The impact of the COVID-19 pandemic is far reaching, with devastating effects on individuals, communities, and societies across the world. People with chronic health conditions may be at greater risk of contracting or experiencing complications from COVID-19. In addition to illness or death for those who contract the virus, the physical distancing required to flatten the curve of new cases is having a negative impact on the economy, the effects of which intersect with mental health and other existing health concerns, thus affecting marginalized communities. Given that HIV also has a disproportionate impact on marginalized communities, COVID-19 is affecting people with HIV (PWH) in unique ways and will continue to have an impact on HIV research and treatment after the COVID-19 crisis passes. Using the biopsychosocial framework to contextualize the impact of COVID-19 on PWH, the purpose of this review article is to: (1) outline the similarities and differences between the COVID-19 and HIV pandemics; (2) describe the current and future impact of COVID-19 on PWH; and (3) outline a call to action for scientists and practitioners to respond to the impact of COVID-19 on HIV prevention and treatment.", "qid": 9, "docid": "53b4lrk2", "rank": 67, "score": 0.7548811435699463}, {"content": "Title: The impact of COVID\u201019 on the provision of cardiac surgical services Content: The global pandemic caused by COVID\u201019 has had a significant global impact on healthcare systems. One implication of this pandemic is the cancellation of elective cardiac surgeries and the centralization of services. As a result, hospitals in Europe, North America, and the United Kingdom have had to alter the services offered to patients to be able to cope with service provision for COVID infected patients. Data should be collected during this period to provide a good insight following the lockdown period to understand the implication of such service alteration. Future research should also focus on the effects on long\u2010term mortality and morbidity as well as financial implications on hospitals as a result of these changes.", "qid": 9, "docid": "r711cdgn", "rank": 68, "score": 0.754680871963501}, {"content": "Title: Impact of the COVID-19 Pandemic on Adult Mental Health Content: The outbreak of the Novel Coronavirus (COVID-19) in December 2019 has progressed to the status of a global pandemic, with countries across the seven continents adversely affected and the number of human cases exceeding two million. With no available vaccine, the treatment is primarily symptomatic for those affected and preventative for those at risk. Most countries have taken action to curtail the spread of COVID-19 through measures such as lockdowns, social distancing and voluntary self-isolation. Whilst necessary, such measures and the disease itself, may have an adverse impact on mental health. In view of research from previous pandemic crises, it is known that such situations are likely to increase stress levels and have negative psychiatric effects. The impact is likely to be felt by the general public, sufferers of COVID-19, their families and friends, persons with pre-existing mental health conditions and healthcare workers.", "qid": 9, "docid": "880lwnde", "rank": 69, "score": 0.7542644739151001}, {"content": "Title: COVID-19 outbreak: Migration, effects on society, global environment and prevention Content: The COVID-19 pandemic is considered as the most crucial global health calamity of the century and the greatest challenge that the humankind faced since the 2nd World War. In December 2019, a new infectious respiratory disease emerged in Wuhan, Hubei province, China and was named by the World Health Organization as COVID-19 (coronavirus disease 2019). A new class of corona virus, known as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has been found to be responsible for occurrence of this disease. As far as the history of human civilization is concerned there are instances of severe outbreaks of diseases caused by a number of viruses. According to the report of the World Health Organization (WHO as of April 18 2020), the current outbreak of COVID-19, has affected over 2164111 people and killed more than 146,198 people in more than 200 countries throughout the world. Till now there is no report of any clinically approved antiviral drugs or vaccines that are effective against COVID-19. It has rapidly spread around the world, posing enormous health, economic, environmental and social challenges to the entire human population. The coronavirus outbreak is severely disrupting the global economy. Almost all the nations are struggling to slow down the transmission of the disease by testing & treating patients, quarantining suspected persons through contact tracing, restricting large gatherings, maintaining complete or partial lock down etc. This paper describes the impact of COVID-19 on society and global environment, and the possible ways in which the disease can be controlled has also been discussed therein.", "qid": 9, "docid": "v0bt747q", "rank": 70, "score": 0.7542482614517212}, {"content": "Title: The Australian response to the COVID-19 pandemic and diabetes - Lessons learned Content: The COVID-19 pandemic has had a significant impact on the economy and health system of most countries in the world and this is also true of Australia. Australia has not seen the huge surge of COVID-19 positive cases and subsequent hospitalisations and deaths experienced in other parts of the world. However there have been important social and health strategies to \"flatten\" the curve, to reduce infections and to manage those infected. These have included closure of international and interstate borders, local lockdown measures, physical distancing, shift to work from home, closure of non-essential businesses and full or partial closure of all schools and tertiary education facilities. From the diabetes care perspective, there was a significant and concerted diversion of hospital resources and staff to COVID-19 specific activities. Reduced access to primary care, diagnostic and hospital services for diabetes, combined with fear of exposure to the virus in these settings, led to a significant drop in access to usual diabetes care. Provision of outpatient and private sector diabetes services via telehealth was encouraged and supported by expanded and new government subsidies. Importantly, for the first time, there was government funded subsidy for care delivered via the telephone and inclusion of credentialled diabetes educators in funded telephone/telehealth support. The Australian health professional and consumer organisations worked cooperatively producing guidelines, position statements and other educational resources specific for the COVID-19 setting. Once the COVID-19 pandemic is over, review of all the changes will be important, determining which should be permanently implemented. The learnings from COVID-19 should help prepare Australia for future pandemics or other major health crises.", "qid": 9, "docid": "w56ddzaw", "rank": 71, "score": 0.7540979981422424}, {"content": "Title: The coronavirus (COVID\u201019) pandemic's impact on mental health Content: Throughout the world, the public is being informed about the physical effects of SARS\u2010CoV\u20102 infection and steps to take to prevent exposure to the coronavirus and manage symptoms of COVID\u201019 if they appear. However, the effects of this pandemic on one's mental health have not been studied at length and are still not known. As all efforts are focused on understanding the epidemiology, clinical features, transmission patterns, and management of the COVID\u201019 outbreak, there has been very little concern expressed over the effects on one's mental health and on strategies to prevent stigmatization. People's behavior may greatly affect the pandemic's dynamic by altering the severity, transmission, disease flow, and repercussions. The present situation requires raising awareness in public, which can be helpful to deal with this calamity. This perspective article provides a detailed overview of the effects of the COVID\u201019 outbreak on the mental health of people.", "qid": 9, "docid": "0n5n7p4b", "rank": 72, "score": 0.754056990146637}, {"content": "Title: Pandemic Parliaments: Canadian Legislatures in a Time of Crisis Content: Canadian legislatures\u2019 responses to the COVID-19 pandemic have raised questions about whether and how parliaments should continue to meet during the pandemic (Reid, 2020; Thomas, 2020a). The purpose of this research note is twofold: (1) to document how Canadian legislatures have changed in response to the COVID-19 pandemic and (2) to assess the effect of these responses on legislatures\u2019 ability to fulfill their core functions. Through an analysis of parliamentary records from all elected federal, provincial and territorial legislatures in Canada, we find that the role of parliaments as sites of citizen representation has suffered the most, whereas the scrutinizing and legislative functions of parliaments have tended to be preserved, albeit in a significantly truncated form. We argue that patterns in legislatures' varied responses to the pandemic reveal which aspects of parliamentary functioning these bodies de facto prioritize and which are at risk of being eroded.", "qid": 9, "docid": "hxn46xnn", "rank": 73, "score": 0.7538124322891235}, {"content": "Title: COVID-19 is likely to impact animal health Content: Responses to the ongoing COVID-19 pandemic have included travel bans and social distancing with \u201cshelter in place\u201d orders, resulting in sudden changes in human activity and subsequent effects on the global and national economy. We speculate that animal health will likely be impacted by COVID-19 through the immediate consequences of sudden human confinement and inactivity, and through the long-term consequences of the upcoming economic crisis on farmer livelihoods and veterinary service capacities. We expect the COVID-19 pandemic and the subsequent economic crisis to impact negatively on the control of diseases that are already present in Europe, as well as on the European capacity to prevent and respond in a timely manner to new and emerging animal diseases. We also expect an increased attention to the animal health implications of coronavirus infections in animals. Mechanisms explaining these outcomes include increased wildlife-livestock contacts due to human confinement; disruption of ongoing testing schemes for endemic diseases; lower disease surveillance efforts; and lower capacity for managing populations of relevant wildlife reservoirs. The main mitigation action consists in adapting animal health management strategies to the available resources.", "qid": 9, "docid": "y5e1utju", "rank": 74, "score": 0.7536011338233948}, {"content": "Title: On the assessment of more reliable COVID-19 infected number: the italian case. Content: COVID-19 (SARS-CoV-2) is the most recent pandemic disease the world is currently managing. It started in China at the end of 2019, and it is diffusing throughout Italy, one of the most affected countries, and it is currently spreading through European countries and USA. Patients affected by COVID-19 are identified employing medical swabs applied mainly to (i) citizens with COVID-19 symptoms such as flu or high temperature, or (ii) citizens that had contacts with COVID-19 patients. A percentage of COVID-19 affected patients needs hospitalisation, whereas a portion needs to be treated in Intensive Care Units (ICUs). Nevertheless, it is a matter of current intuition that COVID-19 infected citizens are more than those detected, and sometime the infection is detected too late. Thus there are many efforts in both tracking people activities as well as diffusing low cost reliable COVID-19 tests for early detection. Starting from mortality rates of diseases caused by viruses in the same family (e.g. MERS, SARS, H1N1), we study the relations between the number of COVID-19 infections and the number of deaths, through Italian regions. We thus assess several infections being higher than the ones currently measured. We thus focus on the characterisation of the pandemic diffusion by estimating the infected number of patients versus the number of death. We use such an estimated number of infections, to foresee the effects of restriction actions adopted by governments to constrain virus diffusion. We finally think that our model can support the healthcare system to react when COVID-19 is increasing.", "qid": 9, "docid": "7hqn997j", "rank": 75, "score": 0.7533285617828369}, {"content": "Title: In the shadow of HIV & TB: A commentary on the COVID epidemic in South Africa Content: While COVID-19 has become a global pandemic that has spread to all regions of the globe, local historic, health, and socio-environmental factors shape the epidemiological contours, response, and social challenges present within each affected nation. Thus, while countries like China, Italy, Iran, Brazil, and the United States have all been hard hit by the pandemic, there are critical differences across these nations in a number of variables (e.g. demographic features, health histories, healthcare systems, infection case rates, case fatality rates, national responses). In other words, within the global pandemic there are multiple importantly distinct national epidemics. Overcoming the grave threats to public health presented by COVID-19 requires both international cooperation and country-specific efforts that reflect local histories, needs, and resources. Already concerns are being expressed among health officials about how COVID-19 might be devastating in Africa. Currently, South Africa has the highest number of diagnosed COVID-19 cases on the continent and has been identified as being at high risk in the pandemic. This paper examines the public health response to the COVID-19 threat, how the prior and ongoing HIV and TB epidemics shape the COVID-19 epidemic and influence the response, and the potential ramifications of the response.", "qid": 9, "docid": "2kyeiima", "rank": 76, "score": 0.7526405453681946}, {"content": "Title: In the shadow of HIV & TB: A commentary on the COVID epidemic in South Africa. Content: While COVID-19 has become a global pandemic that has spread to all regions of the globe, local historic, health, and socio-environmental factors shape the epidemiological contours, response, and social challenges present within each affected nation. Thus, while countries like China, Italy, Iran, Brazil, and the United States have all been hard hit by the pandemic, there are critical differences across these nations in a number of variables (e.g. demographic features, health histories, healthcare systems, infection case rates, case fatality rates, national responses). In other words, within the global pandemic there are multiple importantly distinct national epidemics. Overcoming the grave threats to public health presented by COVID-19 requires both international cooperation and country-specific efforts that reflect local histories, needs, and resources. Already concerns are being expressed among health officials about how COVID-19 might be devastating in Africa. Currently, South Africa has the highest number of diagnosed COVID-19 cases on the continent and has been identified as being at high risk in the pandemic. This paper examines the public health response to the COVID-19 threat, how the prior and ongoing HIV and TB epidemics shape the COVID-19 epidemic and influence the response, and the potential ramifications of the response.", "qid": 9, "docid": "dau5bs2x", "rank": 77, "score": 0.7526405453681946}, {"content": "Title: Show me a man or a woman alone and I'll show you a saint: Changes in the frequency of criminal incidents during the COVID-19 pandemic Content: OBJECTIVES: To investigate the effect of the COVID-19 pandemic on the frequency of various crime types (property, violent, and mischief) in Vancouver, Canada. METHODS: Crime data representing residential burglary, commercial burglary, theft of vehicle, theft from vehicle, theft, violence, and mischief are analysed at the city level using interrupted time series techniques. RESULTS: While COVID-19 has not had an impact on all crime types, statistically significant change has been identified in a number of cases. Depending on the crime type, the magnitude and direction of the change in frequency varies. It is argued that (mandated) social restrictions, shifted activity patterns and opportunity structures which are responsible for these findings. CONCLUSIONS: We find support for changes in the frequency of particular crime types during the COVID-19 pandemic. This is important for criminal justice and social service practitioners when operating within an extraordinary event.", "qid": 9, "docid": "ssv1arr1", "rank": 78, "score": 0.752503514289856}, {"content": "Title: Public Policy and Constitutional Rights in Times of Crisis Content: Federal and provincial policy responses to the COVID-19 pandemic raise a host of constitutional issues that decision makers must pay heed to or risk serious violations of individual rights under the Charter of Rights and Freedoms. This research note will examine a number of policy challenges as they relate to mobility rights (s. 6), legal rights (ss. 7 through 14), and equality rights (s. 15) and will articulate the factors that policy makers should consider in design and implementation. Other important constitutional questions, such as those relating to the division of powers, emergency powers and the relationship between the executive and Parliament, have also emerged in Canada but are beyond the scope of this note.", "qid": 9, "docid": "miadomgn", "rank": 79, "score": 0.752454400062561}, {"content": "Title: Reduced COVID-19-Related Critical Illness and Death, and High Risk of Epidemic Resurgence, After Physical Distancing in Ontario, Canada Content: We explored the impact of physical distancing measures on COVID-19 transmission in the population of Ontario, Canada using a previously described age- and health-status stratified transmission model. The model was fit to confirmed cases occupying intensive care unit (ICU) beds and mortality among hospitalized COVID-19 cases for the time period 19 March to 26 April 2020. We projected that mortality would have been 4.6-fold what was observed had physical distancing measures not been implemented in the province. Relaxation of physical distancing measures without compensatory increases in case detection, isolation, and/or contact tracing was projected to result in resurgence of disease activity. Return to normal or near-normal levels of contact would rapidly result in cases exceeding ICU capacity. Maintaining physical distancing for a longer period of time, allowing for the initial wave of infections to subside, delayed this resurgence, but the level of contacts post-restrictive distancing was the major factor determining how quickly ICU capacity was expected to be overwhelmed. Using a model, we demonstrate the marked impact strong public health measures had in reducing ICU admissions and mortality in Ontario. We also show that this hard-earned success is tenuous: relaxation of physical distancing measures in the near-term is projected to result in a rapid resurgence of disease activity.", "qid": 9, "docid": "bp2ilntr", "rank": 80, "score": 0.7519974708557129}, {"content": "Title: Mathematical modeling of COVID-19 containment strategies with considerations for limited medical resources Content: The outbreak of SARS-CoV-2 in China has spread around the world, infecting millions and causing governments to implement strict policies to counteract the spread of the disease. One of the most effective strategies in reducing the severity of the pandemic is social distancing, where members of the population systematically reduce their interactions with others to limit the transmission rate of the virus. However, the implementation of social distancing can be difficult and costly, making it imperative that both policy makers and the citizenry understand the potential benefits if done correctly and the risks if not. In this work, a mathematical model is developed to study the effects of social distancing on the spread of the SARS-CoV-2 virus in Canada. The model is based upon a standard epidemiological SEIRD model that has been stratified to directly incorporate the proportion of individuals who are following social distancing protocols. The model parameters characterizing the disease are estimated from current epidemiological data on COVID-19 using machine learning techniques. The results of the model show that social distancing policies in Canada have already saved thousands of lives and that the prolonged adherence to social distancing guidelines could save thousands more. Importantly, our model indicates that social distancing can significantly delay the onset of infection peaks, allowing more time for the production of a vaccine or additional medical resources. Furthermore, our results stress the importance of easing social distancing restrictions gradually, rather than all at once, in order to prevent a second wave of infections. Model results are compared to the current capacity of the Canadian healthcare system by examining the current and future number of ventilators available for use, emphasizing the need for the increased production of additional medical resources.", "qid": 9, "docid": "51g3vhcx", "rank": 81, "score": 0.7519670128822327}, {"content": "Title: Canadians Think that Nearly All of Us Will Be Allowed Back to Work around August Content: Business closures and work-from-home orders have been a central part of Canada's plan to slow the spread of COVID-19. The success of these measures hinges on public support, which cannot be taken for granted as the orders induce considerable economic pain. As governments consider when to re-open the economy, one relevant variable is when the public expects the economy to re-open. At minimum, if public perceptions differ from government plans then additional government messaging is required to better align expectations.", "qid": 9, "docid": "otybfxom", "rank": 82, "score": 0.7517399787902832}, {"content": "Title: The economic impact of the Coronavirus 2019 (Covid-2019): Implications for the mining industry Content: The Coronavirus 2019 (Covid-19) global pandemic has not only caused infections and deaths, but it has also wreaked havoc with the global economy on a scale not seen since at least the Great Depression. Covid-19 has the potential to destroy individual livelihoods, businesses, industries and entire economies. The mining sector is not immune to these impacts, and the crisis has the potential to have severe consequences in the short, medium and long-term for the industry. Understanding these impacts, and analysing their significance for the industry, and the role it plays in wider economic development is a crucial task for academic research.", "qid": 9, "docid": "mf2vqro7", "rank": 83, "score": 0.7517374753952026}, {"content": "Title: Cardiovascular Clinical Trials in a Pandemic: Immediate Implications of Coronavirus Disease 2019 Content: The coronavirus disease 2019 (COVID-19) pandemic started in Wuhan, Hubei Province, China, in December 2019, and by 24 April 2020, it had affected >2.73 million people in 185 countries and caused >192,000 deaths. Despite diverse societal measures to reduce transmission of the severe acute respiratory syndrome coronavirus 2, such as implementing social distancing, quarantine, curfews and total lockdowns, its control remains challenging. Healthcare practitioners are at the frontline of defence against the virus, with increasing institutional and governmental supports. Nevertheless, new or ongoing clinical trials, not related to the disease itself, remain important for the development of new therapies, and require interactions among patients, clinicians and research personnel, which is challenging, given isolation measures. In this article, the authors summarise the acute effects and consequences of the COVID-19 pandemic on current cardiovascular trials.", "qid": 9, "docid": "gduhterq", "rank": 84, "score": 0.7515090703964233}, {"content": "Title: The psychological impact of COVID-19 pandemic on physicians in Saudi Arabia: A cross-sectional study. Content: Background/Aim COVID-19 pandemic exposed physicians to extraordinary stress and made them vulnerable to various types of psychological illnesses. The aim of this study was to evaluate the impact that the COVID-19 pandemic had on the psychological well-being of physicians. Materials and Methods We performed a cross-sectional, survey-based study, targeting physicians in Saudi Arabia during the COVID-19 pandemic. The primary outcome was to assess the psychological impact that the pandemic had on physicians by using a questionnaire that was previously designed and used by Reynold's et al. to survey Canadians during the SARS outbreak in 2003. The questionnaire assessed respondents' understanding of the rationale for quarantine, quarantine behaviors (including difficulties and compliance), as well as socio-economic and psychological impacts through answers that are based on a Likert scale. We also assessed the possible risk factors for psychological disorders related to the pandemic. Results The study included 529 physicians from various regions in Saudi Arabia. The enrolled physicians were practicing different specialties and branches in medicine. We classified them based on their workplace in relation to COVID-19 exposure to: COVID-19 designated center vs. non-COVID-19 designated centers. Furthermore, we subdivided the physicians who work in COVID-19 designated centers to those who work in high-risk areas such as ER, ICU and COVID-19 isolation wards and other areas as low-risk areas. The most common feelings reported by the physicians during the pandemic were: worry (357, 67.5%), isolation (301, 56.9%) and fear (263, 49.7%). According to logistic regression analysis, physicians older than age 60 were less likely to feel isolated (OR = 0.08, 95% CI = 0.01-0.96, P = 0.05), female physicians were more likely to experience fear (OR = 2.96, 95% CI = 1.20 - 7.27, P = 0.02) and worry (OR = 2.87,95% CI = 1.23 - 6.69, P = 0.02), while physicians with a previous exposure to similar traumatic events were less likely to experience fear (OR = 0.24, 0.10 - 0.64, P = 0.004) during the COVID-19 pandemic. Conclusions The COVID-19 pandemic had a negative psychological effect on physicians in Saudi Arabia. Gender, age, and previous exposure to similar traumatic events were predictive of psychological reactions to the pandemic in this population.", "qid": 9, "docid": "xqtgao57", "rank": 85, "score": 0.7510175108909607}, {"content": "Title: Analysis of Outbreak and Global Impacts of the COVID-19 Content: Corona viruses are a large family of viruses that are not only restricted to causing illness in humans but also affect animals such as camels, cattle, cats, and bats, thus affecting a large group of living species The outbreak of Corona virus in late December 2019 (also known as COVID-19) raised major concerns when the outbreak started getting tremendous While the first case was discovered in Wuhan, China, it did not take long for the disease to travel across the globe and infect every continent (except Antarctica), killing thousands of people Since it has become a global concern, different countries have been working toward the treatment and generation of vaccine, leading to different speculations While some argue that the vaccine may only be a few weeks away, others believe that it may take some time to create the vaccine Given the increasing number of deaths, the COVID-19 has caused havoc worldwide and is a matter of serious concern Thus, there is a need to study how the disease has been propagating across continents by numbers as well as by regions This study incorporates a detailed description of how the COVID-19 outbreak started in China and managed to spread across the globe rapidly We take into account the COVID-19 outbreak cases (confirmed, recovered, death) in order to make some observations regarding the pandemic Given the detailed description of the outbreak, this study would be beneficial to certain industries that may be affected by the outbreak in order to take timely precautionary measures in the future Further, the study lists some industries that have witnessed the impact of the COVID-19 outbreak on a global scale", "qid": 9, "docid": "x51o4gyn", "rank": 86, "score": 0.7508705258369446}, {"content": "Title: Observed and Potential Impacts of the COVID-19 Pandemic on the Environment Content: Various environmental factors influence the outbreak and spread of epidemic or even pandemic events which, in turn, may cause feedbacks on the environment. The novel coronavirus disease (COVID-19) was declared a pandemic on 13 March 2020 and its rapid onset, spatial extent and complex consequences make it a once-in-a-century global disaster. Most countries responded by social distancing measures and severely diminished economic and other activities. Consequently, by the end of April 2020, the COVID-19 pandemic has led to numerous environmental impacts, both positive such as enhanced air and water quality in urban areas, and negative, such as shoreline pollution due to the disposal of sanitary consumables. This study presents an early overview of the observed and potential impacts of the COVID-19 on the environment. We argue that the effects of COVID-19 are determined mainly by anthropogenic factors which are becoming obvious as human activity diminishes across the planet, and the impacts on cities and public health will be continued in the coming years.", "qid": 9, "docid": "pr1j71r9", "rank": 87, "score": 0.7508084774017334}, {"content": "Title: The psychological impact of COVID-19 pandemic on physicians in Saudi Arabia: A cross-sectional study Content: Background/Aim: COVID-19 pandemic exposed physicians to extraordinary stress and made them vulnerable to various types of psychological illnesses. The aim of this study was to evaluate the impact that the COVID-19 pandemic had on the psychological well-being of physicians. Materials and Methods: We performed a cross-sectional, survey-based study, targeting physicians in Saudi Arabia during the COVID-19 pandemic. The primary outcome was to assess the psychological impact that the pandemic had on physicians by using a questionnaire that was previously designed and used by Reynold's et al. to survey Canadians during the SARS outbreak in 2003. The questionnaire assessed respondents' understanding of the rationale for quarantine, quarantine behaviors (including difficulties and compliance), as well as socio-economic and psychological impacts through answers that are based on a Likert scale. We also assessed the possible risk factors for psychological disorders related to the pandemic. Results: The study included 529 physicians from various regions in Saudi Arabia. The enrolled physicians were practicing different specialties and branches in medicine. We classified them based on their workplace in relation to COVID-19 exposure to: COVID-19 designated center vs. non-COVID-19 designated centers. Furthermore, we subdivided the physicians who work in COVID-19 designated centers to those who work in high-risk areas such as ER, ICU and COVID-19 isolation wards and other areas as low-risk areas. The most common feelings reported by the physicians during the pandemic were: worry (357, 67.5%), isolation (301, 56.9%) and fear (263, 49.7%). According to logistic regression analysis, physicians older than age 60 were less likely to feel isolated (OR = 0.08, 95% CI = 0.01-0.96, P = 0.05), female physicians were more likely to experience fear (OR = 2.96, 95% CI = 1.20 - 7.27, P = 0.02) and worry (OR = 2.87,95% CI = 1.23 - 6.69, P = 0.02), while physicians with a previous exposure to similar traumatic events were less likely to experience fear (OR = 0.24, 0.10 - 0.64, P = 0.004) during the COVID-19 pandemic. Conclusions: The COVID-19 pandemic had a negative psychological effect on physicians in Saudi Arabia. Gender, age, and previous exposure to similar traumatic events were predictive of psychological reactions to the pandemic in this population.", "qid": 9, "docid": "lkupo7x9", "rank": 88, "score": 0.7502644062042236}, {"content": "Title: Depression and anxiety during 2019 coronavirus disease pandemic in Saudi Arabia: a cross-sectional study Content: Background: COVID 19 outbreak in 2020 was associated with a high rate of depression and anxiety among individuals in the affected countries. The aim of this study is to explore the influence of the COVID 19 epidemic on the psychological distress of residents of the Kingdom of Saudi Arabia. Methods: A cross sectional study using an online survey was conducted in Saudi Arabia between 27th of March and 27th of April 2020. The Patient Health Questionnaire (PHQ 9) and Generalized Anxiety Disorder-7 (GAD 7) were used to assess depression and anxiety. Logistic regression analysis was used to identify predictors of depression and anxiety. Results: The prevalence of depression and anxiety among the entire study participants was 9.4% and 7.3%, respectively. Non-Saudi residents, aged 50 years and above, divorced, retired, university students, and those with income (2000 to 10,000 RS) were at higher risk of developing depression. Saudi individuals, married, unemployed, and those with high income (> 10,000 RS) were at higher risk of developing anxiety. Conclusions: There is a wide range of the Saudi residents who are at higher risk of mental illness during COVID 19 pandemic. Policymakers and mental healthcare providers are advised to provide continuous monitoring of the psychological consequences during this pandemic, and provide mental support.", "qid": 9, "docid": "gphud9yx", "rank": 89, "score": 0.7500320672988892}, {"content": "Title: COVID-19 is likely to impact animal health Content: Responses to the ongoing COVID-19 pandemic have included travel bans and social distancing with \"shelter in place\" orders, resulting in sudden changes in human activity and subsequent effects on the global and national economy. We speculate that animal health will likely be impacted by COVID-19 through the immediate consequences of sudden human confinement and inactivity, and through the long-term consequences of the upcoming economic crisis on farmer livelihoods and veterinary service capacities. We expect the COVID-19 pandemic and the subsequent economic crisis to impact negatively on the control of diseases that are already present in Europe, as well as on the European capacity to prevent and respond in a timely manner to new and emerging animal diseases. We also expect an increased attention to the animal health implications of coronavirus infections in animals. Mechanisms explaining these outcomes include increased wildlife-livestock contacts due to human confinement; disruption of ongoing testing schemes for endemic diseases; lower disease surveillance efforts; and lower capacity for managing populations of relevant wildlife reservoirs. The main mitigation action consists in adapting animal health management strategies to the available resources.", "qid": 9, "docid": "fx0c4bcp", "rank": 90, "score": 0.7499871253967285}, {"content": "Title: Personal View: Managing The Covid-19 Pandemic As A National Radiation Oncology Centre In Singapore Content: Abstract COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a global pandemic in March 2020. It has impacted the world medically, financially, politically and socially, with countries such as China and Italy adopting a full lockdown of their cities to mitigate the transmission. The current mortality rate is 5.4%, with 1 056 159 people infected worldwide. The disease is reminiscent of SARS in 2002, from which the healthcare system of Singapore has garnered many lessons and applied them in the current climate. As a result of the high transmissibility of the virus, hospitals in Singapore have reduced clinic loads and elective treatments to halt propagation of the virus and also to allow redistribution of healthcare workforce to the frontline. Cancer patients, who are often immunocompromised, are at risk of contracting the disease and becoming seriously ill. At the same time, delaying treatment such as radiotherapy in cancer patients can be detrimental. Here, we describe our experience as a large radiation oncology department in Singapore, including the challenges we encountered and how we managed our patient flow.", "qid": 9, "docid": "8nvrt5y7", "rank": 91, "score": 0.7495889663696289}, {"content": "Title: A simple method to quantify country-specific effects of COVID-19 containment measures Content: Most of the world is currently fighting to limit the impact of the COVID-19 pandemic. Italy, the Western country with most COVID-19 related deaths, was the first to implement drastic containment measures in early March, 2020. Since then most other European countries, the USA, Canada and Australia, have implemented similar restrictions, ranging from school closures, banning of recreational activities and large events, to complete lockdown. Such limitations, and softer promotion of social distancing, may be more effective in one society than in another due to cultural or political differences. It is therefore important to evaluate the effectiveness of these initiatives by analyzing country-specific COVID-19 data. We propose to model COVID-19 dynamics with a SIQR (susceptible - infectious - quarantined - recovered) model, since confirmed positive cases are isolated and do not transmit the disease. We provide an explicit formula that is easily implemented and permits us to fit official COVID-19 data in a series of Western countries. We found excellent agreement with data-driven estimation of the day-of-change in disease dynamics and the dates when official interventions were introduced. Our analysis predicts that for most countries only the more drastic restrictions have reduced virus spreading. Further, we predict that the number of unidentified COVID-19-positive individuals at the beginning of the epidemic is \u223c10 times the number of confirmed cases. Our results provide important insight for future planning of non-pharmacological interventions aiming to contain spreading of COVID-19 and similar diseases.", "qid": 9, "docid": "aqwdg489", "rank": 92, "score": 0.7489715814590454}, {"content": "Title: COVID-19 in Canada: Predictions for the future and control lessons from Asia Content: COVID-19 has spread with unequal efficiency in various parts of the world. In several European countries including Italy, the increase in the number of COVID-19 cases has followed a consistent, exponential pattern of spread. However, some countries, notably Taiwan and Hong Kong, have achieved a different outcome and have managed to bring the COVID-19 outbreak in their countries rapidly under control, without entering the exponential pattern and with very few cases. They have used several different approaches to COVID-19 outbreak control, including the innovative use of smartphone technology and the widespread use of surgical face masks. We show through our models, that Canada has followed the same, consistent COVID-19 exponential growth pattern that is seen in Italy. Both nationally and in its most heavily affected provinces, there is exponential growth of COVID-19 cases, making it possible to make predictions for the future, if no further interventions are made in public health policy. In particular, we argue for the urgent introduction of surgical face masks in health care and other settings and the harnessing of the power of smartphone technology on a national scale.", "qid": 9, "docid": "ieobv7q8", "rank": 93, "score": 0.7484440803527832}, {"content": "Title: COVID-19 highlights risks of healthcare and social care workers attending work while ill Content: As COVID-19 affects healthcare and social care systems around the world, reports of infection among healthcare and social care workers continue to accumulate.", "qid": 9, "docid": "vjtg1nfq", "rank": 94, "score": 0.7482054233551025}, {"content": "Title: COVID-19 highlights risks of healthcare and social care workers attending work while ill. Content: As COVID-19 affects healthcare and social care systems around the world, reports of infection among healthcare and social care workers continue to accumulate.", "qid": 9, "docid": "xnksy6eq", "rank": 95, "score": 0.7482054233551025}, {"content": "Title: Attempting to understand the spread of SARS-CoV-2: Associations between the number of cases in regions and selected economic and geographic parameters Content: We present in this work some results from analysing the spread of Covid-19 in different countries and regions around the world and the potential relations with climate, geographical location, and GDP. While the situation remains dynamic, we believe this analysis has the potential to uncover certain underlying trends. We primarily intend the results to drive further, more detailed analysis of the relevant data by other researchers that would help us gather a better understanding of the situation, aiding our preparedness. Our observations show that countries in high latitudes, with temperate and/or continental climate, and with reasonably\"open\"economies are the most vulnerable to this outbreak.", "qid": 9, "docid": "7bg4tx9q", "rank": 96, "score": 0.7481659054756165}, {"content": "Title: COVID-19's Impact on Italian Urology. Content: The COVID-19 pandemic has impacted our lives, our habits and our healthcare system. Italy is one of the countries affected first and more aggressively from the outbreak. Our rapidity has been guide for other healthcare systems from around the World. We describe the impact of COVID-19 on Urology, how the Urological scientific community responded to the emergency and our experience in a high-volume Roman University hospital. The aim of our work is to share our experience providing suggestions for other global hospitals on how to manage the COVID-19 emergency.", "qid": 9, "docid": "2tqxj0ua", "rank": 97, "score": 0.7480078339576721}, {"content": "Title: COVID-19's Impact on Italian Urology Content: The COVID-19 pandemic has impacted our lives, our habits and our healthcare system. Italy is one of the countries affected first and more aggressively from the outbreak. Our rapidity has been guide for other healthcare systems from around the World. We describe the impact of COVID-19 on Urology, how the Urological scientific community responded to the emergency and our experience in a high-volume Roman University hospital. The aim of our work is to share our experience providing suggestions for other global hospitals on how to manage the COVID-19 emergency.", "qid": 9, "docid": "j5sb8cvl", "rank": 98, "score": 0.7480077743530273}, {"content": "Title: Atypical skin manifestations during immune checkpoint blockage in COVID19-infected lung cancer patients Content: Abstract A new coronavirus, named SARS-CoV-2 by the World Health Organization (WHO), has rapidly spread around the world since its first reported case in late December of 2019 from Wuhan, China. As of mid-April 2020, this virus has affected more than 180 countries and territories, infecting more than 1,650,000 individuals and causing over 100.000 deaths. With \u224820 million new cases per year globally, cancer affects a significant portion of the population. Individuals affected by cancer are more susceptible to infections due to coexisting chronic diseases (cardiovascular, pulmonary and diabetes), overall poor health status, and systemic immunosuppressive states caused by both cancer and anticancer treatments. As a consequence, patients with malignancies, and especially with lung cancer who develop COVID19 experience more difficult outcomes. A recent multicenter study developed by the Hubei Anti-Cancer Association also documented that lung cancer patients had an increased risk of death, ICU requirement, risk of presenting severe or critical symptoms, and use of invasive mechanical ventilation. Here we present two representative cases of patients with lung cancer and COVID19 without respiratory compromise and with atypical and severe skin manifestations, findings that could be influenced by the chronic use of anti-PD1 antibodies.", "qid": 9, "docid": "12b1slbp", "rank": 99, "score": 0.7475866079330444}, {"content": "Title: La pandemia de Coronavirus SARS-CoV-2 (COVID-19): Situaci\u00f3n actual e implicaciones para M\u00e9xico Content: The Coronavirus pandemic (COVID-19) is one of the most devastating in this century It originated in China in December 2019 caused by the SARS-Cov-2 virus, and in less than a month it had been classified as an &quot;International Public Health Emergency&quot; To date there are nearly 3 million people infected and more than 250,000 deaths caused by the disease worldwide Initially it affects the respiratory tract with atypical pneumonia and in severe cases it produces systemic inflammation with cytokine storm that can cause rapid deterioration with circulatory and respiratory failure, coagulopathy and a lethality rate of approximately 7% In Mexico, the first case was detected in February 2020, and to date there are 26,616 confirmed cases and 2,961 deaths throughout the country The low number of diagnostic tests conducted in our country clearly underestimates the real incidence and impact of the disease The most affected groups are those with risk factors such as age over 60, presence of hypertension, diabetes or cardiovascular disease Of the confirmed cases, 15% are healthcare workers There is no specific treatment or vaccine yet, so it is important to have hygiene, social isolation and personal protection measures Health, social and economic consequences could have great impact in the near future", "qid": 9, "docid": "vwergkpx", "rank": 100, "score": 0.7475806474685669}]}
{"query": "are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19?", "hits": [{"content": "Title: Treatment of patients with COVID-19 and concomitant cardiovascular diseases: Do not Forget about the Principles of Evidence-based Medicine/ \u041b\u0435\u0447\u0435\u043d\u0438\u0435 \u0431\u043e\u043b\u044c\u043d\u044b\u0445 \u0441 COVID-19 \u0438 \u0441\u043e\u043f\u0443\u0442\u0441\u0442\u0432\u0443\u044e\u0449\u0438\u043c\u0438 \u0441\u0435\u0440\u0434\u0435\u0447\u043d\u043e-\u0441\u043e\u0441\u0443\u0434\u0438\u0441\u0442\u044b\u043c\u0438 \u0437\u0430\u0431\u043e\u043b\u0435\u0432\u0430\u043d\u0438\u044f\u043c\u0438: \u043d\u0435 \u0437\u0430\u0431\u044b\u0432\u0430\u0442\u044c \u043e \u043f\u0440\u0438\u043d\u0446\u0438\u043f\u0430\u0445 \u0434\u043e\u043a\u0430\u0437\u0430\u0442\u0435\u043b\u044c\u043d\u043e\u0439 \u043c\u0435\u0434\u0438\u0446\u0438\u043d\u044b Content: The recent discussion about the dangers of using angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II receptor antagonists (ARA) in patients with COVID-19 is analyzed in the article. There is controversy over the hypothesis that these drugs can be factors contributing to an unfavorable outcome of a viral disease, as well as the absence of any clinical evidence for this hypothesis. The opinion that withdrawal of ACE inhibitors and ARA in patients with COVID-19 may increase the risk of adverse outcomes is presented.", "qid": 20, "docid": "i7scw9mu", "rank": 1, "score": 0.8864355683326721}, {"content": "Title: A consensus statement on the use of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in relation to COVID-19 (corona virus disease 2019). Content: There has been a lot of speculation that patients with coronavirus disease 2019 (COVID-19) who are receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) may be at increased risk for adverse outcomes. We reviewed the available evidence, and have not found this to be the case. We recommend that patients on such medications should continue on them unless there is a clinical indication to stop their use.", "qid": 20, "docid": "z3l6eden", "rank": 2, "score": 0.8778575658798218}, {"content": "Title: A consensus statement on the use of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in relation to COVID-19 (corona virus disease 2019) Content: There has been a lot of speculation that patients with coronavirus disease 2019 (COVID-19) who are receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) may be at increased risk for adverse outcomes We reviewed the available evidence, and have not found this to be the case We recommend that patients on such medications should continue on them unless there is a clinical indication to stop their use", "qid": 20, "docid": "53107z56", "rank": 3, "score": 0.8750128746032715}, {"content": "Title: Renin-angiotensin-aldosterone system inhibitors and COVID-19 infection or hospitalization: a cohort study Content: There are plausible mechanisms by which angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase the risk of COVID-19 infection or affect disease severity. To examine the association between these medications and COVID-19 infection or hospitalization, we conducted a retrospective cohort study within a US integrated healthcare system. Among people aged [\u2265]18 years enrolled in the health plan for at least 4 months as of 2/29/2020, current ACEI and ARB use was identified from pharmacy data, and the estimated daily dose was calculated and standardized across medications. COVID-19 infections were identified through 6/14/2020 from laboratory and hospitalization data. We used logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals. Among 322,044 individuals, 720 developed COVID-19 infection. Among people using ACEI/ARBs, 183/56,105 developed COVID-19 (3.3 per 1000 individuals) compared with 537/265,939 without ACEI/ARB use (2.0 per 1000), yielding an adjusted OR of 0.94 (95% CI 0.75-1.16). For use of < 1 defined daily dose vs. nonuse, the adjusted OR for infection was 0.89 (95% CI 0.62-1.26); for 1 to < 2 defined daily doses, 0.97 (95% CI 0.71-1.31); and for [\u2265]2 defined daily doses, 0.94 (95% CI 0.72-1.23). The OR was similar for ACEIs and ARBs and in subgroups by age and sex. 29% of people with COVID-19 infection were hospitalized; the adjusted OR for hospitalization in relation to ACEI/ARB use was 0.92 (95% CI 0.54-1.57), and there was no association with dose. These findings support current recommendations that individuals on these medications continue their use.", "qid": 20, "docid": "01xdd8zf", "rank": 4, "score": 0.8687450885772705}, {"content": "Title: ACEI/ARB Use and Risk of Infection or Severity or Mortality of COVID-19: A Systematic Review and Meta-analysis Content: We have sparse knowledge of the effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on the risk of COVID-19 infection and the progression of this disease. We systematically assessed these relationships. Unrestricted searches of the PubMed, Embase, and Cochrane Library databases were conducted, with an end date of May 9, 2020, to identify relevant studies that met predetermined inclusion criteria. Random-effects models were adopted to estimate the overall relative risk. Fourteen articles involving more than 19000 COVID-19 cases were included. Our results showed that ACEI/ARB exposure is not associated with a higher risk of COVID-19 infection (OR = 0.99; 95% CI, 0.95-1.04; P = 0.672). Among those with COVID-19 infection, ACEI/ARB exposure is not associated with a higher risk of severity (OR = 0.98; 95%CI 0.87-1.09; P = 0.69) or mortality (OR = 0.73, 95%CI 0.5-1.07; P = 0.111). However, ACEI/ARB exposure was associated with a lower risk of mortality compared those with non-ACEI/ARB antihypertensive drugs (OR = 0.48, 95% CI 0.29-0.81; P = 0.006). In conclusion, current evidence did not confirm previous concern regarding a harmful role of ACEI/ARB in COVID-19 patients. The present study support current professional society guidelines to not discontinue ACEIs or ARBs in the setting of the COVID-19 pandemic or COVID-19 patients.", "qid": 20, "docid": "cvj1t0gi", "rank": 5, "score": 0.8686832189559937}, {"content": "Title: ACE\u2010inhibitors and Angiotensin\u20102 Receptor Blockers are not associated with severe SARS\u2010COVID19 infection in a multi\u2010site UK acute Hospital Trust Content: AIMS: The SARS\u2010Cov2 virus binds to the ACE2 receptor for cell entry. It has been suggested that ACE\u2010inhibitors (ACEi) and Angiotensin\u20102 Blockers (ARB), which are commonly used in patients with hypertension or diabetes and may raise tissue ACE2 levels, could increase the risk of severe COVID19 infection. METHODS AND RESULTS: We evaluated this hypothesis in a consecutive cohort of 1200 acute inpatients with COVID19 at two hospitals with a multi\u2010ethnic catchment population in London (UK). The mean age was 68 \u00b1 17 years (57% male) and 74% of patients had at least 1 comorbidity. 415 patients (34.6%) reached the primary endpoint of death or transfer to a critical care unit for organ support within 21\u2010days of symptom onset. 399 patients (33.3%) were taking ACEi or ARB. Patients on ACEi/ARB were significantly older and had more comorbidities. The odds ratio (OR) for the primary endpoint in patients on ACEi and ARB, after adjustment for age, sex and co\u2010morbidities, was 0.63 (CI 0.47\u20130.84, p < 0.01). CONCLUSIONS: There was no evidence for increased severity of COVID19 disease in hospitalised patients on chronic treatment with ACEi or ARB. A trend towards a beneficial effect of ACEi/ARB requires further evaluation in larger meta\u2010analyses and randomised clinical trials. This article is protected by copyright. All rights reserved.", "qid": 20, "docid": "akancd4c", "rank": 6, "score": 0.8614464998245239}, {"content": "Title: ACEI/ARB use and risk of infection or severity or mortality of COVID-19: A systematic review and meta-analysis Content: The effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on the risk of COVID-19 infection and disease progression are yet to be investigated. The relationship between ACEI/ARB use and COVID-19 infection was systematically reviewed. To identify relevant studies that met predetermined inclusion criteria, unrestricted searches of the PubMed, Embase, and Cochrane Library databases were conducted. The search strategy included clinical date published until May 9, 2020. Twelve articles involving more than 19,000 COVID-19 cases were included. To estimate overall risk, random-effects models were adopted. Our results showed that ACEI/ARB exposure was not associated with a higher risk of COVID-19 infection (OR = 0.99; 95 % CI, 0-1.04; P = 0.672). Among those with COVID-19 infection, ACEI/ARB exposure was also not associated with a higher risk of having severe infection (OR = 0.98; 95 % CI, 0.87-1.09; P = 0.69) or mortality (OR = 0.73, 95 %CI, 0.5-1.07; P = 0.111). However, ACEI/ARB exposure was associated with a lower risk of mortality compared to those on non-ACEI/ARB antihypertensive drugs (OR = 0.48, 95 % CI, 0.29-0.81; P = 0.006). In conclusion, current evidence did not confirm the concern that ACEI/ARB exposure is harmful in patientswith COVID-19 infection. This study supports the current guidelines that discourage discontinuation of ACEIs or ARBs in COVID-19 patients and the setting of the COVID-19 pandemic.", "qid": 20, "docid": "v8tfxd6a", "rank": 7, "score": 0.8602913618087769}, {"content": "Title: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are not associated with severe COVID-19 infection in a multi-site UK acute hospital trust Content: AIMS: The SARS-CoV-2 virus binds to the angiotensin-converting enzyme 2 (ACE2) receptor for cell entry. It has been suggested that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB), which are commonly used in patients with hypertension or diabetes and may raise tissue ACE2 levels, could increase the risk of severe COVID-19 infection. METHODS AND RESULTS: We evaluated this hypothesis in a consecutive cohort of 1200 acute inpatients with COVID-19 at two hospitals with a multi-ethnic catchment population in London (UK). The mean age was 68 \u00b1 17 years (57% male) and 74% of patients had at least one comorbidity. Overall, 415 patients (34.6%) reached the primary endpoint of death or transfer to a critical care unit for organ support within 21 days of symptom onset. A total of 399 patients (33.3%) were taking ACEi or ARB. Patients on ACEi/ARB were significantly older and had more comorbidities. The odds ratio for the primary endpoint in patients on ACEi and ARB, after adjustment for age, sex and co-morbidities, was 0.63 (95% confidence interval 0.47-0.84, P < 0.01). CONCLUSIONS: There was no evidence for increased severity of COVID-19 in hospitalised patients on chronic treatment with ACEi or ARB. A trend towards a beneficial effect of ACEi/ARB requires further evaluation in larger meta-analyses and randomised clinical trials.", "qid": 20, "docid": "aj1yup6a", "rank": 8, "score": 0.8598761558532715}, {"content": "Title: Risk of severe COVID-19 in hypertensive patients treated with renin-angiotensin-aldosterone system inhibitors Content: INTRODUCTION: There is controversy concerning the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type-I receptor blockers (ARB) for treating hypertensive patients with Covid-19. It has been hypothesized that these drugs might increase the risk of severe Covid-19, but some authors suggested that blocking the renin-angiotensin system might actually decrease this risk. METHODS: Retrospective cohort study of all the consecutive hypertensive patients with confirmed SARS-CoV-2 infection in a health area. The outcome variable was hospitalization because of severe Covid-19. RESULTS: 539 subjects were diagnosed of SARS-CoV-2 infection. Of these, 157 (29.1%) had hypertension and were included in the study. Sixty-nine cases (43.9%) were hospitalized because of severe Covid-19. In multivariable analysis older age, diabetes and hypertensive myocadiopathy were related to a higher risk of hospital admission. ARB treatment was associated with a significantly lower risk of hospitalization (HR: 0.29, 95% CI: 0.10 - 0.88). A similar albeit not significant trend was observed for ACEI. CONCLUSION: ARB or ACEI treatment was not associated with a worse clinical outcome in consecutive hypertensive patients infected by SARS-CoV-2.", "qid": 20, "docid": "bwg3tzx8", "rank": 9, "score": 0.8567969799041748}, {"content": "Title: Risk of severe COVID-19 in hypertensive patients treated with renin-angiotensin-aldosterone system inhibitors: Content: Abstract Introduction There is controversy concerning the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type-I receptor blockers (ARB) for treating hypertensive patients with Covid-19. It has been hypothesized that these drugs might increase the risk of severe Covid-19, but some authors suggested that blocking the renin-angiotensin system might actually decrease this risk. Methods Retrospective cohort study of all the consecutive hypertensive patients with confirmed SARS-CoV-2 infection in a health area. The outcome variable was hospitalization because of severe Covid-19. Results 539 subjects were diagnosed of SARS-CoV-2 infection. Of these, 157 (29.1%) had hypertension and were included in the study. Sixty-nine cases (43.9%) were hospitalized because of severe Covid-19. In multivariable analysis older age, diabetes and hypertensive myocadiopathy were related to a higher risk of hospital admission. ARB treatment was associated with a significantly lower risk of hospitalization (HR: 0.29, 95% CI: 0.10 \u2013 0.88). A similar albeit not significant trend was observed for ACEI. Conclusion ARB or ACEI treatment was not associated with a worse clinical outcome in consecutive hypertensive patients infected by SARS-CoV-2.", "qid": 20, "docid": "wxpfg25n", "rank": 10, "score": 0.8553304672241211}, {"content": "Title: Compliance of Antihypertensive Medication and Risk of Coronavirus Disease 2019: a Cohort Study Using Big Data from the Korean National Health Insurance Service Content: BACKGROUND: There is a controversy whether it is safe to continue renin-angiotensin system blockers in patients with coronavirus disease 2019 (COVID-19). We analyzed big data to investigate whether angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers have any significant effect on the risk of COVID-19. Population-based cohort study was conducted based on the prescription data from nationwide health insurance records. METHODS: We investigated the 1,374,381 residents aged \u2265 40 years living in Daegu, the epicenter of the COVID-19 outbreak, between February and March 2020. Prescriptions of antihypertensive medication during the year before the outbreak were extracted from the National Health Insurance Service registry. Medications were categorized by types and stratified by the medication possession ratios (MPRs) of antihypertensive medications after controlling for the potential confounders. The risk of COVID-19 was estimated using a difference in difference analysis. RESULTS: Females, older individuals, low-income earners, and recently hospitalized patients had a higher risk of infection. Patients with higher MPRs of antihypertensive medications had a consistently lower risk of COVID-19 than those with lower MPRs of antihypertensive medications and non-users. Among patients who showed complete compliance, there was a significantly lower risk of COVID-19 for those prescribed angiotensin II receptor blockers (relative risk [RR], 0.751; 95% confidence interval [CI], 0.587\u20130.960) or calcium channel blockers (RR, 0.768; 95% CI, 0.601\u20130.980). CONCLUSION: Renin-angiotensin system blockers or other antihypertensive medications do not increase the risk of COVID-19. Patients should not stop antihypertensive medications, including renin-angiotensin system blockers, because of concerns of COVID-19.", "qid": 20, "docid": "pnk1tt3w", "rank": 11, "score": 0.8504741191864014}, {"content": "Title: Treatment with ACE-inhibitors is associated with less severe disease with SARS-Covid-19 infection in a multi-site UK acute Hospital Trust Content: Abstract: Background: The SARS-Cov2 virus binds to the ACE2 receptor for cell entry. It has been suggested that ACE-inhibitors, which are commonly used in patients with hypertension or diabetes and which raise ACE2 levels, may increase the risk of severe COVID-19 infection. Methods: We evaluated this hypothesis in an early cohort of 205 acute inpatients with COVID-19 at King's College Hospital and Princess Royal University Hospital, London, UK with the primary endpoint being death or transfer to a critical care unit for organ support within 7-days of symptom onset. Findings: 53 patients out of 205 patients reached the primary endpoint. Contrary to the hypothesis, treatment with ACE-inhibitors was associated with a reduced risk of rapidly deteriorating severe disease. There was a lower rate of death or transfer to a critical care unit within 7 days in patients on an ACE-inhibitor OR 0.29 (CI 0.10-0.75, p<0.01), adjusting for age, gender, comorbidities (hypertension, diabetes mellitus, ischaemic heart disease and heart failure). Interpretation: Although a small sample size, we do not see evidence for ACE-inhibitors increasing the short-term severity of COVID-19 disease and patients on treatment with ACE-inhibitors should continue these drugs during their COVID-19 illness. A potential beneficial effect needs to be explored as more data becomes available.", "qid": 20, "docid": "60wcvkbn", "rank": 12, "score": 0.8494576215744019}, {"content": "Title: Compliance of Antihypertensive Medication and Risk of Coronavirus Disease 2019: a Cohort Study Using Big Data from the Korean National Health Insurance Service Content: BACKGROUND: There is a controversy whether it is safe to continue renin-angiotensin system blockers in patients with coronavirus disease 2019 (COVID-19). We analyzed big data to investigate whether angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers have any significant effect on the risk of COVID-19. Population-based cohort study was conducted based on the prescription data from nationwide health insurance records. METHODS: We investigated the 1,374,381 residents aged &#8805; 40 years living in Daegu, the epicenter of the COVID-19 outbreak, between February and March 2020. Prescriptions of antihypertensive medication during the year before the outbreak were extracted from the National Health Insurance Service registry. Medications were categorized by types and stratified by the medication possession ratios (MPRs) of antihypertensive medications after controlling for the potential confounders. The risk of COVID-19 was estimated using a difference in difference analysis. RESULTS: Females, older individuals, low-income earners, and recently hospitalized patients had a higher risk of infection. Patients with higher MPRs of antihypertensive medications had a consistently lower risk of COVID-19 than those with lower MPRs of antihypertensive medications and non-users. Among patients who showed complete compliance, there was a significantly lower risk of COVID-19 for those prescribed angiotensin II receptor blockers (relative risk [RR], 0.751; 95% confidence interval [CI], 0.587-0.960) or calcium channel blockers (RR, 0.768; 95% CI, 0.601-0.980). CONCLUSION: Renin-angiotensin system blockers or other antihypertensive medications do not increase the risk of COVID-19. Patients should not stop antihypertensive medications, including renin-angiotensin system blockers, because of concerns of COVID-19.", "qid": 20, "docid": "7xzlcsbv", "rank": 13, "score": 0.849295973777771}, {"content": "Title: Use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in context of COVID-19 outbreak: a retrospective analysis Content: The possible effects of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on COVID-19 disease severity have generated considerable debate. We performed a single-center, retrospective analysis of hospitalized adult COVID-19 patients in Wuhan, China, who had definite clinical outcome (dead or discharged) by February 15, 2020. Patients on anti-hypertensive treatment with or without ACEI/ARB were compared on their clinical characteristics and outcomes. The medical records from 702 patients were screened. Among the 101 patients with a history of hypertension and taking at least one anti-hypertensive medication, 40 patients were receiving ACEI/ARB as part of their regimen, and 61 patients were on antihypertensive medication other than ACEI/ARB. We observed no statistically significant differences in percentages of in-hospital mortality (28% vs. 34%, P = 0.46), ICU admission (20% vs. 28%, P = 0.37) or invasive mechanical ventilation (18% vs. 26%, P = 0.31) between patients with or without ACEI/ARB treatment. Further multivariable adjustment of age and gender did not provide evidence for a significant association between ACEI/ARB treatment and severe COVID-19 outcomes. Our findings confirm the lack of an association between chronic receipt of renin-angiotensin system antagonists and severe outcomes of COVID-19. Patients should continue previous anti-hypertensive therapy until further evidence is available.", "qid": 20, "docid": "hfnqcw5d", "rank": 14, "score": 0.8475772142410278}, {"content": "Title: Association between chronic ACE inhibitor exposure and decreased odds of severe disease in patients with COVID-19 Content: OBJECTIVE: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Renin-angiotensin-aldosterone-system (RAAS) inhibitors may increase the expression of angiotensin-converting enzyme 2, which is the receptor for SARSCoV-2 Spike protein. The consequences of using angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) during the COVID-19 pandemic are unknown. METHODS: A retrospective cohort study aiming to identify the odds of severe disease (defined as either hospitalization of &#8805;14 days, admission to the intensive care unit, or death) associated with exposure to ACEi or ARB was conducted. Adult patients (age &#8805;18 years) with COVID-19 admitted to the Istanbul Faculty of Medicine Corona Center between March 9 and May 11, 2020, were included. Chronic users of ACEi, ARB, or other antihypertensive drugs were matched according to age, sex, sick days before hospitalization, comorbidities, smoking, number of antihypertensive regimens, doxazosin use, furosemide use, and serum creatinine level. Odds ratios (OR) of having severe disease were calculated. RESULTS: In total, 611 patients were admitted with COVID-19, confirmed by either reverse-transcriptase polymerase chain reaction or computed tomography (CT). There were 363 males, and the age ranged from 18 to 98 years, with an average age of 57\u00b115 years. Of these, 165 participants had severe disease (53 deaths, case fatality rate: 8.7%). Among those with hypertension (n=249), ARB exposure was compatible with decreased odds (OR=0.60, 95% CI: 0.27-1.36, p=0.31) of severe disease though not statistically significant, while ACEi exposure significantly reduced the risk of severe disease (OR=0.37, 95% CI: 0.15-0.87, p=0.03). ACEi exposure was associated with milder infiltrations seen on baseline CT, lower C-reactive protein and ferritin, higher monocytes, shorter hospitalization, and less requirement for specific empirical treatments (favipiravir and meropenem). CONCLUSION: Our data suggest that exposure to ACEi drugs may have favorable effects in the context of COVID-19 pneumonia.", "qid": 20, "docid": "3qs8mnf1", "rank": 15, "score": 0.8471581339836121}, {"content": "Title: A systematic review to evaluate the clinical outcomes in COVID -19 patients on angiotensin converting enzyme inhibitors or angiotensin receptor blockers Content: Introduction: Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) share their target receptor site with the SARS-CoV-2 virus, that may cause ACE2 receptor upregulation which raised concerns regarding ACEI and ARB use in COVID-19 patients. However, many medical professional societies recommended their continued use given the paucity of clinical evidence but there is need for an updated systematic review of latest clinical studies. Methods: A search was conducted on PubMed, Google Scholar, EMBASE and various preprint servers for studies comparing clinical outcomes and mortality in COVID-19 patients on ACEI and/or ARB. Results: A total of eight studies were included in the review. There were conflicting findings reported in several studies as Meng J. et al, Liu Y. et al and Feng Y. reported that patients on ACE inhibitors/ARB had lower rates of severe outcomes whereas Richardson S. et al reported higher rates of invasive ventilation and intensive care unit (ICU) admissions in patients on ACE inhibitors/ARB as compared to non-users. However, Zhang P. et al found slightly higher rates of ICU admissions in patients on ACE inhibitors and ARB as compared to non-users. Similarly, there were conflicting results in the rate of mortality reported by the various clinical studies as well. Meng J. et al, Li J. et al and Zhang P. et al reported lower rates of mortality in ACE inhibitors/ARB users versus non-users whereas Guo J. et al reported higher rates of mortality in patients on ACE inhibitors/ARB as compared to non-users. Additionally, a large study conducted in New York by Richardson S. et al raised concerns with worse mortality outcomes in patients on ACEI/ ARB. Conclusion: It is concluded that ACEI and ARB should be continued in COVID-19 patients, albeit while exercising caution until larger clinical studies and randomized controlled trials confirm their safety. Additionally, the individual patient factors like ACE2 polymorphisms which might confer higher risk of adverse outcomes need to be evaluated further.", "qid": 20, "docid": "a0asoy8j", "rank": 16, "score": 0.8454622030258179}, {"content": "Title: Renin\u2013Angiotensin\u2013Aldosterone System Blockers and the Risk of Covid-19 Content: BACKGROUND: A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting\u2013enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied. METHODS: We carried out a population-based case\u2013control study in the Lombardy region of Italy. A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence. Information about the use of selected drugs and patients\u2019 clinical profiles was obtained from regional databases of health care use. Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression. RESULTS: Among both case patients and controls, the mean (\u00b1SD) age was 68\u00b113 years, and 37% were women. The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile. Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex. CONCLUSIONS: In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease. However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19.", "qid": 20, "docid": "1pahpghb", "rank": 17, "score": 0.8453997373580933}, {"content": "Title: Renin-Angiotensin-Aldosterone System Blockers and the Risk of Covid-19 Content: BACKGROUND: A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting-enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied. METHODS: We carried out a population-based case-control study in the Lombardy region of Italy. A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence. Information about the use of selected drugs and patients' clinical profiles was obtained from regional databases of health care use. Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression. RESULTS: Among both case patients and controls, the mean (\u00b1SD) age was 68\u00b113 years, and 37% were women. The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile. Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex. CONCLUSIONS: In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease. However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19.", "qid": 20, "docid": "3twud97m", "rank": 18, "score": 0.8452420234680176}, {"content": "Title: Anti-RAS drugs and SARS-CoV-2 infection Content: \u2022 There is no enough evidence to indicate that ACEIs and ARBs result in ACE2 upregulation. \u2022 The level of ACE2 expression is not completely related with the risk of COVID-19 infection. \u2022 There is currently no evidence that ACEI/ARB increase risk for COVID-19 infection from clinical trials. \u2022 It is not recommended that COVID-19 patients with hypertension or normal hypertensive patients at risk for exposure to stop using ACEI/ARB or change to other antihypertensive drugs.", "qid": 20, "docid": "5y8cc5eb", "rank": 19, "score": 0.8449654579162598}, {"content": "Title: Angiotensin Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Use Among Outpatients Diagnosed with COVID-19 Content: Coronavirus disease 2019 (COVID-19) is a viral pandemic precipitated by the severe acute respiratory syndrome coronavirus 2. Since previous reports suggested that viral entry into cells may involve angiotensin converting enzyme 2, there has been growing concern that angiotensin converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) use may exacerbate the disease severity. In this retrospective, single-center US study of adult patients diagnosed with COVID-19, we evaluated the association of ACEI/ARB use with hospital admission. Secondary outcomes included: ICU admission, mechanical ventilation, length of hospital stay, use of inotropes, and all-cause mortality. Propensity score matching was performed to account for potential confounders. Among 590 unmatched patients diagnosed with COVID-19, 78 patients were receiving ACEI/ARB (median age 63 years and 59.7% male) and 512 patients were non-users (median age 42 years and 47.1% male). In the propensity matched population, multivariate logistic regression analysis adjusting for age, gender and comorbidities demonstrated that ACEI/ARB use was not associated with hospital admission (OR 1.2, 95% CI 0.5-2.7, p = 0.652). CAD and CKD/ESRD remained independently associated with admission to hospital. All-cause mortality, ICU stay, need for ventilation, and inotrope use was not significantly different between the 2 study groups. In conclusion, among patients who were diagnosed with COVID-19, ACEI/ARB use was not associated with increased risk of hospital admission.", "qid": 20, "docid": "ps9xawlp", "rank": 20, "score": 0.8443575501441956}, {"content": "Title: Role of Drugs Affecting the Renin-Angiotensin-Aldosterone System on Susceptibility and Severity of COVID-19: A Large Case-Control Study from Zheijang Province, China. Content: Background. Medical editorials have suggested that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) should not be given to people with arterial hypertension during the coronavirus disease 2019 (COVID-19) pandemic because of a potential increased risk of worse clinical outcomes and that calcium channel blockers (CCBs) should be used as an alternative. Methods Using a cohort of 610 COVID-19 cases and 48,667 population-based controls from Zheijang, China we have tested the role of usage of ACEIs, ARBs, CCBs and other medications on risk and severity of COVID 19. Analyses were adjusted for age, sex and BMI and for presence of relevant comorbidities. Findings: Higher BMI, diabetes and cardio/ cerebrovascular disease as independent risk factors for the development of COVID-19. Individuals with hypertension taking CCBs had significantly increased risk [odds ratio (OR)= 1.67 (95% CI 1.2-2.9)) of manifesting symptoms of COVID-19 whereas those taking ARBs and diuretics had significantly lower disease risk (OR=0.24; 95%CI 0.17-0.34 and OR=0.32; 95%CI 0.19-0.57 respectively). Other antihypertensive drugs were not associated with increased risk of severe or critical form of the infection. Use of glucocorticoids was significantly associated with a severe/critical form of COVID-19 (OR= 7.56; 95%CI 1.17-48.93). Interpretation: we found no evidence to alter ARBs or ACEIs therapy in the context of the pandemic. Patients on corticosteroids with COVID-19 are at higher risk of developing a severe form of COVID-19and therefore should be monitored closely.", "qid": 20, "docid": "llzfc1r7", "rank": 21, "score": 0.8443523645401001}, {"content": "Title: Association between chronic ACE inhibitor exposure and decreased odds of severe disease in patients with COVID-19. Content: OBJECTIVE Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Renin-angiotensin-aldosterone-system (RAAS) inhibitors may increase the expression of angiotensin-converting enzyme 2, which is the receptor for SARSCoV-2 Spike protein. The consequences of using angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) during the COVID-19 pandemic are unknown. METHODS A retrospective cohort study aiming to identify the odds of severe disease (defined as either hospitalization of \u226514 days, admission to the intensive care unit, or death) associated with exposure to ACEi or ARB was conducted. Adult patients (age \u226518 years) with COVID-19 admitted to the \u0130stanbul Faculty of Medicine Corona Center between March 9 and May 11, 2020, were included. Chronic users of ACEi, ARB, or other antihypertensive drugs were matched according to age, sex, sick days before hospitalization, comorbidities, smoking, number of antihypertensive regimens, doxazosin use, furosemide use, and serum creatinine level. Odds ratios (OR) of having severe disease were calculated. RESULTS In total, 611 patients were admitted with COVID-19, confirmed by either reverse-transcriptase polymerase chain reaction or computed tomography (CT). There were 363 males, and the age ranged from 18 to 98 years, with an average age of 57\u00b115 years. Of these, 165 participants had severe disease (53 deaths, case fatality rate: 8.7%). Among those with hypertension (n=249), ARB exposure was compatible with decreased odds (OR=0.60, 95% CI: 0.27-1.36, p=0.31) of severe disease though not statistically significant, while ACEi exposure significantly reduced the risk of severe disease (OR=0.37, 95% CI: 0.15-0.87, p=0.03). ACEi exposure was associated with milder infiltrations seen on baseline CT, lower C-reactive protein and ferritin, higher monocytes, shorter hospitalization, and less requirement for specific empirical treatments (favipiravir and meropenem). CONCLUSION Our data suggest that exposure to ACEi drugs may have favorable effects in the context of COVID-19 pneumonia.", "qid": 20, "docid": "z82u8dik", "rank": 22, "score": 0.8442618250846863}, {"content": "Title: RAAS inhibitors do not increase the risk of COVID-19 Content: According to five new studies, therapy with angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) is not associated with an increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or with an increased risk of severe disease or in-hospital death among patients with COVID-19.", "qid": 20, "docid": "nxrg9fi6", "rank": 23, "score": 0.8441987037658691}, {"content": "Title: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults Content: BACKGROUND: The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in COVID-19 disease susceptibility, severity, and treatment is unclear. PURPOSE: To evaluate, on an ongoing basis, whether use of ACEIs or ARBs either increases risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or is associated with worse COVID-19 disease outcomes, and to assess the efficacy of these medications for COVID-19 treatment. DATA SOURCES: MEDLINE (Ovid) and Cochrane Database of Systematic Reviews from 2003 to 4 May 2020, with planned ongoing surveillance for 1 year; the World Health Organization database of COVID-19 publications and medRxiv.org through 17 April 2020; and ClinicalTrials.gov to 24 April 2020, with planned ongoing surveillance. STUDY SELECTION: Observational studies and trials in adults that examined associations and effects of ACEIs or ARBs on risk for SARS-CoV-2 infection and COVID-19 disease severity and mortality. DATA EXTRACTION: Single-reviewer abstraction confirmed by another reviewer, independent evaluation by 2 reviewers of study quality, and collective assessment of certainty of evidence. DATA SYNTHESIS: Two retrospective cohort studies found that ACEI and ARB use was not associated with a higher likelihood of receiving a positive SARS-CoV-2 test result, and 1 case-control study found no association with COVID-19 illness in a large community (moderate-certainty evidence). Fourteen observational studies, involving a total of 23 565 adults with COVID-19, showed consistent evidence that neither medication was associated with more severe COVID-19 illness (high-certainty evidence). Four registered randomized trials plan to evaluate ACEIs and ARBs for treatment of COVID-19. LIMITATION: Half the studies were small and did not adjust for important confounding variables. CONCLUSION: High-certainty evidence suggests that ACEI or ARB use is not associated with more severe COVID-19 disease, and moderate-certainty evidence suggests no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain. PRIMARY FUNDING SOURCE: None. (PROSPERO: registration number pending).", "qid": 20, "docid": "0nwmoua3", "rank": 24, "score": 0.8433117866516113}, {"content": "Title: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults: A Living Systematic Review Content: BACKGROUND: The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in COVID-19 disease susceptibility, severity, and treatment is unclear. PURPOSE: To evaluate, on an ongoing basis, whether use of ACEIs or ARBs either increases risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or is associated with worse COVID-19 disease outcomes, and to assess the efficacy of these medications for COVID-19 treatment. DATA SOURCES: MEDLINE (Ovid) and Cochrane Database of Systematic Reviews from 2003 to 4 May 2020, with planned ongoing surveillance for 1 year; the World Health Organization database of COVID-19 publications and medRxiv.org through 17 April 2020; and ClinicalTrials.gov to 24 April 2020, with planned ongoing surveillance. STUDY SELECTION: Observational studies and trials in adults that examined associations and effects of ACEIs or ARBs on risk for SARS-CoV-2 infection and COVID-19 disease severity and mortality. DATA EXTRACTION: Single-reviewer abstraction confirmed by another reviewer, independent evaluation by 2 reviewers of study quality, and collective assessment of certainty of evidence. DATA SYNTHESIS: Two retrospective cohort studies found that ACEI and ARB use was not associated with a higher likelihood of receiving a positive SARS-CoV-2 test result, and 1 case\u2013control study found no association with COVID-19 illness in a large community (moderate-certainty evidence). Fourteen observational studies, involving a total of 23 565 adults with COVID-19, showed consistent evidence that neither medication was associated with more severe COVID-19 illness (high-certainty evidence). Four registered randomized trials plan to evaluate ACEIs and ARBs for treatment of COVID-19. LIMITATION: Half the studies were small and did not adjust for important confounding variables. CONCLUSION: High-certainty evidence suggests that ACEI or ARB use is not associated with more severe COVID-19 disease, and moderate-certainty evidence suggests no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain. PRIMARY FUNDING SOURCE: None. (PROSPERO: registration number pending)", "qid": 20, "docid": "z22a5yzo", "rank": 25, "score": 0.8421834707260132}, {"content": "Title: Association between angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers use and the risk of infection and clinical outcome of COVID-19: a comprehensive systematic review and meta-analysis. Content: Background The effect of using Angiotensin-converting enzyme inhibitors (ACEIs) and Angiotensin-receptor blockers (ARBs) on the risk of coronavirus disease 2019 (COVID-19) is a topic of recent debate. Although studies have examined the potential association between them, the results remain controversial. This study aims to determine the true effect of ACEI/ARBs use on the risk of infection and clinical outcome of COVID-19. Methods Five electronic databases (PubMed, Web of science, Cochrane library, China National Knowledge Infrastructure database, medRxiv preprint server) were retrieved to find eligible studies. Meta-analysis was performed to examine the association between ACEI/ARBs use and the risk of infection and clinical outcome of COVID-19. Results 22 articles containing 157,328 patients were included. Use of ACEI/ARBs was not associated with increased risk of infection (Adjusted OR: 0.96, 95% CI: 0.91-1.01, I2=5.8%) or increased severity (Adjusted OR: 0.90, 95% CI: 0.77-1.05, I2=27.6%) of COVID-19. The use of ACEI/ARBs was associated with lower risk of death from COVID-19 (Adjusted OR: 0.66, 95% CI: 0.44-0.99, I2=57.9%). Similar results of reduced risk of death were also found for ACEI/ARB use in COVID-19 patients with hypertension (Adjusted OR: 0.36, 95% CI: 0.17-0.77, I2=0). Conclusion This study provides evidence that ACEI/ARBs use for COVID-19 patients does not lead to harmful outcomes and may even provide a beneficial role and decrease mortality from COVID-19. Clinicians should not discontinue ACEI/ARBs for patients diagnosed with COVID-19 if they are already on these agents. Keywords: COVID-19; Angiotensin-converting enzyme inhibitor; Angiotensin-receptor blockers; risk; systematic review; meta-analysis", "qid": 20, "docid": "7necpu7c", "rank": 26, "score": 0.8412179350852966}, {"content": "Title: ACE inhibitors, AT1 receptor blockers and COVID-19: clinical epidemiology evidences for a continuation of treatments. The ACER-COVID study Content: Aims: The question of interactions between the renin angiotensin aldosterone system drugs and the incidence and prognosis of COVID-19 infection has been raised by the medical community. We hypothesised that if patients treated with ACE inhibitors (ACEI) or AT1 receptor blockers (ARB) were more prone to SARS-CoV2 infection and had a worse prognosis than untreated patients, the prevalence of consumption of these drugs would be higher in patients with COVID-19 compared to the general population. Methods and results: We used a clinical epidemiology approach based on the estimation of standardised prevalence ratio (SPR) of consumption of ACEI and ARB in four groups of patients (including 187 COVID-19 positive) with increasing severity referred to the University hospital of Lille and in three French reference samples (the exhaustive North population (n=1,569,968), a representative sample of the French population (n=414,046), a random sample of Lille area (n=1,584)). The SPRs of ACEI and ARB did not differ as the severity of the COVID-19 patients increased, being similar to the regular consumption of these drugs in the North of France population with the same non-significant increase for both treatment (1.17 [0.83-1.67]). A statistically significant increase in the SPR of ARB (1.56 [1.02-2.39]) was observed in intensive care unit patients only. After stratification on obesity, this increase was limited to the high risk subgroup of obese patients. Conclusions: Our results strongly support the recommendation that ACEI and ARB should be continued in the population and in COVID-19 positive patients, reinforcing the position of several scientific societies.", "qid": 20, "docid": "6baw4hmt", "rank": 27, "score": 0.8397566080093384}, {"content": "Title: Renin\u2013Angiotensin\u2013Aldosterone System Inhibitors and Risk of Covid-19 Content: BACKGROUND: There is concern about the potential of an increased risk related to medications that act on the renin\u2013angiotensin\u2013aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS: We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS: Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS: We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.", "qid": 20, "docid": "oapjfamm", "rank": 28, "score": 0.8388016223907471}, {"content": "Title: Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Covid-19 Content: BACKGROUND: There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS: We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS: Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS: We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.", "qid": 20, "docid": "fskfnmig", "rank": 29, "score": 0.838752031326294}, {"content": "Title: The use of renin angiotensin system inhibitor on mortality in patients with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis Content: BACKGROUND: and Aims; To investigate the association between use of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB) and outcomes of hypertensive COVID-19 patients, a systematic review and meta-analysis were performed. METHODS: We systematically searched PubMed, EuropePMC, ProQuest, and Cochrane Central Databases using the terms \"(COVID-19 OR SARS-CoV-2) AND (angiotensin converting enzyme OR angiotensin receptor blocker)\". The primary and second outcomes were mortality (non-survivor) and severe COVID-19, respectively. RESULTS: Totally, 7410 patients were included from 15 studies. Pooled analysis showed that the use of ACEI/ARB was not associated with mortality (OR 0.73 [0.38, 1.40], p = 0.34; I2: 81%) and severity (OR 1.03 [0.73, 1.45], p = 0.87; I2: 65%). Pooled adjusted OR showed no risk/benefit associated with ACEI/ARB use in terms of mortality (OR 0.83 [0.54, 1.27], p = 0.38; I2: 0%). Subgroup analysis showed that the use of ARB was associated with reduced mortality (OR 0.51 [0.29, 0.90], p = 0.02; I2: 22%) but not ACEI subgroup (OR 0.68 [0.39, 1.17], p = 0.16; I2: 0%). Meta-regression showed that the association between ACEI/ARB use and mortality in patients with COVID-19 do not varies by gender (p = 0.104). GRADE showed a very low certainty of evidence for effect of ACEI/ARB on mortality and severity. The certainty of evidence was very low for both ACEI and ARB subgroups. CONCLUSION: Administration of a renin angiotensin system (RAS) inhibitor, was not associated with increased mortality or severity of COVID-19 in patients with hypertension. Specifically, ARB and not ACEI use, was associated with lower mortality.", "qid": 20, "docid": "kfhfwq5e", "rank": 30, "score": 0.8383215665817261}, {"content": "Title: The use of renin angiotensin system inhibitor on mortality in patients with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis Content: BACKGROUND: and Aims; To investigate the association between use of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB) and outcomes of hypertensive COVID-19 patients, a systematic review and meta-analysis were performed. METHODS: We systematically searched PubMed, EuropePMC, ProQuest, and Cochrane Central Databases using the terms \u201c(COVID-19 OR SARS-CoV-2) AND (angiotensin converting enzyme OR angiotensin receptor blocker)\u201d. The primary and second outcomes were mortality (non-survivor) and severe COVID-19, respectively. RESULTS: Totally, 7410 patients were included from 15 studies. Pooled analysis showed that the use of ACEI/ARB was not associated with mortality (OR 0.73 [0.38, 1.40], p = 0.34; I(2): 81%) and severity (OR 1.03 [0.73, 1.45], p = 0.87; I(2): 65%). Pooled adjusted OR showed no risk/benefit associated with ACEI/ARB use in terms of mortality (OR 0.83 [0.54, 1.27], p = 0.38; I(2): 0%). Subgroup analysis showed that the use of ARB was associated with reduced mortality (OR 0.51 [0.29, 0.90], p = 0.02; I(2): 22%) but not ACEI subgroup (OR 0.68 [0.39, 1.17], p = 0.16; I(2): 0%). Meta-regression showed that the association between ACEI/ARB use and mortality in patients with COVID-19 do not varies by gender (p = 0.104). GRADE showed a very low certainty of evidence for effect of ACEI/ARB on mortality and severity. The certainty of evidence was very low for both ACEI and ARB subgroups. CONCLUSION: Administration of a renin angiotensin system (RAS) inhibitor, was not associated with increased mortality or severity of COVID-19 in patients with hypertension. Specifically, ARB and not ACEI use, was associated with lower mortality.", "qid": 20, "docid": "ax5gd3fq", "rank": 31, "score": 0.8382670879364014}, {"content": "Title: Renin-angiotensin system inhibition in COVID-19 patients Content: Angiotensin-converting enzyme (ACE) inhibitors (ACEIs) and angiotensin II type\u20111 receptor blockers (ARBs) are among the most widely prescribed drugs for the treatment of arterial hypertension, heart failure and chronic kidney disease. A number of studies, mainly in animals and not involving the lungs, have indicated that these drugs can increase expression of angiotensin-converting enzyme 2 (ACE2). ACE2 is the cell entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) that is currently battering the globe. This has led to the hypothesis that use of ACEIs and ARBs may increase the risk of developing severe COVID-19. In this point of view paper, possible scenarios regarding the impact of ACEI/ARB pharmacotherapy on COVID-19 are discussed in relation to the currently available evidence. Although further research on the influence of blood-pressure-lowering drugs, including those not targeting the renin-angiotensin system, is warranted, there are presently no compelling clinical data showing that ACEIs and ARBs increase the likelihood of contracting COVID-19 or worsen the outcome of SARS-CoV\u20112 infections. Thus, unless contraindicated, use of ACEIs/ARBs in COVID-19 patients should be continued in line with the recent recommendations of medical societies.", "qid": 20, "docid": "d9wfmvp8", "rank": 32, "score": 0.8378177881240845}, {"content": "Title: Renin-angiotensin system inhibition in COVID-19 patients Content: Angiotensin-converting enzyme (ACE) inhibitors (ACEIs) and angiotensin II type\u00ad1 receptor blockers (ARBs) are among the most widely prescribed drugs for the treatment of arterial hypertension, heart failure and chronic kidney disease. A number of studies, mainly in animals and not involving the lungs, have indicated that these drugs can increase expression of angiotensin-converting enzyme 2 (ACE2). ACE2 is the cell entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) that is currently battering the globe. This has led to the hypothesis that use of ACEIs and ARBs may increase the risk of developing severe COVID-19. In this point of view paper, possible scenarios regarding the impact of ACEI/ARB pharmacotherapy on COVID-19 are discussed in relation to the currently available evidence. Although further research on the influence of blood-pressure-lowering drugs, including those not targeting the renin-angiotensin system, is warranted, there are presently no compelling clinical data showing that ACEIs and ARBs increase the likelihood of contracting COVID-19 or worsen the outcome of SARS-CoV\u00ad2 infections. Thus, unless contraindicated, use of ACEIs/ARBs in COVID-19 patients should be continued in line with the recent recommendations of medical societies.", "qid": 20, "docid": "3l1nru0l", "rank": 33, "score": 0.8352153897285461}, {"content": "Title: COVID-19 and Hypertension: The Role of ACE2 and the Renin-Angiotensin System Content: ABSTRACT Hypertension emerged from early reports as a potential risk factor for worse outcomes for persons with coronavirus disease 2019 (COVID-19). Among the putative links between hypertension and COVID-19 is a key counter-regulatory component of the renin-angiotensin system (RAS): angiotensin-converting enzyme 2 (ACE2). ACE2 facilitates entry of SARS-CoV-2, the virus responsible for COVID-19, into host cells. Since RAS inhibitors have been suggested to increase ACE2 expression, healthcare providers and patients have grappled with the decision of whether to discontinue these medications during the COVID-19 pandemic. However, experimental models of analogous viral pneumonias suggest RAS inhibitors may exert protective effects against acute lung injury. We review how RAS and ACE2 biology may affect outcomes in COVID-19 through pulmonary and other systemic effects. In addition, we briefly detail the data for and against continuation of RAS inhibitors in persons with COVID-19 and summarize the current consensus recommendations from select specialty organizations.", "qid": 20, "docid": "4ined9rx", "rank": 34, "score": 0.8349734544754028}, {"content": "Title: Renin-angiotensin system blockers and susceptibility to COVID-19: a multinational open science cohort study Content: INTRODUCTION: Angiotensin converting enzyme inhibitors (ACEs) and angiotensin receptor blockers (ARBs) could influence infection risk of coronavirus disease (COVID-19). Observational studies to date lack pre-specification, transparency, rigorous ascertainment adjustment and international generalizability, with contradictory results. METHODS: Using electronic health records from Spain (SIDIAP) and the United States (Columbia University Irving Medical Center and Department of Veterans Affairs), we conducted a systematic cohort study with prevalent ACE, ARB, calcium channel blocker (CCB) and thiazide diuretic (THZ) users to determine relative risk of COVID-19 diagnosis and related hospitalization outcomes. The study addressed confounding through large-scale propensity score adjustment and negative control experiments. RESULTS: Following over 1.1 million antihypertensive users identified between November 2019 and January 2020, we observed no significant difference in relative COVID-19 diagnosis risk comparing ACE/ARB vs CCB/THZ monotherapy (hazard ratio: 0.98; 95% CI 0.84 \u2013 1.14), nor any difference for mono/combination use (1.01; 0.90 \u2013 1.15). ACE alone and ARB alone similarly showed no relative risk difference when compared to CCB/THZ monotherapy or mono/combination use. Directly comparing ACE vs. ARB demonstrated a moderately lower risk with ACE, non-significant for monotherapy (0.85; 0.69 \u2013 1.05) and marginally significant for mono/combination users (0.88; 0.79 \u2013 0.99). We observed, however, no significant difference between drug-classes for COVID-19 hospitalization or pneumonia risk across all comparisons. CONCLUSION: There is no clinically significant increased risk of COVID-19 diagnosis or hospitalization with ACE or ARB use. Users should not discontinue or change their treatment to avoid COVID-19.", "qid": 20, "docid": "7jzsj3xl", "rank": 35, "score": 0.8346815705299377}, {"content": "Title: Estimation of Renin-Angiotensin-Aldosterone-System (RAAS)-Inhibitor effect on COVID-19 outcome: A Meta-analysis Content: BACKGROUND AND RATIONALE: Some studies of hospitalized patients suggested that the risk of death and/or severe illness due to COVID-19 is not associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin II receptor type 1 blockers (ARBs). Nevertheless, some controversy still exists and there is limited information of the ACEIs/ARBs effect size on COVID-19 prognosis. AIM AND METHODS: We aimed to measure the effect of ACEIs and/or ARBs on COVID-19 severe clinical illness by a meta-analysis. Literature search included all studies published since the COVID-19 outbreak began (December 2019) until May 9, 2020. We analyzed information from studies that included tested COVID-19 patients with arterial hypertension as comorbidity prior to hospital admission and history of taking ACEIs, ARBs, or ACEIs/ARBs. RESULTS: We included 16 studies that involved 24,676 COVID-19 patients, and we compared patients with critical (n\u00e2\u0080\u00af=\u00e2\u0080\u00af4134) vs. non-critical (n\u00e2\u0080\u00af=\u00e2\u0080\u00af20,542) outcomes. The overall assessment by estimating random effects shows that the use of ACEIs/ARBs is not associated with higher risk of in-hospital-death and/or severe illness among hypertensive patients with COVID-19 infection. On the contrary, effect estimate shows an overall protective effect of RAAS inhibitors/blockers (ACEIs, ARBs, and/or ACEIs/ARBs) with \u00e2\u0088\u00bc 23 % reduced risk of death and/or critical disease (OR: 0.768, 95%CI: 0.651-0.907, p=0.0018). The use of ACEIs (OR:0.652, 95%CI:0.478-0.891, p=0.0072) but not ACEIs/ARBs (OR:0.867, 95%CI:0.638-1.179, p =NS) or ARBs alone (OR:0.810, 95%CI:0.629-1.044, p=NS) may explain the overall protection displayed by RAAS intervention combined. CONCLUSION: RAAS inhibitors might be associated with better COVID-19 prognosis.", "qid": 20, "docid": "1edsm58s", "rank": 36, "score": 0.8344818353652954}, {"content": "Title: Use of RAAS inhibitors and risk of clinical deterioration in COVID-19: results from an Italian cohort of 133 hypertensives Content: BACKGROUND: The effect of chronic use of renin\u2013angiotensin\u2013aldosterone system (RAAS) inhibitors on the severity of COVID-19 infection is still unclear in patients with hypertension. We aimed to investigate the association between chronic use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and COVID-19 related outcomes in hypertensive patients. METHODS: A single center study was conducted on 133 consecutive hypertensive subjects presenting to the Emergency Department with acute respiratory symptoms and/or fever who were diagnosed with COVID-19 infection between 9(th) and 31(st) March 2020. RESULTS: All patients were grouped according to their chronic antihypertensive medications (ACEIs, N=40; ARBs, N=42; not on RAAS inhibitors, N=51). There was no statistical difference between ACEIs and ARBs groups in terms of hospital admission rate, oxygen therapy and need for non-invasive ventilation. Patients chronically treated with RAAS inhibitors showed a significantly lower rate of admission to semi-intensive/intensive care units, when compared to the non-RAAS population (odds ratio [OR] 0.25, CI95% 0.09-0.66 p=0.006). Similarly, the risk of mortality was lower in the former group, although not reaching statistical significance (OR 0.56, CI95% 0.17-1.83, p=0.341). CONCLUSIONS: Our data suggest that chronic use of RAAS inhibitors does not negatively affect clinical course of COVID-19 in hypertensive patients. Further studies are needed to confirm this finding and determine whether RAAS inhibitors may have a protective effect on COVID 19-related morbidity and mortality.", "qid": 20, "docid": "82m84n4w", "rank": 37, "score": 0.8344290256500244}, {"content": "Title: Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality. Content: Importance It has been hypothesized that angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) may make patients more susceptible to coronavirus disease 2019 (COVID-19) and to worse outcomes through upregulation of the functional receptor of the virus, angiotensin-converting enzyme 2. Objective To examine whether use of ACEI/ARBs was associated with COVID-19 diagnosis and worse outcomes in patients with COVID-19. Design, Setting, and Participants To examine outcomes among patients with COVID-19, a retrospective cohort study using data from Danish national administrative registries was conducted. Patients with COVID-19 from February 22 to May 4, 2020, were identified using ICD-10 codes and followed up from day of diagnosis to outcome or end of study period (May 4, 2020). To examine susceptibility to COVID-19, a Cox regression model with a nested case-control framework was used to examine the association between use of ACEI/ARBs vs other antihypertensive drugs and the incidence rate of a COVID-19 diagnosis in a cohort of patients with hypertension from February 1 to May 4, 2020. Exposures ACEI/ARB use was defined as prescription fillings 6 months prior to the index date. Main Outcomes and Measures In the retrospective cohort study, the primary outcome was death, and a secondary outcome was a composite outcome of death or severe COVID-19. In the nested case-control susceptibility analysis, the outcome was COVID-19 diagnosis. Results In the retrospective cohort study, 4480 patients with COVID-19 were included (median age, 54.7 years [interquartile range, 40.9-72.0]; 47.9% men). There were 895 users (20.0%) of ACEI/ARBs and 3585 nonusers (80.0%). In the ACEI/ARB group, 18.1% died within 30 days vs 7.3% in the nonuser group, but this association was not significant after adjustment for age, sex, and medical history (adjusted hazard ratio [HR], 0.83 [95% CI, 0.67-1.03]). Death or severe COVID-19 occurred in 31.9% of ACEI/ARB users vs 14.2% of nonusers by 30 days (adjusted HR, 1.04 [95% CI, 0.89-1.23]). In the nested case-control analysis of COVID-19 susceptibility, 571 patients with COVID-19 and prior hypertension (median age, 73.9 years; 54.3% men) were compared with 5710 age- and sex-matched controls with prior hypertension but not COVID-19. Among those with COVID-19, 86.5% used ACEI/ARBs vs 85.4% of controls; ACEI/ARB use compared with other antihypertensive drugs was not significantly associated with higher incidence of COVID-19 (adjusted HR, 1.05 [95% CI, 0.80-1.36]). Conclusions and Relevance Prior use of ACEI/ARBs was not significantly associated with COVID-19 diagnosis among patients with hypertension or with mortality or severe disease among patients diagnosed as having COVID-19. These findings do not support discontinuation of ACEI/ARB medications that are clinically indicated in the context of the COVID-19 pandemic.", "qid": 20, "docid": "kc6dls2z", "rank": 38, "score": 0.8343819379806519}, {"content": "Title: Use of inhibitors of the renin angiotensin system and COVID-19 prognosis: a systematic review and meta-analysis Content: Background: controversy has arisen in the scientific community on whether the use of renin angiotensin system (RAS) inhibitors in the context of COVID-19 would be of benefit or harmful. A meta-analysis of eligible studies comparing the occurrence of severe and fatal COVID-19 in infected patients who were under treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) vs no treatment or other antihypertensives was conducted. Methods: PubMed, Google Scholar, the Cochrane Library, MedRxiv and BioRxiv were searched for relevant studies. Fixed-effect models or random-effect models were used depending on the heterogeneity between estimates. Results: a total of fifteen studies with 21,614 patients were included. The use of RAS inhibitors was associated with a non-significant 20% decreased risk of the composite outcome (death, admission to intensive care unit, mechanical ventilation requirement or progression to severe or critical pneumonia): RR 0.81 (95%CI: 0.63-1.04), p=0.10, I2=82%. In a subgroup analysis that included hypertensive subjects only, ACEI/ARB were associated with a 27% significant decrease in the risk of the composite outcome (RR 0.73 (95%CI: 0.56-0.96), p=0.02, I2=65%). Conclusion: the results of this pooled analysis suggest that the use of ACEI/ARB does not worsen the prognosis, and could even be protective in hypertensive subjects. Patients should continue these drugs during their COVID-19 illness.", "qid": 20, "docid": "lboa7rtn", "rank": 39, "score": 0.8340973854064941}, {"content": "Title: COVID-19 and Angiotensin-Converting Enzyme Inhibitor/Angiotensin-Receptor Blocker Therapy Content: Mackey and colleagues reported a systematic review that found high-certainty evidence that angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers are not associated with greater illness severity in patients with COVID-19. The editorialist discusses the findings and emphasizes that, unless further data show otherwise, clinicians should continue to prescribe these drugs for their standard indications in patients with COVID-19.", "qid": 20, "docid": "7ae0galy", "rank": 40, "score": 0.8339223861694336}, {"content": "Title: Estimation of RAAS-Inhibitor effect on the COVID-19 outcome: A Meta-analysis Content: BACKGROUND AND RATIONALE: Some studies of hospitalized patients suggested that the risk of death and/or severe illness due to COVID-19 is not associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin II receptor type 1 blockers (ARBs). Nevertheless, some controversy still exists and there is limited information of the ACEIs/ARBs effect size on COVID-19 prognosis. AIM AND METHODS: We aimed to measure the effect of ACEIs and/or ARBs on COVID-19 severe clinical illness by a meta-analysis. Literature search included all studies published since the COVID-19 outbreak began (December 2019) until May 9, 2020. We analyzed information from studies that included tested COVID-19 patients with arterial hypertension as comorbidity prior to hospital admission and history of taking ACEIs, ARBs, or ACEIs/ARBs. RESULTS: We included 16 studies that involved 24,676 COVID-19 patients, and we compared patients with critical (n = 4134) vs. non-critical (n = 20,542) outcomes. The overall assessment by estimating random effects shows that the use of ACEIs/ARBs is not associated with higher risk of in-hospital-death and/or severe illness among hypertensive patients with COVID-19 infection. On the contrary, effect estimate shows an overall protective effect of RAAS inhibitors/blockers (ACEIs, ARBs, and/or ACEIs/ARBs) with \u223c 23 % reduced risk f death and/or critical disease (OR: 0.768, 95%CI: 0.651-0.907, p=0.0018). The use of ACEIs (OR:0.652, 95%CI:0.478-0.891, p=0.0072) but not ACEIs/ARBs (OR:0.867, 95%CI:0.638-1.179, p =NS) or ARBs alone (OR:0.810, 95%CI:0.629-1.044, p=NS) may explain the overall protection displayed by RAAS intervention combined. CONCLUSION: RAAS inhibitors might be associated with better COVID-19 prognosis.", "qid": 20, "docid": "npzzycis", "rank": 41, "score": 0.8336513042449951}, {"content": "Title: Dangers of ACE inhibitor and ARB usage in COVID-19: evaluating the evidence Content: Background: Concerns have been raised regarding the safety of Angiotensin Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs) in patients with COVID-19, based on the hypothesis that such medications may raise expression of ACE2, the receptor for SARS-CoV-2. Methods: We conducted a literature review of studies (n=12) in experimental animals and human subjects (n=11) and evaluated the evidence regarding the impact of administration of ACEIs and ARBs on ACE2 expression. We prioritized studies that assessed ACE2 protein expression data, measured directly or inferred from ACE2 activity assays. Results: The findings in animals are inconsistent with respect to an increase in ACE2 expression in response to treatment with ACEIs or ARBs. Control/sham animals show little to no effect in the plurality of studies. Those studies that report increases in ACE2 expression tend to involve acute injury models and/or higher doses than typically administered to patients. Data from human studies overwhelmingly imply that administration of ACEIs/ARBs does not increase ACE2 expression. Conclusion: Available evidence, in particular, data from human studies, does not support the hypothesis that ACEI/ARB use increases ACE2 expression and the risk of complications from COVID-19. We conclude that patients being treated with ACEIs and ARBs should continue their use for approved indications.", "qid": 20, "docid": "mgp38mdz", "rank": 42, "score": 0.833016037940979}, {"content": "Title: Use of RAAS inhibitors and risk of clinical deterioration in COVID-19: results from an Italian cohort of 133 hypertensives Content: BACKGROUND: The effect of chronic use of renin-angiotensin-aldosterone system (RAAS) inhibitors on the severity of COVID-19 infection is still unclear in patients with hypertension. We aimed to investigate the association between chronic use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and COVID-19 related outcomes in hypertensive patients. METHODS: A single center study was conducted on 133 consecutive hypertensive subjects presenting to the Emergency Department with acute respiratory symptoms and/or fever who were diagnosed with COVID-19 infection between 9th and 31st March 2020. RESULTS: All patients were grouped according to their chronic antihypertensive medications (ACEIs, N=40; ARBs, N=42; not on RAAS inhibitors, N=51). There was no statistical difference between ACEIs and ARBs groups in terms of hospital admission rate, oxygen therapy and need for non-invasive ventilation. Patients chronically treated with RAAS inhibitors showed a significantly lower rate of admission to semi-intensive/intensive care units, when compared to the non-RAAS population (odds ratio [OR] 0.25, CI95% 0.09-0.66 p=0.006). Similarly, the risk of mortality was lower in the former group, although not reaching statistical significance (OR 0.56, CI95% 0.17-1.83, p=0.341). CONCLUSIONS: Our data suggest that chronic use of RAAS inhibitors does not negatively affect clinical course of COVID-19 in hypertensive patients. Further studies are needed to confirm this finding and determine whether RAAS inhibitors may have a protective effect on COVID 19-related morbidity and mortality.", "qid": 20, "docid": "w2bhtu9f", "rank": 43, "score": 0.832826554775238}, {"content": "Title: Renin-angiotensin system inhibitors in management of hypertension during the COVID-19 pandemic Content: COVID-19, which is caused by the single-stranded RNA severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has introduced significant therapeutic dilemmas in several areas. One of these is concern regarding the use of renin-angiotensin system (RAS) inhibitors. Dysfunction of the RAS has been observed in COVID-19 patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs), are associated with improved or worse clinical outcomes, remains unclear. RAS inhibitors are currently widely used in the treatment of hypertension. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with co-morbidities such as hypertension, coronary heart disease, and diabetes mellitus, particularly in the elderly. Therefore, several recently published research papers have focused on the management of hypertension during the COVID-19 pandemic, as this co-morbidity was found to be the most common in patients with coronavirus infections. SARS-CoV-2 viral surface protein is known to attach angiotensin converting enzyme-2 (ACE-2) on the cell membrane to facilitate viral entry into the cytoplasm. While the SARS-CoV-2 viral load remains the highest in upper respiratory tract of COVID-19 patients, it has also been reported in multiple sites in COVID-19, and patients not infrequently require the Intensive Care Units (ICU) admission. However, despite the theoretical concerns of possible increased ACE2 expression by RAS blockade, there is no evidence that RAS inhibitors are harmful during COVID-19 infection, and indeed they have been shown to be beneficial in some animal studies. In this review we summarise the pathophysiology of the interaction between RAS, ACEIs/ARBs inhibitors and COVID-19, and conclude, on the basis of current data, that RAS blockade should be maintained during the current coronavirus pandemic.", "qid": 20, "docid": "wumtwdi5", "rank": 44, "score": 0.8327944278717041}, {"content": "Title: Renin-angiotensin system inhibitors in management of hypertension during the COVID-19 pandemic. Content: COVID-19, which is caused by the single-stranded RNA severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has introduced significant therapeutic dilemmas in several areas. One of these is concern regarding the use of renin-angiotensin system (RAS) inhibitors. Dysfunction of the RAS has been observed in COVID-19 patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs), are associated with improved or worse clinical outcomes, remains unclear. RAS inhibitors are currently widely used in the treatment of hypertension. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with co-morbidities such as hypertension, coronary heart disease, and diabetes mellitus, particularly in the elderly. Therefore, several recently published research papers have focused on the management of hypertension during the COVID-19 pandemic, as this co-morbidity was found to be the most common in patients with coronavirus infections. SARS-CoV-2 viral surface protein is known to attach angiotensin converting enzyme-2 (ACE-2) on the cell membrane to facilitate viral entry into the cytoplasm. While the SARS-CoV-2 viral load remains the highest in upper respiratory tract of COVID-19 patients, it has also been reported in multiple sites in COVID-19, and patients not infrequently require the Intensive Care Units (ICU) admission. However, despite the theoretical concerns of possible increased ACE2 expression by RAS blockade, there is no evidence that RAS inhibitors are harmful during COVID-19 infection, and indeed they have been shown to be beneficial in some animal studies. In this review we summarise the pathophysiology of the interaction between RAS, ACEIs/ARBs inhibitors and COVID-19, and conclude, on the basis of current data, that RAS blockade should be maintained during the current coronavirus pandemic.", "qid": 20, "docid": "vv9ssqb8", "rank": 45, "score": 0.8327944278717041}, {"content": "Title: Association of Renin Angiotensin System Blockers with Outcomes in Patients with Covid-19: A Systematic Review and Meta-analysis Content: Background: Patients with cardiovascular disease are at increased risk of critical illness and mortality from Covid-19 disease. Conflicting findings have raised concerns regarding the association of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) use with likelihood or severity of infection during this pandemic. Objective: To study the cumulative evidence for association of ACEI/ARB use with outcomes among patients with confirmed Covid-19. Methods: The MEDLINE and EMBASE databases were thoroughly searched from November 01, 2019 to May 15, 2020 for studies reporting on outcomes based on ACEI/ARB use in patients with confirmed Covid-19. Preferred reporting items for systematic review and meta-analysis guidelines were used for the present study. Relevant data was collected and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using random-effects model. Main Outcome measures: In-hospital mortality was the primary end of interest. Second end-point was severe or critical illness defined as either need for intensive care unit, invasive mechanical ventilation, or mortality. Results: Fifteen studies with total of 23,822 patients (N ACEI/ARB=6,650) were included in the present analysis. Overall, prevalence of ACEI/ARB use ranged from 7.7% to 46.2% across studies. Among 10 studies, patients using ACEI/ARB had similar odds of mortality [OR 1.03 (0.69-1.55)] and severe or critical illness [1.18 (0.91-1.54)] compared to those not on ACEI/ARB. In an analysis restricted to patients with hypertension, ACEI/ARB use was associated with significantly lower mortality [0.64 (0.45-0.89)], while the odds of severe/critical illness [0.76(0.52-1.12); p=0.16] remained non-significant compared with non-ACEI/ARB users. Conclusion: There is no evidence for increased risk of severe illness or mortality in patients using ACEI/ARB compared with non-users. In patients with hypertension, ACE/ARB use might be associated with reduced mortality, however these findings need to be confirmed in prospective randomized controlled trials.", "qid": 20, "docid": "6vajr6w7", "rank": 46, "score": 0.8320996761322021}, {"content": "Title: Covid-19 and cardiovascular risk: susceptibility to infection to SARS-CoV-2, severity and prognosis of Covid-19 and blockade of the renin-angiotensin-aldosterone system. An evidence-based viewpoint Content: Abstract The presence of cardiovascular co-morbidities and the known effects of coronaviruses on the cardiovascular system have called attention to the potential implications for patients with cardiovascular risk factors. This evidence-based viewpoint will address two questions: (a) are individuals with underlying cardiovascular risk factors (e.g. high blood pressure or diabetes) or overt disease (e.g. coronary heart disease, heart failure, kidney disease) more likely to develop severe Covid-19 and to die than those without underlying conditions? (b) does the regular use of angiotensin-converting enzyme inhibitors (ACE-i) or angiotensin-receptor blockers (ARB) make patients more likely to get infected and to die of Covid-19? With a necessary cautionary note that the evidence around the links between Covid-19 and cardiovascular disease is accruing at a fast pace, to date we can conclude that: (a) the greater susceptibility of individuals with underlying cardiovascular conditions to develop more severe Covid-19 with higher mortality rate is likely to be confounded, in part, by age and the type of co-morbidities. Patients with heart failure or chronic kidney disease might show an excess risk; (b) neither ACE-i nor ARB are associated with greater risk of SARS-Cov2 infection, or severity or risk of death in patients with Covid-19. Patients on these drugs should not stop them, unless under strict medical supervision and with the addition of a suitable replacement medicine.", "qid": 20, "docid": "ym8ue50x", "rank": 47, "score": 0.8319867253303528}, {"content": "Title: Inflammation Level Severity and Death in Patients With COVID-19: A Rapid Systematic Review and Meta-Analysis Content: Background: An association among the use of angiotensin-converting-enzyme(ACE) inhibitors and angiotensin-receptor blockers(ARBs) with the clinical outcomes of coronavirus disease 2019 (COVID-19) is unclear. Methods: PubMed, EMBASE, and the preprint databases MedRxiv and BioRxiv were searched for relevant studies that assessed the association among inflammation level, application of ACEI/ARB, infection severity and death in patients with COVID-19. Odd risks(OR) and 95% confidence interval (CI) were combined using random-effects or fixed models depending on heterogeneity. Results: Eleven studies were included with a total of 33,483 patients. Our review showed ACEI/ARB therapy might be associated with the reduced inflammatory factor (interleukin-6) and elevated level of immune cells(CD3, CD8). Meta-analysis showed no significant increase in the risk of COVID-19 infection(OR:0.95, 95%CI:0.89-1.05) in patients receiving ACEI/ARB therapy, and ACEI/ARB therapy was associated with a decreased risk of severe COVID-19 (OR:0.75, 95%CI: 0.59-0.96) and mortality (OR:0.52, 95%CI: 0.35-0.79). Subgroup analyses showed that, among the general population, application of ACEI/ARB therapy was associated with reduced risks of all-cause death(OR:0.31, 95%CI: 0.13-0.75), and the risk of severe COVID-19(OR:0.79, 95%CI: 0.60-1.05) infection and COVID-19 infection(OR:0.85, 95% CI: 0.66-1.08) were not increased. Among patients with hypertension, the use of an ACEI/ARB was associated with a lower severity of COVID-19(OR:0.73, 95%CI: 0.51-1.03) and lower mortality(OR:0.57, 95%CI: 0.37-0.87), without evidence of an increased risk of COVID-19 infection(OR:1.00, 95%CI: 0.90-1.12). Conclusion: On the basis of the available evidence, this is the first meta-analysis showed that, in general population, the use of ACEI/ARB therapy was safe without an increased risk of COVID-19 infection and with a decreasing trend of severe COVID-19 infection and lower mortality. In patients with hypertension, the use of ACEI/ARB therapy should be encouraged, without increased risk of COVID-19 inflection, and better prognosis (a decreasing trends of severe COVID-19 and reduced all-cause death). Overall, ACEI/ARB therapy should be continued in patients who are at risk for, or have COVID-19, either in general population or hypertension patients. Our results need to be interpreted with caution considering the potential for residual confounders, and more well-designed studies that control the clinical confounders are necessary to confirm our findings. Key Words COVID-19; ACEI/ARB; SARS-COV-2; pneumonia; infectious disease; lung, hypertension", "qid": 20, "docid": "93hgg2py", "rank": 48, "score": 0.8311494588851929}, {"content": "Title: Mortality and use of angiotensin converting enzyme inhibitors in Covid 19 disease - a systematic review. Content: Background. Interest exits concerning the use of angiotensin converting enzyme inhibitors (ACEi) in patients with Covid-19 disease. Objectives. To perform a systematic review on mortality associated to the use of ACEi in patients with Covid 19 disease. Methods. Search in Medline (PubMed) and in ISI Web of Knowledge; use of other sources. Results. A total of 19 articles were evaluated. Four studies were selected and used to produce the meta-analyses. These four studies involved a total number of 1.423 patients treated with ACEi and 11.868 not treated with ACEi. Significant heterogeneity was seen concerning mortality associated to the use of ACEi in the context of Covid-19 disease. One report showed significantly decreased mortality associated to ACEi use, but this finding was not confirmed by the three other studies. No significant difference in mortality was seen in the meta-analysis (ACEi users versus non-users; random effects; odds ratio, 0.93; 95% confidence interval [CI], 0.44 to 1.94; P=0.84). When compared to mortality in patients treated with angiotensin receptor blockers, mortality of patients treated with ACEi was not significantly different, although a trend was noted to exist (odds ratio, 0.74; 95% confidence interval [CI], 0.41 to 1.34; P=0.32). The population studied in the report showing decreased mortality associated to ACEi use had a mean age under 50 years, whereas two other reports had a mean or median patient age over 60 years. Conclusions. The data now presented argue in favor of carrying out clinical trials studying ACEi in Covid-19 patients, to explore the hypothesis that ACEi use has a protective effect in populations with a mean age under 50 years, but not necessarily in those with a mean age over 60 years.", "qid": 20, "docid": "8hsqnwyj", "rank": 49, "score": 0.831134557723999}, {"content": "Title: Currently prescribed drugs in the UK that could up or downregulate ACE2 in COVID-19 disease: A systematic review Content: Objective: To review evidence on routinely prescribed drugs in the UK that could up or downregulate Angiotensin Converting Enzyme 2 (ACE2) and potentially affect COVID-19 disease Design: Systematic review Data source: MEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science Study selection: Any design with animal or human models examining a currently prescribed UK drug compared to a control, placebo or sham group, and reporting an effect on ACE2 level, activity or gene expression. Data extraction and synthesis: MEDLINE, EMBASE, CINAHL, the Cochrane Library, Web of Science and OpenGrey from inception to 1st April 2020. Methodological quality was assessed using the SYRCLE's risk of bias tool for animal studies and Cochrane risk of bias tool for human studies. Results: We screened 3,360 titles and included 112 studies with 21 different drug classes identified as influencing ACE2 activity. Ten studies were in humans and 102 were in animal models None examined ACE2 in human lungs. The most frequently examined drugs were Angiotensin Receptor Blockers (ARBs) (n= 55) and Angiotensin-Converting Enzyme- Inhibitors (ACE-I) (n= 22). More studies reported upregulation than downregulation with ACE-I (n=22), ARBs (n=55), insulin (n=8), thiazolidinedione (n=7) aldosterone agonists (n=3), statins (n=5), oestrogens (n=5) calcium channel-blockers (n=3) GLP-1 agonists (n=2) and NSAIDs (n=2). Conclusions: There is an abundance of academic literature and media reports on the potential of drugs that could attenuate or exacerbate COVID-19 disease. This is leading to trials of repurposed drugs and uncertainty amongst patients and clinicians concerning continuation or cessation of prescribed medications. Our review indicates that the impact of currently prescribed drugs on ACE2 has been poorly studied in-vivo, particularly in human lungs where the SARS-CoV-2 virus appears to enact its pathogenic effects. We found no convincing evidence to justify starting or stopping currently prescribed drugs to influence outcomes of COVID-19 disease.", "qid": 20, "docid": "nkc5dxw5", "rank": 50, "score": 0.8310184478759766}, {"content": "Title: The effect of angiotensin converting enzyme inhibitors and angiotensin receptor blockers on death and severity of disease in patients with coronavirus disease 2019 (COVID-19): A meta-analysis Content: Background: Effect of angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) on outcomes in patients with coronavirus disease 2019 (COVID-19) is uncertain. Available evidence is limited to a few retrospective observational studies with small number of patients. Methods: We did a meta-analysis to assess the effect of ACEi/ARB in patients with COVID-19 on severity of disease, risk for hospitalisation, and death compared to those not on ACEi/ARB. We searched the Cochrane library, PubMed, Embase, ClinicalTrial.gov and medRxiv for studies published until 21.04.2020. Inclusion criteria included all studies with patients with confirmed COVID-19 either taking, or not taking, ACEi/ARB. Depending on degree of heterogeneity, fixed or random effect model was selected to calculate effect size (Odds ratio). Findings: Five studies were eligible for meta-analysis. These included 308 patients on ACEi/ARB, and 1172 not on ACEi/ARB. Compared to patients with COVID-19 not on ACEi/ARB, there was a statistically significant 44% reduction in odds of developing severe disease (OR: 0.56; 95% CI: 0.34-1.89, I2=68.15), and 62% reduction in odds of death (OR: 0.38; 95% CI: 0.19-0.74, I2=0.000) in those on ACEi/ARB. There was a non-significant 19% (OR 0.81; 95% CI: 0.42-1.55, I2: 0.000) reduction in odds of hospitalisation among those on ACEi/ARB. Interpretation: It is safe to use ACEi/ARB in patients with COVID-19 requiring these medications for associated comorbidities. Although limited by confounding factors typical of a meta-analysis of retrospective observational studies, our data suggests that use of these medications may reduce risk of developing severe disease and death. Funding Source: None", "qid": 20, "docid": "dwcu6vyp", "rank": 51, "score": 0.8308836817741394}, {"content": "Title: Inhibidores de la enzima convertidora de angiotensina y antagonistas del receptor de angiotensina II: \u00bfAumentan el riesgo de padecer COVID-19? Content: Abstract A new coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was discovered in December 2019 in Wuhan, China; the virus escalated rapidly and on March 11, 2020, the World Health Organization declared it a pandemic.Emerging data suggests that older patients with COVID-19 associated with other comorbid conditions such as diabetes, hypertension, heart and lung diseases are particularly more susceptible, compared to general populations, and have higher mortality. It is not yet clear whether this increased association of high blood pressure with COVID-19 and the increased risk of mortality are directly related to high blood pressure or other associated comorbidities, or to antihypertensive treatment.Although the underlying pathogenic mechanism linking hypertension and severity of COVID-19 infection remains to be elucidated, it has been hypothesized that excessive activation of the renin-angiotensin system (RAS) could contribute to the progression of COVID-19 related lung injury.Concern about whether angiotensin II receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors may have deleterious effects on morbidity and mortality in patients with COVID-19 is based on speculation that these drugs would increase the regulation of angiotensin II converting enzyme (ACE2), a receptor for SARS-CoV-2, which would increase viral load and lung damage.Recent studies are consistent with the recommendations of scientific societies that propose avoiding the suspension or change of antihypertensive medication, as there is no evidence that shows that these can be taken as risk factors for severity or mortality from COVID-19.", "qid": 20, "docid": "ynias4ga", "rank": 52, "score": 0.8307449817657471}, {"content": "Title: Hypertension prevalence in human Coronavirus: The role of ACE system in infection spread and severity Content: Summary The prevalence of hypertension is high in patients affected by COVID infection and it appears related to increased risk of mortality in many epidemiological studies. The ACE system is not uniformly expressed in all the human races, and current differences could hypothesize some geographical discrepancies of infection around the world. However, animal studies showed that ACE2 receptor is a potential pathway for host infection. Because two third of the hypertensive patients take ACE-i/ARB, several concerns have been raised about the detrimental role of current drugs. In this report we summarized the current evidences in favour or against the administration of ACE blockade in the COVID era.", "qid": 20, "docid": "7a8ouzma", "rank": 53, "score": 0.8306185603141785}, {"content": "Title: Covid-19 and cardiovascular risk: Susceptibility to infection to SARS-CoV-2, severity and prognosis of Covid-19 and blockade of the renin-angiotensin-aldosterone system. An evidence-based viewpoint Content: The presence of cardiovascular co-morbidities and the known effects of coronaviruses on the cardiovascular system have called attention to the potential implications for patients with cardiovascular risk factors. This evidence-based viewpoint will address two questions: (a) are individuals with underlying cardiovascular risk factors (e.g. high blood pressure or diabetes) or overt disease (e.g. coronary heart disease, heart failure, kidney disease) more likely to develop severe Covid-19 and to die than those without underlying conditions? (b) does the regular use of angiotensin-converting enzyme inhibitors (ACE-i) or angiotensin-receptor blockers (ARB) make patients more likely to get infected and to die of Covid-19? With a necessary cautionary note that the evidence around the links between Covid-19 and cardiovascular disease is accruing at a fast pace, to date we can conclude that: (a) the greater susceptibility of individuals with underlying cardiovascular conditions to develop more severe Covid-19 with higher mortality rate is likely to be confounded, in part, by age and the type of co-morbidities. Patients with heart failure or chronic kidney disease might show an excess risk; (b) neither ACE-i nor ARB are associated with greater risk of SARS-Cov2 infection, or severity or risk of death in patients with Covid-19. Patients on these drugs should not stop them, unless under strict medical supervision and with the addition of a suitable replacement medicine.", "qid": 20, "docid": "nfjkcmxu", "rank": 54, "score": 0.8301936388015747}, {"content": "Title: The effects of ARBs, ACEIs and statins on clinical outcomes of COVID-19 infection among nursing home residents Content: Abstract Objectives Angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB) and HMG-CoA reductase inhibitors (\u2018statins\u2019) have been hypothesised to impact COVID-19 severity. However, up till now, no studies investigating this association were conducted in the most vulnerable and affected population groups, i.e. older adults residing in nursing homes. The objective of this study has been to explore the association of ACEi/ARB and/or statins with clinical manifestations in COVID-19 infected older adults residing in nursing homes. Design We undertook a retrospective multi-centre cohort study to analyse the association between ACEi/ARB and/or statin use with clinical outcome of COVID-19. The outcomes were 1) serious COVID-19 defined as long-stay hospital admission or death within 14 days of disease onset, and 2) asymptomatic, i.e. no disease symptoms in the whole study-period while still being PCR diagnosed. Setting and participants A total of 154 COVID-19 positive subjects was identified, residing in one of two Belgian nursing homes that experienced similar COVID-19 outbreaks. Measures Logistic regression models were applied with age, sex, functional status, diabetes and hypertension as covariates. Results We found a statistically significant association between statin intake and the absence of symptoms during COVID-19 (OR 2.91; CI 1.27-6.71), which remained statistically significant after adjusting for covariates (OR 2.65; CI 1.13-6.68). Although the effects of statin intake on serious clinical outcome were in the same beneficial direction, these were not statistically significant (OR 0.75; CI 0.24-1.87). There was also no statistically significant association between ACEi/ARB and asymptomatic status (OR 2.72; CI 0.59-25.1) or serious clinical outcome (OR 0.48; CI 0.10-1.97). Conclusions and Implications Our data indicate that statin intake in old, frail adults could be associated with a considerable beneficial effect on COVID-19 clinical symptoms. The role of statins and renin-angiotensin system drugs need to be further explored in larger observational studies as well as randomised clinical trials.", "qid": 20, "docid": "5znm0mq5", "rank": 55, "score": 0.8301414251327515}, {"content": "Title: Anti-RAS drugs and SARS-CoV-2 infection Content: \u00e2\u0080\u00a2There is no enough evidence to indicate that ACEIs and ARBs result in ACE2 upregulation.\u00e2\u0080\u00a2The level of ACE2 expression is not completely related with the risk of COVID-19 infection.\u00e2\u0080\u00a2There is currently no evidence that ACEI/ARB increase risk for COVID-19 infection from clinical trials.\u00e2\u0080\u00a2It is not recommended that COVID-19 patients with hypertension or normal hypertensive patients at risk for exposure to stop using ACEI/ARB or change to other antihypertensive drugs.", "qid": 20, "docid": "z3w87lsj", "rank": 56, "score": 0.82942795753479}, {"content": "Title: ARB/ACEI use and severe COVID-19: a nationwide case-control study Content: Background: Angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) have anti-inflammatory effects. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the membrane protein angiotensin-converting enzyme 2 (ACE2), which is increased by ARB/ACEI treatment, as a cell entry receptor. Therefore, the use of ARBs/ACEIs for COVID-19 remains controversial. Methods: A retrospective case-control study was conducted using COVID-19 patients previously diagnosed with hypertension before COVID-19 onset. The primary outcome was severe infection or all-cause mortality. Cases included ARB/ACEI use for 30 days or longer during the 6 months before COVID-19 onset. Primary controls included antihypertensive use other than ARBs/ACEIs (narrow control); secondary controls included all other hypertension patients (broad control). We investigated ARB/ACEI association with outcomes in general and by subgroups (age, sex, and presence of diabetes) using logistic regression models with propensity score matching. Findings: Of 234427 suspected COVID-19 patients we screened, 1585 hypertension patients were analyzed. In the 892 cases, 428 narrow controls, and 693 broad controls, severe infection or death occurred in 8.6%, 22.2%, and 16.7%, respectively. ARB/ACEI use was associated with a reduced risk of severe infection or death relative to the narrow control group (adjusted odds ratio [aOR] 0.43, 95% confidence interval [CI] 0.28-0.65) and broad control group (aOR 0.49, 95% CI 0.33-0.71). The association was smaller for newly diagnosed hypertension patients (aOR 0.11, 95% CI 0.03-0.42 compared to narrow control group). ARB/ACEI protective effects against severe infection or death were significantly observed in male and diabetic patients. Interpretation: ARB/ACEI use was associated with a lower risk of severe infection or mortality compared to other antihypertensives or ARB/ACEI nonuse.", "qid": 20, "docid": "vla7tt6s", "rank": 57, "score": 0.828619122505188}, {"content": "Title: Controversial Relationship between Renin-Angiotensin System Inhibitors and Severity of COVID-19: Announcing a Large Multicentre Case-Control Study in Italy. Content: The hypothesis has been proposed that patients COVID-19 positive, under anti-hypertensive treatment with angiotensin enzyme inhibitors or angiotensin receptor-blockers, might have a worse or a better clinical prognosis. This might be due to the fact that ACE2 is the receptor for the virus to enter human cells, but, on the contrary, that ACE2 expression is downregulated following SARS-1 infection, resulting in disproportionate activation of renin-angiotensin-aldosterone system and exacerbated pneumonia progression. However, no solid clinical data are available at the present moment to support or disprove such hypotheses. We announce in this letter that a large multicentre case-control study has been started in Italy that is the country with a very high impact of COVID-19 infection. We hope that our letter will encourage other clinical centres, even outside Italy, to join our study.", "qid": 20, "docid": "pm5htiqb", "rank": 58, "score": 0.828527569770813}, {"content": "Title: A systematic review and meta-analysis to evaluate the clinical outcomes in COVID-19 patients on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers Content: INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share their target receptor site with the SARS-CoV-2 virus, that may cause ACE2 receptor up-regulation which raised concerns regarding ACEI and ARB use in COVID-19 patients. However, many medical professional societies recommended their continued use given the paucity of clinical evidence, but there is a need for an updated systematic review and meta-analysis of the latest clinical studies. METHODS AND RESULTS: A search was conducted on PubMed, Google Scholar, EMBASE, and various preprint servers for studies comparing clinical outcomes and mortality in COVID-19 patients on ACEIs and/or ARBs, and a meta-analysis was performed. A total of 16 studies were included for the review and meta-analysis. There were conflicting findings reported in the rates of severity and mortality in several studies. In a pooled analysis of four studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of developing severe disease vs. non-users [odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.41-1.58, I2=50.52, P-value = 0.53). In a pooled analysis of six studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of mortality as compared with non-users (OR = 0.86, 95% CI = 0.53-1.41, I2 = 79.12, P-value = 0.55). CONCLUSION: It is concluded that ACEIs and ARBs should be continued in COVID-19 patients, reinforcing the recommendations made by several medical societies. Additionally, the individual patient factors such as ACE2 polymorphisms which might confer higher risk of adverse outcomes need to be evaluated further.", "qid": 20, "docid": "lk7vkbav", "rank": 59, "score": 0.8282623291015625}, {"content": "Title: A systematic review and meta-analysis to evaluate the clinical outcomes in COVID-19 patients on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers Content: INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share their target receptor site with the SARS-CoV-2 virus, that may cause ACE2 receptor up-regulation which raised concerns regarding ACEI and ARB use in COVID-19 patients. However, many medical professional societies recommended their continued use given the paucity of clinical evidence, but there is a need for an updated systematic review and meta-analysis of the latest clinical studies. METHODS AND RESULTS: A search was conducted on PubMed, Google Scholar, EMBASE, and various preprint servers for studies comparing clinical outcomes and mortality in COVID-19 patients on ACEIs and/or ARBs, and a meta-analysis was performed. A total of 16 studies were included for the review and meta-analysis. There were conflicting findings reported in the rates of severity and mortality in several studies. In a pooled analysis of four studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of developing severe disease vs. non-users [odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.41\u20131.58, I(2)=50.52, P-value = 0.53). In a pooled analysis of six studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of mortality as compared with non-users (OR = 0.86, 95% CI = 0.53\u20131.41, I(2) = 79.12, P-value = 0.55). CONCLUSION: It is concluded that ACEIs and ARBs should be continued in COVID-19 patients, reinforcing the recommendations made by several medical societies. Additionally, the individual patient factors such as ACE2 polymorphisms which might confer higher risk of adverse outcomes need to be evaluated further.", "qid": 20, "docid": "s4ty52kb", "rank": 60, "score": 0.8274608850479126}, {"content": "Title: Is Hypertension a Real Risk Factor for Poor Prognosis in the COVID-19 Pandemic? Content: PURPOSE OF REVIEW: There is increasing evidence indicating an association between several risk factors and worse prognosis in patients with coronavirus disease 2019 (COVID-19), including older age, hypertension, heart failure, diabetes, and pulmonary disease. Hypertension is of particular interest because it is common in adults and there are concerns related to the use of renin-angiotensin system (RAS) inhibitors in patients with hypertension infected with COVID-19. Levels of angiotensin-converting enzyme 2 (ACE2), a protein that facilitates entry of coronavirus into cells, may increase in patients using RAS inhibitors. Thus, chronic use of RAS inhibition could potentially lead to a more severe and fatal form of COVID-19. In this review, we provide a critical review to the following questions: (1) Does hypertension influence immunity or ACE2 expression favoring viral infections? (2) Are the risks of complications in hypertension mediated by its treatment? (3) Is aging a major factor associated with worse prognosis in patients with COVID-19 and hypertension? RECENT FINDINGS: Despite the potential involvement of immune responses in the pathogenesis of hypertension, there is no evidence supporting that hypothesis that hypertension or RAS inhibitors contributes to unfavorable outcomes in viral infections. Future investigations adopting a strict protocol for confirming hypertension status as well as assessing associated comorbidities that may influence outcomes are necessary. From the therapeutic perspective, recombinant ACE2 may serve as a potential therapy, but relevant studies in humans are lacking. Definitive evidence regarding the use of RAS inhibitors in patients with COVID-19 is needed; 5 randomized trials examining this issue are currently underway. SUMMARY: There is no current scientific support for claiming that hypertension or its treatment with RAS inhibitors contribute to unfavorable outcomes in COVID-19.", "qid": 20, "docid": "n4dgqo73", "rank": 61, "score": 0.8270379304885864}, {"content": "Title: Is the use of ACE inb/ARBs associated with higher in-hospital mortality in Covid-19 pneumonia patients? Content: INTRODUCTION The present research aimed to determine the relation between the use of angiotensin-converting enzyme inhibitors (ACE inh) and angiotensinogen receptor blockers (ARBs) and in-hospital mortality of hypertensive patients diagnosed with Covid-19 pneumonia. MATERIAL AND METHOD In this retrospective study, we included 113 consecutive hypertensive patients admitted due to Covid-19 infection. In all patients, Covid-19 infection was confirmed with using reverse-transcription polymerase chain reaction. All patients were on ACE inh/ARBs or other antihypertensive therapy unless no contraindication was present. The primary outcome of the study was the in-hospital all-cause mortality. RESULTS In total, 113 hypertensive Covid-19 patients were included, of them 74 patients were using ACE inh/ARBs. During in-hospital follow up, 30.9% [n = 35 patients] of patients died. The frequency of admission to the ICU and endotracheal intubation were significantly higher in patients using ACE inh/ARBs. In a multivariable analysis, the use of ACE inh/ARBs was an independent predictor of in-hospital mortality (OR: 3.66; 95%CI: 1.11-18.18; p= .032). Kaplan-Meir curve analysis displayed that patients on ACE inh/ARBs therapy had higher incidence of in-hospital death than those who were not. CONCLUSION The present study has found that the use of ACE inh/ARBs therapy might be associated with an increased in-hospital mortality in patients who were diagnosed with Covid-19 pneumonia. It is likely that ACE inh/ARBs therapy might not be beneficial in the subgroup of hypertensive Covid-19 patients despite the fact that there might be the possibility of some unmeasured residual confounders to affect the results of the study.", "qid": 20, "docid": "9o4fymyg", "rank": 62, "score": 0.8267551064491272}, {"content": "Title: Renin-angiotensin system inhibitors in COVID-19 Content: Concerns have been raised about the potential for renin-angiotensin system (RAS) inhibitors to upregulate expression of angiotensin-converting enzyme 2 (ACE2) and thus increase susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry. Currently, there is no evidence that even if RAS inhibitors increase expression and activity of ACE2, that they would increase the risk of SARS-CoV-2 infection by facilitating greater viral entry or worsen outcomes in patients with COVID-19. At this time, there is no clinical evidence to suggest that treatment with RAS inhibitors should be discontinued in stable patients with COVID-19. In hospitalized patients with severe COVID-19, decisions about these medications should be based on clinical condition, including hemodynamic status and renal function.", "qid": 20, "docid": "aqh90wmk", "rank": 63, "score": 0.8266674280166626}, {"content": "Title: Renin-angiotensin system inhibitors in COVID-19. Content: Concerns have been raised about the potential for renin-angiotensin system (RAS) inhibitors to upregulate expression of angiotensin-converting enzyme 2 (ACE2) and thus increase susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry. Currently, there is no evidence that even if RAS inhibitors increase expression and activity of ACE2, that they would increase the risk of SARS-CoV-2 infection by facilitating greater viral entry or worsen outcomes in patients with COVID-19. At this time, there is no clinical evidence to suggest that treatment with RAS inhibitors should be discontinued in stable patients with COVID-19. In hospitalized patients with severe COVID-19, decisions about these medications should be based on clinical condition, including hemodynamic status and renal function.", "qid": 20, "docid": "paxcmex6", "rank": 64, "score": 0.8266674280166626}, {"content": "Title: Therapy with agents acting on the renin-angiotensin system and risk of SARS-CoV-2 infection Content: Exposure to agents acting on the renin-angiotensin system was not associated to a risk increase of COVID-19 infection in two Italian matched case-control studies, one nested in hypertensive patients and the other in patients with cardiovascular diseases or diabetes.", "qid": 20, "docid": "2d8qyymo", "rank": 65, "score": 0.8264313340187073}, {"content": "Title: Therapy with agents acting on the renin-angiotensin system and risk of SARS-CoV-2 infection. Content: Exposure to agents acting on the renin-angiotensin system was not associated to a risk increase of COVID-19 infection in two Italian matched case-control studies, one nested in hypertensive patients and the other in patients with cardiovascular diseases or diabetes.", "qid": 20, "docid": "0yumc7em", "rank": 66, "score": 0.8264313340187073}, {"content": "Title: Risks of ACE Inhibitor and ARB Usage in COVID-19: Evaluating the Evidence Content: Concerns have been raised regarding the safety of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with coronavirus disease of 2019 (COVID-19), based on the hypothesis that such medications may raise expression of ACE2, the receptor for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). We conducted a literature review of studies (n = 12) in experimental animals and human subjects (n = 12) and evaluated the evidence regarding the impact of administration of ACEIs and ARBs on ACE2 expression. We prioritized studies that assessed ACE2 protein expression data, measured directly or inferred from ACE2 activity assays. The findings in animals are inconsistent with respect to an increase in ACE2 expression in response to treatment with ACEIs or ARBs. Control/sham animals show little to no effect in the plurality of studies. Those studies that report increases in ACE2 expression tend to involve acute injury models and/or higher doses of ACEIs or ARBs than are typically administered to patients. Data from human studies overwhelmingly imply that administration of ACEIs/ARBs does not increase ACE2 expression. Available evidence, in particular, data from human studies, does not support the hypothesis that ACEI/ARB use increases ACE2 expression and the risk of complications from COVID-19. We conclude that patients being treated with ACEIs and ARBs should continue their use for approved indications.", "qid": 20, "docid": "xnu55d2t", "rank": 67, "score": 0.8264083862304688}, {"content": "Title: Angiotensin-Converting Enzyme 2 and Antihypertensives (Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors) in Coronavirus Disease 2019 Content: Abstract Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is being defined as the worst pandemic disease of modern times. Several professional health organizations have published position papers stating that there is no evidence to change the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in the management of elevated blood pressure in the context of avoiding or treating COVID-19 infection. In this article, we review the evidence on the relationship between the renin-angiotensin-aldosterone system and COVID-19 infection. In agreement with current guidelines, patients with hypertension should continue taking antihypertensive medications as prescribed without interruption. Because ACEIs and ARBs are also used to retard the progression of chronic kidney disease, we suggest that these recommendations also apply to the use of these agents in chronic kidney disease. No differences generally exist between ARBs and ACEIs in terms of efficacy in decreasing blood pressure and improving other outcomes, such as all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. The ACEIs are associated with cough secondary to accumulation of bradykinin and angioedema, and withdrawal rates due to adverse events are lower with ARBs. Given their equal efficacy but fewer adverse events, ARBs could potentially be a more favorable treatment option in patients with COVID-19 at higher risk for severe forms of disease.", "qid": 20, "docid": "7lonkj5p", "rank": 68, "score": 0.8259392976760864}, {"content": "Title: Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality Content: Importance: It has been hypothesized that angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) may make patients more susceptible to coronavirus disease 2019 (COVID-19) and to worse outcomes through upregulation of the functional receptor of the virus, angiotensin-converting enzyme 2. Objective: To examine whether use of ACEI/ARBs was associated with COVID-19 diagnosis and worse outcomes in patients with COVID-19. Design, Setting, and Participants: To examine outcomes among patients with COVID-19, a retrospective cohort study using data from Danish national administrative registries was conducted. Patients with COVID-19 from February 22 to May 4, 2020, were identified using ICD-10 codes and followed up from day of diagnosis to outcome or end of study period (May 4, 2020). To examine susceptibility to COVID-19, a Cox regression model with a nested case-control framework was used to examine the association between use of ACEI/ARBs vs other antihypertensive drugs and the incidence rate of a COVID-19 diagnosis in a cohort of patients with hypertension from February 1 to May 4, 2020. Exposures: ACEI/ARB use was defined as prescription fillings 6 months prior to the index date. Main Outcomes and Measures: In the retrospective cohort study, the primary outcome was death, and a secondary outcome was a composite outcome of death or severe COVID-19. In the nested case-control susceptibility analysis, the outcome was COVID-19 diagnosis. Results: In the retrospective cohort study, 4480 patients with COVID-19 were included (median age, 54.7 years [interquartile range, 40.9-72.0]; 47.9% men). There were 895 users (20.0%) of ACEI/ARBs and 3585 nonusers (80.0%). In the ACEI/ARB group, 18.1% died within 30 days vs 7.3% in the nonuser group, but this association was not significant after adjustment for age, sex, and medical history (adjusted hazard ratio [HR], 0.83 [95% CI, 0.67-1.03]). Death or severe COVID-19 occurred in 31.9% of ACEI/ARB users vs 14.2% of nonusers by 30 days (adjusted HR, 1.04 [95% CI, 0.89-1.23]). In the nested case-control analysis of COVID-19 susceptibility, 571 patients with COVID-19 and prior hypertension (median age, 73.9 years; 54.3% men) were compared with 5710 age- and sex-matched controls with prior hypertension but not COVID-19. Among those with COVID-19, 86.5% used ACEI/ARBs vs 85.4% of controls; ACEI/ARB use compared with other antihypertensive drugs was not significantly associated with higher incidence of COVID-19 (adjusted HR, 1.05 [95% CI, 0.80-1.36]). Conclusions and Relevance: Prior use of ACEI/ARBs was not significantly associated with COVID-19 diagnosis among patients with hypertension or with mortality or severe disease among patients diagnosed as having COVID-19. These findings do not support discontinuation of ACEI/ARB medications that are clinically indicated in the context of the COVID-19 pandemic.", "qid": 20, "docid": "hn6wni8d", "rank": 69, "score": 0.8257393836975098}, {"content": "Title: Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19 Content: RATIONALE: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. OBJECTIVE: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19. METHODS AND RESULTS: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55\u201368] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57\u201369]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19\u20130.92]; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15\u20130.89]; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12\u20130.70]; P=0.01) in patients with COVID-19 and coexisting hypertension. CONCLUSIONS: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.", "qid": 20, "docid": "zmk8bbcd", "rank": 70, "score": 0.8256182074546814}, {"content": "Title: Is the use of ACE inb/ARBs associated with higher in-hospital mortality in Covid-19 pneumonia patients? Content: INTRODUCTION: The present research aimed to determine the relation between the use of angiotensin-converting enzyme inhibitors (ACE inh) and angiotensinogen receptor blockers (ARBs) and in-hospital mortality of hypertensive patients diagnosed with Covid-19 pneumonia. MATERIAL AND METHOD: In this retrospective study, we included 113 consecutive hypertensive patients admitted due to Covid-19 infection. In all patients, Covid-19 infection was confirmed with using reverse-transcription polymerase chain reaction. All patients were on ACE inh/ARBs or other antihypertensive therapy unless no contraindication was present. The primary outcome of the study was the in-hospital all-cause mortality. RESULTS: In total, 113 hypertensive Covid-19 patients were included, of them 74 patients were using ACE inh/ARBs. During in-hospital follow up, 30.9% [n = 35 patients] of patients died. The frequency of admission to the ICU and endotracheal intubation were significantly higher in patients using ACE inh/ARBs. In a multivariable analysis, the use of ACE inh/ARBs was an independent predictor of in-hospital mortality (OR: 3.66; 95%CI: 1.11-18.18; p= .032). Kaplan-Meir curve analysis displayed that patients on ACE inh/ARBs therapy had higher incidence of in-hospital death than those who were not. CONCLUSION: The present study has found that the use of ACE inh/ARBs therapy might be associated with an increased in-hospital mortality in patients who were diagnosed with Covid-19 pneumonia. It is likely that ACE inh/ARBs therapy might not be beneficial in the subgroup of hypertensive Covid-19 patients despite the fact that there might be the possibility of some unmeasured residual confounders to affect the results of the study.", "qid": 20, "docid": "o2zoy270", "rank": 71, "score": 0.8255845308303833}, {"content": "Title: Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19 Content: RATIONALE: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. OBJECTIVE: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19. METHODS AND RESULTS: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension. CONCLUSIONS: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.", "qid": 20, "docid": "h3xwg8uy", "rank": 72, "score": 0.8253508806228638}, {"content": "Title: The angiotensin-converting enzyme 2 (ACE2) receptor in the prevention and treatment of COVID-19 are distinctly different paradigms Content: There is current debate concerning the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers (ARBs), for hypertension management, during COVID-19 infection. Specifically, the suggestion has been made that ACE inhibitors or ARBs could theoretically contribute to infection via increasing ACE2 receptor expression and hence increase viral load. The ACE2 receptor is responsible for binding the SAR-CoV2 viral spike and causing COVID-19 infection. What makes the argument somewhat obtuse for ACE inhibitors or ARBs is that ACE2 receptor expression can be increased by compounds that activate or increase the expression of SIRT1. Henceforth common dietary interventions, vitamins and nutrients may directly or indirectly influence the cellular expression of the ACE2 receptor. There are many common compounds that can increase the expression of the ACE2 receptor including Vitamin C, Metformin, Resveratrol, Vitamin B3 and Vitamin D. It is important to acknowledge that down-regulation or blocking the cellular ACE2 receptor will likely be pro-inflammatory and may contribute to end organ pathology and mortality in COVID-19. In conclusion from the perspective of the ACE2 receptor, COVID-19 prevention and treatment are distinctly different. This letter reflects on this current debate and suggests angiotensin-converting enzyme inhibitors and ARBs are likely beneficial during COVID-19 infection for hypertensive and normotensive patients.", "qid": 20, "docid": "ux844b25", "rank": 73, "score": 0.8252227306365967}, {"content": "Title: Is Hypertension a Real Risk Factor for Poor Prognosis in the COVID-19 Pandemic? Content: PURPOSE OF REVIEW: There is increasing evidence indicating an association between several risk factors and worse prognosis in patients with coronavirus disease 2019 (COVID-19), including older age, hypertension, heart failure, diabetes, and pulmonary disease. Hypertension is of particular interest because it is common in adults and there are concerns related to the use of renin-angiotensin system (RAS) inhibitors in patients with hypertension infected with COVID-19. Levels of angiotensin-converting enzyme 2 (ACE2), a protein that facilitates entry of coronavirus into cells, may increase in patients using RAS inhibitors. Thus, chronic use of RAS inhibition could potentially lead to a more severe and fatal form of COVID-19. In this review, we provide a critical review to the following questions: (1) Does hypertension influence immunity or ACE2 expression favoring viral infections? (2) Are the risks of complications in hypertension mediated by its treatment? (3) Is aging a major factor associated with worse prognosis in patients with COVID-19 and hypertension? RECENT FINDINGS: Despite the potential involvement of immune responses in the pathogenesis of hypertension, there is no evidence supporting that hypothesis that hypertension or RAS inhibitors contributes to unfavorable outcomes in viral infections. Future investigations adopting a strict protocol for confirming hypertension status as well as assessing associated comorbidities that may influence outcomes are necessary. From the therapeutic perspective, recombinant ACE2 may serve as a potential therapy, but relevant studies in humans are lacking. Definitive evidence regarding the use of RAS inhibitors in patients with COVID-19 is needed; 5 randomized trials examining this issue are currently underway. There is no current scientific support for claiming that hypertension or its treatment with RAS inhibitors contribute to unfavorable outcomes in COVID-19.", "qid": 20, "docid": "gwefujal", "rank": 74, "score": 0.8250411748886108}, {"content": "Title: [Renin-angiotensin-aldosterone blockers and Covic-19 infection : friends or enemies ?] Content: ACE2 is not only an enzyme that counters the effects of the renin-angiotensin-aldosterone system (RAAS) but is also the entry receptor for SARS-CoV-2, the virus of the Covid-19 pandemic. Some experimental data suggest that ACE inhibitors and ARBs increase ACE2 levels, thus raising concerns on their security in Covid-19 positive patients. However, some studies have shown protection by these drugs in lower tract respiratory infections and ARDS. The actual consensus is to continue the treatment with RAAS inhibitors, abrupt withdrawal, especially in patients with cardiac or renal conditions, being hazardous in terms of cardiovascular outcomes, except in patients hospitalized in intensive care with hemodynamic instability. This position statement is actually unanimous among all international learned societies.", "qid": 20, "docid": "eccv9401", "rank": 75, "score": 0.8249202370643616}, {"content": "Title: Risks of ACE Inhibitor and ARB Usage in COVID\u201019: Evaluating the Evidence Content: Concerns have been raised regarding the safety of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with coronavirus disease of 2019 (COVID\u201019), based on the hypothesis that such medications may raise expression of ACE2, the receptor for severe acute respiratory syndrome\u2010coronavirus 2 (SARS\u2010CoV\u20102). We conducted a literature review of studies (n = 12) in experimental animals and human subjects (n = 12) and evaluated the evidence regarding the impact of administration of ACEIs and ARBs on ACE2 expression. We prioritized studies that assessed ACE2 protein expression data, measured directly or inferred from ACE2 activity assays. The findings in animals are inconsistent with respect to an increase in ACE2 expression in response to treatment with ACEIs or ARBs. Control/sham animals show little to no effect in the plurality of studies. Those studies that report increases in ACE2 expression tend to involve acute injury models and/or higher doses of ACEIs or ARBs than are typically administered to patients. Data from human studies overwhelmingly imply that administration of ACEIs/ARBs does not increase ACE2 expression. Available evidence, in particular, data from human studies, does not support the hypothesis that ACEI/ARB use increases ACE2 expression and the risk of complications from COVID\u201019. We conclude that patients being treated with ACEIs and ARBs should continue their use for approved indications.", "qid": 20, "docid": "3ysa4twk", "rank": 76, "score": 0.8249106407165527}, {"content": "Title: COVID-19 - Does This Disease Kill Due to Imbalance of the Renin Angiotensin System (RAS) Caused by Genetic and Gender Differences in the Response to Viral ACE 2 Attack? Content: Debate continues in the medical literature on the role of the renin angiotensin system (RAS) in Coronavirus disease 2019 (COVID-19) pathophysiology and the implications for the use of cardiovascular drugs acting on the RAS. Could these drugs - which include angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptors blockers (ARBs) - be harmful or potential key therapeutic agents in COVID-19? And, could potentially helpful measures be available and in plain view on the pharmacy shelf?", "qid": 20, "docid": "nw4b5hmz", "rank": 77, "score": 0.8248517513275146}, {"content": "Title: Long-Term ACE Inhibitor/ARB Use Is Associated with Severe Renal Dysfunction and Acute Kidney Injury in Patients with severe COVID-19: Results from a Referral Center Cohort in the North East of France Content: BACKGROUND: In patients with severe COVID-19, data are scarce and conflicting regarding whether chronic use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) influences disease outcomes. In patients with severe COVID-19, we assessed the association between chronic ACEI/ARB use and the occurrence of kidney, lung, heart, and liver dysfunctions and the severity of the inflammatory reaction as evaluated by biomarkers kinetics, and their association with disease outcomes. METHODS: We performed a retrospective longitudinal cohort study on consecutive patients with newly diagnosed severe COVID-19. Independent predictors were assessed through receiver operating characteristic analysis, time-series analysis, logistic regression analysis, and multilevel modeling for repeated measures. RESULTS: On the 149 patients included in the study 30% (44/149) were treated with ACEI/ARB. ACEI/ARB use was independently associated with the following biochemical variations: phosphorus >40 mg/L (odds ratio [OR], 3.35, 95% CI, 1.83-6.14), creatinine >10.1 mg/L (OR, 3.22, 2.28-4.54), and urea nitrogen (UN) >0.52 g/L (OR, 2.65, 1.89-3.73). ACEI/ARB use was independently associated with acute kidney injury, AKI stage &#8805;1 (OR, 3.28, 2.17-4.94). The daily dose of ACEI/ARB was independently associated with altered kidney markers with an increased risk of +25 to +31% per each 10 mg increment of lisinopril-dose equivalent. In multivariable multilevel modeling, UN >0.52 g/L was independently associated with the risk of acute respiratory failure (OR, 3.54, 1.05-11.96). CONCLUSIONS: Patients chronically treated with ACEI/ARB who have severe COVID-19 are at increased risk of acute kidney injury. In these patients, the increase in UN associated with ACEI/ARB use could predict the development of acute respiratory failure.", "qid": 20, "docid": "7om3bpby", "rank": 78, "score": 0.8248494267463684}, {"content": "Title: Effects Of ARBs And ACEIs On Virus Infection, Inflammatory Status And Clinical Outcomes In COVID-19 Patients With Hypertension: A Single Center Retrospective Study. Content: With the capability of inducing elevated expression of ACE2, the cellular receptor for SARS-CoV-2, angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (ARBs/ACEIs) treatment may have a controversial role in both facilitating virus infection and reducing pathogenic inflammation. We aimed to evaluate the effects of ARBs/ACEIs on COVID-19 in a retrospective, single-center study. 126 COVID-19 patients with preexisting hypertension at Hubei Provincial Hospital of Traditional Chinese Medicine (HPHTCM) in Wuhan from January 5 to February 22, 2020 were retrospectively allocated to ARBs/ACEIs group (n=43) and non-ARBs/ACEIs group (n=83) according to their antihypertensive medication. 125 age- and sex-matched COVID-19 patients without hypertension were randomly selected as non-hypertension controls. In addition, the medication history of 1942 hypertension patients that were admitted to HPHTCM from November 1 to December 31, 2019 before COVID-19 outbreak were also reviewed for external comparison. Epidemiological, demographic, clinical and laboratory data were collected, analyzed and compared between these groups. The frequency of ARBs/ACEIs usage in hypertension patients with or without COVID-19 were comparable. Among COVID-19 patients with hypertension, those received either ARBs/ACEIs or non-ARBs/ACEIs had comparable blood pressure. However, ARBs/ACEIs group had significantly lower concentrations of CRP (p=0.049) and procalcitonin (PCT, p=0.008). Furthermore, a lower proportion of critical patients (9.3% vs 22.9%; p=0.061), and a lower death rate (4.7% vs 13.3%; p=0.216) were observed in ARBs/ACEIs group than non-ARBs/ACEIs group, although these differences failed to reach statistical significance. Our findings thus support the use of ARBs/ACEIs in COVID-19 patients with preexisting hypertension.", "qid": 20, "docid": "yomcxz43", "rank": 79, "score": 0.8248069286346436}, {"content": "Title: Treatment with ACE inhibitors or ARBs and risk of severe/lethal COVID-19: a meta-analysis. Content: OBJECTIVE It has been hypothesised that the use of ACE inhibitors and angiotensin receptor blockers (ARBs) might either increase or reduce the risk of severe or lethal COVID-19. The findings from the available observational studies varied, and summary estimates are urgently needed to elucidate whether these drugs should be suspended during the pandemic, or patients and physicians should be definitely reassured. This meta-analysis of adjusted observational data aimed to summarise the existing evidence on the association between these medications and severe/lethal COVID-19. METHODS We searched MedLine, Scopus and preprint repositories up to 8 June 2020 to retrieve cohort or case-control studies comparing the risk of severe/fatal COVID-19 (either mechanical ventilation, intensive care unit admission or death), among hypertensive subjects treated with: (1) ACE inhibitors, (2) ARBs and (3) both, versus untreated subjects. Data were combined using a random-effect generic inverse variance approach. RESULTS Ten studies, enrolling 9890 hypertensive subjects were included in the analyses. Compared with untreated subjects, those using either ACE inhibitors or ARBs showed a similar risk of severe or lethal COVID-19 (summary OR: 0.90; 95% CI 0.65 to 1.26 for ACE inhibitors; 0.92; 95% CI 0.75 to 1.12 for ARBs). The results did not change when both drugs were considered together, when death was the outcome and excluding the studies with significant, divergent results. CONCLUSION The present meta-analysis strongly supports the recommendation of several scientific societies to continue ARBs or ACE inhibitors for all patients, unless otherwise advised by their physicians who should thus be reassured.", "qid": 20, "docid": "9vywrvw3", "rank": 80, "score": 0.8244426250457764}, {"content": "Title: Treatment with ACE inhibitors or ARBs and risk of severe/lethal COVID-19: a meta-analysis Content: OBJECTIVE: It has been hypothesised that the use of ACE inhibitors and angiotensin receptor blockers (ARBs) might either increase or reduce the risk of severe or lethal COVID-19. The findings from the available observational studies varied, and summary estimates are urgently needed to elucidate whether these drugs should be suspended during the pandemic, or patients and physicians should be definitely reassured. This meta-analysis of adjusted observational data aimed to summarise the existing evidence on the association between these medications and severe/lethal COVID-19. METHODS: We searched MedLine, Scopus and preprint repositories up to 8 June 2020 to retrieve cohort or case-control studies comparing the risk of severe/fatal COVID-19 (either mechanical ventilation, intensive care unit admission or death), among hypertensive subjects treated with: (1) ACE inhibitors, (2) ARBs and (3) both, versus untreated subjects. Data were combined using a random-effect generic inverse variance approach. RESULTS: Ten studies, enrolling 9890 hypertensive subjects were included in the analyses. Compared with untreated subjects, those using either ACE inhibitors or ARBs showed a similar risk of severe or lethal COVID-19 (summary OR: 0.90; 95% CI 0.65 to 1.26 for ACE inhibitors; 0.92; 95% CI 0.75 to 1.12 for ARBs). The results did not change when both drugs were considered together, when death was the outcome and excluding the studies with significant, divergent results. CONCLUSION: The present meta-analysis strongly supports the recommendation of several scientific societies to continue ARBs or ACE inhibitors for all patients, unless otherwise advised by their physicians who should thus be reassured.", "qid": 20, "docid": "lbp6fquk", "rank": 81, "score": 0.8243845105171204}, {"content": "Title: Long-Term ACE Inhibitor/ARB Use Is Associated with Severe Renal Dysfunction and Acute Kidney Injury in Patients with severe COVID-19: Results from a Referral Center Cohort in the North East of France. Content: BACKGROUND In patients with severe COVID-19, data are scarce and conflicting regarding whether chronic use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) influences disease outcomes. In patients with severe COVID-19, we assessed the association between chronic ACEI/ARB use and the occurrence of kidney, lung, heart, and liver dysfunctions and the severity of the inflammatory reaction as evaluated by biomarkers kinetics, and their association with disease outcomes. METHODS We performed a retrospective longitudinal cohort study on consecutive patients with newly diagnosed severe COVID-19. Independent predictors were assessed through receiver operating characteristic analysis, time-series analysis, logistic regression analysis, and multilevel modeling for repeated measures. RESULTS On the 149 patients included in the study 30% (44/149) were treated with ACEI/ARB. ACEI/ARB use was independently associated with the following biochemical variations: phosphorus >40 mg/L (odds ratio [OR], 3.35, 95% CI, 1.83-6.14), creatinine >10.1 mg/L (OR, 3.22, 2.28-4.54), and urea nitrogen (UN) >0.52 g/L (OR, 2.65, 1.89-3.73). ACEI/ARB use was independently associated with acute kidney injury, AKI stage \u22651 (OR, 3.28, 2.17-4.94). The daily dose of ACEI/ARB was independently associated with altered kidney markers with an increased risk of +25 to +31% per each 10 mg increment of lisinopril-dose equivalent. In multivariable multilevel modeling, UN >0.52 g/L was independently associated with the risk of acute respiratory failure (OR, 3.54, 1.05-11.96). CONCLUSIONS Patients chronically treated with ACEI/ARB who have severe COVID-19 are at increased risk of acute kidney injury. In these patients, the increase in UN associated with ACEI/ARB use could predict the development of acute respiratory failure.", "qid": 20, "docid": "pfzklmyw", "rank": 82, "score": 0.8242124915122986}, {"content": "Title: Angiotension-converting enzyme inhibitors and angiotensin-receptor blockers are not associated with increased risk of SARS-CoV-2 infection Content: In a large Israeli dataset of 14 520 individuals tested for SARS-CoV-2, angiotension-converting enzyme inhibitors and angiotensin-receptor blockers were not found to be associated with increased SARS-CoV-2 infection after adjusting for major confounders. Patients on these medications should not stop their medication prophylactically.", "qid": 20, "docid": "amgkcxaw", "rank": 83, "score": 0.8241714239120483}, {"content": "Title: Association of Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Testing Positive for Coronavirus Disease 2019 (COVID-19) Content: Importance: The role of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in the setting of the coronavirus disease 2019 (COVID-19) pandemic is hotly debated. There have been recommendations to discontinue these medications, which are essential in the treatment of several chronic disease conditions, while, in the absence of clinical evidence, professional societies have advocated their continued use. Objective: To study the association between use of ACEIs/ARBs with the likelihood of testing positive for COVID-19 and to study outcome data in subsets of patients taking ACEIs/ARBs who tested positive with severity of clinical outcomes of COVID-19 (eg, hospitalization, intensive care unit admission, and requirement for mechanical ventilation). Design, Setting, and Participants: Retrospective cohort study with overlap propensity score weighting was conducted at the Cleveland Clinic Health System in Ohio and Florida. All patients tested for COVID-19 between March 8 and April 12, 2020, were included. Exposures: History of taking ACEIs or ARBs at the time of COVID-19 testing. Main Outcomes and Measures: Results of COVID-19 testing in the entire cohort, number of patients requiring hospitalizations, intensive care unit admissions, and mechanical ventilation among those who tested positive. Results: A total of 18\u00e2\u0080\u00af472 patients tested for COVID-19. The mean (SD) age was 49 (21) years, 7384 (40%) were male, and 12\u00e2\u0080\u00af725 (69%) were white. Of 18\u00e2\u0080\u00af472 patients who underwent COVID-19 testing, 2285 (12.4%) were taking either ACEIs or ARBs. A positive COVID-19 test result was observed in 1735 of 18\u00e2\u0080\u00af472 patients (9.4%). Among patients who tested positive, 421 (24.3%) were admitted to the hospital, 161 (9.3%) were admitted to an intensive care unit, and 111 (6.4%) required mechanical ventilation. Overlap propensity score weighting showed no significant association of ACEI and/or ARB use with COVID-19 test positivity (overlap propensity score-weighted odds ratio, 0.97; 95% CI, 0.81-1.15). Conclusions and Relevance: This study found no association between ACEI or ARB use and COVID-19 test positivity. These clinical data support current professional society guidelines to not discontinue ACEIs or ARBs in the setting of the COVID-19 pandemic. However, further study in larger numbers of hospitalized patients receiving ACEI and ARB therapy is needed to determine the association with clinical measures of COVID-19 severity.", "qid": 20, "docid": "v10tfut9", "rank": 84, "score": 0.8230278491973877}, {"content": "Title: Association of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers with the Risk of Hospitalization and Death in Hypertensive Patients with Coronavirus Disease-19 Content: BACKGROUND: Whether angiotensin-converting enzyme (ACE) Inhibitors and angiotensin receptor blockers (ARBs) mitigate or exacerbate SARS-CoV-2 infection remains uncertain. In a national study, we evaluated the association of ACE inhibitors and ARB with coronavirus disease-19 (COVID-19) hospitalization and mortality among individuals with hypertension. METHODS: Among Medicare Advantage and commercially insured individuals, we identified 2,263 people with hypertension, receiving \u22651 antihypertensive agents, and who had a positive outpatient SARS-CoV-2 test (outpatient cohort). In a propensity score-matched analysis, we determined the association of ACE inhibitors and ARBs with the risk of hospitalization for COVID-19. In a second study of 7,933 individuals with hypertension who were hospitalized with COVID-19 (inpatient cohort), we tested the association of these medications with in-hospital mortality. We stratified all our assessments by insurance groups. RESULTS: Among individuals in the outpatient and inpatient cohorts, 31.9% and 29.8%, respectively, used ACE inhibitors and 32.3% and 28.1% used ARBs. In the outpatient study, over a median 30.0 (19.0 - 40.0) days after testing positive, 12.7% were hospitalized for COVID-19. In propensity score-matched analyses, neither ACE inhibitors (HR, 0.77 [0.53, 1.13], P = 0.18), nor ARBs (HR, 0.88 [0.61, 1.26], P = 0.48), were significantly associated with risk of hospitalization. In analyses stratified by insurance group, ACE inhibitors, but not ARBs, were associated with a significant lower risk of hospitalization in the Medicare group (HR, 0.61 [0.41, 0.93], P = 0.02), but not the commercially insured group (HR: 2.14 [0.82, 5.60], P = 0.12; P-interaction 0.09). In the inpatient study, 14.2% died, 59.5% survived to discharge, and 26.3% had an ongoing hospitalization. In propensity score-matched analyses, neither use of ACE inhibitor (0.97 [0.81, 1.16]; P = 0.74) nor ARB (1.15 [0.95, 1.38]; P = 0.15) was associated with risk of in-hospital mortality, in total or in the stratified analyses. CONCLUSIONS: The use of ACE inhibitors and ARBs was not associated with the risk of hospitalization or mortality among those infected with SARS-CoV-2. However, there was a nearly 40% lower risk of hospitalization with the use of ACE inhibitors in the Medicare population. This finding merits a clinical trial to evaluate the potential role of ACE inhibitors in reducing the risk of hospitalization among older individuals, who are at an elevated risk of adverse outcomes with the infection.", "qid": 20, "docid": "roj3om68", "rank": 85, "score": 0.8230050802230835}, {"content": "Title: Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China. Content: Importance Data are lacking whether patients with hypertension who are taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have increased severity or risk of mortality during hospitalization for coronavirus disease 2019 (COVID-19). Objective To investigate the association between ACEIs/ARBs and severity of illness and mortality in patients with hypertension hospitalized for COVID-19 infection. Design, Setting, and Participants Retrospective, single-center case series of the 1178 hospitalized patients with COVID-19 infections at the Central Hospital of Wuhan, China, from January 15 to March 15, 2020. Main Outcomes and Measures COVID-19 was confirmed by real-time reverse transcription-polymerase chain reaction and epidemiologic, clinical, radiologic, laboratory, and drug therapy data were analyzed in all patients. The percentage of patients with hypertension taking ACEIs/ARBs was compared between those with severe vs nonsevere illness and between survivors vs nonsurvivors. Results Of the 1178 patients with COVID-19, the median age was 55.5 years (interquartile range, 38-67 years) and 545 (46.3%) were men. The overall in-hospital mortality was 11.0%. There were 362 patients with hypertension (30.7% of the total group; median age, 66.0 years [interquartile range, 59-73 years]; 189 [52.2%] were men), of whom 115 (31.8%) were taking ACEI/ARBs. The in-hospital mortality in the patients with hypertension was 21.3%. The percentage of patients with hypertension taking ACEIs/ARBs did not differ between those with severe and nonsevere infections (32.9% vs 30.7%; P = .65) nor did it differ between nonsurvivors and survivors (27.3% vs 33.0%; P = .34). Similar findings were observed when data were analyzed for patients taking ACEIs and those taking ARBs. Conclusions and Relevance This study provides clinical data on the association between ACEIs/ARBs and outcomes in patients with hypertension hospitalized with COVID-19 infections, suggesting that ACEIs/ARBs are not associated with the severity or mortality of COVID-19 in such patients. These data support current guidelines and societal recommendations for treating hypertension during the COVID-19 pandemic.", "qid": 20, "docid": "p10cya94", "rank": 86, "score": 0.822895348072052}, {"content": "Title: Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China Content: Importance: Data are lacking whether patients with hypertension who are taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have increased severity or risk of mortality during hospitalization for coronavirus disease 2019 (COVID-19). Objective: To investigate the association between ACEIs/ARBs and severity of illness and mortality in patients with hypertension hospitalized for COVID-19 infection. Design, Setting, and Participants: Retrospective, single-center case series of the 1178 hospitalized patients with COVID-19 infections at the Central Hospital of Wuhan, China, from January 15 to March 15, 2020. Main Outcomes and Measures: COVID-19 was confirmed by real-time reverse transcription-polymerase chain reaction and epidemiologic, clinical, radiologic, laboratory, and drug therapy data were analyzed in all patients. The percentage of patients with hypertension taking ACEIs/ARBs was compared between those with severe vs nonsevere illness and between survivors vs nonsurvivors. Results: Of the 1178 patients with COVID-19, the median age was 55.5 years (interquartile range, 38-67 years) and 545 (46.3%) were men. The overall in-hospital mortality was 11.0%. There were 362 patients with hypertension (30.7% of the total group; median age, 66.0 years [interquartile range, 59-73 years]; 189 [52.2%] were men), of whom 115 (31.8%) were taking ACEI/ARBs. The in-hospital mortality in the patients with hypertension was 21.3%. The percentage of patients with hypertension taking ACEIs/ARBs did not differ between those with severe and nonsevere infections (32.9% vs 30.7%; P = .65) nor did it differ between nonsurvivors and survivors (27.3% vs 33.0%; P = .34). Similar findings were observed when data were analyzed for patients taking ACEIs and those taking ARBs. Conclusions and Relevance: This study provides clinical data on the association between ACEIs/ARBs and outcomes in patients with hypertension hospitalized with COVID-19 infections, suggesting that ACEIs/ARBs are not associated with the severity or mortality of COVID-19 in such patients. These data support current guidelines and societal recommendations for treating hypertension during the COVID-19 pandemic.", "qid": 20, "docid": "m6pth0tu", "rank": 87, "score": 0.8224246501922607}, {"content": "Title: Association of Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Testing Positive for Coronavirus Disease 2019 (COVID-19). Content: Importance The role of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in the setting of the coronavirus disease 2019 (COVID-19) pandemic is hotly debated. There have been recommendations to discontinue these medications, which are essential in the treatment of several chronic disease conditions, while, in the absence of clinical evidence, professional societies have advocated their continued use. Objective To study the association between use of ACEIs/ARBs with the likelihood of testing positive for COVID-19 and to study outcome data in subsets of patients taking ACEIs/ARBs who tested positive with severity of clinical outcomes of COVID-19 (eg, hospitalization, intensive care unit admission, and requirement for mechanical ventilation). Design, Setting, and Participants Retrospective cohort study with overlap propensity score weighting was conducted at the Cleveland Clinic Health System in Ohio and Florida. All patients tested for COVID-19 between March 8 and April 12, 2020, were included. Exposures History of taking ACEIs or ARBs at the time of COVID-19 testing. Main Outcomes and Measures Results of COVID-19 testing in the entire cohort, number of patients requiring hospitalizations, intensive care unit admissions, and mechanical ventilation among those who tested positive. Results A total of 18 472 patients tested for COVID-19. The mean (SD) age was 49 (21) years, 7384 (40%) were male, and 12 725 (69%) were white. Of 18 472 patients who underwent COVID-19 testing, 2285 (12.4%) were taking either ACEIs or ARBs. A positive COVID-19 test result was observed in 1735 of 18 472 patients (9.4%). Among patients who tested positive, 421 (24.3%) were admitted to the hospital, 161 (9.3%) were admitted to an intensive care unit, and 111 (6.4%) required mechanical ventilation. Overlap propensity score weighting showed no significant association of ACEI and/or ARB use with COVID-19 test positivity (overlap propensity score-weighted odds ratio, 0.97; 95% CI, 0.81-1.15). Conclusions and Relevance This study found no association between ACEI or ARB use and COVID-19 test positivity. These clinical data support current professional society guidelines to not discontinue ACEIs or ARBs in the setting of the COVID-19 pandemic. However, further study in larger numbers of hospitalized patients receiving ACEI and ARB therapy is needed to determine the association with clinical measures of COVID-19 severity.", "qid": 20, "docid": "pn4cz2bf", "rank": 88, "score": 0.821577787399292}, {"content": "Title: Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension Content: The dysfunction of the renin-angiotensin system (RAS) has been observed in coronavirus infection disease (COVID-19) patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), are associated with clinical outcomes remains unknown. COVID-19 patients with hypertension were enrolled to evaluate the effect of RAS inhibitors. We observed that patients receiving ACEI or ARB therapy had a lower rate of severe diseases and a trend toward a lower level of IL-6 in peripheral blood. In addition, ACEI or ARB therapy increased CD3 and CD8 T cell counts in peripheral blood and decreased the peak viral load compared to other antihypertensive drugs. This evidence supports the benefit of using ACEIs or ARBs to potentially contribute to the improvement of clinical outcomes of COVID-19 patients with hypertension.", "qid": 20, "docid": "wz28xxhn", "rank": 89, "score": 0.8211979269981384}, {"content": "Title: Impact of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on COVID-19 in a western population. CARDIOVID registry Content: INTRODUCTION AND OBJECTIVES: Coronavirus disease (COVID-19) has been designated a global pandemic by the World Health Organization. It is unclear whether previous treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) affects the prognosis of COVID-19 patients. The aim of this study was to evaluate the clinical implications of previous treatment with ACEI/ARB on the prognosis of patients with COVID-19 infection. METHODS: Single-center, retrospective, observational cohort study based on all the inhabitants of our health area. Analyses of main outcomes (mortality, heart failure, hospitalization, intensive care unit [ICU] admission, and major acute cardiovascular events [a composite of mortality and heart failure]) were adjusted by multivariate logistic regression and propensity score matching models. RESULTS: Of the total population, 447 979 inhabitants, 965 patients (0.22%) were diagnosed with COVID-19 infection, and 210 (21.8%) were under ACEI or ARB treatment at the time of diagnosis. Treatment with ACEI/ARB (combined and individually) had no effect on mortality (OR, 0.62; 95%CI, 0.17-2.26; P=.486), heart failure (OR, 1.37; 95%CI, 0.39-4.77; P=.622), hospitalization rate (OR, 0.85; 95%CI, 0.45-1.64; P=.638), ICU admission (OR, 0.87; 95%CI, 0.30-2.50; P=.798), or major acute cardiovascular events (OR, 1.06; 95%CI, 0.39-2.83; P=.915). This neutral effect remained in a subgroup analysis of patients requiring hospitalization. CONCLUSIONS: Previous treatment with ACEI/ARB in patients with COVID-19 had no effect on mortality, heart failure, requirement for hospitalization, or ICU admission. Withdrawal of ACEI/ARB in patients testing positive for COVID-19 would not be justified, in line with current recommendations of scientific societies and government agencies.", "qid": 20, "docid": "6kzrc2ud", "rank": 90, "score": 0.8210422992706299}, {"content": "Title: Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors Usage is Associated with Improved Inflammatory Status and Clinical Outcomes in COVID-19 Patients With Hypertension Content: With the capability of inducing elevated expression of ACE2, the cellular receptor for SARS-CoV-2, angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (ARBs/ACEIs) treatment may have a controversial role in both facilitating virus infection and reducing pathogenic inflammation. We aimed to evaluate the correlation of ARBs/ACEIs usage with the pathogenesis of COVID-19 in a retrospective, single-center study. 126 COVID-19 patients with preexisting hypertension at Hubei Provincial Hospital of Traditional Chinese Medicine (HPHTCM) in Wuhan from January 5 to February 22, 2020 were retrospectively allocated to ARBs/ACEIs group (n=43) and non-ARBs/ACEIs group (n=83) according to their antihypertensive medication. 125 age- and sex-matched COVID-19 patients without hypertension were randomly selected as non-hypertension controls. In addition, the medication history of 1942 hypertension patients that were admitted to HPHTCM from November 1 to December 31, 2019 before COVID-19 outbreak were also reviewed for external comparison. Epidemiological, demographic, clinical and laboratory data were collected, analyzed and compared between these groups. The frequency of ARBs/ACEIs usage in hypertension patients with or without COVID-19 were comparable. Among COVID-19 patients with hypertension, those received either ARBs/ACEIs or non-ARBs/ACEIs had comparable blood pressure. However, ARBs/ACEIs group had significantly lower concentrations of CRP (p=0.049) and procalcitonin (PCT, p=0.008). Furthermore, much lower proportion of critical patients (9.3% vs 22.9%; p=0.061), and a lower death rate (4.7% vs 13.3%; p=0.216) were observed in ARBs/ACEIs group than non-ARBs/ACEIs group, although these differences failed to reach statistical significance. Our findings thus support the use of ARBs/ACEIs in COVID-19 patients with preexisting hypertension.", "qid": 20, "docid": "mwttkclk", "rank": 91, "score": 0.8208415508270264}, {"content": "Title: Use of renin\u2013angiotensin\u2013aldosterone system inhibitors and risk of COVID-19 requiring admission to hospital: a case-population study Content: BACKGROUND: Concerns have been raised about the possibility that inhibitors of the renin\u2013angiotensin\u2013aldosterone system (RAAS) could predispose individuals to severe COVID-19; however, epidemiological evidence is lacking. We report the results of a case-population study done in Madrid, Spain, since the outbreak of COVID-19. METHODS: In this case-population study, we consecutively selected patients aged 18 years or older with a PCR-confirmed diagnosis of COVID-19 requiring admission to hospital from seven hospitals in Madrid, who had been admitted between March 1 and March 24, 2020. As a reference group, we randomly sampled ten patients per case, individually matched for age, sex, region (ie, Madrid), and date of admission to hospital (month and day; index date), from Base de datos para la Investigaci\u00f3n Farmacoepidemiol\u00f3gica en Atenci\u00f3n Primaria (BIFAP), a Spanish primary health-care database, in its last available year (2018). We extracted information on comorbidities and prescriptions up to the month before index date (ie, current use) from electronic clinical records of both cases and controls. The outcome of interest was admission to hospital of patients with COVID-19. To minimise confounding by indication, the main analysis focused on assessing the association between COVID-19 requiring admission to hospital and use of RAAS inhibitors compared with use of other antihypertensive drugs. We calculated odds ratios (ORs) and 95% CIs, adjusted for age, sex, and cardiovascular comorbidities and risk factors, using conditional logistic regression. The protocol of the study was registered in the EU electronic Register of Post-Authorisation Studies, EUPAS34437. FINDINGS: We collected data for 1139 cases and 11 390 population controls. Among cases, 444 (39\u00b70%) were female and the mean age was 69\u00b71 years (SD 15\u00b74), and despite being matched on sex and age, a significantly higher proportion of cases had pre-existing cardiovascular disease (OR 1\u00b798, 95% CI 1\u00b762\u20132\u00b741) and risk factors (1\u00b746, 1\u00b723\u20131\u00b773) than did controls. Compared with users of other antihypertensive drugs, users of RAAS inhibitors had an adjusted OR for COVID-19 requiring admission to hospital of 0\u00b794 (95% CI 0\u00b777\u20131\u00b715). No increased risk was observed with either angiotensin-converting enzyme inhibitors (adjusted OR 0\u00b780, 0\u00b764\u20131\u00b700) or angiotensin-receptor blockers (1\u00b710, 0\u00b788\u20131\u00b737). Sex, age, and background cardiovascular risk did not modify the adjusted OR between use of RAAS inhibitors and COVID-19 requiring admission to hospital, whereas a decreased risk of COVID-19 requiring admission to hospital was found among patients with diabetes who were users of RAAS inhibitors (adjusted OR 0\u00b753, 95% CI 0\u00b734\u20130\u00b780). The adjusted ORs were similar across severity degrees of COVID-19. INTERPRETATION: RAAS inhibitors do not increase the risk of COVID-19 requiring admission to hospital, including fatal cases and those admitted to intensive care units, and should not be discontinued to prevent a severe case of COVID-19. FUNDING: Instituto de Salud Carlos III.", "qid": 20, "docid": "10l12wgu", "rank": 92, "score": 0.8199219703674316}, {"content": "Title: Could anti-hypertensive drug therapy affect the clinical prognosis of hypertensive patients with COVID-19 infection? Data from centers of southern Italy Content: Background Coronavirus-19 (COVID-19) is the cause of a pandemic disease, with severe acute respiratory syndrome by binding target epithelial lung cells through angiotensin converting enzyme 2 (ACE2) in humans. Thus, hypertensive patients with COVID-19 could have worse prognosis. Indeed, angiotensin converting enzyme (ACEi) inhibitors and/or angiotensin receptor blockers (ARBs) may interfere with ACE2 expression/activity. Thus, hypertensive patients undergoing ACEi and/or ARBs drug therapy may be at a higher risk of contracting a serious COVID-19 infection and should be monitored. Moreover, in the present study we investigated the effects of ACEi vs. ARBs vs. calcium channel blockers on clinical outcomes as mechanical ventilation, Intensive Care Unit (ICU) admissions, heart injury and death in 62 hypertensive patients hospitalized for COVID-19 infection. Methods and Results The multicenter study was prospectively conducted at Department of Infectious Diseases of Sant'Anna Hospital of Caserta, and of University of Campania \"Luigi Vanvitelli\" of Naples, at Department of Advanced Surgical and Medical Sciences of University of Campania \"Luigi Vanvitelli\", Naples, and at General Medical Assistance Unit \"FIMG\", Naples, Italy. Lowest values of left ventricle ejection fraction predicted deaths (1.142; [1.008-1.294], p <0.05), while highest values of interleukin 6 (IL6) predicted the admission to ICU (1.617; [1.094-2.389]), mechanical ventilation (1.149; [1.082-1.219]), heart injuries (1.367; [1.054-1.772]) and deaths (4.742; [1.788-8.524]). ConclusionsAnti-hypertensive drugs didn't affect the prognosis in COVID-19 patients. Consequently, tailored anti-inflammatory and immune therapies in addition to chronic antihypertensive therapy, could prevent a worse prognosis, as well as improve the clinical outcomes in hypertensive patients with COVID-19 infection.", "qid": 20, "docid": "75apu1m4", "rank": 93, "score": 0.8192266225814819}, {"content": "Title: Could anti-hypertensive drug therapy affect the clinical prognosis of hypertensive patients with COVID-19 infection? Data from centers of southern Italy. Content: Background Coronavirus-19 (COVID-19) is the cause of a pandemic disease, with severe acute respiratory syndrome by binding target epithelial lung cells through angiotensin converting enzyme 2 (ACE2) in humans. Thus, hypertensive patients with COVID-19 could have worse prognosis. Indeed, angiotensin converting enzyme (ACEi) inhibitors and/or angiotensin receptor blockers (ARBs) may interfere with ACE2 expression/activity. Thus, hypertensive patients undergoing ACEi and/or ARBs drug therapy may be at a higher risk of contracting a serious COVID-19 infection and should be monitored. Moreover, in the present study we investigated the effects of ACEi vs. ARBs vs. calcium channel blockers on clinical outcomes as mechanical ventilation, Intensive Care Unit (ICU) admissions, heart injury and death in 62 hypertensive patients hospitalized for COVID-19 infection. Methods and Results The multicenter study was prospectively conducted at Department of Infectious Diseases of Sant'Anna Hospital of Caserta, and of University of Campania \"Luigi Vanvitelli\" of Naples, at Department of Advanced Surgical and Medical Sciences of University of Campania \"Luigi Vanvitelli\", Naples, and at General Medical Assistance Unit \"FIMG\", Naples, Italy. Lowest values of left ventricle ejection fraction predicted deaths (1.142; [1.008-1.294], p <0.05), while highest values of interleukin 6 (IL6) predicted the admission to ICU (1.617; [1.094-2.389]), mechanical ventilation (1.149; [1.082-1.219]), heart injuries (1.367; [1.054-1.772]) and deaths (4.742; [1.788-8.524]). ConclusionsAnti-hypertensive drugs didn't affect the prognosis in COVID-19 patients. Consequently, tailored anti-inflammatory and immune therapies in addition to chronic antihypertensive therapy, could prevent a worse prognosis, as well as improve the clinical outcomes in hypertensive patients with COVID-19 infection.", "qid": 20, "docid": "rbi4kg69", "rank": 94, "score": 0.8192266225814819}, {"content": "Title: Renin-Angiotensin-Aldosterone Inhibitors and COVID-19 Content: The Corona Virus Disease 2019 (COVID-19) outbreak has rapidly spread throughout the world, accounting for significant morbidity and mortality. There is a concern that renin-angiotensin-aldosterone inhibitors increase susceptibility to COVID-19. Currently there are no clinical data demonstrating beneficial or adverse effects of these medications on COVID-19 outcomes. Renin-angiotensin-aldosterone inhibitors should be continued in patients in otherwise stable conditions who are at risk for or having COVID-19.", "qid": 20, "docid": "sew2sx9v", "rank": 95, "score": 0.8191704750061035}, {"content": "Title: The effects of ARBs, ACEIs and statins on clinical outcomes of COVID-19 infection among nursing home residents Content: Background. COVID-19 infection has limited preventive or therapeutic drug options at this stage. Some of common existing drugs like angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB) and the HMG-CoA reductase inhibitors (statins) have been hypothesised to impact on disease severity. However, up till now, no studies investigating this association were conducted in the most vulnerable and affected population groups, i.e. older people residing in nursing homes. The purpose of this study has been to explore the association of ACEi/ARB and/or statins with clinical manifestations in COVID-19 infected older people residing in nursing homes. Methods and Findings. We undertook a retrospective multi-centre cohort study in two Belgian nursing homes that experienced similar COVID-19 outbreaks. COVID-19 diagnoses were based on clinical suspicion and/or viral presence using PCR of nasopharyngeal samples. A total of 154 COVID-19 positive subjects was identified. The outcomes were defined as 1) serious COVID-19 defined as a long-stay hospital admission (length of stay [\u2265] 7 days) or death (at hospital or nursing home) within 14 days of disease onset, and 2) asymptomatic, i.e. no disease symptoms in the whole study-period while still being PCR diagnosed. Disease symptoms were defined as any COVID-19-related clinical symptom (e.g. coughing, dyspnoea, sore throat) or sign (low oxygen saturation and fever) for [\u2265] 2 days out of 3 consecutive days. Logistic regression models with Firth corrections were applied on these 154 subjects to analyse the association between ACEi/ARB and/or statin use with the outcomes. Age, sex, functional status, diabetes and hypertension were used as covariates. Sensitivity analyses were conducted to evaluate the robustness of our statistical significant findings. We found a statistically significant association between statin intake and the absence of symptoms during COVID-19 infection (unadjusted OR 2.91; CI 1.27-6.71; p=0.011), which remained statistically significant after adjusting for age, sex, functional status, diabetes mellitus and hypertension. The strength of this association was considerable and clinically important. Although the effects of statin intake on serious clinical outcome (long-stay hospitalisation or death) were in the same beneficial direction, these were not statistically significant (OR 0.75; CI 0.25-1.85; p=0.556). There was also no statistically significant association between ACEi/ARB and asymptomatic status (OR 1.52; CI 0.62-3.50; p=0.339) or serious clinical outcome (OR 0.79; CI 0.26-1.95; p=0.629). Conclusions. Our data indicate that statin intake in old, frail people could be associated with a considerable beneficial effect on COVID-19 related clinical symptoms. The role of statins and any interaction with renin-angiotensin system drugs need to be further explored in larger observational studies as well as randomised clinical trials.", "qid": 20, "docid": "rky7tip0", "rank": 96, "score": 0.818812370300293}, {"content": "Title: COVID-19 and hypertension-evidence and practical management: Guidance from the HOPE Asia Network Content: There are several risk factors for worse outcomes in patients with coronavirus 2019 disease (COVID-19). Patients with hypertension appear to have a poor prognosis, but there is no direct evidence that hypertension increases the risk of new infection or adverse outcomes independent of age and other risk factors. There is also concern about use of renin-angiotensin system (RAS) inhibitors due to a key role of angiotensin-converting enzyme 2 receptors in the entry of the SARS-CoV-2 virus into cells. However, there is little evidence that use of RAS inhibitors increases the risk of SARS-CoV-2 virus infection or worsens the course of COVID-19. Therefore, antihypertensive therapy with these agents should be continued. In addition to acute respiratory distress syndrome, patients with severe COVID-19 can develop myocardial injury and cytokine storm, resulting in heart failure, arteriovenous thrombosis, and kidney injury. Troponin, N-terminal pro-B-type natriuretic peptide, D-dimer, and serum creatinine are biomarkers for these complications and can be used to monitor patients with COVID-19 and for risk stratification. Other factors that need to be incorporated into patient management strategies during the pandemic include regular exercise to maintain good health status and monitoring of psychological well-being. For the ongoing management of patients with hypertension, telemedicine-based home blood pressure monitoring strategies can facilitate maintenance of good blood pressure control while social distancing is maintained. Overall, multidisciplinary management of COVID-19 based on a rapidly growing body of evidence will help ensure the best possible outcomes for patients, including those with risk factors such as hypertension.", "qid": 20, "docid": "jhkc8of3", "rank": 97, "score": 0.8186746835708618}, {"content": "Title: Angiotensin-Converting Enzyme 2 and Antihypertensives (Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors) in Coronavirus Disease 2019 Content: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is being defined as the worst pandemic disease of modern times. Several professional health organizations have published position papers stating that there is no evidence to change the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in the management of elevated blood pressure in the context of avoiding or treating COVID-19 infection. In this article, we review the evidence on the relationship between the renin-angiotensin-aldosterone system and COVID-19 infection. In agreement with current guidelines, patients with hypertension should continue taking antihypertensive medications as prescribed without interruption. Because ACEIs and ARBs are also used to retard the progression of chronic kidney disease, we suggest that these recommendations also apply to the use of these agents in chronic kidney disease. No differences generally exist between ARBs and ACEIs in terms of efficacy in decreasing blood pressure and improving other outcomes, such as all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. The ACEIs are associated with cough secondary to accumulation of bradykinin and angioedema, and withdrawal rates due to adverse events are lower with ARBs. Given their equal efficacy but fewer adverse events, ARBs could potentially be a more favorable treatment option in patients with COVID-19 at higher risk for severe forms of disease.", "qid": 20, "docid": "kxtxzt9f", "rank": 98, "score": 0.81818026304245}, {"content": "Title: Use of renin-angiotensin-aldosterone system inhibitors and risk of COVID-19 requiring admission to hospital: a case-population study Content: BACKGROUND: Concerns have been raised about the possibility that inhibitors of the renin-angiotensin-aldosterone system (RAAS) could predispose individuals to severe COVID-19; however, epidemiological evidence is lacking. We report the results of a case-population study done in Madrid, Spain, since the outbreak of COVID-19. METHODS: In this case-population study, we consecutively selected patients aged 18 years or older with a PCR-confirmed diagnosis of COVID-19 requiring admission to hospital from seven hospitals in Madrid, who had been admitted between March 1 and March 24, 2020. As a reference group, we randomly sampled ten patients per case, individually matched for age, sex, region (ie, Madrid), and date of admission to hospital (month and day; index date), from Base de datos para la Investigaci\u00f3n Farmacoepidemiol\u00f3gica en Atenci\u00f3n Primaria (BIFAP), a Spanish primary health-care database, in its last available year (2018). We extracted information on comorbidities and prescriptions up to the month before index date (ie, current use) from electronic clinical records of both cases and controls. The outcome of interest was admission to hospital of patients with COVID-19. To minimise confounding by indication, the main analysis focused on assessing the association between COVID-19 requiring admission to hospital and use of RAAS inhibitors compared with use of other antihypertensive drugs. We calculated odds ratios (ORs) and 95% CIs, adjusted for age, sex, and cardiovascular comorbidities and risk factors, using conditional logistic regression. The protocol of the study was registered in the EU electronic Register of Post-Authorisation Studies, EUPAS34437. FINDINGS: We collected data for 1139 cases and 11\u00e2\u0080\u0088390 population controls. Among cases, 444 (39\u00b70%) were female and the mean age was 69\u00b71 years (SD 15\u00b74), and despite being matched on sex and age, a significantly higher proportion of cases had pre-existing cardiovascular disease (OR 1\u00b798, 95% CI 1\u00b762-2\u00b741) and risk factors (1\u00b746, 1\u00b723-1\u00b773) than did controls. Compared with users of other antihypertensive drugs, users of RAAS inhibitors had an adjusted OR for COVID-19 requiring admission to hospital of 0\u00b794 (95% CI 0\u00b777-1\u00b715). No increased risk was observed with either angiotensin-converting enzyme inhibitors (adjusted OR 0\u00b780, 0\u00b764-1\u00b700) or angiotensin-receptor blockers (1\u00b710, 0\u00b788-1\u00b737). Sex, age, and background cardiovascular risk did not modify the adjusted OR between use of RAAS inhibitors and COVID-19 requiring admission to hospital, whereas a decreased risk of COVID-19 requiring admission to hospital was found among patients with diabetes who were users of RAAS inhibitors (adjusted OR 0\u00b753, 95% CI 0\u00b734-0\u00b780). The adjusted ORs were similar across severity degrees of COVID-19. INTERPRETATION: RAAS inhibitors do not increase the risk of COVID-19 requiring admission to hospital, including fatal cases and those admitted to intensive care units, and should not be discontinued to prevent a severe case of COVID-19. FUNDING: Instituto de Salud Carlos III.", "qid": 20, "docid": "d8n4rpod", "rank": 99, "score": 0.8177970051765442}, {"content": "Title: COVID\u201019 and hypertension\u2014evidence and practical management: Guidance from the HOPE Asia Network Content: There are several risk factors for worse outcomes in patients with coronavirus 2019 disease (COVID\u201019). Patients with hypertension appear to have a poor prognosis, but there is no direct evidence that hypertension increases the risk of new infection or adverse outcomes independent of age and other risk factors. There is also concern about use of renin\u2010angiotensin system (RAS) inhibitors due to a key role of angiotensin\u2010converting enzyme 2 receptors in the entry of the SARS\u2010CoV\u20102 virus into cells. However, there is little evidence that use of RAS inhibitors increases the risk of SARS\u2010CoV\u20102 virus infection or worsens the course of COVID\u201019. Therefore, antihypertensive therapy with these agents should be continued. In addition to acute respiratory distress syndrome, patients with severe COVID\u201019 can develop myocardial injury and cytokine storm, resulting in heart failure, arteriovenous thrombosis, and kidney injury. Troponin, N\u2010terminal pro\u2010B\u2010type natriuretic peptide, D\u2010dimer, and serum creatinine are biomarkers for these complications and can be used to monitor patients with COVID\u201019 and for risk stratification. Other factors that need to be incorporated into patient management strategies during the pandemic include regular exercise to maintain good health status and monitoring of psychological well\u2010being. For the ongoing management of patients with hypertension, telemedicine\u2010based home blood pressure monitoring strategies can facilitate maintenance of good blood pressure control while social distancing is maintained. Overall, multidisciplinary management of COVID\u201019 based on a rapidly growing body of evidence will help ensure the best possible outcomes for patients, including those with risk factors such as hypertension.", "qid": 20, "docid": "254z62e4", "rank": 100, "score": 0.8177176713943481}]}
{"query": "what are the mortality rates overall and in specific populations", "hits": [{"content": "Title: Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970-2016: a systematic analysis for the Global Burden of Disease Study 2016. Content: BACKGROUND Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. METHODS We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15-60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0\u00b75% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. FINDINGS Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5-24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates-a measure of relative inequality-increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86\u00b79 years (95% UI 86\u00b77-87\u00b72), and for men in Singapore, at 81\u00b73 years (78\u00b78-83\u00b77) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, and the gap between male and female life expectancy increased with progression to higher levels of SDI. Some countries with exceptional health performance in 1990 in terms of the difference in observed to expected life expectancy at birth had slower progress on the same measure in 2016. INTERPRETATION Globally, mortality rates have decreased across all age groups over the past five decades, with the largest improvements occurring among children younger than 5 years. However, at the national level, considerable heterogeneity remains in terms of both level and rate of changes in age-specific mortality; increases in mortality for certain age groups occurred in some locations. We found evidence that the absolute gap between countries in age-specific death rates has declined, although the relative gap for some age-sex groups increased. Countries that now lead in terms of having higher observed life expectancy than that expected on the basis of development alone, or locations that have either increased this advantage or rapidly decreased the deficit from expected levels, could provide insight into the means to accelerate progress in nations where progress has stalled. FUNDING Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.", "qid": 21, "docid": "eet3v4cs", "rank": 1, "score": 0.746772050857544}, {"content": "Title: Global patterns of mortality in international migrants: a systematic review and meta-analysis. Content: BACKGROUND 258 million people reside outside their country of birth; however, to date no global systematic reviews or meta-analyses of mortality data for these international migrants have been done. We aimed to review and synthesise available mortality data on international migrants. METHODS In this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Library, and Google Scholar databases for observational studies, systematic reviews, and randomised controlled trials published between Jan 1, 2001, and March 31, 2017, without language restrictions. We included studies reporting mortality outcomes for international migrants of any age residing outside their country of birth. Studies that recruited participants exclusively from intensive care or high dependency hospital units, with an existing health condition or status, or a particular health exposure were excluded. We also excluded studies limited to maternal or perinatal outcomes. We screened studies using systematic review software and extracted data from published reports. The main outcomes were all-cause and International Classification of Diseases, tenth revision (ICD-10) cause-specific standardised mortality ratios (SMRs) and absolute mortality rates. We calculated summary estimates using random-effects models. This study is registered with PROSPERO, number CRD42017073608. FINDINGS Of the 12 480 articles identified by our search, 96 studies were eligible for inclusion. The studies were geographically diverse and included data from all global regions and for 92 countries. 5464 mortality estimates for more than 15\u00b72 million migrants were included, of which 5327 (97%) were from high-income countries, 115 (2%) were from middle-income countries, and 22 (<1%) were from low-income countries. Few studies included mortality estimates for refugees (110 estimates), asylum seekers (144 estimates), or labour migrants (six estimates). The summary estimate of all-cause SMR for international migrants was lower than one when compared with the general population in destination countries (0\u00b770 [95% CI 0\u00b765-0\u00b776]; I2=99\u00b78%). All-cause SMR was lower in both male migrants (0\u00b772 [0\u00b763-0\u00b781]; I2=99\u00b78%) and female migrants (0\u00b775 [0\u00b767-0\u00b784]; I2=99\u00b78%) compared with the general population. A mortality advantage was evident for refugees (SMR 0\u00b750 [0\u00b746-0\u00b754]; I2=89\u00b78%), but not for asylum seekers (1\u00b705 [0\u00b789-1\u00b724]; I2=54\u00b74%), although limited data was available on these groups. SMRs for all causes of death were lower in migrants compared with the general populations in the destination country across all 13 ICD-10 categories analysed, with the exception of infectious diseases and external causes. Heterogeneity was high across the majority of analyses. Point estimates of all-cause age-standardised mortality in migrants ranged from 420 to 874 per 100 000 population. INTERPRETATION Our study showed that international migrants have a mortality advantage compared with general populations, and that this advantage persisted across the majority of ICD-10 disease categories. The mortality advantage identified will be representative of international migrants in high-income countries who are studying, working, or have joined family members in these countries. However, our results might not reflect the health outcomes of more marginalised groups in low-income and middle-income countries because little data were available for these groups, highlighting an important gap in existing research. Our results present an opportunity to reframe the public discourse on international migration and health in high-income countries. FUNDING Wellcome Trust, National Institute for Health Research, Medical Research Council, Alliance for Health Policy and Systems Research, Department for International Development, Fogarty International Center, Grand Challenges Canada, International Development Research Centre Canada, Inter-American Institute for Global Change Research, National Cancer Institute, National Heart, Lung and Blood Institute, National Institute of Mental Health, Swiss National Science Foundation, World Diabetes Foundation, UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, and European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group Research Funding for the ESCMID Study Group for Infections in Travellers and Migrants.", "qid": 21, "docid": "ppwviewr", "rank": 2, "score": 0.7387057542800903}, {"content": "Title: Motor vehicle-related death rates--United States, 1999-2005. Content: In 2005, the most recent year for which data are available, 45,520 deaths in the United States were related to motor vehicles. A Healthy People 2010 objective calls for reducing the rate of deaths related to motor vehicles to 9.2 per 100,000 population from a baseline of 15.6 in 1998. To assess progress toward the Healthy People objective and to examine characteristics of motor vehicle--related death rates, CDC analyzed data from the National Vital Statistics System (NVSS) for the period 1999--2005. This report summarizes the results of that analysis, which determined that, during 1999--2005, although annual age-adjusted motor vehicle--related death rates overall were nearly unchanged (range: 15.2--15.7 per 100,000 population), substantial differences were observed by state, U.S. Census region, sex, race, and age group. Among states, the average annual death rate ranged from 7.9 per 100,000 population in Massachusetts to 31.9 in Mississippi. Among regions, the rate ranged from 9.8 per 100,000 population in the Northeast to 19.5 in the South. The rate for men (21.7 per 100,000 population) was more than double the rate for women (9.4); the rate for American Indians/Alaska Natives (27.2) was nearly twice the rate for whites (15.7) and blacks (15.2), and the rate for persons aged 15--24 years (26.8) was 74% higher than the average annual rate overall (15.4). Additional analysis and research to determine the causes of geographic and demographic variations in motor vehicle--related deaths might result in more effective targeted interventions among the states, regions, and populations at greatest risk.", "qid": 21, "docid": "yjt2g95o", "rank": 3, "score": 0.7253141403198242}, {"content": "Title: Estimating Lower Bounds for COVID-19 Mortality from Northern Italian Towns Content: For COVID-19 the Infection Fatality Rate or IFR - a crucial variable in epidemiological modeling - is difficult to estimate because many cases are asymptomatic and the overall infection rate is generally not known. Circumstances in the Italian provinces of Milano, Bergamo, Brescia, and Lodi allow estimation of lower bounds for age- and sex-specific all-cause excess mortality (a proxy for IFR) since anecdotal reports indicate some towns were close to fully infected. Using data from ISTAT on mortality from January 1 through April 15 for 2020 and the three preceding years, I estimate excess mortality by sex and age categories (0-14, 15-54, 55-64, 65-74, and 75+ years) while controlling for town-specific mortality that proxies for town-specific infection rate. The 99th percentile from the tail of the town distribution gives a lower-bound estimate for COVID-19 mortality. The overall population-weighted mortality at the 99th percentile is 1.09 percent (95% CI 1.06-1.14). The age- and sex-specific rates vary considerably: for men age 65-74 the estimate is 2.10 percent (95% CI 1.94-2.28) which is 3.5-times higher than men 55-64 and 2.7-times higher than women 65-74.", "qid": 21, "docid": "0ie6tkgm", "rank": 4, "score": 0.7098987698554993}, {"content": "Title: Reassessing the Global Mortality Burden of the 1918 Influenza Pandemic Content: Mortality estimates of the 1918 influenza pandemic vary considerably, and recent estimates have suggested that there were 50 million to 100 million deaths worldwide. We investigated the global mortality burden using an indirect estimation approach and 2 publicly available data sets: the Human Mortality Database (13 countries) and data extracted from the records of the Statistical Abstract for British India. The all-cause Human Mortality Database was used to estimate mortality annually for 1916\u20131921 for detailed age groups. Three different calculation methods were applied to the data (low, medium, and high scenarios), and we used a multilevel regression model to control for distorting factors (e.g., war and the underlying time trend in mortality). Total pandemic mortality was an estimated 15 million deaths worldwide in 1918 (n = 2.5 million in 1919) after including the rates for British India and controlling for wars and the underlying mortality trend. According to our validity analysis, simulations of total number of deaths being greater than 25 million are not realistic based on the underlying mortality rates included in Human Mortality Database and in British India. Our results suggest the global death impact of the 1918 pandemic was important (n = 17.4 million) but not as severe as most frequently cited estimates.", "qid": 21, "docid": "yb6rs8q7", "rank": 5, "score": 0.7039161920547485}, {"content": "Title: Why Do COVID-19 Fatality Rates Differ Across Countries? An Explorative Cross-country Study Based on Select Indicators Content: In this article, we analyse the factors that determine the fatality rates across 29 economies spread across both the developing and developed world. Recent emerging literature and expert opinions in popular media have indicated various factors that may explain cross-country difference in fatality rates. These factors range from access to public health infrastructure, BCG vaccination policies, demographic structure, restrictive policy interventions and the weather. In addition, articles are examining different kinds of fatality rates that can be explained. Progressing beyond fragmented databases and anecdotal evidence, we have developed a database for such factors, have explored various econometric models to test the explanatory power of these factors in explaining several kinds of fatality rates. Based on available data, our study reveals that factors such as public health system, population age structure, poverty level and BCG vaccination are powerful contributory factors in determining fatality rates. Interactions between factors such as poverty level and BCG vaccination provide interesting insights into the complex interplay of factors. Our analysis suggests that poor citizens\u2019 access to the public healthcare system are worse in many countries irrespective of whether they are developed or developing countries.", "qid": 21, "docid": "98n6ycwe", "rank": 6, "score": 0.7022759914398193}, {"content": "Title: Trends in childhood cancer mortality--United States, 1990-2004. Content: Cancer is the fourth most common cause of death (after unintentional injury, homicide, and suicide) among persons aged 1-19 years in the United States. Because recent childhood cancer mortality has not been well characterized in terms of temporal, demographic, and geographic trends, CDC analyzed cancer death rates among children (defined as aged 0-14 years) and adolescents (defined as aged 15-19 years) for the period 1990-2004 by sex, age group, race, ethnicity, U.S. Census region, and primary cancer site/leading diagnosis, using the most recent data available from the National Vital Statistics System (NVSS). This report describes the results of that analysis, which indicated that, overall, age-adjusted childhood cancer death rates decreased significantly during 1990-2004 among both sexes, both age groups, all races (except American Indians/Alaska Natives [AI/ANs]), Hispanics, non-Hispanics, and all U.S. Census regions. However, decreases in death rates varied among U.S. Census regions and between Hispanics and non-Hispanics. Eliminating racial/ethnic health disparities is one of the overarching goals of Healthy People 2010. Further research is needed to understand geographic and ethnic disparities in childhood cancer death rates. Moreover, cancer prevention and intervention measures should be designed to reach populations that are underserved and at high risk.", "qid": 21, "docid": "0falsc4z", "rank": 7, "score": 0.6998380422592163}, {"content": "Title: Excess mortality from seasonal influenza is negligible below the age of 50 in Israel: implications for vaccine policy Content: PURPOSE: Evaluation of the severity of pandemic influenza requires reliable estimates of mortality attributable to the seasonal influenza. METHODS: Excess age-specific mortality during periods of influenza activity was evaluated in Israel during the period 1999\u20132006 for three death categories. For each respiratory year, the lowest monthly moving average for the mortality rate was subtracted from each month in the period of influenza activity. Average mortality rates in years with minimal influenza activity were deducted from corresponding months to exclude winter mortality unrelated to influenza. The sums of these results were used as estimates of excess mortality rates. RESULTS: Overall excess mortality rates ranged from 7.7 to 36.1 per 100,000 for all causes, and from 4.4 to 24.4 per 100,000 for respiratory and circulatory causes. Influenza was associated with an average of 869 (range 280\u20131,516) deaths annually from respiratory and circulatory diseases during seasons with significant influenza activity. About 90% of the influenza-associated mortality from respiratory and circulatory diseases was in the age group 65+ years and about 1% in the age group <50 years. The age group <50 years accounted for an annual average of seven deaths from respiratory and circulatory diseases. CONCLUSION: Annual mortality associated with seasonal influenza is highly variable. Under the age of 50 years, there is minimal seasonal influenza associated mortality. This information provides an important baseline for evaluating the severity of the A(H1N1) 2009 influenza pandemic, where persons under 50 years of age were often disproportionately represented.", "qid": 21, "docid": "j5p5mtiq", "rank": 8, "score": 0.6953567266464233}, {"content": "Title: Predicted COVID-19 fatality rates based on age, sex, comorbidities, and health system capacity Content: Early reports suggest the fatality rate from COVID-19 varies greatly across countries, but non-random testing and incomplete vital registration systems render it impossible to directly estimate the infection fatality rate (IFR) in many low- and middle-income countries. To fill this gap, we estimate the adjustments required to extrapolate estimates of the IFR from high- to lower-income regions. Accounting for differences in the distribution of age, sex, and relevant comorbidities yields substantial differences in the predicted IFR across 21 world regions, ranging from 0.11% in Western Sub-Saharan Africa to 0.95% for High Income Asia Pacific. However, these predictions must be treated as lower bounds, as they are grounded in fatality rates from countries with advanced health systems. In order to adjust for health system capacity, we incorporate regional differences in the relative odds of infection fatality from childhood influenza. This adjustment greatly diminishes, but does not entirely erase, the demography-based advantage predicted in the lowest income settings, with regional estimates of the predicted COVID-19 IFR ranging from 0.43% in Western Sub-Saharan Africa to 1.74% for Eastern Europe.", "qid": 21, "docid": "oamrcna5", "rank": 9, "score": 0.6940388679504395}, {"content": "Title: Social Disparities in the Evolution of an Epidemiological Profile: Transition Processes in Mortality Between 1971 and 2008 in an Industrialized Middle Income Country: The Case of Hungary Content: The present paper seeks to understand the transformation of mortality patterns in Hungary, by which mortality inequalities by education began to appear in the early 1980s, continued to grow in the following 25 years, and now seem to be stabilising. The first part of this paper overviews the theoretical innovations of the last decades regarding the interpretation of cause-specific mortality dynamics, often referred to as epidemiological transition theories, and their relevance for the analysis of mortality inequalities. The paper then analyses the cause-specific trends of mortality for two educational classes between 1971 and 2008. The trends were corrected for changes in the coding system and divided into linear (stagnating, increasing or decreasing) periods. Causes of death were grouped according to the relationship between the sequences of these periods for the two educational classes. The 57 causes of death were finally clustered into six groups. One group, which is dominated by nutrition-related and cardiovascular diseases, is largely responsible for the onset of mortality inequalities in 1980. The results imply that the quality of nutrition has diverged for the educational classes since 1980, and this fact has left its footprint on the pattern of mortality. The history of food production and availability seems to be in line with nutrition-related mortality, and it is argued that nutrition transition theory provides a very plausible explanatory framework for the growth of mortality inequalities.", "qid": 21, "docid": "yhi83hgq", "rank": 10, "score": 0.6920865774154663}, {"content": "Title: The Contribution of Age Structure to the Number of Deaths from Covid-19 in the UK by Geographical Units Content: This study investigates the contribution of population age structure to mortality from Covid-19 in the UK by geographical units. We project death rates at various spatial scales by applying data on age-specific fatality rates to the area's population by age and sex. Our analysis shows a significant variation in the projected death rates between the constituent countries of the UK, between its regions and within regions. First, Scotland and Wales have higher projected fatality levels from Covid-19 than England, whereas Northern Ireland has lower rate. Second, the infection fatality rates are projected to be substantially higher in small towns and rural areas than those in large urban areas. Third, our analysis shows that within urban regions there are also 'pockets' of high projected death rates. Overall, the areas with high and low fatality rates tend to cluster because of the high residential separation of different population age-groups in the UK. Our analysis also reveals that the Welsh-, Gaelic- and Cornish-speaking communities with relatively old populations are likely to experience heavy population losses if the virus spreads widely across the UK.", "qid": 21, "docid": "vpakh3jk", "rank": 11, "score": 0.6908352971076965}, {"content": "Title: EXCESS MORTALITY FROM COVID-19. WEEKLY EXCESS DEATH RATES BY AGE AND SEX FOR SWEDEN. Content: Objectives: Mortality from Covid-19 is monitored in detail both within as well as between countries with different strategies against the virus. However, death counts and relative risks based on crude numbers can be misleading. Instead, age specific death rates should be used for comparability. Given the difficulty of ascertainment of Covid-19 specific deaths, excess all-cause mortality is currently more appropriate for comparisons. By estimating age- and sex-specific death rates we aim to get more accurate estimates of the excess mortality attributed to Covid-19, as well as the difference between men and women in Sweden. Design: We make use of Swedish register data about total weekly deaths, total population at risk, and estimate age- and sex-specific weekly death rates for 2020 and the 5 previous years. The data is provided by Statistics Sweden. Results: From the first week of April and onwards, the death rates at all ages above 60 are higher than those in previous years in Sweden. Persons above age 80 are dis-proportionally more affected, and men suffer higher levels of excess mortality than women at all ages with 75% higher death rates for males and 50% higher for females. Current excess mortality corresponds to a decline in remaining life expectancy of 3 years for men and 2 years for women. Conclusion: The Covid-19 pandemic has so far had a clear and consistent effect on total mortality in Sweden, with male death rates being comparably more affected. What consequences the pandemic will eventually have on mortality and life expectancy will depend on the progression of the pandemic, the extent that some of the deaths would have occurred in the absence of the pandemic, only somewhat later, the consequences for other health conditions, as well as the health care sector at large.", "qid": 21, "docid": "0o3wjvpx", "rank": 12, "score": 0.6904910802841187}, {"content": "Title: Trends in maternal and neonatal mortality in South Africa: a systematic review. Content: BACKGROUND Measuring and monitoring progress towards Millennium Development Goals (MDG) 4 and 5 required valid and reliable estimates of maternal and child mortality. In South Africa, there are conflicting reports on the estimates of maternal and neonatal mortality, derived from both direct and indirect estimation techniques. This study aimed to systematically review the estimates made of maternal and neonatal mortality in the period from 1990 to 2015 in South Africa and determine trends over this period. METHODS Nationally-representative studies reporting on maternal and neonatal mortality in South Africa were included for synthesis. Literature search for eligible studies was conducted in five electronic databases: Medline, Africa-Wide Information, Scopus, Web of Science and CINAHL. Searches were restricted to articles written in English and presenting data covering the period between 1990 and 2015. Reference lists of retrieved articles were screened for additional publications, and grey literature was searched for relevant documents for the review. Three independent reviewers were involved in study selection, data extractions and achieving consensus. RESULTS In total, 969 studies were retrieved and 670 screened for eligibility yielding 25 studies reporting data on maternal mortality and 14 studies on neonatal mortality. Most of the studies had a low risk of bias. Estimates from the institutional reporting differed from the international metrics with wide uncertainty/confidence intervals. Moreover, modelled estimates were widely divergent from estimates obtained through empirical methods. In the last two decades, both maternal and neonatal mortality appear to have increased up to 2009, followed by a decrease, more pronounced in the care of maternal mortality. CONCLUSION Estimates from both global metrics and institutional reporting, although widely divergent, indicate South Africa has not achieved MDG 4a and 5a goals but made a significant progress in reducing maternal and neonatal mortality. To obtain more accurate estimates, there is a need for applying additional estimation techniques which utilise available multiple data sources to correct for underreporting of these outcomes, perhaps the capture-recapture method. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42016042769.", "qid": 21, "docid": "cjbzogmf", "rank": 13, "score": 0.6901980638504028}, {"content": "Title: The confounded crude case-fatality rates for COVID-19 hide more than they reveal - a comparison of age-specific and age-adjusted rates between six countries Content: Background The reported crude case-fatality rates (CFRs) vary widely between countries. The serious limitations of using crude rates for comparisons are sometimes overlooked. In this paper we examined to what extent the age distribution of the cases is responsible for the differences in CFRs between countries. Methods Data on COVID-19 were extracted from the reports of individual countries. Overall and age-specific CFRs were available for six countries. The CFRs by country were adjusted for age using the direct method, using the combined age-specific number of cases of all six countries as the standard population. Findings The age distribution of the cases varied widely between countries. The crude CFRs varied between 1.6% and 11%. The differences in the age-specific CFRs were much smaller and the age-adjusted rates were much closer than the crude rates. The ratio of the crude CFR for the country with the highest to that with the lowest, was reduced substantially from 7.4 to 2.3 for the age-adjusted rates. Conclusions The age structure of the cases dramatically impacts on the differences in the crude CFRs between countries. Adjusting for age substantially reduces this variation. Other factors such as the differences in the definition of the denominators, the definition of a case and the standard of healthcare are likely to account for much of the residual variation. It is misleading to compare the crude COVID-19 CFRs between countries and should be avoided. Comparisons should be based on age-specific and age-adjusted rates. Key words: COVID-19, case-fatality rates, age-specific rates, age-adjusted rates, confounding", "qid": 21, "docid": "2apo9imk", "rank": 14, "score": 0.6894378662109375}, {"content": "Title: Mortality, morbidity and health in developed societies: a review of data sources Content: The purpose of this paper is to review the major sources of data on mortality, morbidity and health in Europe and in other developed regions in order to examine their potential for analysing mortality and morbidity levels and trends. The review is primarily focused on routinely collected information covering a whole country. No attempt is made to draw up an inventory of sources by country; the paper deals instead with the pros and cons of each source for mortality and morbidity studies in demography. While each source considered separately can already yield useful, though partial, results, record linkage among data sources can significantly improve the analysis. Record linkage can also lead to the detection of possible causal associations that could eventually be confirmed. More generally, Big Data can reveal changing mortality and morbidity trends and patterns that could lead to preventive measures being taken rather than more costly curative ones.", "qid": 21, "docid": "cs9zddms", "rank": 15, "score": 0.688924252986908}, {"content": "Title: Morbidity and mortality in homeless individuals, prisoners, sex workers, and individuals with substance use disorders in high-income countries: a systematic review and meta-analysis. Content: BACKGROUND Inclusion health focuses on people in extremely poor health due to poverty, marginalisation, and multimorbidity. We aimed to review morbidity and mortality data on four overlapping populations who experience considerable social exclusion: homeless populations, individuals with substance use disorders, sex workers, and imprisoned individuals. METHODS For this systematic review and meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library for studies published between Jan 1, 2005, and Oct 1, 2015. We included only systematic reviews, meta-analyses, interventional studies, and observational studies that had morbidity and mortality outcomes, were published in English, from high-income countries, and were done in populations with a history of homelessness, imprisonment, sex work, or substance use disorder (excluding cannabis and alcohol use). Studies with only perinatal outcomes and studies of individuals with a specific health condition or those recruited from intensive care or high dependency hospital units were excluded. We screened studies using systematic review software and extracted data from published reports. Primary outcomes were measures of morbidity (prevalence or incidence) and mortality (standardised mortality ratios [SMRs] and mortality rates). Summary estimates were calculated using a random effects model. FINDINGS Our search identified 7946 articles, of which 337 studies were included for analysis. All-cause standardised mortality ratios were significantly increased in 91 (99%) of 92 extracted datapoints and were 11\u00b786 (95% CI 10\u00b742-13\u00b730; I2=94\u00b71%) in female individuals and 7\u00b788 (7\u00b703-8\u00b774; I2=99\u00b71%) in men. Summary SMR estimates for the International Classification of Diseases disease categories with two or more included datapoints were highest for deaths due to injury, poisoning, and other external causes, in both men (7\u00b789; 95% CI 6\u00b740-9\u00b737; I2=98\u00b71%) and women (18\u00b772; 13\u00b773-23\u00b771; I2=91\u00b75%). Disease prevalence was consistently raised across the following categories: infections (eg, highest reported was 90% for hepatitis C, 67 [65%] of 103 individuals for hepatitis B, and 133 [51%] of 263 individuals for latent tuberculosis infection), mental health (eg, highest reported was 9 [4%] of 227 individuals for schizophrenia), cardiovascular conditions (eg, highest reported was 32 [13%] of 247 individuals for coronary heart disease), and respiratory conditions (eg, highest reported was 9 [26%] of 35 individuals for asthma). INTERPRETATION Our study shows that homeless populations, individuals with substance use disorders, sex workers, and imprisoned individuals experience extreme health inequities across a wide range of health conditions, with the relative effect of exclusion being greater in female individuals than male individuals. The high heterogeneity between studies should be explored further using improved data collection in population subgroups. The extreme health inequity identified demands intensive cross-sectoral policy and service action to prevent exclusion and improve health outcomes in individuals who are already marginalised. FUNDING Wellcome Trust, National Institute for Health Research, NHS England, NHS Research Scotland Scottish Senior Clinical Fellowship, Medical Research Council, Chief Scientist Office, and the Central and North West London NHS Trust.", "qid": 21, "docid": "h9gfyeb8", "rank": 16, "score": 0.6888515949249268}, {"content": "Title: Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Content: BACKGROUND Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). METHODS We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. FINDINGS The highest globally observed HALE at birth for both women and men was in Singapore, at 75\u00b72 years (95% uncertainty interval 71\u00b79-78\u00b76) for females and 72\u00b70 years (68\u00b78-75\u00b71) for males. The lowest for females was in the Central African Republic (45\u00b76 years [42\u00b70-49\u00b75]) and for males was in Lesotho (41\u00b75 years [39\u00b70-44\u00b70]). From 1990 to 2016, global HALE increased by an average of 6\u00b724 years (5\u00b797-6\u00b748) for both sexes combined. Global HALE increased by 6\u00b704 years (5\u00b774-6\u00b727) for males and 6\u00b749 years (6\u00b708-6\u00b777) for females, whereas HALE at age 65 years increased by 1\u00b778 years (1\u00b761-1\u00b793) for males and 1\u00b796 years (1\u00b769-2\u00b713) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2\u00b73% [-5\u00b79 to 0\u00b79]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16\u00b71% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. INTERPRETATION At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. FUNDING Bill & Melinda Gates Foundation.", "qid": 21, "docid": "kzz677r2", "rank": 17, "score": 0.6880760192871094}, {"content": "Title: Calibrating Gompertz in reverse: What is your longevity-risk-adjusted global age?() Content: This paper develops a computational framework for inverting Gompertz\u2013Makeham mortality hazard rates, consistent with compensation laws of mortality for heterogeneous populations, to define a longevity-risk-adjusted global (L-RaG) age. To illustrate its salience and possible applications, the paper calibrates and presents L-RaG values using country data from the Human Mortality Database (HMD). Among other things, the author demonstrates that when properly benchmarked, the longevity-risk-adjusted global age of a 55-year-old Swedish male is 48, whereas a 55-year-old Russian male is closer in age to 67. The paper also discusses the connection between the proposed L-RaG age and the related concept of Biological age, from the medical and gerontology literature. Practically speaking, in a world of growing mortality heterogeneity, the L-RaG age could be used for pension and retirement policy. In the language of behavioral finance and economics, a salient metric that adjusts chronological age for longevity risk might help capture the public\u2019s attention, educate them about lifetime uncertainty and induce many of them to take action \u2014 such as working longer and/or retiring later.", "qid": 21, "docid": "1pezihg6", "rank": 18, "score": 0.6878525018692017}, {"content": "Title: Use of the prevented fraction for the population to determine deaths averted by existing prevalence of physical activity: a descriptive study Content: BACKGROUND: Disease and mortality burdens of unhealthy lifestyle behaviours are often reported. In contrast, the positive narrative around the burdens that an existing behaviour have averted is rarely acknowledged. We aimed to estimate the prevented fraction for the population (PFP) for premature mortality averted by physical activity on a global scale. METHODS: In this descriptive study, we obtained previously published data on physical activity prevalence (2001\u201316) and relative risks of all-cause mortality for 168 countries. We combined the data in Monte-Carlo simulations to estimate country-specific, mean PFP values, corresponding to percentage of mortality averted, and their 95% CIs. High prevented fractions indicated an increased proportion of deaths averted due to physical activity. Using mortality data for all people in a country aged 40\u201374 years, we estimated the number of premature deaths averted for all adults and by gender. We present the median and range of the prevented fractions globally, by WHO region, and by World Bank income classification. FINDINGS: The global median PFP was 15\u00b70% (range 6\u00b76\u201320\u00b75), conservatively equating to 3\u00b79 million (95% CI 2\u00b75\u20135\u00b76) premature deaths averted annually. The African region had the highest median prevented fraction (16\u00b76% [range 12\u00b71\u201320\u00b75]) and the Americas had the lowest (13\u00b71% [10\u00b78\u201316\u00b76]). Low-income countries tended to have higher prevented fractions (group median 17\u00b79% [12\u00b73\u201320\u00b75]) than high-income countries (14\u00b71% [6\u00b76\u201317\u00b78]). Globally, the median prevented fraction was higher for men (16\u00b70% [7\u00b78\u201320\u00b77] than women (14\u00b71% [5\u00b70\u201320\u00b74]). INTERPRETATION: Existing physical activity prevalence has contributed to averting premature mortality across all countries. PFP has utility as an advocacy tool to promote healthy lifestyle behaviours. By making the case of what has been achieved, the prevented fraction can show the value of current investment and services, which might be conducive to political support. FUNDING: UK Medical Research Council, British Heart Foundation, Cancer Research UK, Economic and Social Research Council, National Institute for Health Research, Wellcome Trust, Heart Foundation Australia.", "qid": 21, "docid": "o38tfjh7", "rank": 19, "score": 0.6866258382797241}, {"content": "Title: The potential effect of the African population age structure on COVID-19 mortality Content: Currently (mid May 2020), most active cases of COVID-19 are found in Europe and North America while it is still in the initial phases in Africa. As COVID-19 mortality occurs mainly in elderly and as Africa has a comparably young population, the death rates should be lower than on other continents. We calculated standardised mortality ratios (SMR) using age-specific case fatality rates for COVID-19 and the age structure of the population of Africa and of other continents. Compared to a European or Northern American population, the standardised mortality ratio was only 0.22 and 0.25, respectively, corresponding to reduction of deaths rates to a quarter. Compared to the Asian and Latin American & Caribbean population, the SMR was 0.43 and 0.44, respectively, corresponding to half the death rate for Africa. It is useful to quantify the isolated effect of the African age-structure on potential COVID-19 mortality for illustrative and communication purposes, keeping in mind the importance of public health measures that have been shown to be effective in reducing cases and deaths. The different aspect of age pyramids of a European and an African population are striking and the potential implications for the pandemic are often discussed but rarely quantified.", "qid": 21, "docid": "vzmn6zep", "rank": 20, "score": 0.6866238117218018}, {"content": "Title: Black, Asian and Minority Ethnic groups in England are at increased risk of death from COVID-19: indirect standardisation of NHS mortality data. Content: Background: International and UK data suggest that Black, Asian and Minority Ethnic (BAME) groups are at increased risk of infection and death from COVID-19. We aimed to explore the risk of death in minority ethnic groups in England using data reported by NHS England. Methods: We used NHS data on patients with a positive COVID-19 test who died in hospitals in England published on 28th April, with deaths by ethnicity available from 1st March 2020 up to 5pm on 21 April 2020. We undertook indirect standardisation of these data (using the whole population of England as the reference) to produce ethnic specific standardised mortality ratios (SMRs) adjusted for age and geographical region. Results: The largest total number of deaths in minority ethnic groups were Indian (492 deaths) and Black Caribbean (460 deaths) groups. Adjusting for region we found a lower risk of death for White Irish (SMR 0.52; 95%CIs 0.45-0.60) and White British ethnic groups (0.88; 95%CIs 0.86-0.0.89), but increased risk of death for Black African (3.24; 95%CIs 2.90-3.62), Black Caribbean (2.21; 95%CIs 2.02-2.41), Pakistani (3.29; 95%CIs 2.96-3.64), Bangladeshi (2.41; 95%CIs 1.98-2.91) and Indian (1.70; 95%CIs 1.56-1.85) minority ethnic groups. Conclusion: Our analysis adds to the evidence that BAME people are at increased risk of death from COVID-19 even after adjusting for geographical region, but was limited by the lack of data on deaths outside of NHS settings and ethnicity denominator data being based on the 2011 census. Despite these limitations, we believe there is an urgent need to take action to reduce the risk of death for BAME groups and better understand why some ethnic groups experience greater risk. Actions that are likely to reduce these inequities include ensuring adequate income protection, reducing occupational risks, reducing barriers in accessing healthcare and providing culturally and linguistically appropriate public health communications.", "qid": 21, "docid": "519b3ir1", "rank": 21, "score": 0.6860350370407104}, {"content": "Title: Estimated inequities in COVID-19 infection fatality rates by ethnicity for Aotearoa New Zealand Content: There is limited evidence as to how COVID-19 infection fatality rates (IFR) may vary by ethnicity. We combine demographic and health data for ethnic groupings in Aotearoa New Zealand with international data on IFR for different age groups to estimate inequities in IFR by ethnicity. We find that, if age is the dominant factor determining IFR, estimated IFR for M\u0101ori is around 50% higher than non-M\u0101ori. If underlying health conditions are more important than age per se, then estimated IFR for M\u0101ori is more than 2.5 times that of New Zealand European, and estimated IFR for Pasifika is almost double that of New Zealand European. IFRs for M\u0101ori and Pasifika are likely to be increased above these estimates by racism within the healthcare system and other inequities not reflected in official data. IFR does not account for differences among ethnicities in COVID-19 incidence, which could be higher in M\u0101ori and Pasifika as a result of crowded housing and higher inter-generational contact rates. These factors should be included in future disease incidence modelling. The communities at the highest risk will be those with elderly populations, and M\u0101ori and Pasifika communities, where the compounded effects of underlying health conditions, socioeconomic disadvantage, and structural racism result in imbricated risk of contracting COVID-19, becoming unwell, and death.", "qid": 21, "docid": "kxhq5hok", "rank": 22, "score": 0.6858972311019897}, {"content": "Title: Influenza-associated Deaths in Tropical Singapore Content: We used a regression model to examine the impact of influenza on death rates in tropical Singapore for the period 1996\u20132003. Influenza A (H3N2) was the predominant circulating influenza virus subtype, with consistently significant and robust effect on mortality rates. Influenza was associated with an annual death rate from all causes, from underlying pneumonia and influenza, and from underlying circulatory and respiratory conditions of 14.8 (95% confidence interval 9.8\u201319.8), 2.9 (1.0\u20135.0), and 11.9 (8.3\u201315.7) per 100,000 person-years, respectively. These results are comparable with observations in the United States and subtropical Hong Kong. An estimated 6.5% of underlying pneumonia and influenza deaths were attributable to influenza. The proportion of influenza-associated deaths was 11.3 times higher in persons age >65 years than in the general population. Our findings support the need for influenza surveillance and annual influenza vaccination for at-risk populations in tropical countries.", "qid": 21, "docid": "suw7yov6", "rank": 23, "score": 0.6857284903526306}, {"content": "Title: Improved measurement of racial/ethnic disparities in COVID-19 mortality in the United States Content: Different estimation methods produce diverging accounts of racial/ethnic disparities in COVID-19 mortality in the United States. The Center for Disease Control's decision to present the racial/ethnic distribution of COVID-19 deaths at the state level alongside the weighted racial/ethnic distribution of the counties within each state reporting those death -- in effect, a geographic adjustment -- makes it seem that Whites have the highest death rates. Age adjustment procedures used by others, including the New York City Department of Health and Mental Hygiene, lead to the opposite conclusion that Blacks and Hispanics are dying from COVID-19 at higher rates than Whites. In this paper, we use indirect standardization methods to adjust per capita death rates for both age and geography simultaneously, avoiding the one-sided adjustment procedures currently in use. Using CDC data, we find age-and-place-adjusted COVID-19 death rates are 80% higher for Blacks and over 50% higher for Hispanics, relative to Whites, on a national level. State-specific estimates show wide variation in mortality disparities. Comparison with nonepidemic mortality reveals potential roles for preexisting health disparities and differential rates of infection and care.", "qid": 21, "docid": "fyna1euk", "rank": 24, "score": 0.6848770380020142}, {"content": "Title: Death, Demography and the Denominator:New Influenza-18 Mortality Estimates for Ireland Content: Using the Irish experience of the Spanish flu, we demonstrate that pandemic mortality statistics are sensitive to the demographic composition of a country. We build a new demographic database for Ireland's 32 counties with vital statistics on births, ageing, migration and deaths. We then show how age-at-death statistics in 1918 and 1919 should be reinterpreted in light of these data. Our new estimates suggest the very young were most impacted by the flu. New studies of the economic impact of Influenza-18 must better control for demographic factors if they are to yield useful policy-relevant results. Covid-19 mortality statistics must go through a similar procedure so policymakers can better target their public health interventions.", "qid": 21, "docid": "hyz6fwt9", "rank": 25, "score": 0.6837692260742188}, {"content": "Title: The effects of environmental stressors on the mortality of the oldest old male population in Hong Kong, 1977-2006. Content: Although age-sex-specific mortality rates were decreasing over the years, such a trend was not observed for the male population aged 85 or above (the oldest old) in Hong Kong. Despite literature suggesting that environmental stressors were associated with higher mortality, the adverse effects of socioeconomic and political events were seldom included. Hence, this study explored the relationship between environmental stressors covering adverse weather conditions as well as key socioeconomic and political events and fluctuations in the oldest old mortality rates in Hong Kong during the period 1977 to 2006. The oldest old mortality rates in Hong Kong were observed to have a likelihood of being associated with these environmental stressors. Furthermore, men appeared to be more susceptible to these risk factors than did women. More care and attention should be given to the oldest old men, in particular, during periods of socioeconomic or political upheavals. A cohort study would be useful to study these stressors in greater detail.", "qid": 21, "docid": "l855jlqu", "rank": 26, "score": 0.6805148124694824}, {"content": "Title: Evidence for ethnic inequalities in mortality related to COVID-19 infections: Findings from an ecological analysis of England and Wales Content: Background In the absence of direct data on ethnic inequalities in COVID-19 related mortality in the UK, we examine the relationship between ethnic composition of an area and rate of mortality in the area. Methods Ecological analysis using COVID-19 related mortality rates occurring by 24th April 2020, and ethnic composition of the population, across local authorities in England and Wales. Account is taken of age, population density, area deprivation and pollution. Results For every 1% rise in proportion of the population who are ethnic minority, COVID-19 related deaths increased by 5.10 (3.99 to 6.21) per million. This rise is present for each ethnic minority category examined. The size of this increase is a little reduced in a fully adjusted model, suggesting that some of the association results from ethnic minority people living in more densely populated, more polluted and more deprived areas. This estimate suggests that the average England and Wales COVID-19 related death rate would rise by 25% in a local authority with twice the average number of ethnic minority people. Discussion We find clear evidence that rates of COVID-19 related mortality within a local authority increase as the proportion of the population who are ethnic minority increases. We suggest that this is a consequence of social and economic inequalities, including among key workers, driven by entrenched structural and institutional racism and racial discrimination. We argue that these factors should be central to any investigation of ethnic inequalities in COVID-19 outcomes.", "qid": 21, "docid": "2xs29l81", "rank": 27, "score": 0.6804533004760742}, {"content": "Title: Black, Asian and Minority Ethnic groups in England are at increased risk of death from COVID-19: indirect standardisation of NHS mortality data Content: Background: International and UK data suggest that Black, Asian and Minority Ethnic (BAME) groups are at increased risk of infection and death from COVID-19. We aimed to explore the risk of death in minority ethnic groups in England using data reported by NHS England. Methods: We used NHS data on patients with a positive COVID-19 test who died in hospitals in England published on 28th April, with deaths by ethnicity available from 1st March 2020 up to 5pm on 21 April 2020. We undertook indirect standardisation of these data (using the whole population of England as the reference) to produce ethnic specific standardised mortality ratios (SMRs) adjusted for age and geographical region. Results: The largest total number of deaths in minority ethnic groups were Indian (492 deaths) and Black Caribbean (460 deaths) groups. Adjusting for region we found a lower risk of death for White Irish (SMR 0.52; 95%CIs 0.45-0.60) and White British ethnic groups (0.88; 95%CIs 0.86-0.0.89), but increased risk of death for Black African (3.24; 95%CIs 2.90-3.62), Black Caribbean (2.21; 95%CIs 2.02-2.41), Pakistani (3.29; 95%CIs 2.96-3.64), Bangladeshi (2.41; 95%CIs 1.98-2.91) and Indian (1.70; 95%CIs 1.56-1.85) minority ethnic groups. Conclusion: Our analysis adds to the evidence that BAME people are at increased risk of death from COVID-19 even after adjusting for geographical region. We believe there is an urgent need to take action to reduce the risk of death for BAME groups and better understand why some ethnic groups experience greater risk. Actions that are likely to reduce these inequities include ensuring adequate income protection (so that low paid and zero-hours contract workers can afford to follow social distancing recommendations), reducing occupational risks (such as ensuring adequate personal protective equipment), reducing barriers in accessing healthcare and providing culturally and linguistically appropriate public health communications.", "qid": 21, "docid": "2xeccfji", "rank": 28, "score": 0.6795760989189148}, {"content": "Title: How Large Was the Mortality Increase Directly and Indirectly Caused by the COVID-19 Epidemic? An Analysis on All-Causes Mortality Data in Italy Content: Objective: Overall mortality is a relevant indicator of the population burden during an epidemic. It informs on both undiagnosed cases and on the effects of health system disruption. Methods: We aimed at evaluating the extent of the total death excess during the COVID-19 epidemic in Italy. Data from 4433 municipalities providing mortality reports until April 15th, 2020 were included for a total of 34.5 million residents from all Italian regions. Data were analyzed by region, sex and age, and compared to expected from 2015\u20132019. Results: In both genders, overall mortality was stable until February 2020 and abruptly increased from March 1st onwards. Within the municipalities studied, 77,339 deaths were observed in the period between March 1st to April 15th, 2020, in contrast to the 50,822.6 expected. The rate ratio was 1.11 before age 60 and 1.55 afterwards. Both sexes were affected. The excess was greater in the regions most affected by COVID-19 but always exceeded the deaths attributed to COVID-19. The extrapolation to the total Italian population suggests an excess of 45,033 deaths in the study period, while the number of COVID\u201319 deaths was 21,046. Conclusion: Our paper shows a large death excess during the COVID-19 epidemic in Italy; greater than the number attributed to it. Possible causes included both the undetected cases and the disruption of the Health Service organization. Timely monitoring of overall mortality based on unbiased nationwide data is an essential tool for epidemic control.", "qid": 21, "docid": "t9qdiz7n", "rank": 29, "score": 0.6795012950897217}, {"content": "Title: How Large Was the Mortality Increase Directly and Indirectly Caused by the COVID-19 Epidemic? An Analysis on All-Causes Mortality Data in Italy Content: Objective: Overall mortality is a relevant indicator of the population burden during an epidemic. It informs on both undiagnosed cases and on the effects of health system disruption. Methods: We aimed at evaluating the extent of the total death excess during the COVID-19 epidemic in Italy. Data from 4433 municipalities providing mortality reports until April 15th, 2020 were included for a total of 34.5 million residents from all Italian regions. Data were analyzed by region, sex and age, and compared to expected from 2015-2019. Results: In both genders, overall mortality was stable until February 2020 and abruptly increased from March 1st onwards. Within the municipalities studied, 77,339 deaths were observed in the period between March 1st to April 15th, 2020, in contrast to the 50,822.6 expected. The rate ratio was 1.11 before age 60 and 1.55 afterwards. Both sexes were affected. The excess was greater in the regions most affected by COVID-19 but always exceeded the deaths attributed to COVID-19. The extrapolation to the total Italian population suggests an excess of 45,033 deaths in the study period, while the number of COVID-19 deaths was 21,046. Conclusion: Our paper shows a large death excess during the COVID-19 epidemic in Italy; greater than the number attributed to it. Possible causes included both the undetected cases and the disruption of the Health Service organization. Timely monitoring of overall mortality based on unbiased nationwide data is an essential tool for epidemic control.", "qid": 21, "docid": "ekxz577j", "rank": 30, "score": 0.6793848276138306}, {"content": "Title: Long-term trends in seasonality of mortality in urban Madagascar: the role of the epidemiological transition Content: Background: Seasonal patterns of mortality have been identified in Sub-Saharan Africa but their changes over time are not well documented. Objective: Based on death notification data from Antananarivo, the capital city of Madagascar, this study assesses seasonal patterns of all-cause and cause-specific mortality by age groups and evaluates how these patterns changed over the period 1976\u20132015. Methods: Monthly numbers of deaths by cause were obtained from death registers maintained by the Municipal Hygiene Office in charge of verifying deaths before the issuance of burial permits. Generalized Additive Mixed regression models (GAMM) were used to test for seasonality in mortality and its changes over the last four decades, controlling for long-term trends in mortality. Results: Among children, risks of dying were the highest during the hot and rainy season, but seasonality in child mortality has significantly declined since the mid-1970s, as a result of declines in the burden of infectious diseases and nutritional deficiencies. In adults aged 60 and above, all-cause mortality rates are the highest in the dry and cold season, due to peaks in cardiovascular diseases, with little change over time. Overall, changes in the seasonality of all-cause mortality have been driven by shifts in the hierarchy of causes of death, while changes in the seasonality within broad categories of causes of death have been modest. Conclusion: Shifts in disease patterns brought about by the epidemiological transition, rather than changes in seasonal variation in cause-specific mortality, are the main drivers of trends in the seasonality of all-cause mortality.", "qid": 21, "docid": "z68j0c63", "rank": 31, "score": 0.6789649724960327}, {"content": "Title: Beyond Deaths per Capita: Three CoViD-19 Mortality Indicators for Temporal and International Comparisons Content: CoViD-19 deaths to population size ratios fail to account for well-documented age and sex differences in CoViD-19 mortality. To assess trends across populations for which CoViD-19 deaths might not be available by age and sex, an indirect age-and-sex adjustment can still be performed. The corresponding Comparative CoViD-19 Mortality Ratio (CCMR) only requires population age and sex compositions. To compare CoViD-19 and overall mortality levels, the Crude Death Rate (CDR) and life expectancy at birth for recent calendar years are the most widely available overall mortality indicators. Readily comparable to an annual CDR, a Crude CoViD-19 Death Rate (CCDR) can be calculated for periods of any duration. CoViD-19-induced declines in projected life expectancy at birth for 2020 can also be calculated from existing life tables. We calculate the CCMR and CCDR for the period from their first CoViD-19 death to the present using US age and sex data and current estimates of CoViD-19 deaths in 166 Countries whose population composition is available from the UN, 28 Provinces in China, the 50 United States and DC. Across these 245 populations, 14 States and 11 Countries have CCMR values above 1\u2014the US value by construction. Most affected to date, the period CCDR in New York exceeds its CDR for the most recent year available (7.83 per thousand in 2017). We also calculate CCMR and CCDR values corresponding to projections for the 50 States and DC, and for 49 countries, for which we can additionally calculate reductions in 2020 life expectancy at birth using UN life tables. This suggests life-expectancy reductions between .5 and 1 year for 7 European Countries, 3 South-American Countries and the US. The .55 reduction in the U.S. amounts to nearly twice the largest single-year decline induced by HIV/AIDS (\u2212.3 between 1992 and 1993) or the total decline induced by opioid overdoses (also \u2212.3 between 2014 and 2017), and would bring US life expectancy at birth down to its lowest level since 2008. As current CoViD-19 death counts likely underestimate the total increase in deaths and current projections do not account for possible new infection waves later this year, the impact on 2020 life expectancies at birth should be expected to exceed these figures.", "qid": 21, "docid": "peg0m87x", "rank": 32, "score": 0.6777920126914978}, {"content": "Title: Did elderly people living in small towns or rural areas suffer heavier disease burden during the COVID-19 epidemic? Content: Background: Health disparities were often overlooked during the emerging epidemic. Objectives: This study examined geographic differences in the rates of health care use and deaths among elderly patients. Methods: Based on individual patient records, multivariate Poisson and logistic models were used to calculate adjusted incidences of COVID-19 and probabilities of emergency department (ED) visits, hospitalizations and deaths. Results: Of 8,203 elderly patients, 11% died. Elderly people living in small metropolitan areas were half as likely to be diagnosed with COVID-19. Elderly female patients living in small metropolitan areas had much lower rates of ED visits (23% vs. 34%; Odds Ratio (OR): 0.58; 95%confidence interval (CI): 0.41-0.81; p=0.002) and hospitalizations (22% vs. 31%; OR: 0.62; 95%CI: 0.44 - 0.87; p=0.006) than those living in large metropolitan areas. Furthermore, those living in non-metropolitan areas were more likely to be hospitalized than those living in large metropolitan areas (44% vs. 33%; OR: 1.46; 95%CI: 1.07-1.99; p=0.016), especially among elderly men (51% vs. 35%; OR:1.86; 95%CI: 1.18-2.93; p=0.008). Finally, there was a significant linear trend in hospitalization rates among elderly male patients (p for trend = 0.01). Conclusions: Profound health disparities exist in the time of emerging epidemic.", "qid": 21, "docid": "m71rwh67", "rank": 33, "score": 0.6777360439300537}, {"content": "Title: Ethnic variations in morbidity and mortality from lower respiratory tract infections: a retrospective cohort study. Content: OBJECTIVE There is evidence of substantial ethnic variations in asthma morbidity and the risk of hospitalisation, but the picture in relation to lower respiratory tract infections is unclear. We carried out an observational study to identify ethnic group differences for lower respiratory tract infections. DESIGN A retrospective, cohort study. SETTING Scotland. PARTICIPANTS 4.65 million people on whom information was available from the 2001 census, followed from May 2001 to April 2010. MAIN OUTCOME MEASURES Hospitalisations and deaths (any time following first hospitalisation) from lower respiratory tract infections, adjusted risk ratios and hazard ratios by ethnicity and sex were calculated. We multiplied ratios and confidence intervals by 100, so the reference Scottish White population's risk ratio and hazard ratio was 100. RESULTS Among men, adjusted risk ratios for lower respiratory tract infection hospitalisation were lower in Other White British (80, 95% confidence interval 73-86) and Chinese (69, 95% confidence interval 56-84) populations and higher in Pakistani groups (152, 95% confidence interval 136-169). In women, results were mostly similar to those in men (e.g. Chinese 68, 95% confidence interval 56-82), although higher adjusted risk ratios were found among women of the Other South Asians group (145, 95% confidence interval 120-175). Survival (adjusted hazard ratio) following lower respiratory tract infection for Pakistani men (54, 95% confidence interval 39-74) and women (31, 95% confidence interval 18-53) was better than the reference population. CONCLUSIONS Substantial differences in the rates of lower respiratory tract infections amongst different ethnic groups in Scotland were found. Pakistani men and women had particularly high rates of lower respiratory tract infection hospitalisation. The reasons behind the high rates of lower respiratory tract infection in the Pakistani community are now required.", "qid": 21, "docid": "nvmncuzn", "rank": 34, "score": 0.6771522760391235}, {"content": "Title: Severe Acute Respiratory Illness Deaths in Sub-Saharan Africa and the Role of Influenza: A Case Series From 8 Countries Content: Background. Data on causes of death due to respiratory illness in Africa are limited. Methods. From January to April 2013, 28 African countries were invited to participate in a review of severe acute respiratory illness (SARI)\u2013associated deaths identified from influenza surveillance during 2009\u20132012. Results. Twenty-three countries (82%) responded, 11 (48%) collect mortality data, and 8 provided data. Data were collected from 37 714 SARI cases, and 3091 (8.2%; range by country, 5.1%\u201325.9%) tested positive for influenza virus. There were 1073 deaths (2.8%; range by country, 0.1%\u20135.3%) reported, among which influenza virus was detected in 57 (5.3%). Case-fatality proportion (CFP) was higher among countries with systematic death reporting than among those with sporadic reporting. The influenza-associated CFP was 1.8% (57 of 3091), compared with 2.9% (1016 of 34 623) for influenza virus\u2013negative cases (P < .001). Among 834 deaths (77.7%) tested for other respiratory pathogens, rhinovirus (107 [12.8%]), adenovirus (64 [6.0%]), respiratory syncytial virus (60 [5.6%]), and Streptococcus pneumoniae (57 [5.3%]) were most commonly identified. Among 1073 deaths, 402 (37.5%) involved people aged 0\u20134 years, 462 (43.1%) involved people aged 5\u201349 years, and 209 (19.5%) involved people aged \u226550 years. Conclusions. Few African countries systematically collect data on outcomes of people hospitalized with respiratory illness. Stronger surveillance for deaths due to respiratory illness may identify risk groups for targeted vaccine use and other prevention strategies.", "qid": 21, "docid": "la23vxdt", "rank": 35, "score": 0.6771512031555176}, {"content": "Title: The sociospatial factors of death: Analyzing effects of geospatially-distributed variables in a Bayesian mortality model for Hong Kong Content: Human mortality is in part a function of multiple socioeconomic factors that differ both spatially and temporally. Adjusting for other covariates, the human lifespan is positively associated with household wealth. However, the extent to which mortality in a geographical region is a function of socioeconomic factors in both that region and its neighbors is unclear. There is also little information on the temporal components of this relationship. Using the districts of Hong Kong over multiple census years as a case study, we demonstrate that there are differences in how wealth indicator variables are associated with longevity in (a) areas that are affluent but neighbored by socially deprived districts versus (b) wealthy areas surrounded by similarly wealthy districts. We also show that the inclusion of spatially-distributed variables reduces uncertainty in mortality rate predictions in each census year when compared with a baseline model. Our results suggest that geographic mortality models should incorporate nonlocal information (e.g., spatial neighbors) to lower the variance of their mortality estimates, and point to a more in-depth analysis of sociospatial spillover effects on mortality rates.", "qid": 21, "docid": "x35haoyb", "rank": 36, "score": 0.6769874095916748}, {"content": "Title: Differences in race and other state\u2010level characteristics and associations with mortality from COVID\u201019 infection Content: As reporting of COVID\u201019 at the US state level has become more granular, many states have reported a higher proportion of deaths among African\u2010Americans. In our study, we assessed state level data on race, population density, age, obesity rates, insurance data, GDP, per capita healthcare resources (hospital\u2010beds/ventilators per\u2010capita), median household income and high\u2010school graduation rates. We report a higher death rate among states with a greater proportion of African\u2010American residents despite adjusting for case rates and state\u2010level factors. To the best of our knowledge this is the first study looking at state level data (from across the US) and mortality with COVID\u201019. This article is protected by copyright. All rights reserved.", "qid": 21, "docid": "rxgnrrx8", "rank": 37, "score": 0.6766751408576965}, {"content": "Title: Serology-informed estimates of SARS-COV-2 infection fatality risk in Geneva, Switzerland Content: The infection fatality risk (IFR) is the average number of deaths per infection by a pathogen and is key to characterizing the severity of infection across the population and for specific demographic groups. To date, there are few empirical estimates of IFR published due to challenges in measuring infection rates. Outside of closed, closely surveilled populations where infection rates can be monitored through viral surveillance, we must rely on indirect measures of infection, like specific antibodies. Representative seroprevalence studies provide an important avenue for estimating the number of infections in a community, and when combined with death counts can lead to robust estimates of the IFR. We estimated overall and age-specific IFR for the canton of Geneva, Switzerland using age-stratified daily case and death incidence reports combined with five weekly population-based seroprevalence estimates. From February 24th to June 2nd there were 5'039 confirmed cases and 286 reported deaths within Geneva (population of 506'765). We inferred age-stratified (5-9, 10-19, 20-49, 50-65 and 65+) IFRs by linking the observed number of deaths to the estimated number of infected individuals from each serosurvey. We account for the delays between infection and seroconversion as well as between infection and death. Inference is drawn in a Bayesian framework that incorporates uncertainty in seroprevalence estimates (supplement). Of the 286 reported deaths caused by SARS-CoV-2, the youngest person to die was 31 years old. Infected individuals younger than 50 years experienced statistically similar IFRs (range 0.00032-0.0016%), which increases to 0.14% (95% CrI 0.096-0.19) for those 50-64 years old to 5.6% (95% CrI 4.3-7.4) for those 65 years and older (supplement). After accounting for demography and age-specific seroprevalence, we estimate a population-wide IFR of 0.64% (95% CrI 0.38-0.98). Our results are subject to two notable limitations. Among the 65+ age group that died of COVID-19 within Geneva, 50% were reported among residents of assisted care facilities, where around 0.8% of the Geneva population resides. While the serosurvey protocol did not explicitly exclude these individuals, they are likely to have been under-represented. This would lead to an overestimation of the IFR in the 65+ age group if seroprevalence in this institutionalized population was higher than in the general population (supplement). Further, our IFR estimates are based on current evidence regarding post-infection antibody kinetics, which may differ between severe and mild infections. If mild infections have significantly lower and short-lived antibody responses, our estimates of IFR may be biased upwards. Estimates of IFR are key for understanding the true pandemic burden and for weighing different risk reduction strategies. The IFR is not solely determined by host and pathogen biology, but also by the capacity of health systems to treat severe cases. Despite having among the highest per capita incidence in Switzerland, Geneva's health system accommodated the influx of cases needing intensive care (peak of 80/110 ICU-beds including surge capacity) while maintaining care quality standards. As such, our IFR estimates can be seen as a best-case scenario with respect to health system capacity. Our results reveal that population-wide estimates of IFR mask great heterogeneity by age and point towards the importance of age-targeted interventions to reduce exposures among those at highest risk of death.", "qid": 21, "docid": "zr74ec1u", "rank": 38, "score": 0.6753020286560059}, {"content": "Title: Estimating excess 1- year mortality from COVID-19 according to underlying conditions and age in England: a rapid analysis using NHS health records in 3.8 million adults Content: RAPID COMMUNICATION 22 March 2020 Estimating excess 1- year mortality from COVID-19 according to underlying conditions and age in England: a rapid analysis using NHS health records in 3.8 million adults Background: The medical, health service, societal and economic impact of the COVID-19 emergency has unknown effects on overall population mortality. Previous models of population mortality are based on death over days among infected people, nearly all of whom (to date at least) have underlying conditions. Models have not incorporated information on high risk conditions or their longer term background (pre-COVID-19) mortality. We estimated the excess number of deaths over 1 year under different COVID-19 incidence rates and differing mortality impacts. Methods: Using population based linked primary and secondary care electronic health records in England (HDR UK - CALIBER), we report the prevalence of underlying conditions defined by UK Public Health England COVID-19 guidelines (16 March 2020) in 3,862,012 individuals aged \u226530 years from 1997-2017. We used previously validated phenotypes, openly available (https://caliberresearch.org/portal), for each condition using ICD-10 diagnosis, Read, procedure and medication codes. We estimated the 1-year mortality in each condition, and developed simple models of excess COVID-19-related deaths assuming relative risk (RR) of the impact of the emergency (compared to background mortality) of 1.2, 1.5 and 2.0. Findings: 20.0% of the population are at risk according to current PHE guidelines, of which; 13.7% were age>70 years and 6.3% aged \u226470 years with \u22651 underlying condition (cardiovascular disease (2.3%), diabetes (2.2%), steroid therapy (1.9%), severe obesity (0.9%), chronic kidney disease (0.6%) and chronic obstructive pulmonary disease, COPD (0.5%). Multimorbidity (co-occurrence of \u22652 conditions in an individual) was common (10.1%). The 1-year mortality in the at-risk population was 4.46%, and age and underlying conditions combine to influence background risk, varying markedly across conditions (5.9% in age>70 years, 8.6% for COPD and 13.1% in those with \u22653 or more conditions). In a suppression scenario (at SARS CoV2 rates of 0.001% of the UK population), there would be minimal excess deaths (3 and 7 excess deaths at relative risk, RR, 1.5 and 2.0 respectively). At SARS CoV2 rates of 10% of the UK population (mitigation) the model estimates the numbers of excess deaths as: 13791, 34479 and 68957 (at RR 1.2, 1.5 and 2.0 respectively). At SARS CoV2 rates of 80% in the UK population (do-nothing), the model estimates the number of excess deaths as 110332, 275,830 and 551,659 (at RR 1.2, 1.5 and 2.0) respectively. Interpretation: We provide the public, researchers and policy makers a simple model to estimate the excess mortality over 1 year from COVID-19, based on underlying conditions at different ages. If the relative mortality impact of COVID-19 were to be about 20% (similar magnitude as the established winter vs summer mortality excess), then the excess deaths would be 0 when 1 in 100 000 (suppression), 13791 when 1 in 10 (mitigation) and 110332 when 8 in 10 are infected (do nothing) scenario. However, the relative impact of COVID-19 is unknown. If the emergency were to double the mortality risk, then we estimate 7, 68957 and 551,659 excess deaths in the same scenarios. These results may inform the need for more stringent suppression measures as well as efforts to target those at highest risk for a range of preventive interventions.", "qid": 21, "docid": "11hi1jel", "rank": 39, "score": 0.675221860408783}, {"content": "Title: A Note on UK Covid19 death rates by religion: which groups are most at risk? Content: There has been great concern in the UK that people from the BAME (Black And Minority Ethnic) community have a far higher risk of dying from Covid19 than those of other ethnicities. However, the overall fatalities data from the Government's ONS (Office of National Statistics) most recent report on deaths by religion shows that Jews (very few of whom are classified as BAME) have a much higher risk than those of religions (Hindu, Sikh, Muslim) with predominantly BAME people. This apparently contradictory result is, according to the ONS statistical analysis, implicitly explained by age as the report claims that, when 'adjusted for age' Muslims have the highest fatality risk. However, the report fails to provide the raw data to support this. There are many factors other than just age that must be incorporated into any analysis of the observed data before making definitive conclusions about risk based on religion/ethnicity. We propose the need for a causal model for this. If we discount unknown genetic factors, then religion and ethnicity have NO impact at all on a person's Covid19 death risk once we know their age, underlying medical conditions, work/living conditions, and extent of social distancing.", "qid": 21, "docid": "4aool4q0", "rank": 40, "score": 0.6752029657363892}, {"content": "Title: Racial and Ethnic Disparities in Population Level Covid-19 Mortality Content: Background: Current reporting of Covid-19 mortality data by race and ethnicity across the United States could bias our understanding of population-mortality disparities. Moreover, stark differences in age distribution by race and ethnicity groups are seldom accounted for in analyses. Methods: To address these gaps, we conducted a cross-sectional study using publicly-reported Covid-19 mortality data to assess the quality of race and ethnicity data (Black, Latinx, white), and estimated age-adjusted disparities using a random effects meta-analytic approach. Results: We found only 28 states, and NYC, reported race and ethnicity-stratified Covid-19 mortality along with large variation in the percent of missing race and ethnicity data by state. Aggregated relative risk of death estimates for Black compared to the white population was 3.57 (95% CI: 2.84-4.48). Similarly, Latinx population displayed 1.88 (95% CI: 1.61-2.19) times higher risk of death than white patients. Discussion: In states providing race and ethnicity data, we identified significant population-level Covid-19 mortality disparities. We demonstrated the importance of adjusting for age differences across population groups to prevent underestimating disparities in younger population groups. The availability of high-quality and comprehensive race and ethnicity data is necessary to address factors contributing to inequity in Covid-19 mortality.", "qid": 21, "docid": "7kevqevo", "rank": 41, "score": 0.6751441955566406}, {"content": "Title: TRACKing Excess Deaths (TRACKED): an interactive online tool to monitor excess deaths associated with COVID-19 pandemic in the United Kingdom Content: Aim: We aimed to describe trends of excess mortality in the United Kingdom (UK) stratified by nation and cause of death, and to develop an online tool for reporting the most up to date data on excess mortality. Methods: Population statistics agencies in the UK including the Office for National Statistics (ONS), National Records of Scotland (NRS), and Northern Ireland Statistics and Research Agency (NISRA) publish weekly data on deaths. We used mortality data up to 22nd May in the ONS and the NISRA and 24th May in the NRS. Crude mortality for non-COVID deaths (where there is no mention of COVID-19 on the death certificate) calculated. Excess mortality defined as difference between observed mortality and expected average of mortality from previous 5 years. Results: There were 56,961 excess deaths and 8,986 were non-COVID excess deaths. England had the highest number of excess deaths per 100,000 population (85) and Northern Ireland the lowest (34). Non-COVID mortality increased from 23rd March and returned to the 5-year average on 10th May. In Scotland, where underlying cause mortality data besides COVID-related deaths was available, the percentage excess over the 8-week period when COVID-related mortality peaked was: dementia 49%, other causes 21%, circulatory diseases 10%, and cancer 5%. We developed an online tool (TRACKing Excess Deaths - TRACKED) to allow dynamic exploration and visualisation of the latest mortality trends. Conclusions: Continuous monitoring of excess mortality trends and further integration of age- and gender-stratified and underlying cause of death data beyond COVID-19 will allow dynamic assessment of the impacts of indirect and direct mortality of the COVID-19 pandemic.", "qid": 21, "docid": "v76ech81", "rank": 42, "score": 0.6750722527503967}, {"content": "Title: Estimating excess 1-year mortality associated with the COVID-19 pandemic according to underlying conditions and age: a population-based cohort study Content: BACKGROUND: The medical, societal, and economic impact of the coronavirus disease 2019 (COVID-19) pandemic has unknown effects on overall population mortality. Previous models of population mortality are based on death over days among infected people, nearly all of whom thus far have underlying conditions. Models have not incorporated information on high-risk conditions or their longer-term baseline (pre-COVID-19) mortality. We estimated the excess number of deaths over 1 year under different COVID-19 incidence scenarios based on varying levels of transmission suppression and differing mortality impacts based on different relative risks for the disease. METHODS: In this population-based cohort study, we used linked primary and secondary care electronic health records from England (Health Data Research UK-CALIBER). We report prevalence of underlying conditions defined by Public Health England guidelines (from March 16, 2020) in individuals aged 30 years or older registered with a practice between 1997 and 2017, using validated, openly available phenotypes for each condition. We estimated 1-year mortality in each condition, developing simple models (and a tool for calculation) of excess COVID-19-related deaths, assuming relative impact (as relative risks [RRs]) of the COVID-19 pandemic (compared with background mortality) of 1\u00b75, 2\u00b70, and 3\u00b70 at differing infection rate scenarios, including full suppression (0\u00b7001%), partial suppression (1%), mitigation (10%), and do nothing (80%). We also developed an online, public, prototype risk calculator for excess death estimation. FINDINGS: We included 3\u00e2\u0080\u0088862\u00e2\u0080\u0088012 individuals (1\u00e2\u0080\u0088957\u00e2\u0080\u0088935 [50\u00b77%] women and 1\u00e2\u0080\u0088904\u00e2\u0080\u0088077 [49\u00b73%] men). We estimated that more than 20% of the study population are in the high-risk category, of whom 13\u00b77% were older than 70 years and 6\u00b73% were aged 70 years or younger with at least one underlying condition. 1-year mortality in the high-risk population was estimated to be 4\u00b746% (95% CI 4\u00b741-4\u00b751). Age and underlying conditions combined to influence background risk, varying markedly across conditions. In a full suppression scenario in the UK population, we estimated that there would be two excess deaths (vs baseline deaths) with an RR of 1\u00b75, four with an RR of 2\u00b70, and seven with an RR of 3\u00b70. In a mitigation scenario, we estimated 18\u00e2\u0080\u0088374 excess deaths with an RR of 1\u00b75, 36\u00e2\u0080\u0088749 with an RR of 2\u00b70, and 73\u00e2\u0080\u0088498 with an RR of 3\u00b70. In a do nothing scenario, we estimated 146\u00e2\u0080\u0088996 excess deaths with an RR of 1\u00b75, 293\u00e2\u0080\u0088991 with an RR of 2\u00b70, and 587\u00e2\u0080\u0088982 with an RR of 3\u00b70. INTERPRETATION: We provide policy makers, researchers, and the public a simple model and an online tool for understanding excess mortality over 1 year from the COVID-19 pandemic, based on age, sex, and underlying condition-specific estimates. These results signal the need for sustained stringent suppression measures as well as sustained efforts to target those at highest risk because of underlying conditions with a range of preventive interventions. Countries should assess the overall (direct and indirect) effects of the pandemic on excess mortality. FUNDING: National Institute for Health Research University College London Hospitals Biomedical Research Centre, Health Data Research UK.", "qid": 21, "docid": "qsk9lmsc", "rank": 43, "score": 0.6742743849754333}, {"content": "Title: Estimating excess 1-year mortality associated with the COVID-19 pandemic according to underlying conditions and age: a population-based cohort study Content: BACKGROUND: The medical, societal, and economic impact of the coronavirus disease 2019 (COVID-19) pandemic has unknown effects on overall population mortality. Previous models of population mortality are based on death over days among infected people, nearly all of whom thus far have underlying conditions. Models have not incorporated information on high-risk conditions or their longer-term baseline (pre-COVID-19) mortality. We estimated the excess number of deaths over 1 year under different COVID-19 incidence scenarios based on varying levels of transmission suppression and differing mortality impacts based on different relative risks for the disease. METHODS: In this population-based cohort study, we used linked primary and secondary care electronic health records from England (Health Data Research UK\u2013CALIBER). We report prevalence of underlying conditions defined by Public Health England guidelines (from March 16, 2020) in individuals aged 30 years or older registered with a practice between 1997 and 2017, using validated, openly available phenotypes for each condition. We estimated 1-year mortality in each condition, developing simple models (and a tool for calculation) of excess COVID-19-related deaths, assuming relative impact (as relative risks [RRs]) of the COVID-19 pandemic (compared with background mortality) of 1\u00b75, 2\u00b70, and 3\u00b70 at differing infection rate scenarios, including full suppression (0\u00b7001%), partial suppression (1%), mitigation (10%), and do nothing (80%). We also developed an online, public, prototype risk calculator for excess death estimation. FINDINGS: We included 3 862 012 individuals (1 957 935 [50\u00b77%] women and 1 904 077 [49\u00b73%] men). We estimated that more than 20% of the study population are in the high-risk category, of whom 13\u00b77% were older than 70 years and 6\u00b73% were aged 70 years or younger with at least one underlying condition. 1-year mortality in the high-risk population was estimated to be 4\u00b746% (95% CI 4\u00b741\u20134\u00b751). Age and underlying conditions combined to influence background risk, varying markedly across conditions. In a full suppression scenario in the UK population, we estimated that there would be two excess deaths (vs baseline deaths) with an RR of 1\u00b75, four with an RR of 2\u00b70, and seven with an RR of 3\u00b70. In a mitigation scenario, we estimated 18 374 excess deaths with an RR of 1\u00b75, 36 749 with an RR of 2\u00b70, and 73 498 with an RR of 3\u00b70. In a do nothing scenario, we estimated 146 996 excess deaths with an RR of 1\u00b75, 293 991 with an RR of 2\u00b70, and 587 982 with an RR of 3\u00b70. INTERPRETATION: We provide policy makers, researchers, and the public a simple model and an online tool for understanding excess mortality over 1 year from the COVID-19 pandemic, based on age, sex, and underlying condition-specific estimates. These results signal the need for sustained stringent suppression measures as well as sustained efforts to target those at highest risk because of underlying conditions with a range of preventive interventions. Countries should assess the overall (direct and indirect) effects of the pandemic on excess mortality. FUNDING: National Institute for Health Research University College London Hospitals Biomedical Research Centre, Health Data Research UK.", "qid": 21, "docid": "ml4fpf2o", "rank": 44, "score": 0.6741425395011902}, {"content": "Title: The Longevity-Frailty Hypothesis: Evidence from COVID-19 Death Rates in Europe Content: COVID-19 death rates vary strikingly across Europe. The death rate in Spain, for example, is greater than the death rate in Germany by more than a factor of ten. Few if any epidemiological indicators distinguish the countries of Europe by such a vast margin. Evidence on age-specific case-fatality rates (deaths over observed infections) and age-specific death rates (deaths over population) indicate that COVID-19 disproportionately afflicts the elderly and frail, suggesting that the share of elderly population (\u2265 65 years of age) in a country ought to be a strong predictor of the COVID-19 death rate. However, the COVID-19 death rate and the share of elderly population are statistically uncorrelated (r = 0.163, p = 0.399). Share of population \u2265 65 years of age is confounded by mortality selection, as well as other demographic dynamics. By contrast, elderly longevity or life expectancy at 65 more effectively captures population survival and the accumulation of age-related frailty in society. We find a strong statistical relationship between the COVID-19 death rate (r = 0.839, p < .001) and elderly longevity, and a moderately strong relationship between the date of epidemic timing and elderly longevity (r = \u22120.634, p < .001). These relationships are robust to the inclusion of statistical controls for international tourism inflow and hospital bed capacity. While the countries of Europe vary meaningfully in healthcare system capacity and in the timing and intensity of non-pharmaceutical interventions, the striking variation in COVID-19 death rates across these countries is statistically and intuitively associated with elderly survival and consequent frailty.", "qid": 21, "docid": "9p0dsyqx", "rank": 45, "score": 0.6741172671318054}, {"content": "Title: Health Inequalities, General Trends in Mortality and Morbidity, and Associated Factors Content: All measures of health status are ultimately derived from observations of individuals. At the field level we have such measures as self-assessed health status, report of a specific disease, record of a particular death, or an individual\u2019s test on a biomarker, such as blood pressure or serum cholesterol. The observations for individuals are combined and summarized to represent subnational geographic areas, demographic or socioeconomic groups within countries, or national populations. The summary measures, whether they are percentages, averages, or rates, apply to groups. A problem arises when the measures that are based on groups are assumed to represent individuals. The analysis becomes especially problematic when the units analyzed are geographic areas and inferences are being made about individuals from the analysis for these geographic areas.", "qid": 21, "docid": "cqlt5mq2", "rank": 46, "score": 0.674095869064331}, {"content": "Title: Pathogen Genomics and the Potential for Understanding Diseases in the Developing World Content: Approximately 46% and 32% of deaths among children under five globally occur in sub-Saharan Africa and South Asia, respectively. Over 80% of the 4.2 million child deaths in Africa are caused by infectious diseases, sharply contrasted to Europe where 39% of the 0.15 million child deaths are attributable to infectious diseases (Fig. 5.1) (Black et al. 2010). Hence, despite the remarkable public health advancements in hygiene, sanitation, antimicrobial drugs and vaccine strategies of the twenty-first century, the burden of infectious diseases remains unacceptably high in the developing world.", "qid": 21, "docid": "h62e6ils", "rank": 47, "score": 0.6732078194618225}, {"content": "Title: Age-specific and sex-specific morbidity and mortality from avian influenza A(H7N9) Content: Abstract We used data on age and sex for 136 laboratory confirmed human A(H7N9) cases reported as of 11 August 2013 to compare age-specific and sex-specific patterns of morbidity and mortality from the avian influenza A(H7N9) virus with those of the avian influenza A(H5N1) virus. Human A(H7N9) cases exhibit high degrees of age and sex bias: mortality is heavily biased toward males >50 years, no deaths have been reported among individuals <25 years old, and relatively few cases documented among children or adolescents. The proportion of fatal cases (PFC) for human A(H7N9) cases as of 11 August 2013 was 32%, compared to a cumulative PFC for A(H5N1) of 83% in Indonesia and 36% in Egypt. Approximately 75% of cases of all A(H7N9) cases occurred among individuals >45 years old. Morbidity and mortality from A(H7N9) are lowest among individuals between 10 and 29 years, the age group which exhibits the highest cumulative morbidity and case fatality rates from A(H5N1). Although individuals <20 years old comprise nearly 50% of all human A(H5N1) cases, only 7% of all reported A(H7N9) cases and no deaths have been reported among individuals in this age group. Only 4% of A(H7N9) cases occurred among children<5 years old, and only one case from the 10 to 20 year age group. Age- and sex-related differences in morbidity and mortality from emerging zoonotic diseases can provide insights into ecological, economic, and cultural factors that may contribute to the emergence and proliferation of novel zoonotic diseases in human populations.", "qid": 21, "docid": "sgg922q5", "rank": 48, "score": 0.6731641888618469}, {"content": "Title: Diagnoses made in an Emergency Department in rural sub-Saharan Africa. Content: BACKGROUND Information on diagnoses made in emergency departments situated in rural sub-Saharan Africa is scarce. The aim was: to evaluate the frequency of different diagnoses made in a new emergency department to define relevant healthcare requirements; and to find out if in-hospital mortality rates would decrease after the implementation of the emergency department. METHODS In this observational study, we prospectively collated diagnoses of all patients presenting to the emergency department of the St Francis Referral Hospital in Ifakara, Tanzania during 1 year. In addition, we compared in-hospital mortality rates before and after the implementation of the emergency department. RESULTS From July 2016 through to June 2017, a total of 35,903 patients were included. The median age was 33.6 years (range 1 day to 100 years), 57% were female, 25% were children <5 years, 4% were pregnant and 9% were hospitalised. The most common diagnoses were respiratory tract infection (12.6%), urinary tract infection (11.4%), trauma (9.8%), undifferentiated febrile illness (5.4%), and malaria (5.2%). The most common clinical diagnoses per age group were: lower respiratory tract infection (16.1%) in children <5 years old; trauma (21.6%) in 5- to 17-year-olds; urinary tract infection (13.5%) in 18- to 50-year-olds; and hypertensive emergency (12.4%) in >50-year-olds. Respiratory tract infections peaked in April during the rainy season, whereas malaria peaked 3 months after the rainy season. In-hospital mortality rates did not decrease during the study period (5.6% in 2015 vs 7.6% in 2017). CONCLUSIONS The majority of diagnosed disorders were of infectious or traumatic origin. The majority of febrile illnesses were poorly defined because of the lack of diagnostic methods. Trauma systems and inexpensive accurate diagnostic methods for febrile illnesses are needed in rural sub-Saharan Africa.", "qid": 21, "docid": "glajrupe", "rank": 49, "score": 0.6731451749801636}, {"content": "Title: Age-Specific Excess Mortality Patterns During the 1918\u20131920 Influenza Pandemic in Madrid, Spain Content: Although much progress has been made to uncover age-specific mortality patterns of the 1918 influenza pandemic in populations around the world, more studies in different populations are needed to make sense of the heterogeneous death impact of this pandemic. We assessed the absolute and relative magnitudes of 3 pandemic waves in the city of Madrid, Spain, between 1918 and 1920, on the basis of age-specific all-cause and respiratory excess death rates. Excess death rates were estimated using a Serfling model with a parametric bootstrapping approach to calibrate baseline death levels with quantified uncertainty. Excess all-cause and pneumonia and influenza mortality rates were estimated for different pandemic waves and age groups. The youngest and oldest persons experienced the highest excess mortality rates, and young adults faced the highest standardized mortality risk. Waves differed in strength; the peak standardized mortality risk occurred during the herald wave in spring 1918, but the highest excess rates occurred during the fall and winter of 1918/1919. Little evidence was found to support a \u201cW\u201d-shaped, age-specific excess mortality curve. Acquired immunity may have tempered a protracted fall wave, but recrudescent waves following the initial 2 outbreaks heightened the total pandemic mortality impact.", "qid": 21, "docid": "36fljyl2", "rank": 50, "score": 0.6726092100143433}, {"content": "Title: Are men dying more than women by COVID-19? Content: We aimed to clarify if the infection and death rate by COVID-19 differ among gender in the top 50 countries with the highest death rates. Also, we investigated if secondary variables such as HDI, number of hospital beds, average age, temperature, percentage of elderly, smoker and obesity are contributing to the variability observed among countries. Meta-analyses and meta-regressions approaches were applied to official public data reported by the Word Health Organization and governments until May, 2020. A random effect model was used for the meta-analysis and heterogeneity was calculated by I2 statistic. There was not significative difference between men and women to be infected by COVID-19 (P = 0.42), though a significative difference was observed for death rate (P < 0.0001). High heterogeneity was observed among countries. For both infection and death rates this variability was mainly explained by the HDI (42.3% and 54.2%), average age (40.9% and 40.3%) and temperature (30.1% and 39.3%). Man are dying more than women around the word by COVID-19. Countries with highest HDI present less difference between sexes. These results reinforce that public politics promoting social isolation, health care and general well-being of the population are key factors in combating COVID-19.", "qid": 21, "docid": "0ekb6c8e", "rank": 51, "score": 0.6724262833595276}, {"content": "Title: Population-level COVID-19 mortality risk for non-elderly individuals overall and for non-elderly individuals without underlying diseases in pandemic epicenters Content: OBJECTIVE: To provide estimates of the relative rate of COVID-19 death in people <65 years old versus older individuals in the general population, the absolute risk of COVID-19 death at the population level during the first epidemic wave, and the proportion of COVID-19 deaths in non-elderly people without underlying diseases in epicenters of the pandemic. ELIGIBLE DATA: Cross-sectional survey of countries and US states with at least 800 COVID-19 deaths as of April 24, 2020 and with information on the number of deaths in people with age <65. Data were available for 14 countries (Belgium, Canada, France, Germany, India, Ireland, Italy, Mexico, Netherlands, Portugal, Spain, Sweden, Switzerland, UK) and 13 US states (California, Connecticut, Florida, Georgia, Illinois, Indiana, Louisiana, Maryland, Massachusetts, Michigan, New Jersey, New York, Pennsylvania). We also examined available data on COVID-19 deaths in people with age <65 and no underlying diseases. MAIN OUTCOME MEASURES: Proportion of COVID-19 deaths in people <65 years old; relative mortality rate of COVID-19 death in people <65 versus \u226565 years old; absolute risk of COVID-19 death in people <65 and in those \u226580 years old in the general population as of June 17, 2020; absolute COVID-19 mortality rate expressed as equivalent of mortality rate from driving a motor vehicle. RESULTS: Individuals with age <65 account for 4.5\u201311.2% of all COVID-19 deaths in European countries and Canada, 8.3\u201322.7% in the US locations, and were the majority in India and Mexico. People <65 years old had 30- to 100-fold lower risk of COVID-19 death than those \u226565 years old in 11 European countries and Canada, 16- to 52-fold lower risk in US locations, and less than 10-fold in India and Mexico. The absolute risk of COVID-19 death as of June 17, 2020 for people <65 years old in high-income countries ranged from 10 (Germany) to 349 per million (New Jersey) and it was 5 per million in India and 96 per million in Mexico. The absolute risk of COVID-19 death for people \u226580 years old ranged from 0.6 (Florida) to 17.5 per thousand (Connecticut). The COVID-19 mortality rate in people <65 years old during the period of fatalities from the epidemic was equivalent to the mortality rate from driving between 4 and 82 miles per day for 13 countries and 5 states, and was higher (equivalent to the mortality rate from driving 106\u2013483 miles per day) for 8 other states and the UK. People <65 years old without underlying predisposing conditions accounted for only 0.7\u20133.6% of all COVID-19 deaths in France, Italy, Netherlands, Sweden, Georgia, and New York City and 17.7% in Mexico. CONCLUSIONS: People <65 years old have very small risks of COVID-19 death even in pandemic epicenters and deaths for people <65 years without underlying predisposing conditions are remarkably uncommon. Strategies focusing specifically on protecting high-risk elderly individuals should be considered in managing the pandemic.", "qid": 21, "docid": "f3eogz0n", "rank": 52, "score": 0.672339677810669}, {"content": "Title: Changing pattern of premature mortality burden over 6 years of rapid growth of the economy in suburban south-west China: 1998\u20132003 Content: Summary Background This study was conducted in Kunming, the capital of Yunnan, a poor province in south-west China experiencing rapid economic growth. The study examined the short-term trend in premature mortality burden from common causes of death in a suburban region between 1998 and 2003. Methods Years of life lost (YLL) per 1000 population and mortality rate per 100,000 population were calculated from medical death certificates, and broken down by cause of death, sex and year without age weighting but with a discounting rate of 3%. Results Non-communicable diseases contributed over 80% of all causes of YLL, with a slightly increasing trend. The combined rate for communicable, maternal, prenatal and nutritional deficiencies declined from 4.7 to 2.4 per 1000 population. Remarkably, declining trends in YLL were also seen for chronic obstructive pulmonary disease, drug use and road traffic accidents, whereas increasing trends were seen for ischaemic heart disease (IHD) and liver cancer (males). The YLL rate for stroke, self-inflicted injuries, lung cancer and stomach cancer fluctuated over time. Conclusions The region should focus on further control of IHD and liver cancer.", "qid": 21, "docid": "lf90j7mm", "rank": 53, "score": 0.6722984313964844}, {"content": "Title: Erratum: COVID-19, Australia: Epidemiology Report 15 (Reporting week to 23:59 AEST 3 May 2020) Content: An error in data processing resulted in the tabulation of incorrect crude case fatality rate values, for age groups of 50-59 and above, in Table 5 (Crude Case Fatality Rate of all cases and hospitalised cases, by age group) as originally published in the COVID-19 (Australia) epidemiology report 14. The table below provides the corrected values.", "qid": 21, "docid": "f59ov4i6", "rank": 54, "score": 0.672013521194458}, {"content": "Title: Erratum: COVID-19, Australia: Epidemiology Report 15 (Reporting week to 23:59 AEST 3 May 2020). Content: An error in data processing resulted in the tabulation of incorrect crude case fatality rate values, for age groups of 50-59 and above, in Table 5 (Crude Case Fatality Rate of all cases and hospitalised cases, by age group) as originally published in the COVID-19 (Australia) epidemiology report 14. The table below provides the corrected values.", "qid": 21, "docid": "qh8ljx56", "rank": 55, "score": 0.6720133423805237}, {"content": "Title: Homicide rates among persons aged 10-24 years - United States, 1981-2010. Content: Homicide disproportionately affects persons aged 10-24 years in the United States and consistently ranks in the top three leading causes of death in this age group, resulting in approximately 4,800 deaths and an estimated $9 billion in lost productivity and medical costs in 2010. To investigate trends in homicide among persons aged 10-24 years for the period 1981-2010, CDC analyzed National Vital Statistics System data on deaths caused by homicide of persons in this age group and examined trends by sex, age, race/ethnicity, and mechanism of injury. This report describes the results of that analysis, which indicated that homicide rates varied substantially during the study period, with a sharp rise from 1985 to 1993 followed by a decline that has slowed since 1999. During the period 2000-2010, rates declined for all groups, although the decline was significantly slower for males compared with females and for blacks compared with Hispanics and persons of other racial/ethnic groups. By mechanism of injury, the decline for firearm homicides from 2000 to 2010 was significantly slower than for nonfirearm homicides. The homicide rate among persons aged 10-24 years in 2010 was 7.5 per 100,000, the lowest in the 30-year study period. Primary prevention strategies remain critical, particularly among groups at increased risk for homicide.", "qid": 21, "docid": "fpz3aikk", "rank": 56, "score": 0.6718612909317017}, {"content": "Title: The male excess in case-fatality rates for COVID-19. A meta-analytic study of the age-related differences and consistency over six countries Content: Background Early in the COVID-19 pandemic, it was noted that males seemed to be more affected than females. We examined the magnitude and consistency of the sex differences in age-specific case-fatality rates (CFRs) in six countries. Methods Data on the cases and deaths from COVID-19, by sex and age group, were extracted from the published reports from Denmark, England, Israel, Italy, Spain, and the United States . Age-specific CFRs were computed for males and females separately. The ratio of the male to female CFRs were computed and meta-analytic methods were used to obtained pooled estimates of the male to female ratio of the CFRs over the six countries, for seven age-groups. Findings The CFRs were consistently higher in males at all ages. The differences were greater in the younger age groups. The pooled M:F CFR ratios were 2.53, 2.92, 2.57, 1.83, 1.57, 1.58 and 1.48 for ages 0-39, 40-49, 50-59, 60-69, 70-79, 80-89 and 90+. There was remarkable consistency between countries in the magnitude of the M:F CFRs, in each age group. In meta-regression, age group explained almost all the heterogeneity in the CFR ratios. Conclusions The sex differences in the CFRs are intriguing and are compatible with the male dominance in the incidence rates of many infectious diseases. For COVID-19, factors such as sex differences in the prevalence of underlying diseases may play a part in the CFR differences. However, the greater severity of the disease in males, particularly at younger ages, may be part of the disease mechanism and should be explored further.", "qid": 21, "docid": "xiitqf6k", "rank": 57, "score": 0.6717827320098877}, {"content": "Title: Racial/ethnic disparities in fatal unintentional drowning among persons aged \u2264 29 years - United States, 1999-2010. Content: In the United States, almost 4,000 persons die from drowning each year. Drowning is responsible for more deaths among children aged 1-4 years than any other cause except congenital anomalies. For persons aged \u226429 years, drowning is one of the top three causes of unintentional injury death (2). Previous research has identified racial/ethnic disparities in drowning rates. To describe these differences by age of decedent and drowning setting, CDC analyzed 12 years of combined mortality data from 1999-2010 for those aged \u226429 years. Among non-Hispanics, the overall drowning rate for American Indians/Alaska Natives (AI/AN) was twice the rate for whites, and the rate for blacks was 1.4 times the rate for whites. Disparities were greatest in swimming pools, with swimming pool drowning rates among blacks aged 5-19 years 5.5 times higher than those among whites in the same age group. This disparity was greatest at ages 11-12 years; at these ages, blacks drown in swimming pools at 10 times the rate of whites. Drowning prevention strategies include using barriers (e.g., fencing) and life jackets, actively supervising or lifeguarding, teaching basic swimming skills and performing bystander cardiopulmonary resuscitation (CPR). The practicality and effectiveness of these strategies varies by setting; however, basic swimming skills can be beneficial across all settings.", "qid": 21, "docid": "pjt4uphj", "rank": 58, "score": 0.671671986579895}, {"content": "Title: A Chain Multinomial Model for Estimating the Real-Time Fatality Rate of a Disease, with an Application to Severe Acute Respiratory Syndrome Content: It is well known that statistics using cumulative data are insensitive to changes. World Health Organization (WHO) estimates of fatality rates are of the above type, which may not be able to reflect the latest changes in fatality due to treatment or government policy in a timely fashion. Here, the authors propose an estimate of a real-time fatality rate based on a chain multinomial model with a kernel function. It is more accurate than the WHO estimate in describing fatality, especially earlier in the course of an epidemic. The estimator provides useful information for public health policy makers for understanding the severity of the disease or evaluating the effects of treatments or policies within a shorter time period, which is critical in disease control during an outbreak. Simulation results showed that the performance of the proposed estimator is superior to that of the WHO estimator in terms of its sensitivity to changes and its timeliness in reflecting the severity of the disease.", "qid": 21, "docid": "uy25ll4p", "rank": 59, "score": 0.6713811159133911}, {"content": "Title: Global Variability in Reported Mortality for Critical Illness during the 2009-10 Influenza A(H1N1) Pandemic: A Systematic Review and Meta-Regression to Guide Reporting of Outcomes during Disease Outbreaks Content: PURPOSE: To determine how patient, healthcare system and study-specific factors influence reported mortality associated with critical illness during the 2009\u20132010 Influenza A (H1N1) pandemic. METHODS: Systematic review with meta-regression of studies reporting on mortality associated with critical illness during the 2009\u20132010 Influenza A (H1N1) pandemic. DATA SOURCES: Medline, Embase, LiLACs and African Index Medicus to June 2009-March 2016. RESULTS: 226 studies from 50 countries met our inclusion criteria. Mortality associated with H1N1-related critical illness was 31% (95% CI 28\u201334). Reported mortality was highest in South Asia (61% [95% CI 50\u201371]) and Sub-Saharan Africa (53% [95% CI 29\u201375]), in comparison to Western Europe (25% [95% CI 22\u201330]), North America (25% [95% CI 22\u201327]) and Australia (15% [95% CI 13\u201318]) (P<0.0001). High income economies had significantly lower reported mortality compared to upper middle income economies and lower middle income economies respectively (P<0.0001). Mortality for the first wave was non-significantly higher than wave two (P = 0.66). There was substantial variability in reported mortality among the specific subgroups of patients: unselected critically ill adults (27% [95% CI 24\u201330]), acute respiratory distress syndrome (37% [95% CI 32\u201344]), acute kidney injury (44% [95% CI 26\u201364]), and critically ill pregnant patients (10% [95% CI 5\u201319]). CONCLUSION: Reported mortality for outbreaks and pandemics may vary substantially depending upon selected patient characteristics, the number of patients described, and the region and economic status of the outbreak location. Outcomes from a relatively small number of patients from specific regions may lead to biased estimates of outcomes on a global scale.", "qid": 21, "docid": "bule5ys8", "rank": 60, "score": 0.6709209680557251}, {"content": "Title: Non\u2010parametric estimation of the case fatality ratio with competing risks data: an application to Severe Acute Respiratory Syndrome (SARS) Content: For diseases with some level of associated mortality, the case fatality ratio measures the proportion of diseased individuals who die from the disease. In principle, it is straightforward to estimate this quantity from individual follow\u2010up data that provides times from onset to death or recovery. In particular, in a competing risks context, the case fatality ratio is defined by the limiting value of the sub\u2010distribution function, F (1)(t) = Pr(T \u2a7dt and J = 1), associated with death, as t \u2192 \u221e, where T denotes the time from onset to death (J = 1) or recovery (J = 2). When censoring is present, however, estimation of F (1)(\u221e) is complicated by the possibility of little information regarding the right tail of F (1), requiring use of estimators of F (1)(t(*)) or F (1)(t (*))/(F (1)(t (*))+F (2)(t (*))) where t (*) is large, with F (2)(t) = Pr(T \u2a7dt and J = 2) being the analogous sub\u2010distribution function associated with recovery. With right censored data, the variability of such estimators increases as t (*) increases, suggesting the possibility of using estimators at lower values of t (*) where bias may be increased but overall mean squared error be smaller. These issues are investigated here for non\u2010parametric estimators of F (1) and F (2). The ideas are illustrated on case fatality data for individuals infected with Severe Acute Respiratory Syndrome (SARS) in Hong Kong in 2003. Copyright \u00a9 2006 John Wiley & Sons, Ltd.", "qid": 21, "docid": "y20azr7b", "rank": 61, "score": 0.67075514793396}, {"content": "Title: Trends in Infectious Disease Mortality, South Korea, 1983\u20132015 Content: We used national statistics from 1983\u20132015 to evaluate trends in mortality caused by infectious diseases in South Korea. Age-standardized mortality from infectious disease decreased from 43.5/100,000 population in 1983 to 16.5/100,000 in 1996, and then increased to 44.6/100,000 in 2015. Tuberculosis was the most common cause of death in 1983 and respiratory tract infections in 2015. We observed a significant decline in infant deaths caused by infectious diseases, but mortality in persons age >65 years increased from 135 deaths/100,000 population in 1996 to 307/100,000 in 2015. The relative inequality indices for respiratory tract infections, sepsis, and tuberculosis tended to increase over time. Although substantial progress has been achieved in terms of infant mortality, death rates from infectious disease has not decreased overall. Elderly populations with lower education levels and subgroups susceptible to respiratory infections and sepsis should be the focus of preventive policies.", "qid": 21, "docid": "osyoizng", "rank": 62, "score": 0.6707346439361572}, {"content": "Title: Disparities in premature deaths from heart disease--50 States and the District of Columbia, 2001. Content: In 2001, heart disease accounted for approximately 29.0% of deaths among U.S. residents; 16.8% of those deaths occurred among persons aged <65 years. Although mortality rates from heart disease have decreased, the decline has not been uniform for all populations. One of the two overall national health objectives for 2010 is to eliminate health disparities among different segments of the U.S. population. To better understand these disparities, CDC analyzed death certificate data for premature deaths from heart disease occurring in 2001. This report summarizes the results of that analysis, which indicated that the proportion of premature heart disease deaths varied by state and was higher among blacks, American Indians/Alaska Natives (AI/ANs), Asians/Pacific Islanders (A/PIs), and Hispanics. Reducing premature death from heart disease and eliminating disparities will require preventing, detecting, treating, and controlling risk factors for heart disease in young and middle-aged adults.", "qid": 21, "docid": "03q86e1d", "rank": 63, "score": 0.6702439188957214}, {"content": "Title: Is investing in religious institutions a viable pathway to reduce mortality in the population? Content: There is established and consistent findings from epidemiologic studies, among individuals, that religion\u2014 broadly assessed through frequency of attending worship services\u2014is associated with lower all-cause and cause-specific mortality attributed to suicide, alcohol, cardiovascular disease and cancer. Religious norms, social support, character, virtue, compassion, love, generosity, and religious community are among some mechanisms purported to explain lower mortality, on aggregate. The religious ecology or characteristics of religion within an area or geographic level (e.g., county, ZIP-code, country), has been linked with overall and cause-specific mortality, but directions of findings are mixed. Mechanisms to explain the links between the religious ecology and mortality included social integration, civic engagement, and social control. The manuscript (SSM-D-19-03928R2) adds a fresh and timely perspective by investigating another mechanism: investment in local healthcare spending. The study found some support of an indirect association from county-level religious denominational composition, through investments in health spending, on Black and White all-cause mortality rates. Should society or government invest finances in religious institutions to indirectly improve population health? This work adds evidence to debate that question. Future work on the topic will need to address several conceptual and methodological challenges. Conceptually, is investigating the market share of religious denominations (i.e., % Catholics vs % Protestants) relevant today given diversity in population and declining trends of worship attendance? Is mortality the most relevant for moving policy or should the focus be on well-being? Methodologically, are there alternate observable measures religious investments/spending in the local economy? Mechanisms, challenges, and opportunities for social epidemiology research on this topic are discussed.", "qid": 21, "docid": "l42w2jyk", "rank": 64, "score": 0.6696888208389282}, {"content": "Title: What does and does not correlate with COVID-19 death rates Content: We correlate county-level COVID-19 death rates with key variables using both linear regression and negative binomial mixed models, although we focus on linear regression models. We include four sets of variables: socio-economic variables, county-level health variables, modes of commuting, and climate and pollution patterns. Our analysis studies daily death rates from April 4, 2020 to May 27, 2020. We estimate correlation patterns both across states, as well as within states. For both models, we find higher shares of African American residents in the county are correlated with higher death rates. However, when we restrict ourselves to correlation patterns within a given state, the statistical significance of the correlation of death rates with the share of African Americans, while remaining positive, wanes. We find similar results for the share of elderly in the county. We find that higher amounts of commuting via public transportation, relative to telecommuting, is correlated with higher death rates. The correlation between driving into work, relative to telecommuting, and death rates is also positive across both models, but statistically significant only when we look across states and counties. We also find that a higher share of people not working, and thus not commuting either because they are elderly, children or unemployed, is correlated with higher death rates. Counties with higher home values, higher summer temperatures, and lower winter temperatures have higher death rates. Contrary to past work, we do not find a correlation between pollution and death rates. Also importantly, we do not find that death rates are correlated with obesity rates, ICU beds per capita, or poverty rates. Finally, our model that looks within states yields estimates of how a given state's death rate compares to other states after controlling for the variables included in our model; this may be interpreted as a measure of how states are doing relative to others. We find that death rates in the Northeast are substantially higher compared to other states, even when we control for the four sets of variables above. Death rates are also statistically significantly higher in Michigan, Louisiana, Iowa, Indiana, and Colorado. California's death rate is the lowest across all states.", "qid": 21, "docid": "flkd7u9u", "rank": 65, "score": 0.6695533990859985}, {"content": "Title: Thermal stress associated mortality risk and effect modification by sex and obesity in an elderly cohort of Chinese in Hong Kong Content: We assessed the effects of apparent temperature (AT) on mortality and the effect modifications attributable to individual characteristics in Hong Kong with subtropical climate conditions. Two datasets are used for analyses: one from mortality data of the general elderly population in 1998\u20132009; the other from an elderly cohort with 66,820 subjects recruited in 1998\u20132001 with mortality outcomes followed up until 2009. We found that AT below 20.8 \u00b0C was associated with an increase in mortality risk of 1.99% (95% confidence interval: 0.64%, 2.64%) for all causes, 2.48% (0.57%, 4.36%) for cardiovascular disease, and 3.19% (0.59%, 5.73%) for respiratory disease for every 1 \u00b0C decrease in AT over the following 3 days. The associations were modified by sex and body mass index, in particular stronger associations were observed for females and for obese subjects.", "qid": 21, "docid": "1dygn0rw", "rank": 66, "score": 0.6695510149002075}, {"content": "Title: Incidence and Mortality Rates of Disasters and Mass Casualty Incidents in Korea: A Population-Based Cross-Sectional Study, 2000-2009 Content: The objective of study was to evaluate the incidence and mortality rates of disasters and mass casualty incidents (MCIs) over the past 10 yr in the administrative system of Korea administrative system and to examine their relationship with population characteristics. This was a population-based cross-sectional study. We calculated the nationwide incidence, as well as the crude mortality and injury incidence rates, of disasters and MCIs. The data were collected from the administrative database of the National Emergency Management Agency (NEMA) and from provincial fire departments from January 2000 to December 2009. A total of 47,169 events were collected from the NEMA administrative database. Of these events, 115 and 3,079 cases were defined as disasters and MCIs that occurred in Korea, respectively. The incidence of technical disasters/MCIs was approximately 12.7 times greater than that of natural disasters/MCIs. Over the past 10 yr, the crude mortality rates for disasters and MCIs were 2.36 deaths per 100,000 persons and 6.78 deaths per 100,000 persons, respectively. The crude injury incidence rates for disasters and MCIs were 25.47 injuries per 100,000 persons and 152 injuries per 100,000 persons, respectively. The incidence and mortality of disasters/MCIs in Korea seem to be low compared to that of trend around the world.", "qid": 21, "docid": "ysyz3grd", "rank": 67, "score": 0.6692743301391602}, {"content": "Title: Epidemiology of Traumatic Brain Injury in Europe: A Living Systematic Review. Content: This systematic review provides a comprehensive, up-to-date summary of traumatic brain injury (TBI) epidemiology in Europe, describing incidence, mortality, age, and sex distribution, plus severity, mechanism of injury, and time trends. PubMed, CINAHL, EMBASE, and Web of Science were searched in January 2015 for observational, descriptive, English language studies reporting incidence, mortality, or case fatality of TBI in Europe. There were no limitations according to date, age, or TBI severity. Methodological quality was assessed using the Methodological Evaluation of Observational Research checklist. Data were presented narratively. Sixty-six studies were included in the review. Country-level data were provided in 22 studies, regional population or treatment center catchment area data were reported by 44 studies. Crude incidence rates varied widely. For all ages and TBI severities, crude incidence rates ranged from 47.3 per 100,000, to 694 per 100,000 population per year (country-level studies) and 83.3 per 100,000, to 849 per 100,000 population per year (regional-level studies). Crude mortality rates ranged from 9 to 28.10 per 100,000 population per year (country-level studies), and 3.3 to 24.4 per 100,000 population per year (regional-level studies.) The most common mechanisms of injury were traffic accidents and falls. Over time, the contribution of traffic accidents to total TBI events may be reducing. Case ascertainment and definitions of TBI are variable. Improved standardization would enable more accurate comparisons.", "qid": 21, "docid": "co5guolc", "rank": 68, "score": 0.6689191460609436}, {"content": "Title: Trends in maternal and neonatal mortality in South Africa: a systematic review protocol. Content: BACKGROUND Measuring and monitoring progress towards Millennium Development Goals (MDG) 4 and 5 requires valid and reliable estimates of maternal and neonatal mortality. In South Africa, there are conflicting reports on the estimates of maternal and neonatal mortality, derived from both direct and indirect estimation techniques. This study aims to systematically review the estimates made of maternal and neonatal mortality in the period from 1990 to 2015 in South Africa and determine trends over this period. METHODS For the purpose of this review, searches for eligible studies will be conducted in MEDLINE, Africa-Wide Information, African Index Medicus, African Journals Online, Scopus, Web of Science and CINAHL databases. Searches will be restricted to articles written in English and presenting data covering the period between 1990 and 2015. Reference lists of retrieved articles will also be screened for additional publications. Three independent reviewers will be involved in the study selection, data extractions and achieving consensus. Study quality and risk of bias will thereafter be assessed by two authors. The results will be presented as rates/ratio with their corresponding 95% confidence/uncertainty intervals. DISCUSSION Identifying trends in maternal and neonatal mortality will help to track progress in MDGs 4 and 5 and will serve in evaluating interventions focusing on reducing maternal and child mortality in the country. This study will, in particular, provide the context for understanding inconsistencies in reported estimates of maternal and neonatal mortality by considering estimation methods, data sources and definitions used. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42016042769.", "qid": 21, "docid": "abk3exnv", "rank": 69, "score": 0.6676545143127441}, {"content": "Title: Mortality estimates among adult patients with severe acute respiratory infections from two sentinel hospitals in southern Arizona, United States, 2010\u20132014 Content: BACKGROUND: From October 2010 through February 2016, Arizona conducted surveillance for severe acute respiratory infections (SARI) among adults hospitalized in the Arizona-Mexico border region. There are few accurate mortality estimates in SARI patients, particularly in adults \u2265 65 years old. The purpose of this study was to generate mortality estimates among SARI patients that include deaths occurring shortly after hospital discharge and identify risk factors for mortality. METHODS: Patients admitted to two sentinel hospitals between 2010 and 2014 who met the SARI case definition were enrolled. Demographic data were used to link SARI patients to Arizona death certificates. Mortality within 30 days after the date of admission was calculated and risk factors were identified using logistic regression models. RESULTS: Among 258 SARI patients, 47% were females, 51% were white, non-Hispanic and 39% were Hispanic. The median age was 63 years (range, 19 to 97 years) and 80% had one or more pre-existing health condition; 9% died in hospital. Mortality increased to 12% (30/258, 30% increase) when electronic vital records and a 30-day post-hospitalization time frame were used. Being age \u2265 65 years (OR = 4.0; 95% CI: 1.6\u20139.9) and having an intensive care unit admission (OR = 7.4; 95% CI: 3.0\u201317.9) were independently associated with mortality. CONCLUSION: The use of electronic vital records increased SARI-associated mortality estimates by 30%. These findings may help guide prevention and treatment measures, particularly in high-risk persons in this highly fluid border population.", "qid": 21, "docid": "pcj7rkif", "rank": 70, "score": 0.6672712564468384}, {"content": "Title: SARS hits hard Content: Death rates higher than expected, but control measures seem to be working.", "qid": 21, "docid": "oqdzv3v3", "rank": 71, "score": 0.6671004891395569}, {"content": "Title: Analysis of Austrian COVID-19 deaths by age and sex Content: We analyze the age and sex distribution of the reported COVID-19 deaths in Austria. In accordance with international studies, the Austrian data also suggests that the risk of death increases substantially with age. The observed age dependency of the proportions of registered COVID-19 deaths in relation to the population sizes in the age groups is approximately exponential, similar to the age dependency of the general age specific mortality rate. Furthermore, we compare the general age specific mortality rate in Austria with the estimates of the SARS-CoV\u20112 infection fatality rate by Ferguson et al. (2020). The parallels to the general age specific mortality rates do not imply that COVID-19 does not pose an additional risk. On the contrary, it follows from the structure and magnitude of the infection fatality rate that it is substantial, especially for higher age groups. However, since in many cases persons with severe pre-existing conditions are affected, it is not yet possible to estimate what effects COVID-19 will have on life expectancy.", "qid": 21, "docid": "e6k1bp9n", "rank": 72, "score": 0.6670937538146973}, {"content": "Title: Analysis of Austrian COVID-19 deaths by age and sex Content: We analyze the age and sex distribution of the reported COVID-19 deaths in Austria. In accordance with international studies, the Austrian data also suggests that the risk of death increases substantially with age. The observed age dependency of the proportions of registered COVID-19 deaths in relation to the population sizes in the age groups is approximately exponential, similar to the age dependency of the general age specific mortality rate. Furthermore, we compare the general age specific mortality rate in Austria with the estimates of the SARS-CoV\u00ad2 infection fatality rate by Ferguson et al. (2020). The parallels to the general age specific mortality rates do not imply that COVID-19 does not pose an additional risk. On the contrary, it follows from the structure and magnitude of the infection fatality rate that it is substantial, especially for higher age groups. However, since in many cases persons with severe pre-existing conditions are affected, it is not yet possible to estimate what effects COVID-19 will have on life expectancy.", "qid": 21, "docid": "zt9mxom1", "rank": 73, "score": 0.6668938994407654}, {"content": "Title: Determinants of COVID-19 incidence and mortality: A cross-country analysis Content: Objective: We undertook this study to explore the role of important determinants affecting global COVID-19 incidence and mortality taking multifactorial disease dynamics into consideration. Design: Secondary data as on March 28, 2020 were obtained for 97 countries. Association of COVID-19 cumulative incidence and mortality measures were assessed with ten indictors representing health system characteristics, climate, demography, promptness of international travel restriction and population movement using Generalized Linear Modelling. Main outcome measures: Country-specific COVID-19 cumulative incidence, cumulative cause-specific mortality and case fatality rate. Results: Significant inter-country variation in incidence and mortality rates were observed. Five variables were found to be associated with cumulative incidence: testing rate per 1000 population ({beta} = 0.119, p < 0.01), UHC index ({beta} = 0.043, p = 0.04), percentage elderly population ({beta} = 0.122, p < 0.01), percentage below-poverty line population ({beta} = -0.048, p < 0.01) and disability adjusted life years due to NCDs ({beta} = -0.013, p < 0.01). Case fatality rate was observed to be associated with testing rate per 1000 population ({beta} = -0.058, p = 0.03) and population density ({beta} = 0.002, p = 0.02), while the cumulative cause-specific mortality was associated with only percentage elderly population ({beta} = 0.096, p = 0.04) in the country. Conclusions: Health system response, population susceptibility and demography were the most important factors determining the progression. Policy response should focus towards increasing testing, primarily targeting high population density areas. Health system strengthening and reduction in population risk factors should be long term goals for a better response to such epidemics.", "qid": 21, "docid": "u72yj5kx", "rank": 74, "score": 0.6667147874832153}, {"content": "Title: Infection fatality risk of the pandemic A(H1N1)2009 virus in Hong Kong. Content: One measure of the severity of a pandemic influenza outbreak at the individual level is the risk of death among people infected by the new virus. However, there are complications in estimating both the numerator and denominator. Regarding the numerator, statistical estimates of the excess deaths associated with influenza virus infections tend to exceed the number of deaths associated with laboratory-confirmed infection. Regarding the denominator, few infections are laboratory confirmed, while differences in case definitions and approaches to case ascertainment can lead to wide variation in case fatality risk estimates. Serological surveillance can be used to estimate the cumulative incidence of infection as a denominator that is more comparable across studies. We estimated that the first wave of the influenza A(H1N1)pdm09 virus in 2009 was associated with approximately 232 (95% confidence interval: 136, 328) excess deaths of all ages in Hong Kong, mainly among the elderly. The point estimates of the risk of death on a per-infection basis increased substantially with age, from below 1 per 100,000 infections in children to 1,099 per 100,000 infections in those 60-69 years of age. Substantial variation in the age-specific infection fatality risk complicates comparison of the severity of different influenza strains.", "qid": 21, "docid": "rwmn3jbs", "rank": 75, "score": 0.6663109064102173}, {"content": "Title: Occupational Deaths among Healthcare Workers Content: Recent experiences with severe acute respiratory syndrome and the US smallpox vaccination program have demonstrated the vulnerability of healthcare workers to occupationally acquired infectious diseases. However, despite acknowledgment of risk, the occupational death rate for healthcare workers is unknown. In contrast, the death rate for other professions with occupational risk, such as police officer or firefighter, has been well defined. With available information from federal sources and calculating the additional number of deaths from infection by using data on prevalence and natural history, we estimate the annual death rate for healthcare workers from occupational events, including infection, is 17\u201357 per 1 million workers. However, a much more accurate estimate of risk is needed. Such information could inform future interventions, as was seen with the introduction of safer needle products. This information would also heighten public awareness of this often minimized but essential aspect of patient care.", "qid": 21, "docid": "93m011gz", "rank": 76, "score": 0.6662362813949585}, {"content": "Title: Maternal, neonatal, and child health in southeast Asia: towards greater regional collaboration Content: Although maternal and child mortality are on the decline in southeast Asia, there are still major disparities, and greater equity is key to achieve the Millennium Development Goals. We used comparable cross-national data sources to document mortality trends from 1990 to 2008 and to assess major causes of maternal and child deaths. We present inequalities in intervention coverage by two common measures of wealth quintiles and rural or urban status. Case studies of reduction in mortality in Thailand and Indonesia indicate the varying extents of success and point to some factors that accelerate progress. We developed a Lives Saved Tool analysis for the region and for country subgroups to estimate deaths averted by cause and intervention. We identified three major patterns of maternal and child mortality reduction: early, rapid downward trends (Brunei, Singapore, Malaysia, and Thailand); initially high declines (sustained by Vietnam but faltering in the Philippines and Indonesia); and high initial rates with a downward trend (Laos, Cambodia, and Myanmar). Economic development seems to provide an important context that should be coupled with broader health-system interventions. Increasing coverage and consideration of the health-system context is needed, and regional support from the Association of Southeast Asian Nations can provide increased policy support to achieve maternal, neonatal, and child health goals.", "qid": 21, "docid": "nu4typ7j", "rank": 77, "score": 0.6658159494400024}, {"content": "Title: Explaining national differences in the mortality of Covid-19: individual patient simulation model to investigate the effects of testing policy and other factors on apparent mortality. Content: There has been extensive speculation on the apparent differences in mortality between countries reporting on the confirmed cases and deaths due to Covid-19. A number of explanations have been suggested, but there is no clear evidence about how apparent fatality rates may be expected to vary with the different testing regimes, admission policies and other variables. An individual patient simulation model was developed to address this question. Parameters and sensitivity analysis based upon recent international data sources for Covid-19 and results were averaged over 100 iterations for a simulated cohort of over 500,000 patients. Different testing regimes for Covid-19 were considered; testing admitted patients only, various rates of community testing of symptomatic cases and active contact-tracing and screening. In the base case analysis, apparent mortality ranged from 10.5% under a policy of testing only admitted patients to 0.4% with intensive contact tracing and community testing. These findings were sensitive to assumptions regarding admission rates and the rate of spread, with more selective admission policies and suppression of spread increasing the apparent mortality and the potential for apparent mortality rates to exceed 18% under some circumstances. Under all scenarios the proportion of patients tested in the community had the greatest impact on apparent mortality. Whilst differences in mortality due to health service and demographic factors cannot be excluded, the current international differences in reported mortality are all consistent with differences in practice regarding screening, community testing and admission policies.", "qid": 21, "docid": "gkd1h8yi", "rank": 78, "score": 0.6658013463020325}, {"content": "Title: A Comparison of Generalized Stochastic Milevsky-Promislov Mortality Models with Continuous Non-Gaussian Filters Content: The ability to precisely model mortality rates [Formula: see text] plays an important role from the economic point of view in healthcare. The aim of this article is to propose a comparison of the estimation of the mortality rates based on a class of stochastic Milevsky-Promislov mortality models. We assume that excitations are modeled by second, fourth and sixth order polynomials of outputs from a linear non-Gaussian filter. To estimate the model parameters we use the first and second moments of [Formula: see text]. The theoretical values obtained in both cases were compared with theoretical [Formula: see text] based on a classical Lee-Carter model. The obtained results confirm the usefulness of the switched model based on the continuous non-Gaussian processes used for modeling [Formula: see text].", "qid": 21, "docid": "bvgzy7yq", "rank": 79, "score": 0.6657764911651611}, {"content": "Title: Using research to prepare for outbreaks of severe acute respiratory infection Content: Severe acute respiratory infections (SARI) remain one of the leading causes of mortality around the world in all age groups. There is large global variation in epidemiology, clinical management and outcomes, including mortality. We performed a short period observational data collection in critical care units distributed globally during regional peak SARI seasons from 1 January 2016 until 31 August 2017, using standardised data collection tools. Data were collected for 1 week on all admitted patients who met the inclusion criteria for SARI, with follow-up to hospital discharge. Proportions of patients across regions were compared for microbiology, management strategies and outcomes. Regions were divided geographically and economically according to World Bank definitions. Data were collected for 682 patients from 95 hospitals and 23 countries. The overall mortality was 9.5%. Of the patients, 21.7% were children, with case fatality proportions of 1% for those less than 5 years. The highest mortality was in those above 60 years, at 18.6%. Case fatality varied by region: East Asia and Pacific 10.2% (21 of 206), Sub-Saharan Africa 4.3% (8 of 188), South Asia 0% (0 of 35), North America 13.6% (25 of 184), and Europe and Central Asia 14.3% (9 of 63). Mortality in low-income and low-middle-income countries combined was 4% as compared with 14% in high-income countries. Organ dysfunction scores calculated on presentation in 560 patients where full data were available revealed Sequential Organ Failure Assessment (SOFA) scores on presentation were significantly associated with mortality and hospital length of stay. Patients in East Asia and Pacific (48%) and North America (24%) had the highest SOFA scores of >12. Multivariable analysis demonstrated that initial SOFA score and age were independent predictors of hospital survival. There was variability across regions and income groupings for the critical care management and outcomes of SARI. Intensive care unit-specific factors, geography and management features were less reliable than baseline severity for predicting ultimate outcome. These findings may help in planning future outbreak severity assessments, but more globally representative data are required.", "qid": 21, "docid": "59m284oq", "rank": 80, "score": 0.665635347366333}, {"content": "Title: The basic principles of migration health: Population mobility and gaps in disease prevalence Content: Currently, migrants and other mobile individuals, such as migrant workers and asylum seekers, are an expanding global population of growing social, demographic and political importance. Disparities often exist between a migrant population's place of origin and its destination, particularly with relation to health determinants. The effects of those disparities can be observed at both individual and population levels. Migration across health and disease disparities influences the epidemiology of certain diseases globally and in nations receiving migrants. While specific disease-based outcomes may vary between migrant group and location, general epidemiological principles may be applied to any situation where numbers of individuals move between differences in disease prevalence. Traditionally, migration health activities have been designed for national application and lack an integrated international perspective. Present and future health challenges related to migration may be more effectively addressed through collaborative global undertakings. This paper reviews the epidemiological relationships resulting from health disparities bridged by migration and describes the growing role of migration and population mobility in global disease epidemiology. The implications for national and international health policy and program planning are presented.", "qid": 21, "docid": "xne08vbd", "rank": 81, "score": 0.6652876734733582}, {"content": "Title: Burden and changes in HIV/AIDS morbidity and mortality in Southern Africa Development Community Countries, 1990\u20132017 Content: BACKGROUND: The 16 Southern Africa Development Community (SADC) countries remain the epicentre of the HIV/AIDS epidemic with the largest number of people living with HIV/AIDS. Anti-retroviral treatment (ART) has improved survival and prevention of mother-to-child transmission (PMTCT) of HIV, but the disease remains a serious cause of mortality. We conducted a descriptive epidemiological analysis of HIV/AIDS burden for the 16 SADC countries using secondary data from the Global Burden of Diseases, Injuries and Risk Factor (GBD) Study. METHODS: The GBD study is a systematic, scientific effort by the Institute for Health Metrics and Evaluation (IHME) to quantify the comparative magnitude of health loss due to diseases, injuries, and risk factors by age, sex, and geographies for specific points in time. We analyzed the following outcomes: mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to HIV/AIDS for SADC. Input data for GBD was extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service utilisation, disease notifications, and other sources. Country- and cause-specific HIV/AIDS-related death rates were calculated using the Cause of Death Ensemble model (CODEm) and spatiotemporal Gaussian process regression (ST-GPR). Deaths were multiplied by standard life expectancy at each age-group to calculate YLLs. Cause-specific mortality was estimated using a Bayesian meta-regression modelling tool, DisMod-MR. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases to calculate YLDs. Crude and age-adjusted rates per 100,000 population and changes between 1990 and 2017 were determined for each country. RESULTS: In 2017, HIV/AIDS caused 336,175 deaths overall in SADC countries, and more than 20 million DALYs. This corresponds to a 3-fold increase from 113,631 deaths (6,915,170 DALYs) in 1990. The five leading countries with the proportion of deaths attributable to HIV/AIDS in 2017 were Botswana at the top with 28.7% (95% UI; 23.7\u201335.2), followed by South Africa 28.5% (25.8\u201331.6), Lesotho, 25.1% (21.2\u201330.4), eSwatini 24.8% (21.3\u201328.6), and Mozambique 24.2% (20.6\u201329.3). The five countries had relative attributable deaths that were at least 14 times greater than the global burden of 1.7% (1.6\u20131.8). Similar patterns were observed with YLDs, YLLs, and DALYs. Comoros, Seychelles and Mauritius were on the lower end, with attributable proportions less than 1%, below the global proportion. CONCLUSIONS: Great progress in reducing HIV/AIDS burden has been achieved since the peak but more needs to be done. The post-2005 decline is attributed to PMTCT of HIV, resources provided through the US President\u2019s Emergency Plan For AIDS Relief (PEPFAR), and behavioural change. The five countries with the highest burden of HIV/AIDS as measured by proportion of death attributed to HIV/AIDS and age-standardized mortaility rate were Botswana, South Africa, Lesotho, eSwatini, and Mozambique. SADC countries should cooperate, work with donors, and embrace the UN Fast-Track approach, which calls for frontloading investment from domestic or other sources to prevent and treat HIV/AIDS. Robust tracking, testing, and early treatment are required, as well as refinement of individual treatment strategies for transient individuals in the region.", "qid": 21, "docid": "hs9cfdsu", "rank": 82, "score": 0.6650242805480957}, {"content": "Title: Relative Coronavirus Disease 2019 Mortality: A Swiss Population-based Study Content: Objective: Severity of the coronavirus disease 2019 (covid-19) has been assessed in terms of absolute mortality in SARS-CoV-2 positive cohorts. An assessment of mortality relative to mortality in the general population is presented. Design: Retrospective population-based study. Setting: Individual information on symptomatic confirmed SARS-CoV-2 patients and subsequent deaths from any cause were compared to the all-cause mortality in the Swiss population of 2018. Starting February 23, 2020, mortality in covid-19 patients was monitored for 80 days and compared to the population mortality observed in the same time-of-year starting February 23, 2018. Participants: 5 160 595 inhabitants of Switzerland aged 35 to 95 without covid-19 (general population in spring 2018) and 20 769 persons tested positively for covid-19 (spring 2020). Measurements: Sex- and age-specific mortality rates were estimated using Cox proportional hazards models. Absolute probabilities of death were predicted and risk was assessed in terms of relative mortality by taking the ratio between the sex- and age-specific absolute mortality in covid19 patients and the corresponding mortality in the 2018 general population. Results: A confirmed SARS-CoV-2 infection substantially increased the probability of death across all patient groups, ranging from nine (6 to 15) times the population mortality in 35-year old infected females to a 53-fold increase (46 to 59) for 95 year old infected males. The highest relative risks were observed among males and older patients. The magnitude of these effects was smaller compared to increases observed in absolute mortality risk. Male covid-19 patients exceeded the population hazard for males (hazard ratio 1.20, 1.00 to 1.44). Each additional year of age increased the population hazard in covid-19 patients (hazard ratio 1.04, 1.03 to 1.05). Limitations: Information about the distribution of relevant comorbidities was not available on population level and the associated risk was not quantified. Conclusions: Health care professionals, decision makers, and societies are provided with an additional population-adjusted assessment of covid-19 mortality risk. In combination with absolute measures of risk, the relative risks presented here help to develop a more comprehensive understanding of the actual impact of covid-19.", "qid": 21, "docid": "92ipp5ge", "rank": 83, "score": 0.6649075746536255}, {"content": "Title: [Democracy and Covid-19 mortality in Europe.] Content: OBJECTIVE: In Europe there is a great variability in mortality by Covid-19 among different countries While some countries, such as Greece, Belarus or Ukraine, have a mortality rate of less than 5 cases/100,000 inhabitants, other countries such as Belgium, Spain or the United Kingdom have a mortality rate of well over 50 cases/100,000 inhabitants It is generally considered that the reason for this variability is multifactorial (including political reasons), but there are few studies that associate factors related to this variability The objective of this work was to analyse political risk factors/markers that could explain the variability in mortality due to Covid-19 among different European countries METHODS: This is a retrospective, multinational, ecological study based on the exploitation of the database provided by the European Centre for Disease Prevention and Control which collects daily information worldwide on new cases and deaths The accumulated mortality of Covid-19 in European countries (with more than 100 deaths on 01/05/2020) was calculated up to 29/05/2020 Political variables were compiled from different sources in the countries included in the study The variables analysed were: the democracy index and the different factors included in it, the country's political system and the country's corruption index On the other hand, specific political measures implemented in the different countries were collected, such as the number of days elapsed from the notification of the first infected person to 100 infected persons, to lockdown, to the closure of schools or the cancelation of meetings The number of people infected up to the date of lockdown was also registered For the statistical analysis of the association between the dependent variable (mortality) and the factors studied, correlation index were calculated, and the association was studied through univariate and multivariate linear regression models RESULTS: At May 1 2020, 27 European countries had at least 100 deaths The mean mortality was 19 83 cases/100,000 inhabitants (SD 22 4) and a median of 7 95 Mortality varied from a minimum of 1 49 cases/100,000 population in Ukraine to 82 19 cases/100,000 population in Belgium About factors analyzed both the democracy index (as well as the factors included in it), the political system (full democracy vs no) and the corruption index were statistically associated with mortality Also, the time until the implementation of the political measures was associated with mortality CONCLUSIONS: In Europe, there is a west to east (from highest to lowest) gradient in the mortality of Covid-19 Some of the observed mortality variability can be explained by political factors", "qid": 21, "docid": "6w02vzcw", "rank": 84, "score": 0.6645221710205078}, {"content": "Title: Age effects in monetary valuation of reduced mortality risks: the relevance of age-specific hazard rates Content: This paper highlights the relevance of age-specific hazard rates in explaining the age variation in \u201cvalue of statistical life\u201d (VSL) figures. The analysis\u2014which refers to a stated preference framework\u2014contributes to the ongoing discussion of whether benefits resulting from reduced mortality risk should be valued differently depending on the age of the beneficiaries. By focussing on a life-threatening environmental phenomenon I show that the consideration of the individual\u2019s age-specific hazard rate is important. If a particular risk affects all individuals regardless of their age so that their hazard rate is age-independent, VSL is rather constant for people at different age; if hazard rate varies with age, VSL estimates are sensitive to age. The results provide an explanation for the mixed outcomes in empirical studies and illustrate in which cases an adjustment to age may or may not be justified. Efficient provision of live-saving measures requires that such differences to be taken into account.", "qid": 21, "docid": "um9kefk4", "rank": 85, "score": 0.6636459827423096}, {"content": "Title: [Democracy and Covid-19 mortality in Europe.] Content: OBJECTIVE In Europe there is a great variability in mortality by Covid-19 among different countries. While some countries, such as Greece, Belarus or Ukraine, have a mortality rate of less than 5 cases/100,000 inhabitants, other countries such as Belgium, Spain or the United Kingdom have a mortality rate of well over 50 cases/100,000 inhabitants. It is generally considered that the reason for this variability is multifactorial (including political reasons), but there are few studies that associate factors related to this variability. The objective of this work was to analyse political risk factors/markers that could explain the variability in mortality due to Covid-19 among different European countries. METHODS This is a retrospective, multinational, ecological study based on the exploitation of the database provided by the European Centre for Disease Prevention and Control which collects daily information worldwide on new cases and deaths. The accumulated mortality of Covid-19 in European countries (with more than 100 deaths on 01/05/2020) was calculated up to 29/05/2020. Political variables were compiled from different sources in the countries included in the study. The variables analysed were: the democracy index and the different factors included in it, the country's political system and the country's corruption index. On the other hand, specific political measures implemented in the different countries were collected, such as the number of days elapsed from the notification of the first infected person to 100 infected persons, to lockdown, to the closure of schools or the cancelation of meetings. The number of people infected up to the date of lockdown was also registered. For the statistical analysis of the association between the dependent variable (mortality) and the factors studied, correlation index were calculated, and the association was studied through univariate and multivariate linear regression models. RESULTS At May 1 2020, 27 European countries had at least 100 deaths. The mean mortality was 19.83 cases/100,000 inhabitants (SD 22.4) and a median of 7.95. Mortality varied from a minimum of 1.49 cases/100,000 population in Ukraine to 82.19 cases/100,000 population in Belgium. About factors analyzed both the democracy index (as well as the factors included in it), the political system (full democracy vs. no) and the corruption index were statistically associated with mortality. Also, the time until the implementation of the political measures was associated with mortality. CONCLUSIONS In Europe, there is a west to east (from highest to lowest) gradient in the mortality of Covid-19. Some of the observed mortality variability can be explained by political factors.", "qid": 21, "docid": "yuk8r3gt", "rank": 86, "score": 0.6634092926979065}, {"content": "Title: Estimating the Size of High-risk Populations for COVID-19 Mortality across 442 US Cities Content: A variety of predisposing factors have been associated with serious illness and death from COVID-19. Understanding the distribution of risks associated with these factors by local communities can provide important opportunities for targeting interventions. We characterize the distribution of risk for COVID-19 mortality for populations at large across 442 US cities, by utilizing recently published estimates of risk associated with age, gender, ethnicity, social deprivation and 12 health conditions from a very large UK-based study, combined with the information available on prevalence and co-occurrence of these factors in the US through a variety of population-based public databases. We estimate that across all the cities, an underlying weighted risk-score can identify a total of approximately 12.65 million, 4.09 million and 1.34 million individuals who are at 2-, 5- and 10-fold higher risk, respectively, compared to the average risk for the US population. The percentage of population which exceed the respective risk thresholds varies across the cities in the range (1st-99th percentile), 3.6%-20.1%, 0.7%-8.0% and 0.1%-3.2%, respectively. The percentage of deaths within a city that are expected to occur above these risk-thresholds varies in the range of 20.1%-53.5%, 8.5%-38.2% and 2.9%-25.4%, respectively. Our analysis can provide guidance to national and local policy makers regarding resources needed to protect the most vulnerable populations in these communities, and how much utility such interventions may have in reducing the total population burden of death.", "qid": 21, "docid": "9n9irx70", "rank": 87, "score": 0.6631410121917725}, {"content": "Title: A geographic analysis of population density thresholds in the influenza pandemic of 1918\u201319 Content: BACKGROUND: Geographic variables play an important role in the study of epidemics. The role of one such variable, population density, in the spread of influenza is controversial. Prior studies have tested for such a role using arbitrary thresholds for population density above or below which places are hypothesized to have higher or lower mortality. The results of such studies are mixed. The objective of this study is to estimate, rather than assume, a threshold level of population density that separates low-density regions from high-density regions on the basis of population loss during an influenza pandemic. We study the case of the influenza pandemic of 1918\u201319 in India, where over 15 million people died in the short span of less than one year. METHODS: Using data from six censuses for 199 districts of India (n=1194), the country with the largest number of deaths from the influenza of 1918\u201319, we use a sample-splitting method embedded within a population growth model that explicitly quantifies population loss from the pandemic to estimate a threshold level of population density that separates low-density districts from high-density districts. RESULTS: The results demonstrate a threshold level of population density of 175 people per square mile. A concurrent finding is that districts on the low side of the threshold experienced rates of population loss (3.72%) that were lower than districts on the high side of the threshold (4.69%). CONCLUSIONS: This paper introduces a useful analytic tool to the health geographic literature. It illustrates an application of the tool to demonstrate that it can be useful for pandemic awareness and preparedness efforts. Specifically, it estimates a level of population density above which policies to socially distance, redistribute or quarantine populations are likely to be more effective than they are for areas with population densities that lie below the threshold.", "qid": 21, "docid": "hwkouyzd", "rank": 88, "score": 0.66258704662323}, {"content": "Title: Changes in cold-related mortalities between 1995 and 2016 in South East England Content: Abstract Objective The aim of the study was to examine trends in cold-related mortalities between 1995 and 2016. Study design This is a longitudinal mortality study. Methods For men and women aged 65\u201374 years or those older than 85 years in South East England, the relationship between daily mortality (deaths per million population) and outdoor temperatures below 18 \u00b0C, with allowance for influenza epidemics, was assessed by linear regression on an annual basis. The regression coefficients were expressed as a percentage of the mortality at 18 \u00b0C to adjust for changes in mortality through health care. Trends in \u2018specific\u2019 cold-related mortalities were then examined over two periods, 1977\u20131994 and 1995\u20132016. Results In contrast to the early period, annual trends in cold-related specific mortalities showed no decline between 1995 and 2016. \u2018Specific\u2019 cold-related mortality of women, but not men, in the age group older than 85 years showed a significant increase over the 1995\u20132016 period, which was different from the trend over the earlier period (P < 0.01). Conclusion Despite state-funded benefits to help alleviate fuel poverty and public health advice, very elderly women appear to be at increasing risk of cold-related mortality\u2014greater help may be necessary.", "qid": 21, "docid": "wdhsxj16", "rank": 89, "score": 0.6623480319976807}, {"content": "Title: Mortality of people with intellectual disabilities during the 2017/2018 influenza epidemic in the Netherlands: potential implications for the COVID\u201019 pandemic Content: BACKGROUND: Data on the development of Covid\u201019 among people with intellectual disabilities (IDs) are scarce and it is uncertain to what extent general population data applies to people with ID. To give an indication of possible implications, this study investigated excess mortality patterns during a previous influenza epidemic. METHODS: Using Dutch population and mortality registers, a historical cohort study was designed to compare mortality during the 2017\u20132018 influenza epidemic with mortality in the same period in the three previous years. People with ID were identified by entitlements to residential ID\u2010care services as retrieved from a national database. RESULTS: Data covered the entire adult Dutch population (12.6 million; GenPop), of which 91 064 individuals were identified with an ID. During the influenza epidemic, mortality among people with ID increased almost three times as much than in the GenPop (15.2% vs. 5.4%), and more among male individuals with ID (+19.5%) than among female individuals with ID (+10.6%), as compared with baseline. In both cohorts, comparable increases in mortality within older age groups and due to respiratory causes were seen. Particularly in the ID\u2010cohort, excess deaths also occurred in younger age groups, due to endocrine diseases and ID\u2010specific causes. CONCLUSIONS: During the 2017\u20132018 influenza epidemic, excess mortality among people with ID was three times higher than in the general Dutch population, appeared more often at young age and with a broader range of underlying causes. These findings suggest that a pandemic may disproportionally affect people with ID while population data may not immediately raise warnings. Early detection of diverging patterns and faster implementation of tailored strategies therefore require collection of good quality data.", "qid": 21, "docid": "rmcsjck3", "rank": 90, "score": 0.6621241569519043}, {"content": "Title: Deaths in SARS-Cov-2 Positive Patients in Italy: The Influence of Underlying Health Conditions on Lethality Content: This study aims to underline the clinical characteristics of patients who died after testing positive for SARS-CoV-2 infection in one region of Italian and to evaluate the influence of underlying health conditions on the fatal outcome. A matched case-control study was designed by analyzing the data regarding positive subjects observed up to April 21, 2020. The case fatality rate was 7.9%, with a higher proportion of deaths in men than women. The specific standardized mortality ratio was 0.15\u20140.13 for males and 0.2 for females, showing that mortality is much lower than expected. Cardiovascular diseases, chronic lung diseases and diabetes mellitus showed a significant association with the outcome. Although the case fatality rate in Sardinia in regard to age and gender patterns seems to be similar to that for Italy as a whole, its quantitative value was far lower than the national one and possible explanations might include the genetic characteristics of the Sardinian population or the immediate closure of its borders as soon as the epidemic started. Our results highlighted that lethality is strongly dependent on the presence of multiple concomitant serious diseases. It is important to have epidemiological strategies for effective guidance on public health actions in order to improve chances of survival.", "qid": 21, "docid": "h7r3xsth", "rank": 91, "score": 0.662093997001648}, {"content": "Title: Early Epidemiological Assessment of the Virulence of Emerging Infectious Diseases: A Case Study of an Influenza Pandemic Content: BACKGROUND: The case fatality ratio (CFR), the ratio of deaths from an infectious disease to the number of cases, provides an assessment of virulence. Calculation of the ratio of the cumulative number of deaths to cases during the course of an epidemic tends to result in a biased CFR. The present study develops a simple method to obtain an unbiased estimate of confirmed CFR (cCFR), using only the confirmed cases as the denominator, at an early stage of epidemic, even when there have been only a few deaths. METHODOLOGY/PRINCIPAL FINDINGS: Our method adjusts the biased cCFR by a factor of underestimation which is informed by the time from symptom onset to death. We first examine the approach by analyzing an outbreak of severe acute respiratory syndrome in Hong Kong (2003) with known unbiased cCFR estimate, and then investigate published epidemiological datasets of novel swine-origin influenza A (H1N1) virus infection in the USA and Canada (2009). Because observation of a few deaths alone does not permit estimating the distribution of the time from onset to death, the uncertainty is addressed by means of sensitivity analysis. The maximum likelihood estimate of the unbiased cCFR for influenza may lie in the range of 0.16\u20134.48% within the assumed parameter space for a factor of underestimation. The estimates for influenza suggest that the virulence is comparable to the early estimate in Mexico. Even when there have been no deaths, our model permits estimating a conservative upper bound of the cCFR. CONCLUSIONS: Although one has to keep in mind that the cCFR for an entire population is vulnerable to its variations among sub-populations and underdiagnosis, our method is useful for assessing virulence at the early stage of an epidemic and for informing policy makers and the public.", "qid": 21, "docid": "7v4y02j6", "rank": 92, "score": 0.6620675325393677}, {"content": "Title: How do environmental, economic and health factors influence regional vulnerability to COVID-19? Content: We have studied the correlations between twelve environmental, economic and health variables, by carrying out a statistical analysis of the fatality rate of COVID-19 in 14 countries. Our statistical analysis indicates that, among the 12 variables, the diabetes percentage of the total population and the extent of the population ages 65 and older in each country are correlated most strongly with the total number of deaths in them. Although the strength of the correlations between the variables and the total ND may change as the ongoing pandemic evolves, the study highlights the importance of integrating regional-specific variables in the modelling efforts aimed at projecting how the spread of the virus may influence different parts of the world.", "qid": 21, "docid": "dhy80rkn", "rank": 93, "score": 0.66191565990448}, {"content": "Title: Mortality of Life\u2010Insured Swedish Cats during 1999\u20132006: Age, Breed, Sex, and Diagnosis Content: Background: A cat life insurance database can potentially be used to study feline mortality. Hypothesis: The aim was to describe patterns of mortality in life\u2010insured Swedish cats. Cats: All cats (<13 years of age) with life insurance during the period 1999\u20132006 were included. Methods: Age\u2010standardized mortality rates (MR) were calculated with respect to sex (males and females), age, breed, and diagnosis. Survival to various ages is presented by time period and breed. Results: The total number of cats insured was 49,450 and the number of cat\u2010years at risk (CYAR) was 142,049. During the period, 6,491 cats died and of these 4,591 cats (71%) had a diagnosis, ie, were claimed for life insurance. The average annual MR was 462 deaths per 10,000 CYAR (95% confidence interval, 431\u2013493). Sex\u2010specific rates did not differ significantly. The overall mortality of the Persian and the Siamese groups was higher than that of several other breeds. Overall and breed\u2010specific (for most breeds) survival increased with time when analyzed by 2\u2010year periods. The 6 most common diagnostic categories (ignoring cats recorded as dead with no diagnosis) were urinary, traumatic, neoplastic, infectious, cardiovascular, and gastrointestinal. The MR within diagnostic categories varied by age and breed. Conclusions and Clinical Importance: In this mainly purebred, insured cat population, the overall mortality varied with age and breed but not with sex. The increase in survival over time is likely a reflection of willingness to keep pet cats longer and increased access to and sophistication of veterinary care.", "qid": 21, "docid": "al3p52uj", "rank": 94, "score": 0.6611254215240479}, {"content": "Title: Impact of COVID-19 on 2020 US life expectancy for the Black and Latino populations Content: The Black and Latino populations have experienced a disproportionate burden of COVID-19 morbidity and mortality, reflecting persistent structural inequalities that increase risk of exposure to COVID-19 and risk of death for those infected. According to the National Center for Health Statistics, as of July 4, 2020, deaths to Black and Latino individuals comprised 23% and 17%, respectively, of the approximately 115,000 COVID-19 deaths. COVID-19 mortality is likely to result in a larger decline in life expectancy during 2020 than the US has experienced for decades as well as a particularly large reduction for Black and Latino individuals. We estimate life expectancy at birth and at age 65 for 2020, by race and ethnicity, using four scenarios of deaths-one in which the COVID-19 pandemic had not occurred and three including COVID-19 mortality projections produced by the Institute for Health Metrics and Evaluation. Our most likely estimate indicates a reduction in life expectancy at birth greater than 1.5 years for both the Black and Latino populations, which is one year larger than the reduction for whites. This would imply that the Black-white gap would increase by 30%, from 3.6 to 4.7 years, thereby eliminating progress made in reducing this differential since 2008 and reversing an overall trend of steeper mortality declines among the Black population since the early 1990s. Latinos, who have consistently experienced lower mortality than whites (a phenomenon known as the Latino or Hispanic paradox), would see their survival advantage decline by 36%, equivalent to its magnitude in 2006.", "qid": 21, "docid": "bjvg2ivr", "rank": 95, "score": 0.6609277725219727}, {"content": "Title: Total COVID-19 Mortality in Italy: Excess Mortality and Age Dependence through Time-Series Analysis Content: We perform a counterfactual time series analysis using two different Data Science methods applied to 2020 mortality data reported from towns in Italy, with data from the previous five years as control. We find an excess mortality that is correlated in time with the COVID-19 reported death rate time series. Our analysis shows good agreement with reported COVID-19 mortality for age<70 years, but an excess in total mortality increasing with age above 70 years, suggesting there is a large population of predominantly old people missing from the official fatality statistics. We estimate that the number of COVID-19 deaths in Italy is 52,000 \u00b1 2000 as of April 18 2020, more than a factor of 2 higher than the official number. The Population Fatality Rate (PFR) has reached 0.22% in the most affected region of Lombardia and 0.57% in the most affected province of Bergamo,which constitutes a lower bound to the Infection Fatality Rate (IFR). We estimate PFR as a function of age, finding a steep age dependence: in Lombardia (Bergamo province) 0.6% (1.7%) of the total population in age group 70-79 died, 1.6% (4.6%) in age group 80-89, and 3.41% (10.2%) in the age group above 90. We combine this with the Test Positivity Rate to estimate the lower bound of 0.84% on the IFR for Lombardia. We observe IFR to trace the Yearly Mortality Rate (YMR) above 60 years, which can be used to estimate the IFR for other regions in the world. We predict an IFR lower bound of 0.5% for NYC and 26% of total COVID-19 mortality arising from the population below 65 years, in agreement with the existing data and several times higher than Lombardia. Combining PFR with the Princess Diamond cruise ship IFR for ages above 70 we estimate the infection rates(IR) of regions in Italy, which peak in Lombardia at 23% (12%-41%, 95% c.l.), and for provinces in Bergamo at 67% (33%-100%, 95% c.l.). This suggests that Bergamo may have reached herd immunity, and that the number of infected people greatly exceeds the number of positive tests, by a factor of 35 in Lombardia.", "qid": 21, "docid": "vg96f35h", "rank": 96, "score": 0.6608247756958008}, {"content": "Title: Staphylococcus aureus Colonization and Long-Term Risk for Death, United States. Content: To examine the association of colonization by Staphylococcus aureus and general population mortality, we followed 10,598 adults for 8.5 years on average. Methicillin-susceptible S. aureus colonization was not associated with death. Methicillin-resistant S. aureus carriage predicted death in a crude analysis but not after adjustment for socioeconomic status and co-morbidities.", "qid": 21, "docid": "pzdssyiu", "rank": 97, "score": 0.660821795463562}, {"content": "Title: Deaths in SARS-Cov-2 Positive Patients in Italy: The Influence of Underlying Health Conditions on Lethality Content: This study aims to underline the clinical characteristics of patients who died after testing positive for SARS-CoV-2 infection in one region of Italian and to evaluate the influence of underlying health conditions on the fatal outcome. A matched case-control study was designed by analyzing the data regarding positive subjects observed up to April 21, 2020. The case fatality rate was 7.9%, with a higher proportion of deaths in men than women. The specific standardized mortality ratio was 0.15-0.13 for males and 0.2 for females, showing that mortality is much lower than expected. Cardiovascular diseases, chronic lung diseases and diabetes mellitus showed a significant association with the outcome. Although the case fatality rate in Sardinia in regard to age and gender patterns seems to be similar to that for Italy as a whole, its quantitative value was far lower than the national one and possible explanations might include the genetic characteristics of the Sardinian population or the immediate closure of its borders as soon as the epidemic started. Our results highlighted that lethality is strongly dependent on the presence of multiple concomitant serious diseases. It is important to have epidemiological strategies for effective guidance on public health actions in order to improve chances of survival.", "qid": 21, "docid": "1efmb8ow", "rank": 98, "score": 0.6607893705368042}, {"content": "Title: Worldwide differences in COVID-19-related mortality Content: Mortality statistics due to COVID-19 worldwide are compared, by adjusting for the size of the population and the stage of the pandemic. Data from the European Centre for Disease Control and Prevention, and Our World in Data websites were used. Analyses are based on number of deaths per one million inhabitants. In order to account for the stage of the pandemic, the baseline date was defined as the day in which the 10th death was reported. The analyses included 78 countries and territories which reported 10 or more deaths by April 9. On day 10, India had 0.06 deaths per million, Belgium had 30.46 and San Marino 618.78. On day 20, India had 0.27 deaths per million, China had 0.71 and Spain 139.62. On day 30, four Asian countries had the lowest mortality figures, whereas eight European countries had the highest ones. In Italy and Spain, mortality on day 40 was greater than 250 per million, whereas in China and South Korea, mortality was below 4 per million. Mortality on day 10 was moderately correlated with life expectancy, but not with population density. Asian countries presented much lower mortality figures as compared to European ones. Life expectancy was found to be correlated with mortality.", "qid": 21, "docid": "xwpqae0r", "rank": 99, "score": 0.6605721712112427}, {"content": "Title: Worldwide differences in COVID-19-related mortality. Content: Mortality statistics due to COVID-19 worldwide are compared, by adjusting for the size of the population and the stage of the pandemic. Data from the European Centre for Disease Control and Prevention, and Our World in Data websites were used. Analyses are based on number of deaths per one million inhabitants. In order to account for the stage of the pandemic, the baseline date was defined as the day in which the 10th death was reported. The analyses included 78 countries and territories which reported 10 or more deaths by April 9. On day 10, India had 0.06 deaths per million, Belgium had 30.46 and San Marino 618.78. On day 20, India had 0.27 deaths per million, China had 0.71 and Spain 139.62. On day 30, four Asian countries had the lowest mortality figures, whereas eight European countries had the highest ones. In Italy and Spain, mortality on day 40 was greater than 250 per million, whereas in China and South Korea, mortality was below 4 per million. Mortality on day 10 was moderately correlated with life expectancy, but not with population density. Asian countries presented much lower mortality figures as compared to European ones. Life expectancy was found to be correlated with mortality.", "qid": 21, "docid": "inhxonsk", "rank": 100, "score": 0.6605721712112427}]}
{"query": "are cardiac complications likely in patients with COVID-19?", "hits": [{"content": "Title: Coronavirus Disease-2019 (COVID-19) and Cardiovascular Complications Content: The coronavirus disease-2019 (COVID-19) has become a global pandemic. It has spread to more than 100 countries, and more than 1 million cases have been confirmed. Although coronavirus causes severe respiratory infections in humans, accumulating data have demonstrated cardiac complications and poor outcome in patients with COVID-19. A large percent of patients have underlying cardiovascular disease, and they are at a high risk of developing cardiac complications. The basics of the virus, the clinical manifestations, and the possible mechanisms of cardiac complications in patients with COVID-19 are reviewed. Before an effective vaccine or medicine is available, supportive therapy and identifying patients who are at high risk of cardiac complications are important.", "qid": 22, "docid": "wkp58iov", "rank": 1, "score": 0.9028692245483398}, {"content": "Title: Coronavirus disease 2019 (COVID-19) and cardiovascular complications Content: Abstract The coronavirus disease 2019 (COVID-19) has become a global pandemic. It has been spread to more than 100 countries and more than 1 million patients have been confirmed. Although coronavirus causes severe respiratory infections in human, accumulating data have demonstrated cardiac complications and poor outcome in patients with coronavirus disease 2019. A large percent of patients have underlying cardiovascular disease and they are at a high risk of developing cardiac complications. We review the basics of the virus, the clinical manifestation, and the possible mechanisms of cardiac complications in patients with coronavirus disease 2019. Before the effective vaccine or medicine is available, supportive therapy and identifying patients who are at high risk of cardiac complications are important.", "qid": 22, "docid": "v3qgqfwr", "rank": 2, "score": 0.8852611780166626}, {"content": "Title: Cardiovascular complications in COVID-19 Content: BACKGROUND: The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur. OBJECTIVE: This brief report evaluates cardiovascular complications in the setting of COVID-19 infection. DISCUSSION: The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death. The virus binds and enters through angiotensin-converting enzyme 2 (ACE2). COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness. The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events. Current therapies for COVID-19 may interact with cardiovascular medications. CONCLUSIONS: Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.", "qid": 22, "docid": "hl225efn", "rank": 3, "score": 0.8832639455795288}, {"content": "Title: SARS-CoV-2 Infection and Cardiovascular Disease: COVID-19 Heart Content: Coronavirus disease (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The symptoms of the disease range from asymptomatic to mild respiratory symptoms and even potentially life-threatening cardiovascular and pulmonary complications. Cardiac complications include acute myocardial injury, arrhythmias, cardiogenic shock and even sudden death. Furthermore, drug interactions with COVID-19 therapies may place the patient at risk for arrhythmias, cardiomyopathy and sudden death. In this review, we summarise the cardiac manifestations of COVID-19 infection and propose a simplified algorithm for patient management during the COVID-19 pandemic.", "qid": 22, "docid": "0376d6vf", "rank": 4, "score": 0.8752896189689636}, {"content": "Title: Cardiac involvement in COVID-19 patients: Risk factors, predictors, and complications: A review Content: BACKGROUND: Respiratory complications have been well remarked in the novel coronavirus disease (SARS-CoV-2/COVID-19), yet an emerging body of research indicates that cardiac involvement may be implicated in poor outcomes for these patients. AIMS: This review seeks to gather and distill the existing body of literature that describes the cardiac implications of COVID-19. MATERIALS AND METHODS: The English literature was reviewed for papers dealing with the cardiac effects of COVID-19. RESULTS: Notably, COVID-19 patients with pre-existing cardiovascular disease are counted in greater frequency in intensive care unit settings, and ultimately suffer greater rates of mortality. Other studies have noted cardiac presentations for COVID-19, rather than respiratory, such as acute pericarditis and left ventricular dysfunction. In some patients there has been evidence of acute myocardial injury, with correspondingly increased serum troponin I levels. With regard to surgical interventions, there is a dearth of data describing myocardial protection during cardiac surgery for COVID-19 patients. Although some insights have been garnered in the study of cardiovascular diseases for these patients, these insights remain fragmented and have yet to cement clear guidelines for actionable clinical practice. CONCLUSION: While some information is available, further studies are imperative for a more cohesive understanding of the cardiac pathophysiology in COVID-19 patients to promote more informed treatment and, ultimately, better clinical outcomes.", "qid": 22, "docid": "0ec1cu8q", "rank": 5, "score": 0.8747768998146057}, {"content": "Title: Cardiovascular complications in COVID-19 Content: Abstract Background The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur. Objective This brief report evaluates cardiovascular complications in the setting of COVID-19 infection. Discussion The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death. The virus binds and enters through angiotensin-converting enzyme 2 (ACE2). COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness. The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events. Current therapies for COVID-19 may interact with cardiovascular medications. Conclusions Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.", "qid": 22, "docid": "mbbnk3la", "rank": 6, "score": 0.8742382526397705}, {"content": "Title: Cardiovascular Risks in Patients with COVID-19: Potential Mechanisms and Areas of Uncertainty Content: PURPOSE OF REVIEW: COronaVirus Disease 2019 (COVID-19) has spread at unprecedented speed and scale into a global pandemic with cardiovascular risk factors and complications emerging as important disease modifiers. We aim to review available clinical and biomedical literature on cardiovascular risks of COVID-19. RECENT FINDINGS: SARS-CoV2, the virus responsible for COVID-19, enters the cell via ACE2 expressed in select organs. Emerging epidemiological evidence suggest cardiovascular risk factors are associated with increased disease severity and mortality in COVID-19 patients. Patients with a more severe form of COVID-19 are also more likely to develop cardiac complications such as myocardial injury and arrhythmia. The true incidence of and mechanism underlying these events remain elusive. SUMMARY: Cardiovascular diseases appear intricately linked with COVID-19, with cardiac complications contributing to the elevated morbidity/mortality of COVID-19. Robust epidemiologic and biologic studies are urgently needed to better understand the mechanism underlying these associations to develop better therapies.", "qid": 22, "docid": "lfjud2aq", "rank": 7, "score": 0.8730800151824951}, {"content": "Title: Cardiovascular Risks in Patients with COVID-19: Potential Mechanisms and Areas of Uncertainty Content: PURPOSE OF REVIEW: COronaVirus Disease 2019 (COVID-19) has spread at unprecedented speed and scale into a global pandemic with cardiovascular risk factors and complications emerging as important disease modifiers. We aim to review available clinical and biomedical literature on cardiovascular risks of COVID-19. RECENT FINDINGS: SARS-CoV2, the virus responsible for COVID-19, enters the cell via ACE2 expressed in select organs. Emerging epidemiological evidence suggest cardiovascular risk factors are associated with increased disease severity and mortality in COVID-19 patients. Patients with a more severe form of COVID-19 are also more likely to develop cardiac complications such as myocardial injury and arrhythmia. The true incidence of and mechanism underlying these events remain elusive. Cardiovascular diseases appear intricately linked with COVID-19, with cardiac complications contributing to the elevated morbidity/mortality of COVID-19. Robust epidemiologic and biologic studies are urgently needed to better understand the mechanism underlying these associations to develop better therapies.", "qid": 22, "docid": "ejsqsn59", "rank": 8, "score": 0.8707937002182007}, {"content": "Title: O Cora\u00e7\u00e3o e a COVID-19: O que o Cardiologista Precisa Saber./ O Cora\u00e7\u00e3o e a COVID-19: O que o Cardiologista Precisa Saber./ The Heart and COVID-19: What Cardiologists Need to Know Content: In face of the pandemic of the novel coronavirus disease 2019 (COVID-19), the management of patients with cardiovascular risk factors and/or disease is challenging. The cardiovascular complications evidenced in patients with COVID-19 derive from several mechanisms, ranging from direct viral injury to complications secondary to the inflammatory and thrombotic responses to the infection. The proper care of patients with COVID-19 requires special attention to the cardiovascular system aimed at better outcomes.", "qid": 22, "docid": "tp2tm0vn", "rank": 9, "score": 0.8695333003997803}, {"content": "Title: The Heart and COVID-19: What Cardiologists Need to Know. Content: In face of the pandemic of the novel coronavirus disease 2019 (COVID-19), the management of patients with cardiovascular risk factors and/or disease is challenging. The cardiovascular complications evidenced in patients with COVID-19 derive from several mechanisms, ranging from direct viral injury to complications secondary to the inflammatory and thrombotic responses to the infection. The proper care of patients with COVID-19 requires special attention to the cardiovascular system aimed at better outcomes.", "qid": 22, "docid": "7icw3be3", "rank": 10, "score": 0.8695333003997803}, {"content": "Title: Cardiac involvement in COVID\u201019 patients: Risk factors, predictors, and complications: A review Content: BACKGROUND: Respiratory complications have been well remarked in the novel coronavirus disease (SARS\u2010CoV\u20102/COVID\u201019), yet an emerging body of research indicates that cardiac involvement may be implicated in poor outcomes for these patients. AIMS: This review seeks to gather and distill the existing body of literature that describes the cardiac implications of COVID\u201019. MATERIALS AND METHODS: The English literature was reviewed for papers dealing with the cardiac effects of COVID\u201019. RESULTS: Notably, COVID\u201019 patients with pre\u2010existing cardiovascular disease are counted in greater frequency in intensive care unit settings, and ultimately suffer greater rates of mortality. Other studies have noted cardiac presentations for COVID\u201019, rather than respiratory, such as acute pericarditis and left ventricular dysfunction. In some patients there has been evidence of acute myocardial injury, with correspondingly increased serum troponin I levels. With regard to surgical interventions, there is a dearth of data describing myocardial protection during cardiac surgery for COVID\u201019 patients. Although some insights have been garnered in the study of cardiovascular diseases for these patients, these insights remain fragmented and have yet to cement clear guidelines for actionable clinical practice. CONCLUSION: While some information is available, further studies are imperative for a more cohesive understanding of the cardiac pathophysiology in COVID\u201019 patients to promote more informed treatment and, ultimately, better clinical outcomes.", "qid": 22, "docid": "qsy2kex1", "rank": 11, "score": 0.867752194404602}, {"content": "Title: Myocardial and Microvascular Injury Due to Coronavirus Disease 2019 Content: Over the past few months, health systems worldwide have been put to the test with the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though the leading clinical manifestations of the SARS-CoV-2 infection involve the respiratory tract, there is a non-negligible risk of systemic involvement leading to the onset of multi-organ failure with fatal consequences. Since the onset of COVID-19, patients with underlying cardiovascular disease have been at increased risk of poor clinical outcomes with higher death rates. Moreover, the occurrence of new-onset cardiac complications is not uncommon among patients hospitalised for COVID-19. Of importance, a significant portion of COVID-19 patients present with myocardial injury. Herein, the authors discuss the mechanisms leading to myocardial and microvascular injury in SARS-CoV-2 infection and their clinical implications.", "qid": 22, "docid": "uo88b0mk", "rank": 12, "score": 0.8656555414199829}, {"content": "Title: Mechanisms of Myocardial Injury in Coronavirus Disease 2019 Content: Coronavirus disease 2019 (COVID-19) predominantly presents with symptoms of fever, fatigue, cough and respiratory failure. However, it appears to have a unique interplay with cardiovascular disease (CVD); patients with pre-existing CVD are at highest risk for mortality from COVID-19, along with the elderly. COVID-19 contributes to cardiovascular complications including arrhythmias, myocardial dysfunction and myocardial inflammation. Although the exact mechanism of myocardial inflammation in patients with COVID-19 is not known, several plausible mechanisms have been proposed based on early observational reports. In this article, the authors summarise the available literature on mechanisms of myocardial injury in COVID-19.", "qid": 22, "docid": "h2xmxwd1", "rank": 13, "score": 0.8641127347946167}, {"content": "Title: Emerging cardiological issues during the COVID\u201019 pandemic Content: Today the modern world is facing an unprecedented health crisis. The COVID\u201019 pandemic is putting extensive strain on health care systems, hospitals and medical workers worldwide. Epidemiological data are emerging that COVID\u201019 patients with cardiac risk factors or pre\u2010existing cardiac conditions are at increased risk for complications and mortality from COVID\u201019. As we just begin to understand the pathophysiology underlying the disease, the involvement of the heart, whether through direct myocardial infection and damage or due to cardiac complications, is already evident.", "qid": 22, "docid": "6p39cx2e", "rank": 14, "score": 0.8610466718673706}, {"content": "Title: Involvement of Cardiovascular System As The Critical Point in Coronavirus Disease 2019 (COVID-19) Prognosis and Recovery Content: The novel coronavirus disease (COVID-19) pandemic has already caused more than 300,000 deaths worldwide. Several studies have elucidated the central role of cardiovascular complications in the disease course. Herein, we provide a concise review of current knowledge regarding the involvement of cardiovascular system in the pathogenesis and prognosis of COVID-19. We summarize data from 21 studies involving in total more than 21,000 patients from Asia, Europe and the USA indicating that severe disease is associated with the presence of myocardial injury, heart failure and arrhythmias. Additionally, we present the clinical and laboratory differences between recovered and deceased patients highlighting the importance of cardiac manifestations. For the infected patients, underlying cardiovascular comorbidities and especially existing cardiovascular disease seem to predispose to the development of cardiovascular complications, which are in turn associated with higher mortality rates. We provide mechanistic insights into the underlying mechanisms including direct myocardial damage by the virus and the consequences of the hyperinflammatory syndrome developed later in the disease course. Finally, we summarize current knowledge on therapeutic modalities and recommendations by scientific societies and experts regarding the cardiovascular management of COVID-19 patients.", "qid": 22, "docid": "fzmrvjtl", "rank": 15, "score": 0.8606801629066467}, {"content": "Title: COVID-19 Cardiovascular Epidemiology, Cellular Pathogenesis, Clinical Manifestations and Management Content: Abstract Coronavirus Disease 2019 (COVID-19) is a rapidly progressing global pandemic that may present with a variety of cardiac manifestations including, but not limited to, myocardial injury, myocardial infarction, arrhythmias, heart failure, cardiomyopathy, shock, thromboembolism, and cardiac arrest. These cardiovascular effects are worse in patients who have pre-existing cardiac conditions such as coronary artery disease, hypertension, diabetes mellitus, and coagulation abnormalities. Other predisposing risk factors include advanced age, immunocompromised state, and underlying systemic inflammatory conditions. Here we review the cellular pathophysiology, clinical manifestations and treatment modalities of the cardiac manifestations seen in patients with COVID-19.", "qid": 22, "docid": "dl8vjwfn", "rank": 16, "score": 0.8475291132926941}, {"content": "Title: Cardiovascular manifestations and treatment considerations in covid-19 Content: Since its recognition in December 2019, covid-19 has rapidly spread globally causing a pandemic. Pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease are associated with a greater severity and higher fatality rate of covid-19. Furthermore, covid-19 contributes to cardiovascular complications, including acute myocardial injury as a result of acute coronary syndrome, myocarditis, stress-cardiomyopathy, arrhythmias, cardiogenic shock, and cardiac arrest. The cardiovascular interactions of covid-19 have similarities to that of severe acute respiratory syndrome, Middle East respiratory syndrome and influenza. Specific cardiovascular considerations are also necessary in supportive treatment with anticoagulation, the continued use of renin-angiotensin-aldosterone system inhibitors, arrhythmia monitoring, immunosuppression or modulation, and mechanical circulatory support.", "qid": 22, "docid": "873txs85", "rank": 17, "score": 0.8424614667892456}, {"content": "Title: Possible molecular and paracrine involvement underlying the pathogenesis of COVID-19 cardiovascular complications Content: Coronavirus disease 2019 (COVID-19) has been declared a pandemic on 11 March 2020 by the WHO Despite being mainly a respiratory virus, cardiac complications have been described These range from sudden cardiac death to subtle diastolic dysfunction after recovery from COVID-19 The commonest cardiac presentation to date is acute heart failure resulting from biventricular or left ventricular hypokinesis and elevation of cardiac troponins It has been shown that COVID-19 downregulates angiotensin-converting enzyme-2, which has protective effects on the endothelium and cardiomyocytes It has also been proven that COVID-19 induces a state of hypercytokinaemia, some cytokines such as interleukin-1 and interleukin-6 have an injurious effect on the myocardium and endothelium, respectively Such pathogenic mechanisms might play a crucial role in induction of cardiomyocyte injury and impaired myocardial perfusion probably through coronary endothelial dysfunction The understanding and linking of such mechanisms might help in tailoring drug repurposing for treatment or prophylaxis of COVID-19 cardiovascular complications Received 6 April 2020 Accepted 14 April 2020 Correspondence to Antoine Fakhry AbdelMassih, MD, Pediatrics\u2019 Department, Pediatric Cardiology unit, Cairo University Children Hospital, Faculty of Medicine, Cairo University, Kasr Al Ainy Street, Cairo 12411, Egypt, E-mail: antoine abdelmassih@kasralainy edu eg \u00a9 2020Wolters Kluwer Health Lippincott Williams Wilkins", "qid": 22, "docid": "tkbctdyj", "rank": 18, "score": 0.8421383500099182}, {"content": "Title: Possible effects of coronavurus infection (COVID-19) on the cardiovascular system/ \u0412\u041b\u0418\u042f\u041d\u0418\u0415 \u041a\u041e\u0420\u041e\u041d\u0410\u0412\u0418\u0420\u0423\u0421\u041d\u041e\u0419 \u0418\u041d\u0424\u0415\u041a\u0426\u0418\u0418 (COVID-19) \u041d\u0410 \u0421\u0415\u0420\u0414\u0415\u0427\u041d\u041e-\u0421\u041e\u0421\u0423\u0414\u0418\u0421\u0422\u0423\u042e \u0421\u0418\u0421\u0422\u0415\u041c\u0423 Content: Acute viral respiratory infections can increase the risk of progression of a pre-existing condition, including a cardiovascular pathology. Life-threatening complications of Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitate research into the cardiovascular effects of COVID-19 crucial for developing adequate treatment strategy for infected patients, especially those of advanced age. This article reviews the literature on the clinical and functional characteristics of patients with COVID-19, including those with poor outcomes. The article looks at the pathophysiological processes occurring in the cardiovascular system in the setting of SARS-CoV-2 infection, risk factors and death predictors. It also discusses continuation of therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in patients with COVID-19.", "qid": 22, "docid": "8dfkddal", "rank": 19, "score": 0.8389759659767151}, {"content": "Title: SARS-CoV-2 pandemic and the cardiovascular system: What the non-cardiologist needs to know Content: There has been the need to make major modifications to the way cardiology is practised in light of the COVID-19 pandemic. There has also been the need to recognise the complex cardiovascular manifestations and complications of COVID-19. In this article we provide guidance on the management of cardiac patients without COVID-19 in the current pandemic as well as patients with cardiac disease and COVID-19 and patients with cardiac complications of COVID-19. There is also a focus on indications and interpretation of commonly performed cardiac investigations in the setting of COVID-19. References are included from a number of specialist societies and groups.", "qid": 22, "docid": "2k1n07on", "rank": 20, "score": 0.8387688994407654}, {"content": "Title: SARS-CoV-2 pandemic and the cardiovascular system: What the non-cardiologist needs to know. Content: There has been the need to make major modifications to the way cardiology is practised in light of the COVID-19 pandemic. There has also been the need to recognise the complex cardiovascular manifestations and complications of COVID-19. In this article we provide guidance on the management of cardiac patients without COVID-19 in the current pandemic as well as patients with cardiac disease and COVID-19 and patients with cardiac complications of COVID-19. There is also a focus on indications and interpretation of commonly performed cardiac investigations in the setting of COVID-19. References are included from a number of specialist societies and groups.", "qid": 22, "docid": "8ysfaww2", "rank": 21, "score": 0.8387688994407654}, {"content": "Title: Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the COVID-19 Pandemic Content: The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients. First, those with COVID-19 and pre-existing cardiovascular disease have an increased risk of severe disease and death. Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism. Third, therapies under investigation for COVID-19 may have cardiovascular side effects. Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions. Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become hosts or vectors of virus transmission. We hereby review the peer-reviewed and pre-print reports pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.", "qid": 22, "docid": "e9k6pnr3", "rank": 22, "score": 0.8379920721054077}, {"content": "Title: COVID-19 and Cardiovascular diseases. Scoping review study. Content: BACKGROUND Many patients with COVID-19 have pre-existing cardiovascular (CV) co-morbidities or develop acute heart damage during the course of the disease. OBJECTIVES To study the risk of COVID-19 infection in the presence of preexisting CV diseases and to describe new CV manifestations during COVID-19. METHODS A \"scoping review\" was carried out via PubMed, to synthesize the results of research currently published on this subject. RESULTS Patients with cardiovascular disease were at greater risk of developing COVID-19, especially in its severe form. These patients were five to ten times more at risk of death. Cardiac manifestations, de novo, were dominated by acute myocardial damage, defined by a significant elevation of cardiac troponins. These occurred in 7 to 17% of hospitalized patients. The presence of a new heart lesion in patients with COVID-19 was consistently associated with a poor prognosis. CONCLUSION Given the enormous cardiovascular challenge posed by the COVID-19 pandemic and the prognostic impact of heart damage, additional research at a high level of evidence will be necessary.", "qid": 22, "docid": "x4093iad", "rank": 23, "score": 0.837834894657135}, {"content": "Title: COVID-19 and Cardiovascular diseases. Scoping review study Content: BACKGROUND: Many patients with COVID-19 have pre-existing cardiovascular (CV) co-morbidities or develop acute heart damage during the course of the disease. OBJECTIVES: To study the risk of COVID-19 infection in the presence of preexisting CV diseases and to describe new CV manifestations during COVID-19. METHODS: A \"scoping review\" was carried out via PubMed, to synthesize the results of research currently published on this subject. RESULTS: Patients with cardiovascular disease were at greater risk of developing COVID-19, especially in its severe form. These patients were five to ten times more at risk of death. Cardiac manifestations, de novo, were dominated by acute myocardial damage, defined by a significant elevation of cardiac troponins. These occurred in 7 to 17% of hospitalized patients. The presence of a new heart lesion in patients with COVID-19 was consistently associated with a poor prognosis. CONCLUSION: Given the enormous cardiovascular challenge posed by the COVID-19 pandemic and the prognostic impact of heart damage, additional research at a high level of evidence will be necessary.", "qid": 22, "docid": "20zujaha", "rank": 24, "score": 0.837802529335022}, {"content": "Title: Cardiovascular disease and COVID-19 Content: BACKGROUND AND AIMS: Many patients with coronavirus disease 2019 (COVID-19) have underlying cardiovascular (CV) disease or develop acute cardiac injury during the course of the illness. Adequate understanding of the interplay between COVID-19 and CV disease is required for optimum management of these patients. METHODS: A literature search was done using PubMed and Google search engines to prepare a narrative review on this topic. RESULTS: Respiratory illness is the dominant clinical manifestation of COVID-19; CV involvement occurs much less commonly. Acute cardiac injury, defined as significant elevation of cardiac troponins, is the most commonly reported cardiac abnormality in COVID-19. It occurs in approximately 8-12% of all patients. Direct myocardial injury due to viral involvement of cardiomyocytes and the effect of systemic inflammation appear to be the most common mechanisms responsible for cardiac injury. The information about other CV manifestations in COVID-19 is very limited at present. Nonetheless, it has been consistently shown that the presence of pre-existing CV disease and/or development of acute cardiac injury are associated with significantly worse outcome in these patients. CONCLUSIONS: Most of the current reports on COVID-19 have only briefly described CV manifestations in these patients. Given the enormous burden posed by this illness and the significant adverse prognostic impact of cardiac involvement, further research is required to understand the incidence, mechanisms, clinical presentation and outcomes of various CV manifestations in COVID-19 patients.", "qid": 22, "docid": "659lz92w", "rank": 25, "score": 0.8369060754776001}, {"content": "Title: COVID-19 pandemic and the impact on the cardiovascular disease patient care Content: The COVID-19 pandemic has emerged as a serious global threat causing a large number of fatalities and putting enormous strain on the health care resources across the world. This has resulted in preferentially triaging the coronavirus infected patients and placing others, especially cardiovascular patients at increased risk for adverse complications. The effective management of cardiac patients in the hospital environment during this COVID-19 pandemic has emerged as a real challenge. We try to address this issue and also highlight the interplay between COVID-19 and cardiovascular diseases. We hereby review the available literature and emerging guidelines about cardiovascular implications related to COVID-19 which will have a bearing on the patient care, health care professionals and cardiac centres.", "qid": 22, "docid": "5gd0q8yq", "rank": 26, "score": 0.8366892337799072}, {"content": "Title: COVID-19 pandemic and the impact on the cardiovascular disease patient care. Content: The COVID-19 pandemic has emerged as a serious global threat causing a large number of fatalities and putting enormous strain on the health care resources across the world. This has resulted in preferentially triaging the coronavirus infected patients and placing others, especially cardiovascular patients at increased risk for adverse complications. The effective management of cardiac patients in the hospital environment during this COVID-19 pandemic has emerged as a real challenge. We try to address this issue and also highlight the interplay between COVID-19 and cardiovascular diseases. We hereby review the available literature and emerging guidelines about cardiovascular implications related to COVID-19 which will have a bearing on the patient care, health care professionals and cardiac centres.", "qid": 22, "docid": "nj0ue2c2", "rank": 27, "score": 0.8366892337799072}, {"content": "Title: Cardiac and arrhythmic complications in patients with COVID-19 Content: In December 2019, the world started to face a new pandemic situation, the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Although coronavirus disease (COVID-19) clinical manifestations are mainly respiratory, major cardiac complications are being reported. Cardiac manifestations etiology seems to be multifactorial, comprising direct viral myocardial damage, hypoxia, hypotension, enhanced inflammatory status, ACE2-receptors downregulation, drug toxicity, endogenous catecholamine adrenergic status, among others. Studies evaluating patients with COVID-19 presenting cardiac injury markers show that it is associated with poorer outcomes, and arrhythmic events are not uncommon. Besides, drugs currently used to treat the COVID-19 are known to prolong the QT interval and can have a proarrhythmic propensity. This review focus on COVID-19 cardiac and arrhythmic manifestations and, in parallel, makes an appraisal of other virus epidemics as SARS-CoV, Middle East respiratory syndrome coronavirus, and H1N1 influenza.", "qid": 22, "docid": "rmio55bx", "rank": 28, "score": 0.8366453647613525}, {"content": "Title: COVID-19 and Heart: From Clinical Features to Pharmacological Implications. Content: A highly pathogenic human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been recently recognized in Wuhan, China, as the cause of the coronavirus disease 2019 (COVID-19) outbreak which has spread rapidly from China to other countries in the world, causing a pandemic with alarming morbidity and mortality. The emerging epidemiological data about COVID-19 patients suggest an association between cardiovascular diseases (CVD) and SARS-CoV-2 infection, in term of clinical features at hospital admission and prognosis for disease severity. The aim of our review is to describe the cardiological features of COVID-19 patients at admission, the acute cardiac presentation, the clinical outcome for patients with underlying CVD and the pharmacological implications for disease management.", "qid": 22, "docid": "d5vmviai", "rank": 29, "score": 0.8355817794799805}, {"content": "Title: COVID-19 et maladies cardiovasculaires./ [COVID-19 andcardiovascular diseases] Content: COVID-2019 disease mainly affects the respiratory tract and can progress in severe cases to pneumonia, acute respiratory distress syndrome and multi-organ failure. Patients with prior cardiovascular disease are at higher risk of developing an infection and progressing to a severe form of the disease. Also, due to the growing number of infected cases, it is clear that, in addition to the typical respiratory symptoms caused by the infection, some patients suffer from cardiovascular damage. This condition can, in fact, cause significant myocardial damage, which worsens the disease and affects the prognosis. Based on the results of currently published research, it seems important to discuss the manifestations and characteristics of myocardial damage induced by COVID-19 and its impact on patient prognosis.", "qid": 22, "docid": "f7ne994m", "rank": 30, "score": 0.8342119455337524}, {"content": "Title: [COVID-19 andcardiovascular diseases]. Content: COVID-2019 disease mainly affects the respiratory tract and can progress in severe cases to pneumonia, acute respiratory distress syndrome and multi-organ failure. Patients with prior cardiovascular disease are at higher risk of developing an infection and progressing to a severe form of the disease. Also, due to the growing number of infected cases, it is clear that, in addition to the typical respiratory symptoms caused by the infection, some patients suffer from cardiovascular damage. This condition can, in fact, cause significant myocardial damage, which worsens the disease and affects the prognosis. Based on the results of currently published research, it seems important to discuss the manifestations and characteristics of myocardial damage induced by COVID-19 and its impact on patient prognosis.", "qid": 22, "docid": "w996v6od", "rank": 31, "score": 0.8342117071151733}, {"content": "Title: Cardiovascular comorbidities and complications associated with coronavirus disease 2019 Content: Coronavirus disease 2019 (COVID-19) has caused a devastating global pandemic and continues to overwhelm the health-care facilities and shatter the economies of countries worldwide. Although it primarily affects the lungs, it shares a strong interplay with the cardiovascular system. The presence of underlying cardiovascular disease and its risk factors (diabetes, hypertension) predispose the patients to increased severity and mortality associated with COVID-19. On the other hand, COVID-19 itself leads to various cardiovascular complications, which increase its associated morbidity and mortality in affected patients. It is, therefore, prudent to review the rapidly evolving data in this field and understand the mechanisms behind the cardiovascular involvement of this lethal disease.", "qid": 22, "docid": "o6a30irm", "rank": 32, "score": 0.8338655829429626}, {"content": "Title: Cardiovascular disease and COVID-19 Content: Abstract Background and aims Many patients with coronavirus disease 2019 (COVID-19) have underlying cardiovascular (CV) disease or develop acute cardiac injury during the course of the illness. Adequate understanding of the interplay between COVID-19 and CV disease is required for optimum management of these patients. Methods A literature search was done using PubMed and Google search engines to prepare a narrative review on this topic. Results Respiratory illness is the dominant clinical manifestation of COVID-19; CV involvement occurs much less commonly. Acute cardiac injury, defined as significant elevation of cardiac troponins, is the most commonly reported cardiac abnormality in COVID-19. It occurs in approximately 8\u201312% of all patients. Direct myocardial injury due to viral involvement of cardiomyocytes and the effect of systemic inflammation appear to be the most common mechanisms responsible for cardiac injury. The information about other CV manifestations in COVID-19 is very limited at present. Nonetheless, it has been consistently shown that the presence of pre-existing CV disease and/or development of acute cardiac injury are associated with significantly worse outcome in these patients. Conclusions Most of the current reports on COVID-19 have only briefly described CV manifestations in these patients. Given the enormous burden posed by this illness and the significant adverse prognostic impact of cardiac involvement, further research is required to understand the incidence, mechanisms, clinical presentation and outcomes of various CV manifestations in COVID-19 patients.", "qid": 22, "docid": "wztm0rbx", "rank": 33, "score": 0.8335727453231812}, {"content": "Title: Coronavirus Disease 2019 Myocarditis: Insights into Pathophysiology and Management Content: The world is dealing with a global pandemic of severe acute respiratory coronavirus 2 (SARS-CoV-2). Coronavirus disease 2019 (COVID-19), which is the illness caused by SARS-CoV-2, is overwhelming healthcare systems around the world. Although the main clinical manifestations of COVID-19 are respiratory symptoms, several reports have noted myocarditis, cardiomyopathy, arrhythmias and cardiac arrests as COVID-19 complications. Here, the authors highlight the current understanding of the pathophysiology of myocarditis related to COVID-19 and its management.", "qid": 22, "docid": "8bhahzys", "rank": 34, "score": 0.8324448466300964}, {"content": "Title: Prognostic Value of Cardiovascular Biomarkers in COVID-19: A Review Content: In early December 2019, the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in Wuhan, China. As of May 10th, 2020, a total of over 4 million COVID-19 cases and 280,000 deaths have been reported globally, reflecting the raised infectivity and severity of this virus. Amongst hospitalised COVID-19 patients, there is a high prevalence of established cardiovascular disease (CVD). There is evidence showing that COVID-19 may exacerbate cardiovascular risk factors and preexisting CVD or may lead to cardiovascular complications. With intensive care units operating at maximum capacity and such staggering mortality rates reported, it is imperative during this time-sensitive COVID-19 outbreak to identify patients with an increased risk of adverse outcomes and/or myocardial injury. Preliminary findings from COVID-19 studies have shown the association of biomarkers of acute cardiac injury and coagulation with worse prognosis. While these biomarkers are recognised for CVD, there is emerging prospect that they may aid prognosis in COVID-19, especially in patients with cardiovascular comorbidities or risk factors that predispose to worse outcomes. Consequently, the aim of this review is to identify cardiovascular prognostic factors associated with morbidity and mortality in COVID-19 and to highlight considerations for incorporating laboratory testing of biomarkers of cardiovascular performance in COVID-19 to optimise outcomes.", "qid": 22, "docid": "yqib10gi", "rank": 35, "score": 0.8320436477661133}, {"content": "Title: COVID-19-RELATED AORTIC THROMBOSIS: A REPORT OF FOUR CASES Content: COVID-19 may predispose patients to an increased risk of thrombotic complications through various pathophysiological mechanisms. Most of the reports on a high incidence of thrombotic complications are in relation to deep vein thrombosis and pulmonary embolism, while the evidence about arterial thrombosis in patients with COVID-19 is limited. We describe four cases of aortic thrombosis and associated ischemic complications in patients with severe SARS-CoV-2 infection.", "qid": 22, "docid": "q7yavza2", "rank": 36, "score": 0.8320332765579224}, {"content": "Title: Cardiovascular Considerations for the Internist and Hospitalist in the COVID-19 Era Content: It is clear that existing cardiovascular disease is a major risk factor for COVID-19 and related adverse outcomes. In addition to acute respiratory syndrome, a large cohort also develop myocardial and/or vascular dysfunction, in part from inflammation and renin angiotensin system activation with increased sympathetic outflow, cardiac arrhythmias, ischemia, heart failure, and thromboembolic complications that portend poor COVID-19 outcomes. We summarize here recent information for hospitalists/internists on the front-line of this pandemic regarding its cardiovascular impacts and management and need for cardiovascular consultation.", "qid": 22, "docid": "fitz1vjs", "rank": 37, "score": 0.8318905830383301}, {"content": "Title: A current review of COVID-19 for the cardiovascular specialist Content: Abstract Although Coronavirus Disease 2019 (COVID-19) predominantly disrupts the respiratory system, there is accumulating experience that the disease, particularly in its more severe manifestations, also affects the cardiovascular system. Cardiovascular risk factors and chronic cardiovascular conditions are prevalent among patients affected by COVID-19 and associated with adverse outcomes. However, whether pre-existing cardiovascular disease is an independent determinant of higher mortality risk with COVID-19 remains uncertain. Acute cardiac injury, manifest by increased blood levels of cardiac troponin, electrocardiographic abnormalities, or myocardial dysfunction, occurs in up to ~60% of hospitalized patients with severe COVID-19. Potential contributors to acute cardiac injury in the setting of COVID-19 include 1) acute changes in myocardial demand and supply due to tachycardia, hypotension, and hypoxemia resulting in type 2 myocardial infarction; 2) acute coronary syndrome due to acute atherothrombosis in a virally-induced thrombotic and inflammatory milieu; 3) microvascular dysfunction due to diffuse microthrombi or vascular injury; 4) stress-related cardiomyopathy (Takotsubo syndrome); 5) non-ischemic myocardial injury due to a hyperinflammatory cytokine storm; or 6) direct viral cardiomyocyte toxicity and myocarditis. Diffuse thrombosis is emerging as an important contributor to adverse outcomes in patients with COVID-19. Practitioners should be vigilant for cardiovascular complications of COVID-19. Monitoring may include serial cardiac troponin and natriuretic peptides, along with fibrinogen, d-dimer, and inflammatory biomarkers. Management decisions should rely on the clinical assessment for the probability of ongoing myocardial ischemia, as well as alternative non-ischemic causes of injury, integrating the level of suspicion for COVID-19.", "qid": 22, "docid": "dm9nefdg", "rank": 38, "score": 0.8303971886634827}, {"content": "Title: Electrical Storm in COVID-19 Content: Abstract COVID-19 is a global pandemic caused by SARS-CoV-2. Infection is associated with significant morbidity and mortality. Individuals with pre-existing cardiovascular disease or evidence of myocardial injury are at risk for severe disease and death. Little is understood about the mechanisms of myocardial injury or life-threatening cardiovascular sequelae.", "qid": 22, "docid": "98xisxg7", "rank": 39, "score": 0.8299624919891357}, {"content": "Title: COVID-19-Related Aortic Thrombosis: A Report of Four Cases Content: COVID-19 may predispose patients to an increased risk of thrombotic complications through various pathophysiological mechanisms. Most of the reports on a high incidence of thrombotic complications are in relation to deep vein thrombosis and pulmonary embolism, while the evidence about arterial thrombosis in patients with COVID-19 is limited. We describe 4 cases of aortic thrombosis and associated ischemic complications in patients with severe SARS-CoV-2 infection.", "qid": 22, "docid": "ir6d85fr", "rank": 40, "score": 0.8298085331916809}, {"content": "Title: A current review of COVID-19 for the cardiovascular specialist Content: Although coronavirus disease 2019 (COVID-19) predominantly disrupts the respiratory system, there is accumulating experience that the disease, particularly in its more severe manifestations, also affects the cardiovascular system. Cardiovascular risk factors and chronic cardiovascular conditions are prevalent among patients affected by COVID-19 and associated with adverse outcomes. However, whether pre-existing cardiovascular disease is an independent determinant of higher mortality risk with COVID-19 remains uncertain. Acute cardiac injury, manifest by increased blood levels of cardiac troponin, electrocardiographic abnormalities, or myocardial dysfunction, occurs in up to ~60% of hospitalized patients with severe COVID-19. Potential contributors to acute cardiac injury in the setting of COVID-19 include (1) acute changes in myocardial demand and supply due to tachycardia, hypotension, and hypoxemia resulting in type 2 myocardial infarction; (2) acute coronary syndrome due to acute atherothrombosis in a virally induced thrombotic and inflammatory milieu; (3) microvascular dysfunction due to diffuse microthrombi or vascular injury; (4) stress-related cardiomyopathy (Takotsubo syndrome); (5) nonischemic myocardial injury due to a hyperinflammatory cytokine storm; or (6) direct viral cardiomyocyte toxicity and myocarditis. Diffuse thrombosis is emerging as an important contributor to adverse outcomes in patients with COVID-19. Practitioners should be vigilant for cardiovascular complications of COVID-19. Monitoring may include serial cardiac troponin and natriuretic peptides, along with fibrinogen, D-dimer, and inflammatory biomarkers. Management decisions should rely on the clinical assessment for the probability of ongoing myocardial ischemia, as well as alternative nonischemic causes of injury, integrating the level of suspicion for COVID-19.", "qid": 22, "docid": "umhj7nk7", "rank": 41, "score": 0.8283029794692993}, {"content": "Title: The Novel Coronavirus Disease (COVID-19) and Its Impact on Cardiovascular Disease Content: The coronavirus disease 2019 (COVID-19) pandemic has placed a significant strain on healthcare providers. As the number of patients continue to surge, healthcare workers are now forced to find different approaches to practicing medicine that may affect patient care. In addition, COVID-19 has many cardiovascular complications that affect the clinical course of patients. In this article, we summarize the cardiovascular impact of COVID-19 and some of the challenges that patients and the healthcare system will face during this pandemic.", "qid": 22, "docid": "blok70nn", "rank": 42, "score": 0.8277581930160522}, {"content": "Title: A care pathway for the cardiovascular complications of COVID-19: Insights from an institutional response Content: The infection caused by severe acute respiratory syndrome coronavirus-2, or COVID-19, can result in myocardial injury, heart failure, and arrhythmias. In addition to the viral infection itself, investigational therapies for the infection can interact with the cardiovascular system. As cardiologists and cardiovascular service lines will be heavily involved in the care of patients with COVID-19, our division organized an approach to manage these complications, attempting to balance resource utilization and risk to personnel with optimal cardiovascular care. The model presented can provide a framework for other institutions to organize their own approaches and can be adapted to local constraints, resource availability, and emerging knowledge.", "qid": 22, "docid": "38ltcpcw", "rank": 43, "score": 0.8273918628692627}, {"content": "Title: A review of cardiac manifestations and predictors of outcome in patients with COVID \u2013 19 Content: Abstract Coronavirus disease (COVID-19) pandemic has so far involved 184 countries and more than 2.79 million patients worldwide. Over the past three months, it has attributed to more than 196, 000 deaths, with more than 50, 000 deaths in the United States alone. Pulmonary manifestations are predominant and have been well identified. Cardiac involvement is also common. Acute cardiac injury, the most common cardiac manifestation of this disease can be seen in patients even without prior cardiac comorbidities. Established cardiovascular risk factors such as diabetes mellitus, hypertension, and coronary artery disease predispose to cardiac injury, the severity of illness and mortality. Non-ischemic myocardial injury secondary to cytokine storm is thought to be the predominant mechanism of acute cardiac injury associated with COVID-19. Multiple mechanisms and processes contribute to cardiac injury resulting in a poor outcome. Some of these are not clearly understood. Clinical and diagnostic details of cardiovascular involvement in these patients are mostly limited to biochemical markers. Multiple therapeutic agents have been tried with questionable efficacy and without clinical evidence. Interactions of comorbidities, cardiovascular drugs, the cardiac effect of therapeutic agents on the illness continue to be under investigation. With an increasing number of patients, newer promising therapies, and ongoing clinical trials, the exact mechanisms and extent to which these risk factors contribute to outcomes will be clearer in the future.", "qid": 22, "docid": "lbt57ccs", "rank": 44, "score": 0.8271449208259583}, {"content": "Title: Pathologies cardiovasculaires et Covid-19 : particularit\u00e9s chez les personnes \u00e2g\u00e9es./ COVID-19 and cardiovascular diseases: viewpoint for older patients Content: The coronavirus disease-2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. The link between cardiovascular disease and COVID-19 appears to be twofold. First, some reports of data indicate that certain groups of patients are more at risk of COVID-19. This includes patients with cardiovascular risk factors or pre-existing cardiovascular conditions and older patients. In addition, these patients incur disproportionately worse outcome. Second, SARS-CoV2 infection can be complicated by life-threatening cardiovascular acute diseases. Despite the rapid evolution of data on this pandemic, this review aims to highlight the cardiovascular considerations related to COVID-19 whether as comorbidities including concerns and uncertainty regarding the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on angiotensin conversion enzyme 2 or related to acute cardiovascular complications.", "qid": 22, "docid": "pjtlk8ni", "rank": 45, "score": 0.8271154165267944}, {"content": "Title: COVID-19 and cardiovascular diseases: viewpoint for older patients. Content: The coronavirus disease-2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. The link between cardiovascular disease and COVID-19 appears to be twofold. First, some reports of data indicate that certain groups of patients are more at risk of COVID-19. This includes patients with cardiovascular risk factors or pre-existing cardiovascular conditions and older patients. In addition, these patients incur disproportionately worse outcome. Second, SARS-CoV2 infection can be complicated by life-threatening cardiovascular acute diseases. Despite the rapid evolution of data on this pandemic, this review aims to highlight the cardiovascular considerations related to COVID-19 whether as comorbidities including concerns and uncertainty regarding the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on angiotensin conversion enzyme 2 or related to acute cardiovascular complications.", "qid": 22, "docid": "7rf532b9", "rank": 46, "score": 0.8271154165267944}, {"content": "Title: Acute cardiac injury in patients with COVID-19 Content: Introduction: Cardiac complications of COVID-19 are potentially life-threatening. The occurrence of myocardial injury in the context of COVID-19 is multifactorial and has generated increasing interest. Methods: A systematic review with meta-analysis of the literature was performed. MEDLINE and EMBASE were searched. Two independente reviewers evaluated the selected manuscripts for the outcome myocardial injury, defined by troponin elevation above the 99th percentile. Study heterogeneity and risk of bias were evaluated. Results: Eight studies, with a total of 1229 patients, were included. The frequency of myocardial injury was 16% (95% CI: 9% - 27%). The heterogeneity among studies was high (93%). Conclusions: Myocardial injury may occur in patients with COVID-19, with a frequency of 16% among current studies. Continuous research is needed to update these findings, as the pandemic evolves, and to define the implications of myocardial injury in the context of this infection.", "qid": 22, "docid": "wvxybca4", "rank": 47, "score": 0.8268153667449951}, {"content": "Title: Management of Cardiovascular Disease During Coronavirus Disease (COVID-19) Pandemic Content: Patients with pre-existing cardiovascular disease and risk factors are more likely to experience adverse outcomes associated with the novel coronavirus disease-2019 (COVID-19). Additionally, consistent reports of cardiac injury and de novo cardiac complications, including possible myocarditis, arrhythmia, and heart failure in patients without prior cardiovascular disease or significant risk factors, are emerging, possibly due to an accentuated host immune response and cytokine release syndrome. As the spread of the virus increases exponentially, many patients will require medical care either for COVID-19 related or traditional cardiovascular issues. While the COVID-19 pandemic is dominating the attention of the healthcare system, there is an unmet need for a standardized approach to deal with COVID-19 associated and other traditional cardiovascular issues during this period. We provide consensus guidance for the management of various cardiovascular conditions during the ongoing COVID-19 pandemic with the goal of providing the best care to all patients and minimizing the risk of exposure to frontline healthcare workers.", "qid": 22, "docid": "scddzn5t", "rank": 48, "score": 0.8266623020172119}, {"content": "Title: Pharmaco-invasive Therapy for STEMI in a Patient with COVID-19: A Case Report Content: Coronavirus disease 2019 (COVID-19) is a pandemic that started in the Wuhan province of China in December 2019 It is associated with increased morbidity and mortality mainly due to severe acute respiratory syndrome 2 (SARS-Cov-2) Cardiac manifestations related to COVID-19 include demand ischemia, fulminant myocarditis, myocardial infarction and arrhythmias In this report, we present a case of ST-segment elevation myocardial infarction (STEMI) in a 68-year-old man with COVID-19 who initially presented with chest pain and shortness of breath Patient's STEMI was managed with pharmaco-invasive strategy with tissue plasminogen activator (t-PA) He then developed acute hypoxic respiratory failure that was managed in the intensive care unit (ICU), together with multi-organ failure from which the patient died 2 days after presentation Although the pathophysiologic mechanisms of STEMI in COVID-19 patients has not been clearly established, we hypothesize that interrelated pathogenetic factors, that we highlight in this report, can play a role in the development of STEMI, including plaque rupture secondary to systemic inflammation, increased pro-coagulants, endothelial dysfunction, impaired fibrinolysis and impaired oxygen utilization leading to demand/supply mismatch and myocardial ischemia", "qid": 22, "docid": "946qlhuc", "rank": 49, "score": 0.8258804678916931}, {"content": "Title: Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the Coronavirus Disease 2019 (COVID-19) Pandemic Content: Abstract The coronavirus disease-2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients. First, those with COVID-19 and preexisting cardiovascular disease (CVD) have an increased risk of severe disease and death. Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias and venous thromboembolism. Third, therapies under investigation for COVID-19 may have cardiovascular side effects. Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions. Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become host or vectors of virus transmission. We hereby review the peer-reviewed and preprint literature pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.", "qid": 22, "docid": "w49i0xkz", "rank": 50, "score": 0.8254432678222656}, {"content": "Title: A Review of Acute Myocardial Injury in Coronavirus Disease 2019 Content: In December 2019, an outbreak of pneumonia caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred in Wuhan, Hubei province, China, and it has spread rapidly across the world, causing the coronavirus disease 2019 (COVID-19) pandemic. Although SARS-CoV-2 infection predominantly results in pulmonary issues, accumulating evidence suggests the increased frequency of a variety of cardiovascular complications in patients with COVID-19. Acute cardiac injury, defined as elevated cardiac troponin levels, is the most reported cardiac abnormality in COVID-19 and strongly associated with mortality. In this article, we summarize the currently available data on the association of SARS-CoV-2 and COVID-19 with acute myocardial injury.", "qid": 22, "docid": "ja0wyr5w", "rank": 51, "score": 0.8254107236862183}, {"content": "Title: A review of cardiac manifestations and predictors of outcome in patients with COVID - 19 Content: Coronavirus disease (COVID-19) pandemic has so far involved 184 countries and more than 2.79 million patients worldwide. Over the past three months, it has attributed to more than 196,000 deaths, with more than 50,000 deaths in the United States alone. Pulmonary manifestations are predominant and have been well identified. Cardiac involvement is also common. Acute cardiac injury, the most common cardiac manifestation of this disease can be seen in patients even without prior cardiac comorbidities. Established cardiovascular risk factors such as diabetes mellitus, hypertension, and coronary artery disease predispose to cardiac injury, the severity of illness and mortality. Non-ischemic myocardial injury secondary to cytokine storm is thought to be the predominant mechanism of acute cardiac injury associated with COVID-19. Multiple mechanisms and processes contribute to cardiac injury resulting in a poor outcome. Some of these are not clearly understood. Clinical and diagnostic details of cardiovascular involvement in these patients are mostly limited to biochemical markers. Multiple therapeutic agents have been tried with questionable efficacy and without clinical evidence. Interactions of comorbidities, cardiovascular drugs, the cardiac effect of therapeutic agents on the illness continue to be under investigation. With an increasing number of patients, newer promising therapies, and ongoing clinical trials, the exact mechanisms and extent to which these risk factors contribute to outcomes will be clearer in the future.", "qid": 22, "docid": "bus1nb6t", "rank": 52, "score": 0.8239247798919678}, {"content": "Title: Impact of COVID-19 on the Cardiovascular System: A Review Content: The recent outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has been declared a public health emergency of international concern. COVID-19 may present as acute respiratory distress syndrome in severe cases, and patients with pre-existing cardiovascular comorbidities are reported to be the most vulnerable. Notably, acute myocardial injury, determined by elevated high-sensitivity troponin levels, is commonly observed in severe cases, and is strongly associated with mortality. Therefore, understanding the effects of COVID-19 on the cardiovascular system is essential for providing comprehensive medical care for critically ill patients. In this review, we summarize the rapidly evolving data and highlight the cardiovascular considerations related to COVID-19.", "qid": 22, "docid": "cm7lvoxj", "rank": 53, "score": 0.8238517045974731}, {"content": "Title: COVID-19 and Its Impact on Cardiovascular Disease. Content: The COVID-19 pandemic has placed a significant strain on healthcare providers. As the number of patients continue to surge, healthcare workers are now forced to find different approaches to practicing medicine that may affect patient care. In addition, COVID-19 has many cardiovascular complications that affect the clinical course of patients. In this article we summarize the cardiovascular impact of COVID-19 and some of the challenges that patients and the healthcare system will face during this pandemic.", "qid": 22, "docid": "7zhpw74p", "rank": 54, "score": 0.8234288096427917}, {"content": "Title: Myocardial injury in patients with COVID-19 Content: In patients with COVID-19, myocardial injury is prevalent and is associated with an adverse prognosis and increased mortality, according to two retrospective cohort studies from China and the USA.", "qid": 22, "docid": "jwu0az6g", "rank": 55, "score": 0.8231514692306519}, {"content": "Title: Management of Cardiovascular Disease During Coronavirus Disease (COVID-19) Pandemic Content: ABSTRACT Patients with pre-existing cardiovascular disease and risk factors are more likely to experience adverse outcomes associated with the novel coronavirus disease-2019 (COVID-19). Additionally, consistent reports of cardiac injury and de novo cardiac complications, including possible myocarditis, arrhythmia, and heart failure in patients without prior cardiovascular disease or significant risk factors, are emerging, possibly due to an accentuated host immune response and cytokine release syndrome. As the spread of the virus increases exponentially, many patients will require medical care either for COVID-19 related or traditional cardiovascular issues. While the COVID-19 pandemic is dominating the attention of the healthcare system, there is an unmet need for a standardized approach to deal with COVID-19 associated and other traditional cardiovascular issues during this period. We provide consensus guidance for the management of various cardiovascular conditions during the ongoing COVID-19 pandemic with the goal of providing the best care to all patients and minimizing the risk of exposure to frontline healthcare workers.", "qid": 22, "docid": "ynt2koko", "rank": 56, "score": 0.8220851421356201}, {"content": "Title: Cardiovigilance in COVID 19 Content: The COVID19 (Corona Virus Disease: pandemic started in 2019) pandemic has created not only a public health problem, but as a clinical challenge as well. To the cardiologist, COVID 19 presents a wide spectrum of possibilities for clinical decision-making intervention and improvement. Cardiac dysfunction has been identified as a risk factor, a prognostic factor, a diagnostic tool, differential diagnosis, a complication of COVID 19, and a side effect of its treatment. Certain cardiotropic drugs have been implicated in the pathogenesis of COVID 19. The risk of transmission of COVID 19 is an occupational hazard which cannot be ignored by cardiologists. This review discusses the need and scope of cardio vigilance in COVID 19 management.", "qid": 22, "docid": "70csiv7d", "rank": 57, "score": 0.8211740255355835}, {"content": "Title: Cardiovigilance in COVID 19. Content: The COVID19 (Corona Virus Disease: pandemic started in 2019) pandemic has created not only a public health problem, but as a clinical challenge as well. To the cardiologist, COVID 19 presents a wide spectrum of possibilities for clinical decision-making intervention and improvement. Cardiac dysfunction has been identified as a risk factor, a prognostic factor, a diagnostic tool, differential diagnosis, a complication of COVID 19, and a side effect of its treatment. Certain cardiotropic drugs have been implicated in the pathogenesis of COVID 19. The risk of transmission of COVID 19 is an occupational hazard which cannot be ignored by cardiologists. This review discusses the need and scope of cardio vigilance in COVID 19 management.", "qid": 22, "docid": "vc9vyenb", "rank": 58, "score": 0.8211740255355835}, {"content": "Title: Familial hypercholesterolemia and COVID-19: triggering of increased sustained cardiovascular risk. Content: Early data from Wuhan, China show that patients with COVID-19 are typically male, aged 40 to 60 years, and about one-third have comorbidities. Moreover, of 138 COVID-19 patients hospitalized in Wuhan and treated in an intensive care unit (ICU), 25% had cardiovascular disease and 58% hypertension; the respective figures for non-ICU-treated COVID-19 patients were 10% and 22% [1]. Based on these early data, a predisposition to acute cardiac complications related to underlying atherosclerotic cardiovascular disease (ASCVD) may significantly increase the severity of COVID-19 in susceptible individuals.", "qid": 22, "docid": "io8hm94a", "rank": 59, "score": 0.8211596608161926}, {"content": "Title: A Review of Cardiac Complications in Coronavirus Disease 2019 Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has shown an association with acute myocardial injury, cardiomyopathy, and myocarditis. Individuals with myocardial involvement in association with the coronavirus disease 2019 (COVID-19) may be at increased risk of developing severe illness. Cardiomyopathies are a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually exhibit inappropriate ventricular hypertrophy or dilation and are due to a variety of causes that frequently are genetic. It has been primarily divided into three subsets: genetic, mixed, and acquired cardiomyopathy. We anticipate that, because of the high inflammatory response, other cardiovascular complications may also occur in COVID-19 patients with severe symptoms. This review explores new information as it pertains to COVID-19 and cardiac complications.", "qid": 22, "docid": "u6vq5ohr", "rank": 60, "score": 0.8210680484771729}, {"content": "Title: SARS-CoV-2 and Cardiovascular Complications: from Molecular Mechanisms to Pharmaceutical Management Content: The coronavirus disease 2019 (COVID-19), elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a pandemic public health emergency of global concern. Other than the profound severe pulmonary damage, SARS-CoV-2 infection also leads to a series of cardiovascular abnormalities, including myocardial injury, myocarditis and pericarditis, arrhythmia and cardiac arrest, cardiomyopathy, heart failure, cardiogenic shock, and coagulation abnormalities. Meanwhile, COVID-19 patients with preexisting cardiovascular diseases are often at a much higher risk of increased morbidity and mortality. Up\u2013to-date, a number of mechanisms have been postulated for COVID-19-associated cardiovascular damage including SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) activation, cytokine storm, hypoxemia, stress and cardiotoxicity of antiviral drugs. In this context, special attention should be given towards COVID-19 patients with concurrent cardiovascular diseases, and special cardiovascular attention is warranted for treatment of COVID-19.", "qid": 22, "docid": "5fn1nfpf", "rank": 61, "score": 0.8206394910812378}, {"content": "Title: The Association of Cardiovascular Diseases and Diabetes Mellitus with COVID-19 (SARS-CoV-2) and Their Possible Mechanisms Content: Coronavirus disease 2019 (COVID-19) has become a global concern and public health issue due to its higher infection and mortality rate; particularly, the risk is very higher among the patients who have cardiovascular diseases (CVD) and/or diabetes mellitus (DM). In this review, we analyzed the recently published literature on CVD and DM associated with COVD-19 infections and highlight their association with potential mechanisms. The findings revealed that without any previous history of CVD, the COVID-19 patients have developed some CVD complications like myocardial injury, cardiomyopathy, and venous thromboembolism after being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and required for those patients an emergency clinical support to be aware to manage those complications. Though the association between DM and COVID-19-induced severe complications is still unclear, the limited data predict that different markers like interleukin (IL)-1, IL-6, C-reactive protein, and D-dimer linked with the severity of COVID-19 infection in diabetic individuals. Further studies on a large scale are urgently needed to explore the underlying mechanisms between CVD, DM, and COVID-19 for better treatment.", "qid": 22, "docid": "9uymi395", "rank": 62, "score": 0.8204526901245117}, {"content": "Title: SARS-CoV-2 and cardiovascular complications: From molecular mechanisms to pharmaceutical management Content: The coronavirus disease 2019 (COVID-19), elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a pandemic public health emergency of global concern. Other than the profound severe pulmonary damage, SARS-CoV-2 infection also leads to a series of cardiovascular abnormalities, including myocardial injury, myocarditis and pericarditis, arrhythmia and cardiac arrest, cardiomyopathy, heart failure, cardiogenic shock, and coagulation abnormalities. Meanwhile, COVID-19 patients with preexisting cardiovascular diseases are often at a much higher risk of increased morbidity and mortality. Up-to-date, a number of mechanisms have been postulated for COVID-19-associated cardiovascular damage including SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) activation, cytokine storm, hypoxemia, stress and cardiotoxicity of antiviral drugs. In this context, special attention should be given towards COVID-19 patients with concurrent cardiovascular diseases, and special cardiovascular attention is warranted for treatment of COVID-19.", "qid": 22, "docid": "ye7yxtd3", "rank": 63, "score": 0.8203167915344238}, {"content": "Title: Coronavirus Disease 2019 and Cardiovascular System: A Narrative Review Content: At the end of 2019, a viral pneumonia disease called coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), emerged in Wuhan, China. This novel disease rapidly spread at an alarming rate that as a result, it has now been declared pandemic by the World Health Organization. Although this infective disease is mostly characterized by respiratory tract symptoms, increasing numbers of evidence had shown considerable amounts of patients with cardiovascular involvements and these were associated with higher mortality among COVID-19 patients. Cardiac involvement as a possible late phenomenon of the viral respiratory infection is an issue that should be anticipated in patients with COVID-19. Cardiovascular manifestation in COVID-19 patients include myocardial injury (MI), arrhythmias, cardiac arrests, heart failure and coagulation abnormality, ranging from 7.2% up to 33%. The mechanism of cardiac involvement in COVID-19 patients involves direct injury to myocardial cells mediated by angiotensin-converting enzyme 2 (ACE2) receptors as suggested by some studies, while the other studies suggest that systemic inflammation causing indirect myocyte injury may also play a role. Combination of proper triage, close monitoring, and avoidance of some drugs that have cardiovascular toxicity are important in the management of cardiovascular system involvement in COVID-19 patients. The involvement of the cardiovascular system in COVID-19 patients is prevalent, variable, and debilitating. Therefore, it requires our attention and comprehensive management.", "qid": 22, "docid": "kt6t41ff", "rank": 64, "score": 0.8202784061431885}, {"content": "Title: Cardiac Manifestations of Coronavirus Disease 2019 (COVID-19): A Comprehensive Review Content: Since its origin in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a pandemic and spread to 209 countries. As coronavirus disease 2019 (COVID-19) is a very rapidly emerging disease, organ-specific studies related to it have been reported. Apart from respiratory findings, some studies have highlighted inflammatory consequences in the heart, kidney, and/or liver as well. Cardiac involvement in COVID-19 seems to be a result of an inflammatory storm in response to the infection. Moreover, direct viral invasion of cardiomyocytes, as well as a myocardial injury due to oxidative stress, may account for acute cardiac injury in COVID-19. Nevertheless, the mechanism of heart injury in COVID-19 is not clear yet. However, multiple studies that highlight the clinical features, laboratory findings, and prognosis of acute myocardial injury (AMI) in COVID-19-affected individuals have been published. In this review, we have summarized the findings of all those studies as well as the clinical features and management of cardiac injury discussed by some case reports.", "qid": 22, "docid": "qmp2tqtb", "rank": 65, "score": 0.8202542662620544}, {"content": "Title: The role of cardiac imaging in hospitalized COVID-19-positive patients Content: COVID-19 infection is associated with several cardiac complications with high rates of adverse outcomes. Cardiac imaging has different utility in different clinical scenarios, and the importance of minimizing healthcare worker exposure should be considered. Cardiac imaging should only be ordered if its benefits outweigh its risks, with anticipated changes in acute treatment and outcomes, and no suitable alternative of sufficient adequacy is available. Indications for advanced cardiac imaging for COVID-19 patients in the acute phase are limited, although follow-up imaging in the convalescent stage may provide prognostic importance in recovered COVID-19 patients with positive troponin or decompensated heart failure.", "qid": 22, "docid": "ozy39172", "rank": 66, "score": 0.8200546503067017}, {"content": "Title: The role of cardiac imaging in hospitalized COVID-19-positive patients. Content: COVID-19 infection is associated with several cardiac complications with high rates of adverse outcomes. Cardiac imaging has different utility in different clinical scenarios, and the importance of minimizing healthcare worker exposure should be considered. Cardiac imaging should only be ordered if its benefits outweigh its risks, with anticipated changes in acute treatment and outcomes, and no suitable alternative of sufficient adequacy is available. Indications for advanced cardiac imaging for COVID-19 patients in the acute phase are limited, although follow-up imaging in the convalescent stage may provide prognostic importance in recovered COVID-19 patients with positive troponin or decompensated heart failure.", "qid": 22, "docid": "q5p0ie3j", "rank": 67, "score": 0.8200546503067017}, {"content": "Title: Acute Myocardial Injury of Patients with Coronavirus Disease 2019 Content: Background: Since the outbreak of the Coronavirus Disease 2019 (COVID-19) in China, respiratory manifestations of the disease have been observed. However, as a fatal comorbidity, acute myocardial injury (AMI) in COVID-19 patients has not been previously investigated in detail. We investigated the clinical characteristics of COVID-19 patients with AMI and determined the risk factors for AMI in them. Methods: We analyzed data from 53 consecutive laboratory-confirmed and hospitalized COVID-19 patients (28 men, 25 women; age, 19-81 years). We collected information on epidemiological and demographic characteristics, clinical features, routine laboratory tests (including cardiac injury biomarkers), echocardiography, electrocardiography, imaging findings, management methods, and clinical outcomes. Results: Cardiac complications were found in 42 of the 53 (79.25%) patients: tachycardia (n=15), electrocardiography abnormities (n=11), diastolic dysfunction (n=20), elevated myocardial enzymes (n=30), and AMI (n=6). All the six AMI patients were aged >60 years; five of them had two or more underlying comorbidities (hypertension, diabetes, cardiovascular diseases, and chronic obstructive pulmonary disease). Novel coronavirus pneumonia (NCP) severity was higher in the AMI patients than in patients with non-definite AMI (p<0.001). All the AMI patients required care in intensive care unit; of them, three died, two remain hospitalized. Multivariate analyses showed that C-reactive protein (CRP) levels, NCP severity, and underlying comorbidities were the risk factors for cardiac abnormalities in COVID-19 patients. Conclusions: Cardiac complications are common in COVID-19 patients. Elevated CRP levels, underlying comorbidities, and NCP severity are the main risk factors for cardiac complications in COVID-19 patients.", "qid": 22, "docid": "jg6v644y", "rank": 68, "score": 0.8194461464881897}, {"content": "Title: Heart and Lung Multimodality Imaging in COVID-19 Content: Abstract SARS-CoV-2 outbreak has rapidly reached a pandemic proportion and has become a major threaten to global health. Although the predominant clinical feature of COVID-19 is an acute respiratory syndrome of varying severity, ranging from mild symptomatic interstitial pneumonia to acute respiratory distress syndrome, the cardiovascular system can be involved with several facets. As many as 40% hospitalized patients presenting with COVID-19 have pre-existing history of cardiovascular disease and current estimates report a proportion of myocardial injury in COVID-19 patients ranging up to 12%. Multiple pathways have been advocated to explain this finding and the related clinical scenarios, encompassing local and systemic inflammatory response and oxygen supply-demand imbalance. From a clinical point of view, cardiac involvement during COVID-19 may present a wide spectrum of severity ranging from subclinical myocardial injury to well-defined clinical entities (myocarditis, myocardial infarction, pulmonary embolism and heart failure), whose incidence and prognostic implications are currently largely unknown due to a significant lack of imaging data. The use of integrated heart and lung multimodality imaging plays a central role in different clinical settings and is essential in diagnosis, risk stratification and management of COVID-19 patients. Aim of this review is to summarize imaging-oriented pathophysiological mechanisms of lung and cardiac involvement in COVID-19 and to provide a guide for an integrated imaging assessment in these patients.", "qid": 22, "docid": "7y1la856", "rank": 69, "score": 0.8192353844642639}, {"content": "Title: Cardiac and arrhythmic complications in patients with COVID\u201019 Content: In December 2019, the world started to face a new pandemic situation, the severe acute respiratory syndrome\u2010coronavirus 2 (SARS\u2010CoV\u20102). Although coronavirus disease (COVID\u201019) clinical manifestations are mainly respiratory, major cardiac complications are being reported. Cardiac manifestations etiology seems to be multifactorial, comprising direct viral myocardial damage, hypoxia, hypotension, enhanced inflammatory status, ACE2\u2010receptors downregulation, drug toxicity, endogenous catecholamine adrenergic status, among others. Studies evaluating patients with COVID\u201019 presenting cardiac injury markers show that it is associated with poorer outcomes, and arrhythmic events are not uncommon. Besides, drugs currently used to treat the COVID\u201019 are known to prolong the QT interval and can have a proarrhythmic propensity. This review focus on COVID\u201019 cardiac and arrhythmic manifestations and, in parallel, makes an appraisal of other virus epidemics as SARS\u2010CoV, Middle East respiratory syndrome coronavirus, and H1N1 influenza.", "qid": 22, "docid": "xhum1ykr", "rank": 70, "score": 0.8186459541320801}, {"content": "Title: COVID-19 and myocarditis: What do we know so far? Content: COVID-19 has been declared a global pandemic by the World Health Organization and is responsible for hundreds of thousands of deaths worldwide. COVID-19 is caused by SARS-CoV-2, and common clinical symptoms include fever, cough, sore throat, headache, and fatigue. Myocardial injury is relatively common in COVID-19, accounting for 7-23% of cases, and is associated with a higher morbidity and mortality. There is a discrepancy in the literature about myocarditis as the etiology of myocardial injury in COVID-19; although many anecdotal reports of myocarditis have been noted, there are only a handful of case reports in the literature about myocarditis related to COVID-19. This review summarizes the most up-to-date literature around the association between COVID-19 and myocarditis and gives clinicians a practical framework about the clinical manifestations, diagnostic tools and treatment options currently available. Importantly, this review will heighten suspicion for myocarditis as an etiology of myocardial injury in COVID-19 patients, therefore improving clinical outcomes and encouraging shared clinical decision-making. This will also open the door for further research to build around this review. Emergent treatment options for COVID-19 are in clinical trials and may be of benefit to COVID-19 patients with myocarditis in addition to current guideline-based recommendations.", "qid": 22, "docid": "wq89wtwf", "rank": 71, "score": 0.817893922328949}, {"content": "Title: Arterial thromboembolic complications in COVID\u201019 in low\u2010risk patients despite prophylaxis Content: We present a case series of three patients with COVID-19 who developed arterial vascular complications, one who developed an acute CVA, one who developed popliteal artery occlusion and one who developed both during their hospital course. We present a case series of three patients admitted to Northwell Plainview Hospital in Plainview, New York with COVID-19 as confirmed by PCR. The clinical disease course of COVID-19 has been well documented in China and Europe and most recently, the United States. Publications highlighting the non-respiratory complications of COVID-19 have been limited.[1, 2] Acute cardiac injury and arrhythmia in the ICU have been described as major complications of COVID-19.[3] A few publications have highlighted the incidence of venous thromboembolic complications in COVID-19.[4, 5].", "qid": 22, "docid": "01yzk0au", "rank": 72, "score": 0.817812442779541}, {"content": "Title: Cardiovascular Complications in Patients with COVID-19: Consequences of Viral Toxicities and Host Immune Response Content: PURPOSE OF REVIEW: Coronavirus disease of 2019 (COVID-19) is a cause of significant morbidity and mortality worldwide. While cardiac injury has been demonstrated in critically ill COVID-19 patients, the mechanism of injury remains unclear. Here, we review our current knowledge of the biology of SARS-CoV-2 and the potential mechanisms of myocardial injury due to viral toxicities and host immune responses. RECENT FINDINGS: A number of studies have reported an epidemiological association between history of cardiac disease and worsened outcome during COVID infection. Development of new onset myocardial injury during COVID-19 also increases mortality. While limited data exist, potential mechanisms of cardiac injury include direct viral entry through the angiotensin-converting enzyme 2 (ACE2) receptor and toxicity in host cells, hypoxia-related myocyte injury, and immune-mediated cytokine release syndrome. Potential treatments for reducing viral infection and excessive immune responses are also discussed. SUMMARY: COVID patients with cardiac disease history or acquire new cardiac injury are at an increased risk for in-hospital morbidity and mortality. More studies are needed to address the mechanism of cardiotoxicity and the treatments that can minimize permanent damage to the cardiovascular system.", "qid": 22, "docid": "xkg0ylz8", "rank": 73, "score": 0.8176559209823608}, {"content": "Title: Cardiovascular Complications in Patients with COVID-19: Consequences of Viral Toxicities and Host Immune Response Content: PURPOSE OF REVIEW: Coronavirus disease of 2019 (COVID-19) is a cause of significant morbidity and mortality worldwide. While cardiac injury has been demonstrated in critically ill COVID-19 patients, the mechanism of injury remains unclear. Here, we review our current knowledge of the biology of SARS-CoV-2 and the potential mechanisms of myocardial injury due to viral toxicities and host immune responses. RECENT FINDINGS: A number of studies have reported an epidemiological association between history of cardiac disease and worsened outcome during COVID infection. Development of new onset myocardial injury during COVID-19 also increases mortality. While limited data exist, potential mechanisms of cardiac injury include direct viral entry through the angiotensin-converting enzyme 2 (ACE2) receptor and toxicity in host cells, hypoxia-related myocyte injury, and immune-mediated cytokine release syndrome. Potential treatments for reducing viral infection and excessive immune responses are also discussed. COVID patients with cardiac disease history or acquire new cardiac injury are at an increased risk for in-hospital morbidity and mortality. More studies are needed to address the mechanism of cardiotoxicity and the treatments that can minimize permanent damage to the cardiovascular system.", "qid": 22, "docid": "6f8la6sw", "rank": 74, "score": 0.8174782395362854}, {"content": "Title: 2019 Novel-coronavirus: Cardiovascular Insights about Risk Factors, Myocardial Injury, Therapy and Clinical Implications Content: From December 31th, 2019, a novel highly pathogenic coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide, reaching at present the dimension of a pandemic. In addition to damaging the lungs, SARS-CoV-2 may also damage the heart and this is corroborated by the evidence that cardiovascular comorbidities are associated with a higher mortality and poor clinical outcomes in patient infected by the virus. During the infection myocardial injury, myocarditis and arrhythmias have also been reported, but the pathophysiological mechanisms of these complications are yet to be understood. Great attention is also being posed on the potential beneficial/harmful role of angiotensin converting enzyme (ACE) inhibitors, as far as the virus binds to angiotensin converting enzyme 2 (ACE2) to infect cells, but evidences lack. Furthermore, SARS-CoV-2 can also affect the aspect of acute coronary syndromes, not only because these two distinct pathological entities share pathogenic aspects (such as the systemic inflammatory state and cytokine release), but also and above all for the consequences that the need to contain the infection has on the management of cardiological urgencies. Aim of this review is therefore to summarize the relationship between the virus and the cardiovascular system.", "qid": 22, "docid": "myj3gw8d", "rank": 75, "score": 0.8168449997901917}, {"content": "Title: COVID-19 y enfermedad cardiovascular Content: In December 2019, in Wuhan in the province of Hubei in China, there was a report on a group of 27 patients with a pneumonia of unknown origin, linked to exposure in a market with shellfish, fish, and live animals. In January 2020, a new strain of coronavirus (SARS-CoV-2) was isolated in these patients. The disease caused by this virus has been given the name of COVID-19. During the initial stages of the pandemic, and given the scarcity of studies published about this, it was believed that this coronavirus only caused respiratory symptoms. However, as the number of patients increased, it was observed that cardiovascular disease had a fundamental role in the development and prognosis of the infection. The most important risk factors associated with mortality are age and the presence of comorbidities, particularly cardiovascular ones. The increase in the levels of troponin, natriuretic peptides, and D-dimer are of prognostic values in patients with an infection due to SARS-CoV-2. Patients with COVID-19 have an increased risk of acute myocardial infarction, myocarditis, heart failure, shock, arrhythmias, and sudden death, in relation to the systematic response to the virus and to the treatments needed in the acute phase. A review is presented in this article of the cardiovascular involvement due to SARS-CoV-2 (COVID-19).", "qid": 22, "docid": "up929iw0", "rank": 76, "score": 0.8159412145614624}, {"content": "Title: COVID-19 (SARS-Cov-2) and the heart \u2013 An ominous association Content: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cardiovascular manifestations of COVID-19 are diverse and complex and include acute coronary syndrome, myocarditis masquerading as ST-segment elevation myocardial infarction, pericarditis and pericardial effusion. We present 2 cases of COVID-19 infection with myocardial involvement with distinct mechanistic pathways and outcomes. Important decision strategies such as the timing of cardiac catheterization (when indicated) and requirement of early hemodynamic support in critically ill patients are discussed.", "qid": 22, "docid": "rsyiemgn", "rank": 77, "score": 0.8144915103912354}, {"content": "Title: COVID-19 (SARS-Cov-2) and the heart - An ominous association Content: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cardiovascular manifestations of COVID-19 are diverse and complex and include acute coronary syndrome, myocarditis masquerading as ST-segment elevation myocardial infarction, pericarditis and pericardial effusion. We present 2 cases of COVID-19 infection with myocardial involvement with distinct mechanistic pathways and outcomes. Important decision strategies such as the timing of cardiac catheterization (when indicated) and requirement of early hemodynamic support in critically ill patients are discussed.", "qid": 22, "docid": "q0qjfoc0", "rank": 78, "score": 0.8144915103912354}, {"content": "Title: COVID-19 pandemic and cardiovascular disease: where do we stand? Content: INTRODUCTION Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19) which recently has been characterized as a pandemic by the World Health Organization (WHO) having killed almost 250,000 people worldwide as of May 4th 2020. Despite the fact that SARS-CoV-2 seems to predominantly affect the respiratory system leading to pneumonia and acute respiratory distress syndrome, it is now evident that it may also affect the cardiovascular system in multiple ways. EVIDENCE ACQUISITION The current paper is a review of the most recent literature regarding SARS-CoV-2 infection and its associated main cardiovascular clinical manifestations. EVIDENCE SYNTHESIS Cardiovascular disease represents a prevalent underlying comorbidity associated with increased mortality rates among COVID-19 affected individuals. In addition, various cardiovascular manifestations have been linked to the viral insult, including among others acute coronary syndromes, myocarditis, acute heart failure, cardiac injury, arrhythmias and acute pulmonary embolism. CONCLUSIONS Further studies are required in order to establish the complicated association between SARS-CoV-2 infection and its effects on the cardiovascular system. Our knowledge regarding diagnostic approaches, therapeutic management and preventive measures is constantly enriched throughout an abundance of ongoing research in the respective fields.", "qid": 22, "docid": "bfipcprw", "rank": 79, "score": 0.8138593435287476}, {"content": "Title: 2019-Novel Coronavirus-Related Acute Cardiac Injury Cannot Be Ignored Content: PURPOSE OF THE REVIEW: Coronavirus disease 2019 (COVID-19), a new infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has reached a pandemic status. Although SARSCoV-2 causes primarily respiratory problems, concurrent cardiac injury cannot be ignored since it may be an independent predictor for adverse outcomes. To resolve these issues, we aim to summarize the prevalence and its underlying mechanisms of acute cardiac injury in the setting of SARS-CoV-2 infection. RECENT FINDINGS: The main clinical manifestation of SARS-CoV-2 infection is pneumonia, cardiovascular complications have also been identified in the earliest reported cases from Wuhan, the epicenter of the outbreak. Given the SARS-CoV-2 likely uses the angiotensin-converting enzyme-2 (ACE2) receptors as its host receptor, ACE2-related signaling pathways may play a key role in mediating myocardial injury. SUMMARY: SARS-CoV-2 infection related acute cardiac injury cannot be ignored, and its underlying mechanisms remain speculated. We would suggest that health professionals investigate cardiac function as part of the routine care.", "qid": 22, "docid": "uhmxkvit", "rank": 80, "score": 0.8129391670227051}, {"content": "Title: COVID-19 and the Heart. Content: Infection with the novel coronavirus, SARS-CoV-2, produces a clinical syndrome known as COVID-19. When severe, COVID-19 is a systemic illness characterized by hyperinflammation, cytokine storm and elevations of cardiac injury biomarkers. Here we review what is known about the pathophysiology of COVID-19, its cardiovascular manifestations, and emerging therapeutic prospects. In this rapidly moving field, this review was comprehensive as of April 3, 2020.", "qid": 22, "docid": "d4h49d8b", "rank": 81, "score": 0.8128852248191833}, {"content": "Title: COVID-19 and congenital heart disease: Results from a nationwide survey Content: Background. The pandemic of Novel Coronavirus Disease 2019 (COVID-19) is challenging, given the large number of hospitalized patients. Cardiovascular co-morbidities are linked to a higher mortality risk. Thus, patients with Congenital Heart Disease (CHD) might represent a high-risk population. Nevertheless, no data about them are available, yet. Hence, we conducted a nationwide survey to assess clinical characteristics and outcomes in patients with congenital heart disease affected by COVID-19. Methods and Results. This is a multi-centre, observational, nationwide survey, involving high-volume Italian CHD centres. COVID-19 diagnosis was defined as either \u201cclinically suspected\u201d or \u201cconfirmed\u201d, where a severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) test had been performed and was positive. Cardiovascular comorbidities were observed among adult patients\u2014atrial fibrillation (seven; 9%), hypertension (five; 7%), obesity (seven; 9%) and diabetes (one; 1%)\u2014but were absent among children. Cardiovascular complications were mainly observed in the \u201cconfirmed\u201d COVID-19+group, consisting of heart failure (9%), palpitations/arrhythmias (3%), stroke/TIA (3%) and pulmonary hypertension (3%). Cardiovascular symptoms such as chest pain (1%), myocardial injury (1%) and pericardial effusion (1%) were also recorded. On the contrary, CHD patients from the clinically suspected COVID-19 group presented no severe symptoms or complications. Conclusions. Despite previous reports pointing to a higher case-fatality rate among patients with cardiovascular co-morbidities, we observed a mild COVID-19 clinical course in our cohort of CHD patients. Although these results should be confirmed in larger cohorts to investigate the underlying mechanisms, the findings of low cardiovascular complications rates and no deaths are reassuring for CHD patients.", "qid": 22, "docid": "wenp9sgs", "rank": 82, "score": 0.8128206729888916}, {"content": "Title: COVID-19 pandemic and cardiovascular disease: where do we stand? Content: INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19) which recently has been characterized as a pandemic by the World Health Organization (WHO) having killed almost 250,000 people worldwide as of May 4th 2020. Despite the fact that SARS-CoV-2 seems to predominantly affect the respiratory system leading to pneumonia and acute respiratory distress syndrome, it is now evident that it may also affect the cardiovascular system in multiple ways. EVIDENCE ACQUISITION: The current paper is a review of the most recent literature regarding SARS-CoV-2 infection and its associated main cardiovascular clinical manifestations. EVIDENCE SYNTHESIS: Cardiovascular disease represents a prevalent underlying comorbidity associated with increased mortality rates among COVID-19 affected individuals. In addition, various cardiovascular manifestations have been linked to the viral insult, including among others acute coronary syndromes, myocarditis, acute heart failure, cardiac injury, arrhythmias and acute pulmonary embolism. CONCLUSIONS: Further studies are required in order to establish the complicated association between SARS-CoV-2 infection and its effects on the cardiovascular system. Our knowledge regarding diagnostic approaches, therapeutic management and preventive measures is constantly enriched throughout an abundance of ongoing research in the respective fields.", "qid": 22, "docid": "4m6labtz", "rank": 83, "score": 0.8124295473098755}, {"content": "Title: Pharmaco-invasive Therapy for STEMI in a Patient with COVID-19: A Case Report Content: Coronavirus disease 2019 (COVID-19) is a pandemic that started in the Wuhan province of China in December 2019. It is associated with increased morbidity and mortality mainly due to severe acute respiratory syndrome 2 (SARS-Cov-2). Cardiac manifestations related to COVID-19 include demand ischemia, fulminant myocarditis, myocardial infarction and arrhythmias. In this report, we present a case of ST-segment elevation myocardial infarction (STEMI) in a 68-year-old man with COVID-19 who initially presented with chest pain and shortness of breath. Patient\u2019s STEMI was managed with pharmaco-invasive strategy with tissue plasminogen activator (t-PA). He then developed acute hypoxic respiratory failure that was managed in the intensive care unit (ICU), together with multi-organ failure from which the patient died 2 days after presentation. Although the pathophysiologic mechanisms of STEMI in COVID-19 patients has not been clearly established, we hypothesize that interrelated pathogenetic factors, that we highlight in this report, can play a role in the development of STEMI, including plaque rupture secondary to systemic inflammation, increased pro-coagulants, endothelial dysfunction, impaired fibrinolysis and impaired oxygen utilization leading to demand/supply mismatch and myocardial ischemia.", "qid": 22, "docid": "8fgwskfj", "rank": 84, "score": 0.8124136924743652}, {"content": "Title: 2019-Novel Coronavirus-Related Acute Cardiac Injury Cannot Be Ignored Content: PURPOSE OF THE REVIEW: Coronavirus disease 2019 (COVID-19), a new infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has reached a pandemic status. Although SARSCoV-2 causes primarily respiratory problems, concurrent cardiac injury cannot be ignored since it may be an independent predictor for adverse outcomes. To resolve these issues, we aim to summarize the prevalence and its underlying mechanisms of acute cardiac injury in the setting of SARS-CoV-2 infection. RECENT FINDINGS: The main clinical manifestation of SARS-CoV-2 infection is pneumonia, cardiovascular complications have also been identified in the earliest reported cases from Wuhan, the epicenter of the outbreak. Given the SARS-CoV-2 likely uses the angiotensin-converting enzyme-2 (ACE2) receptors as its host receptor, ACE2-related signaling pathways may play a key role in mediating myocardial injury. SARS-CoV-2 infection related acute cardiac injury cannot be ignored, and its underlying mechanisms remain speculated. We would suggest that health professionals investigate cardiac function as part of the routine care.", "qid": 22, "docid": "o988xoxn", "rank": 85, "score": 0.8118946552276611}, {"content": "Title: Cardiovascular Complications of COVID-19: Pharmacotherapy Perspective Content: Coronavirus disease of 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly the world over. The disease was declared \u201cpandemic\u201d by the World Health Organization. An approved therapy for patients with COVID-19 has yet to emerge; however, there are some medications used in the treatment of SARS-CoV-2 infection globally including hydroxychloroquine, remdesivir, dexamethasone, protease inhibitors, and anti-inflammatory agents. Patients with underlying cardiovascular disease are at increased risk of mortality and morbidity from COVID-19. Moreover, patients with chronic stable states and even otherwise healthy individuals might sustain acute cardiovascular problems due to COVID-19 infection. This article seeks to review the latest evidence with a view to explaining possible pharmacotherapies for the cardiovascular complications of COVID-19 including acute coronary syndrome, heart failure, myocarditis, arrhythmias, and venous thromboembolism, as well as possible interactions between these medications and those currently administered (or under evaluation) in the treatment of COVID-19.", "qid": 22, "docid": "qvsoinfy", "rank": 86, "score": 0.811600387096405}, {"content": "Title: Suspected myocardial injury in patients with COVID-19: Evidence from front-line clinical observation in Wuhan, China Content: BACKGROUND: A novel coronavirus disease (COVID-19) in Wuhan has caused an outbreak and become a major public health issue in China and great concern from international community. Myocarditis and myocardial injury were suspected and may even be considered as one of the leading causes for death of COVID-19 patients. Therefore, we focused on the condition of the heart, and sought to provide firsthand evidence for whether myocarditis and myocardial injury were caused by COVID-19. METHODS: We enrolled patients with confirmed diagnosis of COVID-19 retrospectively and collected heart-related clinical data, mainly including cardiac imaging findings, laboratory results and clinical outcomes. Serial tests of cardiac markers were traced for the analysis of potential myocardial injury/myocarditis. RESULTS: 112 COVID-19 patients were enrolled in our study. There was evidence of myocardial injury in COVID-19 patients and 14 (12.5%) patients had presented abnormalities similar to myocarditis. Most of patients had normal levels of troponin at admission, that in 42 (37.5%) patients increased during hospitalization, especially in those that died. Troponin levels were significantly increased in the week preceding the death. 15 (13.4%) patients have presented signs of pulmonary hypertension. Typical signs of myocarditis were absent on echocardiography and electrocardiogram. CONCLUSIONS: The clinical evidence in our study suggested that myocardial injury is more likely related to systemic consequences rather than direct damage by the 2019 novel coronavirus. The elevation in cardiac markers was probably due to secondary and systemic consequences and can be considered as the warning sign for recent adverse clinical outcomes of the patients.", "qid": 22, "docid": "5ql7876p", "rank": 87, "score": 0.8113095164299011}, {"content": "Title: COVID-19 and the Cerebro-Cardiovascular Systems: What do we Know so Far? Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic of 2019-2020 has resulted in multiple hospitalizations, deaths and economic hardships worldwide. Though respiratory involvement in patients with coronavirus disease 2019 (COVID-19) is well-known, the potential cardiovascular and cerebrovascular manifestations are less-understood. We performed a PubMed and Google Scholar search and reviewed relevant literature regarding COVID-19 and cardiovascular system involvement. SARS-CoV-2 possesses high-affinity for angiotensin converting enzyme 2 (ACE2) receptor, which is highly concentrated in the lungs and cardiovascular tissue, thereby provoking concern for cardiovascular involvement in COVID-19 cases. Pre-existing cardiovascular and cerebrovascular disease has been shown in previous reports to be a risk-factor for severe infection. Based on our review of published studies, COVID-19 patients may be more likely to experience acute cardiac injury, arrhythmia, coagulation defects and acute stroke and are likely to have poorer outcomes as a result. As the COVID-19 pandemic continues, more data regarding potential cardiovascular and cerebrovascular manifestations of the disease is required.", "qid": 22, "docid": "sam3usz7", "rank": 88, "score": 0.8111597299575806}, {"content": "Title: Cardiovascular conditions and COVID-19 Content: Although COVID-19 primarily affects the respiratory system, cardiovascular involvement is common, especially in individuals who are severely ill.", "qid": 22, "docid": "cn6dxf6g", "rank": 89, "score": 0.8109032511711121}, {"content": "Title: Cardiovascular conditions and COVID-19. Content: Although COVID-19 primarily affects the respiratory system, cardiovascular involvement is common, especially in individuals who are severely ill.", "qid": 22, "docid": "1cntwm22", "rank": 90, "score": 0.8109031915664673}, {"content": "Title: Myocardial injury and COVID-19: Possible mechanisms Content: Abstract Coronavirus Disease 2019 (COVID-19) has quickly progressed to a global health emergency. Respiratory illness is the major cause of morbidity and mortality in these patients with the disease spectrum ranging from asymptomatic subclinical infection, to severe pneumonia progressing to acute respiratory distress syndrome. There is growing evidence describing pathophysiological resemblance of SARS-CoV-2 infection with other coronavirus infections such as Severe Acute Respiratory Syndrome coronavirus and Middle East Respiratory Syndrome coronavirus (MERS-CoV). Angiotensin Converting Enzyme-2 receptors play a pivotal role in the pathogenesis of the virus. Disruption of this receptor leads to cardiomyopathy, cardiac dysfunction, and heart failure. Patients with cardiovascular disease are more likely to be infected with SARS-CoV-2 and they are more likely to develop severe symptoms. Hypertension, arrhythmia, cardiomyopathy and coronary heart disease are amongst major cardiovascular disease comorbidities seen in severe cases of COVID-19. There is growing literature exploring cardiac involvement in SARS-CoV-2. Myocardial injury is one of the important pathogenic features of COVID-19. As a surrogate for myocardial injury, multiple studies have shown increased cardiac biomarkers mainly cardiac troponins I and T in the infected patients especially those with severe disease. Myocarditis is depicted as another cause of morbidity amongst COVID-19 patients. The exact mechanisms of how SARS-CoV-2 can cause myocardial injury are not clearly understood. The proposed mechanisms of myocardial injury are direct damage to the cardiomyocytes, systemic inflammation, myocardial interstitial fibrosis, interferon mediated immune response, exaggerated cytokine response by Type 1 and 2 helper T cells, in addition to coronary plaque destabilization, and hypoxia.", "qid": 22, "docid": "ter67nri", "rank": 91, "score": 0.810856819152832}, {"content": "Title: Cardiovascular implications of the COVID-19 pandemic: a global perspective Content: The Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), represents the pandemic of the century, with approximately 3.5 million cases and 250,000 deaths worldwide as of May 2020. Although respiratory symptoms usually dominate the clinical presentation, COVID-19 is now known to also have potentially serious cardiovascular consequences, including myocardial injury, myocarditis, acute coronary syndromes, pulmonary embolism, stroke, arrhythmias, heart failure, and cardiogenic shock. The cardiac manifestations of COVID-19 might be related to the adrenergic drive, systemic inflammatory milieu and cytokine-release syndrome caused by SARS-CoV-2, direct viral infection of myocardial and endothelial cells, hypoxia due to respiratory failure, electrolytic imbalances, fluid overload, and side effects of certain COVID-19 medications. COVID-19 has profoundly reshaped usual care of both ambulatory and acute cardiac patients, by leading to the cancellation of elective procedures and by reducing the efficiency of existing pathways of urgent care, respectively. Decreased utilization of healthcare services for acute conditions by non-COVID-19 patients has also been reported and attributed to concerns about acquiring in-hospital infection. Innovative approaches that leverage modern technologies to tackle the COVID-19 pandemic have been introduced, which include telemedicine, dissemination of educational material over social media, smartphone apps for case tracking, and artificial intelligence for pandemic modelling, among others. This article provides a comprehensive overview of the pathophysiology and cardiovascular implications of COVID-19, its impact on existing pathways of care, the role of modern technologies to tackle the pandemic, and a proposal of novel management algorithms for the most common acute cardiac conditions.", "qid": 22, "docid": "dthdszdn", "rank": 92, "score": 0.8107219934463501}, {"content": "Title: Cardiovascular system and COVID-19: perspectives from a developing country Content: A novel coronavirus, SARS-CoV-2, thought to have originated from bats causes COVID-19 infection which was first reported from Wuhan, China in December 2019. This virus has a high infectivity rate and has impacted a significant chunk of the population worldwide. The spectrum of disease ranges from mild to severe with respiratory system being the most commonly affected. Cardiovascular system often gets involved in later stages of the disease with acute cardiac injury, heart failure and arrhythmias being the common complications. In addition, the presence of cardiovascular co-morbidities such as hypertension, coronary artery disease in these patients are often associated with poor prognosis. It is still not clear regarding the exact mechanism explaining cardiovascular system involvement in COVID-19. Multiple theories have been put forward however, more robust studies are required to fully elucidate the \"heart and virus\" link. The disease has already made its presence felt on the global stage and its impact in the developing countries is going to be profound. These nations not only have a poorly developed healthcare system but there is also a huge burden of cardiovascular diseases. As a result, COVID-19 would adversely impact the already overburdened healthcare network leading to impaired cardiovascular care delivery especially for acute coronary syndrome and heart failure patients.", "qid": 22, "docid": "iqbc09sz", "rank": 93, "score": 0.8106718063354492}, {"content": "Title: Cardiovascular system and COVID-19: perspectives from a developing country. Content: A novel coronavirus, SARS-CoV-2, thought to have originated from bats causes COVID-19 infection which was first reported from Wuhan, China in December 2019. This virus has a high infectivity rate and has impacted a significant chunk of the population worldwide. The spectrum of disease ranges from mild to severe with respiratory system being the most commonly affected. Cardiovascular system often gets involved in later stages of the disease with acute cardiac injury, heart failure and arrhythmias being the common complications. In addition, the presence of cardiovascular co-morbidities such as hypertension, coronary artery disease in these patients are often associated with poor prognosis. It is still not clear regarding the exact mechanism explaining cardiovascular system involvement in COVID-19. Multiple theories have been put forward however, more robust studies are required to fully elucidate the \"heart and virus\" link. The disease has already made its presence felt on the global stage and its impact in the developing countries is going to be profound. These nations not only have a poorly developed healthcare system but there is also a huge burden of cardiovascular diseases. As a result, COVID-19 would adversely impact the already overburdened healthcare network leading to impaired cardiovascular care delivery especially for acute coronary syndrome and heart failure patients.", "qid": 22, "docid": "5ylq8jps", "rank": 94, "score": 0.8106718063354492}, {"content": "Title: Coronavirus Disease 2019 (COVID-19) Pandemic Implications in Pediatric and Adult Congenital Heart Disease Content: The corona virus disease -2019 (COVID-19) is a recently described infectious disease caused by the severe acute respiratory syndrome corona virus 2 with significant cardiovascular implications. Given the increased risk for severe COVID-19 observed in adults with underlying cardiac involvement, there is concern that patients with pediatric and congenital heart disease (CHD) may likewise be at increased risk for severe infection. The cardiac manifestations of COVID-19 include myocarditis, arrhythmia and myocardial infarction. Importantly, the pandemic has stretched health care systems and many care team members are at risk for contracting and possibly transmitting the disease which may further impact the care of patients with cardiovascular disease. In this review, we describe the effects of COVID-19 in the pediatric and young adult population and review the cardiovascular involvement in COVID-19 focusing on implications for patients with congenital heart disease in particular.", "qid": 22, "docid": "dcf82t8n", "rank": 95, "score": 0.8100820779800415}, {"content": "Title: Coronavirus Disease 2019 (COVID-19) Pandemic Implications in Pediatric and Adult Congenital Heart Disease. Content: The corona virus disease -2019 (COVID-19) is a recently described infectious disease caused by the severe acute respiratory syndrome corona virus 2 with significant cardiovascular implications. Given the increased risk for severe COVID-19 observed in adults with underlying cardiac involvement, there is concern that patients with pediatric and congenital heart disease (CHD) may likewise be at increased risk for severe infection. The cardiac manifestations of COVID-19 include myocarditis, arrhythmia and myocardial infarction. Importantly, the pandemic has stretched health care systems and many care team members are at risk for contracting and possibly transmitting the disease which may further impact the care of patients with cardiovascular disease. In this review, we describe the effects of COVID-19 in the pediatric and young adult population and review the cardiovascular involvement in COVID-19 focusing on implications for patients with congenital heart disease in particular.", "qid": 22, "docid": "5f9ofdsc", "rank": 96, "score": 0.8100820779800415}, {"content": "Title: Cardiovascular manifestations in severe and critical patients with COVID-19 Content: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could cause virulent infection leading to Corona Virus Disease 2019 (COVID-19)-related pneumonia as well as multiple organ injuries. HYPOTHESIS: COVID-19 infection may result in cardiovascular manifestations leading to worse clinical outcome. METHODS: Fifty four severe and critical patients with confirmed COVID-19 were enrolled. Risk factors predicting the severity of COVID-19 were analyzed. RESULTS: Of the 54 patients (56.1 \u00b1 13.5 years old, 66.7% male) with COVID-19, 39 were diagnosed as severe and 15 as critical cases. The occurrence of diabetes, the level of D-dimer, inflammatory and cardiac markers in critical cases were significantly higher. Troponin I (TnI) elevation occurred in 42.6% of all the severe and critical patients. Three patients experienced hypotension at admission and were all diagnosed as critical cases consequently. Hypotension was found in one severe case and seven critical cases during hospitalization. Sinus tachycardia is the most common type of arrythmia and was observed in 23 severe patients and all the critical patients. Atrioventricular block and ventricular tachycardia were observed in critical patients at end stage while bradycardia and atrial fibrillation were less common. Mild pericardial effusion was observed in one severe case and five critical cases. Three critical cases suffered new onset of heart failure. Hypotension during treatment, severe myocardial injury and pericardial effusion were independent risk factors predicting the critical status of COVID-19 infection. CONCLUSION: This study has systemically observed the impact of COVID-19 on cardiovascular system, including myocardial injury, blood pressure, arrythmia and cardiac function in severe and critical cases. Monitoring of vital signs and cardiac function of COVID-19 patients and applying potential interventions especially for those with hypotension during treatment, severe myocardial injury or pericardial effusion, is of vital importance.", "qid": 22, "docid": "x9qxnybj", "rank": 97, "score": 0.8099645972251892}, {"content": "Title: COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options Content: The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.", "qid": 22, "docid": "ubhntliy", "rank": 98, "score": 0.8093386888504028}, {"content": "Title: Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. Content: Importance Coronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. However, information on cardiac injury in patients affected by COVID-19 is limited. Objective To explore the association between cardiac injury and mortality in patients with COVID-19. Design, Setting, and Participants This cohort study was conducted from January 20, 2020, to February 10, 2020, in a single center at Renmin Hospital of Wuhan University, Wuhan, China; the final date of follow-up was February 15, 2020. All consecutive inpatients with laboratory-confirmed COVID-19 were included in this study. Main Outcomes and Measures Clinical laboratory, radiological, and treatment data were collected and analyzed. Outcomes of patients with and without cardiac injury were compared. The association between cardiac injury and mortality was analyzed. Results A total of 416 hospitalized patients with COVID-19 were included in the final analysis; the median age was 64 years (range, 21-95 years), and 211 (50.7%) were female. Common symptoms included fever (334 patients [80.3%]), cough (144 [34.6%]), and shortness of breath (117 [28.1%]). A total of 82 patients (19.7%) had cardiac injury, and compared with patients without cardiac injury, these patients were older (median [range] age, 74 [34-95] vs 60 [21-90] years; P < .001); had more comorbidities (eg, hypertension in 49 of 82 [59.8%] vs 78 of 334 [23.4%]; P < .001); had higher leukocyte counts (median [interquartile range (IQR)], 9400 [6900-13 800] vs 5500 [4200-7400] cells/\u03bcL) and levels of C-reactive protein (median [IQR], 10.2 [6.4-17.0] vs 3.7 [1.0-7.3] mg/dL), procalcitonin (median [IQR], 0.27 [0.10-1.22] vs 0.06 [0.03-0.10] ng/mL), creatinine kinase-myocardial band (median [IQR], 3.2 [1.8-6.2] vs 0.9 [0.6-1.3] ng/mL), myohemoglobin (median [IQR], 128 [68-305] vs 39 [27-65] \u03bcg/L), high-sensitivity troponin I (median [IQR], 0.19 [0.08-1.12] vs <0.006 [<0.006-0.009] \u03bcg/L), N-terminal pro-B-type natriuretic peptide (median [IQR], 1689 [698-3327] vs 139 [51-335] pg/mL), aspartate aminotransferase (median [IQR], 40 [27-60] vs 29 [21-40] U/L), and creatinine (median [IQR], 1.15 [0.72-1.92] vs 0.64 [0.54-0.78] mg/dL); and had a higher proportion of multiple mottling and ground-glass opacity in radiographic findings (53 of 82 patients [64.6%] vs 15 of 334 patients [4.5%]). Greater proportions of patients with cardiac injury required noninvasive mechanical ventilation (38 of 82 [46.3%] vs 13 of 334 [3.9%]; P < .001) or invasive mechanical ventilation (18 of 82 [22.0%] vs 14 of 334 [4.2%]; P < .001) than those without cardiac injury. Complications were more common in patients with cardiac injury than those without cardiac injury and included acute respiratory distress syndrome (48 of 82 [58.5%] vs 49 of 334 [14.7%]; P < .001), acute kidney injury (7 of 82 [8.5%] vs 1 of 334 [0.3%]; P < .001), electrolyte disturbances (13 of 82 [15.9%] vs 17 of 334 [5.1%]; P = .003), hypoproteinemia (11 of 82 [13.4%] vs 16 of 334 [4.8%]; P = .01), and coagulation disorders (6 of 82 [7.3%] vs 6 of 334 [1.8%]; P = .02). Patients with cardiac injury had higher mortality than those without cardiac injury (42 of 82 [51.2%] vs 15 of 334 [4.5%]; P < .001). In a Cox regression model, patients with vs those without cardiac injury were at a higher risk of death, both during the time from symptom onset (hazard ratio, 4.26 [95% CI, 1.92-9.49]) and from admission to end point (hazard ratio, 3.41 [95% CI, 1.62-7.16]). Conclusions and Relevance Cardiac injury is a common condition among hospitalized patients with COVID-19 in Wuhan, China, and it is associated with higher risk of in-hospital mortality.", "qid": 22, "docid": "qxqo23i9", "rank": 99, "score": 0.809120774269104}, {"content": "Title: Approach to Acute Cardiovascular Complications in COVID-19 Infection Content: The novel coronavirus disease 2019, otherwise known as COVID-19, is a global pandemic with primary respiratory manifestations in those who are symptomatic. It has spread to >187 countries with a rapidly growing number of affected patients. Underlying cardiovascular disease is associated with more severe manifestations of COVID-19 and higher rates of mortality. COVID-19 can have both primary (arrhythmias, myocardial infarction, and myocarditis) and secondary (myocardial injury/biomarker elevation and heart failure) cardiac involvement. In severe cases, profound circulatory failure can result. This review discusses the presentation and management of patients with severe cardiac complications of COVID-19 disease, with an emphasis on a Heart-Lung team approach in patient management. Furthermore, it focuses on the use of and indications for acute mechanical circulatory support in cardiogenic and/or mixed shock.", "qid": 22, "docid": "sw0xtwno", "rank": 100, "score": 0.8091111779212952}]}
{"query": "what kinds of complications related to COVID-19 are associated with hypertension?", "hits": [{"content": "Title: Cardiovascular comorbidity and its impact on patients with Covid-19 Content: Comorbid hypertension correlates with poorer outcomes in patients with Covid-19.", "qid": 23, "docid": "z28bws23", "rank": 1, "score": 0.8304550051689148}, {"content": "Title: Cardiovascular manifestations and treatment considerations in covid-19 Content: Since its recognition in December 2019, covid-19 has rapidly spread globally causing a pandemic. Pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease are associated with a greater severity and higher fatality rate of covid-19. Furthermore, covid-19 contributes to cardiovascular complications, including acute myocardial injury as a result of acute coronary syndrome, myocarditis, stress-cardiomyopathy, arrhythmias, cardiogenic shock, and cardiac arrest. The cardiovascular interactions of covid-19 have similarities to that of severe acute respiratory syndrome, Middle East respiratory syndrome and influenza. Specific cardiovascular considerations are also necessary in supportive treatment with anticoagulation, the continued use of renin-angiotensin-aldosterone system inhibitors, arrhythmia monitoring, immunosuppression or modulation, and mechanical circulatory support.", "qid": 23, "docid": "873txs85", "rank": 2, "score": 0.8280129432678223}, {"content": "Title: COVID-19: What are the risks in hypertensive patients? Content: Considering the number of patients affected by SARS-CoV-2, the World Health Organization declared a pandemic on 11 March 2020. A number of publications regarding the course of COVID-19 infection and its relation to comorbidities have appeared since December 2019, when the first cases of atypical pneumonia were diagnosed in China. There is evidence of the higher susceptibility and higher risk of unfavourable outcomes in comorbid patients, including those with hypertension. We summarize the available data on the association with the COVID-19 infection and arterial hypertension, and discuss potential risks, e. g. the risks and benefits of antihypertensive therapy (in particular, related to the blockers of renin-angiotensin-aldosterone system) and the management approaches.", "qid": 23, "docid": "ta9g9ceh", "rank": 3, "score": 0.8272966742515564}, {"content": "Title: SARS-CoV-2 (COVID 19) Infection in Hypertensive Patients and in Patients With Cardiac Disease Content: COVID 19, caused by the SARS-CoV-2 virus, a newly discovered coronavirus, has caused the global pandemic of early 2020. The first case was described in December 2019 in Wuhan, China, and by March 2020, most countries around the world have put in place some of the strictest restrictions seen in decades in order to slow down the spread of the disease. Patients with pre-existing hypertension and cardiovascular comorbidities were reported to be at an increased risk of serious infections caused by SARS-CoV-2. Considering that those are among the most common chronic medical conditions in the Western world, the potential impact of it is huge. The proposed mechanism behind those associations is the expression of angiotensin converting enzyme II (ACE II) in those patients. Furthermore, the association between ACE inhibitors/AR blockers, which are among the most frequently prescribed medications, and serious cases of COVID 19 has been studied with the same mechanism in mind. The reports on the association between hypertension and COVID 19 morbidity and mortality are less clear, and the International Society of Hypertension even claims that there is none. The reports on the association between heart failure or coronary disease and COVID 19 are more uniform, and all seem to point to a greater risk from serious infections faced by patients with those comorbidities. A significant effort will need to be invested by the scientific community into finding strategies for protecting those patients from contracting the virus in the first place and then, once infected, into developing management plans aimed at preserving cardiac function as much as possible.", "qid": 23, "docid": "xw817l53", "rank": 4, "score": 0.8236356973648071}, {"content": "Title: The importance of hypertension as a risk factor for severe illness and mortality in COVID\u201019 Content: The virus responsible for COVID-19 binds to the angiotensin converting enzyme-2 (ACE-2) receptor [1]. Several articles have noted that hypertension is a risk factor for COVID-19 [2-7]. It is currently difficult to distinguish between hypertension as an independent risk factor in COVID-19 from one that co-varies with other patient factors such as age and cardiovascular disease. It is difficult from individual reports to determine whether hypertension is a risk factor for development of symptomatic disease or hospitalisation or for more severe disease. Reviewing the literature that reports rates of hypertension amongst included patients indicates a consistent association with more severe disease and increased mortality.", "qid": 23, "docid": "4ko4lwjz", "rank": 5, "score": 0.8222728371620178}, {"content": "Title: Cardiovascular complications in COVID-19 Content: BACKGROUND: The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur. OBJECTIVE: This brief report evaluates cardiovascular complications in the setting of COVID-19 infection. DISCUSSION: The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death. The virus binds and enters through angiotensin-converting enzyme 2 (ACE2). COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness. The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events. Current therapies for COVID-19 may interact with cardiovascular medications. CONCLUSIONS: Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.", "qid": 23, "docid": "hl225efn", "rank": 6, "score": 0.8211283683776855}, {"content": "Title: Association of hypertension with the severity and fatality of SARS-CoV-2 infection: A meta-analysis Content: Hypertension is a common comorbidity in COVID-19 patients. However, the association of hypertension with the severity and fatality of COVID-19 remain unclear. In the present meta-analysis, relevant studies reported the impacts of hypertension on SARS-CoV-2 infection were identified by searching PubMed, Elsevier Science Direct, Web of Science, Wiley Online Library, Embase and CNKI up to 20 March 2020. As the results shown, 12 publications with 2389 COVID-19 patients (674 severe cases) were included for the analysis of disease severity. The severity rate of COVID-19 in hypertensive patients was much higher than in non-hypertensive cases (37.58% vs 19.73%, pooled OR: 2.27, 95% CI: 1.80-2.86). Moreover, the pooled ORs of COVID-19 severity for hypertension vs. non-hypertension was 2.21 (95% CI: 1.58-3.10) and 2.32 (95% CI: 1.70-3.17) in age <50 years and \u00e2\u00a9\u00be50 years patients, respectively. Additionally, six studies with 151 deaths of 2116 COVID-19 cases were included for the analysis of disease fatality. The results showed that hypertensive patients carried a nearly 3.48-fold higher risk of dying from COVID-19 (95% CI: 1.72-7.08). Meanwhile, the pooled ORs of COVID-19 fatality for hypertension vs. non-hypertension was 6.43 (95% CI: 3.40-12.17) and 2.66 (95% CI: 1.27-5.57) in age <50 years and \u00e2\u00a9\u00be50 years patients, respectively. Neither considerable heterogeneity nor publication bias was observed in the present analysis. Therefore, our present results provided further evidence that hypertension could significantly increase the risks of severity and fatality of SARS-CoV-2 infection.", "qid": 23, "docid": "u7fqjti5", "rank": 7, "score": 0.8211151957511902}, {"content": "Title: Association of hypertension with the severity and fatality of SARS-CoV-2 infection: A meta-analysis Content: Hypertension is a common comorbidity in COVID-19 patients. However, the association of hypertension with the severity and fatality of COVID-19 remain unclear. In the present meta-analysis, relevant studies reported the impacts of hypertension on SARS-CoV-2 infection were identified by searching PubMed, Elsevier Science Direct, Web of Science, Wiley Online Library, Embase and CNKI up to 20 March 2020. As the results shown, 12 publications with 2389 COVID-19 patients (674 severe cases) were included for the analysis of disease severity. The severity rate of COVID-19 in hypertensive patients was much higher than in non-hypertensive cases (37.58% vs 19.73%, pooled OR: 2.27, 95% CI: 1.80\u20132.86). Moreover, the pooled ORs of COVID-19 severity for hypertension vs. non-hypertension was 2.21 (95% CI: 1.58\u20133.10) and 2.32 (95% CI: 1.70\u20133.17) in age <50 years and \u2a7e50 years patients, respectively. Additionally, six studies with 151 deaths of 2116 COVID-19 cases were included for the analysis of disease fatality. The results showed that hypertensive patients carried a nearly 3.48-fold higher risk of dying from COVID-19 (95% CI: 1.72\u20137.08). Meanwhile, the pooled ORs of COVID-19 fatality for hypertension vs. non-hypertension was 6.43 (95% CI: 3.40\u201312.17) and 2.66 (95% CI: 1.27\u20135.57) in age <50 years and \u2a7e50 years patients, respectively. Neither considerable heterogeneity nor publication bias was observed in the present analysis. Therefore, our present results provided further evidence that hypertension could significantly increase the risks of severity and fatality of SARS-CoV-2 infection.", "qid": 23, "docid": "lnjlyaex", "rank": 8, "score": 0.8198216557502747}, {"content": "Title: Cardiovascular Risks in Patients with COVID-19: Potential Mechanisms and Areas of Uncertainty Content: PURPOSE OF REVIEW: COronaVirus Disease 2019 (COVID-19) has spread at unprecedented speed and scale into a global pandemic with cardiovascular risk factors and complications emerging as important disease modifiers. We aim to review available clinical and biomedical literature on cardiovascular risks of COVID-19. RECENT FINDINGS: SARS-CoV2, the virus responsible for COVID-19, enters the cell via ACE2 expressed in select organs. Emerging epidemiological evidence suggest cardiovascular risk factors are associated with increased disease severity and mortality in COVID-19 patients. Patients with a more severe form of COVID-19 are also more likely to develop cardiac complications such as myocardial injury and arrhythmia. The true incidence of and mechanism underlying these events remain elusive. SUMMARY: Cardiovascular diseases appear intricately linked with COVID-19, with cardiac complications contributing to the elevated morbidity/mortality of COVID-19. Robust epidemiologic and biologic studies are urgently needed to better understand the mechanism underlying these associations to develop better therapies.", "qid": 23, "docid": "lfjud2aq", "rank": 9, "score": 0.8184943199157715}, {"content": "Title: Cardiovascular Risks in Patients with COVID-19: Potential Mechanisms and Areas of Uncertainty Content: PURPOSE OF REVIEW: COronaVirus Disease 2019 (COVID-19) has spread at unprecedented speed and scale into a global pandemic with cardiovascular risk factors and complications emerging as important disease modifiers. We aim to review available clinical and biomedical literature on cardiovascular risks of COVID-19. RECENT FINDINGS: SARS-CoV2, the virus responsible for COVID-19, enters the cell via ACE2 expressed in select organs. Emerging epidemiological evidence suggest cardiovascular risk factors are associated with increased disease severity and mortality in COVID-19 patients. Patients with a more severe form of COVID-19 are also more likely to develop cardiac complications such as myocardial injury and arrhythmia. The true incidence of and mechanism underlying these events remain elusive. Cardiovascular diseases appear intricately linked with COVID-19, with cardiac complications contributing to the elevated morbidity/mortality of COVID-19. Robust epidemiologic and biologic studies are urgently needed to better understand the mechanism underlying these associations to develop better therapies.", "qid": 23, "docid": "ejsqsn59", "rank": 10, "score": 0.8157793283462524}, {"content": "Title: Unusually Rapid Development of Pulmonary Hypertension and Right Ventricular Failure after COVID-19 Pneumonia Content: COVID-19 is a novel viral disease caused by SARS-CoV-2. The mid- and long-term outcomes have not yet been determined. COVID-19 infection is increasingly being associated with systemic and multi-organ involvement, encompassing cytokine release syndrome and thromboembolic, vascular and cardiac events. The patient described experienced unusually rapid development of pulmonary hypertension (PH) and right ventricular failure after recent severe COVID-19 pneumonia with cytokine release syndrome, which initially was successfully treated with methylprednisolone and tocilizumab. The development of pulmonary hypertension and right ventricular failure \u2013 in the absence of emboli on multiple CT angiograms \u2013 was most likely caused by progressive pulmonary parenchymal abnormalities combined with microvascular damage of the pulmonary arteries (group III and IV pulmonary hypertension, respectively). To the best of our knowledge, these complications have not previously been described and therefore awareness of PH as a complication of COVID-19 is warranted. LEARNING POINTS: COVID-19 increasingly presents with systemic and multi-organ involvement with vascular, thromboembolic and cardiac events. Patients with severe COVID-19 pneumonia and concomitant cytokine release syndrome may be particularly at risk for the development of secondary pulmonary hypertension and right ventricular failure. Pulmonary hypertension can develop unusually rapidly following COVID-19 pneumonia and probably results from progressive pulmonary interstitial and microvascular abnormalities due to COVID-19.", "qid": 23, "docid": "7xqmuoye", "rank": 11, "score": 0.8155452013015747}, {"content": "Title: Hypertension and its severity or mortality in Coronavirus Disease 2019 (COVID-19): a pooled analysis. Content: INTRODUCTION As the coronavirus disease 2019 (COVID-19) outbreak, identification of clinical predictors of severe or fatal disease are necessary to enable risk stratification and optimize allocation of limited resources. Hypertension has been widely reported to be associated with increase disease severity, however, other studies have reported different findings. OBJECTIVES To evaluate the association of hypertension and severe and fatal COVID-19. PATIENTS AND METHODS Scopus, Medline, and Web of Science was performed to identify studies reporting the rate of hypertension in COVID-19 patients with severe or non-severe disease or among survivors and non-survivors. The obtained data was pooled into a meta-analysis to calculate odds ratio (OR) with 95% confidence intervals (95%CI). RESULTS Hypertension was associated with a nearly 2.5-fold significantly increased risk of severe COVID-19 disease (OR: 2.49 [95%CI: 1.98-3.12] I2=24%), as well as with a similarly significant higher risk of mortality (OR: 2.42 [95%CI: 1.51-3.90] I2=0%). In meta-regression, a significant correlation was observed with an increase in mean age of patients with severe COVID-19 associated with increased log odds of hypertension and severity (p=0.03). CONCLUSIONS The results of this pooled analysis of the current scientific literature would suggest that hypertension may be associated with an up to 2.5-fold higher risk of severe and fatal COVID-19, especially among older individuals.", "qid": 23, "docid": "komx6t5h", "rank": 12, "score": 0.8130255937576294}, {"content": "Title: COVID-19 and arterial hypertension: Hypothesis or evidence? Content: Investigations reported that hypertension, diabetes, and cardiovascular diseases were the most prevalent comorbidities among the patients with coronavirus disease 2019 (COVID-19). Hypertension appeared consistently as the most prevalent risk factors in COVID-19 patients. Some investigations speculated about the association between renin-angiotensin-aldosterone system (RAAS) and susceptibility to COVID-19, as well as the relationship between RAAS inhibitors and increased mortality in these patients. This raised concern about the potential association between hypertension (and its treatment) and propensity for COVID-19. There are only a few follow-up studies that investigated the impact of comorbidities on outcome in these patients with conflicting findings. Hypertension has been proven to be more prevalent in patients with an adverse outcome (admission in intensive care unit, use of mechanical ventilation, or death). So far, there is no study that demonstrated independent predictive value of hypertension on mortality in COVID-19 patients. There are many speculations about this coronavirus and its relation with different risk factors and underlying diseases. The aim of this review was to summarize the current knowledge about the relationship between hypertension and COVID-19 and the role of hypertension on outcome in these patients.", "qid": 23, "docid": "9nbj3ckb", "rank": 13, "score": 0.8125733137130737}, {"content": "Title: SGLT2 inhibition and COVID-19: The road not taken Content: The COVID-19 pandemic, caused by SARS-CoV-2, is an immense challenge for global healthcare. Diabetes mellitus, hypertension and obesity have been shown to portend poor prognosis in COVID-19 despite no greater susceptibility to the infection (1). Chronic hypertension is commonly associated with vasculopathy which can predispose to severe infection. In patients with diabetes, severity is attributable to impaired innate, adaptive immunity, upregulation of ACE2 (entry receptor for SARS-CoV2) by acute hyperglycemia and diabetic vasculopathy. The background of chronic low grade inflammation characterised by increased levels of IL-6 and CRP in diabetes and obesity can also lead to an enhanced 'cytokine storm' in COVID-19 (2). ACE2 expression on endothelial cells has been reported to cause viral mediated endothelitis and precipitate vascular dysfunction manifesting as acute respiratory distress syndrome as well as myocarditis, heart failure, arrhythmias, myocardial infarction and renal failure (3). In patients with pre-existing comorbidities like hypertension, diabetes, obesity and chronic kidney disease, this new-onset organ dysfunction can have deleterious additive effects.", "qid": 23, "docid": "ojoqsdn1", "rank": 14, "score": 0.8112353086471558}, {"content": "Title: SGLT2 inhibition and COVID-19: The road not taken. Content: The COVID-19 pandemic, caused by SARS-CoV-2, is an immense challenge for global healthcare. Diabetes mellitus, hypertension and obesity have been shown to portend poor prognosis in COVID-19 despite no greater susceptibility to the infection (1). Chronic hypertension is commonly associated with vasculopathy which can predispose to severe infection. In patients with diabetes, severity is attributable to impaired innate, adaptive immunity, upregulation of ACE2 (entry receptor for SARS-CoV2) by acute hyperglycemia and diabetic vasculopathy. The background of chronic low grade inflammation characterised by increased levels of IL-6 and CRP in diabetes and obesity can also lead to an enhanced 'cytokine storm' in COVID-19 (2). ACE2 expression on endothelial cells has been reported to cause viral mediated endothelitis and precipitate vascular dysfunction manifesting as acute respiratory distress syndrome as well as myocarditis, heart failure, arrhythmias, myocardial infarction and renal failure (3). In patients with pre-existing comorbidities like hypertension, diabetes, obesity and chronic kidney disease, this new-onset organ dysfunction can have deleterious additive effects.", "qid": 23, "docid": "md9dbxb5", "rank": 15, "score": 0.8112353086471558}, {"content": "Title: COVID\u201019 and arterial hypertension: Hypothesis or evidence? Content: Investigations reported that hypertension, diabetes, and cardiovascular diseases were the most prevalent comorbidities among the patients with coronavirus disease 2019 (COVID\u201019). Hypertension appeared consistently as the most prevalent risk factors in COVID\u201019 patients. Some investigations speculated about the association between renin\u2010angiotensin\u2010aldosterone system (RAAS) and susceptibility to COVID\u201019, as well as the relationship between RAAS inhibitors and increased mortality in these patients. This raised concern about the potential association between hypertension (and its treatment) and propensity for COVID\u201019. There are only a few follow\u2010up studies that investigated the impact of comorbidities on outcome in these patients with conflicting findings. Hypertension has been proven to be more prevalent in patients with an adverse outcome (admission in intensive care unit, use of mechanical ventilation, or death). So far, there is no study that demonstrated independent predictive value of hypertension on mortality in COVID\u201019 patients. There are many speculations about this coronavirus and its relation with different risk factors and underlying diseases. The aim of this review was to summarize the current knowledge about the relationship between hypertension and COVID\u201019 and the role of hypertension on outcome in these patients.", "qid": 23, "docid": "hzb2fkj5", "rank": 16, "score": 0.8110864758491516}, {"content": "Title: Hypertension in patients with coronavirus disease 2019 (COVID-19): a pooled analysis Content: INTRODUCTION: As the outbreak of coronavirus disease 2019 (COVID\u00ad19) was recognized, the clinical predictors of severe or fatal course of the disease should be identified to enable risk stratification and to allocate limited resources optimally. Hypertension has been widely reported to be associated with increased disease severity; however, some studies reported different findings. OBJECTIVES: The study aimed to evaluate the association between hypertension and severe and fatal COVID\u00ad19. PATIENTS AND METHODS: The Scopus, Medline, and Web of Science databases were searched to identify studies reporting the rate of hypertensive patients in the population diagnosed with severe or nonsevere COVID\u00ad19 or in COVID-19 survivors and nonsurvivors. The obtained data were pooled into a meta\u00adanalysis to calculate odds ratios (ORs) with 95% CIs. RESULTS: Hypertension was associated with a nearly 2.5\u00adfold increased risk of severe COVID\u00ad19 (OR, 2.49; 95% CI, 1.98-3.12; I2 = 24%), as well as with a similarly significant higher mortality risk (OR, 2.42; 95% CI, 1.51-3.90; I2 = 0%). In a meta\u00adregression analysis, a correlation was observed between an increase in the mean age of patients with severe COVID\u00ad19 and an increased log OR of hypertension and COVID-19 severity (P = 0.03). CONCLUSIONS: This pooled analysis of the current literature would suggest that hypertension may be associated with an up to 2.5\u00adfold higher risk of severe or fatal COVID\u00ad19, especially in older individuals.", "qid": 23, "docid": "g484ymy9", "rank": 17, "score": 0.8103559017181396}, {"content": "Title: Involvement of Cardiovascular System As The Critical Point in Coronavirus Disease 2019 (COVID-19) Prognosis and Recovery Content: The novel coronavirus disease (COVID-19) pandemic has already caused more than 300,000 deaths worldwide. Several studies have elucidated the central role of cardiovascular complications in the disease course. Herein, we provide a concise review of current knowledge regarding the involvement of cardiovascular system in the pathogenesis and prognosis of COVID-19. We summarize data from 21 studies involving in total more than 21,000 patients from Asia, Europe and the USA indicating that severe disease is associated with the presence of myocardial injury, heart failure and arrhythmias. Additionally, we present the clinical and laboratory differences between recovered and deceased patients highlighting the importance of cardiac manifestations. For the infected patients, underlying cardiovascular comorbidities and especially existing cardiovascular disease seem to predispose to the development of cardiovascular complications, which are in turn associated with higher mortality rates. We provide mechanistic insights into the underlying mechanisms including direct myocardial damage by the virus and the consequences of the hyperinflammatory syndrome developed later in the disease course. Finally, we summarize current knowledge on therapeutic modalities and recommendations by scientific societies and experts regarding the cardiovascular management of COVID-19 patients.", "qid": 23, "docid": "fzmrvjtl", "rank": 18, "score": 0.8095552325248718}, {"content": "Title: Cardiovascular comorbidities and complications associated with coronavirus disease 2019 Content: Coronavirus disease 2019 (COVID-19) has caused a devastating global pandemic and continues to overwhelm the health-care facilities and shatter the economies of countries worldwide. Although it primarily affects the lungs, it shares a strong interplay with the cardiovascular system. The presence of underlying cardiovascular disease and its risk factors (diabetes, hypertension) predispose the patients to increased severity and mortality associated with COVID-19. On the other hand, COVID-19 itself leads to various cardiovascular complications, which increase its associated morbidity and mortality in affected patients. It is, therefore, prudent to review the rapidly evolving data in this field and understand the mechanisms behind the cardiovascular involvement of this lethal disease.", "qid": 23, "docid": "o6a30irm", "rank": 19, "score": 0.8086197376251221}, {"content": "Title: COVID-19-RELATED AORTIC THROMBOSIS: A REPORT OF FOUR CASES Content: COVID-19 may predispose patients to an increased risk of thrombotic complications through various pathophysiological mechanisms. Most of the reports on a high incidence of thrombotic complications are in relation to deep vein thrombosis and pulmonary embolism, while the evidence about arterial thrombosis in patients with COVID-19 is limited. We describe four cases of aortic thrombosis and associated ischemic complications in patients with severe SARS-CoV-2 infection.", "qid": 23, "docid": "q7yavza2", "rank": 20, "score": 0.8073334693908691}, {"content": "Title: COVID-19, hypertension and cardiovascular diseases: Should we change the therapy? Content: The coronavirus disease (COVID-19) has spread all around the world in a very short period of time. Recent data are showing significant prevalence of arterial hypertension and cardiovascular diseases (CVD) among patients with COVID-19, which raised many questions about higher susceptibility of patients with these comorbidities to the novel coronavirus, as well as the role of hypertension and CVD in progression and the prognosis of COVID-19 patients. There is a very limited amount of data, usually obtained from a small population, regarding the effect of the underlying disease on the outcome in patients with COVID-19. The evaluation of the treatment of these comorbidities at baseline and during COVID-19 is scarce and the results are conflicting. Hypertension and CVD, after the adjustment for other clinical and demographic parameters, primarily age, did not remain independent predictors of the lethal outcome in COVID-19 patients. Some investigations speculated about the association between the renin-angiotensin-aldosterone system (RAAS) and susceptibility to COVID-19, as well as the relationship between RAAS inhibitors and the adverse outcome in these patients. Withdrawing or switching RAAS inhibitors would have uncertain benefits, but it would definitely have many disadvantages such as uncontrolled hypertension, cardiac function deterioration and renal function impairment, which could potentially induce more complications in patients with COVID-19 than the infection of coronavirus itself. The aim of this review article was to summarize the prevalence of hypertension and CVD in patients with COVID-19, their influence on the outcome and the effect of treatment of hypertension and CVD in COVID-19 patients.", "qid": 23, "docid": "bwkad2s0", "rank": 21, "score": 0.8069609999656677}, {"content": "Title: COVID-19-Related Aortic Thrombosis: A Report of Four Cases Content: COVID-19 may predispose patients to an increased risk of thrombotic complications through various pathophysiological mechanisms. Most of the reports on a high incidence of thrombotic complications are in relation to deep vein thrombosis and pulmonary embolism, while the evidence about arterial thrombosis in patients with COVID-19 is limited. We describe 4 cases of aortic thrombosis and associated ischemic complications in patients with severe SARS-CoV-2 infection.", "qid": 23, "docid": "ir6d85fr", "rank": 22, "score": 0.8046030402183533}, {"content": "Title: Hypertension prevalence in human coronavirus disease: the role of ACE system in infection spread and severity Content: The prevalence of hypertension is high in patients affected by coronavirus disease 2019 (COVID-2019) and it appears to be related to an increased risk of mortality, as shown in many epidemiological studies. The angiotensin-converting enzyme (ACE) system is not uniformly expressed in all of the human races, and current differences could explain some of the geographical discrepancies in infection around the world. Furthermore, animal studies have shown that the ACE2 receptor is a potential pathway for host infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. As two-thirds of hypertensive patients take ACE inhibitors/angiotensin receptor blockers, several concerns have been raised about the detrimental role of current antihypertensive drugs in COVID-19. This report summarizes the recent evidence for and against the administration of ACE blockade in the COVID-19 era.", "qid": 23, "docid": "ih8oxr40", "rank": 23, "score": 0.801957368850708}, {"content": "Title: Cardiovascular complications in COVID-19 Content: Abstract Background The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur. Objective This brief report evaluates cardiovascular complications in the setting of COVID-19 infection. Discussion The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death. The virus binds and enters through angiotensin-converting enzyme 2 (ACE2). COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness. The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events. Current therapies for COVID-19 may interact with cardiovascular medications. Conclusions Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.", "qid": 23, "docid": "mbbnk3la", "rank": 24, "score": 0.8017709851264954}, {"content": "Title: Could there be a link between oral hygiene and the severity of SARS-CoV-2 infections? Content: On 30 January 2020, the World Health Organisation identified COVID-19, caused by the virus SARS-CoV-2, to be a global emergency. The risk factors already identified for developing complications from a COVID-19 infection are age, gender and comorbidities such as diabetes, hypertension, obesity and cardiovascular disease. These risk factors, however, do not account for the other 52% of deaths arising from COVID-19 in often seemingly healthy individuals. This paper investigates the potential link between SARS-CoV-2 and bacterial load, questioning whether bacteria may play a role in bacterial superinfections and complications such as pneumonia, acute respiratory distress syndrome and sepsis. The connection between COVID-19 complications and oral health and periodontal disease is also examined, as the comorbidities at highest risk of COVID-19 complications also cause imbalances in the oral microbiome and increase the risk of periodontal disease. We explore the connection between high bacterial load in the mouth and post-viral complications, and how improving oral health may reduce the risk of complications from COVID-19.", "qid": 23, "docid": "vxi3uttf", "rank": 25, "score": 0.8013388514518738}, {"content": "Title: Inhibidores de la enzima convertidora de angiotensina y antagonistas del receptor de angiotensina II: \u00bfAumentan el riesgo de padecer COVID-19? Content: Abstract A new coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was discovered in December 2019 in Wuhan, China; the virus escalated rapidly and on March 11, 2020, the World Health Organization declared it a pandemic.Emerging data suggests that older patients with COVID-19 associated with other comorbid conditions such as diabetes, hypertension, heart and lung diseases are particularly more susceptible, compared to general populations, and have higher mortality. It is not yet clear whether this increased association of high blood pressure with COVID-19 and the increased risk of mortality are directly related to high blood pressure or other associated comorbidities, or to antihypertensive treatment.Although the underlying pathogenic mechanism linking hypertension and severity of COVID-19 infection remains to be elucidated, it has been hypothesized that excessive activation of the renin-angiotensin system (RAS) could contribute to the progression of COVID-19 related lung injury.Concern about whether angiotensin II receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors may have deleterious effects on morbidity and mortality in patients with COVID-19 is based on speculation that these drugs would increase the regulation of angiotensin II converting enzyme (ACE2), a receptor for SARS-CoV-2, which would increase viral load and lung damage.Recent studies are consistent with the recommendations of scientific societies that propose avoiding the suspension or change of antihypertensive medication, as there is no evidence that shows that these can be taken as risk factors for severity or mortality from COVID-19.", "qid": 23, "docid": "ynias4ga", "rank": 26, "score": 0.8007593750953674}, {"content": "Title: Association of diabetes and hypertension with disease severity in covid-19 patients: a systematic literature review and exploratory meta-analysis Content: AIM: The novel coronavirus infection (COVID-19), now a worldwide public health concern is associated with varied fatality. Patients with chronic underlying conditions like diabetes and hypertension have shown worst outcomes. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. The aim of the meta-analysis was to assess the association of diabetes and hypertension with severity of disease. METHODS: A literature search was conducted using the databases PubMed and Cochrane until March 31, 2020. Seven studies were included in the meta- analysis, including 2018 CIVID-19 patients. RESULTS: Diabetes was lower in the survivors (OR: 0.56; 95%CI: 0.35-0.90; p=0.017; I2: 0.0%) and non-severe (OR: 1.66; 95%CI: 1.20-2.30; p=0.002; I2: 0.0%) patients. No association of diabetes was found with ICU care. Hypertension was positively associated with death (OR: 0.49; 95%CI: 0.34-0.73; p=0.000; I2: 0.0%), ICU care (OR: 0.42; 95%CI: 0.22-0.81; p=0.009; I2: 0.0%) and severity (OR: 2.69; 95%CI: 1.27-5.73; p=0.01; I2: 52.4%). CONCLUSIONS: Our findings suggest that diabetes and hypertension have a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid diabetes and hypertension are urgently needed to understand the magnitude of these vexatious comorbidities.", "qid": 23, "docid": "04s7w017", "rank": 27, "score": 0.8004484176635742}, {"content": "Title: COVID-19 and diabetes: Is there enough evidence? Content: The pandemic of COVID-19, a disease caused by a novel coronavirus SARS-CoV-2, is associated with significant morbidity and mortality. Recent data showed that hypertension, diabetes mellitus, cardiovascular diseases, and chronic obstructive pulmonary disease were the most prevalent comorbidities in COVID-19 patients. Additionally, data indicate that hypertension, diabetes, and cardiovascular diseases are important risk factors for progression and unfavorable outcome in COVID-19 patients. There is only limited amount of data regarding follow-up of these patients, and they provided conflicting results. The main limitation is a small number of participants and particularly those who experienced primary composite outcome (admission in intensive care unit, use of mechanical ventilation, or death). Additionally, the limited number of patients was essential obstacle for performing analysis that would include many confounding factors such as advanced age, smoking status, and obesity and potentially change conclusion. So far, there is no study that demonstrated independent predictive value of diabetes on mortality in COVID-19 patients, but there are many speculations about the association between diabetes and susceptibility to novel coronavirus, as well as its impact on progression and prognosis of COVID-19. The aim of this review article was to summarize the current knowledge about the relationship between diabetes and COVID-19 and its role in outcome in these patients.", "qid": 23, "docid": "f0pwjxfv", "rank": 28, "score": 0.7987946271896362}, {"content": "Title: COVID-19 and Multiorgan Response Content: Since the outbreak and rapid spread of COVID-19 starting late December 2019, it has been apparent that disease prognosis has largely been influenced by multiorgan involvement. Comorbidities such as cardiovascular diseases have been the most common risk factors for severity and mortality. The hyperinflammatory response of the body, coupled with the plausible direct effects of severe acute respiratory syndrome on body-wide organs via angiotensin-converting enzyme 2, has been associated with complications of the disease. Acute respiratory distress syndrome, heart failure, renal failure, liver damage, shock, and multiorgan failure have precipitated death. Acknowledging the comorbidities and potential organ injuries throughout the course of COVID-19 is therefore crucial in the clinical management of patients. This paper aims to add onto the ever-emerging landscape of medical knowledge on COVID-19, encapsulating its multiorgan impact.", "qid": 23, "docid": "fmri74v7", "rank": 29, "score": 0.7969011068344116}, {"content": "Title: Impact of Chronic Comorbidities on Progression and Prognosis in Patients with COVID-19: A Retrospective Cohort Study in 1031 Hospitalized Cases in Wuhan, China Content: Background The recent outbreak of COVID-19 has rapidly spread worldwide. A large proportion of COVID-19 patients with chronic underlying complications have been reported to be in severe condition and show unpromising clinical outcomes. But whether chronic comorbidities are risk factors affecting the severity of COVID-19 has not been well described. Methods We included COVID-19 patients who had been admitted to Tongji Hospital, Tongji medical college of HUST (Wuhan, China) from January, 27, 2020 to March, 8, 2020 in this retrospective cohort study. The final date of follow-up was March, 30, 2020. All patients were diagnosed with COVID-19 according to Prevention and control Scheme for Novel Coronavirus Pneumonia published by National Health Commission of the People' s Republic of China and WHO interim. Demographic data, medical history, clinical symptoms and signs, laboratory findings, chest computed tomography (CT), treatment and clinical outcomes were extracted from electronic medical records with standardized data collection forms and compared among different groups. Results 1031 COVID-19 inpatients were included in this study, of whom 866 were discharged and 165 were dead in hospital. 73% of 165 dead patients had complicated chronic comorbidities. Of the 1031 patients, 514 (50%) were combined with chronic comorbidities, and showed CFR 2.8 times as that of patients without any underlying disease. The number of patients with hypertension accounted for three fourths of those with concomitant underlying diseases. The univariable regression revealed that patients in the simple hypertension group showed overall risk higher than those in the simple diabetes mellitus group. In the age-grouped research, patients in the hypertension senile group were proved to be at the highest risk, which might be associated with the level of LDH and eGFR. In this retrospective cohort study, 166 (43%) patients with hypertension took CCB during the hospitalization, the odds ratio of CFR in patients with hypertension taking CCB group was 0.68 (P = 0.155), compared to those not. Conclusion Our data shows that the clinical manifestations of most hospitalized patients with COVID-19 are actually systemic syndromes, although COVID-19 is defined as novel coronavirus pneumonia in China. Hypertension is not just a chronic underlying comorbidity, but also a risk factor affecting the severity of COVID-19 and does play a critical role in improving patients' clinical outcomes. Therefore, hypertension management in patients with COVID-19 should be a major challenge in the diagnostic and therapeutic strategies, including optimal management of blood pressure and pathophysiological status.", "qid": 23, "docid": "d7q7m7zz", "rank": 30, "score": 0.7963533401489258}, {"content": "Title: Coronavirus Disease-2019 (COVID-19) and Cardiovascular Complications Content: The coronavirus disease-2019 (COVID-19) has become a global pandemic. It has spread to more than 100 countries, and more than 1 million cases have been confirmed. Although coronavirus causes severe respiratory infections in humans, accumulating data have demonstrated cardiac complications and poor outcome in patients with COVID-19. A large percent of patients have underlying cardiovascular disease, and they are at a high risk of developing cardiac complications. The basics of the virus, the clinical manifestations, and the possible mechanisms of cardiac complications in patients with COVID-19 are reviewed. Before an effective vaccine or medicine is available, supportive therapy and identifying patients who are at high risk of cardiac complications are important.", "qid": 23, "docid": "wkp58iov", "rank": 31, "score": 0.7961452007293701}, {"content": "Title: Controversies of renin\u2013angiotensin system inhibition during the COVID-19 pandemic Content: The current COVID-19 pandemic is associated with unprecedented morbidity and mortality. Early reports suggested an association between disease severity and hypertension but did not account for sources of confounding. However, the responsible virus \u2014 SARS-CoV-2 \u2014 gains entry to host cells via angiotensin-converting enzyme 2 (ACE2), highlighting the need to understand the relationship between the virus and the renin\u2013angiotensin system (RAS) and how this might be affected by RAS inhibitors.", "qid": 23, "docid": "va34p27b", "rank": 32, "score": 0.7960895299911499}, {"content": "Title: The Association of Cardiovascular Diseases and Diabetes Mellitus with COVID-19 (SARS-CoV-2) and Their Possible Mechanisms Content: Coronavirus disease 2019 (COVID-19) has become a global concern and public health issue due to its higher infection and mortality rate; particularly, the risk is very higher among the patients who have cardiovascular diseases (CVD) and/or diabetes mellitus (DM). In this review, we analyzed the recently published literature on CVD and DM associated with COVD-19 infections and highlight their association with potential mechanisms. The findings revealed that without any previous history of CVD, the COVID-19 patients have developed some CVD complications like myocardial injury, cardiomyopathy, and venous thromboembolism after being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and required for those patients an emergency clinical support to be aware to manage those complications. Though the association between DM and COVID-19-induced severe complications is still unclear, the limited data predict that different markers like interleukin (IL)-1, IL-6, C-reactive protein, and D-dimer linked with the severity of COVID-19 infection in diabetic individuals. Further studies on a large scale are urgently needed to explore the underlying mechanisms between CVD, DM, and COVID-19 for better treatment.", "qid": 23, "docid": "9uymi395", "rank": 33, "score": 0.7956355214118958}, {"content": "Title: Hypertension, the renin-angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19 Content: Systemic arterial hypertension (referred to as hypertension herein) is a major risk factor of mortality worldwide, and its importance is further emphasized in the context of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection referred to as COVID-19. Patients with severe COVID-19 infections commonly are older and have a history of hypertension. Almost 75% of patients who have died in the pandemic in Italy had hypertension. This raised multiple questions regarding a more severe course of COVID-19 in relation to hypertension itself as well as its treatment with renin-angiotensin system (RAS) blockers, e.g. angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). We provide a critical review on the relationship of hypertension, RAS, and risk of lung injury. We demonstrate lack of sound evidence that hypertension per se is an independent risk factor for COVID-19. Interestingly, ACEIs and ARBs may be associated with lower incidence and/or improved outcome in patients with lower respiratory tract infections. We also review in detail the molecular mechanisms linking the RAS to lung damage and the potential clinical impact of treatment with RAS blockers in patients with COVID-19 and a high cardiovascular and renal risk. This is related to the role of angiotensin-converting enzyme 2 (ACE2) for SARS-CoV-2 entry into cells, and expression of ACE2 in the lung, cardiovascular system, kidney, and other tissues. In summary, a critical review of available evidence does not support a deleterious effect of RAS blockers in COVID-19 infections. Therefore, there is currently no reason to discontinue RAS blockers in stable patients facing the COVID-19 pandemic.", "qid": 23, "docid": "69qefbbo", "rank": 34, "score": 0.7948524951934814}, {"content": "Title: Hypertension, the renin\u2013angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19: European Society of Hypertension COVID-19 Task Force Review of Evidence Content: Systemic arterial hypertension (referred to as hypertension herein) is a major risk factor of mortality worldwide, and its importance is further emphasized in the context of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection referred to as COVID-19. Patients with severe COVID-19 infections commonly are older and have a history of hypertension. Almost 75% of patients who have died in the pandemic in Italy had hypertension. This raised multiple questions regarding a more severe course of COVID-19 in relation to hypertension itself as well as its treatment with renin\u2013angiotensin system (RAS) blockers, e.g. angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). We provide a critical review on the relationship of hypertension, RAS, and risk of lung injury. We demonstrate lack of sound evidence that hypertension per se is an independent risk factor for COVID-19. Interestingly, ACEIs and ARBs may be associated with lower incidence and/or improved outcome in patients with lower respiratory tract infections. We also review in detail the molecular mechanisms linking the RAS to lung damage and the potential clinical impact of treatment with RAS blockers in patients with COVID-19 and a high cardiovascular and renal risk. This is related to the role of angiotensin-converting enzyme 2 (ACE2) for SARS-CoV-2 entry into cells, and expression of ACE2 in the lung, cardiovascular system, kidney, and other tissues. In summary, a critical review of available evidence does not support a deleterious effect of RAS blockers in COVID-19 infections. Therefore, there is currently no reason to discontinue RAS blockers in stable patients facing the COVID-19 pandemic.", "qid": 23, "docid": "y4h95kb4", "rank": 35, "score": 0.7944358587265015}, {"content": "Title: Perspective: cardiovascular disease and the Covid-19 pandemic Content: We summarize the cardiovascular risks associated with Covid-19 pandemic, discussing the risks for both infected and non-infected patients.", "qid": 23, "docid": "wrrybwda", "rank": 36, "score": 0.7941027283668518}, {"content": "Title: COVID\u201019 and diabetes: Is there enough evidence? Content: The pandemic of COVID\u201019, a disease caused by a novel coronavirus SARS\u2010CoV\u20102, is associated with significant morbidity and mortality. Recent data showed that hypertension, diabetes mellitus, cardiovascular diseases, and chronic obstructive pulmonary disease were the most prevalent comorbidities in COVID\u201019 patients. Additionally, data indicate that hypertension, diabetes, and cardiovascular diseases are important risk factors for progression and unfavorable outcome in COVID\u201019 patients. There is only limited amount of data regarding follow\u2010up of these patients, and they provided conflicting results. The main limitation is a small number of participants and particularly those who experienced primary composite outcome (admission in intensive care unit, use of mechanical ventilation, or death). Additionally, the limited number of patients was essential obstacle for performing analysis that would include many confounding factors such as advanced age, smoking status, and obesity and potentially change conclusion. So far, there is no study that demonstrated independent predictive value of diabetes on mortality in COVID\u201019 patients, but there are many speculations about the association between diabetes and susceptibility to novel coronavirus, as well as its impact on progression and prognosis of COVID\u201019. The aim of this review article was to summarize the current knowledge about the relationship between diabetes and COVID\u201019 and its role in outcome in these patients.", "qid": 23, "docid": "sntawlnf", "rank": 37, "score": 0.793880820274353}, {"content": "Title: COVID-19 and Multi-Organ Response Content: Abstract Since the outbreak and rapid spread of COVID-19 starting late December 2019, it has been apparent that disease prognosis has largely been influenced by multi-organ involvement. Comorbidities such as cardiovascular diseases have been the most common risk factors for severity and mortality. The hyperinflammatory response of the body, coupled with the plausible direct effects of SARS-CoV-2 on body-wide organs via ACE2, has been associated with complications of the disease. Acute respiratory distress syndrome, heart failure, renal failure, liver damage, shock and multi-organ failure have precipitated death. Acknowledging the comorbidities and potential organ injuries throughout the course of COVID-19 is therefore crucial in the clinical management of patients. This paper aims to add onto the ever-emerging landscape of medical knowledge on COVID-19, encapsulating its multi-organ impact.", "qid": 23, "docid": "yhynqeo1", "rank": 38, "score": 0.7924247980117798}, {"content": "Title: Autoimmune haemolytic anaemia associated with COVID\u201019 infection Content: Among patients with SARS-CoV-2 infection (also known as Covid-19), pneumonia, respiratory failure, and acute respiratory distress syndrome are frequently encountered complications (Zhou et al, 2020). Although the pathophysiology underlying severe Covid-19 remains poorly understood, accumulating evidence argue for hyperinflammatory syndrome causing fulminant and fatal cytokines release associated with disease severity and poor outcome (Mehta et al, 2020). However, the spectrum of complications is broader and include among others various auto-immune disorders such as autoimmune thrombocytopenia, Guillain-Barr\u00e9 and antiphospholipid syndrome (Zhang et al, 2020; Zulfiqar et al, 2020; Toscano et al, 2020). In this report we describe 7 patients from 6 French and Belgian Hospitals who developed a first episode of autoimmune hemolytic anemia (AIHA) during a Covid-19 infection.", "qid": 23, "docid": "wm5297kw", "rank": 39, "score": 0.7917150259017944}, {"content": "Title: Hypertension is associated with increased mortality and severity of disease in COVID-19 pneumonia: A systematic review, meta-analysis and meta-regression Content: OBJECTIVE: To investigate the association between hypertension and outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia. METHODS: We performed a systematic literature search from several databases on studies that assess hypertension and outcome in COVID-19. Composite of poor outcome, comprising of mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care and disease progression were the outcomes of interest. RESULTS: A total of 6560 patients were pooled from 30 studies. Hypertension was associated with increased composite poor outcome (risk ratio (RR) 2.11 (95% confidence interval (CI) 1.85, 2.40), p < 0.001; I2, 44%) and its sub-group, including mortality (RR 2.21 (1.74, 2.81), p < 0.001; I2, 66%), severe COVID-19 (RR 2.04 (1.69, 2.47), p < 0.001; I2 31%), ARDS (RR 1.64 (1.11, 2.43), p = 0.01; I2,0%, p = 0.35), ICU care (RR 2.11 (1.34, 3.33), p = 0.001; I2 18%, p = 0.30), and disease progression (RR 3.01 (1.51, 5.99), p = 0.002; I2 0%, p = 0.55). Meta-regression analysis showed that gender (p = 0.013) was a covariate that affects the association. The association was stronger in studies with a percentage of males < 55% compared to \u00e2\u00a9\u00be 55% (RR 2.32 v. RR 1.79). CONCLUSION: Hypertension was associated with increased composite poor outcome, including mortality, severe COVID-19, ARDS, need for ICU care and disease progression in patients with COVID-19.", "qid": 23, "docid": "z9u229yg", "rank": 40, "score": 0.7914913296699524}, {"content": "Title: The liaison between respiratory failure and high blood pressure: evidence from COVID-19 patients Content: In COVID-19 patients respiratory failure is associated with increase systemic blood pressure conceivably due to the modulation of renin-angiotensin-aldosterone system by SARS-CoV-2 infection.", "qid": 23, "docid": "u36nf6jq", "rank": 41, "score": 0.7911417484283447}, {"content": "Title: Hypertension is associated with increased mortality and severity of disease in COVID-19 pneumonia: A systematic review, meta-analysis and meta-regression Content: OBJECTIVE: To investigate the association between hypertension and outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia. METHODS: We performed a systematic literature search from several databases on studies that assess hypertension and outcome in COVID-19. Composite of poor outcome, comprising of mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care and disease progression were the outcomes of interest. RESULTS: A total of 6560 patients were pooled from 30 studies. Hypertension was associated with increased composite poor outcome (risk ratio (RR) 2.11 (95% confidence interval (CI) 1.85, 2.40), p < 0.001; I(2), 44%) and its sub-group, including mortality (RR 2.21 (1.74, 2.81), p < 0.001; I(2), 66%), severe COVID-19 (RR 2.04 (1.69, 2.47), p < 0.001; I(2) 31%), ARDS (RR 1.64 (1.11, 2.43), p = 0.01; I(2),0%, p = 0.35), ICU care (RR 2.11 (1.34, 3.33), p = 0.001; I(2) 18%, p = 0.30), and disease progression (RR 3.01 (1.51, 5.99), p = 0.002; I(2) 0%, p = 0.55). Meta-regression analysis showed that gender (p = 0.013) was a covariate that affects the association. The association was stronger in studies with a percentage of males < 55% compared to \u2a7e 55% (RR 2.32 v. RR 1.79). CONCLUSION: Hypertension was associated with increased composite poor outcome, including mortality, severe COVID-19, ARDS, need for ICU care and disease progression in patients with COVID-19.", "qid": 23, "docid": "ucimsb8d", "rank": 42, "score": 0.7910772562026978}, {"content": "Title: Prevalence of Comorbidities Among Individuals With COVID-19: A Rapid Review of current Literature Content: On February 11, 2020 WHO designated the name \u201cCOVID-19\u201d for the disease caused by \u201csevere acute respiratory syndrome coronavirus 2\u201d (SARS-CoV-2), a novel virus that first occurred in Wuhan, China, but quickly turned into a global pandemic. As of June 29, 2020, it has claimed 502,947 lives and is present in more than 213 countries worldwide. Risks associated with acquiring the virus and with its severe outcomes have been reported in various studies, which has led health organizations and governments to develop and institute a variety of preventative and control measures. With constantly growing scientific understanding on this topic, updated information can help equip health and public sectors with the most current knowledge. In this literature review we explore the prevalence of comorbidity among individuals with COVID-19 and summarize our findings based on information available as of May 15, 2020. Overall, we found that comorbidities including Hypertension (27.4%), Diabetes (17.4%), and Cardiovascular Disease (8.9%) are quite prevalent in COVID-19 patients across major epicenters worldwide and is associated with increased disease severity but not clearly to fatality (OR 0.83, CI[0.60-0.99], p <0.05). Understanding of COVID-19 characteristics and association to common global health problems may provide support and direction to policy makers, clinicians, and researchers in developing shielding strategies to mitigate the COVID-19 pandemic and its severe outcomes.", "qid": 23, "docid": "afz8r1ox", "rank": 43, "score": 0.7907932996749878}, {"content": "Title: Emerging cardiological issues during the COVID\u201019 pandemic Content: Today the modern world is facing an unprecedented health crisis. The COVID\u201019 pandemic is putting extensive strain on health care systems, hospitals and medical workers worldwide. Epidemiological data are emerging that COVID\u201019 patients with cardiac risk factors or pre\u2010existing cardiac conditions are at increased risk for complications and mortality from COVID\u201019. As we just begin to understand the pathophysiology underlying the disease, the involvement of the heart, whether through direct myocardial infection and damage or due to cardiac complications, is already evident.", "qid": 23, "docid": "6p39cx2e", "rank": 44, "score": 0.7904641628265381}, {"content": "Title: Is Hypertension a Real Risk Factor for Poor Prognosis in the COVID-19 Pandemic? Content: PURPOSE OF REVIEW: There is increasing evidence indicating an association between several risk factors and worse prognosis in patients with coronavirus disease 2019 (COVID-19), including older age, hypertension, heart failure, diabetes, and pulmonary disease. Hypertension is of particular interest because it is common in adults and there are concerns related to the use of renin-angiotensin system (RAS) inhibitors in patients with hypertension infected with COVID-19. Levels of angiotensin-converting enzyme 2 (ACE2), a protein that facilitates entry of coronavirus into cells, may increase in patients using RAS inhibitors. Thus, chronic use of RAS inhibition could potentially lead to a more severe and fatal form of COVID-19. In this review, we provide a critical review to the following questions: (1) Does hypertension influence immunity or ACE2 expression favoring viral infections? (2) Are the risks of complications in hypertension mediated by its treatment? (3) Is aging a major factor associated with worse prognosis in patients with COVID-19 and hypertension? RECENT FINDINGS: Despite the potential involvement of immune responses in the pathogenesis of hypertension, there is no evidence supporting that hypothesis that hypertension or RAS inhibitors contributes to unfavorable outcomes in viral infections. Future investigations adopting a strict protocol for confirming hypertension status as well as assessing associated comorbidities that may influence outcomes are necessary. From the therapeutic perspective, recombinant ACE2 may serve as a potential therapy, but relevant studies in humans are lacking. Definitive evidence regarding the use of RAS inhibitors in patients with COVID-19 is needed; 5 randomized trials examining this issue are currently underway. SUMMARY: There is no current scientific support for claiming that hypertension or its treatment with RAS inhibitors contribute to unfavorable outcomes in COVID-19.", "qid": 23, "docid": "n4dgqo73", "rank": 45, "score": 0.7903330326080322}, {"content": "Title: Posterior reversible encephalopathy syndrome in severe SARS-COV-2 infection Content: \u2022 PRES is potentially a complication of severe SARS-CoV-2 infection. \u2022 Consider PRES in COVID-19 patients with altered mentation. \u2022 Consider tight blood pressure control in ventilated patients with COVID-19. \u2022 Hypertensive encephalopathy may prolong ventilator times in COVID-19 patients.", "qid": 23, "docid": "3j68j67i", "rank": 46, "score": 0.7890255451202393}, {"content": "Title: Association of diabetes and hypertension with disease severity in covid-19 patients: a systematic literature review and exploratory meta-analysis Content: Abstract Aim The novel coronavirus infection (COVID-19), now a worldwide public health concern is associated with varied fatality. Patients with chronic underlying conditions like diabetes and hypertension have shown worst outcomes. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. The aim of the meta-analysis was to assess the association of diabetes and hypertension with severity of disease. Methods A literature search was conducted using the databases PubMed and Cochrane until March 31, 2020. Seven studies were included in the meta- analysis, including 2018 CIVID-19 patients. Results Diabetes was lower in the survivors (OR: 0.56; 95%CI: 0.35-0.90; p=0.017; I2 : 0.0%) and non-severe (OR: 1.66; 95%CI: 1.20-2.30; p=0.002; I2 : 0.0%) patients. No association of diabetes was found with ICU care. Hypertension was positively associated with death (OR: 0.49; 95%CI: 0.34-0.73; p=0.000; I2 : 0.0%), ICU care (OR: 0.42; 95%CI: 0.22-0.81; p=0.009; I2 : 0.0%) and severity (OR: 2.69; 95%CI: 1.27-5.73; p=0.01; I2 : 52.4%). Conclusions Our findings suggest that diabetes and hypertension have a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid diabetes and hypertension are urgently needed to understand the magnitude of these vexatious comorbidities.", "qid": 23, "docid": "9qq049qb", "rank": 47, "score": 0.7889946699142456}, {"content": "Title: Long term complications and rehabilitation of COVID-19 patients. Content: With the ongoing pandemic of COVID-19 having caught the world almost unaware millions of people across the globe are presently grappling to deal with its acute effects . Our previous experience with members of the same corona virus family (SARS and MERS) which have caused two major epidemics in the past albeit of much lower magnitude , has taught us that the harmful effect of such outbreaks are not limited to acute complications alone .Long term cardiopulmonary, glucometabolic and neuropsychiatric complications have been documented following these infections .In the given circumstance it is therefore imperative to keep in mind the possible complications that may occur after the acute phase of the disease subsides and to prepare the healthcare system for such challenges.", "qid": 23, "docid": "7s04ygm2", "rank": 48, "score": 0.788800835609436}, {"content": "Title: Long term complications and rehabilitation of COVID-19 patients Content: With the ongoing pandemic of COVID-19 having caught the world almost unaware millions of people across the globe are presently grappling to deal with its acute effects . Our previous experience with members of the same corona virus family (SARS and MERS) which have caused two major epidemics in the past albeit of much lower magnitude , has taught us that the harmful effect of such outbreaks are not limited to acute complications alone .Long term cardiopulmonary, glucometabolic and neuropsychiatric complications have been documented following these infections .In the given circumstance it is therefore imperative to keep in mind the possible complications that may occur after the acute phase of the disease subsides and to prepare the healthcare system for such challenges.", "qid": 23, "docid": "yudrouue", "rank": 49, "score": 0.7888006567955017}, {"content": "Title: Is Hypertension a Real Risk Factor for Poor Prognosis in the COVID-19 Pandemic? Content: PURPOSE OF REVIEW: There is increasing evidence indicating an association between several risk factors and worse prognosis in patients with coronavirus disease 2019 (COVID-19), including older age, hypertension, heart failure, diabetes, and pulmonary disease. Hypertension is of particular interest because it is common in adults and there are concerns related to the use of renin-angiotensin system (RAS) inhibitors in patients with hypertension infected with COVID-19. Levels of angiotensin-converting enzyme 2 (ACE2), a protein that facilitates entry of coronavirus into cells, may increase in patients using RAS inhibitors. Thus, chronic use of RAS inhibition could potentially lead to a more severe and fatal form of COVID-19. In this review, we provide a critical review to the following questions: (1) Does hypertension influence immunity or ACE2 expression favoring viral infections? (2) Are the risks of complications in hypertension mediated by its treatment? (3) Is aging a major factor associated with worse prognosis in patients with COVID-19 and hypertension? RECENT FINDINGS: Despite the potential involvement of immune responses in the pathogenesis of hypertension, there is no evidence supporting that hypothesis that hypertension or RAS inhibitors contributes to unfavorable outcomes in viral infections. Future investigations adopting a strict protocol for confirming hypertension status as well as assessing associated comorbidities that may influence outcomes are necessary. From the therapeutic perspective, recombinant ACE2 may serve as a potential therapy, but relevant studies in humans are lacking. Definitive evidence regarding the use of RAS inhibitors in patients with COVID-19 is needed; 5 randomized trials examining this issue are currently underway. There is no current scientific support for claiming that hypertension or its treatment with RAS inhibitors contribute to unfavorable outcomes in COVID-19.", "qid": 23, "docid": "gwefujal", "rank": 50, "score": 0.7878760099411011}, {"content": "Title: Comorbid Chronic Diseases and Acute Organ Injuries Are Strongly Correlated with Disease Severity and Mortality among COVID-19 Patients: A Systemic Review and Meta-Analysis Content: The recent outbreak of COVID-19 has been rapidly spreading on a global scale. To date, there is no specific vaccine against the causative virus, SARS-CoV-2, nor is there an effective medicine for treating COVID-19, thus raising concerns with respect to the effect of risk factors such as clinical course and pathophysiological parameters on disease severity and outcome in patients with COVID-19. By extracting and analyzing all available published clinical data, we identified several major clinical characteristics associated with increased disease severity and mortality among patients with COVID-19. Specifically, preexisting chronic conditions such as hypertension, cardiovascular disease, chronic kidney disease, and diabetes are strongly associated with an increased risk of developing severe COVID-19; surprisingly, however, we found no correlation between chronic liver disease and increased disease severity. In addition, we found that both acute cardiac injury and acute kidney injury are highly correlated with an increased risk of COVID-19-related mortality. Given the high risk of comorbidity and the high mortality rate associated with tissue damage, organ function should be monitored closely in patients diagnosed with COVID-19, and this approach should be included when establishing new guidelines for managing these high-risk patients. Moreover, additional clinical data are needed in order to determine whether a supportive therapy can help mitigate the development of severe, potentially fatal complications, and further studies are needed to identify the pathophysiology and the mechanism underlying this novel coronavirus-associated infectious disease. Taken together, these findings provide new insights regarding clinical strategies for improving the management and outcome of patients with COVID-19.", "qid": 23, "docid": "mez1k8t0", "rank": 51, "score": 0.7872333526611328}, {"content": "Title: COVID-19 and Hypertension: The Role of ACE2 and the Renin-Angiotensin System Content: ABSTRACT Hypertension emerged from early reports as a potential risk factor for worse outcomes for persons with coronavirus disease 2019 (COVID-19). Among the putative links between hypertension and COVID-19 is a key counter-regulatory component of the renin-angiotensin system (RAS): angiotensin-converting enzyme 2 (ACE2). ACE2 facilitates entry of SARS-CoV-2, the virus responsible for COVID-19, into host cells. Since RAS inhibitors have been suggested to increase ACE2 expression, healthcare providers and patients have grappled with the decision of whether to discontinue these medications during the COVID-19 pandemic. However, experimental models of analogous viral pneumonias suggest RAS inhibitors may exert protective effects against acute lung injury. We review how RAS and ACE2 biology may affect outcomes in COVID-19 through pulmonary and other systemic effects. In addition, we briefly detail the data for and against continuation of RAS inhibitors in persons with COVID-19 and summarize the current consensus recommendations from select specialty organizations.", "qid": 23, "docid": "4ined9rx", "rank": 52, "score": 0.7869918942451477}, {"content": "Title: Effect of hypertension on outcomes of adult inpatients with COVID-19 in Wuhan, China: a propensity score\u2013matching analysis Content: BACKGROUND: Previous studies have shown that Coronavirus Disease 2019 (COVID-19) patients with underlying comorbidities can have worse outcomes. However, the effect of hypertension on outcomes of COVID-19 patients remains unclear. RESEARCH QUESTION: The aim of this study was to explore the effect of hypertension on the outcomes of patients with COVID-19 by using propensity score\u2013matching (PSM) analysis. STUDY DESIGN AND METHODS: Participants enrolled in this study were patients with COVID-19 who had been hospitalized at the Central Hospital of Wuhan, China. Chronic comorbidities and laboratory and radiological data were reviewed; patient outcomes and lengths of stay were obtained from discharge records. We used the Cox proportional-hazard model (CPHM) to analyze the effect of hypertension on these patients\u2019 outcomes and PSM analysis to further validate the abovementioned effect. RESULTS: A total of 226 patients with COVID-19 were enrolled in this study, of whom 176 survived and 50 died. The proportion of patients with hypertension among non-survivors was higher than that among survivors (26.70% vs. 74.00%; P < 0.001). Results obtained via CPHM showed that hypertension could increase risk of mortality in COVID-19 patients (hazard ratio 3.317; 95% CI [1.709\u20136.440]; P < 0.001). Increased D-dimer levels and higher ratio of neutrophils to lymphocytes (N/L) were also found to increase these patients\u2019 mortality risk. After matching on propensity score, we still came to similar conclusions. After we applied the same method in critically ill patients, we found that hypertension also increased risk of death in patients with severe COVID-19. CONCLUSION: Hypertension, increased D-dimer and the ratio of neutrophil to lymphocyte increased mortality in patients with COVID-19, with hypertension in particular.", "qid": 23, "docid": "xj50b7zo", "rank": 53, "score": 0.7869049310684204}, {"content": "Title: O Cora\u00e7\u00e3o e a COVID-19: O que o Cardiologista Precisa Saber./ O Cora\u00e7\u00e3o e a COVID-19: O que o Cardiologista Precisa Saber./ The Heart and COVID-19: What Cardiologists Need to Know Content: In face of the pandemic of the novel coronavirus disease 2019 (COVID-19), the management of patients with cardiovascular risk factors and/or disease is challenging. The cardiovascular complications evidenced in patients with COVID-19 derive from several mechanisms, ranging from direct viral injury to complications secondary to the inflammatory and thrombotic responses to the infection. The proper care of patients with COVID-19 requires special attention to the cardiovascular system aimed at better outcomes.", "qid": 23, "docid": "tp2tm0vn", "rank": 54, "score": 0.7868670225143433}, {"content": "Title: The Heart and COVID-19: What Cardiologists Need to Know. Content: In face of the pandemic of the novel coronavirus disease 2019 (COVID-19), the management of patients with cardiovascular risk factors and/or disease is challenging. The cardiovascular complications evidenced in patients with COVID-19 derive from several mechanisms, ranging from direct viral injury to complications secondary to the inflammatory and thrombotic responses to the infection. The proper care of patients with COVID-19 requires special attention to the cardiovascular system aimed at better outcomes.", "qid": 23, "docid": "7icw3be3", "rank": 55, "score": 0.7868670225143433}, {"content": "Title: Pathologies cardiovasculaires et Covid-19 : particularit\u00e9s chez les personnes \u00e2g\u00e9es./ COVID-19 and cardiovascular diseases: viewpoint for older patients Content: The coronavirus disease-2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. The link between cardiovascular disease and COVID-19 appears to be twofold. First, some reports of data indicate that certain groups of patients are more at risk of COVID-19. This includes patients with cardiovascular risk factors or pre-existing cardiovascular conditions and older patients. In addition, these patients incur disproportionately worse outcome. Second, SARS-CoV2 infection can be complicated by life-threatening cardiovascular acute diseases. Despite the rapid evolution of data on this pandemic, this review aims to highlight the cardiovascular considerations related to COVID-19 whether as comorbidities including concerns and uncertainty regarding the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on angiotensin conversion enzyme 2 or related to acute cardiovascular complications.", "qid": 23, "docid": "pjtlk8ni", "rank": 56, "score": 0.7856994867324829}, {"content": "Title: COVID-19 and cardiovascular diseases: viewpoint for older patients. Content: The coronavirus disease-2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. The link between cardiovascular disease and COVID-19 appears to be twofold. First, some reports of data indicate that certain groups of patients are more at risk of COVID-19. This includes patients with cardiovascular risk factors or pre-existing cardiovascular conditions and older patients. In addition, these patients incur disproportionately worse outcome. Second, SARS-CoV2 infection can be complicated by life-threatening cardiovascular acute diseases. Despite the rapid evolution of data on this pandemic, this review aims to highlight the cardiovascular considerations related to COVID-19 whether as comorbidities including concerns and uncertainty regarding the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on angiotensin conversion enzyme 2 or related to acute cardiovascular complications.", "qid": 23, "docid": "7rf532b9", "rank": 57, "score": 0.7856994867324829}, {"content": "Title: Pand\u00e9mie COVID-19 : impact sur le systeme cardiovasculaire. Donn\u00e9es disponibles au 1er avril 2020./ [COVID-19 pandemia: Impact on the cariovascular system. Data of 1st April 2020] Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells with angiotensin receptors, leading to pneumonia linked to COVID-19. The virus has a double impact on the cardiovascular system, the infection will be more intense if the host has cardiovascular co-morbidities and the virus can cause life-threatening cardiovascular lesions. Therapies associated with COVID-19 may have adverse cardiovascular effects. Therefore, special attention should be given to cardiovascular protection during COVID-19 infection.", "qid": 23, "docid": "uykao62t", "rank": 58, "score": 0.7848834991455078}, {"content": "Title: COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options Content: The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.", "qid": 23, "docid": "ubhntliy", "rank": 59, "score": 0.7847618460655212}, {"content": "Title: Clinical characteristics of coronavirus disease 2019 (COVID-19) patients with hypertension on renin-angiotensin system inhibitors Content: In December 2019, COVID-19 outbroke in Wuhan, China. The current study aimed to explore the clinical characteristics of COVID-19 complicated by hypertension. In this retrospective, single-center study, we recruited 110 discharged patients with COVID-19 at Wuhan Fourth Hospital in Wuhan, China, from January 25 to February 20, 2020. All study cases were grouped according to whether they had a history of hypertension. Then, a subgroup analysis for all hypertensive patients was carried out based on whether to take ACEI or ARB drugs. The mean age of 110 patients was 57.7 years (range, 25-86 years), of which 60 (54.5%) were male patients. The main underlying diseases included hypertension [36 (32.7%)] and diabetes [11 (10.0%)]. Compared with the non-hypertensive group, the lymphocyte count was significantly lower in the hypertensive group (average value, 0.96 \u00d7 109/L vs 1.26 \u00d7 109/L), and analysis of clinical outcomes showed that the crude mortality rate was higher in the hypertensive group [7/36 (19.4%) vs 2/74 (2.7%)]. Patients treated with ACEI or ARB, compared with the control group, were younger (average age, 58.5 years vs 69.2 years), but there was no statistical difference in the crude cure rate [10/15 (66.7%) vs 15/21 (71.4%)] and the crude mortality rate [2/15 (13.3%) vs 5/21 (23.8%)]. In conclusions, the COVID-19 patients with a history of hypertension had a significantly lower lymphocyte count on admission. The elderly and comorbidities such as hypertension may together constitute risk factors for poor prognosis in patients with COVID-19. Taking ACEI or ARB drugs may not change the prognosis of COVID-19 patients with hypertension.", "qid": 23, "docid": "faz8uw2d", "rank": 60, "score": 0.7846366167068481}, {"content": "Title: SARS-CoV-2 Infection and Cardiovascular Disease: COVID-19 Heart Content: Coronavirus disease (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The symptoms of the disease range from asymptomatic to mild respiratory symptoms and even potentially life-threatening cardiovascular and pulmonary complications. Cardiac complications include acute myocardial injury, arrhythmias, cardiogenic shock and even sudden death. Furthermore, drug interactions with COVID-19 therapies may place the patient at risk for arrhythmias, cardiomyopathy and sudden death. In this review, we summarise the cardiac manifestations of COVID-19 infection and propose a simplified algorithm for patient management during the COVID-19 pandemic.", "qid": 23, "docid": "0376d6vf", "rank": 61, "score": 0.7841290831565857}, {"content": "Title: COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options Content: The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) \u2014a homologue of ACE\u2014to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin\u2013angiotensin\u2013aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.", "qid": 23, "docid": "1aal6njl", "rank": 62, "score": 0.7838422656059265}, {"content": "Title: Pharmaco-invasive Therapy for STEMI in a Patient with COVID-19: A Case Report Content: Coronavirus disease 2019 (COVID-19) is a pandemic that started in the Wuhan province of China in December 2019 It is associated with increased morbidity and mortality mainly due to severe acute respiratory syndrome 2 (SARS-Cov-2) Cardiac manifestations related to COVID-19 include demand ischemia, fulminant myocarditis, myocardial infarction and arrhythmias In this report, we present a case of ST-segment elevation myocardial infarction (STEMI) in a 68-year-old man with COVID-19 who initially presented with chest pain and shortness of breath Patient's STEMI was managed with pharmaco-invasive strategy with tissue plasminogen activator (t-PA) He then developed acute hypoxic respiratory failure that was managed in the intensive care unit (ICU), together with multi-organ failure from which the patient died 2 days after presentation Although the pathophysiologic mechanisms of STEMI in COVID-19 patients has not been clearly established, we hypothesize that interrelated pathogenetic factors, that we highlight in this report, can play a role in the development of STEMI, including plaque rupture secondary to systemic inflammation, increased pro-coagulants, endothelial dysfunction, impaired fibrinolysis and impaired oxygen utilization leading to demand/supply mismatch and myocardial ischemia", "qid": 23, "docid": "946qlhuc", "rank": 63, "score": 0.7832790613174438}, {"content": "Title: Neurologic complications of COVID-19 Content: BACKGROUND: Much of the focus regarding the global pandemic of coronavirus disease of 2019 (COVID-19) has been on the cardiovascular, pulmonary, and hematologic complications. However, neurologic complications have arisen as an increasingly recognized area of morbidity and mortality. OBJECTIVE: This brief report summarizes the neurologic complications associated with COVID-19 with an emphasis on the emergency medicine clinician. DISCUSSION: COVID-19 has infected over 3.5 million people and killed over 240,000 people worldwide. While pulmonary complications are profound, the neurologic system is also significantly impacted, with complications including acute cerebrovascular events, encephalitis, Guillain-Barr\u00e9 syndrome, acute necrotizing hemorrhagic encephalopathy, and hemophagocytic lymphohistiocytosis. Additionally, patients on immunosuppressive medications for pre-existing neurologic issues are at an increased risk for complications with COVID-19 infection, and many of the currently proposed COVID-19 therapies can interact with these medications. CONCLUSIONS: When caring for COVID-19 patients, emergency medicine clinicians should be aware of the neurologic complications from COVID-19.", "qid": 23, "docid": "bvm1mrdy", "rank": 64, "score": 0.7825154066085815}, {"content": "Title: Clinical characteristics of coronavirus disease 2019 (COVID-19) patients with hypertension on renin\u2013angiotensin system inhibitors Content: In December 2019, COVID-19 outbroke in Wuhan, China. The current study aimed to explore the clinical characteristics of COVID-19 complicated by hypertension. In this retrospective, single-center study, we recruited 110 discharged patients with COVID-19 at Wuhan Fourth Hospital in Wuhan, China, from January 25 to February 20, 2020. All study cases were grouped according to whether they had a history of hypertension. Then, a subgroup analysis for all hypertensive patients was carried out based on whether to take ACEI or ARB drugs. The mean age of 110 patients was 57.7 years (range, 25\u201386 years), of which 60 (54.5%) were male patients. The main underlying diseases included hypertension [36 (32.7%)] and diabetes [11 (10.0%)]. Compared with the non-hypertensive group, the lymphocyte count was significantly lower in the hypertensive group (average value, 0.96 \u00d7 10(9)/L vs 1.26 \u00d7 10(9)/L), and analysis of clinical outcomes showed that the crude mortality rate was higher in the hypertensive group [7/36 (19.4%) vs 2/74 (2.7%)]. Patients treated with ACEI or ARB, compared with the control group, were younger (average age, 58.5 years vs 69.2 years), but there was no statistical difference in the crude cure rate [10/15 (66.7%) vs 15/21 (71.4%)] and the crude mortality rate [2/15 (13.3%) vs 5/21 (23.8%)]. In conclusions, the COVID-19 patients with a history of hypertension had a significantly lower lymphocyte count on admission. The elderly and comorbidities such as hypertension may together constitute risk factors for poor prognosis in patients with COVID-19. Taking ACEI or ARB drugs may not change the prognosis of COVID-19 patients with hypertension.", "qid": 23, "docid": "d4mf43j9", "rank": 65, "score": 0.782482922077179}, {"content": "Title: COVID-19 y enfermedad cardiovascular y renal: \u00bfD\u00f3nde estamos? \u00bfHacia d\u00f3nde vamos?/ [COVID-19 and cardiovascular and kidney disease: Where are we? Where are we going?] Content: The SARS-CoV-2 pandemic is a global health emergency and we need to know more about it. Patients with cardiovascular risk and previous kidney risk have been identified as especially vulnerable for greater morbidity and mortality when they suffer from COVID-19. A considerable proportion of patients can develop a vascular lesion in the context of the disease that entails a greater lethality. Cardiovascular and renal complications represent a problem and, probably in the near future, may pose a threat to patients who have survived COVID-19. As physicians, we cannot forget that during an epidemic like this, other chronic diseases are present, and patients continue to require care. We are obliged to monitor even more intensely their treatments and control degree. Furthermore, we must not forget that urgent situations continue to arise in this pandemic situation and require prompt attention. In this current situation, it is very likely that many patients, out of fear, have not sought medical attention. The situation during the epidemic and the uncertainty of the post-COVID-19 period, requires intensification in the control and monitoring of cardiovascular and kidney disease in our patients. Primary care constitutes a key level of care for the care of the population with cardiovascular disease. Likewise, and in the face of this new health scenario, we need to promote the prevention and control measures that emanate from the studies currently underway. Now, more than ever, we need research, crucial to improve the cardiovascular and renal prognosis of our patients.", "qid": 23, "docid": "h9hhasz6", "rank": 66, "score": 0.7823176383972168}, {"content": "Title: Arterial and venous thromboembolic disease in a patient with COVID-19: A case report Content: \u2022 Hypercoagulability is a major contributor to COVID-19 related pulmonary complications; \u2022 Commonly used approaches may be insufficient to ameliorate the risk of thromboembolic events in patients with COVID-19; \u2022 Even when on thromboprophylaxis, it is crucial to remain vigilant for the occurrence of VTE in patients with COVID-19.", "qid": 23, "docid": "lmz56pdm", "rank": 67, "score": 0.7821682691574097}, {"content": "Title: COVID-19 patients with hypertension have more severe disease: a multicenter retrospective observational study Content: This study aims to explore the effect of hypertension on disease progression and prognosis in patients with coronavirus disease 2019 (COVID-19). A total of 310 patients diagnosed with COVID-19 were studied. A comparison was made between two groups of patients, those with hypertension and those without hypertension. Their demographic data, clinical manifestations, laboratory indicators, and treatment methods were collected and analyzed. A total of 310 patients, including 113 patients with hypertension and 197 patients without hypertension, were included in the analysis. Compared with patients without hypertension, patients with hypertension were older, were more likely to have diabetes and cerebrovascular disease, and were more likely to be transferred to the intensive care unit. The neutrophil count and lactate dehydrogenase, fibrinogen, and D-dimer levels in hypertensive patients were significantly higher than those in nonhypertensive patients (P < 0.05). However, multivariate analysis (adjusted for age and sex) failed to show that hypertension was an independent risk factor for COVID-19 mortality or severity. COVID-19 patients with hypertension were more likely than patients without hypertension to have severe pneumonia, excessive inflammatory reactions, organ and tissue damage, and deterioration of the disease. Patients with hypertension should be given additional attention to prevent worsening of their condition.", "qid": 23, "docid": "es8ztvq5", "rank": 68, "score": 0.7820367217063904}, {"content": "Title: Clinical Pharmacology Considerations for Developing Small-Molecule Treatments for COVID-19 Content: Numerous drugs are being investigated for the treatment of COVID-19, including antivirals and therapies targeting complications related to COVID-19. The clinical presentation of COVID-19 varies from mild fever, cough, and dyspnea in the early stages of disease to severe complications such as acute respiratory distress syndrome, systemic hyperinflammation, and sepsis. A thorough understanding of the disease pathogenesis and the disease complications is essential to developing effective therapies to treat this potentially life-threatening disease. This review offers key clinical pharmacology considerations involved in the development of small molecules for the treatment of COVID-19. They are based on the major observed disease complications that impact drug absorption, distribution, metabolism, and elimination. We also address considerations regarding potential drug interactions, alternative routes and methods of administration, and dosing in patients on hemodialysis.", "qid": 23, "docid": "s0c9odzd", "rank": 69, "score": 0.7817674875259399}, {"content": "Title: Cardiovascular conditions and COVID-19 Content: Although COVID-19 primarily affects the respiratory system, cardiovascular involvement is common, especially in individuals who are severely ill.", "qid": 23, "docid": "cn6dxf6g", "rank": 70, "score": 0.7814712524414062}, {"content": "Title: Cardiovascular conditions and COVID-19. Content: Although COVID-19 primarily affects the respiratory system, cardiovascular involvement is common, especially in individuals who are severely ill.", "qid": 23, "docid": "1cntwm22", "rank": 71, "score": 0.7814712524414062}, {"content": "Title: COVID-19, hipertensi\u00f3n y enfermedad cardiovascular./ [COVID-19 and its relationship with hypertension and cardiovascular disease] Content: The association between hypertension, diabetes, cardio and cerebrovascular disease and severe and fatal COVID-19, described in different countries, is remarkable. Myocardial damage and myocardial dysfunction are postulated as a possible causal nexus. Frequent findings of elevated troponin levels and electrocardiographic anomalies support this concept. On the other hand, hypotheses in favour and against a deleterious effect of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, a usual treatment for cardiovascular disease, have been raised. There is currently no solid evidence and thus properly designed studies on this subject are urgently needed. In this context, patients with cardiovascular disease should especially avoid being exposed to the virus, should not self-medicate and rapidly seek medical advice should they show symptoms of infection.", "qid": 23, "docid": "f8v51ouz", "rank": 72, "score": 0.7813609838485718}, {"content": "Title: Hypertension in patients hospitalized with COVID-19 in Wuhan, China: A single-center retrospective observational study Content: Objectives: It is unclear whether patients with hypertension are more likely to be infected with SARS-COV-2 than the general population and whether there is a difference in the severity of COVID-19 pneumonia in patients who have taken ACEI/ARB drugs to lower blood pressure compared to those who have not. Methods: This observational study included data from all patients with clinically confirmed COVID-19 who were admitted to the Hankou Hospital, Wuhan, China between January 5 and March 8, 2020. Data were extracted from clinical and laboratory records. Follow-up was cutoff on March 8, 2020. Results: A total of 274 patients, 75 with hypertension and 199 without hypertension, were included in the analysis. Patients with hypertension were older and were more likely to have pre-existing comorbidities, including chronic renal insufficiency, cardiovascular disease, diabetes mellitus, and cerebrovascular disease than patients without hypertension. Moreover, patients with hypertension tended to have higher positive COVID-19 PCR detection rates. Patients with hypertension who had previously taken ACEI/ARB drugs for antihypertensive treatment have an increased tendency to develop severe pneumonia after infection with SARS-COV-2 (P = 0.064). Conclusions: COVID-19 patients with hypertension were significantly older and were more likely to have underlying comorbidities, including chronic renal insufficiency, cardiovascular disease, diabetes mellitus, and cerebrovascular disease. Patients with hypertension who had taken ACEI/ARB drugs for antihypertensive treatment have an increased tendency to develop severe pneumonia after infection with SARS-COV-2. In future studies, a larger sample size and multi-center clinical data will be needed to support our conclusions.", "qid": 23, "docid": "lujxql3a", "rank": 73, "score": 0.7808372974395752}, {"content": "Title: COVID-19 and the Cerebro-Cardiovascular Systems: What do we Know so Far? Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic of 2019-2020 has resulted in multiple hospitalizations, deaths and economic hardships worldwide. Though respiratory involvement in patients with coronavirus disease 2019 (COVID-19) is well-known, the potential cardiovascular and cerebrovascular manifestations are less-understood. We performed a PubMed and Google Scholar search and reviewed relevant literature regarding COVID-19 and cardiovascular system involvement. SARS-CoV-2 possesses high-affinity for angiotensin converting enzyme 2 (ACE2) receptor, which is highly concentrated in the lungs and cardiovascular tissue, thereby provoking concern for cardiovascular involvement in COVID-19 cases. Pre-existing cardiovascular and cerebrovascular disease has been shown in previous reports to be a risk-factor for severe infection. Based on our review of published studies, COVID-19 patients may be more likely to experience acute cardiac injury, arrhythmia, coagulation defects and acute stroke and are likely to have poorer outcomes as a result. As the COVID-19 pandemic continues, more data regarding potential cardiovascular and cerebrovascular manifestations of the disease is required.", "qid": 23, "docid": "sam3usz7", "rank": 74, "score": 0.7804487943649292}, {"content": "Title: COVID-19 and hypertension-evidence and practical management: Guidance from the HOPE Asia Network Content: There are several risk factors for worse outcomes in patients with coronavirus 2019 disease (COVID-19). Patients with hypertension appear to have a poor prognosis, but there is no direct evidence that hypertension increases the risk of new infection or adverse outcomes independent of age and other risk factors. There is also concern about use of renin-angiotensin system (RAS) inhibitors due to a key role of angiotensin-converting enzyme 2 receptors in the entry of the SARS-CoV-2 virus into cells. However, there is little evidence that use of RAS inhibitors increases the risk of SARS-CoV-2 virus infection or worsens the course of COVID-19. Therefore, antihypertensive therapy with these agents should be continued. In addition to acute respiratory distress syndrome, patients with severe COVID-19 can develop myocardial injury and cytokine storm, resulting in heart failure, arteriovenous thrombosis, and kidney injury. Troponin, N-terminal pro-B-type natriuretic peptide, D-dimer, and serum creatinine are biomarkers for these complications and can be used to monitor patients with COVID-19 and for risk stratification. Other factors that need to be incorporated into patient management strategies during the pandemic include regular exercise to maintain good health status and monitoring of psychological well-being. For the ongoing management of patients with hypertension, telemedicine-based home blood pressure monitoring strategies can facilitate maintenance of good blood pressure control while social distancing is maintained. Overall, multidisciplinary management of COVID-19 based on a rapidly growing body of evidence will help ensure the best possible outcomes for patients, including those with risk factors such as hypertension.", "qid": 23, "docid": "jhkc8of3", "rank": 75, "score": 0.7802333831787109}, {"content": "Title: Mechanisms of Myocardial Injury in Coronavirus Disease 2019 Content: Coronavirus disease 2019 (COVID-19) predominantly presents with symptoms of fever, fatigue, cough and respiratory failure. However, it appears to have a unique interplay with cardiovascular disease (CVD); patients with pre-existing CVD are at highest risk for mortality from COVID-19, along with the elderly. COVID-19 contributes to cardiovascular complications including arrhythmias, myocardial dysfunction and myocardial inflammation. Although the exact mechanism of myocardial inflammation in patients with COVID-19 is not known, several plausible mechanisms have been proposed based on early observational reports. In this article, the authors summarise the available literature on mechanisms of myocardial injury in COVID-19.", "qid": 23, "docid": "h2xmxwd1", "rank": 76, "score": 0.779956579208374}, {"content": "Title: Ictus como complicaci\u00f3n y como factor pron\u00f3stico de COVID-19./ Ictus como complicaci\u00f3n y como factor pron\u00f3stico de COVID-19./ Stroke as a complication and prognostic factor of COVID-19 Content: INTRODUCTION: Contradictory data have been reported on the incidence of stroke in patients with COVID-19 and the risk of SARS-CoV-2 infection among patients with history of stroke. METHODS: This study systematically reviews case series reporting stroke as a complication of COVID-19, and analyses the prognosis of patients with COVID-19 and history of stroke. The pathophysiological mechanisms of stroke in patients with COVID-19 are also reviewed. CONCLUSIONS: History of stroke increases the risk of death due to COVID-19 by 3 times. Stroke currently seems not to be one of the main complications of COVID-19.", "qid": 23, "docid": "bms5tkg0", "rank": 77, "score": 0.7797499895095825}, {"content": "Title: Cardiovascular Considerations for the Internist and Hospitalist in the COVID-19 Era Content: It is clear that existing cardiovascular disease is a major risk factor for COVID-19 and related adverse outcomes. In addition to acute respiratory syndrome, a large cohort also develop myocardial and/or vascular dysfunction, in part from inflammation and renin angiotensin system activation with increased sympathetic outflow, cardiac arrhythmias, ischemia, heart failure, and thromboembolic complications that portend poor COVID-19 outcomes. We summarize here recent information for hospitalists/internists on the front-line of this pandemic regarding its cardiovascular impacts and management and need for cardiovascular consultation.", "qid": 23, "docid": "fitz1vjs", "rank": 78, "score": 0.7796577215194702}, {"content": "Title: COVID-19 and Heart: From Clinical Features to Pharmacological Implications. Content: A highly pathogenic human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been recently recognized in Wuhan, China, as the cause of the coronavirus disease 2019 (COVID-19) outbreak which has spread rapidly from China to other countries in the world, causing a pandemic with alarming morbidity and mortality. The emerging epidemiological data about COVID-19 patients suggest an association between cardiovascular diseases (CVD) and SARS-CoV-2 infection, in term of clinical features at hospital admission and prognosis for disease severity. The aim of our review is to describe the cardiological features of COVID-19 patients at admission, the acute cardiac presentation, the clinical outcome for patients with underlying CVD and the pharmacological implications for disease management.", "qid": 23, "docid": "d5vmviai", "rank": 79, "score": 0.7795214056968689}, {"content": "Title: Coronavirus SARS-Cov-2 and arterial hypertension - facts and myths Content: Arterial hypertension is the most common comorbid disease in patients who died as a result of SARS-Cov-2 infection Numerous observational studies indicate a relationship between arterial hypertension and its treatment and SARS-Cov-2 coronavirus infection It is known from experimental studies that SARS-Cov-2 enters the cells by interacting with the ACE2 enzyme, while it is not known whether ACE2 is the only factor that allows the virus to enter the cell There is no clear evidence of a link between the use of medications such as ACE and ARB and an increased risk of SARS-Cov-2 infection It has been shown that the use of recombinant ACE2 can be potentially beneficial in COVID-19 therapy by limiting the entry of the virus into the cell Blood glucose as well as lipid profile should be monitored during SARS-Cov-2 coronavirus infection This article attempts to gather key information on arterial hypertension and COVID-19", "qid": 23, "docid": "yg1mma87", "rank": 80, "score": 0.7793951034545898}, {"content": "Title: Novel Insights on the Pulmonary Vascular Consequences of Covid-19 Content: In the last few months, the number of cases of a new coronavirus-related disease (COVID-19) rose exponentially, reaching the status of a pandemic. Interestingly, early imaging studies documented that pulmonary vascular thickening was specifically associated with COVID-19 pneumonia, implying a potential tropism of the virus for the pulmonary vasculature. Moreover, SARS-CoV-2 infection is associated with inflammation, hypoxia, oxidative stress, mitochondrial dysfunction, DNA damage and lung coagulopathy promoting endothelial dysfunction and microthrombosis. These features are strikingly similar to what is seen in pulmonary vascular diseases. Although the consequences of COVID-19 on the pulmonary circulation remain to be explored, several viruses have been previously thought to be involved in the development of pulmonary vascular diseases. Patients with preexisting pulmonary vascular diseases also appear at increased risk of morbidity and mortality. The present article reviews the molecular factors shared by coronaviruses infection and pulmonary vasculature defects, and the clinical relevance of pulmonary vascular alterations in the context of COVID-19.", "qid": 23, "docid": "owsoyvyz", "rank": 81, "score": 0.7793614864349365}, {"content": "Title: NOVEL INSIGHTS ON THE PULMONARY VASCULAR CONSEQUENCES OF COVID-19. Content: In the last few months, the number of cases of a new coronavirus-related disease (COVID-19) rose exponentially, reaching the status of a pandemic. Interestingly, early imaging studies documented that pulmonary vascular thickening was specifically associated with COVID-19 pneumonia, implying a potential tropism of the virus for the pulmonary vasculature. Moreover, SARS-CoV-2 infection is associated with inflammation, hypoxia, oxidative stress, mitochondrial dysfunction, DNA damage and lung coagulopathy promoting endothelial dysfunction and microthrombosis. These features are strikingly similar to what is seen in pulmonary vascular diseases. Although the consequences of COVID-19 on the pulmonary circulation remain to be explored, several viruses have been previously thought to be involved in the development of pulmonary vascular diseases. Patients with preexisting pulmonary vascular diseases also appear at increased risk of morbidity and mortality. The present article reviews the molecular factors shared by coronaviruses infection and pulmonary vasculature defects, and the clinical relevance of pulmonary vascular alterations in the context of COVID-19.", "qid": 23, "docid": "qbbbro55", "rank": 82, "score": 0.7793614864349365}, {"content": "Title: Association of hypertension, diabetes, stroke, cancer, kidney disease, and high-cholesterol with COVID-19 disease severity and fatality: A systematic review Content: BACKGROUND AND AIMS: To undertake a review and critical appraisal of published/preprint reports that offer methods of determining the effects of hypertension, diabetes, stroke, cancer, kidney issues, and high-cholesterol on COVID-19 disease severity. METHODS: A search was conducted by two authors independently on the freely available COVID-19 Open Research Dataset (CORD-19). We developed an automated search engine to screen a total of 59,000 articles in a few seconds. Filtering of the articles was then undertaken using keywords and questions, e.g. \u201cEffects of diabetes on COVID/normal coronavirus/SARS-CoV-2/nCoV/COVID-19 disease severity, mortality?\u201c. The search terms were repeated for all the comorbidities considered in this paper. Additional articles were retrieved by searching via Google Scholar and PubMed. FINDINGS: A total of 54 articles were considered for a full review. It was observed that diabetes, hypertension, and cholesterol levels possess an apparent relation to COVID-19 severity. Other comorbidities, such as cancer, kidney disease, and stroke, must be further evaluated to determine a strong relationship to the virus. CONCLUSION: Reports associating cancer, kidney disease, and stroke with COVID-19 should be carefully interpreted, not only because of the size of the samples, but also because patients could be old, have a history of smoking, or have any other clinical condition suggesting that these factors might be associated with the poor COVID-19 outcomes rather than the comorbidity itself. Further research regarding this relationship and its clinical management is warranted.", "qid": 23, "docid": "ab5tgbvm", "rank": 83, "score": 0.7791117429733276}, {"content": "Title: COVID-19 and Its Impact on Cardiovascular Disease. Content: The COVID-19 pandemic has placed a significant strain on healthcare providers. As the number of patients continue to surge, healthcare workers are now forced to find different approaches to practicing medicine that may affect patient care. In addition, COVID-19 has many cardiovascular complications that affect the clinical course of patients. In this article we summarize the cardiovascular impact of COVID-19 and some of the challenges that patients and the healthcare system will face during this pandemic.", "qid": 23, "docid": "7zhpw74p", "rank": 84, "score": 0.7786284685134888}, {"content": "Title: COVID\u201019 and hypertension\u2014evidence and practical management: Guidance from the HOPE Asia Network Content: There are several risk factors for worse outcomes in patients with coronavirus 2019 disease (COVID\u201019). Patients with hypertension appear to have a poor prognosis, but there is no direct evidence that hypertension increases the risk of new infection or adverse outcomes independent of age and other risk factors. There is also concern about use of renin\u2010angiotensin system (RAS) inhibitors due to a key role of angiotensin\u2010converting enzyme 2 receptors in the entry of the SARS\u2010CoV\u20102 virus into cells. However, there is little evidence that use of RAS inhibitors increases the risk of SARS\u2010CoV\u20102 virus infection or worsens the course of COVID\u201019. Therefore, antihypertensive therapy with these agents should be continued. In addition to acute respiratory distress syndrome, patients with severe COVID\u201019 can develop myocardial injury and cytokine storm, resulting in heart failure, arteriovenous thrombosis, and kidney injury. Troponin, N\u2010terminal pro\u2010B\u2010type natriuretic peptide, D\u2010dimer, and serum creatinine are biomarkers for these complications and can be used to monitor patients with COVID\u201019 and for risk stratification. Other factors that need to be incorporated into patient management strategies during the pandemic include regular exercise to maintain good health status and monitoring of psychological well\u2010being. For the ongoing management of patients with hypertension, telemedicine\u2010based home blood pressure monitoring strategies can facilitate maintenance of good blood pressure control while social distancing is maintained. Overall, multidisciplinary management of COVID\u201019 based on a rapidly growing body of evidence will help ensure the best possible outcomes for patients, including those with risk factors such as hypertension.", "qid": 23, "docid": "254z62e4", "rank": 85, "score": 0.7774945497512817}, {"content": "Title: COVID-19-associated cardiovascular morbidity in older adults: a position paper from the Italian Society of Cardiovascular Researches Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells following binding with the cell surface ACE2 receptors, thereby leading to coronavirus disease 2019 (COVID-19). SARS-CoV-2 causes viral pneumonia with additional extrapulmonary manifestations and major complications, including acute myocardial injury, arrhythmia, and shock mainly in elderly patients. Furthermore, patients with existing cardiovascular comorbidities, such as hypertension and coronary heart disease, have a worse clinical outcome following contraction of the viral illness. A striking feature of COVID-19 pandemics is the high incidence of fatalities in advanced aged patients: this might be due to the prevalence of frailty and cardiovascular disease increase with age due to endothelial dysfunction and loss of endogenous cardioprotective mechanisms. Although experimental evidence on this topic is still at its infancy, the aim of this position paper is to hypothesize and discuss more suggestive cellular and molecular mechanisms whereby SARS-CoV-2 may lead to detrimental consequences to the cardiovascular system. We will focus on aging, cytokine storm, NLRP3/inflammasome, hypoxemia, and air pollution, which is an emerging cardiovascular risk factor associated with rapid urbanization and globalization. We will finally discuss the impact of clinically available CV drugs on the clinical course of COVID-19 patients. Understanding the role played by SARS-CoV2 on the CV system is indeed mandatory to get further insights into COVID-19 pathogenesis and to design a therapeutic strategy of cardio-protection for frail patients.", "qid": 23, "docid": "swdojn3a", "rank": 86, "score": 0.7773870229721069}, {"content": "Title: COVID-19-Related Stroke Content: The COVID-19 pandemic is associated with neurological symptoms and complications including stroke. There is hypercoagulability associated with COVID-19 that is likely a \u201csepsis-induced coagulopathy\u201d and may predispose to stroke. The SARS-CoV-2 virus binds to angiotensin-converting enzyme 2 (ACE2) present on brain endothelial and smooth muscle cells. ACE2 is a key part of the renin angiotensin system (RAS) and a counterbalance to angiotensin-converting enzyme 1 (ACE1) and angiotensin II. Angiotensin II is proinflammatory, is vasoconstrictive, and promotes organ damage. Depletion of ACE2 by SARS-CoV-2 may tip the balance in favor of the \u201charmful\u201d ACE1/angiotensin II axis and promote tissue injury including stroke. There is a rationale to continue to treat with tissue plasminogen activator for COVID-19-related stroke and low molecular weight heparinoids may reduce thrombosis and mortality in sepsis-induced coagulopathy.", "qid": 23, "docid": "7pxfzuq0", "rank": 87, "score": 0.7773557305335999}, {"content": "Title: Myocardial and Microvascular Injury Due to Coronavirus Disease 2019 Content: Over the past few months, health systems worldwide have been put to the test with the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though the leading clinical manifestations of the SARS-CoV-2 infection involve the respiratory tract, there is a non-negligible risk of systemic involvement leading to the onset of multi-organ failure with fatal consequences. Since the onset of COVID-19, patients with underlying cardiovascular disease have been at increased risk of poor clinical outcomes with higher death rates. Moreover, the occurrence of new-onset cardiac complications is not uncommon among patients hospitalised for COVID-19. Of importance, a significant portion of COVID-19 patients present with myocardial injury. Herein, the authors discuss the mechanisms leading to myocardial and microvascular injury in SARS-CoV-2 infection and their clinical implications.", "qid": 23, "docid": "uo88b0mk", "rank": 88, "score": 0.7772842645645142}, {"content": "Title: COVID-19 y enfermedad cardiovascular y renal: \u00bfD\u00f3nde estamos?; \u00bfhacia d\u00f3nde vamos? Content: ABSTRACT The SARS-CoV-2 pandemic is a global health emergency and we need to know more about it.Patients with cardiovascular risk (CVD) and previous kidney risk have been identified as especially vulnerable for greater morbidity and mortality when they suffer from COVID-19. A considerable proportion of patients can develop a vascular lesion in the context of the disease that entails a greater lethality. Cardiovascular and renal complications represent a problem and, probably in the near future, may pose a threat to patients who have survived COVID-19.As physicians, we cannot forget that during an epidemic like this, other chronic diseases are present, and patients continue to require care. We are obliged to monitor even more intensely their treatments and control degree. Furthermore, we must not forget that urgent situations continue to arise in this pandemic situation and require prompt attention. In this current situation, it is very likely that many patients, out of fear, have not sought medical attention.The situation during the epidemic and the uncertainty of the post-COVID-19 period, requires intensification in the control and monitoring of CVD and kidney in our patients. Primary care constitutes a key level of care for the care of the population with CVD. Likewise, and in the face of this new health scenario, we need to promote the prevention and control measures that emanate from the studies currently underway. Now, more than ever, we need research, crucial to improve the cardiovascular and renal prognosis of our patients.", "qid": 23, "docid": "jb32wevi", "rank": 89, "score": 0.7770954370498657}, {"content": "Title: COVID-19 and pulmonary hypertension Content: Pulmonary hypertension (PH) is a pulmonary vascular disease characterized by pulmonary arterial remodeling and vasoconstriction leading to elevated pulmonary artery pressure and, ultimately, right heart failure. So far, few cases of COVID-19 disease in patients with PH have been reported. Caution is warranted in interpreting this observation as data are evolving and several factors may influence the number of reported cases of PH and COVID-19. Social distancing and quarantine could play a role, especially for patients with chronic diseases who might be more vigilant of their potential for respiratory infection. In addition, PH is a rare disease, and because testing is not universal, we could be underestimating the number of cases. Other hypothetical factors to consider are the underlying pathophysiology of PH and the medications used to treat PH and their implications in COVID-19.", "qid": 23, "docid": "duohnpj2", "rank": 90, "score": 0.776999294757843}, {"content": "Title: COVID-19 and pulmonary hypertension. Content: Pulmonary hypertension (PH) is a pulmonary vascular disease characterized by pulmonary arterial remodeling and vasoconstriction leading to elevated pulmonary artery pressure and, ultimately, right heart failure. So far, few cases of COVID-19 disease in patients with PH have been reported. Caution is warranted in interpreting this observation as data are evolving and several factors may influence the number of reported cases of PH and COVID-19. Social distancing and quarantine could play a role, especially for patients with chronic diseases who might be more vigilant of their potential for respiratory infection. In addition, PH is a rare disease, and because testing is not universal, we could be underestimating the number of cases. Other hypothetical factors to consider are the underlying pathophysiology of PH and the medications used to treat PH and their implications in COVID-19.", "qid": 23, "docid": "q571agza", "rank": 91, "score": 0.776999294757843}, {"content": "Title: Importance of the evaluation of systemic microvascular flow and reactivity in critically ill patients with coronavirus disease 2019 \u2014 COVID-19() Content: Amidst the pandemic that has mesmerized the entire world, as it has not spared anyone according to any specific characteristic, some conditions have, in fact, emerged as risk factors for a complicated evolution of COVID-19. Older age, cardiovascular disease including hypertension, diabetes and pulmonary disease, have been associated with more severe presentations and/or adverse prognosis. In this letter to the editor, we propose that the link between cardiovascular and metabolic diseases and the higher incidence and worse prognosis of COVID-19 patients is the (micro) vascular endothelium.", "qid": 23, "docid": "k3ibkk2v", "rank": 92, "score": 0.7765953540802002}, {"content": "Title: Importance of the evaluation of systemic microvascular flow and reactivity in critically ill patients with coronavirus disease 2019 - COVID-19 Content: Amidst the pandemic that has mesmerized the entire world, as it has not spared anyone according to any specific characteristic, some conditions have, in fact, emerged as risk factors for a complicated evolution of COVID-19. Older age, cardiovascular disease including hypertension, diabetes and pulmonary disease, have been associated with more severe presentations and/or adverse prognosis. In this letter to the editor, we propose that the link between cardiovascular and metabolic diseases and the higher incidence and worse prognosis of COVID-19 patients is the (micro) vascular endothelium.", "qid": 23, "docid": "2nsdx8bs", "rank": 93, "score": 0.7765953540802002}, {"content": "Title: Coronavirus SARS-Cov-2 and arterial hypertension - facts and myths. Content: Arterial hypertension is the most common comorbid disease in patients who died as a result of SARS-Cov-2 infection. Numerous observational studies indicate a relationship between arterial hypertension and its treatment and SARS-Cov-2 coronavirus infection. It is known from experimental studies that SARS-Cov-2 enters the cells by interacting with the ACE2 enzyme, while it is not known whether ACE2 is the only factor that allows the virus to enter the cell. There is no clear evidence of a link between the use of medications such as ACE and ARB and an increased risk of SARS-Cov-2 infection. It has been shown that the use of recombinant ACE2 can be potentially beneficial in COVID-19 therapy by limiting the entry of the virus into the cell. Blood glucose as well as lipid profile should be monitored during SARS-Cov-2 coronavirus infection. This article attempts to gather key information on arterial hypertension and COVID-19.", "qid": 23, "docid": "r7vx32o2", "rank": 94, "score": 0.77625572681427}, {"content": "Title: At the heart of COVID-19 Content: Coronavirus disease (COVID-19) first presented in Wuhan, Hubei province, China in December 2019. Since then, it has rapidly spread across the world, and is now formally considered a pandemic. The disease does not discriminate but increasing age and the presence of comorbidities are associated with severe form of the disease and poor outcomes. Although the prevalence of COVID-19 in patients with cardiovascular disease is under-reported, there is evidence that pre-existing cardiac disease can render individuals vulnerable. It is thought that COVID-19 may have both a direct and indirect effect on the cardiovascular system; however, the primary mechanism of underlying cardiovascular involvement is still uncertain. Of particular interest is the role of angiotensin-converting enzyme 2, which is well known for its cardiovascular effects and is also considered to be important in the pathogenesis of COVID-19. With a range of different drug candidates being suggested, effective anti-virals and vaccines are an area of on-going research. While our knowledge of COVID-19 continues to rapidly expand, this review highlights recent advances in our understanding of the interaction between COVID-19 and the cardiovascular system.", "qid": 23, "docid": "z3esk2dk", "rank": 95, "score": 0.7759003639221191}, {"content": "Title: At the heart of COVID-19. Content: Coronavirus disease (COVID-19) first presented in Wuhan, Hubei province, China in December 2019. Since then, it has rapidly spread across the world, and is now formally considered a pandemic. The disease does not discriminate but increasing age and the presence of comorbidities are associated with severe form of the disease and poor outcomes. Although the prevalence of COVID-19 in patients with cardiovascular disease is under-reported, there is evidence that pre-existing cardiac disease can render individuals vulnerable. It is thought that COVID-19 may have both a direct and indirect effect on the cardiovascular system; however, the primary mechanism of underlying cardiovascular involvement is still uncertain. Of particular interest is the role of angiotensin-converting enzyme 2, which is well known for its cardiovascular effects and is also considered to be important in the pathogenesis of COVID-19. With a range of different drug candidates being suggested, effective anti-virals and vaccines are an area of on-going research. While our knowledge of COVID-19 continues to rapidly expand, this review highlights recent advances in our understanding of the interaction between COVID-19 and the cardiovascular system.", "qid": 23, "docid": "6wy9y2f0", "rank": 96, "score": 0.7759003639221191}, {"content": "Title: The Novel Coronavirus Disease (COVID-19) and Its Impact on Cardiovascular Disease Content: The coronavirus disease 2019 (COVID-19) pandemic has placed a significant strain on healthcare providers. As the number of patients continue to surge, healthcare workers are now forced to find different approaches to practicing medicine that may affect patient care. In addition, COVID-19 has many cardiovascular complications that affect the clinical course of patients. In this article, we summarize the cardiovascular impact of COVID-19 and some of the challenges that patients and the healthcare system will face during this pandemic.", "qid": 23, "docid": "blok70nn", "rank": 97, "score": 0.7754220962524414}, {"content": "Title: Challenging Issues in the Management of Cardiovascular Risk Factors in Diabetes During the COVID-19 Pandemic: A Review of Current Literature Content: The COVID-19 outbreak was declared a pandemic on March 2020. Many patients with SARS-CoV-2 infection have underlying chronic medical conditions such as diabetes, cardiovascular disease (CVD), and hypertension. Patient-related outcomes are worse if there are associated comorbidities. We do not have enough evidence regarding the most appropriate management of patients with diabetes during COVID-19 infection. Insulin resistance and CVD together increase the inflammatory state of the body, which can contribute to and perhaps mediate the increase of COVID-19 severity. Hence, in addition to management of dysglycemia, other CVD risk factors should be targeted. We explore the possible pathophysiologic links between diabetes and COVID-19 and discuss various options to treat dysglycemia, hypertension, and dyslipidemia in the era of COVID-19.", "qid": 23, "docid": "ntv2g7ne", "rank": 98, "score": 0.7749761343002319}, {"content": "Title: 2019 Novel-coronavirus: Cardiovascular Insights about Risk Factors, Myocardial Injury, Therapy and Clinical Implications Content: From December 31th, 2019, a novel highly pathogenic coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide, reaching at present the dimension of a pandemic. In addition to damaging the lungs, SARS-CoV-2 may also damage the heart and this is corroborated by the evidence that cardiovascular comorbidities are associated with a higher mortality and poor clinical outcomes in patient infected by the virus. During the infection myocardial injury, myocarditis and arrhythmias have also been reported, but the pathophysiological mechanisms of these complications are yet to be understood. Great attention is also being posed on the potential beneficial/harmful role of angiotensin converting enzyme (ACE) inhibitors, as far as the virus binds to angiotensin converting enzyme 2 (ACE2) to infect cells, but evidences lack. Furthermore, SARS-CoV-2 can also affect the aspect of acute coronary syndromes, not only because these two distinct pathological entities share pathogenic aspects (such as the systemic inflammatory state and cytokine release), but also and above all for the consequences that the need to contain the infection has on the management of cardiological urgencies. Aim of this review is therefore to summarize the relationship between the virus and the cardiovascular system.", "qid": 23, "docid": "myj3gw8d", "rank": 99, "score": 0.7749758958816528}, {"content": "Title: Cholesterol: A new game player accelerating endothelial injuries caused by SARS-CoV-2? Content: The pandemic of coronavirus disease 2019 (COVID-19) has become a global threat to public health. Functional impairments in multiple organs have been reported in COVID-19 including lungs, heart, kidney, liver, brain and vascular system. Patients with metabolic-associated preconditions such as hypertension, obesity and diabetes are susceptible to experience severe symptoms. The recent emerging evidence of coagulation disorders in COVID-19 suggests that vasculopathy appears to be an independent risk factor promoting disease severity and mortality of affected patients. We have recently found that the decreased levels of low-density lipoprotein cholesterols (LDL-c) correlate with disease severity in COVID-19 patients, indicating pathological interactions between dyslipidemia and vasculopothy in COVID-19 patients. However, this clinical manifestation has been unintentionally underestimated by physicians and scientific communities. As metabolic-associated morbidities are generally accompanied with endothelial cell (EC) dysfunctions, these pre-existing conditions may make ECs more vulnerable to SARS-CoV-2 attack. In this mini-review, we summarize the metabolic and vascular manifestations of COVID-19 with an emphasis on the association between changes in LDL-c levels and the development of severe symptoms as well as the pathophysiologic mechanisms underlying the synergistic effect of LDL-c and SARS-CoV-2 on EC injuries and vasculopathy.", "qid": 23, "docid": "q3rzhy2i", "rank": 100, "score": 0.7746346592903137}]}
{"query": "what kinds of complications related to COVID-19 are associated with diabetes", "hits": [{"content": "Title: The Association of Cardiovascular Diseases and Diabetes Mellitus with COVID-19 (SARS-CoV-2) and Their Possible Mechanisms Content: Coronavirus disease 2019 (COVID-19) has become a global concern and public health issue due to its higher infection and mortality rate; particularly, the risk is very higher among the patients who have cardiovascular diseases (CVD) and/or diabetes mellitus (DM). In this review, we analyzed the recently published literature on CVD and DM associated with COVD-19 infections and highlight their association with potential mechanisms. The findings revealed that without any previous history of CVD, the COVID-19 patients have developed some CVD complications like myocardial injury, cardiomyopathy, and venous thromboembolism after being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and required for those patients an emergency clinical support to be aware to manage those complications. Though the association between DM and COVID-19-induced severe complications is still unclear, the limited data predict that different markers like interleukin (IL)-1, IL-6, C-reactive protein, and D-dimer linked with the severity of COVID-19 infection in diabetic individuals. Further studies on a large scale are urgently needed to explore the underlying mechanisms between CVD, DM, and COVID-19 for better treatment.", "qid": 24, "docid": "9uymi395", "rank": 1, "score": 0.8619269132614136}, {"content": "Title: Practical recommendations for the management of diabetes in patients with COVID-19 Content: Summary Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20\u201350% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. We aim to briefly provide insight into potential mechanistic links between the novel coronavirus infection and diabetes, present practical management recommendations, and elaborate on the differential needs of several patient groups.", "qid": 24, "docid": "118x15od", "rank": 2, "score": 0.8618063926696777}, {"content": "Title: COVID-19 and diabetes: The why, the what and the how Content: BACKGROUND: The novel coronavirus SARS-CoV-2 has taken the world by storm. Alongside COVID-19, diabetes is a long-standing global epidemic. The diabetes population has been reported to suffer adverse outcomes if infected by COVID-19. The aim was to summarise information and resources available on diabetes and COVID-19, highlighting special measures that individuals with diabetes need to follow. METHODS: A search using keywords \u201cCOVID-19\u201d and \u201cDiabetes\u201d was performed using different sources, including PubMed and World Health Organization. RESULTS: COVID-19 may enhance complications in individuals with diabetes through an imbalance in angiotension-converting enzyme 2 (ACE2) activation pathways leading to an inflammatory response. ACE2 imbalance in the pancreas causes acute \u03b2-cell dysfunction and a resultant hyperglycemic state. These individuals may be prone to worsened COVID-19 complications including vasculopathy, coagulopathy as well as psychological stress. Apart from general preventive measures, remaining hydrated, monitoring blood glucose regularly and monitoring ketone bodies in urine if on insulin is essential. All this while concurrently maintaining physical activity and a healthy diet. Different supporting entities are being set up to help this population. CONCLUSION: COVID-19 is a top priority. It is important to remember that a substantial proportion of the world's population is affected by other co-morbidities such as diabetes. These require special attention during this pandemic to avoid adding on to the burden of countries' healthcare systems.", "qid": 24, "docid": "phf2sgw5", "rank": 3, "score": 0.8606085777282715}, {"content": "Title: Practical recommendations for the management of diabetes in patients with COVID-19 Content: Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20-50% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. We aim to briefly provide insight into potential mechanistic links between the novel coronavirus infection and diabetes, present practical management recommendations, and elaborate on the differential needs of several patient groups.", "qid": 24, "docid": "grz8hhal", "rank": 4, "score": 0.8602762222290039}, {"content": "Title: Diabetes and COVID-19: Global and Regional Perspectives Content: The coronavirus disease-2019 (COVID-19) has been designated as a highly contagious infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) since December 2019, when an outbreak of pneumonia cases emerged in Wuhan, China. The COVID-19 pandemic has led to a global health crisis, devastating the social, economic and political aspects of life. Many clinicians, health professionals, scientists, organizations, and governments have actively defeated COVID-19 and shared their experiences of the SARS-CoV2. Diabetes is one of the major risk factors for fatal outcomes from COVID-19. Patients with diabetes are vulnerable to infection because of hyperglycemia; impaired immune function; vascular complications; and comorbidities such as hypertension, dyslipidemia, and cardiovascular disease. In addition, angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV-2 in the human body. Hence, the use of angiotensin-directed medications in patients with diabetes requires attention. The severity and mortality from COVID-19 was significantly higher in patients with diabetes than in those without. Thus, the patients with diabetes should take precautions during the COVID-19 pandemic. Therefore, we review the current knowledge of COVID-19 including the global and regional epidemiology, virology, impact of diabetes on COVID-19, treatment of COVID-19, and standard of care in the management of diabetes during this critical period.", "qid": 24, "docid": "t8wg07ew", "rank": 5, "score": 0.8571853637695312}, {"content": "Title: COVID-19 and diabetes: The why, the what and the how Content: BACKGROUND: The novel coronavirus SARS-CoV-2 has taken the world by storm. Alongside COVID-19, diabetes is a long-standing global epidemic. The diabetes population has been reported to suffer adverse outcomes if infected by COVID-19. The aim was to summarise information and resources available on diabetes and COVID-19, highlighting special measures that individuals with diabetes need to follow. METHODS: A search using keywords \"COVID-19\" and \"Diabetes\" was performed using different sources, including PubMed and World Health Organization. RESULTS: COVID-19 may enhance complications in individuals with diabetes through an imbalance in angiotension-converting enzyme 2 (ACE2) activation pathways leading to an inflammatory response. ACE2 imbalance in the pancreas causes acute \u00df-cell dysfunction and a resultant hyperglycemic state. These individuals may be prone to worsened COVID-19 complications including vasculopathy, coagulopathy as well as psychological stress. Apart from general preventive measures, remaining hydrated, monitoring blood glucose regularly and monitoring ketone bodies in urine if on insulin is essential. All this while concurrently maintaining physical activity and a healthy diet. Different supporting entities are being set up to help this population. CONCLUSION: COVID-19 is a top priority. It is important to remember that a substantial proportion of the world's population is affected by other co-morbidities such as diabetes. These require special attention during this pandemic to avoid adding on to the burden of countries' healthcare systems.", "qid": 24, "docid": "wl1uihn3", "rank": 6, "score": 0.855003297328949}, {"content": "Title: Diabetes and COVID-19: Global and Regional Perspectives Content: Abstract The coronavirus disease-2019 (COVID-19) has been designated as a highly contagious infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) since December 2019, when an outbreak of pneumonia cases emerged in Wuhan, China. The COVID-19 pandemic has led to a global health crisis, devastating the social, economic and political aspects of life. Many clinicians, health professionals, scientists, organizations, and governments have actively defeated COVID-19 and shared their experiences of the SARS-CoV2. Diabetes is one of the major risk factors for fatal outcomes from COVID-19. Patients with diabetes are vulnerable to infection because of hyperglycemia; impaired immune function; vascular complications; and comorbidities such as hypertension, dyslipidemia, and cardiovascular disease. In addition, angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV-2 in the human body. Hence, the use of angiotensin-directed medications in patients with diabetes requires attention. The severity and mortality from COVID-19 was significantly higher in patients with diabetes than in those without. Thus, the patients with diabetes should take precautions during the COVID-19 pandemic. Therefore, we review the current knowledge of COVID-19 including the global and regional epidemiology, virology, impact of diabetes on COVID-19, treatment of COVID-19, and standard of care in the management of diabetes during this critical period.", "qid": 24, "docid": "cvltwjbz", "rank": 7, "score": 0.8546793460845947}, {"content": "Title: Coronavirus Disease 2019 and Diabetes: The Epidemic and the Korean Diabetes Association Perspective Content: Diabetes has been associated with more severe outcomes and higher mortality in coronavirus disease 2019 (COVID-19) patients compare to morbidity and mortality in patients without diabetes. Several mechanisms may play a role in this greater morbidity and mortality, especially uncontrolled hyperglycemia, an impaired immune system, pre-existing proinflammatory states, multiple comorbidities, and dysregulated angiotensin-converting enzyme 2 signaling. Thus, the diabetes medical community emergently needs to know about COVID-19 and its effects on patients with diabetes, as they must take precautions to carefully manage these patients during the COVID-19 pandemic. The Korean Diabetes Association provides some guidance and practical recommendations for the management of diabetes during the pandemic. This report provides insight into the association between diabetes and COVID-19, proper management of diabetes in patients with COVID-19 and an official suggestion by the Korean Diabetes Association for managing the COVID-19 outbreak.", "qid": 24, "docid": "u1c9pusk", "rank": 8, "score": 0.8535933494567871}, {"content": "Title: COVID-19 in diabetic patients: Related risks and specifics of management Content: Diabetes is among the most frequently reported comorbidities in patients infected with COVID-19. According to current data, diabetic patients do not appear to be at increased risk of contracting SARS-CoV-2 compared to the general population. On the other hand, diabetes is a risk factor for developing severe and critical forms of COVID-19, the latter requiring admission to an intensive care unit and/or use of invasive mechanical ventilation, with high mortality rates. The characteristics of diabetic patients at risk for developing severe and critical forms of COVID-19, as well as the prognostic impact of diabetes on the course of COVID-19, are under current investigation. Obesity, the main risk factor for incident type 2 diabetes, is more common in patients with critical forms of COVID-19 requiring invasive mechanical ventilation. On the other hand, COVID-19 is usually associated with poor glycemic control and a higher risk of ketoacidosis in diabetic patients. There are currently no recommendations in favour of discontinuing antihypertensive medications that interact with the renin-angiotensin-aldosterone system. Metformin and SGLT2 inhibitors should be discontinued in patients with severe forms of COVID-19 owing to the risks of lactic acidosis and ketoacidosis. Finally, we advise for systematic screening for (pre)diabetes in patients with proven COVID-19 infection.", "qid": 24, "docid": "lfdeowsl", "rank": 9, "score": 0.8515665531158447}, {"content": "Title: COVID-19 in diabetic patients: related risks and specifics of management Content: Abstract Diabetes is among the most frequently reported comorbidities in patients infected with COVID-19. According to current data, diabetic patients do not appear to be at increased risk of contracting SARS-CoV-2 compared to the general population. On the other hand, diabetes is a risk factor for developing severe and critical forms of COVID-19, the latter requiring admission to an intensive care unit and/or use of invasive mechanical ventilation, with high mortality rates. The characteristics of diabetic patients at risk for developing severe and critical forms of COVID-19, as well as the prognostic impact of diabetes on the course of COVID-19, are under current investigation. Obesity, the main risk factor for incident type 2 diabetes, is more common in patients with critical forms of COVID-19 requiring invasive mechanical ventilation. On the other hand, COVID-19 is usually associated with poor glycemic control and a higher risk of ketoacidosis in diabetic patients. There are currently no recommendations in favor of discontinuing antihypertensive medications that interact with the renin-angiotensin-aldosterone system. Metformin and SGLT2 inhibitors should be discontinued in patients with severe forms of COVID-19 owing to the risks of lactic acidosis and ketoacidosis. Finally, we advise for systematic screening for (pre)diabetes in patients with proven COVID-19 infection.", "qid": 24, "docid": "0tsefy6p", "rank": 10, "score": 0.8512402772903442}, {"content": "Title: COVID-19 and diabetes: Is there enough evidence? Content: The pandemic of COVID-19, a disease caused by a novel coronavirus SARS-CoV-2, is associated with significant morbidity and mortality. Recent data showed that hypertension, diabetes mellitus, cardiovascular diseases, and chronic obstructive pulmonary disease were the most prevalent comorbidities in COVID-19 patients. Additionally, data indicate that hypertension, diabetes, and cardiovascular diseases are important risk factors for progression and unfavorable outcome in COVID-19 patients. There is only limited amount of data regarding follow-up of these patients, and they provided conflicting results. The main limitation is a small number of participants and particularly those who experienced primary composite outcome (admission in intensive care unit, use of mechanical ventilation, or death). Additionally, the limited number of patients was essential obstacle for performing analysis that would include many confounding factors such as advanced age, smoking status, and obesity and potentially change conclusion. So far, there is no study that demonstrated independent predictive value of diabetes on mortality in COVID-19 patients, but there are many speculations about the association between diabetes and susceptibility to novel coronavirus, as well as its impact on progression and prognosis of COVID-19. The aim of this review article was to summarize the current knowledge about the relationship between diabetes and COVID-19 and its role in outcome in these patients.", "qid": 24, "docid": "f0pwjxfv", "rank": 11, "score": 0.8509065508842468}, {"content": "Title: COVID\u201019 and diabetes: Is there enough evidence? Content: The pandemic of COVID\u201019, a disease caused by a novel coronavirus SARS\u2010CoV\u20102, is associated with significant morbidity and mortality. Recent data showed that hypertension, diabetes mellitus, cardiovascular diseases, and chronic obstructive pulmonary disease were the most prevalent comorbidities in COVID\u201019 patients. Additionally, data indicate that hypertension, diabetes, and cardiovascular diseases are important risk factors for progression and unfavorable outcome in COVID\u201019 patients. There is only limited amount of data regarding follow\u2010up of these patients, and they provided conflicting results. The main limitation is a small number of participants and particularly those who experienced primary composite outcome (admission in intensive care unit, use of mechanical ventilation, or death). Additionally, the limited number of patients was essential obstacle for performing analysis that would include many confounding factors such as advanced age, smoking status, and obesity and potentially change conclusion. So far, there is no study that demonstrated independent predictive value of diabetes on mortality in COVID\u201019 patients, but there are many speculations about the association between diabetes and susceptibility to novel coronavirus, as well as its impact on progression and prognosis of COVID\u201019. The aim of this review article was to summarize the current knowledge about the relationship between diabetes and COVID\u201019 and its role in outcome in these patients.", "qid": 24, "docid": "sntawlnf", "rank": 12, "score": 0.8486889004707336}, {"content": "Title: Diabetes, infection risk and COVID-19 Content: BACKGROUND: Individuals with diabetes are at a greater risk of hospitalization and mortality resulting from viral, bacterial, and fungal infections. The coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread quickly to more than 213 countries and claimed 395,779 lives as of June 7, 2020. Notably, in several studies, diabetes is one of the most reported comorbidities in patients with severe COVID-19. SCOPE OF REVIEW: In this review, I summarize the clinical data on the risk for infectious diseases in individuals with diabetes while highlighting the mechanisms for altered immune regulation. The focus is on coronaviruses. Based on the new clinical data obtained from COVID-19 patients, a discussion of mechanisms, such as cytokine storm, pulmonary and endothelial dysfunction, and hypercoagulation, that may render individuals with diabetes more vulnerable to COVID-19 is provided. MAJOR CONCLUSIONS: Epidemiological studies show that poorly controlled diabetes is a risk factor for various infectious diseases. Given the global burden of diabetes and the pandemic nature of coronaviruses, understanding how diabetes affects COVID-19 severity is critical to designing tailored treatments and clinical management of individuals affected by diabetes.", "qid": 24, "docid": "x9h81ij0", "rank": 13, "score": 0.8467235565185547}, {"content": "Title: COVID-19 and diabetes: What does the clinician need to know? Content: COVID-19 and diabetes are currently two global pandemics. Epidemiological studies indicate that diabetes is the second most common comorbidity in COVID-19. This review aims to summarize currently available data about prevalence, possible pathophysiological mechanisms and management of patients with diabetes and COVID-19.", "qid": 24, "docid": "ff04vt1d", "rank": 14, "score": 0.8466289043426514}, {"content": "Title: Infecci\u00f3n por coronavirus en pacientes con diabetes Content: Diabetes mellitus is a complex, multifactorial, chronic disease characterized by impaired metabolism of glucose, fats and proteins Patients who suffer from it frequently have hyperglycemia and coronary artery disease is the leading cause of death The comorbidities associated with diabetes are overweight and obesity, systemic arterial hypertension, atherogenic dyslipidemia and in some patients peripheral vascular disease, kidney damage, neuropathy and retinopathy Chronic lack of control of the disease is associated with increased susceptibility to infections, which generally have few symptoms, but hyperglycemia is generally magnified, which worsens the course of infections Since December 2019, when the disease caused by one of the coronaviruses (coronavirus 2 of severe acute respiratory syndrome, SARS-CoV-2) was identified and has been called coronavirus disease 2019 (COVID-19), there have been some reports that associate the presence of diabetes with an increased risk of mortality In this review article we have focused on four specific points: 1) epidemiology of the prevalence and mortality of COVID 19 in the general population and in the population with type 2 diabetes mellitus;2) pathophysiology related to the binding of SARS-CoV-2 to receptors in subjects with diabetes;3) the immune response induced by SARS-CoV-2, and 4) the outpatient and hospital treatment recommended in patients with diabetes who become infected with SARS-CoV-2", "qid": 24, "docid": "5ps6pw6c", "rank": 15, "score": 0.8462615013122559}, {"content": "Title: Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations Content: Abstract Background and aims High prevalence of diabetes makes it an important comorbidity in patients with COVID-19. We sought to review and analyze the data regarding the association between diabetes and COVID-19, pathophysiology of the disease in diabetes and management of patients with diabetes who develop COVID-19 infection. Methods PubMed database and Google Scholar were searched using the key terms \u2018COVID-19\u2019, \u2018SARS-CoV-2\u2019, \u2018diabetes\u2019, \u2018antidiabetic therapy\u2019 up to April 2, 2020. Full texts of the retrieved articles were accessed. Results There is evidence of increased incidence and severity of COVID-19 in patients with diabetes. COVID-19 could have effect on the pathophysiology of diabetes. Blood glucose control is important not only for patients who are infected with COVID-19, but also for those without the disease. Innovations like telemedicine are useful to treat patients with diabetes in today\u2019s times.", "qid": 24, "docid": "bqxyb61p", "rank": 16, "score": 0.8459353446960449}, {"content": "Title: Challenging Issues in the Management of Cardiovascular Risk Factors in Diabetes During the COVID-19 Pandemic: A Review of Current Literature Content: The COVID-19 outbreak was declared a pandemic on March 2020. Many patients with SARS-CoV-2 infection have underlying chronic medical conditions such as diabetes, cardiovascular disease (CVD), and hypertension. Patient-related outcomes are worse if there are associated comorbidities. We do not have enough evidence regarding the most appropriate management of patients with diabetes during COVID-19 infection. Insulin resistance and CVD together increase the inflammatory state of the body, which can contribute to and perhaps mediate the increase of COVID-19 severity. Hence, in addition to management of dysglycemia, other CVD risk factors should be targeted. We explore the possible pathophysiologic links between diabetes and COVID-19 and discuss various options to treat dysglycemia, hypertension, and dyslipidemia in the era of COVID-19.", "qid": 24, "docid": "ntv2g7ne", "rank": 17, "score": 0.8451230525970459}, {"content": "Title: Laboratory findings that predict a poor prognosis in COVID-19 patients with diabetes: A meta-analysis Content: Diabetes is one of the main comorbidities in patients infected with the SARS-CoV-2 virus, the causative agent of the new coronavirus disease 2019 (COVID-19). Because the presence of diabetes and COVID-19 in the same patient is related to a poor clinical prognosis and a high probability of death, it is necessary to determine what findings allow us to predict a good or bad resolution of the disease in order to opt for a traditional treatment or a more incisive one. In this way, in the present work we analyze which laboratory parameters showed differences in patients with COVID-19 and diabetes who recovered and in those who had complications or died.", "qid": 24, "docid": "tsd6sjcx", "rank": 18, "score": 0.8450402021408081}, {"content": "Title: Association of diabetes mellitus with disease severity and prognosis in COVID-19: A retrospective cohort study Content: AIMS: The 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, China, and was characterized as a pandemic by the World Health Organization. Diabetes is an established risk associated with poor clinical outcomes, but the association of diabetes with COVID-19 has not been reported yet. METHODS: In this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital in Wuhan, China, recruited from January 29 to February 12, 2020. The clinical features, treatment strategies and prognosis data were collected and analyzed. Prognosis was followed up until March 12, 2020. RESULTS: Of the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease conditions with more complications, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR] = 3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR = 1.19; 95% CI: 1.08, 1.31) were associated with the fatality due to COVID-19, adjusting for potential confounders. CONCLUSIONS: Diabetes mellitus is associated with increased disease severity and a higher risk of mortality in patients with COVID-19.", "qid": 24, "docid": "8ydwzl4z", "rank": 19, "score": 0.843950092792511}, {"content": "Title: Diabetes, Obesity and COVID-19: A Complex Interplay Content: With the accumulation of observational data showing association of metabolic comorbidities with adverse outcomes from COVID-19, there is a need to disentangle the contributions of pre-existing macro- and microvascular disease, obesity and glycaemia. This article outlines the complex mechanistic and clinical interplay between diabetes and COVID-19, the clinical and research questions that arise from these; and the types of studies needed to answer them. The authors are clinicians and academics working in diabetes and obesity medicine, but the article is pitched to an audience of generalists with clinical experience or interest in management of COVID-19. This article is protected by copyright. All rights reserved.", "qid": 24, "docid": "msr78qwy", "rank": 20, "score": 0.8436915278434753}, {"content": "Title: Prevention and management of COVID-19 among patients with diabetes: an appraisal of the literature Content: The coronavirus disease 2019 (COVID-19) pandemic has emerged as one of the greatest challenges faced by humankind in the recent past. People with diabetes and related comorbidities are at increased risk of its complications and of COVID-19-related death. Older age, multi-morbidity, hyperglycaemia, cardiac injury and severe inflammatory response are predictors of poor outcome. The complex interplay between COVID-19, diabetes and the effects of related therapies is being explored. Most patients experience a mild illness with COVID-19, while people with diabetes are at increased risk of severe disease. Optimising glycaemic control and adopting measures to prevent disease spread are critical aspects. The management of mild disease is supportive, while very many immunomodulatory and antiviral therapies are being investigated for the treatment of severe disease. Several of these agents have specific considerations for use in people with diabetes. Since mass population lockdowns are considered a key step in controlling disease spread, it follows that, in addition to the direct vulnerability to severe COVID-19, people with diabetes can be affected by limited access to healthcare, insulin, other medications and blood glucose monitoring equipment. Measures to prevent disease spread at the individual and community level are the key to mitigating the rapidly escalating pandemic, while agents for chemoprophylaxis and vaccines are being explored. People with diabetes should be recognised as a vulnerable group for complicated disease and are at risk during times of disturbed social systems. Strategies are needed to safeguard the health of patients with diabetes during the pandemic. This review summarises the current knowledge and perceived challenges for prevention and management of COVID-19 in people with diabetes.", "qid": 24, "docid": "e5mf6qdo", "rank": 21, "score": 0.8433650135993958}, {"content": "Title: Association of Diabetes Mellitus with Disease Severity and Prognosis in COVID-19: A Retrospective Cohort Study Content: Abstract The 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, China, and was characterized as a pandemic by the World Health Organization. Diabetes is an established risk associated with poor clinical outcomes, but the association of diabetes with COVID-19 has not been reported yet. Methods In this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital in Wuhan, China, recruited from January 29 to February 12, 2020. The clinical features, treatment strategies and prognosis data were collected and analyzed. Prognosis was followed up until March 12, 2020. Results Of the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease conditions with more complications, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR]=3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR=1.19; 95% CI: 1.08, 1.31) were associated with the fatality due to COVID-19, adjusting for potential confounders. Conclusions Diabetes mellitus is associated with increased disease severity and a higher risk of mortality in patients with COVID-19.", "qid": 24, "docid": "c2jm0g88", "rank": 22, "score": 0.8431458473205566}, {"content": "Title: COVID 19: Diabetes and Obesity API-ICP Recommendations. Content: Diabetes and Obesity are major risk factors which confer vulnerability to Covid 19 . Diabetes has immune defects which makes the individual susceptible to infections and covid 19 is no exception . Also covid 19 can cause pancreatic damage as well as stress hyperglycaemia in hospitals which may need Insulin . Among diabetes male gender,elderly,hypertension ,heart disease and chronic renal disease are more vulbwdvale to covid 19 and need strict supervision . Diabetes management in hospitalised situation merits early diabetes specific nutrition with Insulin. Adherence to lifestyle with self monitoring of blood glucose and adequate supply of Insulin and Oral antidiabetic agents is encouraged.", "qid": 24, "docid": "25v7qies", "rank": 23, "score": 0.8428877592086792}, {"content": "Title: COVID 19: Diabetes and Obesity API-ICP Recommendations Content: Diabetes and Obesity are major risk factors which confer vulnerability to Covid 19 . Diabetes has immune defects which makes the individual susceptible to infections and covid 19 is no exception . Also covid 19 can cause pancreatic damage as well as stress hyperglycaemia in hospitals which may need Insulin . Among diabetes male gender,elderly,hypertension ,heart disease and chronic renal disease are more vulbwdvale to covid 19 and need strict supervision . Diabetes management in hospitalised situation merits early diabetes specific nutrition with Insulin. Adherence to lifestyle with self monitoring of blood glucose and adequate supply of Insulin and Oral antidiabetic agents is encouraged.", "qid": 24, "docid": "e582ueut", "rank": 24, "score": 0.8428876996040344}, {"content": "Title: Considerations for people with diabetes during the Coronavirus Disease (COVID-19) Pandemic Content: INTRODUCTION: The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) continues to cause havoc globally, resulting in unprecedented healthcare, societal and economic disruption. People with diabetes have been shown to be at higher risk of complications and death when exposed to pneumonia, influenza and other coronaviruses. Despite pandemic scale infection, there is currently limited understanding on the potential impact of SARS-CoV-2 on people with diabetes. AIMS: (1) To characterise the outcomes of SARS-CoV-2 for people with diabetes and (2) add value to current recommendations for healthcare providers and people with diabetes to encourage optimal management. METHODS: A search of PubMed, Embase and MEDLINE to March 2020 was undertaken, using search terms pertaining to diabetes, coronavirus and acute respiratory distress syndrome (ARDS). We briefly reviewed the epidemiology and pathophysiology of SARS-CoV in the context of diabetes. CONCLUSION: People with diabetes are at greater risk of severe infection and death with COVID-19. COVID-19 has significantly impacted the daily lives of individuals living with diabetes through financial implications, food and medication scarcity and its burden on mental health. In Australia, delivery of medical care has been adapted to reduce the risk of transmission, with a particular emphasis on telehealth and remote monitoring.", "qid": 24, "docid": "syqmhjgr", "rank": 25, "score": 0.8422720432281494}, {"content": "Title: Diabetes, Infection Risk And Covid-19 Content: Abstract Background Individuals with diabetes are at a greater risk of hospitalization and mortality resulting from viral, bacterial and fungal infections. The Coronavirus Disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread quickly to more than 213 countries across the world and has claimed 395,779 lives as of June 7, 2020. Notably, in several studies, diabetes is one of the most reported comorbidities in patients with severe COVID-19. Scope of Review In this review, I will summarize the clinical data on the risk for infectious diseases in individuals with diabetes, highlighting the mechanisms for altered immune regulation. A special focus will be given to coronaviruses. In the light of the new clinical data obtained from COVID-19 patients, mechanisms such as cytokine storm, pulmonary and endothelial dysfunction, hypercoagulation that may render individuals with diabetes more vulnerable to COVID-19 will be discussed in the end. Major Conclusions Epidemiological studies show that poorly controlled diabetes is a risk factor for various infectious diseases. Given the global burden of diabetes and pandemic nature of coronaviruses, understanding how diabetes affects COVID-19 severity is critical to design tailored treatments and clinical management of individuals affected by diabetes.", "qid": 24, "docid": "12q9jjbb", "rank": 26, "score": 0.8414369225502014}, {"content": "Title: Clinical Characteristics and Outcomes of Type 2 Diabetes Patients Infected with COVID-19: A Retrospective Study Content: Diabetes and its related metabolic disorders have been reported as the leading comorbidities in patients with coronavirus disease 2019 (COVID-19). This clinical study aims to investigate the clinical features, radiographic and laboratory tests, complications, treatments, and clinical outcomes in COVID-19 patients with or without diabetes. This retrospective study included 208 hospitalized patients (\u2265 45 years old) with laboratory-confirmed COVID-19 during the period between 12 January and 25 March 2020. Information from the medical record, including clinical features, radiographic and laboratory tests, complications, treatments, and clinical outcomes, were extracted for the analysis. 96 (46.2%) patients had comorbidity with type 2 diabetes. In COVID-19 patients with type 2 diabetes, the coexistence of hypertension (58.3% vs. 31.2%), coronary heart disease (17.1% vs. 8.0%), and chronic kidney diseases (6.2% vs. 0%) was significantly higher than in COVID-19 patients without type 2 diabetes. The frequency and degree of abnormalities in computed tomography (CT) chest scans in COVID-19 patients with type 2 diabetes were markedly increased, including ground-glass opacity (85.6% vs. 64.9%, P < 0.001) and bilateral patchy shadowing (76.7% vs. 37.8%, P < 0.001). In addition, the levels of blood glucose (7.23 mmol\u00b7L(-1) (interquartile range (IQR): 5.80\u20139.29) vs. 5.46 mmol\u00b7L(-1) (IQR: 5.00\u20136.46)), blood low-density lipoprotein cholesterol (LDL-C) (2.21 mmol\u00b7L(-1) (IQR: 1.67\u20132.76) vs. 1.75 mmol\u00b7L(-1) (IQR: 1.27\u20132.01)), and systolic pressure (130 mmHg (IQR: 120\u2013142) vs. 122 mmHg (IQR: 110\u2013137), P = 0.001) in COVID-19 patients with diabetes were significantly higher than in patients without diabetes (P < 0.001). The coexistence of type 2 diabetes and other metabolic disorders is common in patients with COVID-19, which may potentiate the morbidity and aggravate COVID-19 progression. Optimal management of the metabolic hemostasis of glucose and lipids is the key to ensuring better clinical outcomes. Increased clinical vigilance is warranted for COVID-19 patients with diabetes and other metabolic diseases that are fundamental and chronic conditions.", "qid": 24, "docid": "fhpvshr2", "rank": 27, "score": 0.8404895067214966}, {"content": "Title: SARS-CoV-2 disease severity and diabetes: why the connection and what is to be done? Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus responsible for the current coronavirus disease 2019 (COVID-19) pandemic, has infected over 3.5 million people all over the world since the first case was reported from Wuhan, China 5 months ago. As more epidemiological data regarding COVID-19 patients is acquired, factors that increase the severity of the infection are being identified and reported. One of the most consistent co-morbidities associated with worse outcome in COVID-19 patients is diabetes, along with age and cardiovascular disease. Studies on the association of diabetes with other acute respiratory infections, namely SARS, MERS, and Influenza, outline what seems to be an underlying factor in diabetic patients that makes them more susceptible to complications. In this review we summarize what we think may be the factors driving this pattern between diabetes, aging and poor outcomes in respiratory infections. We also review therapeutic considerations and strategies for treatment of COVID-19 in diabetic patients, and how the additional challenge of this co-morbidity requires attention to glucose homeostasis so as to achieve the best outcomes possible for patients.", "qid": 24, "docid": "5zb96j4a", "rank": 28, "score": 0.8404202461242676}, {"content": "Title: Prevention and management of COVID-19 among patients with diabetes: an appraisal of the literature Content: The coronavirus disease 2019 (COVID-19) pandemic has emerged as one of the greatest challenges faced by humankind in the recent past. People with diabetes and related comorbidities are at increased risk of its complications and of COVID-19-related death. Older age, multi-morbidity, hyperglycaemia, cardiac injury and severe inflammatory response are predictors of poor outcome. The complex interplay between COVID-19, diabetes and the effects of related therapies is being explored. Most patients experience a mild illness with COVID-19, while people with diabetes are at increased risk of severe disease. Optimising glycaemic control and adopting measures to prevent disease spread are critical aspects. The management of mild disease is supportive, while very many immunomodulatory and antiviral therapies are being investigated for the treatment of severe disease. Several of these agents have specific considerations for use in people with diabetes. Since mass population lockdowns are considered a key step in controlling disease spread, it follows that, in addition to the direct vulnerability to severe COVID-19, people with diabetes can be affected by limited access to healthcare, insulin, other medications and blood glucose monitoring equipment. Measures to prevent disease spread at the individual and community level are the key to mitigating the rapidly escalating pandemic, while agents for chemoprophylaxis and vaccines are being explored. People with diabetes should be recognised as a vulnerable group for complicated disease and are at risk during times of disturbed social systems. Strategies are needed to safeguard the health of patients with diabetes during the pandemic. This review summarises the current knowledge and perceived challenges for prevention and management of COVID-19 in people with diabetes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-020-05164-x) contains peer-reviewed but unedited supplementary material including a slideset of the figures for download, which is available to authorised users.", "qid": 24, "docid": "15hqzcig", "rank": 29, "score": 0.8402104377746582}, {"content": "Title: Coronavirus infection in patients with diabetes. Content: Diabetes mellitus is a complex, multifactorial, chronic disease characterized by impaired metabolism of glucose, fats and proteins. Patients who suffer from it frequently have hyperglycemia and coronary artery disease is the leading cause of death. The comorbidities associated with diabetes are overweight and obesity, systemic arterial hypertension, atherogenic dyslipidemia and in some patients peripheral vascular disease, kidney damage, neuropathy and retinopathy. Chronic lack of control of the disease is associated with increased susceptibility to infections, which generally have few symptoms, but hyperglycemia is generally magnified, which worsens the course of infections. Since December 2019, when the disease caused by one of the coronaviruses (coronavirus 2 of severe acute respiratory syndrome, SARS-CoV-2) was identified and has been called coronavirus disease 2019 (COVID-19), there have been some reports that associate the presence of diabetes with an increased risk of mortality. In this review article we have focused on four specific points: 1) epidemiology of the prevalence and mortality of COVID 19 in the general population and in the population with type 2 diabetes mellitus; 2) pathophysiology related to the binding of SARS-CoV-2 to receptors in subjects with diabetes; 3) the immune response induced by SARS-CoV-2, and 4) the outpatient and hospital treatment recommended in patients with diabetes who become infected with SARS-CoV-2.", "qid": 24, "docid": "ifmwfm43", "rank": 30, "score": 0.8396185636520386}, {"content": "Title: Diabetes and covid-19: more than the sum of two morbidities Content: The coronavirus disease 2019 (covid-19) pandemic has caused a public health emergency worldwide. Risk, severity and mortality of the disease have been associated with non-communicable chronic diseases, such as diabetes mellitus. Accumulated evidence has caused great concern in countries with high prevalence of this morbidity, such as Brazil. This text shows the picture of diabetes in Brazil, followed by epidemiological data and explanatory hypothesis for the association between diabetes and covid-19. We emphasized how the burden of these two morbidities in a middle-income country has aggravated this pandemic scenario. The comprehension of this association and biological plausibility may help face this pandemic and future challenges.", "qid": 24, "docid": "lxjgysp9", "rank": 31, "score": 0.8377094864845276}, {"content": "Title: Clinical Characteristics and Risk Factors for Mortality of COVID-19 Patients With Diabetes in Wuhan, China: A Two-Center, Retrospective Study. Content: OBJECTIVE Diabetes is common in COVID-19 patients and associated with unfavorable outcomes. We aimed to describe the characteristics and outcomes and to analyze the risk factors for in-hospital mortality of COVID-19 patients with diabetes. RESEARCH DESIGN AND METHODS This two-center retrospective study was performed at two tertiary hospitals in Wuhan, China. Confirmed COVID-19 patients with diabetes (N = 153) who were discharged or died from 1 January 2020 to 8 March 2020 were identified. One sex- and age-matched COVID-19 patient without diabetes was randomly selected for each patient with diabetes. Demographic, clinical, and laboratory data were abstracted. Cox proportional hazards regression analyses were performed to identify the risk factors associated with the mortality in these patients. RESULTS Of 1,561 COVID-19 patients, 153 (9.8%) had diabetes, with a median age of 64.0 (interquartile range 56.0-72.0) years. A higher proportion of intensive care unit admission (17.6% vs. 7.8%, P = 0.01) and more fatal cases (20.3% vs. 10.5%, P = 0.017) were identified in COVID-19 patients with diabetes than in the matched patients. Multivariable Cox regression analyses of these 306 patients showed that hypertension (hazard ratio [HR] 2.50, 95% CI 1.30-4.78), cardiovascular disease (HR 2.24, 95% CI 1.19-4.23), and chronic pulmonary disease (HR 2.51, 95% CI 1.07-5.90) were independently associated with in-hospital death. Diabetes (HR 1.58, 95% CI 0.84-2.99) was not statistically significantly associated with in-hospital death after adjustment. Among patients with diabetes, nonsurvivors were older (76.0 vs. 63.0 years), most were male (71.0% vs. 29.0%), and were more likely to have underlying hypertension (83.9% vs. 50.0%) and cardiovascular disease (45.2% vs. 14.8%) (all P values <0.05). Age \u226570 years (HR 2.39, 95% CI 1.03-5.56) and hypertension (HR 3.10, 95% CI 1.14-8.44) were independent risk factors for in-hospital death of patients with diabetes. CONCLUSIONS COVID-19 patients with diabetes had worse outcomes compared with the sex- and age-matched patients without diabetes. Older age and comorbid hypertension independently contributed to in-hospital death of patients with diabetes.", "qid": 24, "docid": "4fqsx5y5", "rank": 32, "score": 0.8369019031524658}, {"content": "Title: Clinical Characteristics and Risk Factors for Mortality of COVID-19 Patients With Diabetes in Wuhan, China: A Two-Center, Retrospective Study Content: OBJECTIVE: Diabetes is common in COVID-19 patients and associated with unfavorable outcomes. We aimed to describe the characteristics and outcomes and to analyze the risk factors for in-hospital mortality of COVID-19 patients with diabetes. RESEARCH DESIGN AND METHODS: This two-center retrospective study was performed at two tertiary hospitals in Wuhan, China. Confirmed COVID-19 patients with diabetes (N = 153) who were discharged or died from 1 January 2020 to 8 March 2020 were identified. One sex- and age-matched COVID-19 patient without diabetes was randomly selected for each patient with diabetes. Demographic, clinical, and laboratory data were abstracted. Cox proportional hazards regression analyses were performed to identify the risk factors associated with the mortality in these patients. RESULTS: Of 1,561 COVID-19 patients, 153 (9.8%) had diabetes, with a median age of 64.0 (interquartile range 56.0-72.0) years. A higher proportion of intensive care unit admission (17.6% vs. 7.8%, P = 0.01) and more fatal cases (20.3% vs. 10.5%, P = 0.017) were identified in COVID-19 patients with diabetes than in the matched patients. Multivariable Cox regression analyses of these 306 patients showed that hypertension (hazard ratio [HR] 2.50, 95% CI 1.30-4.78), cardiovascular disease (HR 2.24, 95% CI 1.19-4.23), and chronic pulmonary disease (HR 2.51, 95% CI 1.07-5.90) were independently associated with in-hospital death. Diabetes (HR 1.58, 95% CI 0.84-2.99) was not statistically significantly associated with in-hospital death after adjustment. Among patients with diabetes, nonsurvivors were older (76.0 vs. 63.0 years), most were male (71.0% vs. 29.0%), and they were more likely to have underlying hypertension (83.9% vs. 50.0%) and cardiovascular disease (45.2% vs. 14.8%) (all P values <0.05). Age &#8805;70 years (HR 2.39, 95% CI 1.03-5.56) and hypertension (HR 3.10, 95% CI 1.14-8.44) were independent risk factors for in-hospital death of patients with diabetes. CONCLUSIONS: COVID-19 patients with diabetes had worse outcomes compared with the sex- and age-matched patients without diabetes. Older age and comorbid hypertension independently contributed to in-hospital death of patients with diabetes.", "qid": 24, "docid": "1pwlctxb", "rank": 33, "score": 0.8365060091018677}, {"content": "Title: Diabetes, Obesity and COVID\u201019: A Complex Interplay Content: With the accumulation of observational data showing association of metabolic comorbidities with adverse outcomes from COVID\u201019, there is a need to disentangle the contributions of pre\u2010existing macro\u2010 and microvascular disease, obesity and glycaemia. This article outlines the complex mechanistic and clinical interplay between diabetes and COVID\u201019, the clinical and research questions that arise from these; and the types of studies needed to answer them. The authors are clinicians and academics working in diabetes and obesity medicine, but the article is pitched to an audience of generalists with clinical experience or interest in management of COVID\u201019. This article is protected by copyright. All rights reserved.", "qid": 24, "docid": "aar38bo6", "rank": 34, "score": 0.8363928198814392}, {"content": "Title: COVID-19 Pandemic, Corona Viruses, and Diabetes Mellitus. Content: The pandemic of COVID-19, a disease caused by a novel coronavirus (CoV), SARS-CoV-2, is causing substantial morbidity and mortality. Older age and presence of diabetes mellitus, hypertension, and obesity significantly increases the risk for hospitalization and death in COVID-19 patients. In this Perspective, informed by the studies on severe acute respiratory syndrome, SARS-CoV, and Middle East respiratory syndrome, MERS-CoV, and the current literature on SARS-CoV-2, we discuss potential mechanisms by which diabetes modulates the host-viral interactions and host-immune responses. We hope to highlight gaps in knowledge that require further studies pertinent to COVID-19 in patients with diabetes.", "qid": 24, "docid": "22vz79nz", "rank": 35, "score": 0.8363367319107056}, {"content": "Title: Diabetes Epidemiology in the COVID-19 Pandemic Content: Diabetes has been identified as an important risk factor for mortality and rates of progression to acute respiratory distress syndrome (ARDS) in hospitalized patients with coronavirus disease 2019 (COVID-19). However, many recent reports on this topic reflect hurried approaches and have lacked careful epidemiologic design, conduct, and analysis. Features of prior studies have posed problems for our understanding of the true contribution of diabetes and other underlying comorbidities to prognosis in COVID-19. In this Perspective, we discuss some of the challenges of interpreting the current literature on diabetes and COVID-19 and discuss opportunities for future epidemiologic studies. We contend that the COVID-19 pandemic is a defining moment for the field of epidemiology and that diabetes epidemiology should play a significant role.", "qid": 24, "docid": "vhmga8rh", "rank": 36, "score": 0.8334970474243164}, {"content": "Title: Diabetes Epidemiology in the COVID-19 Pandemic. Content: Diabetes has been identified as an important risk factor for mortality and rates of progression to acute respiratory distress syndrome (ARDS) in hospitalized patients with coronavirus disease 2019 (COVID-19). However, many recent reports on this topic reflect hurried approaches and have lacked careful epidemiologic design, conduct, and analysis. Features of prior studies have posed problems for our understanding of the true contribution of diabetes and other underlying comorbidities to prognosis in COVID-19. In this Perspective, we discuss some of the challenges of interpreting the current literature on diabetes and COVID-19 and discuss opportunities for future epidemiologic studies. We contend that the COVID-19 pandemic is a defining moment for the field of epidemiology and that diabetes epidemiology should play a significant role.", "qid": 24, "docid": "ina400b0", "rank": 37, "score": 0.8334970474243164}, {"content": "Title: Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication. Content: OBJECTIVE Diabetes is one of the most distinct comorbidities of COVID-19. Here, we describe the clinical characteristics of and outcomes in patients with diabetes in whom COVID-19 has been confirmed or clinically diagnosed (with typical features on lung imaging and symptoms), and their association with glucose-lowering or blood pressure-lowering medications. RESEARCH DESIGN AND METHODS In this retrospective study involving 904 patients with COVID-19 (136 with diabetes, mostly type 2 diabetes), clinical and laboratory characteristics were collected and compared between the group with diabetes and the group without diabetes, and between groups taking different medications. Logistic regression was used in order to explore risk factors associated with mortality or poor prognosis. RESULTS The proportion of comorbid diabetes is similar between cases of confirmed and of clinically diagnosed COVID-19. Risk factors for higher mortality of patients with diabetes and COVID-19 were older age (adjusted odds ratio [aOR] 1.09 [95% CI 1.04, 1.15] per year increase; P = 0.001) and elevated C-reactive protein (aOR 1.12 [95% CI 1.00, 1.24]; P = 0.043). Insulin usage (aOR 3.58 [95% CI 1.37, 9.35]; P = 0.009) was associated with poor prognosis. Clinical outcomes of those who use an ACE inhibitor (ACEI) or angiotensin II type-I receptor blocker (ARB) were comparable with those of patients who do not use ACEI/ARB among patients with diabetes and hypertension who have COVID-19. CONCLUSIONS C-reactive protein may help to identify patients with diabetes who are at greater risk of dying during hospitalization. Older patients with diabetes were prone to death related to COVID-19. Attention needs to be paid to patients with diabetes and COVID-19 who use insulin. ACEI/ARB use showed no significant impact on patients with diabetes and hypertension who have COVID-19.", "qid": 24, "docid": "p536yuvi", "rank": 38, "score": 0.8322581052780151}, {"content": "Title: Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis Content: BACKGROUND: Many studies on COVID-19 have reported diabetes to be associated with severe disease and mortality, however, the data is conflicting. The objectives of this meta-analysis were to explore the relationship between diabetes and COVID-19 mortality and severity, and to determine the prevalence of diabetes in patients with COVID-19. METHODS: We searched the PubMed for case-control studies in English, published between Jan 1 and Apr 22, 2020, that had data on diabetes in patients with COVID-19. The frequency of diabetes was compared between patients with and without the composite endpoint of mortality or severity. Random effects model was used with odds ratio as the effect size. We also determined the pooled prevalence of diabetes in patients with COVID-19. Heterogeneity and publication bias were taken care by meta-regression, sub-group analyses, and trim and fill methods. RESULTS: We included 33 studies (16,003 patients) and found diabetes to be significantly associated with mortality of COVID-19 with a pooled odds ratio of 1.90 (95% CI: 1.37-2.64; p < 0.01). Diabetes was also associated with severe COVID-19 with a pooled odds ratio of 2.75 (95% CI: 2.09-3.62; p < 0.01). The combined corrected pooled odds ratio of mortality or severity was 2.16 (95% CI: 1.74-2.68; p < 0.01). The pooled prevalence of diabetes in patients with COVID-19 was 9.8% (95% CI: 8.7%-10.9%) (after adjusting for heterogeneity). CONCLUSIONS: Diabetes in patients with COVID-19 is associated with a two-fold increase in mortality as well as severity of COVID-19, as compared to non-diabetics. Further studies on the pathogenic mechanisms and therapeutic implications need to be done.", "qid": 24, "docid": "ufasdi1b", "rank": 39, "score": 0.8319520950317383}, {"content": "Title: Diabetes and COVID-19 : Disease-Management-People Content: The current pandemic of SARS-CoV\u00ad2 coronavirus disease 2019 (COVID-19) is a particular challenge for diabetes patients. Diabetes mellitus predisposes to a particularly severe course of the disease and doubles the COVID-19 mortality risk due to pulmonary and cardiac involvement. In addition, diabetes patients often suffer from comorbidities which further worsen clinical outcomes. Glycemic control during infectious diseases is often suboptimal, and antidiabetic drugs and insulin therapy have to be adapted accordingly. On the other hand, access of diabetes patients to outpatient clinics are limited during the ongoing season urging alternative treatment options, particularly the implementation of novel telemedicine strategies. Hence, the opportunity of the COVID 19 crisis should be taken to make a significant step forward in the care for diabetes patients.", "qid": 24, "docid": "7ptxz652", "rank": 40, "score": 0.8313062787055969}, {"content": "Title: Long term complications and rehabilitation of COVID-19 patients. Content: With the ongoing pandemic of COVID-19 having caught the world almost unaware millions of people across the globe are presently grappling to deal with its acute effects . Our previous experience with members of the same corona virus family (SARS and MERS) which have caused two major epidemics in the past albeit of much lower magnitude , has taught us that the harmful effect of such outbreaks are not limited to acute complications alone .Long term cardiopulmonary, glucometabolic and neuropsychiatric complications have been documented following these infections .In the given circumstance it is therefore imperative to keep in mind the possible complications that may occur after the acute phase of the disease subsides and to prepare the healthcare system for such challenges.", "qid": 24, "docid": "7s04ygm2", "rank": 41, "score": 0.8312721252441406}, {"content": "Title: Long term complications and rehabilitation of COVID-19 patients Content: With the ongoing pandemic of COVID-19 having caught the world almost unaware millions of people across the globe are presently grappling to deal with its acute effects . Our previous experience with members of the same corona virus family (SARS and MERS) which have caused two major epidemics in the past albeit of much lower magnitude , has taught us that the harmful effect of such outbreaks are not limited to acute complications alone .Long term cardiopulmonary, glucometabolic and neuropsychiatric complications have been documented following these infections .In the given circumstance it is therefore imperative to keep in mind the possible complications that may occur after the acute phase of the disease subsides and to prepare the healthcare system for such challenges.", "qid": 24, "docid": "yudrouue", "rank": 42, "score": 0.8312720060348511}, {"content": "Title: Comorbid Diabetes Mellitus was Associated with Poorer Prognosis in Patients with COVID-19: A Retrospective Cohort Study Content: Background The 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, Hubei province, China, and was characterized as pandemic by the World Health Organization. Diabetes mellitus is an established risk factor for poor clinical outcomes, but the association of diabetes with the prognosis of COVID-19 have not been reported yet. Methods In this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital of Huazhong University of Science and Technology in Wuhan, China, recruited from January 29 to February 12, 2020. The cases were confirmed by real-time PCR and the demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Prognosis was defined as hospitalization, discharged survivor and death, which was followed up until March 12, 2020. Results Of the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. No significant differences in age and sex were identified between patients with and without diabetes. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease condition with more complications at presentation, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR]=3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR=1.19; 95% CI: 1.08, 1.31) were associated with the fatality of COVID-19, adjusting for potential confounders. Conclusions Diabetes mellitus is associated with greater disease severity and a higher risk of mortality in patients with COVID-19. Primary and secondary prevention strategies are needed for COVID-19 patients with diabetes.", "qid": 24, "docid": "skknfc6h", "rank": 43, "score": 0.8311944007873535}, {"content": "Title: Diabetes and COVID-19: Disease\u2014Management\u2014People Content: The current pandemic of SARS-CoV\u20112 coronavirus disease 2019 (COVID-19) is a particular challenge for diabetes patients. Diabetes mellitus predisposes to a particularly severe course of the disease and doubles the COVID-19 mortality risk due to pulmonary and cardiac involvement. In addition, diabetes patients often suffer from comorbidities which further worsen clinical outcomes. Glycemic control during infectious diseases is often suboptimal, and antidiabetic drugs and insulin therapy have to be adapted accordingly. On the other hand, access of diabetes patients to outpatient clinics are limited during the ongoing season urging alternative treatment options, particularly the implementation of novel telemedicine strategies. Hence, the opportunity of the COVID 19 crisis should be taken to make a significant step forward in the care for diabetes patients.", "qid": 24, "docid": "mx9nyd2q", "rank": 44, "score": 0.8307958841323853}, {"content": "Title: Prognostic factors in patients with diabetes hospitalized for COVID-19: Findings from the CORONADO study and other recent reports Content: Diabetes mellitus is challenging in the context of the COVID-19 pandemic. The prevalence of diabetes patients hospitalized in intensive care units for COVID-19 is two- to threefold higher, and the mortality rate at least double, than that of non-diabetes patients. As the population with diabetes is highly heterogeneous, it is of major interest to determine the risk factors of progression to a more serious life-threatening COVID-19 infection. This brief review discusses the main findings of CORONADO, a prospective observational study in France that specifically addressed this issue as well as related observations from other countries, mainly China and the US. Some prognostic factors beyond old age have been identified: for example, an increased body mass index is a major risk factor for requiring respiratory assistance. Indeed, obesity combines several risk factors, including impaired respiratory mechanics, the presence of other comorbidities and inappropriate inflammatory responses, partly due to ectopic fat deposits. While previous diabetic microvascular (renal) and macrovascular complications also increase risk of death, the quality of past glucose control had no independent influence on hospitalized diabetes patient outcomes, but whether the quality of glucose control might modulate risk of COVID-19 in non-hospitalized diabetes patients is still unknown. In addition, no negative signs regarding the use of RAAS blockers and DPP-4 inhibitors and outcomes of COVID-19 could be identified. Hyperglycaemia at the time of hospital admission is associated with poor outcomes, but it may simply be considered a marker of severity of the infection. Thus, the impact of glucose control during hospitalization on outcomes related to COVID-19, which was not investigated in the CORONADO study, is certainly deserving of specific investigation.", "qid": 24, "docid": "yjugtbg1", "rank": 45, "score": 0.829927384853363}, {"content": "Title: Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication Content: OBJECTIVE: Diabetes is one of the most distinct comorbidities of COVID-19. Here, we describe the clinical characteristics of and outcomes in patients with diabetes in whom COVID-19 was confirmed or clinically diagnosed (with typical features on lung imaging and symptoms) and their association with glucose-lowering or blood pressure-lowering medications. RESEARCH DESIGN AND METHODS: In this retrospective study involving 904 patients with COVID-19 (136 with diabetes, mostly type 2 diabetes), clinical and laboratory characteristics were collected and compared between the group with diabetes and the group without diabetes, and between groups taking different medications. Logistic regression was used to explore risk factors associated with mortality or poor prognosis. RESULTS: The proportion of comorbid diabetes is similar between cases of confirmed and of clinically diagnosed COVID-19. Risk factors for higher mortality of patients with diabetes and COVID-19 were older age (adjusted odds ratio [aOR] 1.09 [95% CI 1.04, 1.15] per year increase; P = 0.001) and elevated C-reactive protein (aOR 1.12 [95% CI 1.00, 1.24]; P = 0.043). Insulin usage (aOR 3.58 [95% CI 1.37, 9.35]; P = 0.009) was associated with poor prognosis. Clinical outcomes of those who use an ACE inhibitor (ACEI) or angiotensin II type-I receptor blocker (ARB) were comparable with those of patients who do not use ACEI/ARB among COVID-19 patients with diabetes and hypertension. CONCLUSIONS: C-reactive protein may help to identify patients with diabetes who are at greater risk of dying during hospitalization. Older patients with diabetes were prone to death related to COVID-19. Attention needs to be paid to patients with diabetes and COVID-19 who use insulin. ACEI/ARB use showed no significant impact on patients with diabetes and hypertension who have COVID-19.", "qid": 24, "docid": "p3qsn8di", "rank": 46, "score": 0.8294413089752197}, {"content": "Title: Patients with diabetes are at higher risk for severe illness from COVID-19 Content: \u2022 It is currently uncertain whether people with diabetes are at higher risk of severe illness from coronavirus disease 2019 (COVID-19). \u2022 We found that diabetes was associated with an approximately 4-fold increased risk of having severe/critical COVID-19 illness. \u2022 This association was independent of age, sex, obesity, hypertension and smoking. \u2022 These findings highlight the urgent need for a multidisciplinary team-based approach to management of this patient population.", "qid": 24, "docid": "z0t43pmx", "rank": 47, "score": 0.8293250799179077}, {"content": "Title: Association of diabetes and hypertension with disease severity in covid-19 patients: a systematic literature review and exploratory meta-analysis Content: AIM: The novel coronavirus infection (COVID-19), now a worldwide public health concern is associated with varied fatality. Patients with chronic underlying conditions like diabetes and hypertension have shown worst outcomes. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. The aim of the meta-analysis was to assess the association of diabetes and hypertension with severity of disease. METHODS: A literature search was conducted using the databases PubMed and Cochrane until March 31, 2020. Seven studies were included in the meta- analysis, including 2018 CIVID-19 patients. RESULTS: Diabetes was lower in the survivors (OR: 0.56; 95%CI: 0.35-0.90; p=0.017; I2: 0.0%) and non-severe (OR: 1.66; 95%CI: 1.20-2.30; p=0.002; I2: 0.0%) patients. No association of diabetes was found with ICU care. Hypertension was positively associated with death (OR: 0.49; 95%CI: 0.34-0.73; p=0.000; I2: 0.0%), ICU care (OR: 0.42; 95%CI: 0.22-0.81; p=0.009; I2: 0.0%) and severity (OR: 2.69; 95%CI: 1.27-5.73; p=0.01; I2: 52.4%). CONCLUSIONS: Our findings suggest that diabetes and hypertension have a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid diabetes and hypertension are urgently needed to understand the magnitude of these vexatious comorbidities.", "qid": 24, "docid": "04s7w017", "rank": 48, "score": 0.8293211460113525}, {"content": "Title: COVID-19 pandemic, coronaviruses, and diabetes mellitus Content: The pandemic of coronavirus disease (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is causing substantial morbidity and mortality. Older age and presence of diabetes mellitus, hypertension, and obesity significantly increases the risk for hospitalization and death in COVID-19 patients. In this Perspective, informed by the studies on SARS-CoV-2, Middle East respiratory syndrome (MERS-CoV), and the current literature on SARS-CoV-2, we discuss potential mechanisms by which diabetes modulates the host-viral interactions and host-immune responses. We hope to highlight gaps in knowledge that require further studies pertinent to COVID-19 in patients with diabetes.", "qid": 24, "docid": "lntg6yb8", "rank": 49, "score": 0.8291882276535034}, {"content": "Title: The Relationship between Diabetes Mellitus and COVID-19 Prognosis: A Retrospective Cohort Study in Wuhan, China Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease, first appeared in Wuhan, China, and quickly spread throughout the world. We aimed to understand the relationship between diabetes mellitus and the prognosis of COVID-19. METHODS: Demographic, clinical, laboratory, radiologic, treatments, complications, and clinical outcomes data were extracted from electronic medical records and compared between diabetes (n=84) and non-diabetes (n=500) groups. Kaplan-Meier method and multivariate Cox analysis were applied to determine the risk factors for the prognosis of COVID-19. RESULTS: Compared to non-diabetic patients, diabetic patients had higher levels of neutrophils (p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.014), c-reactive protein (p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.008), procalcitonin (p < 0.01), and D-dimer (p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.033), and lower levels of lymphocytes (p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.032) and albumin (p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.035). Furthermore, diabetic patients had a significant higher incidence of bilateral pneumonia (86.9%, p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.020). In terms of complications and clinical outcomes, the incidence of respiratory failure (36.9% vs. 24.2%, p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.022), acute cardiac injury (47.4% vs. 21.2%, p < 0.01) and death (20.2% vs. 8.0%, p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.001) in the diabetes group was significantly higher than that in non-diabetes group. Kaplan-Meier survival curve showed that COVID-19 patients with diabetes had a shorter overall survival time. Multivariate Cox analysis indicated that diabetes (HR 2.180, p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.031) was an independent risk factor for COVID-19 prognosis. In subgroup analysis, we divided diabetic patients into insulin required and non-insulin required groups according to whether they needed insulin, and found that diabetic patients requiring insulin may have a higher risk of disease progression and worse prognosis after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CONCLUSIONS: Diabetes is an independent risk factor for the prognosis of COVID-19. More attention should be paid to the prevention and treatment for diabetic patients, especially those who require insulin therapy.", "qid": 24, "docid": "f4qljghz", "rank": 50, "score": 0.8290499448776245}, {"content": "Title: Dissecting the Interaction between Coronavirus Disease 2019 and Diabetes Mellitus Content: Coronavirus disease 2019 (COVID-19) is a global pandemic that is caused by a novel coronavirus, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Data from several countries have demonstrated higher morbidity and mortality among individuals with chronic metabolic diseases such as diabetes mellitus (DM). In this review, we explore the contributing factors for poorer prognosis in these individuals. As a significant proportion of patients with COVID-19 also have DM, this adds another layer of complexity to their management. We explore potential interactions between anti-diabetic medications and renin-angiotensin-aldosterone-system inhibitors with COVID-19. Suggested recommendations for the use of anti-diabetic medications in COVID-19 patients with DM are provided. We also review pertinent clinical considerations in the management of diabetic ketoacidosis in the COVID-19 patient. In addition, we aim to increase the awareness of clinicians to the metabolic effects of promising drug therapies for COVID-19. Finally, we highlight the importance of timely vaccinations for patients with DM.", "qid": 24, "docid": "09qp0sts", "rank": 51, "score": 0.828989565372467}, {"content": "Title: Prognostic factors in patients with diabetes hospitalized for COVID-19: Findings from the CORONADO study and other recent reports Content: Abstract Diabetes mellitus is challenging in the context of the COVID-19 pandemic. The prevalence of diabetes patients hospitalized in intensive care units for COVID-19 is two- to threefold higher, and the mortality rate at least double, than that of non-diabetes patients. As the population with diabetes is highly heterogeneous, it is of major interest to determine the risk factors of progression to a more serious life-threatening COVID-19 infection. This brief review discusses the main findings of CORONADO, a prospective observational study in France that specifically addressed this issue as well as related observations from other countries, mainly China and the US. Some prognostic factors beyond old age have been identified: for example, an increased body mass index is a major risk factor for requiring respiratory assistance. Indeed, obesity combines several risk factors, including impaired respiratory mechanics, the presence of other comorbidities and inappropriate inflammatory responses, partly due to ectopic fat deposits. While previous diabetic microvascular (renal) and macrovascular complications also increase risk of death, the quality of past glucose control had no independent influence on hospitalized diabetes patient outcomes, and whether the quality of glucose control might modulate risk of COVID-19 in non-hospitalized diabetes patients is still unknown. In addition, no negative signs regarding the use of RAAS blockers and DPP-4 inhibitors and outcomes of COVID-19 could be identified. Hyperglycaemia at the time of hospital admission is associated with poor outcomes, but it may simply be considered a marker of severity of the infection. Thus, the impact of glucose control during hospitalization on outcomes related to COVID-19, which was not investigated in the CORONADO study, is certainly deserving of specific investigation.", "qid": 24, "docid": "bjq36px5", "rank": 52, "score": 0.8280365467071533}, {"content": "Title: COVID-19 and type 1 diabetes: dealing with the difficult duo Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) has aroused global health concerns, particularly in relation to diabetes where it has been associated with poorer outcomes. The bulk of the evolving evidence in diabetes and COVID-19 relates to type 2 diabetes (T2D). Since there are a significant number of patients with type 1 diabetes (T1D) with unique concerns and challenges during the ongoing COVID-19 pandemic, we reviewed existing literature, relevant websites, and related guidelines to form this narrative review to help address key questions in this area. METHODS: We systematically searched the PubMed database up to May 31, 2020, and retrieved all the articles published on T1D and COVID-19. RESULTS: We found 18 relevant articles, each of which carried a part of the evidence regarding the risk of contracting COVID-19 in patients with T1D, effect of COVID-19 on development of T1D, outcomes in T1D with COVID-19, and special management issues in T1D in the light of COVID-19. These have been documented in the present review. CONCLUSION: COVID-19 with T1D presents special challenges. While the available evidence does shed some light, we need more evidence to deal with this difficult duo.", "qid": 24, "docid": "l9hfmmbc", "rank": 53, "score": 0.8275744915008545}, {"content": "Title: Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis Content: Abstract Background Many studies on COVID-19 have reported diabetes to be associated with severe disease and mortality, however, the data is conflicting. The objectives of this meta-analysis were to explore the relationship between diabetes and COVID-19 mortality and severity, and to determine the prevalence of diabetes in patients with COVID-19. Methods We searched the PubMed for case-control studies in English, published between Jan 1 and Apr 22, 2020, that had data on diabetes in patients with COVID-19. The frequency of diabetes was compared between patients with and without the composite endpoint of mortality or severity. Random effects model was used with odds ratio as the effect size. We also determined the pooled prevalence of diabetes in patients with COVID-19. Heterogeneity and publication bias were taken care by meta-regression, sub-group analyses, and trim and fill methods. Results We included 33 studies (16,003 patients) and found diabetes to be significantly associated with mortality of COVID-19 with a pooled odds ratio of 1.90 (95% CI: 1.37\u20132.64; p < 0.01). Diabetes was also associated with severe COVID-19 with a pooled odds ratio of 2.75 (95% CI: 2.09\u20133.62; p < 0.01). The combined corrected pooled odds ratio of mortality or severity was 2.16 (95% CI: 1.74\u20132.68; p < 0.01). The pooled prevalence of diabetes in patients with COVID-19 was 9.8% (95% CI: 8.7%\u201310.9%) (after adjusting for heterogeneity). Conclusions Diabetes in patients with COVID-19 is associated with a two-fold increase in mortality as well as severity of COVID-19, as compared to non-diabetics. Further studies on the pathogenic mechanisms and therapeutic implications need to be done.", "qid": 24, "docid": "ja9qu3p8", "rank": 54, "score": 0.8266566395759583}, {"content": "Title: Can We Reduce Mortality of COVID-19 if We do Better in Glucose Control? Content: The SARS-CoV-2 has infected more than 3 million people and caused more than 240,000 death globally. Among the COVID-19 patients, the prevalence of people with other chronic diseases, such as diabetes, high blood pressure, and coronary heart disease is much higher than others. More strikingly, the survival rate of diabetic patients is also much lower than in non-diabetic patients. In addition to the general damage of high glucose to cells and tissues, a recent discovery that high glucose activates interferon regulatory factor 15 promotes influenza virus -induced cytokine storm. This discovery may shed light on the high incidence of diabetes in COVID-19. Several diabetes prevention strategies together with recent significant data-driven diabetes prediction approaches, which may help COVID-19 treatments, have been proposed.", "qid": 24, "docid": "kbj72qye", "rank": 55, "score": 0.8263943195343018}, {"content": "Title: Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study Content: AIMS/HYPOTHESIS: Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown. METHODS: We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10-31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation. RESULTS: The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 \u00b1 13.0 years, median BMI 28.4 (25th-75th percentile: 25.0-32.7) kg/m2; with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin-angiotensin-aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA1c, diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7. CONCLUSIONS/INTERPRETATIONS: In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days. TRIAL REGISTRATION: clinicaltrials.gov NCT04324736.", "qid": 24, "docid": "hlnjp7v6", "rank": 56, "score": 0.8262685537338257}, {"content": "Title: The Relationship between Diabetes Mellitus and COVID-19 Prognosis: A Retrospective Cohort Study in Wuhan, China Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease, first appeared in Wuhan, China, and quickly spread throughout the world. We aimed to understand the relationship between diabetes mellitus and the prognosis of COVID-19. METHODS: Demographic, clinical, laboratory, radiologic, treatments, complications, and clinical outcomes data were extracted from electronic medical records and compared between diabetes (n=84) and non-diabetes (n=500) groups. Kaplan-Meier method and multivariate Cox analysis were applied to determine the risk factors for the prognosis of COVID-19. RESULTS: Compared to non-diabetic patients, diabetic patients had higher levels of neutrophils (p = 0.014), c-reactive protein (p = 0.008), procalcitonin (p < 0.01), and D-dimer (p = 0.033), and lower levels of lymphocytes (p = 0.032) and albumin (p = 0.035). Furthermore, diabetic patients had a significant higher incidence of bilateral pneumonia (86.9%, p = 0.020). In terms of complications and clinical outcomes, the incidence of respiratory failure (36.9% vs. 24.2%, p = 0.022), acute cardiac injury (47.4% vs. 21.2%, p < 0.01) and death (20.2% vs. 8.0%, p = 0.001) in the diabetes group was significantly higher than that in non-diabetes group. Kaplan-Meier survival curve showed that COVID-19 patients with diabetes had a shorter overall survival time. Multivariate Cox analysis indicated that diabetes (HR 2.180, p = 0.031) was an independent risk factor for COVID-19 prognosis. In subgroup analysis, we divided diabetic patients into insulin required and non-insulin required groups according to whether they needed insulin, and found that diabetic patients requiring insulin may have a higher risk of disease progression and worse prognosis after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CONCLUSIONS: Diabetes is an independent risk factor for the prognosis of COVID-19. More attention should be paid to the prevention and treatment for diabetic patients, especially those who require insulin therapy.", "qid": 24, "docid": "zcdkohu6", "rank": 57, "score": 0.8260353803634644}, {"content": "Title: Diabetes and Novel Coronavirus Infection: Implications for Treatment Content: The novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) outbreak originating in December 2019 has resulted in a worldwide pandemic affecting millions across almost 200 countries. People with diabetes appear to develop more severe forms of the disease and to require intensive care unit support and/or mechanical ventilation more frequently than those with other underlying medical conditions. The mortality rate among people with diabetes is also significantly higher than that among people without diabetes. A diagnosis of diabetes is often an indicator of poor underlying metabolic health, and frequently people with diabetes have multiple risk factors for severe coronavirus disease 2019 (COVID-19), including cardiovascular and renal disease. In this review, we discuss the potential biological mechanisms by which SARS-CoV-2 may interact with disease processes implicated in diabetes and discuss how treatments commonly used for people with diabetes may affect COVID-19 severity and progression. There is currently a lack of evidence from human studies, and further trials in this area will prove useful to further expand our understanding of this rapidly developing disease process to improve outcomes for this high-risk group of patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13300-020-00858-2) contains supplementary material, which is available to authorized users.", "qid": 24, "docid": "8t7rrgmp", "rank": 58, "score": 0.8257821798324585}, {"content": "Title: Influence of diabetes mellitus on the severity and fatality of SARS\u2010CoV\u20102 infection Content: AIMS: Diabetes mellitus is one of the most common comorbidities in Coronavirus disease 2019 (COVID\u201019) patients. The objective of this study was to evaluate the influences of diabetes mellitus on the severity and fatality of SARS\u2010CoV\u20102 infection. MATERIALS AND METHODS: Medical records of 66 hospitalized COVID\u201019 patients were collected and classified into non\u2010severe (mild/moderate cases) and severe (severe/critical cases) groups, respectively. Logistic regression analysis was used to estimate the risk of severe COVID\u201019 (severe/critical infection). In addition, a meta\u2010analysis including published studies reported the impacts of diabetes mellitus on severity and fatality of COVID\u201019, and our current study was conducted using fixed\u2010effects models. RESULTS: There were 22 diabetic and 44 non\u2010diabetic cases among the 66 hospitalized COVID\u201019 patients. As the results shown, seven cases (31.82%) were diagnosed as severe COVID\u201019 in diabetic patients, which was significantly higher than that in non\u2010diabetic group (4/44, 9.09%, P = 0.033). After adjustment for age and gender, the results showed that diabetes mellitus was significantly associated with COVID\u201019 severity (OR: 5.29, 95% CI: 1.07\u201326.02). A meta\u2010analysis further confirmed the positive association between diabetes mellitus and COVID\u201019 severity (pooled OR = 2.58, 95% CI: 1.93\u20133.45). Moreover, the diabetic patients infected with SARS\u2010CoV\u20102 showed to have 2.95\u2010fold higher risk of fatality compared to those patients without diabetes mellitus (95% CI: 1.93\u20134.53). CONCLUSIONS: Our findings provide new evidences that diabetes mellitus is associated with a higher risk of severity and fatality of COVID\u201019. Therefore, intensive monitoring and antidiabetic therapy should be considered in diabetic patients with SARS\u2010CoV\u20102 infection. This article is protected by copyright. All rights reserved.", "qid": 24, "docid": "bq7460ca", "rank": 59, "score": 0.825300931930542}, {"content": "Title: Dissecting the Interaction between Coronavirus Disease 2019 and Diabetes Mellitus Content: Coronavirus disease 2019 (COVID\u201019) is a global pandemic that is caused by a novel coronavirus, severe acute respiratory syndrome\u2010coronavirus\u20102 (SARS\u2010CoV\u20102). Data from several countries have demonstrated higher morbidity and mortality among individuals with chronic metabolic diseases such as diabetes mellitus (DM). In this review, we explore the contributing factors for poorer prognosis in these individuals. As a significant proportion of patients with COVID\u201019 also have DM, this adds another layer of complexity to their management. We explore potential interactions between anti\u2010diabetic medications and renin\u2010angiotensin\u2010aldosterone\u2010system inhibitors with COVID\u201019. Suggested recommendations for the use of anti\u2010diabetic medications in COVID\u201019 patients with DM are provided. We also review pertinent clinical considerations in the management of diabetic ketoacidosis in the COVID\u201019 patient. In addition, we aim to increase the awareness of clinicians to the metabolic effects of promising drug therapies for COVID\u201019. Finally, we highlight the importance of timely vaccinations for patients with DM.", "qid": 24, "docid": "r7qqeqpz", "rank": 60, "score": 0.8252236843109131}, {"content": "Title: Considerations for people with diabetes during the Coronavirus Disease (COVID-19) Pandemic Content: Abstract Introduction The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) continues to cause havoc globally, resulting in unprecedented healthcare, societal and economic disruption. People with diabetes have been shown to be at higher risk of complications and death when exposed to pneumonia, influenza and other coronaviruses. Despite pandemic scale infection, there is currently limited understanding on the potential impact of SARS-CoV-2 on people with diabetes. Aims (1) To characterise the outcomes of SARS-CoV-2 for people with diabetes and (2) add value to current recommendations for healthcare providers and people with diabetes to encourage optimal management. Methods A search of PubMed, Embase and MEDLINE to March 2020 was undertaken, using search terms pertaining to diabetes, coronavirus and acute respiratory distress syndrome (ARDS). We briefly reviewed the epidemiology and pathophysiology of SARS-CoV in the context of diabetes. Conclusion People with diabetes are at greater risk of severe infection and death with COVID-19. COVID-19 has significantly impacted the daily lives of individuals living with diabetes through financial implications, food and medication scarcity and its burden on mental health. In Australia, delivery of medical care has been adapted to reduce the risk of transmission, with a particular emphasis on telehealth and remote monitoring.", "qid": 24, "docid": "xtvujuji", "rank": 61, "score": 0.8250964879989624}, {"content": "Title: Association of diabetes and hypertension with disease severity in covid-19 patients: a systematic literature review and exploratory meta-analysis Content: Abstract Aim The novel coronavirus infection (COVID-19), now a worldwide public health concern is associated with varied fatality. Patients with chronic underlying conditions like diabetes and hypertension have shown worst outcomes. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. The aim of the meta-analysis was to assess the association of diabetes and hypertension with severity of disease. Methods A literature search was conducted using the databases PubMed and Cochrane until March 31, 2020. Seven studies were included in the meta- analysis, including 2018 CIVID-19 patients. Results Diabetes was lower in the survivors (OR: 0.56; 95%CI: 0.35-0.90; p=0.017; I2 : 0.0%) and non-severe (OR: 1.66; 95%CI: 1.20-2.30; p=0.002; I2 : 0.0%) patients. No association of diabetes was found with ICU care. Hypertension was positively associated with death (OR: 0.49; 95%CI: 0.34-0.73; p=0.000; I2 : 0.0%), ICU care (OR: 0.42; 95%CI: 0.22-0.81; p=0.009; I2 : 0.0%) and severity (OR: 2.69; 95%CI: 1.27-5.73; p=0.01; I2 : 52.4%). Conclusions Our findings suggest that diabetes and hypertension have a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid diabetes and hypertension are urgently needed to understand the magnitude of these vexatious comorbidities.", "qid": 24, "docid": "9qq049qb", "rank": 62, "score": 0.8240020275115967}, {"content": "Title: SGLT2 inhibition and COVID-19: The road not taken Content: The COVID-19 pandemic, caused by SARS-CoV-2, is an immense challenge for global healthcare. Diabetes mellitus, hypertension and obesity have been shown to portend poor prognosis in COVID-19 despite no greater susceptibility to the infection (1). Chronic hypertension is commonly associated with vasculopathy which can predispose to severe infection. In patients with diabetes, severity is attributable to impaired innate, adaptive immunity, upregulation of ACE2 (entry receptor for SARS-CoV2) by acute hyperglycemia and diabetic vasculopathy. The background of chronic low grade inflammation characterised by increased levels of IL-6 and CRP in diabetes and obesity can also lead to an enhanced 'cytokine storm' in COVID-19 (2). ACE2 expression on endothelial cells has been reported to cause viral mediated endothelitis and precipitate vascular dysfunction manifesting as acute respiratory distress syndrome as well as myocarditis, heart failure, arrhythmias, myocardial infarction and renal failure (3). In patients with pre-existing comorbidities like hypertension, diabetes, obesity and chronic kidney disease, this new-onset organ dysfunction can have deleterious additive effects.", "qid": 24, "docid": "ojoqsdn1", "rank": 63, "score": 0.8238313794136047}, {"content": "Title: SGLT2 inhibition and COVID-19: The road not taken. Content: The COVID-19 pandemic, caused by SARS-CoV-2, is an immense challenge for global healthcare. Diabetes mellitus, hypertension and obesity have been shown to portend poor prognosis in COVID-19 despite no greater susceptibility to the infection (1). Chronic hypertension is commonly associated with vasculopathy which can predispose to severe infection. In patients with diabetes, severity is attributable to impaired innate, adaptive immunity, upregulation of ACE2 (entry receptor for SARS-CoV2) by acute hyperglycemia and diabetic vasculopathy. The background of chronic low grade inflammation characterised by increased levels of IL-6 and CRP in diabetes and obesity can also lead to an enhanced 'cytokine storm' in COVID-19 (2). ACE2 expression on endothelial cells has been reported to cause viral mediated endothelitis and precipitate vascular dysfunction manifesting as acute respiratory distress syndrome as well as myocarditis, heart failure, arrhythmias, myocardial infarction and renal failure (3). In patients with pre-existing comorbidities like hypertension, diabetes, obesity and chronic kidney disease, this new-onset organ dysfunction can have deleterious additive effects.", "qid": 24, "docid": "md9dbxb5", "rank": 64, "score": 0.8238313794136047}, {"content": "Title: Diabetes increases the mortality of patients with COVID-19: a meta-analysis Content: AIMS: Nowadays, the ongoing pandemic of COVID-19 caused by the novel coronavirus Syndrome-Coronavirus-2 (SARS-CoV-2) is an emerging, rapidly evolving situation. Complications such as hypertension, diabetes, COPD, cardiovascular disease, and cerebrovascular disease are major risk factors for patients with COVID-19. METHODS: No meta-analysis has explored if or not diabetes related to mortality of patients with COVID-19. Therefore, this meta-analysis first aims to explore the possible clinical mortality between diabetes and COVID-19, analyze if diabetes patients infected with SARS-CoV-2 are exposed to the worst clinical prognostic risk, and to evaluate the reliability of the evidence. RESULTS: Our results showed a close relationship between diabetes and mortality of COVID-19, with a pooled OR of 1.75 (95% CI 1.31-2.36; P = 0.0002). The pooled data were calculated with the fixed effects model (FEM) as no heterogeneity appeared in the studies. Sensitivity analysis showed that after omitting any single study or converting a random effect model to FEM, the main results still held. CONCLUSIONS: Our meta-analysis showed that diabetes increases the mortality of patients with COVID-19. These results indicated the disturbance of blood glucose in the COVID-19 patients. More importantly, this meta-analysis grades the reliability of evidence for further basic and clinical research into the diabetes dysfunction in COVID-19 patients.", "qid": 24, "docid": "ibpyqrq4", "rank": 65, "score": 0.8237158060073853}, {"content": "Title: Diabetes increases the mortality of patients with COVID-19: a meta-analysis Content: AIMS: Nowadays, the ongoing pandemic of COVID-19 caused by the novel coronavirus Syndrome-Coronavirus-2 (SARS-CoV-2) is an emerging, rapidly evolving situation. Complications such as hypertension, diabetes, COPD, cardiovascular disease, and cerebrovascular disease are major risk factors for patients with COVID-19. METHODS: No meta-analysis has explored if or not diabetes related to mortality of patients with COVID-19. Therefore, this meta-analysis first aims to explore the possible clinical mortality between diabetes and COVID-19, analyze if diabetes patients infected with SARS-CoV-2 are exposed to the worst clinical prognostic risk, and to evaluate the reliability of the evidence. RESULTS: Our results showed a close relationship between diabetes and mortality of COVID-19, with a pooled OR of 1.75 (95% CI 1.31\u20132.36; P = 0.0002). The pooled data were calculated with the fixed effects model (FEM) as no heterogeneity appeared in the studies. Sensitivity analysis showed that after omitting any single study or converting a random effect model to FEM, the main results still held. CONCLUSIONS: Our meta-analysis showed that diabetes increases the mortality of patients with COVID-19. These results indicated the disturbance of blood glucose in the COVID-19 patients. More importantly, this meta-analysis grades the reliability of evidence for further basic and clinical research into the diabetes dysfunction in COVID-19 patients.", "qid": 24, "docid": "f0lo04qq", "rank": 66, "score": 0.8235708475112915}, {"content": "Title: Solving one of the pieces of the puzzle: COVID-19 and type 2 diabetes() Content: The emergence of the COVID-19 pandemic represents an enormous challenge. Given the considerable presence of type 2 diabetes mellitus in the current population, the pandemic is a health issue that requires an effort to provide better responses to our patients who are more vulnerable to the onset of infection and who are candidates for presenting more severe symptoms. This document attempts to address the relationship between COVID-19 infection and type 2 diabetes mellitus. To this end, we will briefly analyse whether the epidemiological data support this association and, subsequently, go in depth on the pathophysiological mechanisms that might connect the 2 diseases.", "qid": 24, "docid": "sdpa0372", "rank": 67, "score": 0.8232944011688232}, {"content": "Title: Resolviendo Una De Las Piezas Del Puzle: Covid-19 Y Diabetes Tipo 2./ [solving One of the Pieces of the Puzzle: Covid-19 and Type 2 Diabetes] Content: The emergence of the COVID-19 pandemic represents an enormous challenge. Given the considerable presence of type 2 diabetes mellitus in the current population, the pandemic is a health issue that requires an effort to provide better responses to our patients who are more vulnerable to the onset of infection and who are candidates for presenting more severe symptoms. This document attempts to address the relationship between COVID-19 infection and type 2 diabetes mellitus. To this end, we will briefly analyse whether the epidemiological data support this association and, subsequently, go in depth on the pathophysiological mechanisms that might connect the two diseases.", "qid": 24, "docid": "luz9q2rd", "rank": 68, "score": 0.8230538964271545}, {"content": "Title: Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study Content: AIMS/HYPOTHESIS: Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown. METHODS: We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10\u201331 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation. RESULTS: The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 \u00b1 13.0 years, median BMI 28.4 (25th\u201375th percentile: 25.0\u201332.7) kg/m(2); with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin\u2013angiotensin\u2013aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA(1c), diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7. CONCLUSIONS/INTERPRETATIONS: In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days. TRIAL REGISTRATION: clinicaltrials.gov NCT04324736. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-020-05180-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users.", "qid": 24, "docid": "97j1gt5k", "rank": 69, "score": 0.822702169418335}, {"content": "Title: Glucovigilance in COVID-19 Content: The coronavirus disease (COVID-19) pandemic has influenced clinical care in unprecedented ways. There is an urgent need to share best practice in providing diabetes care services in areas affected by COVID. This is a brief review for clinicians managing diabetes in low-income countries based on currently available data. The data is rapidly evolving; however, people with diabetes and its related comorbidities have increased risk for severe disease, and prolonged recovery and mortality. This review is also informed by data from severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS), caused by MERS coronavirus (MERS-CoV). These two viruses share similarities with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus with causes COVID-19. SARS-CoV-2 was also known as 2019-nCOV. We discuss glucovigilance in COVID-19, the challenges and the opportunities. We put a spotlight on investigational new drugs for treatment of COVID medications and virtual care. Diabetologists and clinicians handling high-volume diabetes clinics are at increased risk for contracting COVID-19.", "qid": 24, "docid": "xehsijye", "rank": 70, "score": 0.822701632976532}, {"content": "Title: Glucovigilance in COVID-19. Content: The coronavirus disease (COVID-19) pandemic has influenced clinical care in unprecedented ways. There is an urgent need to share best practice in providing diabetes care services in areas affected by COVID. This is a brief review for clinicians managing diabetes in low-income countries based on currently available data. The data is rapidly evolving; however, people with diabetes and its related comorbidities have increased risk for severe disease, and prolonged recovery and mortality. This review is also informed by data from severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS), caused by MERS coronavirus (MERS-CoV). These two viruses share similarities with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus with causes COVID-19. SARS-CoV-2 was also known as 2019-nCOV. We discuss glucovigilance in COVID-19, the challenges and the opportunities. We put a spotlight on investigational new drugs for treatment of COVID medications and virtual care. Diabetologists and clinicians handling high-volume diabetes clinics are at increased risk for contracting COVID-19.", "qid": 24, "docid": "8tuubyaq", "rank": 71, "score": 0.822701632976532}, {"content": "Title: Obesity and diabetes as high-risk factors for severe coronavirus disease 2019 (COVID-19) Content: The outbreak of the coronavirus disease 2019 (Covid-19) has become an evolving worldwide health crisis. With the rising prevalence of obesity and diabetes has come an increasing awareness of their impacts on infectious diseases, including increased risk for various infections, post-infection complications and mortality from critical infections. Although epidemiological and clinical characteristics of Covid-19 have been constantly reported, no article has systematically illustrated the role of obesity and diabetes in Covid-19, or how Covid-19 affects obesity and diabetes, or special treatment in these at-risk populations. Here, we present a synthesis of the recent advances in our understanding of the relationships between obesity, diabetes and Covid-19 along with the underlying mechanisms, and provide special treatment guidance for these at-risk populations.", "qid": 24, "docid": "hs0wu3zu", "rank": 72, "score": 0.8225539922714233}, {"content": "Title: Baseline characteristics and risk factors for short-term outcomes in 132 COVID-19 patients with diabetes in Wuhan China: a retrospective study Content: Abstract Aims To investigate the clinical characteristics, laboratory findings and high- resolution CT (HRCT) features and to explore the risk factors for in-hospital death and complications of coronavirus disease 2019 (COVID-19) patients with diabetes. Methods From Dec 31, 2019, to Apr 5, 2020, a total of 132 laboratory-confirmed COVID-19 patients with diabetes from two hospitals were retrospectively included in our study. Clinical, laboratory and chest CT data were analyzed and compared between the two groups with an admission glucose level of \u226411mmol/L (group 1) and >11mmol/L (group 2). Logistic regression analyses were used to identify the risk factors associated with in-hospital death and complications. Results Of 132 patients, 15 died in hospital and 113 were discharged. Patients in group 2 were more likely to require intensive care unit care (21.4% vs. 9.2%), to develop acute respiratory distress syndrome (ARDS) (23.2% vs. 9.25%) and acute cardiac injury (12.5% vs. 1.3%), and had a higher death rate (19.6% vs. 5.3%) than group 1. In the multivariable analysis, patients with admission glucose of >11 mmol/l had an increased risk of death (OR: 7.629, 95%CI: 1.391-37.984) and in-hospital complications (OR: 3.232, 95%CI: 1.393-7.498). Admission d-dimer of \u22651.5 \u03bcg/mL (OR: 6.645, 95%CI: 1.212-36.444) and HRCT score of \u226510 (OR: 7.792, 95%CI: 2.195-28.958) were associated with increased odds of in-hospital death and complications, respectively. Conclusions In COVID-19 patients with diabetes, poorly-controlled blood glucose (>11mmol/L) \ufeffmay be associated with poor outcomes. Admission hyperglycemia, elevated d-dimer and high HRCT score are potential risk factors for adverse outcomes and death.", "qid": 24, "docid": "5m4ybd1v", "rank": 73, "score": 0.8211667537689209}, {"content": "Title: [Diabetes and COVID-19 infection]. Content: Based on the epidemiological data currently available, diabetes does not seem to be a risk factor for infection with SARS-CoV-2 but may be associated with a more severe course. Diabetes is extremely common in older patients with co-morbidities who are at risk of unfavorable outcomes. As with any other infection, poorly controlled pre-existing diabetes can promote secondary infections and lead to acute complications related to hyperglycemia, worsened itself by the infection. It is important to advise patients to have enough diabetic equipment and supplies at home, to make regular blood glucose self-tests, and to contact a caregiver immediately in case of glycemic imbalance or signs of infection. Antidiabetic therapy may need adjustments following usual sick day rules. Insulin therapy should be considered to treat any persistent hyperglycemia in patients hospitalized for an acute infection.", "qid": 24, "docid": "nih2cnnz", "rank": 74, "score": 0.8210307359695435}, {"content": "Title: Use Stones from Another Mountain to Polish One\u2019s Jade: Learn from MERS Studies toexplore potential mechanisms underlying the effect of diabetes mellitus on COVID-19/ \u4e2d\u534e\u5185\u5206\u6ccc\u4ee3\u8c22\u6742\u5fd7 Content: Epidemiology studies suggest that comorbid diabetes may have negative impact on the progression and severity of the coronavirus disease 2019 (COVID-19), which first occurred in Wuhan. However, the exact mechanism remains unclear. A recent study on another type of coronavirus infection, Middle East Respiratory Syndrome (MERS), investigated its relationship with diabetes. This essay aims to give a brief introduction to this report and related studies, and to propose suggestions on what we can learn from these investigations to conduct further studies on the potential mechanisms underlying the effect of diabetes mellitus on COVID-19.", "qid": 24, "docid": "eqewn6j4", "rank": 75, "score": 0.8205219507217407}, {"content": "Title: Endocrine and metabolic aspects of the COVID-19 pandemic Content: COVID-19 infection has tremendously impacted our daily clinical practice as well as our social living organization. Virtually all organs and biological systems suffer from this new coronavirus infection, either because the virus targets directly specific tissues or because of indirect effects. Endocrine diseases are not an exception and some of endocrine organs are at risk of direct or indirect lesion by COVID-19. Although there is still no evidence of higher predisposition to contract the infection in patients with diabetes and/or obesity, the coexistence of these conditions contributes to a worse prognosis because both conditions confer an impaired immunologic system. Cytokines storm can be amplified by these two latter conditions thereby leading to multisystemic failure and death. Glycaemic control has been demonstrated to be crucial to avoiding long hospital stays, ICU requirement and also prevention of excessive mortality. Endocrine treatment modifications as a consequence of COVID-19 infection are required in a proactive manner, in order to avoid decompensation and eventual hospital admission. This is the case of diabetes and adrenal insufficiency in which prompt increase of insulin dosage and substitutive adrenal steroids through adoption of the sick day's rules should be warranted, as well as easy contact with the health care provider through telematic different modalities. New possible endocrinological targets of COVID-19 have been recently described and warrant a full study in the next future.", "qid": 24, "docid": "tnf37u52", "rank": 76, "score": 0.8203741312026978}, {"content": "Title: Influence of diabetes mellitus on the severity and fatality of SARS-CoV-2 (COVID-19) infection Content: AIM: To evaluate the influence of diabetes on the severity and fatality of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. MATERIALS AND METHODS: The medical records of 66 hospitalized coronavirus disease 2019 (COVID-19) patients were collected and classified into non-severe (mild/moderate cases) and severe (severe/critical cases) groups. Logistic regression analysis was used to estimate the risk of severe COVID-19 (severe/critical infection). In addition, a meta-analysis including published studies reported the impact of diabetes on the severity and fatality of COVID-19. The current study was conducted using fixed effects models. RESULTS: There were 22 diabetes and 44 non-diabetes cases among the 66 hospitalized COVID-19 patients. Seven patients with diabetes (31.82%) were diagnosed as severe COVID-19 cases, which was significantly higher than that in the non-diabetes group (4/44, 9.09%, P = .033). After adjustment for age and gender, diabetes was significantly associated with COVID-19 severity (OR: 5.29, 95% CI: 1.07-26.02). A meta-analysis further confirmed the positive association between diabetes and COVID-19 severity (pooled OR = 2.58, 95% CI: 1.93-3.45). Moreover, the patients with diabetes infected with SARS-CoV-2 had a 2.95-fold higher risk of fatality compared with those patients without diabetes (95% CI: 1.93-4.53). CONCLUSIONS: Our findings provide new evidence that diabetes is associated with a higher risk of severity and fatality of COVID-19. Therefore, intensive monitoring and antidiabetic therapy should be considered in patients with diabetes with SARS-CoV-2 infection.", "qid": 24, "docid": "i8uwia3a", "rank": 77, "score": 0.820298433303833}, {"content": "Title: [Diabetes and COVID-19 infection] Content: Based on the epidemiological data currently available, diabetes does not seem to be a risk factor for infection with SARS-CoV-2 but may be associated with a more severe course Diabetes is extremely common in older patients with co-morbidities who are at risk of unfavorable outcomes As with any other infection, poorly controlled pre-existing diabetes can promote secondary infections and lead to acute complications related to hyperglycemia, worsened itself by the infection It is important to advise patients to have enough diabetic equipment and supplies at home, to make regular blood glucose self-tests, and to contact a caregiver immediately in case of glycemic imbalance or signs of infection Antidiabetic therapy may need adjustments following usual sick day rules Insulin therapy should be considered to treat any persistent hyperglycemia in patients hospitalized for an acute infection", "qid": 24, "docid": "m9d88do0", "rank": 78, "score": 0.8202558159828186}, {"content": "Title: Baseline characteristics and risk factors for short-term outcomes in 132 COVID-19 patients with diabetes in Wuhan China: a retrospective study Content: AIMS: To investigate the clinical characteristics, laboratory findings and high- resolution CT (HRCT) features and to explore the risk factors for in-hospital death and complications of coronavirus disease 2019 (COVID-19) patients with diabetes. METHODS: From Dec 31, 2019, to Apr 5, 2020, a total of 132 laboratory-confirmed COVID-19 patients with diabetes from two hospitals were retrospectively included in our study. Clinical, laboratory and chest CT data were analyzed and compared between the two groups with an admission glucose level of &#8804;11mmol/L (group 1) and >11mmol/L (group 2). Logistic regression analyses were used to identify the risk factors associated with in-hospital death and complications. RESULTS: Of 132 patients, 15 died in hospital and 113 were discharged. Patients in group 2 were more likely to require intensive care unit care (21.4% vs. 9.2%), to develop acute respiratory distress syndrome (ARDS) (23.2% vs. 9.25%) and acute cardiac injury (12.5% vs. 1.3%), and had a higher death rate (19.6% vs. 5.3%) than group 1. In the multivariable analysis, patients with admission glucose of >11 mmol/l had an increased risk of death (OR: 7.629, 95%CI: 1.391-37.984) and in-hospital complications (OR: 3.232, 95%CI: 1.393-7.498). Admission d-dimer of &#8805;1.5 \u00b5g/mL (OR: 6.645, 95%CI: 1.212-36.444) and HRCT score of &#8805;10 (OR: 7.792, 95%CI: 2.195-28.958) were associated with increased odds of in-hospital death and complications, respectively. CONCLUSIONS: In COVID-19 patients with diabetes, poorly-controlled blood glucose (>11mmol/L) \u00ef\u00bb\u00bfmay be associated with poor outcomes. Admission hyperglycemia, elevated d-dimer and high HRCT score are potential risk factors for adverse outcomes and death.", "qid": 24, "docid": "nmolo7rt", "rank": 79, "score": 0.8198109865188599}, {"content": "Title: Endocrine and metabolic aspects of the COVID-19 pandemic Content: COVID-19 infection has tremendously impacted our daily clinical practice as well as our social living organization. Virtually all organs and biological systems suffer from this new coronavirus infection, either because the virus targets directly specific tissues or because of indirect effects. Endocrine diseases are not an exception and some of endocrine organs are at risk of direct or indirect lesion by COVID-19. Although there is still no evidence of higher predisposition to contract the infection in patients with diabetes and/or obesity, the coexistence of these conditions contributes to a worse prognosis because both conditions confer an impaired immunologic system. Cytokines storm can be amplified by these two latter conditions thereby leading to multisystemic failure and death. Glycaemic control has been demonstrated to be crucial to avoiding long hospital stays, ICU requirement and also prevention of excessive mortality. Endocrine treatment modifications as a consequence of COVID-19 infection are required in a proactive manner, in order to avoid decompensation and eventual hospital admission. This is the case of diabetes and adrenal insufficiency in which prompt increase of insulin dosage and substitutive adrenal steroids through adoption of the sick day\u2019s rules should be warranted, as well as easy contact with the health care provider through telematic different modalities. New possible endocrinological targets of COVID-19 have been recently described and warrant a full study in the next future.", "qid": 24, "docid": "ylfc9iro", "rank": 80, "score": 0.8192111253738403}, {"content": "Title: Obesity and diabetes as high\u2010risk factors for severe coronavirus disease 2019 (COVID\u201019) Content: The outbreak of the coronavirus disease 2019 (Covid\u201019) has become an evolving worldwide health crisis. With the rising prevalence of obesity and diabetes has come an increasing awareness of their impacts on infectious diseases, including increased risk for various infections, post\u2010infection complications and mortality from critical infections. Although epidemiological and clinical characteristics of Covid\u201019 have been constantly reported, no article has systematically illustrated the role of obesity and diabetes in Covid\u201019, or how Covid\u201019 affects obesity and diabetes, or special treatment in these at\u2010risk populations. Here, we present a synthesis of the recent advances in our understanding of the relationships between obesity, diabetes and Covid\u201019 along with the underlying mechanisms, and provide special treatment guidance for these at\u2010risk populations.", "qid": 24, "docid": "yftwt72e", "rank": 81, "score": 0.8190276622772217}, {"content": "Title: COVID-19 in people living with diabetes: An international consensus Content: The COVID-19 pandemic has added an enormous toll to the existing challenge of diabetes care world-wide. A large proportion of patients with COVID-19 requiring hospitalization and/or succumbing to the disease have had diabetes and other chronic conditions as underlying risk factors. In particular, individuals belonging to racial/ethnic minorities in the U.S. and other countries have been significantly and disproportionately impacted. Multiple and complex socioeconomic factors have long played a role in increasing the risk for diabetes and now for COVID-19. Since the pandemic began, the global healthcare community has accumulated invaluable clinical experience on providing diabetes care in the setting of COVID-19. In addition, understanding of the pathophysiological mechanisms that link these two diseases is being developed. The current clinical management of diabetes is a work in progress, requiring a shift in patient-provider interaction beyond the walls of clinics and hospitals: the use of tele-medicine when feasible, innovative patient education programs, strategies to ensure medication and glucose testing availability and affordability, as well as numerous ideas on how to improve meal plans and physical activity. Notably, this worldwide experience offers us the possibility to not only prepare better for future disasters but also transform diabetes care beyond the COVID-19 era.", "qid": 24, "docid": "8jyby4xo", "rank": 82, "score": 0.8187817335128784}, {"content": "Title: COVID-19 and Diabetes from IDF MENA Region. Content: The whole world are facing the current COVID-19 pandemic, the most serious health crisis in modern times. All countries with the support of national and international agencies are making great efforts to fight this devastating pandemic with disastrous medical, economic and social consequences. Thispandemic affects allpeople but it's serious in case ofdiabetes, elderly and inchronic andcomplicated diseases. The current work on the theme \"COVID-19 and Diabetes\" attempts to bring together all the data available at MENA level through medical and scientific publications. It also includes all the efforts made by the governments and the responses of associations and their efforts in this field. Even if it is admitted that diabetes with its comorbidity represents a high risk factor for severe forms and mortality, the health consequences of the epidemic, does not seem as dramatic in terms of both morbidity and mortality of COVID-19 with diabetes in the majority of MENA countries. If the crises continues longer, the supply of insulin, oral drugs, self monitoring equipment of diabetes and other tools, will beaffected. To this, we must expect great difficulties in supplying food for many countries. Certainely, it is important to remember that containment and hygiene measures, associated with other factors such as the young average age of the population, the higher temperature in these countries, the differences in the immune status of populations and the role of BCG vaccine have something to do with it. All of this deserves to be studied in depth.", "qid": 24, "docid": "mjim9vgj", "rank": 83, "score": 0.8187274932861328}, {"content": "Title: Beyond the virus: Ensuring continuity of care for people with diabetes during COVID-19 Content: The current COVID-19 pandemic is a major concern for the diabetes community. A meta-analysis in China found that the proportions of people with COVID-19 and diabetes was 9.7% and that having diabetes resulted in a two-fold increased risk of having a severe case. Global guidance on confinement measures for the prevention of COVID-19 have a particular emphasis on vulnerable populations which include people with diabetes. These recommendations are coherent to avoid the spread of SARSCoV-2 infection, but are in contradiction with comprehensive diabetes care, which requires regular patient-provider interactions for patient education, prescriptions and possible management of complications or mental health. Moreover, confinement drives risk for unhealthy diets, decreased physical activity, mental health related concerns, in parallel to delayed care-seeking due to fear of contracting COVID-19. Another weakness in the current COVID-19 response is the focus on hospital care which overlooks the importance of Primary Care in guaranteeing continuity of care. Ensuring the availability of insulin, other medicines, self-monitoring and diagnostic tools is another challenge. These are all global concerns for the diabetes community, as well as for those suffering from other chronic conditions. Undoubtedly, the global priority is to contain the spread and impact of COVID-19. However, health systems still need to meet the needs of the entire population, including individuals with diabetes. Clear guidance for preparedness, crisis and post-crisis management of diabetes and chronic diseases during mass disruptions to health systems are lacking. Therefore, in parallel to the epidemic response efforts to ensure existing healthcare services keep running should be supported to avoid health consequences that might be worse than the epidemic itself. This includes targeted messaging for people with diabetes and vulnerable populations with regards to possible risk of infection as well as their disease-related management; continued support via telephone, video conferencing or even home visits; ensuring access to insulin and other medicines and supplies both nationally and individually; and most importantly, preparing for the future.", "qid": 24, "docid": "u9jffox1", "rank": 84, "score": 0.8183268904685974}, {"content": "Title: Beyond the virus: Ensuring continuity of care for people with diabetes during COVID-19 Content: The current COVID-19 pandemic is a major concern for the diabetes community. A meta-analysis in China found that the proportions of people with COVID-19 and diabetes was 9.7% and that having diabetes resulted in a two-fold increased risk of having a severe case. Global guidance on confinement measures for the prevention of COVID-19 have a particular emphasis on vulnerable populations which include people with diabetes. These recommendations are coherent to avoid the spread of SARSCoV-2 infection, but are in contradiction with comprehensive diabetes care, which requires regular patient\u2013provider interactions for patient education, prescriptions and possible management of complications or mental health. Moreover, confinement drives risk for unhealthy diets, decreased physical activity, mental health related concerns, in parallel to delayed care-seeking due to fear of contracting COVID-19. Another weakness in the current COVID-19 response is the focus on hospital care which overlooks the importance of Primary Care in guaranteeing continuity of care. Ensuring the availability of insulin, other medicines, self-monitoring and diagnostic tools is another challenge. These are all global concerns for the diabetes community, as well as for those suffering from other chronic conditions. Undoubtedly, the global priority is to contain the spread and impact of COVID-19. However, health systems still need to meet the needs of the entire population, including individuals with diabetes. Clear guidance for preparedness, crisis and post-crisis management of diabetes and chronic diseases during mass disruptions to health systems are lacking. Therefore, in parallel to the epidemic response efforts to ensure existing healthcare services keep running should be supported to avoid health consequences that might be worse than the epidemic itself. This includes targeted messaging for people with diabetes and vulnerable populations with regards to possible risk of infection as well as their disease-related management; continued support via telephone, video conferencing or even home visits; ensuring access to insulin and other medicines and supplies both nationally and individually; and most importantly, preparing for the future.", "qid": 24, "docid": "e38nu08a", "rank": 85, "score": 0.8180387020111084}, {"content": "Title: Could there be a link between oral hygiene and the severity of SARS-CoV-2 infections? Content: On 30 January 2020, the World Health Organisation identified COVID-19, caused by the virus SARS-CoV-2, to be a global emergency. The risk factors already identified for developing complications from a COVID-19 infection are age, gender and comorbidities such as diabetes, hypertension, obesity and cardiovascular disease. These risk factors, however, do not account for the other 52% of deaths arising from COVID-19 in often seemingly healthy individuals. This paper investigates the potential link between SARS-CoV-2 and bacterial load, questioning whether bacteria may play a role in bacterial superinfections and complications such as pneumonia, acute respiratory distress syndrome and sepsis. The connection between COVID-19 complications and oral health and periodontal disease is also examined, as the comorbidities at highest risk of COVID-19 complications also cause imbalances in the oral microbiome and increase the risk of periodontal disease. We explore the connection between high bacterial load in the mouth and post-viral complications, and how improving oral health may reduce the risk of complications from COVID-19.", "qid": 24, "docid": "vxi3uttf", "rank": 86, "score": 0.8174716234207153}, {"content": "Title: Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review Content: AIMS: Rising prevalence of non-communicable diseases world-wide has made diabetes an important comorbidity in patients with coronavirus disease-19 (COVID-19). We sought to review the risk, severity and mortality in COVID-19 and its relation to the glycemic control, and role of anti-diabetic agents in patients with diabetes. METHODS: A Boolean search was made in PubMed, MedRxiv and Google Scholar database until May 10, 2020 and full articles with supplementary appendix were retrieved using the specific key words related to the topic. RESULTS: There is a high prevalence of diabetes in patients with COVID-19. Patients with diabetes had a significantly more severe variety of COVID-19 and increased mortality, compared to the groups without diabetes. Moreover, poor glycemic control is associated with a significantly higher severe COVID-19 and increased mortality, compared to the well-controlled glycemic groups. No data currently available for or against any anti-diabetic agents in COVID-19. CONCLUSIONS: Diabetes, in particular poorly-controlled group is associated with a significantly higher risk of severe COVID-19 and mortality. This calls for an optimal glycemic control and an increased emphasis on future preventative therapies including the vaccination programs for these groups in addition to the traditional risk prevention such as social distancing and self-isolation.", "qid": 24, "docid": "dlv0kyb2", "rank": 87, "score": 0.8169693946838379}, {"content": "Title: COVID-19 and diabetes from IDF MENA region Content: The whole world are facing the current COVID-19 pandemic, the most serious health crisis in modern times. All countries with the support of national and international agencies are making great efforts to fight this devastating pandemic with disastrous medical, economic and social consequences. This pandemic affects all people but it's serious in case of diabetes, elderly and in chronic and complicated diseases. The current work on the theme \" COVID-19 and Diabetes\" attempts to bring together all the data available at MENA level through medical and scientific publications. It also includes all the efforts made by the governments and the responses of associations and their efforts in this field. Even if it is admitted that diabetes with its comorbidity represents a high risk factor for severe forms and mortality, the health consequences of the epidemic, does not seem as dramatic in terms of both morbidity and mortality of COVID-19 with diabetes in the majority of MENA countries. If the crises continues longer, the supply of insulin, oral drugs, self monitoring equipment of diabetes and other tools, will be affected. To this, we must expect great difficulties in supplying food for many countries. Certainely, it is important to remember that containment and hygiene measures, associated with other factors such as the young average age of the population, the higher temperature in these countries, the differences in the immune status of populations and the role of BCG vaccine have something to do with it. All of this deserves to be studied in depth.", "qid": 24, "docid": "8vn01luq", "rank": 88, "score": 0.8163190484046936}, {"content": "Title: Endocrinology in the time of COVID-19: Remodelling Diabetes Services and Promoting Innovation. Content: The COVID-19 pandemic is a major international emergency leading to unprecedented medical, economic and societal challenges. Countries around the globe are facing challenges with diabetes care and are similarly adapting care delivery, with local cultural nuances. People with diabetes suffer disproportionately from acute COVID-19 with higher rates of serious complications and death. In-patient services need specialist support to appropriately manage glycaemia in people with known and undiagnosed diabetes presenting with COVID-19. Due to the restrictions imposed by the pandemic, people with diabetes may suffer longer-term harm caused by inadequate clinical support and less frequent monitoring of their condition and diabetes-related complications. Outpatient services need reorganised to maintain advice and support, focusing on proactive care for the highest risk, making use of telehealth and digital services for consultations, self-management and remote monitoring, where appropriate. Stratification of patients for face-to-face or remote follow-up should be based on a balanced risk assessment. Public health and national organisations have generally responded rapidly with guidance on care management, but the pandemic has created a tension around prioritisation of communicable vs non-communicable disease. Resulting challenges in clinical decision making are compounded by a reduced clinical workforce. For many years, increasing diabetes mellitus incidence has been mirrored by rising preventable morbidity and mortality due to complications, yet innovation in service delivery has been slow. While the current focus is on limiting the terrible harm caused by the pandemic, it is possible that a positive lasting legacy of COVID-19 might include accelerated innovation in chronic disease management.", "qid": 24, "docid": "an3apm5g", "rank": 89, "score": 0.8155083656311035}, {"content": "Title: Endocrinology in the time of COVID-19: Remodelling Diabetes Services and Promoting Innovation Content: The COVID-19 pandemic is a major international emergency leading to unprecedented medical, economic and societal challenges. Countries around the globe are facing challenges with diabetes care and are similarly adapting care delivery, with local cultural nuances. People with diabetes suffer disproportionately from acute COVID-19 with higher rates of serious complications and death. In-patient services need specialist support to appropriately manage glycaemia in people with known and undiagnosed diabetes presenting with COVID-19. Due to the restrictions imposed by the pandemic, people with diabetes may suffer longer-term harm caused by inadequate clinical support and less frequent monitoring of their condition and diabetes-related complications. Outpatient services need reorganised to maintain advice and support, focusing on proactive care for the highest risk, making use of telehealth and digital services for consultations, self-management and remote monitoring, where appropriate. Stratification of patients for face-to-face or remote follow-up should be based on a balanced risk assessment. Public health and national organisations have generally responded rapidly with guidance on care management, but the pandemic has created a tension around prioritisation of communicable vs non-communicable disease. Resulting challenges in clinical decision making are compounded by a reduced clinical workforce. For many years, increasing diabetes mellitus incidence has been mirrored by rising preventable morbidity and mortality due to complications, yet innovation in service delivery has been slow. While the current focus is on limiting the terrible harm caused by the pandemic, it is possible that a positive lasting legacy of COVID-19 might include accelerated innovation in chronic disease management.", "qid": 24, "docid": "j5glp7xc", "rank": 90, "score": 0.815508246421814}, {"content": "Title: COVID-19 and diabetes: What have we learned so far? Content: COVID-19 and diabetes are both pandemics with major impacts on global public health. While the response to COVID-19 has been rapid and progressive to reduce risk of harm, the response to the diabetes pandemic has been somewhat more muted. People with diabetes have been disproportionately affected by COVID-19, with growing evidence of higher mortality and morbidity. In this article, we discuss the impact of COVID-19 on our diabetes service in an urban area in the UK. We discuss the impact on our patients and ourselves, and the possible lessons we can carry into the future.", "qid": 24, "docid": "dbclnrwr", "rank": 91, "score": 0.8148974776268005}, {"content": "Title: COVID-19 and diabetes mellitus: An unholy interaction of two pandemics Content: Abstract Background and aims Diabetes mellitus is associated with poor prognosis in patients with COVID-19. On the other hand, COVID-19 contributes to worsening of dysglycemia in people with diabetes mellitus over and above that contributed by stress hyperglycemia. Herein, we have reviewed the two-way interactions between COVID-19 and diabetes mellitus. Methods We have performed an extensive literature search for articles in PubMed, EMBASE and Google Scholar databases till April 25, 2020, with the following keywords: \u201cCOVID-19\u201d, \u201cSARS-CoV-2\u201d, \u201cdiabetes\u201d, \u201cdiabetes mellitus\u201d, \u201cSARS\u201d, \u201cinfection\u201d and \u201cmanagement of diabetes mellitus\u201d with interposition of the Boolean operator \u201cAND\u201d. Results Compromised innate immunity, pro-inflammatory cytokine milieu, reduced expression of ACE2 and use of renin-angiotensin-aldosterone system antagonists in people with DM contribute to poor prognosis in COVID-19. On the contrary, direct \u03b2-cell damage, cytokine-induced insulin resistance, hypokalemia and drugs used in the treatment of COVID-19 (like corticosteroids, lopinavir/ritonavir) can contribute to worsening of glucose control in people with diabetes mellitus. Conclusions The two-way interaction between COVID-19 and diabetes mellitus sets up a vicious cycle wherein COVID-19 leads to worsening of dysglycemia and diabetes mellitus, in turn, exacerbates the severity of COVID-19. Thus, it is imperative that people with DM take all necessary precautions and ensure good glycemic control amid the ongoing pandemic.", "qid": 24, "docid": "fe8f7tk1", "rank": 92, "score": 0.8147400617599487}, {"content": "Title: Multi-Organ Failure in a Patient With Diabetes due to COVID-19 With Clear Lungs Content: The pandemic of coronavirus disease 2019 has emerged in late 2019 infecting millions of people worldwide. Diabetes mellitus (DM) has been associated with severe illness and mortality mainly due to acute respiratory distress syndrome. We report a case of a middle-aged man with DM and COVID-19 who developed seizure and altered mental status, found to have diabetic ketoacidosis (DKA), acute kidney injury, hypovolemic shock, and hyperammonemia all contributing to metabolic encephalopathy. He was admitted to the ICU and subsequently intubated for airway protection; with appropriate management his condition improved and was successfully extubated. The patient had no lung involvement throughout the illness. We report this case to highlight that COVID-19 can lead to multi-organ failure in patients with DM even in the absence of lung involvement which all physicians should be mindful of.", "qid": 24, "docid": "vfcoyezy", "rank": 93, "score": 0.8142334222793579}, {"content": "Title: Impact of diabetes mellitus on clinical outcomes in patients affected by Covid-19 Content: A possible association could exist between type 2 diabetes mellitus (T2DM) and Coronavirus-19 (Covid-19) infection. Indeed, patients with T2DM show high prevalence, severity of disease and mortality during Covid-19 infection. However, the rates of severe disease are significantly higher in patients with diabetes compared with non-diabetes (34.6% vs. 14.2%; p < 0.001). Similarly, T2DM patients have higher rates of need for Intensive Care Unit (ICU, 37.0% vs. 26.7%; p = 0.028). Thus, about the pneumonia of Covid-19, we might speculate that the complicated alveolar-capillary network of lungs could be targeted by T2DM micro-vascular damage. Therefore, T2DM patients frequently report respiratory symptoms and are at increased risk of several pulmonary diseases. In addition, pro-inflammatory pathways as that involving interleukin 6 (IL-6), could be a severity predictor of lung diseases. Therefore, it looks intuitive to speculate that this condition could explain the growing trend of cases, hospitalization and mortality for patients with T2DM during Covid-19 infection. To date, an ongoing experimental therapy with monoclonal antibody against the IL-6 receptor in Italy seems to have beneficial effects on severe lung disease and prognosis in patients with Covid-19 infection. Therefore, should patients with T2DM be treated with more attention to glycemic control and monoclonal antibody against the IL-6 receptor during the Covid-19 infection?", "qid": 24, "docid": "5759p02f", "rank": 94, "score": 0.8131626844406128}, {"content": "Title: Diabetes management and specific considerations for patients with diabetes during coronavirus diseases pandemic: A scoping review Content: BACKGROUND AND AIMS: The global pandemic of coronavirus (COVID-19) affects almost all countries in the world, which potentially alter diabetes management. Many diabetes patients are experiencing barrier of care due to the policy related to COVID-19. This article aims to review the current evidence on diabetes management and specific consideration during the COVID-19 pandemic for people living with diabetes. METHODS: We conducted a scoping review in PubMed, Science Direct, DOAJ and Microsoft Academics databases from January 1 to April 17, 2020. Searching terms included \u201cCOVID-19\", \u201csevere acute respiratory syndrome coronavirus 2\", and \u201cDiabetes Mellitus\u201d were used. Only scientific articles discussing diabetes management and specific considerations were selected and extracted. RESULTS: A total of 7 articles was selected in the analysis. Most were published in diabetes journals (85.71%). All articles (100%) discussed diabetes management and 71.43% of them provided diabetes care in specific considerations. We discussed issue of diabetes management in glycemic control and monitoring, dietary intake, physical activity, medication, education and prevention of COVID-19 infection that applicable for diabetes patients. In addition, specific considerations explored caring for diabetes in children and adolescents, pregnancy, elderly, emergency or critical care, to offer certain concern for raising the awareness. CONCLUSIONS: This review specifies a summary of diabetes management as well as the particular considerations to care people living with diabetes during COVID-19 pandemic. Patients, health care providers, and policy makers could take advantage of the review to assist diabetic people passing through COVID-19 pandemic session with optimum glycemic outcome.", "qid": 24, "docid": "vte52lah", "rank": 95, "score": 0.812476634979248}, {"content": "Title: Diabetes and metabolic syndrome as risk factors for COVID-19 Content: BACKGROUND AND AIMS: Clinical evidence exists that patients with diabetes are at higher risk for Coronavirus disease 2019 (COVID-19). We investigated the physiological origins of this clinical observation linking diabetes with severity and adverse outcome of COVID-19. METHODS: Publication mining was applied to reveal common physiological contexts in which diabetes and COVID-19 have been investigated simultaneously. Overall, we have acquired 1,121,078 publications from PubMed in the time span between 01-01-2000 and 17-04-2020, and extracted knowledge graphs interconnecting the topics related to diabetes and COVID-19. RESULTS: The Data Mining revealed three pathophysiological pathways linking diabetes and COVID-19. The first pathway indicates a higher risk for COVID-19 because of a dysregulation of Angiotensin-converting enzyme 2. The other two important physiological links between diabetes and COVID-19 are liver dysfunction and chronic systemic inflammation. A deep network analysis has suggested clinical biomarkers predicting the higher risk: Hypertension, elevated serum Alanine aminotransferase, high Interleukin-6, and low Lymphocytes count. CONCLUSIONS: The revealed biomarkers can be applied directly in clinical practice. For newly infected patients, the medical history needs to be checked for evidence of a long-term, chronic dysregulation of these biomarkers. In particular, patients with diabetes, but also those with prediabetic state, deserve special attention.", "qid": 24, "docid": "i4t1jq29", "rank": 96, "score": 0.8123414516448975}, {"content": "Title: Caring for patients with diabetes during COVID-19 pandemic: Important considerations for pharmacists Content: The current pandemic of the COVID-19 infection, coupled with the increased global burden of diabetes, has imposed significant challenges to the healthcare providers in providing effective and sustained care to patients with diabetes during the ongoing pandemic. It is, therefore, important for healthcare providers to understand and follow the recommended changes in the delivery of care, lifestyle modifications, and pharmacotherapy to ensure optimal care to the patients during and post-pandemic era. This commentary aims to discuss the impact of COVID-19 on diabetes care and the important considerations for pharmacists during this pandemic.", "qid": 24, "docid": "9w2py1nt", "rank": 97, "score": 0.8118995428085327}, {"content": "Title: Clinical analysis of risk factors for severe COVID-19 patients with type 2 diabetes() Content: AIMS: To describe characteristics of COVID-19 patients with type 2 diabetes and to analyze risk factors for severity. METHODS: Demographics, comorbidities, symptoms, laboratory findings, treatments and outcomes of COVID-19 patients with diabetes were collected and analyzed. RESULTS: Seventy-four COVID-19 patients with diabetes were included. Twenty-seven patients (36.5%) were severe and 10 patients (13.5%) died. Higher levels of blood glucose, serum amyloid A (SAA), C reactive protein and interleukin 6 were associated with severe patients compared to non-severe ones (P < 0.05). Levels of albumin, cholesterol, high density lipoprotein, small and dense low density lipoprotein and CD4(+) T lymphocyte counts in severe patients were lower than those in non-severe patients (P < 0.05). Logistic regression analysis identified decreased CD4(+) T lymphocyte counts (odds ratio [OR] = 0.988, 95%Confidence interval [95%CI] 0.979\u20130.997) and increased SAA levels (OR = 1.029, 95%CI 1.002\u20131.058) as risk factors for severity of COVID-19 with diabetes (P < 0.05). CONCLUSIONS: Type 2 diabetic patients were more susceptible to COVID-19 than overall population, which might be associated with hyperglycemia and dyslipidemia. Aggressive treatment should be suggested, especially when these patients had low CD4(+) T lymphocyte counts and high SAA levels.", "qid": 24, "docid": "ulmm28d5", "rank": 98, "score": 0.8117626309394836}, {"content": "Title: Diabetes and metabolic syndrome as risk factors for COVID-19 Content: BACKGROUND AND AIMS: Clinical evidence exists that patients with diabetes are at higher risk for Coronavirus disease 2019 (COVID-19). We investigated the physiological origins of this clinical observation linking diabetes with severity and adverse outcome of COVID-19. METHODS: Publication mining was applied to reveal common physiological contexts in which diabetes and COVID-19 have been investigated simultaneously. Overall, we have acquired 1,121,078 publications from PubMed in the time span between 01 and 01-2000 and 17-04-2020, and extracted knowledge graphs interconnecting the topics related to diabetes and COVID-19. RESULTS: The Data Mining revealed three pathophysiological pathways linking diabetes and COVID-19. The first pathway indicates a higher risk for COVID-19 because of an upregulation of Angiotensin-converting enzyme 2. The other two important physiological links between diabetes and COVID-19 are liver dysfunction and chronic systemic inflammation. A deep network analysis has suggested clinical biomarkers predicting the higher risk: Hypertension, elevated serum Alanine aminotransferase, high Interleukin-6, and low Lymphocytes count. CONCLUSIONS: The revealed biomarkers can be applied directly in clinical practice. For newly infected patients, the medical history needs to be checked for evidence of a long-term, chronic dysregulation of these biomarkers. In particular, patients with diabetes, but also those with prediabetic state, deserve special attention.", "qid": 24, "docid": "qzev2reb", "rank": 99, "score": 0.8117550015449524}, {"content": "Title: Diabetes and COVID-19: Risks, Management, and Learnings From Other National Disasters Content: Evidence relating to the impact of COVID-19 in people with diabetes (PWD) is limited but continuing to emerge. PWD appear to be at increased risk of more severe COVID-19 infection, though evidence quantifying the risk is highly uncertain. The extent to which clinical and demographic factors moderate this relationship is unclear, though signals are emerging that link higher BMI and higher HbA1c to worse outcomes in PWD with COVID-19. As well as posing direct immediate risks to PWD, COVID-19 also risks contributing to worse diabetes outcomes due to disruptions caused by the pandemic, including stress and changes to routine care, diet, and physical activity. Countries have used various strategies to support PWD during this pandemic. There is a high potential for COVID-19 to exacerbate existing health disparities, and research and practice guidelines need to take this into account. Evidence on the management of long-term conditions during national emergencies suggests various ways to mitigate the risks presented by these events.", "qid": 24, "docid": "a7npp99p", "rank": 100, "score": 0.811640739440918}]}
{"query": "which biomarkers predict the severe clinical course of 2019-nCOV infection?", "hits": [{"content": "Title: Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury Content: The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.", "qid": 25, "docid": "9k8r18x7", "rank": 1, "score": 0.8367712497711182}, {"content": "Title: Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury Content: The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-020-1643-8 and is accessible for authorized users.", "qid": 25, "docid": "t996fbad", "rank": 2, "score": 0.8324868679046631}, {"content": "Title: Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis Content: Background As coronavirus disease 2019 (COVID-19) pandemic rages on, there is urgent need for identification of clinical and laboratory predictors for progression towards severe and fatal forms of this illness. In this study we aimed to evaluate the discriminative ability of hematologic, biochemical and immunologic biomarkers in patients with and without the severe or fatal forms of COVID-19. Methods An electronic search in Medline (PubMed interface), Scopus, Web of Science and China National Knowledge Infrastructure (CNKI) was performed, to identify studies reporting on laboratory abnormalities in patients with COVID-19. Studies were divided into two separate cohorts for analysis: severity (severe vs. non-severe and mortality, i.e. non-survivors vs. survivors). Data was pooled into a meta-analysis to estimate weighted mean difference (WMD) with 95% confidence interval (95% CI) for each laboratory parameter. Results A total number of 21 studies was included, totaling 3377 patients and 33 laboratory parameters. While 18 studies (n = 2984) compared laboratory findings between patients with severe and non-severe COVID-19, the other three (n = 393) compared survivors and non-survivors of the disease and were thus analyzed separately. Patients with severe and fatal disease had significantly increased white blood cell (WBC) count, and decreased lymphocyte and platelet counts compared to non-severe disease and survivors. Biomarkers of inflammation, cardiac and muscle injury, liver and kidney function and coagulation measures were also significantly elevated in patients with both severe and fatal COVID-19. Interleukins 6 (IL-6) and 10 (IL-10) and serum ferritin were strong discriminators for severe disease. Conclusions Several biomarkers which may potentially aid in risk stratification models for predicting severe and fatal COVID-19 were identified. In hospitalized patients with respiratory distress, we recommend clinicians closely monitor WBC count, lymphocyte count, platelet count, IL-6 and serum ferritin as markers for potential progression to critical illness.", "qid": 25, "docid": "apgh3j3r", "rank": 3, "score": 0.819229006767273}, {"content": "Title: Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Content: Background As coronavirus disease 2019 (COVID-19) pandemic rages on, there is urgent need for identification of clinical and laboratory predictors for progression towards severe and fatal forms of this illness. In this study we aimed to evaluate the discriminative ability of hematologic, biochemical and immunologic biomarkers in patients with and without the severe or fatal forms of COVID-19. Methods An electronic search in Medline (PubMed interface), Scopus, Web of Science and China National Knowledge Infrastructure (CNKI) was performed, to identify studies reporting on laboratory abnormalities in patients with COVID-19. Studies were divided into two separate cohorts for analysis: severity (severe vs. non-severe and mortality, i.e. non-survivors vs. survivors). Data was pooled into a meta-analysis to estimate weighted mean difference (WMD) with 95% confidence interval (95% CI) for each laboratory parameter. Results A total number of 21 studies was included, totaling 3377 patients and 33 laboratory parameters. While 18 studies (n = 2984) compared laboratory findings between patients with severe and non-severe COVID-19, the other three (n = 393) compared survivors and non-survivors of the disease and were thus analyzed separately. Patients with severe and fatal disease had significantly increased white blood cell (WBC) count, and decreased lymphocyte and platelet counts compared to non-severe disease and survivors. Biomarkers of inflammation, cardiac and muscle injury, liver and kidney function and coagulation measures were also significantly elevated in patients with both severe and fatal COVID-19. Interleukins 6 (IL-6) and 10 (IL-10) and serum ferritin were strong discriminators for severe disease. Conclusions Several biomarkers which may potentially aid in risk stratification models for predicting severe and fatal COVID-19 were identified. In hospitalized patients with respiratory distress, we recommend clinicians closely monitor WBC count, lymphocyte count, platelet count, IL-6 and serum ferritin as markers for potential progression to critical illness.", "qid": 25, "docid": "fg69m7o0", "rank": 4, "score": 0.819229006767273}, {"content": "Title: Using IL\u20102R/lymphocytes for predicting the clinical progression of patients with COVID\u201019 Content: Effective laboratory markers for the estimation of disease severity and predicting the clinical progression of coronavirus disease\u20102019 (COVID\u201019) is urgently needed. Laboratory tests, including blood routine, cytokine profiles and infection markers, were collected from 389 confirmed COVID\u201019 patients. The included patients were classified into mild (n = 168), severe (n = 169) and critical groups (n = 52). The leukocytes, neutrophils, infection biomarkers [such as C\u2010reactive protein (CRP), procalcitonin (PCT) and ferritin] and the concentrations of cytokines [interleukin (IL)\u20102R, IL\u20106, IL\u20108, IL\u201010 and tumor necrosis factor (TNF)\u2010\u03b1] were significantly increased, while lymphocytes were significantly decreased with increased severity of illness. The amount of IL\u20102R was positively correlated with the other cytokines and negatively correlated with lymphocyte number. The ratio of IL\u20102R to lymphocytes was found to be remarkably increased in severe and critical patients. IL\u20102R/lymphocytes were superior compared with other markers for the identification of COVID\u201019 with critical illness, not only from mild but also from severe illness. Moreover, the cytokine profiles and IL\u20102R/lymphocytes were significantly decreased in recovered patients, but further increased in disease\u2010deteriorated patients, which might be correlated with the outcome of COVID\u201019. Lymphopenia and increased levels of cytokines were closely associated with disease severity. The IL\u20102R/lymphocyte was a prominent biomarker for early identification of severe COVID\u201019 and predicting the clinical progression of the disease.", "qid": 25, "docid": "7dy95eta", "rank": 5, "score": 0.8111737966537476}, {"content": "Title: Neutrophil-to-Lymphocyte Ratio Predicts Severe Illness Patients with 2019 Novel Coronavirus in the Early Stage Content: Background: Severe ill patients with 2019 novel coronavirus (2019-nCoV) infection progressed rapidly to acute respiratory failure. We aimed to select the most useful prognostic factor for severe illness incidence. Methods: The study prospectively included 61 patients with 2019-nCoV infection treated at Beijing Ditan Hospital from January 13, 2020 to January 31, 2020. Prognostic factor of severe illness was selected by the LASSO COX regression analyses, to predict the severe illness probability of 2019-CoV pneumonia. The predictive accuracy was evaluated by concordance index, calibration curve, decision curve and clinical impact curve. Results: The neutrophil-to-lymphocyte ratio (NLR) was identified as the independent risk factor for severe illness in patients with 2019-nCoV infection. The NLR had a c-index of 0.807 (95% confidence interval, 0.676-0.38), the calibration curves fitted well, and the decision curve and clinical impact curve showed that the NLR had superior standardized net benefit. In addition, the incidence of severe illness was 9.1% in age \u2265 50 and NLR < 3.13 patients, and half of patients with age \u2265 50 and NLR \u2265 3.13 would develop severe illness. Based on the risk stratification of NLR with age, the study developed a 2019-nCoV pneumonia management process. Conclusions: The NLR was the early identification of risk factors for 2019-nCoV severe illness. Patients with age \u2265 50 and NLR \u2265 3.13 facilitated severe illness, and they should rapidly access to intensive care unit if necessary.", "qid": 25, "docid": "pd70i3d8", "rank": 6, "score": 0.810469388961792}, {"content": "Title: [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia]. Content: Objective: To analyze the clinical characteristics of 2019 novel coronavirus (2019-nCoV) pneumonia and to investigate the correlation between serum inflammatory cytokines and severity of the disease. Methods: 29 patients with 2019-ncov admitted to the isolation ward of Tongji hospital affiliated to Tongji medical college of Huazhong University of Science and Technology in January 2020 were selected as the study subjects. Clinical data were collected and the general information, clinical symptoms, blood test and CT imaging characteristics were analyzed. According to the relevant diagnostic criteria, the patients were divided into three groups: mild (15 cases), severe (9 cases) and critical (5 cases). The expression levels of inflammatory cytokines and other markers in the serum of each group were detected, and the changes of these indicators of the three groups were compared and analyzed, as well as their relationship with the clinical classification of the disease. Results: (1) The main symptoms of 2019-nCoV pneumonia was fever (28/29) with or without respiratory and other systemic symptoms. Two patients died with underlying disease and co-bacterial infection, respectively. (2) The blood test of the patients showed normal or decreased white blood cell count (23/29), decreased lymphocyte count (20/29), increased hypersensitive C reactive protein (hs-CRP) (27/29), and normal procalcitonin. In most patients, serum lactate dehydrogenase (LDH) was significantly increased (20/29), while albumin was decreased (15/29). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil), serum creatinine (Scr) and other items showed no significant changes. (3) CT findings of typical cases were single or multiple patchy ground glass shadows accompanied by septal thickening. When the disease progresses, the lesion increases and the scope expands, and the ground glass shadow coexists with the solid shadow or the stripe shadow. (4) There were statistically significant differences in the expression levels of interleukin-2 receptor (IL-2R) and IL-6 in the serum of the three groups (P<0.05), among which the critical group was higher than the severe group and the severe group was higher than the mild group. However, there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-\u03b1), IL-1, IL-8, IL-10, hs-CRP, lymphocyte count and LDH among the three groups (P>0.05). Conclusion: The clinical characteristics of 2019-nCoV pneumonia are similar to those of common viral pneumonia. High resolution CT is of great value in the differential diagnosis of this disease. The increased expression of IL-2R and IL-6 in serum is expected to predict the severity of the 2019-nCoV pneumonia and the prognosis of patients.", "qid": 25, "docid": "0deyspy2", "rank": 7, "score": 0.8097060918807983}, {"content": "Title: [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia] Content: Objective: To analyze the clinical characteristics of 2019 novel coronavirus (2019-nCoV) pneumonia and to investigate the correlation between serum inflammatory cytokines and severity of the disease. Methods: 29 patients with 2019-ncov admitted to the isolation ward of Tongji hospital affiliated to Tongji medical college of Huazhong University of Science and Technology in January 2020 were selected as the study subjects. Clinical data were collected and the general information, clinical symptoms, blood test and CT imaging characteristics were analyzed. According to the relevant diagnostic criteria, the patients were divided into three groups: mild (15 cases), severe (9 cases) and critical (5 cases). The expression levels of inflammatory cytokines and other markers in the serum of each group were detected, and the changes of these indicators of the three groups were compared and analyzed, as well as their relationship with the clinical classification of the disease. Results: (1) The main symptoms of 2019-nCoV pneumonia was fever (28/29) with or without respiratory and other systemic symptoms. Two patients died with underlying disease and co-bacterial infection, respectively. (2) The blood test of the patients showed normal or decreased white blood cell count (23/29), decreased lymphocyte count (20/29), increased hypersensitive C reactive protein (hs-CRP) (27/29), and normal procalcitonin. In most patients,serum lactate dehydrogenase (LDH) was significantly increased (20/29), while albumin was decreased(15/29). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil), serum creatinine (Scr) and other items showed no significant changes. (3) CT findings of typical cases were single or multiple patchy ground glass shadows accompanied by septal thickening. When the disease progresses, the lesion increases and the scope expands, and the ground glass shadow coexists with the solid shadow or the stripe shadow. (4) There were statistically significant differences in the expression levels of interleukin-2 receptor (IL-2R) and IL-6 in the serum of the three groups (P<0.05), among which the critical group was higher than the severe group and the severe group was higher than the mildgroup. However, there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-&#945;), IL-1, IL-8, IL-10, hs-CRP, lymphocyte count and LDH among the three groups (P>0.05). Conclusion: The clinical characteristics of 2019-nCoV pneumonia are similar to those of common viral pneumonia. High resolution CT is of great value in the differential diagnosis of this disease. The increased expression of IL-2R and IL-6 in serum is expected to predict the severity of the 2019-nCoV pneumonia and the prognosis of patients.", "qid": 25, "docid": "wmlme0f4", "rank": 8, "score": 0.809669017791748}, {"content": "Title: [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia]. Content: Objective: To analyze the clinical characteristics of 2019 novel coronavirus (2019-nCoV) pneumonia and to investigate the correlation between serum inflammatory cytokines and severity of the disease. Methods: 29 patients with 2019-ncov admitted to the isolation ward of Tongji hospital affiliated to Tongji medical college of Huazhong University of Science and Technology in January 2020 were selected as the study subjects. Clinical data were collected and the general information, clinical symptoms, blood test and CT imaging characteristics were analyzed. According to the relevant diagnostic criteria, the patients were divided into three groups: mild (15 cases), severe (9 cases) and critical (5 cases). The expression levels of inflammatory cytokines and other markers in the serum of each group were detected, and the changes of these indicators of the three groups were compared and analyzed, as well as their relationship with the clinical classification of the disease. Results: (1) The main symptoms of 2019-nCoV pneumonia was fever (28/29) with or without respiratory and other systemic symptoms. Two patients died with underlying disease and co-bacterial infection, respectively. (2) The blood test of the patients showed normal or decreased white blood cell count (23/29), decreased lymphocyte count (20/29), increased hypersensitive C reactive protein (hs-CRP) (27/29), and normal procalcitonin. In most patients,serum lactate dehydrogenase (LDH) was significantly increased (20/29), while albumin was decreased(15/29). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil), serum creatinine (Scr) and other items showed no significant changes. (3) CT findings of typical cases were single or multiple patchy ground glass shadows accompanied by septal thickening. When the disease progresses, the lesion increases and the scope expands, and the ground glass shadow coexists with the solid shadow or the stripe shadow. (4) There were statistically significant differences in the expression levels of interleukin-2 receptor (IL-2R) and IL-6 in the serum of the three groups (P<0.05), among which the critical group was higher than the severe group and the severe group was higher than the mildgroup. However, there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-\u03b1), IL-1, IL-8, IL-10, hs-CRP, lymphocyte count and LDH among the three groups (P>0.05). Conclusion: The clinical characteristics of 2019-nCoV pneumonia are similar to those of common viral pneumonia. High resolution CT is of great value in the differential diagnosis of this disease. The increased expression of IL-2R and IL-6 in serum is expected to predict the severity of the 2019-nCoV pneumonia and the prognosis of patients.", "qid": 25, "docid": "iprkszdn", "rank": 9, "score": 0.809669017791748}, {"content": "Title: Using IL-2R/lymphocytes for predicting the clinical progression of patients with COVID-19 Content: Effective laboratory markers for the estimation of disease severity and predicting the clinical progression of coronavirus disease-2019 (COVID-19) is urgently needed. Laboratory tests, including blood routine, cytokine profiles and infection markers, were collected from 389 confirmed COVID-19 patients. The included patients were classified into mild (n = 168), severe (n = 169) and critical groups (n = 52). The leukocytes, neutrophils, infection biomarkers [such as C-reactive protein (CRP), procalcitonin (PCT) and ferritin] and the concentrations of cytokines [interleukin (IL)-2R, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-&#945;] were significantly increased, while lymphocytes were significantly decreased with increased severity of illness. The amount of IL-2R was positively correlated with the other cytokines and negatively correlated with lymphocyte number. The ratio of IL-2R to lymphocytes was found to be remarkably increased in severe and critical patients. IL-2R/lymphocytes were superior compared with other markers for the identification of COVID-19 with critical illness, not only from mild but also from severe illness. Moreover, the cytokine profiles and IL-2R/lymphocytes were significantly decreased in recovered patients, but further increased in disease-deteriorated patients, which might be correlated with the outcome of COVID-19. Lymphopenia and increased levels of cytokines were closely associated with disease severity. The IL-2R/lymphocyte was a prominent biomarker for early identification of severe COVID-19 and predicting the clinical progression of the disease.", "qid": 25, "docid": "wesk2dhi", "rank": 10, "score": 0.8087119460105896}, {"content": "Title: Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19 Content: BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 was first reported in Wuhan, December 2019, and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. OBJECTIVE: We sought to identify biomarkers for disease severity and progression of COVID-19. METHODS: Forty-eight cytokines in the plasma samples from 50 COVID-19 cases including 11 critically ill, 25 severe, and 14 moderate patients were measured and analyzed in combination with clinical data. RESULTS: Levels of 14 cytokines were found to be significantly elevated in COVID-19 cases and showed different expression profiles in patients with different disease severity. Moreover, expression levels of IFN-\u00ce\u00b3-induced protein 10, monocyte chemotactic protein-3, hepatocyte growth factor, monokine-induced gamma IFN, and macrophage inflammatory protein 1 alpha, which were shown to be highly associated with disease severity during disease progression, were remarkably higher in critically ill patients, followed by severe and then the moderate patients. Serial detection of the 5 cytokines in 16 cases showed that continuously high levels were associated with deteriorated progression of disease and fatal outcome. Furthermore, IFN-\u00ce\u00b3-induced protein 10 and monocyte chemotactic protein-3 were excellent predictors for the progression of COVID-19, and the combination of the 2 cytokines showed the biggest area under the curve of the receiver-operating characteristics calculations with a value of 0.99. CONCLUSIONS: In this study, we report biomarkers that are highly associated with disease severity and progression of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of severe acute respiratory syndrome coronavirus 2 infection, and provide potential therapeutic targets and strategies.", "qid": 25, "docid": "7rjzontt", "rank": 11, "score": 0.807900071144104}, {"content": "Title: Diagnostic and prognostic value of hematological and immunological markers in COVID-19 infection: A meta-analysis of 6320 patients Content: Objective Evidence-based characterization of the diagnostic and prognostic value of the hematological and immunological markers related to the epidemic of Coronavirus Disease 2019 (COVID-19) is critical to understand the clinical course of the infection and to assess in development and validation of biomarkers. Methods Based on systematic search in Web of Science, PubMed, Scopus, and Science Direct up to April 22, 2020, a total of 52 eligible articles with 6,320 laboratory-confirmed COVID-19 cohorts were included. Pairwise comparison between severe versus mild disease, Intensive Care Unit (ICU) versus general ward admission, and expired versus survivors were performed for 36 laboratory parameters. The pooled standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated using the DerSimonian Laird method/random effects model and converted to Odds ratio (OR). The decision tree algorithm was employed to identify the key risk factor(s) attributed to severe COVID-19 disease. Results Cohorts with elevated levels of white blood cells (WBCs) (OR=1.75), neutrophil count (OR=2.62), D-dimer (OR=3.97), prolonged prothrombin time (PT) (OR=1.82), fibrinogen (OR=3.14), erythrocyte sedimentation rate (OR=1.60), procalcitonin (OR=4.76), IL-6 (OR=2.10), and IL-10 (OR=4.93) had higher odds of progression to severe phenotype. Decision tree model (sensitivity=100%, specificity=81%) showed the high performance of neutrophil count at a cut-off value of more than 3.74 x109/L for identifying patients at high risk of severe COVID-19. Likewise, ICU admission was associated with higher levels of WBCs (OR=5.21), neutrophils (OR=6.25), D-dimer (OR=4.19), and prolonged PT (OR=2.18). Patients with high IL-6 (OR=13.87), CRP (OR=7.09), D-dimer (OR=6.36), and neutrophils (OR=6.25) had the highest likelihood of mortality. Conclusions Several hematological and immunological markers, in particular neutrophilic count, could be helpful to be included within the routine panel for COVID-19 infection evaluation to ensure risk stratification and effective management.", "qid": 25, "docid": "8nz2lcsa", "rank": 12, "score": 0.8005675077438354}, {"content": "Title: C\u2010reactive protein correlates with computed tomographic findings and predicts severe COVID\u201019 early Content: COVID\u201019 has developed into a worldwide pandemic; early identification of severe illness is critical for controlling it and improving the prognosis of patients with limited medical resources. The present study aimed to analyze the characteristics of severe COVID\u201019 and identify biomarkers for differential diagnosis and prognosis prediction. In total, 27 consecutive patients with COVID\u201019 and 75 patients with flu were retrospectively enrolled. Clinical parameters were collected from electronic medical records. The disease course was divided into four stages: initial, progression, peak, and recovery stages, according to computed tomography (CT) progress. to mild COVID\u201019, the lymphocytes in the severe COVID\u201019 progressively decreased at the progression and the peak stages, but rebound in the recovery stage. The levels of C\u2010reactive protein (CRP) in the severe group at the initial and progression stages were higher than those in the mild group. Correlation analysis showed that CRP (R = .62; P < .01), erythrocyte sedimentation rate (R = .55; P < .01) and granulocyte/lymphocyte ratio (R = .49; P < .01) were positively associated with the CT severity scores. In contrast, the number of lymphocytes (R = \u2212.37; P < .01) was negatively correlated with the CT severity scores. The receiver\u2010operating characteristic analysis demonstrated that area under the curve of CRP on the first visit for predicting severe COVID\u201019 was 0.87 (95% CI 0.10\u20131.00) at 20.42 mg/L cut\u2010off, with sensitivity and specificity 83% and 91%, respectively. CRP in severe COVID\u201019 patients increased significantly at the initial stage, before CT findings. Importantly, CRP, which was associated with disease development, predicted early severe COVID\u201019.", "qid": 25, "docid": "xfptlkuc", "rank": 13, "score": 0.7985782027244568}, {"content": "Title: Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19 Content: Abstract Background The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, December 2019, and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. Objective To identify biomarkers for disease severity and progression of COVID-19. Methods Forty-eight cytokines in the plasma samples from 50 COVID-19 cases including 11 critically ill, 25 severe and 14 moderate patients were measured and analyzed in combination with clinical data. Results Fourteen cytokines were found to be significantly elevated in COVID-19 cases and showed different expression profiles in patients with different disease severity. Moreover, expression levels of IP-10, MCP-3, HGF, MIG and MIP-1\u03b1, which were shown to be highly associated with disease severity during disease progression, were remarkably higher in critically ill patients, followed by severe and then the moderate patients. Serial detection of the five cytokines in 16 cases showed that continuously high levels were associated with deteriorated progression of disease and fatal outcome. Furthermore, IP-10 and MCP-3 were excellent predictors for the progression of COVID-19, and the combination of the two cytokines showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations with a value of 0.99. Conclusion In this study, we report biomarkers that highly associated with disease severity and progression of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, and provide potential therapeutic targets and strategies.", "qid": 25, "docid": "8ceabd6e", "rank": 14, "score": 0.7961547374725342}, {"content": "Title: [An increased neutrophil/lymphocyte ratio is an early warning signal of severe COVID-19] Content: OBJECTIVE: To identify the biomarkers as early warning signals for severe COVID-19. METHODS: We retrospectively analyzed the clinical data of 63 patients with COVID- 19 from Hubei Provincial Hospital of Integrated Chinese and Western Medicine, including 32 moderate cases and 31 severe cases. The demographic data, underlying diseases, clinical manifestations and laboratory test results were compared between the two groups. Logistic regression analysis was performed to identify the factors that predicted the severity of COVID-19. The receiver- operating characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) was calculated, and the area under the curve (AUC) was determined to estimate the optimal threshold of NLR for predicting severe cases of COVID-19. RESULTS: The patients with moderate and server COVID-19 showed significant differences in the rate of diabetes, NLR, serum amyloid A (SSA), C-reactive protein (CRP) and serum albumin (ALB) levels (P < 0.05). The co- morbidity of diabetes, NLR, SSA and CRP were found to positively correlate and ALB to inversely correlate with the severity of COVID-19 (P < 0.05). Multivariate logistic regression analysis showed that NLR was an independent risk factor for severe COVID-19 (OR=1.264, 95% CI: 1.046-1.526, P=0.015) with an AUC of 0.831 (95% CI: 0.730-0.932), an optimal diagnostic threshold of 4.795, a sensitivity of 0.839, and a specificity of 0.750. CONCLUSIONS: An increased NLR can serve as an early warning signal of severe COVID-19.", "qid": 25, "docid": "u1v2p9wp", "rank": 15, "score": 0.7955567836761475}, {"content": "Title: [An increased neutrophil/lymphocyte ratio is an early warning signal of severe COVID-19]. Content: OBJECTIVE To identify the biomarkers as early warning signals for severe COVID-19. METHODS We retrospectively analyzed the clinical data of 63 patients with COVID- 19 from Hubei Provincial Hospital of Integrated Chinese and Western Medicine, including 32 moderate cases and 31 severe cases. The demographic data, underlying diseases, clinical manifestations and laboratory test results were compared between the two groups. Logistic regression analysis was performed to identify the factors that predicted the severity of COVID-19. The receiver- operating characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) was calculated, and the area under the curve (AUC) was determined to estimate the optimal threshold of NLR for predicting severe cases of COVID-19. RESULTS The patients with moderate and server COVID-19 showed significant differences in the rate of diabetes, NLR, serum amyloid A (SSA), C-reactive protein (CRP) and serum albumin (ALB) levels (P < 0.05). The co- morbidity of diabetes, NLR, SSA and CRP were found to positively correlate and ALB to inversely correlate with the severity of COVID-19 (P < 0.05). Multivariate logistic regression analysis showed that NLR was an independent risk factor for severe COVID-19 (OR=1.264, 95% CI: 1.046-1.526, P=0.015) with an AUC of 0.831 (95% CI: 0.730-0.932), an optimal diagnostic threshold of 4.795, a sensitivity of 0.839, and a specificity of 0.750. CONCLUSIONS An increased NLR can serve as an early warning signal of severe COVID-19.", "qid": 25, "docid": "japmze1b", "rank": 16, "score": 0.7941820621490479}, {"content": "Title: C-reactive protein correlates with computed tomographic findings and predicts severe COVID-19 early Content: COVID-19 has developed into a worldwide pandemic; early identification of severe illness is critical for controlling it and improving the prognosis of patients with limited medical resources. The present study aimed to analyze the characteristics of severe COVID-19 and identify biomarkers for differential diagnosis and prognosis prediction. In total, 27 consecutive patients with COVID-19 and 75 patients with flu were retrospectively enrolled. Clinical parameters were collected from electronic medical records. The disease course was divided into four stages: initial, progression, peak, and recovery stages, according to computed tomography (CT) progress. to mild COVID-19, the lymphocytes in the severe COVID-19 progressively decreased at the progression and the peak stages, but rebound in the recovery stage. The levels of C-reactive protein (CRP) in the severe group at the initial and progression stages were higher than those in the mild group. Correlation analysis showed that CRP (R = .62; P < .01), erythrocyte sedimentation rate (R = .55; P < .01) and granulocyte/lymphocyte ratio (R = .49; P < .01) were positively associated with the CT severity scores. In contrast, the number of lymphocytes (R = -.37; P < .01) was negatively correlated with the CT severity scores. The receiver-operating characteristic analysis demonstrated that area under the curve of CRP on the first visit for predicting severe COVID-19 was 0.87 (95% CI 0.10-1.00) at 20.42 mg/L cut-off, with sensitivity and specificity 83% and 91%, respectively. CRP in severe COVID-19 patients increased significantly at the initial stage, before CT findings. Importantly, CRP, which was associated with disease development, predicted early severe COVID-19.", "qid": 25, "docid": "q37fwcgt", "rank": 17, "score": 0.793972909450531}, {"content": "Title: The role of interleukin\u20106 in monitoring severe case of coronavirus disease 2019 Content: Progression to severe disease is a difficult problem in treating coronavirus disease 2019 (COVID\u201019). The purpose of this study is to explore changes in markers of severe disease in COVID\u201019 patients. Sixty\u2010nine severe COVID\u201019 patients were included. Patients with severe disease showed significant lymphocytopenia. Elevated level of lactate dehydrogenase (LDH), C\u2010reactive protein (CRP), ferritin, and D\u2010dimer was found in most severe cases. Baseline interleukin\u20106 (IL\u20106) was found to be associated with COVID\u201019 severity. Indeed, the significant increase of baseline IL\u20106 was positively correlated with the maximal body temperature during hospitalization and with the increased baseline of CRP, LDH, ferritin, and D\u2010dimer. High baseline IL\u20106 was also associated with more progressed chest computed tomography (CT) findings. Significant decrease in IL\u20106 and improved CT assessment was found in patients during recovery, while IL\u20106 was further increased in exacerbated patients. Collectively, our results suggest that the dynamic change in IL\u20106 can be used as a marker for disease monitoring in patients with severe COVID\u201019.", "qid": 25, "docid": "u21glvb4", "rank": 18, "score": 0.7912472486495972}, {"content": "Title: The role of biomarkers in diagnosis of COVID-19 - A systematic review Content: AIMS: As of the 28th April 2020, the COVID-19 pandemic has infiltrated over 200 countries and affected over three million confirmed people. We review different biomarkers to evaluate if they are able to predict clinical outcomes and correlate with the severity of COVID-19 disease. METHODS: A systematic review of the literature was carried out to identify relevant articles using six different databases. Keywords to refine the search included 'COVID-19', 'SARS-CoV2', 'Biomarkers', among others. Only studies which reported data on pre-defined outcomes were included. KEY FINDINGS: Thirty-four relevant articles were identified which reviewed the following biomarkers: C-reactive protein, serum amyloid A, interleukin-6, lactate dehydrogenase, neutrophil-to-lymphocyte ratio, D-dimer, cardiac troponin, renal biomarkers, lymphocytes and platelet count. Of these, all but two, showed significantly higher levels in patients with severe complications of COVID-19 infection compared to their non-severe counterparts. Lymphocytes and platelet count showed significantly lower levels in severe patients compared to non-severe patients. SIGNIFICANCE: Although research is still in its early stages, the discovery of how different biomarkers behave during the course of the disease could help clinicians in identifying severe disease earlier and subsequently improve prognosis. Nevertheless, we urge for more research across the globe to corroborate these findings.", "qid": 25, "docid": "aph6yf7n", "rank": 19, "score": 0.788996696472168}, {"content": "Title: Blood biomarker score identifies individuals at high risk for severe COVID-19 a decade prior to diagnosis: metabolic profiling of 105,000 adults in the UK Biobank Content: Background: Identification of healthy people at high risk for severe COVID-19 is a global health priority. We investigated whether blood biomarkers measured by high-throughput metabolomics could be predictive of severe pneumonia and COVID-19 hospitalisation years after the blood sampling. Methods: Nuclear magnetic resonance metabolomics was used to quantify a comprehensive biomarker profile in 105,146 plasma samples collected in the UK Biobank during 2007-2010 (age range 39-70). The biomarkers were tested for association with severe pneumonia (2507 cases, defined as diagnosis in hospital or death record occurring during a median of 8.1-year follow-up) and with severe COVID-19 (195 cases, defined as diagnosis in hospital between mid-March to mid-June 2020). A multi-biomarker score was derived for prediction of severe pneumonia based on half of the study population and validated in the other half. We explored how this biomarker score relates to the risk of severe COVID-19. Findings: The biomarker associations with risk of severe COVID-19 followed an overall pattern similar to associations with risk of severe pneumonia (correlation 0.83). The multi-biomarker score, comprised of 25 blood biomarkers including inflammatory proteins, fatty acids, amino acids and advanced lipid measures, was strongly associated with risk of severe pneumonia (odds ratio 1.67 per standard deviation [95% confidence interval 1.59-1.76]; 3.8-fold risk increase for individuals in upper vs lower quintile). The multi-biomarker score was also associated with risk of severe COVID-19 (odds ratio 1.33 [1.17-1.53]; 2.5-fold risk for upper vs lower quintile) and remained significant when adjusting for body mass index, smoking, and existing respiratory and cardiometabolic diseases. Mimicking the decade lag from blood sampling to COVID-19, severe pneumonia events occurring after 7-11 years associated with the multi-biomarker score to a similar magnitude (odds ratio 1.43 [1.29-1.59]; 2.6-fold risk for upper vs lower quintile) as for severe COVID-19. However, the short-term risk of severe pneumonia events associated to the multi-biomarker score at even 3 times higher magnitude (odds ratio 2.21 [1.95-2.50]; 8.0-fold risk for upper vs lower quintile in analysis of the first 2 years after blood sampling). Interpretation: In decade-old blood samples from the UK Biobank, a biomarker score measured by high-throughput metabolomics is indicative of the risk for severe COVID-19. The molecular signature of biomarker changes reflective of risk for severe COVID-19 is similar to that for severe pneumonia, in particular when accounting for the time lag to the COVID-19 pandemic. The even stronger association of the biomarker score with 2-year risk for severe pneumonia lends support to promising screening possibilities for identifying people at high risk for severe COVID-19.", "qid": 25, "docid": "0hxwkzvy", "rank": 20, "score": 0.7883869409561157}, {"content": "Title: C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: a meta-analysis Content: BACKGROUND: Patients critically ill with coronavirus disease-2019 (COVID-19) feature hyperinflammation, and the associated biomarkers may be beneficial for risk stratification. We aimed to investigate the association between several biomarkers, including serum C-reactive protein (CRP), procalcitonin (PCT), D-dimer, and serum ferritin, and COVID-19 severity. METHODS: We performed a comprehensive systematic literature search through electronic databases. The outcome of interest for this study was the composite poor outcome, which comprises mortality, acute respiratory distress syndrome, need for care in an intensive care unit, and severe COVID-19. RESULTS: A total of 5350 patients were pooled from 25 studies. Elevated CRP was associated with an increased composite poor outcome [risk ratio (RR) 1.84 (1.45, 2.33), p < 0.001; I2: 96%] and its severe COVID-19 (RR 1.41; I2: 93%) subgroup. A CRP \u00e2\u00a9\u00be10 mg/L has a 51% sensitivity, 88% specificity, likelihood ratio (LR) + of 4.1, LR- of 0.5, and an area under curve (AUC) of 0.84. An elevated PCT was associated with an increased composite poor outcome [RR 3.92 (2.42, 6.35), p < 0.001; I2: 85%] and its mortality (RR 6.26; I2: 96%) and severe COVID-19 (RR 3.93; I2: 63%) subgroups. A PCT \u00e2\u00a9\u00be0.5 ng/ml has an 88% sensitivity, 68% specificity, LR+ of 2.7, LR- of 0.2, and an AUC of 0.88. An elevated D-dimer was associated with an increased composite poor outcome [RR 2.93 (2.14, 4.01), p < 0.001; I2: 77%], including its mortality (RR 4.15; I2: 83%) and severe COVID-19 (RR 2.42; I2: 58%) subgroups. A D-dimer >0.5 mg/L has a 58% sensitivity, 69% specificity, LR+ of 1.8, LR- of 0.6, and an AUC of 0.69. Patients with a composite poor outcome had a higher serum ferritin with a standardized mean difference of 0.90 (0.64, 1.15), p < 0.0001; I2: 76%. CONCLUSION: This meta-analysis showed that an elevated serum CRP, PCT, D-dimer, and ferritin were associated with a poor outcome in COVID-19. The reviews of this paper are available via the supplemental material section.", "qid": 25, "docid": "s92chxzv", "rank": 21, "score": 0.7875465750694275}, {"content": "Title: The role of biomarkers in diagnosis of COVID-19 \u2013 A systematic review Content: AIMS: As of the 28th April 2020, the COVID-19 pandemic has infiltrated over 200 countries and affected over three million confirmed people. We review different biomarkers to evaluate if they are able to predict clinical outcomes and correlate with the severity of COVID-19 disease. METHODS: A systematic review of the literature was carried out to identify relevant articles using six different databases. Keywords to refine the search included \u2018COVID-19\u2019, \u2018SARS-CoV2\u2019, \u2018Biomarkers\u2019, among others. Only studies which reported data on pre-defined outcomes were included. KEY FINDINGS: Thirty-four relevant articles were identified which reviewed the following biomarkers: C-reactive protein, serum amyloid A, interleukin-6, lactate dehydrogenase, neutrophil-to-lymphocyte ratio, D-dimer, cardiac troponin, renal biomarkers, lymphocytes and platelet count. Of these, all but two, showed significantly higher levels in patients with severe complications of COVID-19 infection compared to their non-severe counterparts. Lymphocytes and platelet count showed significantly lower levels in severe patients compared to non-severe patients. SIGNIFICANCE: Although research is still in its early stages, the discovery of how different biomarkers behave during the course of the disease could help clinicians in identifying severe disease earlier and subsequently improve prognosis. Nevertheless, we urge for more research across the globe to corroborate these findings.", "qid": 25, "docid": "r8mn4lzv", "rank": 22, "score": 0.7875286340713501}, {"content": "Title: Cytokine prediction of mortality in COVID19 patients Content: Coronavirus disease 2019 (COVID19) is a life-threatening infection with uncertain progression and outcome. Assessing the severity of the disease for worsening patients is of importance in making decisions related to supportive mechanical ventilation and aggressive treatments. This was a prospective, non-randomized study that included hospitalized patients diagnosed with COVID19. Pro-inflammatory cytokines were assessed during hospitalization, and we calculated a prediction paradigm for 30-day mortality based on the serum levels of interleukin1\u03b2 (IL1\u03b2), interleukin6 (IL6), interleukin8 (IL8), and tumor necrosis factor alpha (TNF\u03b1) measured by next-generation ELISA. Data of 71 COVID19 patients, mean age 62 years, SD13.8, 50 males, 21 females, were analyzed. Twelve (16.9%) patients died within 7\u201339 days of their first COVID19 positive nasopharyngeal test. Levels of IL6 and TNF\u03b1 were significantly higher in patients that did not survive. IL6 predicted mortality at the cut-off value of 163.4 pg/ml, with a sensitivity of 91.7% and specificity of 57.6%. Our findings demonstrate that IL6 expression is significant for the prediction of 30-day mortality in hospitalized COVID19 patients and, therefore, may assist in treatment decisions.", "qid": 25, "docid": "3mv8pkwu", "rank": 23, "score": 0.7870100736618042}, {"content": "Title: Elevations of serum cancer biomarkers correlate with severity of COVID\u201019 Content: In this retrospective study, we evaluated the levels of a series of serum biomarkers in coronavirus disease 2019 (COVID\u201019) patients (mild: 131; severe: 98; critical: 23). We found that there were significant increases in levels of human epididymis protein 4 (HE4) (73.6 \u00b1 38.3 versus 46.5 \u00b1 14.7, p<0.001), cytokeratin\u201019 fragment (CYFRA21\u20101) (2.2 \u00b1 0.9 versus 1.9 \u00b1 0.8, p<0.001), carcinoembryonic antigen (CEA) (3.4 \u00b1 2.2 versus 2.1 \u00b1 1.2, p<0.001), carbohydrate antigens (CA) 125 (18.1 \u00b1 13.5 versus 10.5 \u00b1 4.6, p<0.001) and 153 (14.4 \u00b1 8.9 versus 10.1 \u00b1 4.4, p<0.001) in COVID\u201019 mild cases as compared to normal control subjects; their levels showed continuous and significant increases in severe and critical cases (HE4, CYFRA21\u20101 and CA125: p<0.001; CEA and CA153: p<0.01). Squamous cell carcinoma antigen (SCC) and CA199 increased significantly only in critical cases of COVID\u201019 as compared with mild and severe cases and normal controls (p<0.01). There were positive associations between levels of C\u2010reactive protein and levels of HE4 (R= 0.631, p<0.001), CYFRA21\u20101(R= 0.431, p<0.001), CEA (R= 0.316, p<0.001), SCC (R= 0.351, p<0.001), CA153 (R= 0.359, p<0.001) and CA125 (R= 0.223, p=0.031). We concluded that elevations of serum cancer biomarkers positively correlated with the pathological progressions of COVID\u201019, demonstrating diffuse and acute lung injuries. This article is protected by copyright. All rights reserved.", "qid": 25, "docid": "i1nehm61", "rank": 24, "score": 0.78544020652771}, {"content": "Title: Longitudinal hematologic and immunologic variations associated with the progression of COVID-19 patients in China Content: BACKGROUND: Crucial roles of hematologic and immunologic responses in progression of coronavirus disease 2019 (COVID-19) remain largely unclear. OBJECTIVE: We sought to address the dynamic changes in hematologic and immunologic biomarkers and their associations with severity and outcomes of COVID-19. METHODS: A retrospective study including 548 patients with COVID-19 with clarified outcome (discharged or deceased) from a national cohort in China was performed. Cross-sectional and longitudinal variations were compared and the associations with different severity and outcomes were analyzed. RESULTS: On admission, the counts of lymphocytes, T-cell subsets, eosinophils, and platelets decreased markedly, especially in severe/critical and fatal patients. Increased neutrophil count and neutrophils-to-lymphocytes ratio were predominant in severe/critical cases or nonsurvivors. During hospitalization, eosinophils, lymphocytes, and platelets showed an increasing trend in survivors, but maintained lower levels or dropped significantly afterwards in nonsurvivors. Nonsurvivors kept a high level or showed an upward trend for neutrophils, IL-6, procalcitonin, D-dimer, amyloid A protein, and C-reactive protein, which were kept stable or showed a downward trend in survivors. Positive correlation between CD8+ T-cell and lymphocytes count was found in survivors but not in nonsurvivors. A multivariate Cox regression model suggested that restored levels of lymphocytes, eosinophils, and platelets could serve as predictors for recovery, whereas progressive increases in neutrophils, basophils, and IL-6 were associated with fatal outcome. CONCLUSIONS: Hematologic and immunologic impairment showed a significantly different profile between survivors and nonsurvivors in patients with COVID-19 with different severity. The longitudinal variations in these biomarkers could serve to predict recovery or fatal outcome.", "qid": 25, "docid": "u0j1atdh", "rank": 25, "score": 0.7845675945281982}, {"content": "Title: C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: a meta-analysis Content: BACKGROUND: Patients critically ill with coronavirus disease-2019 (COVID-19) feature hyperinflammation, and the associated biomarkers may be beneficial for risk stratification. We aimed to investigate the association between several biomarkers, including serum C-reactive protein (CRP), procalcitonin (PCT), D-dimer, and serum ferritin, and COVID-19 severity. METHODS: We performed a comprehensive systematic literature search through electronic databases. The outcome of interest for this study was the composite poor outcome, which comprises mortality, acute respiratory distress syndrome, need for care in an intensive care unit, and severe COVID-19. RESULTS: A total of 5350 patients were pooled from 25 studies. Elevated CRP was associated with an increased composite poor outcome [risk ratio (RR) 1.84 (1.45, 2.33), p < 0.001; I(2): 96%] and its severe COVID-19 (RR 1.41; I(2): 93%) subgroup. A CRP \u2a7e10 mg/L has a 51% sensitivity, 88% specificity, likelihood ratio (LR) + of 4.1, LR- of 0.5, and an area under curve (AUC) of 0.84. An elevated PCT was associated with an increased composite poor outcome [RR 3.92 (2.42, 6.35), p < 0.001; I(2): 85%] and its mortality (RR 6.26; I(2): 96%) and severe COVID-19 (RR 3.93; I(2): 63%) subgroups. A PCT \u2a7e0.5 ng/ml has an 88% sensitivity, 68% specificity, LR+ of 2.7, LR- of 0.2, and an AUC of 0.88. An elevated D-dimer was associated with an increased composite poor outcome [RR 2.93 (2.14, 4.01), p < 0.001; I(2): 77%], including its mortality (RR 4.15; I(2): 83%) and severe COVID-19 (RR 2.42; I(2): 58%) subgroups. A D-dimer >0.5 mg/L has a 58% sensitivity, 69% specificity, LR+ of 1.8, LR- of 0.6, and an AUC of 0.69. Patients with a composite poor outcome had a higher serum ferritin with a standardized mean difference of 0.90 (0.64, 1.15), p < 0.0001; I(2): 76%. CONCLUSION: This meta-analysis showed that an elevated serum CRP, PCT, D-dimer, and ferritin were associated with a poor outcome in COVID-19. The reviews of this paper are available via the supplemental material section.", "qid": 25, "docid": "izzavogm", "rank": 26, "score": 0.7839996814727783}, {"content": "Title: Comparative analysis of laboratory indexes of severe and non-severe patients infected with COVID-19 Content: BACKGROUND: The pandemic coronavirus disease 2019 (COVID-19) has threaten the global health. The characteristics of laboratory findings of coronavirus are of great significance for clinical diagnosis and treatment. We found indicators that may most effectively predict a non-severe COVID-19 patient develop into a severe patient. METHODS: We conducted a meta-analysis to compare the laboratory findings of severe patients with non-severe patients with COVID-19 from searched articles. RESULTS: Through the analysis of laboratory examination information of patients with COVID-19 from 35 articles (5912 patients), we demonstrated that severe cases possessed higher levels of leukocyte (1.20-fold), neutrophil (1.33-fold), CRP (3.04-fold), PCT (2.00-fold), ESR (1.44-fold), AST (1.40-fold), ALT (1.34-fold), LDH (1.54-fold), CK (1.44-fold), CK-MB (1.39-fold), total bilirubin (1.14-fold), urea (1.28-fold), creatine (1.09-fold), PT (1.03-fold) and D-dimer (2.74-fold), as well as lower levels of lymphocytes (1.44-fold), eosinophil (2.00-fold), monocyte (1.08-fold), Hemoglobin (1.53-fold), PLT (1.15-fold), albumin (1.15-fold), and APTT (1.02-fold). Lymphocyte subsets and series of inflammatory cytokines were also different in severe cases with the non-severe ones, including lower levels of CD4 T cells (2.10-fold) and CD8 T cells (2.00-fold), higher levels of IL-1\u00df (1.02-fold), IL-6 (1.93-fold) and IL-10 (1.55-fold). CONCLUSIONS: Some certain laboratory inspections could predict the progress of the COVID-19 changes, especially lymphocytes, CRP, PCT, ALT, AST, LDH, D-dimer, CD4 T cells and IL6, which provide valuable signals for preventing the deterioration of the disease.", "qid": 25, "docid": "o2fgobi1", "rank": 27, "score": 0.7836356163024902}, {"content": "Title: Comparative analysis of laboratory indexes of severe and non-severe patients infected with COVID-19 Content: BACKGROUND: The pandemic coronavirus disease 2019 (COVID-19) has threaten the global health. The characteristics of laboratory findings of coronavirus are of great significance for clinical diagnosis and treatment. We found indicators that may most effectively predict a non-severe COVID-19 patient develop into a severe patient. METHODS: We conducted a meta-analysis to compare the laboratory findings of severe patients with non-severe patients with COVID-19 from searched articles. RESULTS: Through the analysis of laboratory examination information of patients with COVID-19 from 35 articles (5912 patients), we demonstrated that severe cases possessed higher levels of leukocyte (1.20-fold), neutrophil (1.33-fold), CRP (3.04-fold), PCT (2.00-fold), ESR (1.44-fold), AST (1.40-fold), ALT (1.34-fold), LDH (1.54-fold), CK (1.44-fold), CK-MB (1.39-fold), total bilirubin(1.14-fold), urea (1.28-fold), creatine (1.09-fold), PT (1.03-fold) and D-dimer (2.74-fold), as well as lower levels of lymphocytes (1.44-fold), eosinophil (2.00-fold), monocyte (1.08-fold), Hemoglobin (1.53-fold), PLT (1.15-fold), albumin (1.15-fold), and APTT (1.02-fold). Lymphocyte subsets and series of inflammatory cytokines were also different in severe cases with the non-severe ones, including lower levels of CD4 T cells (2.10-fold) and CD8 T cells (2.00-fold), higher levels of IL-1\u03b2 (1.02-fold), IL-6 (1.93-fold) and IL-10 (1.55-fold). CONCLUSIONS: Some certain laboratory inspections could predict the progress of the COVID-19 changes, especially lymphocytes, CRP, PCT, ALT, AST, LDH, D-dimer, CD4 T cells and IL6, which provide valuable signals for preventing the deterioration of the disease.", "qid": 25, "docid": "vrsdi2p3", "rank": 28, "score": 0.7835044860839844}, {"content": "Title: Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019 Content: OBJECTIVE: To explore the clinical value of immune-inflammatory markers to assess the severity of coronavirus disease 2019 (COVID-19). METHODS: 127 consecutive hospitalized patients with confirmed COVID-19 were enrolled in this study, and classified into non-severe and severe groups. Demographics, symptoms, underlying diseases and laboratory data were collected and assessed for predictive value. RESULTS: Of 127 COVID-19 patients, 16 cases (12.60%) were classified into the severe group. High level of interleukin-6 (IL-6), C-reaction protein (CRP) and hypertension were independent risk factors for the severity of COVID-19. The risk model based on IL-6, CRP and hypertension had the highest area under the receiver operator characteristic curve (AUROC). Additionally, the baseline IL-6 was positively correlated with other immune-inflammatory parameters and the dynamic change of IL-6 in the severe cases were parallel to the amelioration of the disease. CONCLUSION: Our study showed that high level of IL-6, CRP and hypertension were independent risk factors for assessing the severity of COVID-19. The risk model established upon IL-6, CRP and hypertension had the highest predictability in this study. Besides, IL-6 played a pivotal role in the severity of COVID-19 and had a potential value for monitoring the process of severe cases.", "qid": 25, "docid": "n75u9qk2", "rank": 29, "score": 0.7834388017654419}, {"content": "Title: The role of interleukin-6 in monitoring severe case of coronavirus disease 2019 Content: Progression to severe disease is a difficult problem in treating coronavirus disease 2019 (COVID-19). The purpose of this study is to explore changes in markers of severe disease in COVID-19 patients. Sixty-nine severe COVID-19 patients were included. Patients with severe disease showed significant lymphocytopenia. Elevated level of lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin, and D-dimer was found in most severe cases. Baseline interleukin-6 (IL-6) was found to be associated with COVID-19 severity. Indeed, the significant increase of baseline IL-6 was positively correlated with the maximal body temperature during hospitalization and with the increased baseline of CRP, LDH, ferritin, and D-dimer. High baseline IL-6 was also associated with more progressed chest computed tomography (CT) findings. Significant decrease in IL-6 and improved CT assessment was found in patients during recovery, while IL-6 was further increased in exacerbated patients. Collectively, our results suggest that the dynamic change in IL-6 can be used as a marker for disease monitoring in patients with severe COVID-19.", "qid": 25, "docid": "6lzdqph8", "rank": 30, "score": 0.7828273177146912}, {"content": "Title: Correlation Analysis Between Disease Severity and Inflammation-related Parameters in Patients with COVID-19 Pneumonia Content: Aim: The new coronavirus pneumonia (COVID-19) outbreaking at the end of 2019 is highly contagious. Crude mortality rate reached 49% in critical patients. Inflammation matters on disease progression. This study analyzed blood inflammation indicators among mild, severe and critical patients, helping to identify severe or critical patients early. Methods: In this cross-sectional study, 100 patients were included and divided to mild, severe or critical groups. Correlation of peripheral blood inflammation-related indicators with disease criticality was analyzed. Cut-off values for critically ill patients were speculated through the ROC curve. Results\uff1aSignificantly, disease severity were associated with age (R=-0.564, P<0.001), interleukin-2 receptor (IL2R) (R=-0.534, P<0.001), interleukin-6 (IL-6) (R=-0.535, P<0.001), interleukin-8 (IL-8) (R=-0.308, P<0.001), interleukin-10 (IL-10) (R=-0.422, P<0.001), tumor necrosis factor \u03b1 (TNF\u03b1) (R=-0.322, P<0.001), C-reactive protein (CRP) (R=-0.604, P<0.001), ferroprotein (R=-0.508, P<0.001), procalcitonin (R=-0.650, P<0.001), white cell counts (WBC) (R=-0.54, P<0.001), lymphocyte counts (LC) (R=-0.56, P<0.001), neutrophil count (NC) (R=-0.585, P<0.001) and eosinophil counts (EC) (R=-0.299, P=0.01). Conclusion\uff1aWith following parameters such as age >67.5 years, IL2R >793.5U/mL, CRP >30.7ng/mL, ferroprotein >2252\u03bcg/L, WBC>9.5*10^9/L or NC >7.305*10^9/L, the progress of COVID-19 to critical stage should be closely observed and possibly prevented. Inflammation is closely related to severity of COVID-19, and IL-6, TNF\u03b1 and IL-8 might be promising therapeutic targets.", "qid": 25, "docid": "370fqkat", "rank": 31, "score": 0.7826235294342041}, {"content": "Title: Early Prediction of Disease Progression in 2019 Novel Coronavirus Pneumonia Patients Outside Wuhan with CT and Clinical Characteristics Content: Objective: To determine the predictive value of CT and clinical characteristics for short-term disease progression in patients with 2019 novel coronavirus pneumonia (NCP). Materials and Methods: 224 patients with confirmed 2019 novel coronavirus (COVID-19) infection outside Wuhan who had chest CT examinations were retrospectively screened. Clinical data were obtained from electronic medical records. CT images were reviewed and scored for lesion distribution, lobe and segment involvement, ground-glass opacities, consolidation, and interstitial thickening. All included patients with moderate NCP were observed for at least 14 days from admission to determine whether they exacerbated to severe NCP (progressive group) or not (stable group). CT and clinical characteristics between the two groups were compared, and multivariate logistic regression and sensitivity analyses were performed to identify the risk factors for developing severe NCP. Results: A total of 141 patients with moderate NCP were included, of which 15 (10.6%) patients developed severe NCP during hospitalization and assigned to the progressive group. Multivariate logistic regression analysis showed that higher neutrophil-to-lymphocyte ratio (NLR) (odds ratio [OR] and 95% confidence interval [CI], 1.26 [1.04-1.53]; P = 0.018) and CT severity score (OR and 95% CI, 1.25 [1.08-1.46]; P = 0.004) on admission were independent predictors for progression to severe NCP, and sensitivity analysis confirmed the consistent results in nonimported patients but not in imported patients. However, no significant difference in lung involvement was found on CT between imported and nonimported patients (all P > 0.05). Patients who were admitted more than 4 days from symptom onset tended to have more severe lung involvement. Spearman correlation analysis showed the close association between CT severity score and inflammatory indexes (r = 0.17~0.47, all P < 0.05). Conclusion: CT severity score was associated with inflammatory levels and higher NLR and CT severity score on admission were independent risk factors for short-term progression in patients with NCP outside Wuhan. Furthermore, early admission and surveillance by CT should be recommended to improve clinical outcomes.", "qid": 25, "docid": "j0ufth5d", "rank": 32, "score": 0.7825876474380493}, {"content": "Title: Elevations of serum cancer biomarkers correlate with severity of COVID-19 Content: In this retrospective study, we evaluated the levels of a series of serum biomarkers in coronavirus disease 2019 (COVID-19) patients (mild: 131; severe: 98; critical: 23). We found that there were significant increases in levels of human epididymis protein 4 (HE4) (73.6 \u00b1 38.3 vs 46.5 \u00b1 14.7 pmol/L; P < .001), cytokeratin-19 fragment (CYFRA21-1) (2.2 \u00b1 0.9 vs 1.9 \u00b1 0.8 \u00b5g/L; P < .001), carcinoembryonic antigen (CEA) (3.4 \u00b1 2.2 vs 2.1 \u00b1 1.2 \u00b5g/L; P < .001), carbohydrate antigens (CA) 125 (18.1 \u00b1 13.5 vs 10.5 \u00b1 4.6 \u00b5g/L; P < .001), and 153 (14.4 \u00b1 8.9 vs 10.1 \u00b1 4.4 \u00b5g/L; P < .001) in COVID-19 mild cases as compared to normal control subjects; their levels showed continuous and significant increases in severe and critical cases (HE4, CYFRA21-1, and CA125: P < .001; CEA and CA153: P < .01). Squamous cell carcinoma antigen (SCC) and CA199 increased significantly only in critical cases of COVID-19 as compared with mild and severe cases and normal controls (P < .01). There were positive associations between levels of C-reactive protein and levels of HE4 (R = .631; P < .001), CYFRA21-1 (R = .431; P < .001), CEA (R = .316; P < .001), SCC (R = .351; P < .001), CA153 (R = .359; P < .001) and CA125 (R = .223; P = .031). We concluded that elevations of serum cancer biomarkers positively correlated with the pathological progressions of COVID-19, demonstrating diffuse and acute pathophysiological injuries in COVID-19.", "qid": 25, "docid": "y5ut2w8r", "rank": 33, "score": 0.7815260887145996}, {"content": "Title: Longitudinal immunological analyses reveal inflammatory misfiring in severe COVID-19 patients Content: Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19)1-4. Yet, longitudinal immunological correlates of disease outcome remain unclear. Here, we serially analysed immune responses in 113 COVID-19 patients with moderate (non-ICU) and severe (ICU) disease. Immune profiling revealed an overall increase in innate cell lineages with a concomitant reduction in T cell number. We identify an association between early, elevated cytokines and worse disease outcomes. Following an early increase in cytokines, COVID-19 patients with moderate disease displayed a progressive reduction in type-1 (antiviral) and type-3 (antifungal) responses. In contrast, patients with severe disease maintained these elevated responses throughout the course of disease. Moreover, severe disease was accompanied by an increase in multiple type 2 (anti-helminths) effectors including, IL-5, IL-13, IgE and eosinophils. Unsupervised clustering analysis of plasma and peripheral blood leukocyte data identified 4 immune signatures, representing (A) growth factors, (B) type-2/3 cytokines, (C) mixed type-1/2/3 cytokines, and (D) chemokines that correlated with three distinct disease trajectories of patients. The immune profile of patients who recovered with moderate disease was enriched in tissue reparative growth factor signature (A), while the profile for those with worsened disease trajectory had elevated levels of all four signatures. Thus, we identified development of a maladapted immune response profile associated with severe COVID-19 outcome and early immune signatures that correlate with divergent disease trajectories.", "qid": 25, "docid": "06gbt9t0", "rank": 34, "score": 0.7813014984130859}, {"content": "Title: Prompt Predicting of Early Clinical Deterioration of Moderate-to-Severe COVID-19 Patients: Usefulness of a Combined Score Using IL-6 in a Preliminary Study Content: BACKGROUND: The early identification of patients at risk of clinical deterioration is of interest considering the timeline of COVID-19 after the onset of symptoms. OBJECTIVE: The aim of our study was to evaluate the usefulness of testing serum IL-6 and other serological and clinical biomarkers, to predict a short-term negative clinical course of patients with noncritical COVID-19. METHODS: A total of 208 patients with noncritical COVID-19 pneumonia at admission were consecutively enrolled. Clinical and laboratory findings obtained on admission were analyzed by using survival analysis and stepwise logistic regression for variable selection. Three-day worsening as outcome in a logistic model to generate a prognostic score was used. RESULTS: Clinical worsening occurred in 63 patients (16 = died; 39 = transferred to intensive care unit; 8 worsening of respiratory failure). Forty-five of them worsened within 3 days after admission. The risk of clinical worsening was progressively enhanced along with increasing quartiles of IL-6 levels. Multivariate analysis showed that IL-6 (P = .005), C-reactive protein (CRP) (P = .003), and SaO2/FiO2 (P = .014) were the best predictors for clinical deterioration in the first 3 days after admission. The combined score yielded an area under the curve = 0.88 (95% confidence interval: 0.83-0.93). A nomogram predicting the probability of 3-day worsening was generated. The score also showed good performance for 7-day and 14- or 21-day worsening and in predicting death occurring during all the follow-up. CONCLUSIONS: Combining IL-6, CRP, and SaO2/FiO2 in a score may help clinicians to identify on admission those patients with COVID-19 who are at high risk for a further 3-day clinical deterioration.", "qid": 25, "docid": "hf9q39m7", "rank": 35, "score": 0.7808380722999573}, {"content": "Title: Blood parameters measured on admission as predictors of outcome for COVID-19; a prospective UK cohort study Content: Abstract: Introduction: COVID-19 has an unpredictable clinical course so prognostic biomarkers would be invaluable when triaging patients on admission to hospital. Many biomarkers have been suggested using large observational datasets but sample timing is crucial to ensure prognostic relevance. The DISCOVER study prospectively recruited patients with COVID-19 admitted to a UK hospital and analysed a panel of putative prognostic biomarkers on the admission blood sample to identify markers of poor outcome. Methods: Consecutive patients admitted to hospital with proven or clinicoradiological suspected COVID-19 were recruited. Admission bloods were extracted from the clinical laboratory. A panel of biomarkers (IL-6, suPAR, KL-6, Troponin, Ferritin, LDH, BNP, Procalcitonin) were performed in addition to routinely performed markers (CRP, neutrophils, lymphocytes, neutrophil:lymphocyte ratio). Age, NEWS score and CURB-65 were included as comparators. All biomarkers were tested in logistic regression against a composite outcome of non-invasive ventilation, intensive care admission, or death, with Area Under the Curve (AUC) figures calculated. Results: 155 patients had 28-day outcomes at the time of analysis. CRP (AUC 0.51 ,CI:0.40-0.62), lymphocyte count (AUC 0.62 ,CI:0.51-0.72), and other routine markers did not predict the primary outcome. IL-6 (AUC: 0.78,0.65-0.89) and suPAR (AUC 0.77 ,CI: 0.66-0.85) showed some promise, but simple clinical features alone such as NEWS score (AUC: 0.74 ,0.64-0.83) or age (AUC: 0.70 ,0.61-0.78) performed nearly as well. Discussion: Admission blood biomarkers have only moderate predictive value for predicting COVID-19 outcomes, while simple clinical features such as age and NEWS score outperform many biomarkers. IL-6 and suPAR had the best performance, and further studies should validate these biomarkers in a prospective fashion.", "qid": 25, "docid": "50ovfwvo", "rank": 36, "score": 0.7803525924682617}, {"content": "Title: Inflammation Profiling of Critically Ill Coronavirus Disease 2019 Patients Content: OBJECTIVES: Coronavirus disease 2019 is caused by severe acute respiratory syndrome-coronavirus-2 infection to which there is no community immunity. Patients admitted to ICUs have high mortality, with only supportive therapies available. Our aim was to profile plasma inflammatory analytes to help understand the host response to coronavirus disease 2019. DESIGN: Daily blood inflammation profiling with immunoassays. SETTING: Tertiary care ICU and academic laboratory. SUBJECTS: All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome-coronavirus-2, using standardized hospital screening methodologies, had daily blood samples collected until either testing was confirmed negative on ICU day 3 (coronavirus disease 2019 negative), or until ICU day 7 if the patient was positive (coronavirus disease 2019 positive). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Age- and sex-matched healthy controls and ICU patients that were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well-balanced with the exception that coronavirus disease 2019 positive patients were more likely than coronavirus disease 2019 negative patients to suffer bilateral pneumonia. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. We measured 57 inflammatory analytes and then analyzed with both conventional statistics and machine learning. Twenty inflammatory analytes were different between coronavirus disease 2019 positive patients and healthy controls (p < 0.01). Compared with coronavirus disease 2019 negative patients, coronavirus disease 2019 positive patients had 17 elevated inflammatory analytes on one or more of their ICU days 1\u20133 (p < 0.01), with feature classification identifying the top six analytes between cohorts as tumor necrosis factor, granzyme B, heat shock protein 70, interleukin-18, interferon-gamma-inducible protein 10, and elastase 2. While tumor necrosis factor, granzyme B, heat shock protein 70, and interleukin-18 were elevated for all seven ICU days, interferon-gamma-inducible protein 10 transiently elevated on ICU days 2 and 3 and elastase 2 increased over ICU days 2\u20137. Inflammation profiling predicted coronavirus disease 2019 status with 98% accuracy, whereas elevated heat shock protein 70 was strongly associated with mortality. CONCLUSIONS: While many inflammatory analytes were elevated in coronavirus disease 2019 positive ICU patients, relative to healthy controls, the top six analytes distinguishing coronavirus disease 2019 positive ICU patients from coronavirus disease 2019 negative ICU patients were tumor necrosis factor, granzyme B, heat shock protein 70, interleukin-18, interferon-gamma-inducible protein 10, and elastase 2.", "qid": 25, "docid": "jlzncyax", "rank": 37, "score": 0.7798632383346558}, {"content": "Title: Expressions of multiple inflammation markers in the patients with 2019 novel coronavirus pneumonia and their clinical values/ \u4e2d\u534e\u68c0\u9a8c\u533b\u5b66\u6742\u5fd7 Content: Objective@#To explore the Expressions of multiple inflammation markers in the patients with 2019 novel coronavirus pneumonia (COVID-19) and their clinical values, and to provide theoretical basis for clinical diagnosis and treatment.@*Methods@#A total of 164 patients, diagnosed with COVID-19 and admitted to Guangzhou Eighth People&apos;s Hospital from January to February 2020, were selected as the research group and divided into three groups (ordinary, severe, and critically severe pneumonia) according to the disease severity. Meandwhile 66 non-infected patients during the same period were selected as negative control group. The expressions of WBC, LYM, CRP, SAA, and PCT were retrospective studied and compared between groups. The diagnostic values of WBC, CRP, SAA and the combination of these three markers in all patients with COVID-19 and in different severity groups were analyzed by ROC curve.@*Results@#Compared with control group (WBC count :8.13(6.51,9.42)\u00d7109/L, LYM count:2.00(1.28,2.43)\u00d7109/L), WBC count [4.94(4.05, 6.67) \u00d7109/L] and LYM count [1.33(0.94, 1.96) \u00d7109/L] of COVID-19 patients were significantly reduced (Z=-7.435, P&lt;0.01; Z=-4.906, P&lt;0.01) . Compared with the control group [CRP: 1.36 (0.57~5.67) mg/ml; SAA:[4.98 (4.80~15.75) mg/mL], CRP [7.93 (2.45~23.98) mg/ml] and SAA [34.13 (4.83~198.40) mg/ml] were increased in research group (Z=-5.72, P&lt;0.01; Z=-4.166, P&lt;0.01) . PCT in the control group and the research group were 0.100 0(0.030 6~0.100 0)ng/ml and 0.044 5(0.031 6~0.077 0)ng/ml, respectively. There was no statistical difference between two groups (Z=-1.451, P=0.147) . The areas under the ROC curve (AUC) of WBC, CRP and SAA in patients with COVID-19 were 0.814, 0.742, 0.673, respectively (P&lt;0.01), while the AUC of the combination of three indexes for COVID-19 diagnosis was 0.882, with 83.33%(55/66) specificity and 84.76% (139/164) sensitivity, P&lt;0.01.The AUCs of WBC, CRP, and SAA for predicting severe and critically severe COVID-19 were 0.799, 0.779, and 0.886 , respectively (P&lt;0.01), and the AUC of the combination of three indexes for the diagnosis of severe and critically severe COVID-19 was 0.924, with 78.67% (118/150) specificity and 14/14 sensitivity (P&lt;0.01).@*Conclusion@#Combining detection of WBC, CRP and SAA can improve the specificity and sensitivity of COVID-19 diagnosis, with a high diagnostic value for severe and critically severe COVID-19.", "qid": 25, "docid": "pwyculzt", "rank": 38, "score": 0.7796580195426941}, {"content": "Title: Potential biochemical markers to identify severe cases among COVID-19 patients Content: There is a high mortality and long hospitalization period for severe cases with 2019 novel coronavirus disease (COVID-19) pneumonia. Therefore, it makes sense to search for a potential biomarker that could rapidly and effectively identify severe cases early. Clinical samples from 28 cases of COVID-19 (8 severe cases, 20 mild cases) in Zunyi District from January 29, 2020 to February 21, 2020 were collected and otherwise statistically analysed for biochemical markers. Serum urea, creatinine (CREA) and cystatin C (CysC) concentrations in severe COVID-19 patients were significantly higher than those in mild COVID-19 patients (P<0.001), and there were also significant differences in serum direct bilirubin (DBIL), cholinesterase (CHE) and lactate dehydrogenase (LDH) concentrations between severe and mild COVID-19 patients (P<0.05). Serum urea, CREA, CysC, DBIL, CHE and LDH could be used to distinguish severe COVID-19 cases from mild COVID-19 cases. In particular, serum biomarkers, including urea, CREA, CysC, which reflect glomerular filtration function, may have some significance as potential indicators for the early diagnosis of severe COVID-19 and to distinguish it from mild COVID-19. Glomerular filtration function injury in severe COVID-19 patients should also be considered by clinicians.", "qid": 25, "docid": "6rs86u5v", "rank": 39, "score": 0.7793639898300171}, {"content": "Title: The profile of peripheral blood lymphocyte subsets and serum cytokines in children with 2019 novel coronavirus pneumonia Content: OBJECTIVES: The study was aimed at investigating the characteristics of peripheral blood lymphocyte subsets and serum cytokines in children with 2019 novel coronavirus (2019-nCoV) pneumonia. METHODS: Children with 2019-nCoV pneumonia or with respiratory syncytial virus (RSV) pneumonia were included. Data including lymphocyte subsets and serum cytokines were collected and analyzed. RESULTS: 56 patients were included in the study, 40 children with 2019-nCoV pneumonia and 16 children with RSV pneumonia. Compared with children with RSV pneumonia, patients with 2019-nCoV pneumonia had higher count of CD3+8+ lymphocyte, higher percentages of CD3+, CD3+8+ lymphocytes and a lower percentage of CD19+ lymphocyte. The serum IL-10 level was significantly higher in children with RSV pneumonia. One 2019-nCoV pneumonia child who was with an obvious increase of IL-10 developed severe pneumonia. CONCLUSIONS: Immune response played a very important role in the development of 2019-nCoV pneumonia. The effective CD8+ T cell response might influence the severity of 2019-nCoV pneumonia. The adaptable change in IL-10 level might contribute to the relatively mild pneumonia symptoms in children with 2019-nCoV pneumonia and bacterial co-infection might be a risk factor of severe 2019-nCoV pneumonia.", "qid": 25, "docid": "97q9e8u7", "rank": 40, "score": 0.779201865196228}, {"content": "Title: The hemocyte counts as a potential biomarker for predicting disease progression in COVID-19: a retrospective study Content: Objectives In December 2019, there was an outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, and since then, the disease has been increasingly spread throughout the world. Unfortunately, the information about early prediction factors for disease progression is relatively limited. Therefore, there is an urgent need to investigate the risk factors of developing severe disease. The objective of the study was to reveal the risk factors of developing severe disease by comparing the differences in the hemocyte count and dynamic profiles in patients with severe and non-severe COVID-19. Methods In this retrospectively analyzed cohort, 141 confirmed COVID-19 patients were enrolled in Taizhou Public Health Medical Center, Taizhou Hospital, Zhejiang Province, China, from January 17, 2020 to February 26, 2020. Clinical characteristics and hemocyte counts of severe and non-severe COVID patients were collected. The differences in the hemocyte counts and dynamic profiles in patients with severe and non-severe COVID-19 were compared. Multivariate Cox regression analysis was performed to identify potential biomarkers for predicting disease progression. A concordance index (C-index), calibration curve, decision curve and the clinical impact curve were calculated to assess the predictive accuracy. Results The data showed that the white blood cell count, neutrophil count and platelet count were normal on the day of hospital admission in most COVID-19 patients (87.9%, 85.1% and 88.7%, respectively). A total of 82.8% of severe patients had lymphopenia after the onset of symptoms, and as the disease progressed, there was marked lymphopenia. Multivariate Cox analysis showed that the neutrophil count (hazard ratio [HR] = 4.441, 95% CI = 1.954-10.090, p = 0.000), lymphocyte count (HR = 0.255, 95% CI = 0.097-0.669, p = 0.006) and platelet count (HR = 0.244, 95% CI = 0.111-0.537, p = 0.000) were independent risk factors for disease progression. The C-index (0.821 [95% CI, 0.746-0.896]), calibration curve, decision curve and the clinical impact curve showed that the nomogram can be used to predict the disease progression in COVID-19 patients accurately. In addition, the data involving the neutrophil count, lymphocyte count and platelet count (NLP score) have something to do with improving risk stratification and management of COVID-19 patients. Conclusions We designed a clinically predictive tool which is easy to use for assessing the progression risk of COVID-19, and the NLP score could be used to facilitate patient stratification management.", "qid": 25, "docid": "rkm6c8z6", "rank": 41, "score": 0.7790745496749878}, {"content": "Title: The hemocyte counts as a potential biomarker for predicting disease progression in COVID-19: a retrospective study. Content: Objectives In December 2019, there was an outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, and since then, the disease has been increasingly spread throughout the world. Unfortunately, the information about early prediction factors for disease progression is relatively limited. Therefore, there is an urgent need to investigate the risk factors of developing severe disease. The objective of the study was to reveal the risk factors of developing severe disease by comparing the differences in the hemocyte count and dynamic profiles in patients with severe and non-severe COVID-19. Methods In this retrospectively analyzed cohort, 141 confirmed COVID-19 patients were enrolled in Taizhou Public Health Medical Center, Taizhou Hospital, Zhejiang Province, China, from January 17, 2020 to February 26, 2020. Clinical characteristics and hemocyte counts of severe and non-severe COVID patients were collected. The differences in the hemocyte counts and dynamic profiles in patients with severe and non-severe COVID-19 were compared. Multivariate Cox regression analysis was performed to identify potential biomarkers for predicting disease progression. A concordance index (C-index), calibration curve, decision curve and the clinical impact curve were calculated to assess the predictive accuracy. Results The data showed that the white blood cell count, neutrophil count and platelet count were normal on the day of hospital admission in most COVID-19 patients (87.9%, 85.1% and 88.7%, respectively). A total of 82.8% of severe patients had lymphopenia after the onset of symptoms, and as the disease progressed, there was marked lymphopenia. Multivariate Cox analysis showed that the neutrophil count (hazard ratio [HR] = 4.441, 95% CI = 1.954-10.090, p = 0.000), lymphocyte count (HR = 0.255, 95% CI = 0.097-0.669, p = 0.006) and platelet count (HR = 0.244, 95% CI = 0.111-0.537, p = 0.000) were independent risk factors for disease progression. The C-index (0.821 [95% CI, 0.746-0.896]), calibration curve, decision curve and the clinical impact curve showed that the nomogram can be used to predict the disease progression in COVID-19 patients accurately. In addition, the data involving the neutrophil count, lymphocyte count and platelet count (NLP score) have something to do with improving risk stratification and management of COVID-19 patients. Conclusions We designed a clinically predictive tool which is easy to use for assessing the progression risk of COVID-19, and the NLP score could be used to facilitate patient stratification management.", "qid": 25, "docid": "nqee1shq", "rank": 42, "score": 0.7790745496749878}, {"content": "Title: A machine learning-based model for survival prediction in patients with severe COVID-19 infection Content: The sudden increase of COVID-19 cases is putting a high pressure on healthcare services worldwide. At the current stage, fast, accurate and early clinical assessment of the disease severity is vital. To support decision making and logistical planning in healthcare systems, this study leverages a database of blood samples from 404 infected patients in the region of Wuhan, China to identify crucial predictive biomarkers of disease severity. For this purpose, machine learning tools selected three biomarkers that predict the survival of individual patients with more than 90% accuracy: lactic dehydrogenase (LDH), lymphocyte and high-sensitivity C-reactive protein (hs-CRP). In particular, relatively high levels of LDH alone seem to play a crucial role in distinguishing the vast majority of cases that require immediate medical attention. This finding is consistent with current medical knowledge that high LDH levels are associated with tissue breakdown occurring in various diseases, including pulmonary disorders such as pneumonia. Overall, this paper suggests a simple and operable formula to quickly predict patients at the highest risk, allowing them to be prioritised and potentially reducing the mortality rate.", "qid": 25, "docid": "s9j21zsy", "rank": 43, "score": 0.7786445617675781}, {"content": "Title: Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019 Content: Abstract Objective To explore the clinical value of immune-inflammatory markers to assess the severity of coronavirus disease 2019 (COVID-19). Methods 127 consecutive hospitalized patients with confirmed COVID-19 were enrolled in this study, and classified into non-severe and severe groups. Demographics, symptoms, underlying diseases and laboratory data were collected and assessed for predictive value. Results Of 127 COVID-19 patients, 16 cases (12.60%) were classified into the severe group. High level of interleukin-6 (IL-6), C-reaction protein (CRP) and hypertension were independent risk factors for the severity of COVID-19. The risk model based on IL-6, CRP and hypertension had the highest area under the receiver operator characteristic curve (AUROC). Additionally, the baseline IL-6 was positively correlated with other immune-inflammatory parameters and the dynamic change of IL-6 in the severe cases were parallel to the amelioration of the disease. Conclusion Our study showed that high level of IL-6, CRP and hypertension were independent risk factors for assessing the severity of COVID-19. The risk model established upon IL-6, CRP and hypertension had the highest predictability in this study. Besides, IL-6 played a pivotal role in the severity of COVID-19 and had a potential value for monitoring the process of severe cases.", "qid": 25, "docid": "8ek694p3", "rank": 44, "score": 0.7785547971725464}, {"content": "Title: Prompt predicting of early clinical deterioration of moderate-to-severe COVID-19 patients: usefulness of a combined score using IL-6 in a preliminary study Content: Abstract Background The early identification of patients at risk of clinical deterioration is of interest considering the timeline of COVID-19 after the onset of symptoms. Objective The aim of our study was to evaluate the usefulness of testing serum IL-6 and other serological and clinical biomarkers, to predict a short-term negative clinical course of non critical COVID-19 patients. Methods 208 patients with non critical COVID-19 pneumonia at admission were consecutively enrolled. Clinical and laboratory findings obtained upon admission were analyzed by using survival analysis and stepwise logistic regression for variable selection. Three-day worsening as outcome in a logistic model to generate a prognostic score was used. Results Clinical worsening occurred in 63 patients (16=died; 39=transferred to Intensive Care Unit; 8 worsening of respiratory failure). Forty-five of them worsened within 3 days after admission. The risk of clinical worsening was progressively enhanced along with increasing quartiles of IL-6 levels. Multivariate analysis showed that IL-6 (p=0.005), CRP (p=0.003) and SaO2/FiO2 (p=0.014) and were the best predictors for clinical deterioration in the first 3 days after admission. The combined score yielded an AUC=0.88 (95% CI 0.83\u20130.93). A nomogram predicting the probability of 3-day worsening was generated. The score also showed good performance for 7-day and 14-day or 21-day worsening and in predicting death occurring during all the follow-up. Conclusions Combining IL-6, CRP and SaO2/FiO2 in a score, may help clinicians to identify upon admission those patients with COVID-19 who are at high risk for a further 3-day clinical deterioration.", "qid": 25, "docid": "zghlogmr", "rank": 45, "score": 0.7783800363540649}, {"content": "Title: Serum KL\u20106 can distinguish between different phenotypes of severe COVID\u201019 Content: We read the article by D'Alessandro Miriana et al. with great interest and appreciate their efforts to evaluate the role of serum Krebs von den Lungen\u20106 (KL\u20106) as a prognostic biomarker of severe coronavirus disease 2019 (COVID\u201019).(1) This article is protected by copyright. All rights reserved.", "qid": 25, "docid": "a0s74x4m", "rank": 46, "score": 0.7774817943572998}, {"content": "Title: Plasma CRP level is positively associated with the severity of COVID-19 Content: AIMS: The coronavirus disease 2019 (COVID-19) is characterized as highly contagious and deadly; however there is no credible and convenient biomarker to predict the severity of the disease. The aim of the present study was to estimate whether the CRP level is able to act as a marker in indicating the severity of COVID-19. METHODS: Patients who complained cough or chest pain with or without fever were enrolled after laboratory confirmed of SARS-CoV-2 viral nucleic acid via qRT-PCR. Chest computed tomography (CT) was then performed to classify the patients into mild, moderate and severe pneumonia groups according to the interim management guideline. Then linear regression models were applied to analyze the association between c-reactive protein (CRP) levels and severity of COVID-19 pneumonia. RESULTS: When compared to mild pneumonia, the adjusted-Odds Ratio were 11.46, p = 0.029 and 23.40, p = 0.025 in moderate and severe pneumonia, respectively. The area under receiver operation curve was 0.898 (95% CI 0.835, 0.962, p < 0.001). Higher plasma CRP level indicated severe COVID-19 pneumonia and longer inpatients duration. CONCLUSIONS: The level of plasma CRP was positively correlated to the severity of COVID-19 pneumonia. Our findings could assist to discern patients of moderate to severe COVID-19 pneumonia from the mild ones. Our findings may be useful as an earlier indicator for severe illness and help physicians to stratify patients for intense care unit transfer.", "qid": 25, "docid": "wbjbf1m0", "rank": 47, "score": 0.7772058248519897}, {"content": "Title: The profile of peripheral blood lymphocyte subsets and serum cytokines in children with 2019 novel coronavirus pneumonia Content: Abstract Objectives The study was aimed at investigating the characteristics of peripheral blood lymphocyte subsets and serum cytokines in children with 2019 novel coronavirus (2019-nCoV) pneumonia. Methods Children with 2019-nCoV pneumonia or with respiratory syncytial virus (RSV) pneumonia were included. Data including lymphocyte subsets and serum cytokines were collected and analyzed. Results : 56 patients were included in the study, 40 children with 2019-nCoV pneumonia and 16 children with RSV pneumonia. Compared with children with RSV pneumonia, patients with 2019-nCoV pneumonia had higher count of CD3+8+ lymphocyte, higher percentages of CD3+, CD3+8+ lymphocytes and a lower percentage of CD19+ lymphocyte. The serum IL-10 level was significantly higher in children with RSV pneumonia. One 2019-nCoV pneumonia child who was with an obvious increase of IL-10 developed severe pneumonia. Conclusions Immune response played a very important role in the development of 2019-nCoV pneumonia. The effective CD8+ T cell response might influence the severity of 2019-nCoV pneumonia. The adaptable change in IL-10 level might contribute to the relatively mild pneumonia symptoms in children with 2019-nCoV pneumonia and bacterial co-infection might be a risk factor of severe 2019-nCoV pneumonia.", "qid": 25, "docid": "i0mnxqa0", "rank": 48, "score": 0.7769308090209961}, {"content": "Title: Can we predict the severity of coronavirus disease 2019 with a routine blood test? Content: INTRODUCTION: The ongoing worldwide pandemic of coronavirus disease 2019 (COVID\u00ad19) has posed a huge threat to global public health. However, the issue as to whether routine blood tests could be used to monitor and predict the severity and prognosis of COVID\u00ad19 has not been comprehensively investigated so far. OBJECTIVES: This study aimed to provide an overview of the association of markers in the routine blood test with the severity of COVID\u00ad19. METHODS: PubMed, Embase, Cochrane Library, Wanfang, and China National Knowledge Infrastructure (CNKI) databases were searched to identify studies reporting data on markers in the routine blood test and the severity of COVID\u00ad19, published until March 20, 2020. The STATA software was used for meta\u00adanalysis. RESULTS: A total of 15 studies with 3090 patients with COVID\u00ad19 were included in this analysis. Patients in the nonsevere group, compared with those in the severe group, had lower counts of white blood cells (weighted mean difference [WMD], -0.85 [\u00d7109/l]; 95% CI, -1.54 to -0.16; P = 0.02) and neutrophils (WMD, -1.57 [\u00d7109/l]; 95% CI, -2.6 to -0.54; P = 0.003), greater counts of lymphocytes (WMD, 0.29 [\u00d7109/l]; 95% CI, 0.22-0.36; P <0.001) and platelets (WMD, 19.05 [\u00d7109/l]; 95% CI, 3.04-35.06; P = 0.02), and a lower neutrophil\u00adto\u00adlymphocyte (NLR) ratio (WMD, -2.48; 95% CI, -3.81 to -1.15; P <0.001). There was no difference in the monocyte count (WMD, 0.01 [\u00d7109/l]; 95% CI, -0.01 to 0.03; P = 0.029) between these 2 groups. Sensitivity analysis and meta\u00adanalysis based on standard mean difference did not change the conclusions regarding neutrophils, lymphocytes, and NLR, but yielded inconsistent results for white blood cells and platelets. CONCLUSIONS: Severe patients had more neutrophils, higher NLR level, and fewer lymphocytes than non-severe patients with COVID-19. Measurement of these markers might assist clinicians to monitor and predict the severity and prognosis of COVID-19.", "qid": 25, "docid": "o2un26ug", "rank": 49, "score": 0.7766255140304565}, {"content": "Title: Characteristics of inflammatory factors and lymphocyte subsets in patients with severe COVID\u201019 Content: To investigate the inflammatory factors and lymphocyte subsets which play an important role in the course of severe coronavirus disease 2019 (COVID\u201019). A total of 27 patients with severe COVID\u201019 who were admitted to Tongji Hospital in Wuhan from 1 to 21 February 2020 were recruited to the study. The characteristics of interleukin\u20101\u03b2 (IL\u20101\u03b2), IL\u20102 receptor (IL\u20102R), IL\u20106, IL\u20108, IL\u201010, tumor necrosis factor\u2010\u03b1 (TNF)\u2010\u03b1, C\u2010reactive protein (CRP), serum ferritin and procalcitonin (PCT), and lymphocyte subsets of these patients were retrospectively compared before and after treatment. Before treatment, there was no significant difference in most inflammatory factors (IL\u20101\u03b2, IL\u20102R, IL\u20106, IL\u20108, IL\u201010, CRP, and serum ferritin) between male and female patients. Levels of IL\u20102R, IL\u20106, TNF\u2010\u03b1, and CRP decreased significantly after treatment, followed by IL\u20108, IL\u201010, and PCT. Serum ferritin was increased in all patients before treatment but did not decrease significantly after treatment. IL\u20101\u03b2 was normal in most patients before treatment. Lymphopenia was common among these patients with severe COVID\u201019. Analysis of lymphocyte subsets showed that CD4+ and particularly CD8+ T lymphocytes increased significantly after treatment. However, B lymphocytes and natural killer cells showed no significant changes after treatment. A pro\u2010inflammatory response and decreased level of T lymphocytes were associated with severe COVID\u201019.", "qid": 25, "docid": "ezbmr4qz", "rank": 50, "score": 0.7756046652793884}, {"content": "Title: Longitudinal hematologic and immunologic variations associated with the progression of COVID-19 patients in China Content: Background Crucial roles of hematologic and immunologic responses in progression of COVID-19 remains largely unclear. Objective We sought to address the dynamic changes of hematologic and immunologic biomarkers and their associations with severity and outcomes of the disease. Methods A retrospective study including 548 COVID-19 patients with clarified outcome (discharged or deceased) from a national cohort in China was performed. Cross-sectional and longitudinal variations were compared and the associations with different severity and outcomes were analyzed. Results On admission, the counts of lymphocytes, T cell subsets, eosinophils and platelets decreased markedly, especially in severe/critical and fatal patients. Increased neutrophil count and neutrophils-to-lymphocytes ratio were predominant in severe/critical cases or non-survivors. During hospitalization, eosinophils, lymphocytes and platelets were shown an increasing trend in survivors, but maintained lower levels or dropped significantly afterwards in non-survivors. Non-survivors kept high level or showed an upward trend for neutrophils, IL-6, procalcitonin, D-dimer, amyloid A protein and C-reactive protein, which were kept stable or shown downward trend in survivors. Positive correlation between CD8+ T cell and lymphocytes count was found in survivors but not in non-survivors. A multivariate Cox regression model suggested that restored levels of lymphocytes, eosinophils and platelets could serve as the predictors for the recovery, while progressive increases in neutrophils, basophils and IL-6 were associated with fatal outcome. Conclusions Hematologic and immunologic impairment showed a significantly different profile between survivors and non-survivors in COVID-19 patients with different severity. The longitudinal variations of these biomarkers could serve to predict recovery or fatal outcome.", "qid": 25, "docid": "mfaza5rg", "rank": 51, "score": 0.7752195596694946}, {"content": "Title: Prediction of the severity of Corona Virus Disease 2019 and its adverse clinical outcomes Content: This study aims to investigate blood and biochemical laboratory findings in patients with severe Corona Virus Disease 2019 (COVID-19) and to develop a joint predictor for predicting the likelihood of severe COVID-19 and its adverse clinical outcomes, to provide more information for treatment. We collected the data of 88 patients with laboratory-confirmed COVID-19. Then patients were divided into a non-severe group and a critical group (including critically ill cases). Univariate analysis showed that the absolute lymphocyte count, albumin level, albumin/globulin (A/G) ratio, lactate dehydrogenase (LDH) level, interleukin-6 (IL-6) level, erythrocyte count, globulin level, blood glucose level, and age were significantly correlated with the severity of COVID-19. The multivariate binary logistic regression model revealed that Age, absolute lymphocyte count, and IL-6 level were independent risk factors in patients with COVID-19. The receiver operating characteristic (ROC) curve revealed that the combination of IL-6 level, absolute lymphocyte count and age is superior to a single factor as predictors for predicting severe COVID-19, regardless of whether it is the area under curve (AUC) or the prediction sensitivity and specificity. Early application is beneficial to early identification of critically ill patients and timing individual treatments to reduce mortality.", "qid": 25, "docid": "2bjn0fmr", "rank": 52, "score": 0.7752009630203247}, {"content": "Title: Prediction of the severity of Corona Virus Disease 2019 and its adverse clinical outcomes. Content: This study aims to investigate blood and biochemical laboratory findings in patients with severe Corona Virus Disease 2019 (COVID-19) and to develop a joint predictor for predicting the likelihood of severe COVID-19 and its adverse clinical outcomes, to provide more information for treatment. We collected the data of 88 patients with laboratory-confirmed COVID-19. Then patients were divided into a non-severe group and a critical group (including critically ill cases). Univariate analysis showed that the absolute lymphocyte count, albumin level, albumin/globulin (A/G) ratio, lactate dehydrogenase (LDH) level, interleukin-6 (IL-6) level, erythrocyte count, globulin level, blood glucose level, and age were significantly correlated with the severity of COVID-19. The multivariate binary logistic regression model revealed that Age, absolute lymphocyte count, and IL-6 level were independent risk factors in patients with COVID-19. The receiver operating characteristic (ROC) curve revealed that the combination of IL-6 level, absolute lymphocyte count and age is superior to a single factor as predictors for predicting severe COVID-19, regardless of whether it is the area under curve (AUC) or the prediction sensitivity and specificity. Early application is beneficial to early identification of critically ill patients and timing individual treatments to reduce mortality.", "qid": 25, "docid": "dmbc8kb4", "rank": 53, "score": 0.7752009630203247}, {"content": "Title: Correlation between the variables collected at admission and progression to severe cases during hospitalization among patients with COVID\u201019 in Chongqing Content: Mortality is high among severe patients with 2019 novel coronavirus\u2010infected disease (COVID\u201019). Early prediction of progression to severe cases is needed. We retrospectively collected patients with COVID\u201019 in two hospital of Chongqing from 1st January to 29th February 2020. At admission, we collected the demographics and laboratory tests to predict whether the patient would progress to severe cases in hospitalization. Severe case was confirmed when one of the following criteria occurred: (a) dyspnea, respiratory rate \u226530 breaths/min, (b) blood oxygen saturation \u226493%, and (c) PaO(2)/FiO(2) \u2264 300 mm Hg. At admission, 348 mild cases were enrolled in this study. Of them, 20 (5.7%) patients progressed to severe cases after median 4.0 days (interquartile range: 2.3\u20106.0). Pulmonary inflammation index, platelet counts, sodium, C\u2010reactive protein, prealbumin, and PaCO(2) showed good distinguishing power to predict progression to severe cases (each area under the curve of receiver operating characteristics [AUC] \u2265 0.8). Age, heart rate, chlorine, alanine aminotransferase, aspartate aminotransferase, procalcitonin, creatine kinase, pH, CD3 counts, and CD4 counts showed moderate distinguishing power (each AUC between 0.7\u20100.8). And potassium, creatinine, temperature, and D\u2010dimer showed mild distinguishing power (each AUC between 0.6\u20100.7). In addition, higher C\u2010reactive protein was associated with shorter time to progress to severe cases (r = \u22120.62). Several easily obtained variables at admission are associated with progression to severe cases during hospitalization. These variables provide a reference for the medical staffs when they manage the patients with COVID\u201019.", "qid": 25, "docid": "m3hwkbqx", "rank": 54, "score": 0.7751842141151428}, {"content": "Title: Time-series plasma cell-free DNA analysis reveals disease severity of COVID-19 patients Content: Symptoms of coronavirus disease 2019 (COVID-19) range from asymptomatic to severe pneumonia and death. Detection of individuals at high risk for critical condition is crucial for control of the disease. Herein, for the first time, we profiled and analyzed plasma cell-free DNA (cfDNA) of mild and severe COVID-19 patients. We found that in comparison between mild and severe COVID-19 patients, Interleukin-37 signaling was one of the most relevant pathways; top significantly altered genes included POTEH, FAM27C, SPATA48, which were mostly expressed in prostate and testis; adrenal glands, small intestines and liver were tissues presenting most differentially expressed genes. Our data thus revealed potential tissue involvement, provided insights into mechanism on COVID-19 progression, and highlighted utility of cfDNA as a noninvasive biomarker for disease severity inspections.", "qid": 25, "docid": "h184u2x2", "rank": 55, "score": 0.7751052379608154}, {"content": "Title: A comprehensive appraisal of laboratory biochemistry tests as major predictors of COVID-19 severity Content: Context: A relevant portion of COVID-19 patients develop severe disease with negative outcomes. Several biomarkers have been proposed to predict COVID-19 severity, but no definite interpretative criteria have been established to date for stratifying risk. Objective: To evaluate six serum biomarkers (C-reactive protein, lactate dehydrogenase, D-dimer, albumin, ferritin and cardiac troponin T) for predicting COVID-19 severity and to define related cut-offs able to aid clinicians in risk stratification of hospitalized patients. Design: A retrospective study of 427 COVID-19 patients was performed. Patients were divided into groups based on their clinical outcome: non-survivors vs. survivors and patients admitted to intensive care unit vs. others. ROC curves and likelihood ratios were employed to define predictive cut-offs for evaluated markers. Results: Marker concentrations at peak were significantly different between groups for both selected outcomes. At univariate logistic regression analysis, all parameters were significantly associated with higher odds of death and intensive care. At the multivariate analysis, high concentrations of lactate dehydrogenase and low concentrations of albumin in serum remained significantly associated with higher odds of death, while only low lactate dehydrogenase activities remained associated with lower odds of intensive care admission. The best cut-offs for death prediction were >731 U/L for lactate dehydrogenase and &#8804;18 g/L for albumin, while a lactate dehydrogenase activity <425 U/L was associated with a negative likelihood ratio of 0.10 for intensive treatment. Conclusions: Our study identifies which biochemistry tests represent major predictors of COVID-19 severity and defines the best cut-offs for their use.", "qid": 25, "docid": "ss6nskfk", "rank": 56, "score": 0.774694561958313}, {"content": "Title: Proteomic and Metabolomic Characterization of COVID-19 Patient Sera Content: Severe COVID-19 patients account for most of the mortality of this disease. Early detection and effective treatment of severe patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model correctly classified severe patients with an accuracy of 93.5%, and was further validated using ten independent patients, seven of which were correctly classified. We identified molecular changes in the sera of COVID-19 patients implicating dysregulation of macrophage, platelet degranulation and complement system pathways, and massive metabolic suppression. This study shows that it is possible to predict progression to severe COVID-19 disease using serum protein and metabolite biomarkers. Our data also uncovered molecular pathophysiology of COVID-19 with potential for developing anti-viral therapies.", "qid": 25, "docid": "nifz133q", "rank": 57, "score": 0.7745093107223511}, {"content": "Title: Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19 Content: Abstract Background The inflammatory response plays a critical role in coronavirus disease 2019 (COVID-19), and inflammatory cytokine storm increases the severity of COVID-19. Objective To investigate the ability of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT) to predict mild and severe cases of COVID-19. Study design This retrospective cohort study included 140 patients diagnosed with COVID-19 from January 18, 2020, to March 12, 2020. The study population was divided into two groups according to disease severity: a mild group (MG) (n = 107) and a severe group (SG) (n = 33). Data on demographic characteristics, baseline clinical characteristics, and the levels of IL-6, CRP, and PCT on admission were collected. Results Among the 140 patients, the levels of IL-6, CRP, and PCT increased in 95 (67.9 %), 91 (65.0 %), and 8 (5.7 %) patients on admission, respectively. The proportion of patients with increased IL-6, CRP, and PCT levels was significantly higher in the SG than in the MG. Cox proportional hazard model showed that IL-6 and CRP could be used as independent factors to predict the severity of COVID-19. Furthermore, patients with IL-6 > 32.1 pg/mL or CRP > 41.8 mg/L were more likely to have severe complications. Conclusion The serum levels of IL-6 and CRP can effectively assess disease severity and predict outcome in patients with COVID-19.", "qid": 25, "docid": "4cr6z7tc", "rank": 58, "score": 0.7742712497711182}, {"content": "Title: The potential role of IL-6 in monitoring severe case of coronavirus disease 2019 Content: Abstract. Background: The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan City, China spreads rapidly since December, 2019. Most patients show mild symptoms, but some of them develop into severe disease. There is currently no specific medication. The purpose of this study is to to explore changes of markers in peripheral blood of severe COVID-19 patients, which may be of value in disease monitoring. Methods Clinical data of patients with nonsevere and severe type COVID-19 diagnosed by laboratory test in our institution were collected. The relationship between peripheral blood cells and cytokines, clinical manifestation and outcome was analyzed. Results A total of 69 severe type COVID-19 patients were included. On admission, the median age of severe cases was 56-year old, with 52.17% female patient. The most common symptoms were fever (79.72%), cough (63.77%), shortness of breath (57.97%) and fatigue (50.72%). Diarrhea is less common. The most common comorbidity is hypertension. Upon admission, the proportion of bilateral pulmonary involvement and interstitial abnormalities evidenced by chest computed tomography (CT) imaging in severe cases was 60.87% and 27.54%, respectively. Compared with patients with nonsevere disease, those with severe disease showed obvious lymphocytopenia. Elevated level of lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin and D-dimer was found in most cases. Two patients (2.9%) needed transfer to the intensive care unit. Baseline immunological parameters and most of the inflammatory parameters were basically within the normal range. However, baseline interleukin-6 (IL-6) was significantly increased in severe type, which was closely related to the maximal body temperature during hospitalization and to CT findings. Baseline IL-6 was also significantly related to the increase of baseline level of CRP, LDH, ferritin and D-dimer. The increase of baseline IL-6 level suggests that it may positively correlate with the severity of COVID-19. Among the 30 severe type patients whose IL-6 was assessed before and after treatment, significant decrease in IL-6 and improved CT assessment was found in 25 patients after treatment. Whereas the IL-6 level was further increased in 3 cases, which was closely related to disease progression. It is suggested that IL-6 may be used as a marker for disease monitoring in severe COVID-19 patients. Conclusions On admission, the baseline level of IL-6, CRP, LDH and ferritin was closely related to the severity of COVID-19, and the elevated IL-6 was significantly related to the clinical manifestation of severe type patients. The decrease of IL-6 was closely related to treatment effectiveness, while the increase of IL-6 indicated disease exacerbation. Collectively, the dynamic change of IL-6 level can be used as a marker for disease monitoring in patients with severe COVID-19.", "qid": 25, "docid": "kbd2h4l0", "rank": 59, "score": 0.7734905481338501}, {"content": "Title: A Tool to Early Predict Severe 2019-Novel Coronavirus Pneumonia (COVID-19) : A Multicenter Study using the Risk Nomogram in Wuhan and Guangdong, China Content: Background Severe cases of coronavirus disease 2019 (COVID-19) rapidly develop acute respiratory distress leading to respiratory failure, with high short-term mortality rates. At present, there is no reliable risk stratification tool for non-severe COVID-19 patients at admission. We aimed to construct an effective model for early identifying cases at high risk of progression to severe COVID-19. Methods SARS-CoV-2 infected patients from one center in Wuhan city and two centers in Guangzhou city, China were included retrospectively. All patients with non-severe COVID-19 during hospitalization were followed for more than 15 days after admission. Patients who deteriorated to severe or critical COVID-19 and patients who kept non-severe state were assigned to the severe and non-severe group, respectively. We compared the demographic, clinical, and laboratory data between severe and non-severe group. Based on baseline data, least absolute shrinkage and selection operator (LASSO) algorithm and logistic regression model were used to construct a nomogram for risk prediction in the train cohort. The predictive accuracy and discriminative ability of nomogram were evaluated by area under the curve (AUC) and calibration curve. Decision curve analysis (DCA) and clinical impact curve analysis (CICA) were conducted to evaluate the clinical applicability of our nomogram. Findings The train cohort consisted of 189 patients, while the two independent validation cohorts consisted of 165 and 18 patients. Among all cases, 72 (19.35%) patients developed severe COVID-19 and 107 (28.76%) patients had one of the following basic disease, including hypertension, diabetes, coronary heart disease, chronic respiratory disease, tuberculosis disease. We found one demographic and six serological indicators (age, serum lactate dehydrogenase, C-reactive protein, the coefficient of variation of red blood cell distribution width (RDW), blood urea nitrogen, albumin, direct bilirubin) are associated with severe COVID-19. Based on these features, we generated the nomogram, which has remarkably high diagnostic accuracy in distinguishing individuals who exacerbated to severe COVID-19 from non-severe COVID-19 (AUC 0.912 [95% CI 0.846-0.978]) in the train cohort with a sensitivity of 85.71 % and specificity of 87.58% ; 0.853 [0.790-0.916] in validation cohort with a sensitivity of 77.5 % and specificity of 78.4%. The calibration curve for probability of severe COVID-19 showed optimal agreement between prediction by nomogram and actual observation. DCA and CICA further indicated that our nomogram conferred significantly high clinical net benefit. Interpretation Our nomogram could help clinicians to early identify patients who will exacerbate to severe COVID-19. And this risk stratification tool will enable better centralized management and early treatment of severe patients, and optimal use of medical resources via patient prioritization and thus significantly reduce mortality rates. The RDW plays an important role in predicting severe COVID-19, implying that the role of RBC in severe disease is underestimated.", "qid": 25, "docid": "51b7hss1", "rank": 60, "score": 0.7734007239341736}, {"content": "Title: Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19 Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) can manifest as a viral-induced hyperinflammation with multiorgan involvement. Such patients often experience rapid deterioration and need for mechanical ventilation. Currently, no prospectively validated biomarker of impending respiratory failure is available. OBJECTIVE: We aimed to identify and prospectively validate biomarkers that allow the identification of patients in need of impending mechanical ventilation. METHODS: Patients with COVID-19 who were hospitalized from February 29 to April 9, 2020, were analyzed for baseline clinical and laboratory findings at admission and during the disease. Data from 89 evaluable patients were available for the purpose of analysis comprising an initial evaluation cohort (n = 40) followed by a temporally separated validation cohort (n = 49). RESULTS: We identified markers of inflammation, lactate dehydrogenase, and creatinine as the variables most predictive of respiratory failure in the evaluation cohort. Maximal IL-6 level before intubation showed the strongest association with the need for mechanical ventilation, followed by maximal CRP level. The respective AUC values for IL-6 and CRP levels in the evaluation cohort were 0.97 and 0.86, and they were similar in the validation cohort (0.90 and 0.83, respectively). The calculated optimal cutoff values during the course of disease from the evaluation cohort (IL-6 level > 80 pg/mL and CRP level > 97 mg/L) both correctly classified 80% of patients in the validation cohort regarding their risk of respiratory failure. CONCLUSION: The maximal level of IL-6, followed by CRP level, was highly predictive of the need for mechanical ventilation. This suggests the possibility of using IL-6 or CRP level to guide escalation of treatment in patients with COVID-19-related hyperinflammatory syndrome.", "qid": 25, "docid": "2w68ynzs", "rank": 61, "score": 0.7723884582519531}, {"content": "Title: Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19 Content: BACKGROUND: The inflammatory response plays a critical role in coronavirus disease 2019 (COVID-19), and inflammatory cytokine storm increases the severity of COVID-19. OBJECTIVE: To investigate the ability of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT) to predict mild and severe cases of COVID-19. STUDY DESIGN: This retrospective cohort study included 140 patients diagnosed with COVID-19 from January 18, 2020, to March 12, 2020. The study population was divided into two groups according to disease severity: a mild group (MG) (n = 107) and a severe group (SG) (n = 33). Data on demographic characteristics, baseline clinical characteristics, and the levels of IL-6, CRP, and PCT on admission were collected. RESULTS: Among the 140 patients, the levels of IL-6, CRP, and PCT increased in 95 (67.9 %), 91 (65.0 %), and 8 (5.7 %) patients on admission, respectively. The proportion of patients with increased IL-6, CRP, and PCT levels was significantly higher in the SG than in the MG. Cox proportional hazard model showed that IL-6 and CRP could be used as independent factors to predict the severity of COVID-19. Furthermore, patients with IL-6 > 32.1 pg/mL or CRP > 41.8 mg/L were more likely to have severe complications. CONCLUSION: The serum levels of IL-6 and CRP can effectively assess disease severity and predict outcome in patients with COVID-19.", "qid": 25, "docid": "zgrr2hdi", "rank": 62, "score": 0.7722100615501404}, {"content": "Title: Can we predict the severity of COVID-19 with a routine blood test? Content: INTRODUCTION The ongoing worldwide pandemic of Coronavirus Disease 2019 (COVID-19) has posed a huge threat to global public health. However, whether routine blood test could be used to monitor and predict the severity and prognosis of COVID-19 has never been comprehensively investigated. OBJECTIVES To provide an overview of the association of markers in routine blood test with the severity of COVID-19. METHODS PubMed, Embase, Cochrane Library, Wanfang and CNKI database were searched to identify studies reporting the markers in the routine blood test with the severity of COVID-19 until March 20, 2020. STATA software was used for the meta- analysis. RESULTS A total of 15 studies with 3090 COVID-19 patients were included in this analysis. Patients in non-severe group had fewer white blood cells (WBC) (WMD = -0.85 [109/L], 95% CI = [-1.54, -0.16], P = 0.02) and neutrophils (WMD = -1.57 [109/L], 95% CI = [-2.60, -0.54], P = 0.003), more lymphocytes (WMD = 0.29 [109/L], 95% CI = [0.22, 0.36], P < 0.001) and platelets (WMD = 19.05 [109/L], 95% CI = [3.04, 35.06], P = 0.02), and lower neutrophil-to-lymphocyte ratio (NLR) level (WMD = -2.48, 95% CI = [-3.81, -1.15], P < 0.001), compared with those in severe group. There was no statistical difference in monocytes (WMD = 0.01 [109/L], 95% CI = [-0.01, 0.03], P = 0.029) between these two groups. Sensitivity analysis and meta-analysis based on standard mean difference (SMD) did not change the conclusions about neutrophils, lymphocytes and NLR while the results were inconsistent in WBC and platelets. CONCLUSIONS Severe patients had more neutrophils, higher NLR level, and fewer lymphocytes than non-severe patients with COVID-19. Measurement of these markers might assist clinicians to monitor and predict the severity and prognosis of COVID-19.", "qid": 25, "docid": "z3pknjbl", "rank": 63, "score": 0.7721998691558838}, {"content": "Title: C-reactive protein: a promising biomarker for poor prognosis in COVID-19 infection Content: BACKGROUND: The novel coronavirus disease 2019 (COVID-19) break out from Wuhan, China, spread over 227 countries and caused approximately 0.3 million death worldwide. Several biomolecules have been explored for possible biomarkers for prognosis outcome. Although increased C reactive protein (CRP) has been associated with death due to COVID-19 infections, results from different populations remain inconsistent. For a conclusive result, the present meta-analysis was performed. METHODS: We conducted a literature survey in PubMed and Scopus database for the association of CRP concentration with COVID-19 disease outcomes. A total of 16 eligible studies were enrolled in the present analysis comprising of 1896 survivors and 849 non-survivors cases. Concentrations of CRP were compared and analyzed by a meta-analysis. RESULTS: Egger\u2019s regression analysis (intercept=0.04, P=0.98, 95%CI=-5.48 to 5.58) and funnel plot revealed an absence of publication bias in the included studies. Due to the presence of significant heterogeneity across the studies (Q=252.03, P(heterogeneity)= 0.000, I(2)=93.65) random model was used for the analysis of the present study. The results of the meta-analysis demonstrated a significant role of CRP in COVID-19 infection outcome (Standard difference in means= 1.371, P=0.000). CONCLUSIONS: Concentrations of CRP remained increased in patients who died in COVID-19 infection and could be a promising biomarker for accessing disease lethality.", "qid": 25, "docid": "h86cufyp", "rank": 64, "score": 0.7720848917961121}, {"content": "Title: A comprehensive appraisal of laboratory biochemistry tests as major predictors of COVID-19 severity. Content: Context: A relevant portion of COVID-19 patients develop severe disease with negative outcomes. Several biomarkers have been proposed to predict COVID-19 severity, but no definite interpretative criteria have been established to date for stratifying risk. Objective: To evaluate six serum biomarkers (C-reactive protein, lactate dehydrogenase, D-dimer, albumin, ferritin and cardiac troponin T) for predicting COVID-19 severity and to define related cut-offs able to aid clinicians in risk stratification of hospitalized patients. Design: A retrospective study of 427 COVID-19 patients was performed. Patients were divided into groups based on their clinical outcome: non-survivors vs. survivors and patients admitted to intensive care unit vs. others. ROC curves and likelihood ratios were employed to define predictive cut-offs for evaluated markers. Results: Marker concentrations at peak were significantly different between groups for both selected outcomes. At univariate logistic regression analysis, all parameters were significantly associated with higher odds of death and intensive care. At the multivariate analysis, high concentrations of lactate dehydrogenase and low concentrations of albumin in serum remained significantly associated with higher odds of death, while only low lactate dehydrogenase activities remained associated with lower odds of intensive care admission. The best cut-offs for death prediction were >731 U/L for lactate dehydrogenase and \u226418 g/L for albumin, while a lactate dehydrogenase activity <425 U/L was associated with a negative likelihood ratio of 0.10 for intensive treatment. Conclusions: Our study identifies which biochemistry tests represent major predictors of COVID-19 severity and defines the best cut-offs for their use.", "qid": 25, "docid": "dakuwflh", "rank": 65, "score": 0.772037148475647}, {"content": "Title: Characteristics of inflammatory factors and lymphocyte subsets in patients with severe COVID-19 Content: To investigate the inflammatory factors and lymphocyte subsets which play an important role in the course of severe coronavirus disease 2019 (COVID-19). A total of 27 patients with severe COVID-19 who were admitted to Tongji Hospital in Wuhan from 1 to 21 February 2020 were recruited to the study. The characteristics of interleukin-1\u00df (IL-1\u00df), IL-2 receptor (IL-2R), IL-6, IL-8, IL-10, tumor necrosis factor-&#945; (TNF)-&#945;, C-reactive protein (CRP), serum ferritin and procalcitonin (PCT), and lymphocyte subsets of these patients were retrospectively compared before and after treatment. Before treatment, there was no significant difference in most inflammatory factors (IL-1\u00df, IL-2R, IL-6, IL-8, IL-10, CRP, and serum ferritin) between male and female patients. Levels of IL-2R, IL-6, TNF-&#945;, and CRP decreased significantly after treatment, followed by IL-8, IL-10, and PCT. Serum ferritin was increased in all patients before treatment but did not decrease significantly after treatment. IL-1\u00df was normal in most patients before treatment. Lymphopenia was common among these patients with severe COVID-19. Analysis of lymphocyte subsets showed that CD4+ and particularly CD8+ T lymphocytes increased significantly after treatment. However, B lymphocytes and natural killer cells showed no significant changes after treatment. A pro-inflammatory response and decreased level of T lymphocytes were associated with severe COVID-19.", "qid": 25, "docid": "zuf19lex", "rank": 66, "score": 0.7708736658096313}, {"content": "Title: Value of leukocytosis and elevated C-reactive protein in predicting severe coronavirus 2019 (COVID-19): A systematic review and meta-analysis Content: BACKGROUND: Since December 2019, coronavirus 2019 (COVID-19) has spread worldwide. Identifying poor prognostic factors is helpful for risk stratification. In this meta-analysis, we investigated the association between severe COVID-19 and a change in white blood cell (WBC) count, an elevation of C-reactive protein (CRP), and fever. Moreover, we aimed to evaluate the diagnostic accuracy of leukocytosis and an elevation of CRP. METHODS: We performed a systematic search of PubMed, EMBASE, Scopus, and the Cochrane Library through April 20th, 2020. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. A sensitivity analysis was conducted according to the study size (>200 or <200) and median age (>55 or <55). Meta-regression analyses were conducted to examine possible sources of heterogeneity. We calculated the diagnostic accuracy of leukocytosis and CRP. RESULTS: Eighteen studies with 3278 patients were selected. Fever, leukocytosis, and elevated CRP were associated with poor outcomes (OR (95% CI) 1.63 (1.06-2.51), 4.51 (2.53-8.04), and 11.97 (4.97-28.8), respectively). Leukopenia was associated with a better prognosis (OR 0.56, 95% CI 0.40-0.78). Sensitivity analyses showed similar tendencies. Meta-regression analysis for leukocytosis indicated that age, dyspnea, and hypertension contributed to heterogeneity. The pooled area under the leukocytosis and CRP curves were 0.70 (0.64-0.76) and 0.89 (0.80-0.99), respectively. CONCLUSION: In patients with COVID-19, fever, leukocytosis, and an elevated CRP were associated with severe outcomes. Leukocytosis and CRP on arrival may predict poor outcomes.", "qid": 25, "docid": "3afoqoef", "rank": 67, "score": 0.770858883857727}, {"content": "Title: Antibody response to infectious diseases and other factors accurately predict COVID-19 infection and severity risk 10\u201314 years later: a retrospective UK Biobank cohort study Content: BACKGROUND: Several risk factors have emerged for novel 2019 coronavirus disease (COVID-19) infection and severity. Yet, it is unknown to what degree these risk factors alone or in combination can accurately predict who is most at risk. It is also worthwhile to consider serological antibody titers to non COVID-19 infectious diseases, which may influence host immunity to COVID-19. METHODS: In this retrospective study of multicenter UK Biobank participants, as of May 26(th) 2020, all COVID-19 testing data was collected by Public Health England for older adult in- and out-patients (69.6 \u00b1 8.8 years). We used linear discriminant analysis with cross-validation and bootstrapping to determine the accuracy, specificity, and sensitivity of baseline data from 2006\u20132010 to predict COVID-19 infection and presumptive severity (i.e., testing at hospital). Receiver operating characteristic (ROC) curves were used to derive the area under the curve (AUC). FINDINGS: This retrospective study included 4,510 unique participants and 7,539 testing instances (i.e., test cases). Testing resulted in 5,329 negative cases and 2,210 positive cases, split into 996 mild and 1,214 severe disease outcomes. Baseline data including demographics, bioimpedance-derived body composition, vitals, serum biochemistry, self-reported illness/disability, and complete blood count. A randomized subset of 80 participants with 124 test cases also had antibody titers for 20 common to rare infectious diseases. Among all test cases, accuracy was modest for final diagnostic models of COVID-19 infection (70.2%; AUC=0.570, CI=0.556\u20130.584) and severity (58.3%; AUC=0.592, CI=0.568\u20130.615). In the serology sub-group, by contrast, final models predicted infection and severity with an accuracy of 93.5% (AUC=0.969, CI=0.934\u20131.000) and 74.4% (AUC=0.803, CI=0.663\u20130.943) respectively. Models included titers to common pathogens (e.g., human cytomegalovirus), age, blood cell counts, lipids, and other biochemical markers. INTERPRETATION: Risk profiles including serological titers and other risk factors could help policy makers and clinicians better identify who may get COVID-19 and require hospitalization.", "qid": 25, "docid": "1zcyz4xz", "rank": 68, "score": 0.7705214023590088}, {"content": "Title: Serum KL-6 can distinguish between different phenotypes of severe COVID-19 Content: We read the article by D'Alessandro Miriana et al. with great interest and appreciate their efforts to evaluate the role of serum Krebs von den Lungen-6 (KL-6) as a prognostic biomarker of severe coronavirus disease 2019 (COVID-19).1 This article is protected by copyright. All rights reserved.", "qid": 25, "docid": "1tyo148f", "rank": 69, "score": 0.7703979015350342}, {"content": "Title: Association of inflammatory markers with the severity of COVID-19 Content: Background: The ongoing worldwide epidemic of Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a huge threat to global public health. However, with regard to the effects of inflammatory markers on the severity of COVID-19, studies have reported associations that vary in strength and direction. Aims: In the meta-analysis, we aimed to provide an overview of the association of inflammatory markers with severity of COVID-19. Methods: The following databases were searched: PubMed, Embase, Cochrane Library, Wanfang database and CNKI (China National Knowledge Infrastructure) database until March 20, 2020. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were pooled using random or fixed-effects models. Results: A total of 16 studies were included in our analysis comprising of 3962 patients with COVID-19. Random-effects results demonstrated that patients with COVID-19 in non-severe group had lower levels for CRP (WMD = -41.78 mg/l, 95% CI = [-52.43, -31.13], P < 0.001), PCT (WMD = -0.13 ng/ml, 95% CI = [-0.20, -0.05], P < 0.001), IL-6 (WMD = -21.32 ng/l, 95% CI = [-28.34, -14.31], P < 0.001), ESR (WMD = -8.40 mm/h, 95% CI = [-14.32, -2.48], P = 0.005), SAA (WMD = -43.35 \u03bcg/ml, 95% CI = [-80.85, -5.85], P = 0.020) and serum ferritin (WMD = -398.80 mg/l, 95% CI = [-625.89, -171.71], P < 0.001), compared with those in severe group. Moreover, survivors had lower level for IL-6 than non-survivors with COVID-19 (WMD = -4.80 ng/ml, 95% CI = [-5.87, -3.73], P < 0.001). These results were consistent through sensitivity analysis and publication bias assessment. Conclusions: The meta-analysis highlights the association of inflammatory markers with the severity of COVID-19. Measurement of inflammatory markers might help clinicians to monitor and evaluate the severity and prognosis of COVID-19.", "qid": 25, "docid": "mn3b6nrs", "rank": 70, "score": 0.7703807353973389}, {"content": "Title: Value of leukocytosis and elevated C-reactive protein in predicting severe coronavirus 2019 (COVID-19): A systematic review and meta-analysis. Content: BACKGROUND Since December 2019, coronavirus 2019 (COVID-19) has spread worldwide. Identifying poor prognostic factors is helpful for risk stratification. In this meta-analysis, we investigated the association between severe COVID-19 and a change in white blood cell (WBC) count, an elevation of C-reactive protein (CRP), and fever. Moreover, we aimed to evaluate the diagnostic accuracy of leukocytosis and an elevation of CRP. METHODS We performed a systematic search of PubMed, EMBASE, Scopus, and the Cochrane Library through April 20th, 2020. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. A sensitivity analysis was conducted according to the study size (>200 or <200) and median age (>55 or <55). Meta-regression analyses were conducted to examine possible sources of heterogeneity. We calculated the diagnostic accuracy of leukocytosis and CRP. RESULTS Eighteen studies with 3,278 patients were selected. Fever, leukocytosis, and elevated CRP were associated with poor outcomes (OR (95% CI) 1.63 (1.06 to 2.51), 4.51 (2.53 to 8.04), and 11.97 (4.97 to 28.8), respectively). Leukopenia was associated with a better prognosis (OR 0.56, 95% CI 0.40 to 0.78). Sensitivity analyses showed similar tendencies. Meta-regression analysis for leukocytosis indicated that age, dyspnea, and hypertension contributed to heterogeneity. The pooled area under the leukocytosis and CRP curves were 0.70 (0.64 to 0.76) and 0.89 (0.80 to 0.99), respectively. CONCLUSION In patients with COVID-19, fever, leukocytosis, and an elevated CRP were associated with severe outcomes. Leukocytosis and CRP on arrival may predict poor outcomes.", "qid": 25, "docid": "vw6vg5b7", "rank": 71, "score": 0.7701511383056641}, {"content": "Title: Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors Content: Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread across many other countries. While the majority of patients were considered mild, critically ill patients involving respiratory failure and multiple organ dysfunction syndrome are not uncommon, which could result death. We hypothesized that cytokine storm is associated with severe outcome. We enrolled 102 COVID-19 patients who were admitted to Renmin Hospital (Wuhan, China). All patients were classified into moderate, severe and critical groups according to their symptoms. 45 control samples of healthy volunteers were also included. Inflammatory cytokines and C-Reactive Protein (CRP) profiles of serum samples were analyzed by specific immunoassays. Results showed that COVID-19 patients have higher serum level of cytokines (TNF-&#945;, IFN-\u00ce\u00b3, IL-2, IL-4, IL-6 and IL-10) and CRP than control individuals. Within COVID-19 patients, serum IL-6 and IL-10 levels are significantly higher in critical group (n = 17) than in moderate (n = 42) and severe (n = 43) group. The levels of IL-10 is positively correlated with CRP amount (r = 0.41, P < 0.01). Using univariate logistic regression analysis, IL-6 and IL-10 are found to be predictive of disease severity and receiver operating curve analysis could further confirm this result (AUC = 0.841, 0.822 respectively). Our result indicated higher levels of cytokine storm is associated with more severe disease development. Among them, IL-6 and IL-10 can be used as predictors for fast diagnosis of patients with higher risk of disease deterioration. Given the high levels of cytokines induced by SARS-CoV-2, treatment to reduce inflammation-related lung damage is critical.", "qid": 25, "docid": "9qahwku6", "rank": 72, "score": 0.7701234817504883}, {"content": "Title: Correlation between the variables collected at admission and progression to severe cases during hospitalization among patients with COVID-19 in Chongqing Content: Mortality is high among severe patients with 2019 novel coronavirus-infected disease (COVID-19). Early prediction of progression to severe cases is needed. We retrospectively collected patients with COVID-19 in two hospital of Chongqing from 1st January to 29th February 2020. At admission, we collected the demographics and laboratory tests to predict whether the patient would progress to severe cases in hospitalization. Severe case was confirmed when one of the following criteria occurred: (a) dyspnea, respiratory rate &#8805;30 breaths/min, (b) blood oxygen saturation &#8804;93%, and (c) PaO2 /FiO2 &#8804; 300 mm Hg. At admission, 348 mild cases were enrolled in this study. Of them, 20 (5.7%) patients progressed to severe cases after median 4.0 days (interquartile range: 2.3-6.0). Pulmonary inflammation index, platelet counts, sodium, C-reactive protein, prealbumin, and PaCO2 showed good distinguishing power to predict progression to severe cases (each area under the curve of receiver operating characteristics [AUC] &#8805; 0.8). Age, heart rate, chlorine, alanine aminotransferase, aspartate aminotransferase, procalcitonin, creatine kinase, pH, CD3 counts, and CD4 counts showed moderate distinguishing power (each AUC between 0.7-0.8). And potassium, creatinine, temperature, and D-dimer showed mild distinguishing power (each AUC between 0.6-0.7). In addition, higher C-reactive protein was associated with shorter time to progress to severe cases (r = -0.62). Several easily obtained variables at admission are associated with progression to severe cases during hospitalization. These variables provide a reference for the medical staffs when they manage the patients with COVID-19.", "qid": 25, "docid": "yzgac737", "rank": 73, "score": 0.769912838935852}, {"content": "Title: C-reactive protein: A promising biomarker for poor prognosis in COVID-19 infection Content: BACKGROUND: The novel coronavirus disease 2019 (COVID-19) first broke out in Wuhan, China, spread over 227 countries and caused approximately 0.3 million death worldwide. Several biomolecules have been explored for possible biomarkers for prognosis outcome. Although increased C reactive protein (CRP) is associated with death due to COVID-19 infections, results from different populations remain inconsistent. For a conclusive result, the present meta-analysis was performed. METHODS: We conducted a literature search in PubMed and Scopus database for the association of CRP concentration with COVID-19 disease outcomes. A total of 16 eligible studies were enrolled in the present analysis comprising of 1896 survivors and 849 non-survivors cases. Concentrations of CRP were compared and analyzed by a meta-analysis. RESULTS: Egger's regression analysis (intercept = 0.04, P = 0.98, 95%CI = -5.48 to 5.58) and funnel plot revealed an absence of publication bias in the included studies. Due to the presence of significant heterogeneity across the studies (Q = 252.03, Pheterogeneity = 0.000, I2 = 93.65) random model was used for the analysis of the present study. The results of the meta-analysis demonstrated a significant role of CRP in COVID-19 infection outcome (Standard difference in means = 1.371, P = 0.000). CONCLUSIONS: Concentrations of CRP remained high in patients who died of COVID-19 infection and could be a promising biomarker for assessing disease lethality.", "qid": 25, "docid": "klhnlz1z", "rank": 74, "score": 0.7698652148246765}, {"content": "Title: Characteristics of lymphocyte subsets and their predicting values for the severity of COVID-19 patients Content: Severe COVID-19 patients showed worse clinical outcomes compared to mild and moderate patients. However, effective indicators are still lacking to predict the severity of the disease. In the present study, we retrospectively analyzed the clinical and laboratory data of 16 COVID-19 patients and found that the absolute counts of three T-cells (CD3+, CD4+, and CD8+) were significantly lower in the moderate and severe patients than those in mild patients and were significantly lower in severe patients than in moderate patients on admission. With the recovery of the COVID-19, serum levels of inflammatory biomarkers (CRP, PCT, and IL6) of moderate and severe patients gradually decreased. In contrast, the counts of lymphocytes and their subsets including CD3+, CD4+, and CD8+ T cells gradually increased in severe patients, and eventually showed comparable levels with moderate patients. ROC analysis showed that the counts of CD3+, CD4+, and CD8+ T-cells with AUC > 0.9 have potential values for predicting the severity of COVID-19 patients. In conclusion, the reduction of CD3+, CD4+, and CD8+ T-cells is related to the severity of COVID-19 and dynamic detection of these T-lymphocyte subsets may help predict the outcome of the patients.", "qid": 25, "docid": "99j84ovg", "rank": 75, "score": 0.7696340084075928}, {"content": "Title: Immune phenotyping based on neutrophil-to-lymphocyte ratio and IgG predicts disease severity and outcome for patients with COVID-19 Content: Background: A recently emerging respiratory disease named coronavirus disease 2019 (COVID-19) has quickly spread across the world. This disease is initiated by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and uncontrolled cytokine storm, but it remains unknown as to whether a robust antibody response is related to clinical deterioration and poor outcome in laboratory-confirmed COVID-19 patients. Methods: Anti-SARS-CoV-2 IgG and IgM antibodies were determined by chemiluminescence analysis (CLIA) in COVID-19 patients from a single center in Wuhan. Median IgG and IgM levels in acute and convalescent-phase sera (within 35 days) for all included patients were calculated and compared among severe and nonsevere patients. Immune response phenotyping based on late IgG levels and neutrophil-to-lymphocyte ratio (NLR) was characterized to stratify patients with different disease severities and outcome. Laboratory parameters in patients with different immune response phenotypes and disease severities were analyzed. Findings: A total of 222 patients were included in this study. IgG was first detected on day 4 of illness, and its peak levels occurred in the fourth week. Severe cases were more frequently found in patients with high IgG levels, compared to those who with low IgG levels (51.8% versus 32.3%; p=0.008). Severity rates for patients with NLRhiIgGhi, NLRhiIgGlo, NLRloIgGhi, and NLRloIgGlo phenotype was 72.3%, 48.5%, 33.3%, and 15.6%, respectively (p<0.0001). Furthermore, severe patients with NLRhiIgGhi, NLRhiIgGlo had higher proinflammatory cytokines levels including IL-2, IL-6 and IL-10, and decreased CD4+ T cell count compared to those with NLRloIgGlo phenotype (p<0.05). Recovery rate for severe patients with NLRhiIgGhi, NLRhiIgGlo, NLRloIgGhi, and NLRloIgGlo phenotype was 58.8% (20/34), 68.8% (11/16), 80.0% (4/5), and 100% (12/12), respectively (p=0.0592). Dead cases only occurred in NLRhiIgGhi and NLRhiIgGlo phenotypes. Interpretation: COVID-19 severity is associated with increased IgG response, and an immune response phenotyping based on late IgG response and NLR could act as a simple complementary tool to discriminate between severe and nonsevere COVID-19 patients, and further predict their clinical outcome.", "qid": 25, "docid": "68193u0a", "rank": 76, "score": 0.7688134908676147}, {"content": "Title: Risk factors associated with disease progression in a cohort of patients infected with the 2019 novel coronavirus Content: BACKGROUND: The emerging infection of the 2019 novel coronavirus (2019-nCoV) in late December, 2019 in Wuhan, China, has caused an extreme health concern, with many patients having progressed to acute respiratory disease or other complications in a short period. Meanwhile, the risk factors associated with the disease progression still remain elusive. METHODS: A cohort of 17 patients with laboratory-confirmed 2019-nCoV infections who were admitted to the Ninth Hospital of Nanchang between January 28 and February 6, 2020, were enrolled in this study. All the patients received standardized treatment. The disease progression was evaluated every 7 days after admission. The clinical, radiologic, and laboratory characteristics were retrospectively analyzed, and the factors associated with the disease progression were screened by binary logistic regression analysis. RESULTS: The cohort comprised 11 women (64.7%) and 6 men (35.3%) between the ages of 18 to 70 years old. All patients had a reported history of contact with infection-confirmed patients. Fever (11/64.7%) and cough (8/47.1%) were the most common symptoms, whereas dyspnea (2/11.8%) and fatigue (3/17.6%) were rare, and there was no patient with diarrhea symptoms. There were 5 patients with aggravated disease at the first disease progression evaluation, and no patient received mechanical ventilation, transferred to the intensive care unit (ICU), or progressed to acute respiratory distress syndrome, septic shock, refractory metabolic acidosis, coagulation dysfunction, or death. Based on the disease progression, patients were divided into the non-aggravation group (12 cases) and the aggravation group (5 cases). There were no significant differences between the 2 groups with respect to their clinical characteristics. Chest computed tomography (CT) on admission revealed there were 8 patients (47.1%) with invasive lesions found bilaterally on the lungs on multiple lobes, 4 patients (23.5%) with invasive lesions on 1 lobe, and 5 patients (29.4%) with normal chest CT. The aggravation group had1 patient (20.0%) with invasive lesions on one lobe, 3 (60.0%) with invasive lesions on multiple lobes, bilaterally, and 1 (20.0%) with normal chest CT; meanwhile, the nonaggravation group had 3 patients (25.0%) with invasive lesions on one lobe, 5 (41.7%) with invasive lesions on multiple lobes, bilaterally, and 4 (33.3%) with normal chest CT. No significant difference was found between the 2 groups. In the aggravation group, the total lymphocyte counts significantly decreased in comparison to that in the non-aggravation group. Further analysis showed that the CD4+ T cell count but not the CD8+ T cell count of the aggravation group was significantly lower than that of the non-aggravation group. Correlation analysis indicated total lymphocyte count was positively correlated with CD4+ T cell count, and no significant differences were found between the 2 groups in other laboratory measurements, including those of white blood cell (WBC) count, C-reactive protein (CRP), albumin, lactate dehydrogenase (LDH), and D-dimer. Finally, a binary logistic regression model was used to identify the factors associated with the disease progression. It was found that total lymphocyte count was a risk factor associated with disease progression in patients infected with 2019-nCoV. CONCLUSIONS: A higher cell count of total lymphocytes may indicate a better outcome of the disease, and immune response may be a vital factor for directing disease progression in the early stage of 2019-nCoV infection.", "qid": 25, "docid": "ijtz50ut", "rank": 77, "score": 0.7685487270355225}, {"content": "Title: Procalcitonin levels in COVID-19 patients Content: Coronavirus disease 2019 (COVID-19) is turning into a pandemic. Here, we analyzed 95 patients infected with SARS-CoV-2. Sixty-two moderate patients, 21 severe patients and 12 critical patients (6 patients died) were included in our study. Our results showed that the mean serum levels of procalcitonin in severe patients were over 4 times higher than those in moderate patients, and they were over 8 times higher in critical patients than in moderate patients. For the discharged patients, both high-normal procalcitonin levels and abnormal procalcitonin levels decreased during recovery. However, in the death cases, the serum levels of procalcitonin increased as the disease worsened. We demonstrate that procalcitonin may be an indicator of severity and may contribute to determining the severity of patients infected with COVID-19; moreover, serial procalcitonin measurements may be useful in predicting prognosis.", "qid": 25, "docid": "imidgnng", "rank": 78, "score": 0.7684836387634277}, {"content": "Title: Clinical Progression and Cytokine Profiles of Middle East Respiratory Syndrome Coronavirus Infection Content: Clinical progression over time and cytokine profiles have not been well defined in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. We included 17 patients with laboratory-confirmed MERS-CoV during the 2015 outbreak in Korea. Clinical and laboratory parameters were collected prospectively. Serum cytokine and chemokine levels in serial serum samples were measured using enzyme-linked immunosorbent assay. All patients presented with fever. The median time to defervescence was 18 days. Nine patients required oxygen supplementation and classified into severe group. In the severe group, chest infiltrates suddenly began to worsen around day 7 of illness, and dyspnea developed at the end of the first week and became apparent in the second week. Median time from symptom onset to oxygen supplementation was 8 days. The severe group had higher neutrophil counts during week 1 than the mild group (4,500 vs. 2,200/\u00b5L, P = 0.026). In the second week of illness, the severe group had higher serum levels of IL-6 (54 vs. 4 pg/mL, P = 0.006) and CXCL-10 (2,642 vs. 382 pg/mL, P < 0.001). IFN-\u03b1 response was not observed in mild cases. Our data shows that clinical condition may suddenly deteriorate around 7 days of illness and the serum levels of IL-6 and CXCL-10 was significantly elevated in MERS-CoV patients who developed severe diseases.", "qid": 25, "docid": "vehb7dal", "rank": 79, "score": 0.7684570550918579}, {"content": "Title: An inflammatory cytokine signature helps predict COVID-19 severity and death Content: The COVID-19 pandemic caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to more than 100,000 deaths in the United States. Several studies have revealed that the hyper-inflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum IL-6, IL-8, TNF-, and IL-1{beta} in hospitalized COVID-19 patients upon admission to the Mount Sinai Health System in New York. Patients (n=1484) were followed up to 41 days (median 8 days) and clinical information, laboratory test results and patient outcomes were collected. In 244 patients, cytokine measurements were repeated over time, and effect of drugs could be assessed. Kaplan-Meier methods were used to compare survival by cytokine strata, followed by Cox regression models to evaluate the independent predictive value of baseline cytokines. We found that high serum IL-6, IL-8, and TNF- levels at the time of hospitalization were strong and independent predictors of patient survival. Importantly, when adjusting for disease severity score, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF- serum levels remained independent and significant predictors of disease severity and death. We propose that serum IL-6 and TNF- levels should be considered in the management and treatment of COVID-19 patients to stratify prospective clinical trials, guide resource allocation and inform therapeutic options. We also propose that patients with high IL-6 and TNF- levels should be assessed for combinatorial blockade of pathogenic inflammation in this disease.", "qid": 25, "docid": "9rgv88qf", "rank": 80, "score": 0.7683337926864624}, {"content": "Title: Characterization of the Inflammatory Response to Severe COVID-19 Illness Content: RATIONALE: Coronavirus disease 2019 (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood. OBJECTIVES: To define the cytokine profile of COVID-19, and to identify evidence of immunometabolic alterations in those with severe illness. METHODS: Levels of interleukin (IL)-1\u00df, IL-6, IL-8, IL-10 and soluble TNF receptor 1 (sTNFR1) were assessed in plasma from healthy volunteers, hospitalized-but-stable COVID-19 patients (COVIDstable), COVID-19 patients requiring intensive care unit (ICU) admission (COVIDICU) and individuals with severe community-acquired pneumonia requiring ICU support (CAPICU). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of alpha-1 antitrypsin (AAT) to COVID-19 was also evaluated. MAIN RESULTS: IL-1\u00df, IL-6, IL-8 and sTNFR1 were all increased in patients with COVID-19. COVIDICU patients could be clearly differentiated from COVIDstable, and demonstrated higher levels of IL-1\u00df, IL-6 and sTNFR1 - but lower IL-10 - than CAPICU. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2, phosphorylated PKM2, HIF-1&#945; and lactate. The production and sialylation of AAT increased in COVID-19, but this anti-inflammatory response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly higher in patients requiring ICU admission (P<0.0001). In critically unwell COVID-19 patients, increases in IL-6:AAT predicted prolonged ICU stay and mortality, while improvement in IL-6:AAT was associated with clinical resolution (P<0.0001). CONCLUSIONS: The COVID-19 cytokinemia is distinct from that of other types of pneumonia leading to organ failure and ICU need. Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness. Cytokine ratios may predict outcomes in this population. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).", "qid": 25, "docid": "z2l2vn1o", "rank": 81, "score": 0.7675971984863281}, {"content": "Title: Gut microbiota may underlie the predisposition of healthy individuals to COVID-19 Content: The COVID-19 pandemic is spreading globally with high disparity in the susceptibility of the disease severity. Identification of the key underlying factors for this disparity is highly warranted. Here we describe constructing a proteomic risk score based on 20 blood proteomic biomarkers which predict the progression to severe COVID-19. We demonstrate that in our own cohort of 990 individuals without infection, this proteomic risk score is positively associated with proinflammatory cytokines mainly among older, but not younger, individuals. We further discovered that a core set of gut microbiota could accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model, and that these gut microbiota features are highly correlated with proinflammatory cytokines in another set of 366 individuals. Fecal metabolomic analysis suggested potential amino acid-related pathways linking gut microbiota to inflammation. This study suggests that gut microbiota may underlie the predisposition of normal individuals to severe COVID-19.", "qid": 25, "docid": "lozkrca3", "rank": 82, "score": 0.7672778964042664}, {"content": "Title: Expansion of myeloid-derived suppressor cells in patients with severe coronavirus disease (COVID-19) Content: SARS-CoV-2 is associated with a 3.4% mortality rate in patients with severe disease. The pathogenesis of severe cases remains unknown. We performed an in-depth prospective analysis of immune and inflammation markers in two patients with severe COVID-19 disease from presentation to convalescence. Peripheral blood from 18 SARS-CoV-2-infected patients, 9 with severe and 9 with mild COVID-19 disease, was obtained at admission and analyzed for T-cell activation profile, myeloid-derived suppressor cells (MDSCs) and cytokine profiles. MDSC functionality was tested in vitro. In four severe and in four mild patients, a longitudinal analysis was performed daily from the day of admission to the early convalescent phase. Early after admission severe patients showed neutrophilia, lymphopenia, increase in effector T cells, a persisting higher expression of CD95 on T cells, higher serum concentration of IL-6 and TGF-\u03b2, and a cytotoxic profile of NK and T cells compared with mild patients, suggesting a highly engaged immune response. Massive expansion of MDSCs was observed, up to 90% of total circulating mononuclear cells in patients with severe disease, and up to 25% in the patients with mild disease; the frequency decreasing with recovery. MDSCs suppressed T-cell functions, dampening excessive immune response. MDSCs decline at convalescent phase was associated to a reduction in TGF-\u03b2 and to an increase of inflammatory cytokines in plasma samples. Substantial expansion of suppressor cells is seen in patients with severe COVID-19. Further studies are required to define their roles in reducing the excessive activation/inflammation, protection, influencing disease progression, potential to serve as biomarkers of disease severity, and new targets for immune and host-directed therapeutic approaches.", "qid": 25, "docid": "78u0ual5", "rank": 83, "score": 0.7672536373138428}, {"content": "Title: The Association of Lymphocyte count and levels of CRP, D-Dimer, and LDH with severe coronavirus disease 2019 (COVID-19): A Meta-Analysis Content: The rapid progression of Coronavirus disease 2019 (COVID-19) and its increasing burden on health systems necessitate the identification of parameters of severe infection to help in monitoring, prognoses and development of treatment algorithms. This review aims to investigate the association of lymphocyte count, CRP, LDH, and D-Dimer with the severe form of COVID-19. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases of MEDLINE/PubMed, WHO-Virtual Health Library (VHL), and ScienceDirect were used for the systematic search. Random effects model was used to estimate the pooled standardized mean differences (SMD) with the corresponding 95% confidence interval (CI), using OpenMeta Analyst software. A total of 11 studies, with 2437 COVID-19 patients, which fulfilled the eligibility criteria were included in the meta-analysis. The analysis revealed that lymphocyte count was significantly lower in patients with the severe form of COVID-19 (SMD = - 1.025, P value <.001). Also, the analysis of SMD showed that patients with severe COVID-19 have a significantly higher serum levels of CRP (SMD = 3.363, P value <.001), D-Dimer (SMD = 1.073, P value <.001), and LDH (SMD = 3.345, P value <.001). Low lymphocyte count and high levels of CRP, LDH, and D-Dimer are associated with severe COVID-19. These laboratory markers could be used as clinical indicators of worsening illness and poor prognosis of COVID-19.", "qid": 25, "docid": "m8x2ryx5", "rank": 84, "score": 0.766829252243042}, {"content": "Title: Treatment to prevent the development of severe COVID-19 Content: The respiratory virus infection COVID-19 caused by the new coronavirus SARS-CoV2 has been reported in China since December 2019 It has been reported that COVID-19 tends to be more severe in the elderly and in patients with underlying diseases including diabetes, heart disease, and chronic lung disease In severe cases, patients require intensive cares including mechanical ventilation in the ICUs So far, no biomarker that predicts the severity, or no therapeutic strategies to prevent the development of severe diseases has been established Pathology of severe COVID-19 has two aspects: viral overgrowth and excess pulmonary inflammation For the former, clinical trials using existing drugs such as remdesivir (nucleic acid drug), lopinavir/ritonavir combination drug (protease inhibitor), favipravir (polymerase inhibitor), and interferon (antiviral drugs) are being conducted in patients with severe COVID-19 in China Furthermore the interest has been focused on immune globulin preparations enriched with pathogen-specific antibodies collected from the plasma of recovered patients For the latter, clinical studies using tocilizumab (IL-6 receptor antibody) and ACE2 protein have been conducted with the purpose of reducing excessive inflammation of the lung In addition, single cell analysis of immune cells and comprehensive repertoire analysis of TCR/BCR using patient blood are in progress overseas, which are useful to elucidate the mechanism of the severe disease progression and identify the useful biomarkers for it", "qid": 25, "docid": "flfnpzsd", "rank": 85, "score": 0.7667794823646545}, {"content": "Title: Risk factors associated with disease progression in a cohort of patients infected with the 2019 novel coronavirus. Content: BACKGROUND The emerging infection of the 2019 novel coronavirus (2019-nCoV) in late December, 2019 in Wuhan, China, has caused an extreme health concern, with many patients having progressed to acute respiratory disease or other complications in a short period. Meanwhile, the risk factors associated with the disease progression still remain elusive. METHODS A cohort of 17 patients with laboratory-confirmed 2019-nCoV infections who were admitted to the Ninth Hospital of Nanchang between January 28 and February 6, 2020, were enrolled in this study. All the patients received standardized treatment. The disease progression was evaluated every 7 days after admission. The clinical, radiologic, and laboratory characteristics were retrospectively analyzed, and the factors associated with the disease progression were screened by binary logistic regression analysis. RESULTS The cohort comprised 11 women (64.7%) and 6 men (35.3%) between the ages of 18 to 70 years old. All patients had a reported history of contact with infection-confirmed patients. Fever (11/64.7%) and cough (8/47.1%) were the most common symptoms, whereas dyspnea (2/11.8%) and fatigue (3/17.6%) were rare, and there was no patient with diarrhea symptoms. There were 5 patients with aggravated disease at the first disease progression evaluation, and no patient received mechanical ventilation, transferred to the intensive care unit (ICU), or progressed to acute respiratory distress syndrome, septic shock, refractory metabolic acidosis, coagulation dysfunction, or death. Based on the disease progression, patients were divided into the non-aggravation group (12 cases) and the aggravation group (5 cases). There were no significant differences between the 2 groups with respect to their clinical characteristics. Chest computed tomography (CT) on admission revealed there were 8 patients (47.1%) with invasive lesions found bilaterally on the lungs on multiple lobes, 4 patients (23.5%) with invasive lesions on 1 lobe, and 5 patients (29.4%) with normal chest CT. The aggravation group had1 patient (20.0%) with invasive lesions on one lobe, 3 (60.0%) with invasive lesions on multiple lobes, bilaterally, and 1 (20.0%) with normal chest CT; meanwhile, the nonaggravation group had 3 patients (25.0%) with invasive lesions on one lobe, 5 (41.7%) with invasive lesions on multiple lobes, bilaterally, and 4 (33.3%) with normal chest CT. No significant difference was found between the 2 groups. In the aggravation group, the total lymphocyte counts significantly decreased in comparison to that in the non-aggravation group. Further analysis showed that the CD4+ T cell count but not the CD8+ T cell count of the aggravation group was significantly lower than that of the non-aggravation group. Correlation analysis indicated total lymphocyte count was positively correlated with CD4+ T cell count, and no significant differences were found between the 2 groups in other laboratory measurements, including those of white blood cell (WBC) count, C-reactive protein (CRP), albumin, lactate dehydrogenase (LDH), and D-dimer. Finally, a binary logistic regression model was used to identify the factors associated with the disease progression. It was found that total lymphocyte count was a risk factor associated with disease progression in patients infected with 2019-nCoV. CONCLUSIONS A higher cell count of total lymphocytes may indicate a better outcome of the disease, and immune response may be a vital factor for directing disease progression in the early stage of 2019-nCoV infection.", "qid": 25, "docid": "z3rpoqao", "rank": 86, "score": 0.7666341066360474}, {"content": "Title: Potential Factors for Prediction of Disease Severity of COVID-19 Patients Content: Abstract: Objective: Coronavirus disease 2019 (COVID-19) is an escalating global epidemic caused by SARS-CoV-2, with a high mortality in critical patients. Effective indicators for predicting disease severity in SARS-CoV-2 infected patients are urgently needed. Methods: In this study, 43 COVID-19 patients admitted in Chongqing Public Health Medical Center were involved. Demographic data, clinical features, and laboratory examinations were obtained through electronic medical records. Peripheral blood specimens were collected from COVID-19 patients and examined for lymphocyte subsets and cytokine profiles by flow cytometry. Potential contributing factors for prediction of disease severity were further analyzed. Results: A total of 43 COVID-19 patients were included in this study, including 29 mild patients and 14 sever patients. Severe patients were significantly older (61.9+/-9.4 vs 44.4+/-15.9) and had higher incidence in co-infection with bacteria compared to mild group (85.7%vs27.6%). Significantly more severe patients had the clinical symptoms of anhelation (78.6%) and asthma (71.4%). For laboratory examination, 57.1% severe cases showed significant reduction in lymphocyte count. The levels of Interluekin-6 (IL6), IL10, erythrocyte sedimentation rate (ESR) and D-Dimer (D-D) were significantly higher in severe patients than mild patients, while the level of albumin (ALB) was remarkably lower in severe patients. Further analysis demonstrated that ESR, D-D, age, ALB and IL6 were the major contributing factors for distinguishing severe patients from mild patients. Moreover, ESR was identified as the most powerful factor to predict disease progression of COVID-19 patients. Conclusion: Age and the levels of ESR, D-D, ALB and IL6 are closely related to the disease severity of COVID-19 patients. ESR can be used as a valuable indicator for distinguishing severe COVID-19 patients in early stage, so as to increase the survival of severe patients. Keyword: COVID-19, erythrocyte sedimentation rate, cytokines, lymphocytes", "qid": 25, "docid": "tv9xsned", "rank": 87, "score": 0.7664440274238586}, {"content": "Title: Biomarkers associated with COVID-19 disease progression Content: The coronavirus disease 2019 (COVID-19) pandemic is a scientific, medical, and social challenge. The complexity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is centered on the unpredictable clinical course of the disease that can rapidly develop, causing severe and deadly complications. The identification of effective laboratory biomarkers able to classify patients based on their risk is imperative in being able to guarantee prompt treatment. The analysis of recently published studies highlights the role of systemic vasculitis and cytokine mediated coagulation disorders as the principal actors of multi organ failure in patients with severe COVID-19 complications. The following biomarkers have been identified: hematological (lymphocyte count, neutrophil count, neutrophil-lymphocyte ratio (NLR)), inflammatory (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT)), immunological (interleukin (IL)-6 and biochemical (D-dimer, troponin, creatine kinase (CK), aspartate aminotransferase (AST)), especially those related to coagulation cascades in disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS). New laboratory biomarkers could be identified through the accurate analysis of multicentric case series; in particular, homocysteine and angiotensin II could play a significant role.", "qid": 25, "docid": "vcpo3qob", "rank": 88, "score": 0.7663463354110718}, {"content": "Title: Biomarkers associated with COVID-19 disease progression Content: The coronavirus disease 2019 (COVID-19) pandemic is a scientific, medical, and social challenge. The complexity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is centered on the unpredictable clinical course of the disease that can rapidly develop, causing severe and deadly complications. The identification of effective laboratory biomarkers able to classify patients based on their risk is imperative in being able to guarantee prompt treatment. The analysis of recently published studies highlights the role of systemic vasculitis and cytokine mediated coagulation disorders as the principal actors of multi organ failure in patients with severe COVID-19 complications. The following biomarkers have been identified: hematological (lymphocyte count, neutrophil count, neutrophil\u2013lymphocyte ratio (NLR)), inflammatory (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT)), immunological (interleukin (IL)-6 and biochemical (D-dimer, troponin, creatine kinase (CK), aspartate aminotransferase (AST)), especially those related to coagulation cascades in disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS). New laboratory biomarkers could be identified through the accurate analysis of multicentric case series; in particular, homocysteine and angiotensin II could play a significant role.", "qid": 25, "docid": "3l2t9w9l", "rank": 89, "score": 0.7660219073295593}, {"content": "Title: A cohort study of 223 patients explores the clinical risk factors for the severity diagnosis of COVID-19 Content: BACKGROUND: Coronavirus Disease 2019 (COVID-19) has recently become a public emergency and a worldwide pandemic. The clinical symptoms of severe and non-severe patients vary, and the case-fatality rate (CFR) in severe COVID-19 patients is very high. However, the information on the risk factors associated with the severity of COVID-19 and of their prognostic potential is limited. METHODS: In this retrospective study, the clinical characteristics, laboratory findings, treatment and outcome data were collected and analyzed from 223 COVID-19 patients stratified into 125 non-severe patients and 98 severe patients. In addition, a pooled large-scale meta-analysis of 1646 cases was performed. RESULTS: We found that the age, gender and comorbidities are the common risk factors associated with the severity of COVID-19. For the diagnosis markers, we found that the levels of D-dimer, C-reactive protein (CRP), lactate dehydrogenase (LDH), procalcitonin (PCT) were significantly higher in severe group compared with the non-severe group on admission (D-Dimer: 87.3% vs. 35.3%, P<0.001; CRP, 65.1% vs. 13.5%, P<0.001; LDH: 83.9% vs. 22.2%, P<0.001; PCT: 35.1% vs. 2.2%, P<0.001), while the levels of aspartate aminotransferase (ASP) and creatinine kinase (CK) were only mildly increased. We also made a large scale meta-analysis of 1646 cases combined with 4 related literatures, and further confirmed the relationship between the COVID-19 severity and these risk factors. Moreover, we tracked dynamic changes during the process of COVID-19, and found CRP, D-dimer, LDH, PCT kept in high levels in severe patient. Among all these markers, D-dimer increased remarkably in severe patients and mostly related with the case-fatality rate (CFR). We found adjuvant antithrombotic treatment in some severe patients achieved good therapeutic effect in the cohort. CONCLUSIONS: The diagnosis markers CRP, D-dimer, LDH and PCT are associated with severity of COVID-19. Among these markers, D-dimer is sensitive for both severity and CFR of COVID-19. Treatment with heparin or other anticoagulants may be beneficial for COVID-19 patients.", "qid": 25, "docid": "5innqoip", "rank": 90, "score": 0.7659598588943481}, {"content": "Title: Prognosis of COVID-19: Changes in laboratory parameters. Content: INTRODUCTION Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV-2) emerged in China and has become a global threat. Comparison of hematological parameters between mild and severe cases of SARS-CoV 2 is so far limited, but significant differences in parameters such as interleukin-6, d-dimers, glucose, fibrinogen and C-reactive protein have been already reported. PURPOSE In this study we analyzed the changes observed in easily measured blood biomarkers in the patients and provided evidence of how these markers can be used as prognostic factors of the disease. METHODS Demographic characteristics, detailed medical history, and laboratory findings of all enrolled SARS-CoV 2 infection positive patients who were referred to Patras University Hospital from the period of March 4th 2020 (when first confirmed case in Greece appeared in our hospital) until April 4th 2020 were extracted from electronic medical records and analyzed. RESULTS We provided evidence that some very common laboratory values can be used as independent predictive factors in SARS-CoV 2 infection. Despite the retrospective nature of this study and the small number of subjects analyzed, we showed that NLR, LDH, d-dimers, CRP, fibrinogen and ferritin can be used early at the patient's first visit for SARS-CoV 2 infection symptoms and can predict the severity of infection. CONCLUSION More studies are warranted to further objectively confirm the clinical value of prognostic factors related to SARS-CoV 2 and establish an easy-to-get panel of laboratory findings for evaluating the disease severity.", "qid": 25, "docid": "ljc7ojzt", "rank": 91, "score": 0.7658365964889526}, {"content": "Title: Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Content: Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread across many other countries. While the majority of patients were considered mild, critically ill patients involving respiratory failure and multiple organ dysfunction syndrome are not uncommon, which could result death. We hypothesized that cytokine storm is associated with severe outcome. We enrolled 102 COVID-19 patients who were admitted to Renmin Hospital (Wuhan, China). All patients were classified into moderate, severe and critical groups according to their symptoms. 45 control samples of healthy volunteers were also included. Inflammatory cytokines and C-Reactive Protein (CRP) profiles of serum samples were analyzed by specific immunoassays. Results showed that COVID-19 patients have higher serum level of cytokines (TNF-\u03b1, IFN-\u03b3, IL-2, IL-4, IL-6 and IL-10) and CRP than control individuals. Within COVID-19 patients, serum IL-6 and IL-10 levels are significantly higher in critical group (n = 17) than in moderate (n = 42) and severe (n = 43) group. The levels of IL-10 is positively correlated with CRP amount (r = 0.41, P < 0.01). Using univariate logistic regression analysis, IL-6 and IL-10 are found to be predictive of disease severity and receiver operating curve analysis could further confirm this result (AUC = 0.841, 0.822 respectively). Our result indicated higher levels of cytokine storm is associated with more severe disease development. Among them, IL-6 and IL-10 can be used as predictors for fast diagnosis of patients with higher risk of disease deterioration. Given the high levels of cytokines induced by SARS-CoV-2, treatment to reduce inflammation-related lung damage is critical.", "qid": 25, "docid": "zuchss0s", "rank": 92, "score": 0.7655780911445618}, {"content": "Title: Prediction Model Based on the Combination of Cytokines and Lymphocyte Subsets for Prognosis of SARS-CoV-2 Infection Content: BACKGROUND: There are currently rare satisfactory markers for predicting the death of patients with coronavirus disease 2019 (COVID-19). The aim of this study is to establish a model based on the combination of serum cytokines and lymphocyte subsets for predicting the prognosis of the disease. METHODS: A total of 739 participants with COVID-19 were enrolled at Tongji Hospital from February to April 2020 and classified into fatal (n = 51) and survived (n = 688) groups according to the patient\u2019s outcome. Cytokine profile and lymphocyte subset analysis was performed simultaneously. RESULTS: The fatal patients exhibited a significant lower number of lymphocytes including B cells, CD4(+) T cells, CD8(+) T cells, and NK cells and remarkably higher concentrations of cytokines including interleukin-2 receptor, interleukin-6, interleukin-8, and tumor necrosis factor-\u03b1 on admission compared with the survived subjects. A model based on the combination of interleukin-8 and the numbers of CD4(+) T cells and NK cells showed a good performance in predicting the death of patients with COVID-19. When the threshold of 0.075 was used, the sensitivity and specificity of the prediction model were 90.20% and 90.26%, respectively. Meanwhile, interleukin-8 was found to have a potential value in predicting the length of hospital stay until death. CONCLUSIONS: Significant increase of cytokines and decrease of lymphocyte subsets are found positively correlated with in-hospital death. A model based on the combination of three markers provides an attractive approach to predict the prognosis of COVID-19. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10875-020-00821-7) contains supplementary material, which is available to authorized users.", "qid": 25, "docid": "3103tqzv", "rank": 93, "score": 0.7655557990074158}, {"content": "Title: Predictors of progression from moderate to severe coronavirus disease 2019: a retrospective cohort Content: OBJECTIVE: Most cases of coronavirus disease 2019 (COVID-19) are identified as moderate, which is defined as having a fever or dry cough and lung imaging with ground-glass opacities. The risk factors and predictors of prognosis in such cohorts remain uncertain. METHODS: All adults with COVID-19 of moderate severity diagnosed using quantitative RT-PCR and hospitalized at the Central Hospital of Wuhan, China, from 1 January to 20 March 2020 were enrolled in this retrospective study. The main outcomes were progression from moderate to severe or critical condition or death. RESULTS: Among the 456 enrolled patients with moderate COVID-19, 251/456 (55.0%) had poor prognosis. Multivariate logistic regression analysis identified higher neutrophil count: lymphocyte count ratio (NLR) on admission (OR 1.032, 95% CI 1.042-1.230, p 0.004) and higher C-reactive protein (CRP) on admission (OR 3.017, 95% CI 1.941-4.690, p < 0.001) were associated with increased OR of poor prognosis. The area under the receiver operating characteristic curve (AUC) for NLR and CRP in predicting progression to critical condition was 0.77 (95% CI 0.694-0.846, p < 0.001) and 0.84 (95% CI 0.780-0.905, p < 0.001), with a cut-off value of 2.79 and 25.95 mg/L, respectively. The AUC of NLR and CRP in predicting death was 0.81 (95% CI 0.732-0.878, p < 0.001) and 0.89 (95% CI 0.825-0.946, p < 0.001), with a cut-off value of 3.19 and 33.4 mg/L, respectively. CONCLUSIONS: Higher levels of NLR and CRP at admission were associated with poor prognosis of individuals with moderate COVID-19. NLR and CRP were good predictors of progression to critical condition and death.", "qid": 25, "docid": "52ewsgwk", "rank": 94, "score": 0.7653997540473938}, {"content": "Title: Longitudinal COVID-19 profiling associates IL-1RA and IL-10 with disease severity and RANTES with mild disease Content: BACKGROUND: Identifying immune correlates of COVID-19 disease severity is an urgent need for clinical management, vaccine evaluation, and drug development. Here, we present a temporal analysis of key immune mediators, cytokines, and chemokines in blood of hospitalized COVID-19 patients from serial sampling and follow-up over 4 weeks. METHODS: A total of 71 patients with laboratory-confirmed COVID-19 admitted to Beijing You'an Hospital in China with either mild (53 patients) or severe (18 patients) disease were enrolled with 18 healthy volunteers. We measured 34 immune mediators, cytokines, and chemokines in peripheral blood every 4-7 days over 1 month per patient using a bioplex multiplex immunoassay. RESULTS: We found that the chemokine RANTES (CCL5) was significantly elevated, from an early stage of the infection, in patients with mild but not severe disease. We also found that early production of inhibitory mediators including IL-10 and IL-1RA were significantly associated with disease severity, and a combination of CCL5, IL-1 receptor antagonist (IL-1RA), and IL-10 at week 1 may predict patient outcomes. The majority of cytokines that are known to be associated with the cytokine storm in virus infections such as IL-6 and IFN-\u00ce\u00b3 were only significantly elevated in the late stage of severe COVID-19 illness. TNF-&#945; and GM-CSF showed no significant differences between severe and mild cases. CONCLUSION: Together, our data suggest that early intervention to increase expression of CCL5 may prevent patients from developing severe illness. Our data also suggest that measurement of levels of CCL5, as well as IL-1RA and IL-10 in blood individually and in combination, might be useful prognostic biomarkers to guide treatment strategies.", "qid": 25, "docid": "rxubph56", "rank": 95, "score": 0.7653243541717529}, {"content": "Title: Neutrophil\u2010to\u2010lymphocyte ratio and lymphocyte\u2010to\u2010C\u2010reactive protein ratio in patients with severe coronavirus disease 2019 (COVID\u201019): A meta\u2010analysis Content: Since March 11, 2020, the World Health Organization (WHO) defined Coronavirus disease 2019 (COVID-19) as a pandemic, with a series of confirmed cases that currently exceeded 300,000 people worldwide and with approximately 14,500 deaths. Accumulated evidence suggests that a subgroup of patients with severe COVID-19 could have a dysregulation of the immune response that allows the development of viral hyperinflammation. Thus, all patients with severe COVID-19 should be screened for hyperinflammation using laboratory parameters in order to improve mortality. Neutrophil-to-Lymphocyte ratio (NLR) and Lymphocyte-to-C-reactive protein ratio (LCR) are established inflammation markers that reflect systemic inflammatory response, and both are available in almost all laboratories. In this study, a meta-analysis was performed to investigate whether NLR and LCR values can help predict clinical severity in patients with COVID-19. This article is protected by copyright. All rights reserved.", "qid": 25, "docid": "u1npw7tw", "rank": 96, "score": 0.7652824521064758}, {"content": "Title: Predicting Disease Progression in COVID19: A Score Based On Lab Tests At Time Of Diagnosis Content: Background COVID19 is worldwide pandemic that is mild in the majority of patients but can result in a pneumonia like illness with progression to acute respiratory distress syndrome and death. Predicting the disease severity at time of diagnosis can be helpful in prioritizing hospital admission and resources. Methods We prospectively recruited 1096 consecutive patients with COVID19 from the Jaber Hospital, a COVID19 facility in Kuwait, between 24 February and 20 April 2020. The primary endpoint of interest was disease severity defined algorithmically. Predefined risk variables were collected at the time of PCR based diagnosis of the infection. Prognostic model development used 5-fold cross-validated regularized logit regression. The cohort was divided into a training and validation cohort and all model development proceeded on the training cohort. Results There were 643 patients with clinical course data of whom 94 developed severe COVID19. In the final model, age, CRP, procalcitonin, lymphocyte and monocyte percentages and serum albumin were independent predictors of a more severe illness course. The final prognostic model demonstrated good discrimination, calibration and internal validity. Conclusion We developed and validated a simple score calculated at time of diagnosis that can predict patients with severe COVID19 disease. Keywords COVID-19, Adverse Outcome, mortality, Procalcitonin, health policy", "qid": 25, "docid": "ommypdxh", "rank": 97, "score": 0.7652260065078735}, {"content": "Title: Elevated interleukin\u20106 and severe COVID\u201019: A meta\u2010analysis Content: Interleukin-6 is an important marker of inflammation. We performed a systematic review and meta-analysis to demonstrate the association of elevated IL-6 with severe Coronavirus disease-2019 (COVID-19). A total of 9 studies were included in the systematic review and meta-analysis. Patients with severe COVID-19 had a significantly higher serum IL-6 levels compared to non-severe patients (mean difference (MD): 38.6 pg/mL, 95% CI: 24.3 - 52.9 pg/mL, p <0.001, I2 = 98.5%). On meta-regression, increasing mean IL-6 level was associated with increased mortality in patients (Coefficient (Q): 0.01, 95% CI: 0.01-0.03, p = 0.03). Given the association of elevated IL-6 with severe COVID-19 and mortality, clinicians should use this as a potential marker to recognize severe disease. IL-6 should be incorporated in a scoring system along with other inflammatory markers to risk stratify the patients for early recognition of severe disease. Our study should encourage researchers to conduct trial evaluating Anti IL-6 antibodies such as Tocilizumab to assess the efficacy in patients with severe COVID-19. This article is protected by copyright. All rights reserved.", "qid": 25, "docid": "gok0wn5b", "rank": 98, "score": 0.7650079727172852}, {"content": "Title: Expansion of myeloid-derived suppressor cells in patients with severe coronavirus disease (COVID-19) Content: SARS-CoV-2 is associated with a 3.4% mortality rate in patients with severe disease. The pathogenesis of severe cases remains unknown. We performed an in-depth prospective analysis of immune and inflammation markers in two patients with severe COVID-19 disease from presentation to convalescence. Peripheral blood from 18 SARS-CoV-2-infected patients, 9 with severe and 9 with mild COVID-19 disease, was obtained at admission and analyzed for T-cell activation profile, myeloid-derived suppressor cells (MDSCs) and cytokine profiles. MDSC functionality was tested in vitro. In four severe and in four mild patients, a longitudinal analysis was performed daily from the day of admission to the early convalescent phase. Early after admission severe patients showed neutrophilia, lymphopenia, increase in effector T cells, a persisting higher expression of CD95 on T cells, higher serum concentration of IL-6 and TGF-\u00df, and a cytotoxic profile of NK and T cells compared with mild patients, suggesting a highly engaged immune response. Massive expansion of MDSCs was observed, up to 90% of total circulating mononuclear cells in patients with severe disease, and up to 25% in the patients with mild disease; the frequency decreasing with recovery. MDSCs suppressed T-cell functions, dampening excessive immune response. MDSCs decline at convalescent phase was associated to a reduction in TGF-\u00df and to an increase of inflammatory cytokines in plasma samples. Substantial expansion of suppressor cells is seen in patients with severe COVID-19. Further studies are required to define their roles in reducing the excessive activation/inflammation, protection, influencing disease progression, potential to serve as biomarkers of disease severity, and new targets for immune and host-directed therapeutic approaches.", "qid": 25, "docid": "fj2clzfx", "rank": 99, "score": 0.7646804451942444}, {"content": "Title: Targeted Immunosuppression Distinguishes COVID-19 from Influenza in Moderate and Severe Disease Content: Coronavirus disease 2019 (COVID-19) is characterized by a high incidence of acute respiratory failure. The underlying immunopathology of that failure and how it compares to other causes of severe respiratory distress, such as influenza virus infection, are not fully understood. Here we addressed this by developing a prospective observational cohort of COVID-19 and influenza subjects with varying degrees of disease severity and assessing the quality and magnitude of their immune responses at the cellular and protein level. Additionally, we performed single-cell RNA transcriptional profiling of peripheral blood mononuclear cells from select subjects. The cohort consists of 79 COVID-19 subjects, 26 influenza subjects, and 15 control subjects, including 35 COVID-19 and 7 influenza subjects with acute respiratory failure. While COVID-19 subjects exhibited largely equivalent or greater activated lymphocyte counts compared to influenza subjects, they had fewer monocytes and lower surface HLA-class II expression on monocytes compared to influenza subjects and controls. At least two distinct immune profiles were observed by cytokine levels in severe COVID-19 patients: 3 of 71 patients were characterized by extreme inflammation, with greater than or equal to ~50% of the 35 cytokines measured greater than 2 standard deviations from the mean level of other severe patients (both influenza and COVID-19); the other immune profile, which characterized 68 of 71 subjects, had a mixed inflammatory signature, where 28 of 35 cytokines in COVID-19 patients had lower mean cytokine levels, though not all were statistically significant. Only 2 cytokines were higher in COVID-19 subjects compared to influenza subjects (IL-6 and IL-8). Influenza and COVID-19 patients could be distinguished statistically based on cytokine module expression, particularly after controlling for the significant effects of age on cytokine expression, but again with lower levels of most cytokines in COVID-19 subjects. Further, high circulating levels of IL-1RA and IL-6 were associated with increased odds of intubation in the combined influenza and COVID-19 cohort [OR = 3.93 and 4.30, respectively] as well as among only COVID-19 patients. Single cell transcriptional profiling of COVID-19 and influenza subjects with respiratory failure identified profound suppression in type I and type II interferon signaling in COVID-19 patients across multiple clusters. In contrast, COVID-19 cell clusters were enriched for alterations in metabolic, stress, and apoptotic pathways. These alterations were consistent with an increased glucocorticoid response in COVID-19 patients compared to influenza. When considered across the spectrum of innate and adaptive immune profiles, the immune pathologies underlying severe influenza and COVID-19 are substantially distinct. The majority of COVID-19 patients with acute respiratory failure do not have a cytokine storm phenotype but instead exhibit profound type I and type II IFN immunosuppression when compared to patients with acute influenza. Upregulation of a small number of inflammatory mediators, including IL-6, predicts acute respiratory failure in both COVID-19 and influenza patients.", "qid": 25, "docid": "z9uu4sj7", "rank": 100, "score": 0.7644268274307251}]}
{"query": "what are the initial symptoms of Covid-19?", "hits": [{"content": "Title: Anosmia as a prominent symptom of COVID-19 infection Content: According to WHO recommendations, everyone must protect themselves against Coronavirus disease 2019 (COVID-19), which will also protect others. Due to the lack of current effective treatment and vaccine for COVID-19, screening, rapid diagnosis and isolation of the patients are essential (1, 2). Therefore, identifying the early symptoms of COVID-19 is of particular importance and is a health system priority. Early studies from COVID-19 outbreak in China have illustrated several non-specific signs and symptoms in infected patients, including fever, dry cough, dyspnea, myalgia, fatigue, lymphopenia, and radiographic evidence of pneumonia (3, 4). Recently, a probability of association between COVID-19 and altered olfactory function has been reported in South Korea, Iran, Italy, France, UK and the United States (5-8). However, to our knowledge, the definite association between COVID-19 and anosmia has not been published.", "qid": 26, "docid": "ils991dx", "rank": 1, "score": 0.7916582822799683}, {"content": "Title: Anosmia as a prominent symptom of COVID-19 infection. Content: According to WHO recommendations, everyone must protect themselves against Coronavirus disease 2019 (COVID-19), which will also protect others. Due to the lack of current effective treatment and vaccine for COVID-19, screening, rapid diagnosis and isolation of the patients are essential (1, 2). Therefore, identifying the early symptoms of COVID-19 is of particular importance and is a health system priority. Early studies from COVID-19 outbreak in China have illustrated several non-specific signs and symptoms in infected patients, including fever, dry cough, dyspnea, myalgia, fatigue, lymphopenia, and radiographic evidence of pneumonia (3, 4). Recently, a probability of association between COVID-19 and altered olfactory function has been reported in South Korea, Iran, Italy, France, UK and the United States (5-8). However, to our knowledge, the definite association between COVID-19 and anosmia has not been published.", "qid": 26, "docid": "k23iyivp", "rank": 2, "score": 0.7916582822799683}, {"content": "Title: Vascular skin symptoms in COVID-19: a french observational study Content: Coronavirus 19 (COVID-19) was declared as a pandemic viral infection by the World Health organization on March 11th 2020. Usual clinical manifestations of COVID-19 infection include fever, fatigue, myalgia, headache, diarrhea, dry cough, dyspnea that may lead to acute respiratory distress syndrome and death (1). Skin symptoms of COVID-19 have been poorly described but may include erythematous rash, urticaria and chicken pox like lesions (2-7). Angiotensin-converting enzyme 2 (ACE2) is a cellular receptor for COVID-19.", "qid": 26, "docid": "vp5xj8m5", "rank": 3, "score": 0.7779515981674194}, {"content": "Title: COVID-19 and Gastrointestinal Symptoms\u2014A Case Report Content: COVID-19, a new illness secondary to a novel Coronavirus emerged in December 2019 in China. Our early understanding of the clinical features of COVID-19 has been based on case series emerging from the first outbreak in Wuhan. These features included fever, a dry cough, myalgia and dyspnea. Gastrointestinal symptoms were rarely reported as a key feature. We present a case report of a 74-year-old male who presented with symptoms of gastroenteritis and subsequently tested positive for COVID-19. This article aims to highlight an uncommon presentation of COVID-19 and that a high index of suspicion is required for COVID-19 in older people given their greater likelihood of presenting atypically.", "qid": 26, "docid": "e43f1xky", "rank": 4, "score": 0.772435188293457}, {"content": "Title: COVID19: A Systematic Approach to Early Identification and Healthcare Worker Protection Content: The COVID-19 outbreak spread rapidly throughout the globe, with worldwide infections and deaths continuing to increase dramatically. To control disease spread and protect healthcare workers, accurate information is necessary. We searched PubMed and Google Scholar for studies published from December 2019 to March 31, 2020 with the terms \u201cCOVID-19,\u201d \u201c2019-nCoV,\u201d \u201cSARS-CoV-2,\u201d or \u201cNovel Coronavirus Pneumonia.\u201d The main symptoms of COVID-19 are fever (83\u201398.6%), cough (59.4\u201382%), and fatigue (38.1\u201369.6%). However, only 43.8% of patients have fever early in the disease course, despite still being infectious. These patients may present to clinics lacking proper precautions, leading to nosocomial transmission, and infection of workers. Potential COVID-19 cases must be identified early to initiate proper triage and distinguish them quickly from similar infections. Early identification, accurate triage, and standardized personal protection protocols can reduce the risk of cross infection. Containing disease spread will require protecting healthcare workers.", "qid": 26, "docid": "qy7dsyz0", "rank": 5, "score": 0.7717282772064209}, {"content": "Title: Clinical time course of COVID-19, its neurological manifestation and some thoughts on its management Content: Coronavirus disease-2019 (COVID-19) has become a global pandemic. COVID-19 runs its course in two phases, the initial incubation phase and later clinical symptomatic phase. Patients in the initial incubation phase often have insidious clinical symptoms, but they are still highly contagious. At the later clinical symptomatic phase, the immune system is fully activated and the disease may enter the severe infection stage in this phase. Although many patients are known for their respiratory symptoms, they had neurological symptoms in their first 1-2 days of clinical symptomatic phase, and ischaemic stroke occurred 2 weeks after the onset of the clinical symptomatic phase. The key is to prevent a patient from progressing to this severe infection from mild infection. We are sharing our experience on prevention and management of COVID-19.", "qid": 26, "docid": "y5ptscri", "rank": 6, "score": 0.7665133476257324}, {"content": "Title: Risk Factors Prediction, Clinical Outcomes, and Mortality of COVID-19 Patients Content: Background: Preventing communicable diseases requires understanding the spread, epidemiology, clinical features, progression, and prognosis of the disease. Early identification of risk factors and clinical outcomes might help to identify critically ill patients, provide proper treatment and prevent mortality. Methods: We conducted a prospective study in patients with flu-like symptoms referred to the imaging department of a tertiary hospital in IRAN between 3 March 2020 and 8 April 2020. Patients with COVID-19 were followed up to check their health condition after two months. The categorical data between groups were analyzed by Fisher exact test and continuous data by Wilcoxon Rank-Sum Test. Findings: 319 patients (mean age 45.48 years, 177 women) were enrolled. Fever, dyspnea, weakness, shivering, C-reactive protein (CRP), fatigue, dry cough, anorexia, anosmia, ageusia, dizziness, sweating and age were the most important symptoms of COVID-19 infection. Traveling in past three months, asthma, taking corticosteroids, liver disease, rheumatological disease, cough with sputum, eczema, conjunctivitis, tobacco use, and chest pain did not have any relationship with COVID-19. Interpretation: Finding clinical symptoms for early diagnosis of COVID-19 is a critical part of prevention. These symptoms can help in the assessment of disease progression. To the best of our knowledge, some of the effective features on the mortality due to COVID-19 are investigated for the first time in this research. Funding: None", "qid": 26, "docid": "fntwg3g8", "rank": 7, "score": 0.7638574838638306}, {"content": "Title: Uncommon presentation of COVID-19: Gastrointestinal bleeding Content: The COVID-19 outbreak has become a pandemic that is threatening global health. The typical clinical manifestations were fever, cough, dyspnea, and myalgia or fatigue. Digestive symptoms such as nausea, vomiting, diarrhea, abdominal pain usually accompany respiratory symptoms. However gastrointestinal bleeding as the first symptom is not reported. Here we reported a case of COVID-19 with gastrointestinal bleeding as the initial symptom to the emergency department with a real-time reverse transcriptase polymerase chain reaction test positive, and normal thorax tomography. The case demonstrate that; clinicians should be alerted to patients about COVID-19 when referring to atypical symptoms and every patient undergoing endoscopy should be considered potentially infected or can infect others.", "qid": 26, "docid": "99c1wgid", "rank": 8, "score": 0.7627291679382324}, {"content": "Title: Maternal mortality from COVID-19 in Mexico. Content: COVID-19, the illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the deadliest pandemic to occur in this century. Common symptoms of COVID-19 include cough, myalgia, fever, chest pain, and headache. However, its clinical presentation ranges from completely asymptomatic to acute respiratory distress syndrome.[1] Pregnant women are susceptible to community spread of COVID-19 because they cannot postpone interactions with healthcare professionals and other women receiving obstetric care.", "qid": 26, "docid": "8noxjjuh", "rank": 9, "score": 0.7617461681365967}, {"content": "Title: COVID-19: A New Virus as a Potential Rapidly Spreading in the Worldwide Content: Covid-19 is a novel virus with high affinity to spread in the community In December 2019, it was first identified in Wuhan, China The symptoms are non-specific, so fever, cough, dyspnea, are prominent features Respiratory failure and mortality have also been reported The most common lung CT scan findings are bilateral ground glass opacities", "qid": 26, "docid": "0em5sf3g", "rank": 10, "score": 0.7614805698394775}, {"content": "Title: Digestive Symptoms in COVID-19 Patients With Mild Disease Severity: Clinical Presentation, Stool Viral RNA Testing, and Outcomes Content: OBJECTIVES: Coronavirus disease 2019 (COVID-19) most commonly presents with respiratory symptoms, including cough, shortness of breath, and sore throat. However, digestive symptoms also occur in patients with COVID-19 and are often described in outpatients with less severe disease. In this study, we sought to describe the clinical characteristics of COVID-19 patients with digestive symptoms and mild disease severity. METHODS: We identified COVID-19 patients with mild disease and one or more digestive symptoms (diarrhea, nausea, and vomiting), with or without respiratory symptoms, and compared them with a group presenting solely with respiratory symptoms. We followed up patients clinically until they tested negative for COVID-19 on at least 2 sequential respiratory tract specimens collected \u226524 hours apart. We then compared the clinical features between those with digestive symptoms and those with respiratory symptoms. RESULTS: There were 206 patients with low severity COVID-19, including 48 presenting with a digestive symptom alone, 69 with both digestive and respiratory symptoms, and 89 with respiratory symptoms alone. Between the 2 groups with digestive symptoms, 67 presented with diarrhea, of whom 19.4% experienced diarrhea as the first symptom in their illness course. The diarrhea lasted from 1 to 14 days, with an average duration of 5.4 \u00b1 3.1 days and a frequency of 4.3 \u00b1 2.2 bowel movements per day. Concurrent fever was found in 62.4% of patients with a digestive symptom. Patients with digestive symptoms presented for care later than those with respiratory symptoms (16.0 \u00b1 7.7 vs 11.6 \u00b1 5.1 days, P < 0.001). Nevertheless, patients with digestive symptoms had a longer duration between symptom onset and viral clearance (P < 0.001) and were more likely to be fecal virus positive (73.3% vs 14.3%, P = 0.033) than those with respiratory symptoms. DISCUSSION: We describe a unique subgroup of COVID-19 patients with mild disease severity marked by the presence of digestive symptoms. These patients are more likely to test positive for viral RNA in stool, to have a longer delay before viral clearance, and to experience delayed diagnosis compared with patients with only respiratory symptoms.", "qid": 26, "docid": "a6avr09j", "rank": 11, "score": 0.7601537704467773}, {"content": "Title: Clinical and epidemiologic profile of the initial COVID-19 patients at a tertiary care centre in India Content: COVID-19 has now become a pandemic. It has spread from Wuhan, China, in December 2019 to a large number of countries within three months. The objective of this work is to report the initial experience with epidemiologic and clinical features, as well as with the management of COVID-19 patients in India. This is a descriptive case series of the first 21 COVID-19 infected patients confirmed with polymerase chain reaction (PCR) and admitted to a tertiary care centre in India from 01.02.2020 to 19.03.2020. Clinical, laboratory, and radiologic data were collected, including age, sex, nationality, travel history, symptoms, duration of stay, and comorbidities. The mean age of the population was 40.3 years with a male preponderance. Thirteen (62%) patients had recent travel history outside India in the previous 30 days, two thirds of whom had travelled to Italy. The most common symptoms were fever and cough (42.9%) followed by sore throat, headache and breathlessness. Vital and laboratory parameters were preserved in all patients and none of them required ventilatory support. Among the first 21 patients diagnosed with COVID-19 infection in India, the typical clinical presentation consisted in a mild upper respiratory tract infection predominantly affecting the young male population. One patient required supplemental oxygen. All patients recovered with no residual symptoms. *The Safdarjung Hospital COVID 2019 working group: Nitesh Gupta, Sumita Agrawal, Pranav Ish, Suruchi Mishra, Rajni Gaind, Ganapathy Usha, Balvinder Singh, Manas Kamal Sen, Shibdas Chakrabarti (Consultant and Head, Pulmonary Medicine); NK Gupta (Professor, Pulmonary medicine); Dipak Bhattacharya (Consultant, Pulmonary medicine); Rohit Kumar (Assistant Professor, Pulmonary Medicine); Siddharth R. Yadav (Assistant Professor, Pulmonary Medicine); Rushika Saksena (Specialist, Microbiology); Rojaleen Das (Assistant Professor, Microbiology); Vikramjeet Dutta (Assistant Professor, Microbiology); Anupam Kr Anveshi (Senior Resident, Microbiology); Santvana Kohli (Assistant Professor, Anaesthesiology); Naveen KV (Assistant Professor, Anaesthesiology); Amandeep Jaswal (Assistant Professor, Anaesthesiology).", "qid": 26, "docid": "d8c1e4pq", "rank": 12, "score": 0.7597967982292175}, {"content": "Title: Clinical and epidemiologic profile of the initial COVID-19 patients at a tertiary care centre in India. Content: COVID-19 has now become a pandemic. It has spread from Wuhan, China, in December 2019 to a large number of countries within three months. The objective of this work is to report the initial experience with epidemiologic and clinical features, as well as with the management of COVID-19 patients in India. This is a descriptive case series of the first 21 COVID-19 infected patients confirmed with polymerase chain reaction (PCR) and admitted to a tertiary care centre in India from 01.02.2020 to 19.03.2020. Clinical, laboratory, and radiologic data were collected, including age, sex, nationality, travel history, symptoms, duration of stay, and comorbidities. The mean age of the population was 40.3 years with a male preponderance. Thirteen (62%) patients had recent travel history outside India in the previous 30 days, two thirds of whom had travelled to Italy. The most common symptoms were fever and cough (42.9%) followed by sore throat, headache and breathlessness. Vital and laboratory parameters were preserved in all patients and none of them required ventilatory support. Among the first 21 patients diagnosed with COVID-19 infection in India, the typical clinical presentation consisted in a mild upper respiratory tract infection predominantly affecting the young male population. One patient required supplemental oxygen. All patients recovered with no residual symptoms. *The Safdarjung Hospital COVID 2019 working group: Nitesh Gupta, Sumita Agrawal, Pranav Ish, Suruchi Mishra, Rajni Gaind, Ganapathy Usha, Balvinder Singh, Manas Kamal Sen, Shibdas Chakrabarti (Consultant and Head, Pulmonary Medicine); NK Gupta (Professor, Pulmonary medicine); Dipak Bhattacharya (Consultant, Pulmonary medicine); Rohit Kumar (Assistant Professor, Pulmonary Medicine); Siddharth R. Yadav (Assistant Professor, Pulmonary Medicine); Rushika Saksena (Specialist, Microbiology); Rojaleen Das (Assistant Professor, Microbiology); Vikramjeet Dutta (Assistant Professor, Microbiology); Anupam Kr Anveshi (Senior Resident, Microbiology); Santvana Kohli (Assistant Professor, Anaesthesiology); Naveen KV (Assistant Professor, Anaesthesiology); Amandeep Jaswal (Assistant Professor, Anaesthesiology).", "qid": 26, "docid": "buzt3884", "rank": 13, "score": 0.7597967982292175}, {"content": "Title: Clinical time course of COVID-19, its neurological manifestation and some thoughts on its management Content: Coronavirus disease-2019 (COVID\u201019) has become a global pandemic. COVID-19 runs its course in two phases, the initial incubation phase and later clinical symptomatic phase. Patients in the initial incubation phase often have insidious clinical symptoms, but they are still highly contagious. At the later clinical symptomatic phase, the immune system is fully activated and the disease may enter the severe infection stage in this phase. Although many patients are known for their respiratory symptoms, they had neurological symptoms in their first 1\u20132 days of clinical symptomatic phase, and ischaemic stroke occurred 2 weeks after the onset of the clinical symptomatic phase. The key is to prevent a patient from progressing to this severe infection from mild infection. We are sharing our experience on prevention and management of COVID-19.", "qid": 26, "docid": "ywsm11aw", "rank": 14, "score": 0.7595936059951782}, {"content": "Title: SARS-COV-2 Presenting as New Onset Atrial Fibrillation: A Case Report Content: Current literature has documented numerous different presentations of SARS-COV-2 (COVID-19). Common symptoms include fever, cough and shortness of breath, however, lack of these symptoms does not exclude COVID-19. Given the incomplete understanding of the virus at this time, healthcare professionals must continue to remain informed of the vast number of clinical presentations of the virus to ensure early supportive treatment, ideally leading to improved outcomes.", "qid": 26, "docid": "bqivjudl", "rank": 15, "score": 0.7593305110931396}, {"content": "Title: Uncommon Presentation Of Covid-19: Gastrointestinal Bleeding Content: SUMMARY The COVID-19 outbreak has become a pandemic that is threatening global health. The typical clinical manifestations were fever, cough, dyspnea, and myalgia or fatigue. Digestive symptoms such as nausea, vomiting, diarrhea, abdominal pain usually accompany respiratory symptoms. However gastrointestinal bleeding as the first symptom is not reported. Here we reported a case of COVID-19 with gastrointestinal bleeding as the initial symptom to the emergency department with a real-time reverse transcriptase polymerase chain reaction test positive, and normal thorax tomography. The case demonstrate that; clinicians should be alerted to patients about COVID-19 when referring to atypical symptoms and every patient undergoing endoscopy should be considered potentially infected or can infect others.", "qid": 26, "docid": "xgr6r6of", "rank": 16, "score": 0.7585750222206116}, {"content": "Title: Digestive Symptoms in COVID-19 Patients With Mild Disease Severity: Clinical Presentation, Stool Viral RNA Testing, and Outcomes Content: OBJECTIVES: Coronavirus disease 2019 (COVID-19) most commonly presents with respiratory symptoms, including cough, shortness of breath, and sore throat. However, digestive symptoms also occur in patients with COVID-19 and are often described in outpatients with less severe disease. In this study, we sought to describe the clinical characteristics of COVID-19 patients with digestive symptoms and mild disease severity. METHODS: We identified COVID-19 patients with mild disease and one or more digestive symptoms (diarrhea, nausea, and vomiting), with or without respiratory symptoms, and compared them with a group presenting solely with respiratory symptoms. We followed up patients clinically until they tested negative for COVID-19 on at least 2 sequential respiratory tract specimens collected &#8805;24 hours apart. We then compared the clinical features between those with digestive symptoms and those with respiratory symptoms. RESULTS: There were 206 patients with low severity COVID-19, including 48 presenting with a digestive symptom alone, 69 with both digestive and respiratory symptoms, and 89 with respiratory symptoms alone. Between the 2 groups with digestive symptoms, 67 presented with diarrhea, of whom 19.4% experienced diarrhea as the first symptom in their illness course. The diarrhea lasted from 1 to 14 days, with an average duration of 5.4 \u00b1 3.1 days and a frequency of 4.3 \u00b1 2.2 bowel movements per day. Concurrent fever was found in 62.4% of patients with a digestive symptom. Patients with digestive symptoms presented for care later than those with respiratory symptoms (16.0 \u00b1 7.7 vs 11.6 \u00b1 5.1 days, P < 0.001). Nevertheless, patients with digestive symptoms had a longer duration between symptom onset and viral clearance (P < 0.001) and were more likely to be fecal virus positive (73.3% vs 14.3%, P = 0.033) than those with respiratory symptoms. DISCUSSION: We describe a unique subgroup of COVID-19 patients with mild disease severity marked by the presence of digestive symptoms. These patients are more likely to test positive for viral RNA in stool, to have a longer delay before viral clearance, and to experience delayed diagnosis compared with patients with only respiratory symptoms.", "qid": 26, "docid": "hdxs9dgu", "rank": 17, "score": 0.7583309412002563}, {"content": "Title: Clinical Pathway for Early Diagnosis of COVID-19: Updates from Experience to Evidence-Based Practice Content: The COVID-19 pandemic is a significant global event in the history of infectious diseases. The SARS-CoV-2 appears to have originated from bats but is now easily transmissible among humans, primarily through droplet or direct contact. Clinical features of COVID-19 include high fever, cough, and fatigue which may progress to ARDS. Respiratory failure can occur rapidly after this. The primary laboratory findings include lymphopenia and eosinopenia. Elevated D-dimer, procalcitonin, and CRP levels may correlate with disease severity. Imaging findings include ground-glass opacities and patchy consolidation on CT scan. Mortality is higher in patients with hypertension, cardiac disease, diabetes mellitus, cancer, and COPD. Elderly patients are more susceptible to severe disease and death, while children seem to have lower rates of infection and lower mortality. Diagnostic criteria and the identification of persons under investigation have evolved as more data has emerged. However, the approach to diagnosis is still very variable from region to region, country to country, and even among different hospitals in the same city. The importance of a clinical pathway to implement the most effective and relevant diagnostic strategy is of critical importance to establish the control of this virus that is responsible for more and more deaths each day.", "qid": 26, "docid": "kbjn7ke8", "rank": 18, "score": 0.7579788565635681}, {"content": "Title: What do surgeons need to know about the digestive disorders and paraclinical abnormalities induced by COVID-19? Content: The symptoms associated with COVID-19 are mainly characterized by a triad composed of fever, dry cough and dyspnea. However, digestive symptoms have also been reported. At first considered as infrequent, they in fact seem to affect more than half of patients. The symptoms mainly include anorexia, diarrhea, nausea and/or vomiting and abdominal pain. Even though prognosis is associated with lung injury, digestive symptoms seem significantly more frequent in patients presenting with severe COVID-19 infection. Digestive presentations, which may be isolated or which can precede pulmonary symptoms, have indeed been reported, with diarrhea as a leading clinical sign. The main biological abnormalities that can suggest COVID-19 infection at an early stage are lymphopenia, elevated CRP and heightened ASAT transaminases. Thoraco-abdominal scan seems useful as a means of on the one hand ruling out digestive pathology not connected with coronavirus and on the other hand searching for pulmonary images consistent with COVID-19 infection. No data exist on the value of digestive endoscopy in cases of persistent digestive symptoms. Moreover, the endoscopists may themselves be at significant risk of contamination. Fecal-oral transmission of the infection is possible, especially insofar as viral shedding in stools seems frequent and of longer duration than at the ENT level, including in patients with negative throat swab and without digestive symptoms. In some doubtful cases, virologic assessment of stool samples can yield definitive diagnosis. In the event of prolonged viral shedding in stools, a patient's persistent contagiousness is conceivable but not conclusively established. Upcoming serology should enable identification of the patients having been infected by the COVID-19 epidemic, particularly among previously undetected pauci-symptomatic members of a health care staff. Resumption of medico-surgical activity should be the object of a dedicated strategy preceding deconfinement.", "qid": 26, "docid": "pbqm2xrg", "rank": 19, "score": 0.757393479347229}, {"content": "Title: Coronavirus 101 Content: COVID-2019 emerged from China in late December. It follows two other coronavirus outbreaks, the SARS-CoV and the MERS-CoV. Coronaviruses usually circulate among animals but sometimes can jump to humans. These three strains have caused severe disease in humans and global transmission concerns. Symptoms of COVID-2019 include cough, fever, and shortness of breath. Related illnesses can range from mild to severe to fatal. Primary care providers must be alert to respiratory symptoms they encounter that are associated with pertinent travel history, be prepared to safely screen, examine and possibly test and/or report suspicions to the health department for further evaluation.", "qid": 26, "docid": "9zetheol", "rank": 20, "score": 0.7566862106323242}, {"content": "Title: Coronavirus Disease 2019 (COVID-19) in adolescents: An update on current clinical and diagnostic characteristics Content: The current outbreak of infections with SARS-CoV-2 is defined as Coronavirus Disease 2019 (COVID-19). The clinical symptoms of COVID-19 include fever, fatigue, cough, breathing difficulty that may lead to respiratory distress; a small population of patients may have diarrhea, nausea or vomiting. The highest infection rate occurs in adults; however, neonates, children, and adolescents can also be infected. As the outbreak continues to spread worldwide, attention has switched toward determinants of clinical manifes- tations and disease severity. The situation surrounding the outbreak is rapidly evolving and the information and recommendations are changing as new information becomes available. This paper summarises the cur- rent findings (April 3,2020) from a systematic literature review on the current knowledge of COVID-19 in adolescents (10-19 years according to the WHO definition) and reports the preliminary epidemiological data stated by the Italian National Institute of Health.", "qid": 26, "docid": "9eijle5e", "rank": 21, "score": 0.7565099596977234}, {"content": "Title: Coronavirus Disease 2019 (COVID-19) in adolescents: An update on current clinical and diagnostic characteristics. Content: The current outbreak of infections with SARS-CoV-2 is defined as Coronavirus Disease 2019 (COVID-19). The clinical symptoms of COVID-19 include fever, fatigue, cough, breathing difficulty that may lead to respiratory distress; a small population of patients may have diarrhea, nausea or vomiting. The highest infection rate occurs in adults; however, neonates, children, and adolescents can also be infected. As the outbreak continues to spread worldwide, attention has switched toward determinants of clinical manifes- tations and disease severity. The situation surrounding the outbreak is rapidly evolving and the information and recommendations are changing as new information becomes available. This paper summarises the cur- rent findings (April 3,2020) from a systematic literature review on the current knowledge of COVID-19 in adolescents (10-19 years according to the WHO definition) and reports the preliminary epidemiological data stated by the Italian National Institute of Health.", "qid": 26, "docid": "gj5mfzxz", "rank": 22, "score": 0.7565099596977234}, {"content": "Title: Oral cavity lesions as a manifestation of the novel virus (COVID-19): a letter-to-editor. Content: In early December 2019, the acute respiratory illness began in the Wuhan, China, which quickly spread around the world, that today known as COVID-19. (Sun, Qie, Liu, Ren, & Xi, 2020) Preliminary studies have shown that hospitalized patients have different symptoms, including myalgia, whooping cough, fatigue, and dyspnea and gastrointestinal complains. (Guo et al., 2020; Zhang et al., 2020) In more recent studies, skin manifestations have also been reported in covid-19 patients.", "qid": 26, "docid": "ncp2tphr", "rank": 23, "score": 0.7561359405517578}, {"content": "Title: Cutaneous manifestations in COVID\u201019: Family cluster of Urticarial Rash Content: Coronavirus disease (COVID\u201019) is rapidly spread across the world. Many clinical manifestations of the virus are described, and new symptoms are emerging, only few cases of patients with skin manifestation were described since the pandemic was announced by the WHO on March. Common clinical features of COVID\u201019 reported include fever, cough, myalgia, fatigue, headache, shortness of breath and diarrhea.", "qid": 26, "docid": "khsvoyhp", "rank": 24, "score": 0.7557024955749512}, {"content": "Title: Clinical Insights into the Gastrointestinal Manifestations of COVID-19 Content: The month of December 2019 became a critical part of the time of humanity when the first case of coronavirus disease 2019 (COVID-19) was reported in the Wuhan, Hubei Province in China. As of April 13th, 2020, there have been approximately 1.9 million cases and 199,000 deaths across the world, which were associated with COVID-19. The COVID-19 is the seventh coronavirus to be identified to infect humans. In the past, Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome were the two coronaviruses that infected humans with a high fatality, particularly among the elderly. Fatalities due to COVID-19 are higher in patients older than 50 years of age or those with multimorbid conditions. The COVID-19 is mainly transmitted through respiratory droplets, with the most common symptoms being high fever, cough, myalgia, atypical symptoms included sputum production, headache, hemoptysis and diarrhea. However, the incubation period can range from 2 to 14 days without any symptoms. It is particularly true with gastrointestinal (GI) symptoms in which patients can still shed the virus even after pulmonary symptoms have resolved. Given the high percentage of COVID-19 patients that present with GI symptoms (e.g., nausea and diarrhea), screening patients for GI symptoms remain essential. Recently, cases of fecal-oral transmission of COVID-19 have been confirmed in the USA and China, indicating that the virus can replicate in both the respiratory and digestive tract. Moreover, the epidemiology, clinical characteristics, diagnostic procedures, treatments and prevention of the gastrointestinal manifestations of COVID-19 remain to be elucidated.", "qid": 26, "docid": "43ngt2qc", "rank": 25, "score": 0.7556920647621155}, {"content": "Title: Clinical Characteristics of COVID-19 Patients With Gastrointestinal Symptoms: An Analysis of Seven Patients in China Content: Objectives: Patients with novel coronavirus disease 2019 (COVID-19) can present with gastrointestinal symptoms as their initial symptoms or as the main manifestations during disease progression, but the clinical characteristics of these patients are still unknown. Methods: We identified COVID-19 patients who admitted to Xiangyang No. 1 People's Hospital and presented with gastrointestinal symptoms as their initial or main symptoms. Their medical records were reviewed by two independent clinical scientists. The epidemiological and clinical characteristics as well as the clinical outcomes were analyzed. Results: Among 142 confirmed COVID-19 cases, 7 (4.9%) of them presented with gastrointestinal symptoms. Three patients had gastrointestinal symptoms as the initial symptoms and chief complaints, and 4 patients as the main symptoms during disease progression. Six patients had symptoms of diarrhea (3\u201316 days), 7 with anorexia (7\u201322 days), 6 with upper abdominal discomfort (1\u20137 days), and 4 with nausea (1\u20137 days), 1 with heartburn lasting 2 days, and 2 with vomiting symptoms (1 day). The chest CT scan showed typical COVID-19 imaging features, and associated with the progression of the disease. During treatment, 2 patients died due to organ failure. Discussion: COVID-19 patients with gastrointestinal symptoms are relatively rare and might be misdiagnosed. The clinical features include watery stools, anorexia, and upper abdominal discomfort. These patients may have severe disease and be associated with a poor prognosis. The underlying mechanisms of SARS-CoV-2 related gastrointestinal symptoms need to clarify in future studies.", "qid": 26, "docid": "0fzwwluc", "rank": 26, "score": 0.7553689479827881}, {"content": "Title: Clinical Insights into the Gastrointestinal Manifestations of COVID-19 Content: The month of December 2019 became a critical part of the time of humanity when the first case of coronavirus disease 2019 (COVID-19) was reported in the Wuhan, Hubei Province in China. As of April 13th, 2020, there have been approximately 1.9 million cases and 199,000 deaths across the world, which were associated with COVID-19. The COVID-19 is the seventh coronavirus to be identified to infect humans. In the past, Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome were the two coronaviruses that infected humans with a high fatality, particularly among the elderly. Fatalities due to COVID-19 are higher in patients older than 50 years of age or those with multimorbid conditions. The COVID-19 is mainly transmitted through respiratory droplets, with the most common symptoms being high fever, cough, myalgia, atypical symptoms included sputum production, headache, hemoptysis and diarrhea. However, the incubation period can range from 2 to 14 days without any symptoms. It is particularly true with gastrointestinal (GI) symptoms in which patients can still shed the virus even after pulmonary symptoms have resolved. Given the high percentage of COVID-19 patients that present with GI symptoms (e.g., nausea and diarrhea), screening patients for GI symptoms remain essential. Recently, cases of fecal\u2013oral transmission of COVID-19 have been confirmed in the USA and China, indicating that the virus can replicate in both the respiratory and digestive tract. Moreover, the epidemiology, clinical characteristics, diagnostic procedures, treatments and prevention of the gastrointestinal manifestations of COVID-19 remain to be elucidated.", "qid": 26, "docid": "ptmxkpae", "rank": 27, "score": 0.7552165389060974}, {"content": "Title: COVID-19 is a Real Headache! Content: After the emergence of a novel coronavirus named SARS-CoV-2, coronavirus disease 2019 (COVID-19) was initially characterized by fever, sore throat, cough, and dyspnea, mainly manifestations of respiratory system. However, other manifestations such as headache, abdominal pain, diarrhea, loss of taste and smell were added to the clinical spectrum, during the course of the COVID-19 pandemic. The reports on the neurological findings are increasing rapidly and headache seems to be the leader on the symptom list. Headache was reported in 11%-34% of the hospitalized COVID-19 patients, but clinical features of these headaches were totally missing in available publications. According to our initial experience, significant features of headache presentation in the symptomatic COVID-19 patients were new-onset, moderate-severe, bilateral headache with pulsating or pressing quality in the temporoparietal, forehead or periorbital region. The most striking features of the headache were sudden to gradual onset and poor response to common analgesics, or high relapse rate, that was limited to the active phase of the COVID-19. Symptomatic COVID-19 patients, around 6%-10%, also reported headache as a presenting symptom. The possible pathophysiological mechanisms of headache include activation of peripheral trigeminal nerve endings by the SARS-CoV-2 directly or through the vasculopathy and/or increased circulating pro-inflammatory cytokines and hypoxia. We concluded that as a common non-respiratory symptom of COVID-19, headache should not be overlooked, and its characteristics should be recorded with scrutiny.", "qid": 26, "docid": "mqp3pjx6", "rank": 28, "score": 0.7542484402656555}, {"content": "Title: Vascular skin symptoms in COVID\u201019: a french observational study Content: Coronavirus 19 (COVID\u201019) was declared as a pandemic viral infection by the World Health organization on March 11(th) 2020. Usual clinical manifestations of COVID\u201019 infection include fever, fatigue, myalgia, headache, diarrhea, dry cough, dyspnea that may lead to acute respiratory distress syndrome and death (1). Skin symptoms of COVID\u201019 have been poorly described but may include erythematous rash, urticaria and chicken pox like lesions (2\u20107). Angiotensin\u2010converting enzyme 2 (ACE2) is a cellular receptor for COVID\u201019.", "qid": 26, "docid": "qreg4emx", "rank": 29, "score": 0.7542462348937988}, {"content": "Title: 2019 Novel Coronavirus (COVID-19) Pneumonia with Hemoptysis as the Initial Symptom: CT and Clinical Features Content: Recently, some global cases of 2019 novel coronavirus (COVID-19) pneumonia have been caused by second- or third-generation transmission of the viral infection, resulting in no traceable epidemiological history. Owing to the complications of COVID-19 pneumonia, the first symptom and imaging features of patients can be very atypical and early diagnosis of COVID-19 infections remains a challenge. It would aid radiologists and clinicians to be aware of the early atypical symptom and imaging features of the disease and contribute to the prevention of infected patients being missed.", "qid": 26, "docid": "i34j6mzv", "rank": 30, "score": 0.7540897130966187}, {"content": "Title: Atypical and novel presentations of Coronavirus Disease 2019: a case series of three children. Content: Typical presentations of Coronavirus Disease 2019 (COVID19) including respiratory symptoms (cough, respiratory distress and hypoxia), fever and dyspnea are considered main symptoms in adults, but atypical presentation children could be a diagnostic challenge We report three children whose initial presentation was gastrointestinal, and in whom COVID-19 infection was found, concluding that cases of acute appendicitis, mesenteric adenitis and flank tenderness may mask and infection with this virus, which should therefore be investigated.", "qid": 26, "docid": "1wyh7mrw", "rank": 31, "score": 0.7539913654327393}, {"content": "Title: Clinical features of 1487 COVID-19 patients with outpatient management in the Greater Paris: the COVID-call study Content: Clinical features of COVID-19 have been mostly described in hospitalized patients with and without ICU admission. Yet, up to 80% of patients are managed in an outpatient setting. This population is poorly documented. In France, health authorities recommend outpatient management of patients presenting mild-to-moderate COVID-19 symptoms. The aim of this study was to describe their clinical characteristics. The study took place in an emergency medical dispatching center located in the Greater Paris region. Patients included in this survey met confirmed COVID-19 infection criteria according to the WHO definition. We investigated clinical features and classified symptoms as general, digestive, ear-nose-throat, thoracic symptoms, and eye disease. Patients were included between March 24 and April 6 2020. 1487 patients included: 700 (47%) males and 752 (51%) females, with a median age of 44 (32-57) years. In addition to dry cough and fever reported in more than 90% of cases, the most common symptoms were general symptoms: body aches/myalgia (N = 845; 57%), headache (N = 824; 55%), and asthenia (N = 886; 60%); shortness of breath (N = 479; 32%) and ear-nose-throat symptoms such as anosmia (N = 415; 28%) and ageusia (N = 422; 28%). Chest pain was reported in 320 (21%) cases and hemoptysis in 41 (3%) cases. The main difference between male and female patients was an increased prevalence of ear-nose-throat symptoms as well as diarrhea, chest pains, and headaches in female patients. General symptoms and ear-nose-throat symptoms were predominant in COVID-19 patients presenting mild-to-moderate symptoms. Shortness of breath and chest pain were remarkably frequent.", "qid": 26, "docid": "z9232nni", "rank": 32, "score": 0.7526571154594421}, {"content": "Title: The need for neurologists in the care of COVID\u201019 patients Content: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulting in severe acute respiratory syndrome in a substantial number of patients. Approximately 5% to 10% of patients need intensive care unit (ICU) admission and mechanical ventilation [1]. The primary symptoms of COVID-19 include fever, dry cough and fatigue [2]. However, a recent report from Shandong, China, disclosed that a subset of patients did not suffer from respiratory symptoms but had neurologic signs and symptoms [3]. Moreover, in a retrospective study from Wuhan, China, neurologic symptoms were observed in 36.4% of the hospitalized patients with COVID-19 infection and pertained to both the central and peripheral nervous system [4].", "qid": 26, "docid": "l21fin9q", "rank": 33, "score": 0.7508355379104614}, {"content": "Title: Clinical characteristics of a case series of children with coronavirus disease 2019 Content: We reported the clinical characteristics of a case series of 10 patients with coronavirus disease 2019 (COVID-19) aged from 1 year to 18 years. Seven patients had contact with confirmed COVID-19 family members before onset. Fever (4 [40.0%]) and cough (3 [30.0%]) were the most common symptoms. No patient showed leucopenia and lymphopenia on admission. Pneumonia was observed in chest CT images in 5 (50.0%) patients. Five (50.0%) patients received antiviral treatment. No patient had severe complications or developed a severe illness in our study. Our study indicated that COVID-19 children present less severe symptoms and have better outcomes.", "qid": 26, "docid": "nb08i303", "rank": 34, "score": 0.7500026226043701}, {"content": "Title: Que doivent savoir les chirurgiens \u00e0 propos des troubles digestifs et des anomalies paracliniques induits par le COVID 19?/ [What do surgeons need to know about the digestive disorders and paraclinical abnormalities induced by COVID-19?] Content: The symptoms associated with COVID-19 are mainly characterized by a triad composed of fever, dry cough and dyspnea. However, digestive symptoms have also been reported; at first considered as infrequent, they in fact seem to affect (to some extent) more than half of patients. The symptoms are mainly manifested by anorexia, diarrhea, nausea and/or vomiting and abdominal pain. Even though prognosis is associated with lung injury, digestive symptoms seem significantly more frequent in patients presenting with severe COVID-19 infection. Digestive forms, which may be isolated or which can precede pulmonary symptoms, have indeed been reported, with diarrhea as a leading clinical sign. The main biological abnormalities that can suggest COVID-19 infection at an early stage are lymphopenia, elevated CRP and heightened ASAT transaminases. Thoraco-abdominal scan seems useful as a means of on the one hand ruling out digestive pathology not connected with coronavirus and on the other hand searching for pulmonary images compatible with COVID-19 infection. No data exist on the interest of digestive endoscopy in cases of persistent digestive symptoms. Moreover, the endoscopic surgeons may themselves be at significant risk of contamination. Fecal-oral transmission of the infection is possible, especially insofar as viral shedding in stools seems frequent and of longer duration than at the ENT level, including in patients with negative throat swab and without digestive symptoms. In some doubtful cases, virologic assessment of stool samples can yield definitive diagnosis. In the event of prolonged viral shedding in stools, a patient's persistent contagiousness is conceivable but not conclusively established. Upcoming serology should enable identification of the patients having been infected by the COVID-19 epidemic, particularly among previously undetected pauci-symptomatic members of a health care staff. Resumption of medico-surgical activity should be the object of a dedicated strategy preceding deconfinement.", "qid": 26, "docid": "sk5eugor", "rank": 35, "score": 0.7495535612106323}, {"content": "Title: Clinical characteristics of coronavirus disease 2019 in patients aged 80 years and older Content: OBJECTIVE: Coronavirus disease 2019 (COVID-19) has raised concern around the world as an epidemic or pandemic. As data on COVID-19 has grown, it has become clear that older adults have a disproportionately high rate of death from COVID-19. This study describes the early clinical characteristics of COVID-19 in patients with more than 80 years of age. METHODS: Epidemiological, clinical, laboratory, radiological, and treatment data from 17 patients diagnosed with COVID-19 between January 20 and February 20, 2020 were collected and analyzed retrospectively. Treatment outcomes among subgroups of patients with non-severe and severe symptoms of COVID-19 were compared. RESULTS: Of the 17 hospitalized patients with COVID-19, the median age was 88.0 years (interquartile range, 86.6\u201390.0 years; range, 80.0\u2013100.0 years) and 12 (70.6%) were men. The age distribution of patients was not significantly different between non-severe group and severe group. All patients had chronic pre-existing conditions. Hypertension and cardiovascular diseases were the most common chronic conditions in both subgroups. The most common symptoms at the onset of COVID-19 were fever (n = 13; 76.5%), fatigue (n = 11; 64.7%), and cough (n = 5; 29.4%). Lymphopenia was observed in all patients, and lymphopenia was significantly more severe in the severe group than that in non-severe group (0.4 \u00d710(9)/L vs 1.2 \u00d710(9)/L, P = 0.014). The level of serum creatinine was higher in the severe group than in the non-severe group (99.0 \u03bcmol/L vs 62.5 \u03bcmol/L, P = 0.038). The most common features of chest computed tomography (CT) images were nodular foci in 10 (58.8%) patients and pleural thickening in 7 (41.2%) patients. All patients received antiviral therapy, while some patients also received intravenous antibiotics therapy (76.5%), Chinese medicinal preparation therapy (Lianhuaqingwen capsule, 64.7%), corticosteroids (35.3%) or immunoglobin (29.4%). Eight patients (47.1%) were transferred to the intensive care unit because of complications. Ten patients (58.8%) received intranasal oxygen, while 3 (17.6%) received non-invasive mechanical ventilation, and 4 (23.5%) received high-flow oxygen. As of June 20, 7 (41.2%) patients had been discharged and 10 (58.8% of this cohort, 77.8% of severe patients) had died. CONCLUSION: The mortality of patients aged 80 years and older with severe COVID-19 symptoms was high. Lymphopenia was a characteristic laboratory result in these patients, and the severity of lymphopenia was indicative of the severity of COVID-19. However, the majority of patients with COVID-19 in this age cohort had atypical symptoms, and early diagnosis depends on prompt use of a viral nucleic acid test. Please cite this article as: Dang JZ, Zhu GY, Yang YJ, Zheng F. Clinical characteristics of coronavirus disease 2019 in patients aged 80 years and older. J Integr Med. 2020; Epub ahead of print.", "qid": 26, "docid": "y3juawja", "rank": 36, "score": 0.7494263648986816}, {"content": "Title: A novel coronavirus (SARS-CoV-2) and COVID-19. Content: By the end of 2019 the first cases of severe pneumonia of unknown origin were reported in Wuhan, China. The causative agent was identified as a novel b-coronavirus SARS-CoV-2 and the disease was named COVID-19. Since the beginning of 2020, the infection has spread worldwide, which led the WHO to declare COVID-19 a public health emergency of international concern and to characterize the current situation as a pandemic. The transmission occurs mainly via respiratory droplets and the incubation period ranges from 2 to 14 days. Most cases are mild, but some patients develop severe pneumonia with acute respiratory distress, septic shock and multi-organ failure. The most common symptoms include fever, dry cough, myalgia and shortness of breath. Characteristic laboratory findings are normal white blood cell count or mild leukopenia, marked lymphopenia, in severe cases elevated CRP, procalcitonin, LDH, and D-dimer are commonly found. Typical imaging findings include multifocal peripherally distributed ground-glass opacities or consolidations, interlobular septal thickening, crazy paving appearance and cystic changes. The overall case fatality rate is estimated to range from 1 to 3 %, however, it is dependent on age and underlying medical comorbidities. Current potential treatment options include hydroxychloroquine, remdesivir, lopinavir/ritonavir and convalescent plasma.", "qid": 26, "docid": "8iyjzd28", "rank": 37, "score": 0.7492184638977051}, {"content": "Title: Risk factors for disease progression in COVID-19 patients Content: BACKGROUND: Coronavirus disease (COVID-19) is rapidly spreading worldwide. Although 10\u201320% of patients with COVID-19 have severe symptoms, little is known about the risk factors related to the aggravation of COVID-19 symptoms from asymptomatic or mild to severe disease states. METHODS: This retrospective study included 211 patients who were asymptomatic or with mild presentations of COVID-19. We evaluated the differences in demographic and clinical data between the cured (discharged to home) and transferred (aggravated to severe-stage COVID-19) groups. RESULTS: A multivariate logistic analysis showed that body temperature, chills, initial chest X-ray findings, and the presence of diabetes were significantly associated with predicting the progression to severe stage of COVID-19 (p < 0.05). The odds ratio of transfer in patients with COVID-19 increased by 12.7-fold for abnormal findings such as haziness or consolidation in initial chest X-ray, 6.32-fold for initial symptom of chills, and 64.1-fold for diabetes. CONCLUSIONS: Even if patients are asymptomatic or have mild symptoms, clinicians should closely observe patients with COVID-19 presenting with chills, body temperature > 37.5 \u00b0C, findings of pneumonia in chest X-ray, or diabetes.", "qid": 26, "docid": "2ootfjhk", "rank": 38, "score": 0.7490736246109009}, {"content": "Title: Risk factors for disease progression in COVID-19 patients Content: BACKGROUND: Coronavirus disease (COVID-19) is rapidly spreading worldwide. Although 10-20% of patients with COVID-19 have severe symptoms, little is known about the risk factors related to the aggravation of COVID-19 symptoms from asymptomatic or mild to severe disease states. METHODS: This retrospective study included 211 patients who were asymptomatic or with mild presentations of COVID-19. We evaluated the differences in demographic and clinical data between the cured (discharged to home) and transferred (aggravated to severe-stage COVID-19) groups. RESULTS: A multivariate logistic analysis showed that body temperature, chills, initial chest X-ray findings, and the presence of diabetes were significantly associated with predicting the progression to severe stage of COVID-19 (p < 0.05). The odds ratio of transfer in patients with COVID-19 increased by 12.7-fold for abnormal findings such as haziness or consolidation in initial chest X-ray, 6.32-fold for initial symptom of chills, and 64.1-fold for diabetes. CONCLUSIONS: Even if patients are asymptomatic or have mild symptoms, clinicians should closely observe patients with COVID-19 presenting with chills, body temperature > 37.5 \u00b0C, findings of pneumonia in chest X-ray, or diabetes.", "qid": 26, "docid": "88n6hwyo", "rank": 39, "score": 0.7489217519760132}, {"content": "Title: Clinical Characteristics of Coronavirus Disease 2019 in China Guan W, Ni Z, Hu Y, et al. N Engl J Med. 2020 Feb 28 [Online ahead of print] DOI: 10.1056/NEJMoa2002032. Content: The novel coronavirus (SARS-CoV-2, causing COVID-19) was originally isolated in Wuhan, China. This virus spread quickly throughout many countries in Asia and now Europe, Australia, North America, leading the World Health Organization to declare COVID-19 a pandemic. Given the rapid spread of cases, the authors sought to provide analysis of patients with COVID-19, their clinical characteristics, and severity of disease. This was a retrospective review of Chinese medical records for laboratory-confirmed COVID-19 reported to the National Health Commission between December 11, 2019 to January 29, 2020. Electronic medical records were used to record various clinical data including exposure risk, signs and symptoms, laboratory findings, and radiologic findings. Several researchers performed chart abstraction and disagreements were made by a third reviewer. If radiologic findings were included, these were reviewed by respiratory medicine attending physicians who interpreted the findings. Incubation periods of less than 1 day were excluded. Fever was defined as an axillary temperature of 37.5 degrees Celsius or higher. Patients were categorized into severe or nonsevere based on the American Thoracic Society guidelines for community acquired pneumonia. The primary composite endpoint was admission to the intensive care unit (ICU), use of mechanical ventilation, or death. Secondary outcomes included death rates from symptom onset until each component of the composite end-point. There were 7736 patients admitted at 552 sites during the study period and data were obtained on 1099 patients (14.2%). The majority were nonsevere disease (926, 84.3%). The median age was 47 years (IQR 35-58), 41.9% were female, and most were nonsmokers (85.4%). Any comorbidity was recorded in 23.7% of patients, with hypertension being the most common (15.0%). The majority of patients (72.3%) had recent contact with a Wuhan resident, although 25.9% had no reported exposure. The median incubation period was 4.0 days (IQR 2.0-7.0). Regarding symptoms, only 43.8% of patients had fever on presentation but 88.7% developed fever during hospitalization. Besides fever, the most common symptoms overall were cough (67.8%), fatigue (38.1%), sputum production (33.7%), and shortness of breath (18.7%). Chest radiograph findings were available for 274 patients, with the majority being abnormal (59.1%). Findings included bilateral patchy shadowing (36.5%), local patchy shadowing (28.1%), ground-glass opacity (20.1%), and interstitial abnormality (4.4%). Chest CT results were available on 975 patients. The majority (86.2%) were abnormal and consisted of ground-glass opacity (56.4%), bilateral patchy shadowing (51.8%), local patchy shadowing (41.9%), and interstitial abnormalities (14.7%). Laboratory testing was available on most, depending on the test, and showed a median white blood cell count of 4700/mm3 (IQR 3500-6000), elevated C-reactive protein (&gt;10mg/L in 60.7%), and normal procalcitonin (&lt;0.5ng/mL in 94.5%). Other notable laboratory abnormalities included elevated D-dimer (&gt; 0.5mg/L in 46.4%) and elevated LDH (&gt;250U/L in 41%). The most common complications were pneumonia (91.1%) followed by acute respiratory distress syndrome (3.4%) and most common treatments were intravenous antibiotics (58.0%), oxygen therapy (41.3%), and oseltamivir (35.8%). Systemic glucocorticoids and immune globulin were less common therapies, and mechanical ventilation was needed in only 6.1%. At the conclusion of the study, 15 (1.4%) of patients had died and 55 (5.0%) had been discharged fro the hospital. The majority of the remaining patients were still hospitalized. Regarding the composite endpoint, there were 67 patients (6.1%) with ICU admission, mechanical ventilation, or death, leading to a cumulative risk of 3.6%. This percentage increased if you were designated as severe disease; in this case 24.9% had the composite outcome, leading to a cumulative risk of 20.6%. The authors concluded that presenting symptoms and workup can be variable, with many patients being afebrile and having normal radiologic studies. Several limitations were noted including missing data for many on incubation periods. Additionally the majority of the patients were still hospitalized at the end of the study and therefore outcomes could not be provided for those patients. Comment: While this study provides helpful clinical information to assist emergency physicians in identifying potential COVID-19 patients, we must understand the limitations. Most significantly, this was only a very small portion of the overall sample size of confirmed COVID-19 patients. Additionally, be cautious in directly applying these results to patients in the United States as populations may differ.", "qid": 26, "docid": "wywhmeow", "rank": 40, "score": 0.7486795783042908}, {"content": "Title: COVID-19: Specific and non-specific clinical manifestations and symptoms: The current state of knowledge Content: Coronavirus disease 2019 (COVID-19), due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become an epidemiological threat and a worldwide concern. SARS-CoV-2 has spread to 210 countries worldwide and more than 6,500,000 confirmed cases and 384,643 deaths have been reported, while the number of both confirmed and fatal cases is continually increasing. COVID-19 is a viral disease that can affect every age group\u2014from infants to the elderly\u2014resulting in a wide spectrum of various clinical manifestations. COVID-19 might present different degrees of severity\u2014from mild or even asymptomatic carriers, even to fatal cases. The most common complications include pneumonia and acute respiratory distress syndrome. Fever, dry cough, muscle weakness, and chest pain are the most prevalent and typical symptoms of COVID-19. However, patients might also present atypical symptoms that can occur alone, which might indicate the possible SARS-CoV-2 infection. The aim of this paper is to review and summarize all of the findings regarding clinical manifestations of COVID-19 patients, which include respiratory, neurological, olfactory and gustatory, gastrointestinal, ophthalmic, dermatological, cardiac, and rheumatologic manifestations, as well as specific symptoms in pediatric patients.", "qid": 26, "docid": "s7b3sw74", "rank": 41, "score": 0.7485111951828003}, {"content": "Title: COVID\u201019 is a Real Headache! Content: After the emergence of a novel coronavirus named SARS\u2010CoV\u20102, coronavirus disease 2019 (COVID\u201019) was initially characterized by fever, sore throat, cough, and dyspnea, mainly manifestations of respiratory system. However, other manifestations such as headache, abdominal pain, diarrhea, loss of taste and smell were added to the clinical spectrum, during the course of the COVID\u201019 pandemic. The reports on the neurological findings are increasing rapidly and headache seems to be the leader on the symptom list. Headache was reported in 11%\u201034% of the hospitalized COVID\u201019 patients, but clinical features of these headaches were totally missing in available publications. According to our initial experience, significant features of headache presentation in the symptomatic COVID\u201019 patients were new\u2010onset, moderate\u2010severe, bilateral headache with pulsating or pressing quality in the temporoparietal, forehead or periorbital region. The most striking features of the headache were sudden to gradual onset and poor response to common analgesics, or high relapse rate, that was limited to the active phase of the COVID\u201019. Symptomatic COVID\u201019 patients, around 6%\u201010%, also reported headache as a presenting symptom. The possible pathophysiological mechanisms of headache include activation of peripheral trigeminal nerve endings by the SARS\u2010CoV\u20102 directly or through the vasculopathy and/or increased circulating pro\u2010inflammatory cytokines and hypoxia. We concluded that as a common non\u2010respiratory symptom of COVID\u201019, headache should not be overlooked, and its characteristics should be recorded with scrutiny.", "qid": 26, "docid": "q7r2vfo1", "rank": 42, "score": 0.7477216720581055}, {"content": "Title: Clinical features of 1487 COVID-19 patients with outpatient management in the Greater Paris: the COVID-call study Content: Clinical features of COVID-19 have been mostly described in hospitalized patients with and without ICU admission. Yet, up to 80% of patients are managed in an outpatient setting. This population is poorly documented. In France, health authorities recommend outpatient management of patients presenting mild-to-moderate COVID-19 symptoms. The aim of this study was to describe their clinical characteristics. The study took place in an emergency medical dispatching center located in the Greater Paris region. Patients included in this survey met confirmed COVID-19 infection criteria according to the WHO definition. We investigated clinical features and classified symptoms as general, digestive, ear\u2013nose\u2013throat, thoracic symptoms, and eye disease. Patients were included between March 24 and April 6 2020. 1487 patients included: 700 (47%) males and 752 (51%) females, with a median age of 44 (32\u201357) years. In addition to dry cough and fever reported in more than 90% of cases, the most common symptoms were general symptoms: body aches/myalgia (N = 845; 57%), headache (N = 824; 55%), and asthenia (N = 886; 60%); shortness of breath (N = 479; 32%) and ear\u2013nose\u2013throat symptoms such as anosmia (N = 415; 28%) and ageusia (N = 422; 28%). Chest pain was reported in 320 (21%) cases and hemoptysis in 41 (3%) cases. The main difference between male and female patients was an increased prevalence of ear\u2013nose\u2013throat symptoms as well as diarrhea, chest pains, and headaches in female patients. General symptoms and ear\u2013nose\u2013throat symptoms were predominant in COVID-19 patients presenting mild-to-moderate symptoms. Shortness of breath and chest pain were remarkably frequent. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11739-020-02379-z) contains supplementary material, which is available to authorized users.", "qid": 26, "docid": "wslp4b3i", "rank": 43, "score": 0.7476003170013428}, {"content": "Title: Gastrointestinal and liver manifestations in patients with COVID-19 Content: As the outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread over the world, the World Health Organization has declared the outbreak of COVID-19 an international public health emergency. Besides typical respiratory symptoms and signs of COVID-19, digestive symptoms and liver injury have been frequently reported during the course of the disease. In this review, we summarized the recent studies reporting of gastrointestinal and liver manifestations during the course of COVID-19. Digestive symptoms, including anorexia, nausea, vomiting, and diarrhea, are not uncommon in patients with COVID-19, and in some cases digestive symptoms may occur in the absence of any respiratory symptoms. Furthermore, SARS-CoV-2 could be detected in the stool of infected patients, implicating the possibility of fecal\u2013oral transmission. Attention should also be paid to monitor liver function during the course of COVID-19, especially in patients with higher disease severity.", "qid": 26, "docid": "muztaqox", "rank": 44, "score": 0.7466855049133301}, {"content": "Title: Gastrointestinal and liver manifestations in patients with COVID-19 Content: As the outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread over the world, the World Health Organization has declared the outbreak of COVID-19 an international public health emergency. Besides typical respiratory symptoms and signs of COVID-19, digestive symptoms and liver injury have been frequently reported during the course of the disease. In this review, we summarized the recent studies reporting of gastrointestinal and liver manifestations during the course of COVID-19. Digestive symptoms, including anorexia, nausea, vomiting, and diarrhea, are not uncommon in patients with COVID-19, and in some cases digestive symptoms may occur in the absence of any respiratory symptoms. Furthermore, SARS-CoV-2 could be detected in the stool of infected patients, implicating the possibility of fecal-oral transmission. Attention should also be paid to monitor liver function during the course of COVID-19, especially in patients with higher disease severity.", "qid": 26, "docid": "xjqbmryh", "rank": 45, "score": 0.7464300394058228}, {"content": "Title: Beware: Gastrointestinal symptoms can be a manifestation of COVID-19 Content: BACKGROUND There is an increasing number of reports on the presentation of gastrointestinal symptoms in cases of COVID-19. AIM To review the studies reporting gastrointestinal symptoms in COVID-19. RESULTS Fifteen articles (2,800 patients) were identified. Gastrointestinal symptom frequency varied from 3.0% to 40.7% and included diarrhea (7.5%), n\u00e1usea (4.5%), anorexia (4.4%), vomiting (1.3%), abdominal pain (0.5%), and belching/reflux (0.3%). Those symptoms can be the first manifestation of COVID-19, but whether they reflect a better or worse prognosis, is controversial. The potential relation of the angiotensin converting enzyme 2 receptor in the digestive tract as an entry route for the virus is discussed. CONCLUSION Gastrointestinal symptoms may be common in COVID-19, in some cases appearing as the first manifestation, even before fever and respiratory symptoms. Therefore, clinicians and gastroenterologists must be aware of those atypical cases during the current pandemic, as well as of the fecal-oral route and corresponding preventive measures.", "qid": 26, "docid": "jdwi0n42", "rank": 46, "score": 0.7460041046142578}, {"content": "Title: Two cases of COVID\u201019 presenting with a clinical picture resembling chilblains: first report from the Middle East Content: Clinical characteristics of COVID-19 disease were identified in a cohort study involving 1099 patients from China. COVID-19 most commonly present with fever, cough, fatigue, and congestion. Two out of 1099 patients were reported to have skin rash, but time of onset and clinical description of rash were missing (Reference B). Another study focused primarily on cutaneous manifestations associated with COVID-19 evaluated 88 patients from Italy. 18 out of the 88 patients developed cutaneous manifestations, but only 8 patients developed skin lesions at onset of disease.", "qid": 26, "docid": "y1ba8ffw", "rank": 47, "score": 0.7458856105804443}, {"content": "Title: COVID-19 in der zentralen Notaufnahme: \u00dcbersicht \u00fcber die klinische Pr\u00e4sentation der ersten 35 Patienten in der Fr\u00fchphase der Pandemie Content: BACKGROUND: The corona pandemic is currently the greatest challenge for health systems of all countries worldwide. The timely detection of the disease and the immediate separation and isolation of suspected cases make a significant contribution to breaking the chain of infection. METHODS: Based on the first 35 patients admitted to the hospital with COVID-19, we evaluated the various symptoms with which patients presented. RESULTS: The majority of patients have respiratory symptoms (e.g., cough and reduced peripheral oxygen saturation) and fever. In individual patients, however, there may only be other symptoms, e.g., gastrointestinal, neurological, or nonspecific symptoms.", "qid": 26, "docid": "pe7as1qp", "rank": 48, "score": 0.7455017566680908}, {"content": "Title: Cutaneous signs in COVID-19 patients: A review Content: Coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the epithelium of the airways. With the increasing involvement of dermatologist in management of this crisis, cutaneous symptoms gained more and more attention. In this review, we will describe cutaneous symptoms of patients of all ages in association with COVID-19. We will focus on such disorders that are caused by direct action of SARS-CoV-2 on tissues, complement, and coagulation system and on nonspecific eruption of the systemic viral infection. Drug-induced reactions are only mentioned in the differential diagnoses. Although more systematic investigations are warranted, it becomes clear that some symptoms are clinical signs of a milder COVID-19 course, while others are a red flag for a more severe course. Knowledge of the cutaneous manifestations of COVID-19 may help in early diagnosis, triage of patients, and risk stratification.", "qid": 26, "docid": "4eus9f0c", "rank": 49, "score": 0.7453763484954834}, {"content": "Title: What do surgeons need to know about the digestive disorders and paraclinical abnormalities induced by COVID-19? Content: Abstract The symptoms associated with COVID-19 are mainly characterized by a triad composed of fever, dry cough and dyspnea. However, digestive symptoms have also been reported; at first considered as infrequent, they in fact seem to affect (to some extent) more than half of patients. The symptoms are mainly manifested by anorexia, diarrhea, nausea and/or vomiting and abdominal pain. Even though prognosis is associated with lung injury, digestive symptoms seem significantly more frequent in patients presenting with severe COVID-19 infection. Digestive forms, which may be isolated or which can precede pulmonary symptoms, have indeed been reported, with diarrhea as a leading clinical sign. The main biological abnormalities that can suggest COVID-19 infection at an early stage are lymphopenia, elevated CRP and heightened ASAT transaminases. Thoraco-abdominal scan seems useful as a means of on the one hand ruling out digestive pathology not connected with coronavirus and on the other hand searching for pulmonary images compatible with COVID-19 infection. No data exist on the interest of digestive endoscopy in cases of persistent digestive symptoms. Moreover, the endoscopic surgeons may themselves be at significant risk of contamination. Fecal-oral transmission of the infection is possible, especially insofar as viral shedding in stools seems frequent and of longer duration than at the ENT level, including in patients with negative throat swab and without digestive symptoms. In some doubtful cases, virologic assessment of stool samples can yield definitive diagnosis. In the event of prolonged viral shedding in stools, a patient\u2019s persistent contagiousness is conceivable but not conclusively established. Upcoming serology should enable identification of the patients having been infected by the COVID-19 epidemic, particularly among previously undetected pauci-symptomatic members of a health care staff. Resumption of medico-surgical activity should be the object of a dedicated strategy preceding deconfinement.", "qid": 26, "docid": "dnv2xl0h", "rank": 50, "score": 0.7452473640441895}, {"content": "Title: Clinical and imaging features of COVID-19 Content: Since December 2019, multiple cases of 2019 coronavirus disease (COVID-19) have been reported in Wuhan in China's Hubei Province, a disease which has subsequently spread rapidly across the entire country. Highly infectious, COVID-19 has numerous transmission channels and humans are highly susceptible to infection. The main clinical symptoms of COVID-19 are fever, fatigue, and a dry cough. Laboratory examination in the early stage of the disease shows a normal or decreased white blood cell count, and a decreased lymphocyte count. While CT examination serves as the screening and diagnostic basis for COVID-19, its accuracy is limited. The nucleic acid testing is the gold standard for the diagnosis of COVID-19, but has a low sensitivity is low. There is clearly a divide between the two means of examination. This paper reviews the published literature, guidelines and consensus, and summarizes the clinical and imaging characteristics of COVID-19, in order to provide a reliable basis for early diagnosis and treatment.", "qid": 26, "docid": "9k0741ct", "rank": 51, "score": 0.745060384273529}, {"content": "Title: Explanation for COVID\u201019 infection neurological damage and reactivations Content: A new pathogenic virus, COVID-19, appeared in 2019, in Wuhan, China, typically causing fever, cough, diarrhea and fatigue and significant mortality (Mao, 2020). From mid-January to mid-February in 2020, 214 patients with both non-severe and severe COVID-19 infections confirmed by nucleic acid tests, were examined by a panel of neurologists. Seventy-eight patients (36.4%) displayed neurological symptoms, including central nervous system symptoms of dizziness, headache, impaired consciousness, acute cerebrovascular disease with either ischemic stroke or cerebral hemorrhage, ataxia, seizures; peripheral nervous system symptoms of taste impairment, smell impairment, vision impairment, and nerve pain; and skeletal muscle injury (Mao, 2020).", "qid": 26, "docid": "s3wo3ten", "rank": 52, "score": 0.7449939250946045}, {"content": "Title: Coronavirus: An emergency for healthcare professionals Content: Coronavirus infection is a transmissible disease. It was first described in China in December, 2019. It has been said to have a person-to-person transmission after prolonged and unprotected exposure. Patients with a potential SARS-CoV-2 exposure present with symptoms of low-grade pyrexia, dry cough, or shortness of breath. People with these symptoms should contact health-care providers before seeking medical intervention so that appropriate preventive actions may be implemented. Health-care facilities should rapidly isolate suspected individuals and notify local health departments for support involved in performing laboratory tests and efforts in containment. The present article describes the nature of virus, method of detection, and its mode of transmission.", "qid": 26, "docid": "yxmkaqo8", "rank": 53, "score": 0.744401216506958}, {"content": "Title: Clinical Profile of Cases of COVID-19 in Far Western Province of Nepal Content: The novel coronavirus (COVID-19) cause various symptoms such as pneumonia, fever, breathing difficult and lung infection. Till now, total 9 cases are reported in Nepal and 4 cases from this province. This case series is to describe the initial clinical features of COVID-19 among the patients admitted in isolation ward of Seti Provincial Hospital. Oropharyngeal swab was taken from all four patients and sample was transfer to national reference laboratory. Three patients were coming from infected country and one is local transmission. Age of patients was range from 20 to 40 years of age with male preponderance. The patient coming from United Arab Emirate was presented with mild symptoms and others were asymptomatic. More tests, contact tracing and keeping them in quarantine are the necessitated action need to be taken by government of Nepal. Keywords: COVID-19; local transmission; oropharyngeal swab.", "qid": 26, "docid": "tw7f32uw", "rank": 54, "score": 0.7440931797027588}, {"content": "Title: Clinical Profile of Cases of COVID-19 in Far Western Province of Nepal. Content: The novel coronavirus (COVID-19) cause various symptoms such as pneumonia, fever, breathing difficult and lung infection. Till now, total 9 cases are reported in Nepal and 4 cases from this province. This case series is to describe the initial clinical features of COVID-19 among the patients admitted in isolation ward of Seti Provincial Hospital. Oropharyngeal swab was taken from all four patients and sample was transfer to national reference laboratory. Three patients were coming from infected country and one is local transmission. Age of patients was range from 20 to 40 years of age with male preponderance. The patient coming from United Arab Emirate was presented with mild symptoms and others were asymptomatic. More tests, contact tracing and keeping them in quarantine are the necessitated action need to be taken by government of Nepal. Keywords: COVID-19; local transmission; oropharyngeal swab.", "qid": 26, "docid": "j8uleim6", "rank": 55, "score": 0.7440931797027588}, {"content": "Title: Immune responses and pathogenesis of SARS-CoV-2 during an outbreak in Iran: Comparison with SARS and MERS Content: The beginning of 2020 has seen the emergence of COVID-19, an outbreak caused by a novel coronavirus, SARS-CoV-2, an important pathogen for humans. There is an urgent need to better understand this new virus and to develop ways to control its spread. In Iran, the first case of the COVID-19 was reported after spread from China and other countries. Fever, cough, and fatigue were the most common symptoms of this virus. In worldwide, the incubation period of COVID-19 was 3 to 7 days and approximately 80% of infections are mild or asymptomatic, 15% are severe, requiring oxygen, and 5% are critical infections, requiring ventilation. To mount an antiviral response, the innate immune system recognizes molecular structures that are produced by the invasion of the virus. COVID-19 infection induces IgG antibodies against N protein that can be detected by serum as early as day 4 after the onset of disease and with most patients seroconverting by day 14. Laboratory evidence of clinical patients showed that a specific T-cell response against SARS-CoV-2 is important for the recognition and killing of infected cells, particularly in the lungs of infected individuals. At present, there is no specific antiviral therapy for COVID-19 and the main treatments are supportive. In this review, we investigated the innate and acquired immune responses in patients who recovered from COVID-19, which could inform the design of prophylactic vaccines and immunotherapy for the future.", "qid": 26, "docid": "3nnlkbph", "rank": 56, "score": 0.743847131729126}, {"content": "Title: Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19 disease Content: BACKGROUND: Some people with SARS-CoV-2 infection remain asymptomatic, whilst in others the infection can cause mild to moderate COVID-19 disease and COVID-19 pneumonia, leading some patients to require intensive care support and, in some cases, to death, especially in older adults. Symptoms such as fever or cough, and signs such as oxygen saturation or lung auscultation findings, are the first and most readily available diagnostic information. Such information could be used to either rule out COVID-19 disease, or select patients for further diagnostic testing. OBJECTIVES: To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID-19 clinics, has COVID-19 disease or COVID-19 pneumonia. SEARCH METHODS: On 27 April 2020, we undertook electronic searches in the Cochrane COVID-19 Study Register and the University of Bern living search database, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. SELECTION CRITERIA: Studies were eligible if they included patients with suspected COVID-19 disease, or if they recruited known cases with COVID-19 disease and controls without COVID-19. Studies were eligible when they recruited patients presenting to primary care or hospital outpatient settings. Studies including patients who contracted SARS-CoV-2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards including reverse transcription polymerase chain reaction (RT-PCR), clinical expertise, imaging, serology tests and World Health Organization (WHO) or other definitions of COVID-19. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently selected all studies, at both title and abstract stage and full-text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and resolved disagreements by discussion with a third review author. Two review authors independently assessed risk of bias using the QUADAS-2 checklist. Analyses were descriptive, presenting sensitivity and specificity in paired forest plots, in ROC (receiver operating characteristic) space and in dumbbell plots. We did not attempt meta-analysis due to the small number of studies, heterogeneity across studies and the high risk of bias. MAIN RESULTS: We identified 16 studies including 7706 participants in total. Prevalence of COVID-19 disease varied from 5% to 38% with a median of 17%. There were no studies from primary care settings, although we did find seven studies in outpatient clinics (2172 participants), and four studies in the emergency department (1401 participants). We found data on 27 signs and symptoms, which fall into four different categories: systemic, respiratory, gastrointestinal and cardiovascular. No studies assessed combinations of different signs and symptoms and results were highly variable across studies. Most had very low sensitivity and high specificity; only six symptoms had a sensitivity of at least 50% in at least one study: cough, sore throat, fever, myalgia or arthralgia, fatigue, and headache. Of these, fever, myalgia or arthralgia, fatigue, and headache could be considered red flags (defined as having a positive likelihood ratio of at least 5) for COVID-19 as their specificity was above 90%, meaning that they substantially increase the likelihood of COVID-19 disease when present. Seven studies carried a high risk of bias for selection of participants because inclusion in the studies depended on the applicable testing and referral protocols, which included many of the signs and symptoms under study in this review. Five studies only included participants with pneumonia on imaging, suggesting that this is a highly selected population. In an additional four studies, we were unable to assess the risk for selection bias. These factors make it very difficult to determine the diagnostic properties of these signs and symptoms from the included studies. We also had concerns about the applicability of these results, since most studies included participants who were already admitted to hospital or presenting to hospital settings. This makes these findings less applicable to people presenting to primary care, who may have less severe illness and a lower prevalence of COVID-19 disease. None of the studies included any data on children, and only one focused specifically on older adults. We hope that future updates of this review will be able to provide more information about the diagnostic properties of signs and symptoms in different settings and age groups. AUTHORS' CONCLUSIONS: The individual signs and symptoms included in this review appear to have very poor diagnostic properties, although this should be interpreted in the context of selection bias and heterogeneity between studies. Based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out disease. Prospective studies in an unselected population presenting to primary care or hospital outpatient settings, examining combinations of signs and symptoms to evaluate the syndromic presentation of COVID-19 disease, are urgently needed. Results from such studies could inform subsequent management decisions such as self-isolation or selecting patients for further diagnostic testing. We also need data on potentially more specific symptoms such as loss of sense of smell. Studies in older adults are especially important.", "qid": 26, "docid": "83z84cts", "rank": 57, "score": 0.7436631917953491}, {"content": "Title: Beware: Gastrointestinal symptoms can be a manifestation of COVID-19 Content: Abstract Background There is a growing number of reports of COVID-19 cases presenting gastrointestinal (GI) symptoms. Aims To review studies reporting GI symptoms among COVID-19 patients. Results Fifteen papers (2800 patients) were identified. Frequency of GI symptoms varied from 3.0% to 39.6%, including diarrhea: 7.5%, nausea: 4.5%, anorexia: 4.4%, vomiting: 1.3%, abdominal pain: 0.5%, belching/reflux: 0.3%. These may be the first manifestation of COVID-19, however, there is controversy whether these reflect better or worst prognosis. Finally, the potential relationship with the angiotensin converting enzyme 2 (ACE2) cell receptor in the digestive tract as the virus entry route, is discussed. Conclusions GI symptoms may be common in COVID-19 may be the first manifestation before fever and respiratory symptoms. Therefore, clinicians and gastroenterologists need to be aware of these atypical cases during the current pandemic and of the fecal\u2013oral transmission, and preventive measures may be implemented.", "qid": 26, "docid": "7c9gju6i", "rank": 58, "score": 0.7432151436805725}, {"content": "Title: Identifying and Ranking Common COVID-19 Symptoms from Arabic Twitter Content: Objective: The aim of this study is to identify the most common symptoms reported by covid-19 patients in the Arabic language and order the symptoms appearance based on the collected data. Methods: We search the Arabic content of Twitter for personal reports of covid-19 symptoms from March 1st to May 27th, 2020. We identify 463 Arabic users who tweeted testing positive for covid-19 and extract the symptoms they publicly associate with covid-19. Furthermore, we ask them directly through personal messages to opt in and rank the appearance of the first three symptoms they experienced right before (or after) diagnosed with covid-19. Finally, we track their Twitter timeline to identify additional symptoms that were mentioned within +-5 days from the day of tweeting having covid-19. In summary, a list of 270 covid-19 reports were collected and symptoms were (at least partially) ranked from early to late. Results: The collected reports contained roughly 900 symptoms originated from 74% (n=201) male and 26% (n=69) female Twitter users. The majority (82%) of the tracked users were living in Saudi Arabia (46%) and Kuwait (36%). Furthermore, 13% (n=36) of the collected reports were asymptomatic. Out of the users with symptoms (n=234), 66% (n=180) provided a chronological order of appearance for at least three symptoms. Fever 59% (n=139), Headache 43% (n=101), and Anosmia 39% (n=91) were found to be the top three symptoms mentioned by the reports. They count also for the top-3 common first symptoms in a way that 28% (n=65) said their covid journey started with a Fever, 15% (n=34) with a Headache and 12% (n=28) with Anosmia. Out of the Saudi symptomatic reported cases (n=110), the most common three symptoms were Fever 59% (n=65), Anosmia 42% (n=46), and Headache 38% (n=42).", "qid": 26, "docid": "isjacgq1", "rank": 59, "score": 0.7431877851486206}, {"content": "Title: Clinical presentation and course of COVID-19. Content: Information about the clinical presentation and course of COVID-19 is rapidly evolving. Data are emerging from retrospective clinical studies conducted in Wuhan, China, showing the symptoms and characteristics of COVID-19 caused by severe acute respiratory virus coronavirus 2 (SARS-CoV-2) infection, including fever, cough, and shortness of breath. Radiographic data on COVID-19 cases reveal bilateral opacities on chest radiography and ground-glass opacities on computed tomography. Data on laboratory markers and mortality and morbidity are also emerging.", "qid": 26, "docid": "g4luqtjv", "rank": 60, "score": 0.7424763441085815}, {"content": "Title: Oral mucosa lesions in COVID-19 Content: SARS-CoV-2 marks a new era in the medical field. The literature has outlined several signs and symptoms of COVID-19 (Lake, 2020), but there are some manifestations not yet confirmed or not entirely described. There have been reported several dermatological conditions associated with COVID-19: rash, urticaria and chickenpox-like vesicles (Recalcati, 2020) and studies on cutaneous manifestations of COVID-19 have been announced (Fernandez-Nieto et al., 2020). The main path of COVID-19 transmission is through droplets (The Chinese Preventive Medicine Association, 2020) from the oral cavity. This is why dental professionals are widely exposed to be infected, but they could also be the first ones to identify SARS-CoV-2 positive patients. Carreras-Presas et al. published a paper presenting three case reports describing oral mucosa vesiculobullous lesions developed by COVID-19 positive or suspected to be positive patients.", "qid": 26, "docid": "3h4x48in", "rank": 61, "score": 0.7423146963119507}, {"content": "Title: Comment on \u2018Two cases of COVID\u201019 presenting with a clinical picture resembling chilblains: first report from the Middle East\u2019: pernio unrelated to COVID\u201019 Content: Dear editor, we have read with interest Dr\u00b4s Alramthan and Aldaraji contribution to the spectrum of COVID-19 clinical manifestations.1 Since COVID-19 outbreak begin, new symptoms have been described.2 Some of them, were not initially highlighted and could be a distinguishing feature of COVID-19 infection, like anosmia or ageusia.3 Therefore, it is believed that a newly reported one, so-called acute acro-ischemia is another novel clinical manifestation of COVID-19 infection.4.", "qid": 26, "docid": "vwfey8of", "rank": 62, "score": 0.7421213388442993}, {"content": "Title: The red half\u2010moon nail sign: a novel manifestation of coronavirus infection Content: The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). The pandemic condition was declared by the WHO on March 11, 2020. The main clinical symptoms are fever, dry cough and dyspnea, although new symptoms are emerging, such as diarrhea, anosmia and ageusia. The virus enters cells, likely including those lining blood vessels, by binding to angiotensin converting enzyme 2 (ACE2) receptors on the cell surface. Infection can also promote blood clots, heart attacks and cardiac inflammation.", "qid": 26, "docid": "1trid65d", "rank": 63, "score": 0.7417330145835876}, {"content": "Title: A prospective clinical study of detailed neurological manifestations in patients with COVID-19 Content: BACKGROUND: COVID-19 is a virus pandemic. According to the first obtained data, COVID-19 has defined with findings such as cough, fever, diarrhea, and fatigue although neurological symptoms of patients with COVID-19 have not been investigated in detail. This study aims to investigate the neurological findings via obtained face-to-face anamnesis and detailed neurological examination in patients with COVID-19. METHODS: Two hundred thirty-nine consecutive inpatients with COVID-19, supported with laboratory tests, were evaluated. Detailed neurological examinations and evaluations of all patients were performed. All evaluations and examinations were performed by two neurologists who have at least five-year experience. RESULTS: This study was carried out 239 patients (133 male + 106 female) with diagnosed COVID-19. Neurological findings were present in 83 of 239 patients (34.7%). The most common neurological finding was a headache (27.6%). D-dimer blood levels were detected to be significantly higher in patients with at least one neurological symptom than patients without the neurological symptom (p < 0.05). IL-6 level was found to be significantly higher in patients with headache than without headache (p < 0.05). Creatine kinase (CK) level was detected to be significantly higher in patients with muscle pain (p < 0.05). CONCLUSION: Neurological symptoms are often seen in patients with COVID-19. Headache was the most common seen neurological symptom in this disease. Dizziness, impaired consciousness, smell and gustation impairments, cerebrovascular disorders, epileptic seizures, and myalgia were detected as other findings apart from the headache. It is suggested that determining these neurological symptoms prevents the diagnosis delay and helps to prohibit virus spread.", "qid": 26, "docid": "rcguim61", "rank": 64, "score": 0.7413220405578613}, {"content": "Title: Management of Breast Cancer during the COVID-19 Pandemic Content: The novel coronavirus disease (COVID-19) arises from the virus SARS-CoV-2 which is similar to the original SARS virus. The most common symptoms of the COVID-19 infection are fever, coughing and shortness of breath. According to the current data, the primary mode of transmission for the COVID-19 virus is between people through respiratory droplets and contact routes. The virus may lead to worse respiratory complications, including pneumonia, especially in older patients and patients with pre-existing illnesses, such as cancer. Cancer patients are at a significantly higher risk of getting infected with COVID-19 since their immune system can be compromised and that reality has to do with both that they have cancer and that they are on therapy for their cancer. COVID-19 crisis has impacted every aspect of the practice, including outpatient, elective, wards, emergency care, conferences, teaching and research. We should make sure cancer patients on active treatment are treated appropriately. In this review, we tried to explain how to prevent the negative effects of the COVID-19 pandemic on the diagnosis and treatment of breast cancer patients.", "qid": 26, "docid": "xot2oj2t", "rank": 65, "score": 0.7412792444229126}, {"content": "Title: Case report of COVID-19 in a kidney transplant recipient: Does immunosuppression alter the clinical presentation? Content: COVID-19 is novel infectious disease with an evolving understanding of its epidemiology and clinical manifestations. Immunocompromised patients often present atypical presentations of viral diseases. Herein we report a case of a COVID-19 infection in a solid organ transplant recipient, in which the first clinical symptoms were of gastrointestinal viral disease and fever, which further progressed to respiratory symptoms in 48 hours. In these high risk populations, protocols for screening for SARS-Cov2 may be needed to be re-evaluated.", "qid": 26, "docid": "qzznrk2y", "rank": 66, "score": 0.7410444617271423}, {"content": "Title: Corona Virus 101 Content: COVID-2019 emerged from China in late December of 2019. It follows 2 other coronavirus outbreaks, the SARS-CoV and the MERS-CoV. Coronaviruses usually circulate among animals but sometimes can jump to humans. These 3 strains have caused severe disease in humans and global transmission concerns. Symptoms of COVID-2019 include cough, fever, and shortness of breath. Related illnesses can range from mild to severe to fatal. Primary care providers must be alert to respiratory symptoms they encounter that are associated with pertinent travel history, be prepared to safely screen, examine, and possibly test and/or report suspicions to the health department for further evaluation.", "qid": 26, "docid": "4nho5wa0", "rank": 67, "score": 0.7409977316856384}, {"content": "Title: Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19 disease. Content: BACKGROUND Some people with SARS-CoV-2 infection remain asymptomatic, whilst in others the infection can cause mild to moderate COVID-19 disease and COVID-19 pneumonia, leading some patients to require intensive care support and, in some cases, to death, especially in older adults. Symptoms such as fever or cough, and signs such as oxygen saturation or lung auscultation findings, are the first and most readily available diagnostic information. Such information could be used to either rule out COVID-19 disease, or select patients for further diagnostic testing. OBJECTIVES To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID-19 clinics, has COVID-19 disease or COVID-19 pneumonia. SEARCH METHODS On 27 April 2020, we undertook electronic searches in the Cochrane COVID-19 Study Register and the University of Bern living search database, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. SELECTION CRITERIA Studies were eligible if they included patients with suspected COVID-19 disease, or if they recruited known cases with COVID-19 disease and controls without COVID-19. Studies were eligible when they recruited patients presenting to primary care or hospital outpatient settings. Studies including patients who contracted SARS-CoV-2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards including reverse transcription polymerase chain reaction (RT-PCR), clinical expertise, imaging, serology tests and World Health Organization (WHO) or other definitions of COVID-19. DATA COLLECTION AND ANALYSIS Pairs of review authors independently selected all studies, at both title and abstract stage and full-text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and resolved disagreements by discussion with a third review author. Two review authors independently assessed risk of bias using the QUADAS-2 checklist. Analyses were descriptive, presenting sensitivity and specificity in paired forest plots, in ROC (receiver operating characteristic) space and in dumbbell plots. We did not attempt meta-analysis due to the small number of studies, heterogeneity across studies and the high risk of bias. MAIN RESULTS We identified 16 studies including 7706 participants in total. Prevalence of COVID-19 disease varied from 5% to 38% with a median of 17%. There were no studies from primary care settings, although we did find seven studies in outpatient clinics (2172 participants), and four studies in the emergency department (1401 participants). We found data on 27 signs and symptoms, which fall into four different categories: systemic, respiratory, gastrointestinal and cardiovascular. No studies assessed combinations of different signs and symptoms and results were highly variable across studies. Most had very low sensitivity and high specificity; only six symptoms had a sensitivity of at least 50% in at least one study: cough, sore throat, fever, myalgia or arthralgia, fatigue, and headache. Of these, fever, myalgia or arthralgia, fatigue, and headache could be considered red flags (defined as having a positive likelihood ratio of at least 5) for COVID-19 as their specificity was above 90%, meaning that they substantially increase the likelihood of COVID-19 disease when present. Seven studies carried a high risk of bias for selection of participants because inclusion in the studies depended on the applicable testing and referral protocols, which included many of the signs and symptoms under study in this review. Five studies only included participants with pneumonia on imaging, suggesting that this is a highly selected population. In an additional four studies, we were unable to assess the risk for selection bias. These factors make it very difficult to determine the diagnostic properties of these signs and symptoms from the included studies. We also had concerns about the applicability of these results, since most studies included participants who were already admitted to hospital or presenting to hospital settings. This makes these findings less applicable to people presenting to primary care, who may have less severe illness and a lower prevalence of COVID-19 disease. None of the studies included any data on children, and only one focused specifically on older adults. We hope that future updates of this review will be able to provide more information about the diagnostic properties of signs and symptoms in different settings and age groups. AUTHORS' CONCLUSIONS The individual signs and symptoms included in this review appear to have very poor diagnostic properties, although this should be interpreted in the context of selection bias and heterogeneity between studies. Based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out disease. Prospective studies in an unselected population presenting to primary care or hospital outpatient settings, examining combinations of signs and symptoms to evaluate the syndromic presentation of COVID-19 disease, are urgently needed. Results from such studies could inform subsequent management decisions such as self-isolation or selecting patients for further diagnostic testing. We also need data on potentially more specific symptoms such as loss of sense of smell. Studies in older adults are especially important.", "qid": 26, "docid": "3062h5on", "rank": 68, "score": 0.7407263517379761}, {"content": "Title: Clinical characteristics of a case series of children with coronavirus disease 2019 Content: We reported the clinical characteristics of a case series of 10 patients with coronavirus disease 2019 (COVID\u201019) aged from 1 year to 18 years. Seven patients had contact with confirmed COVID\u201019 family members before onset. Fever (4 [40.0%]) and cough (3 [30.0%]) were the most common symptoms. No patient showed leucopenia and lymphopenia on admission. Pneumonia was observed in chest CT images in 5 (50.0%) patients. Five (50.0%) patients received antiviral treatment. No patient had severe complications or developed a severe illness in our study. Our study indicated that COVID\u201019 children present less severe symptoms and have better outcomes.", "qid": 26, "docid": "gmo6big4", "rank": 69, "score": 0.740690290927887}, {"content": "Title: Epidemiological and Clinical Characteristics of Cases During the Early Phase of COVID-19 Pandemic: A Systematic Review and Meta-Analysis Content: Background: On 29th December 2019, a cluster of cases displaying the symptoms of a \u201cpneumonia of unknown cause\u201d was identified in Wuhan, Hubei province of China. This systematic review and meta-analysis aims to review the epidemiological and clinical characteristics of COVID-19 cases in the early phase of the COVID-19 pandemic. Methods: The search strategy involved peer-reviewed studies published between 1st January and 11th February 2020 in Pubmed, Google scholar and China Knowledge Resource Integrated database. Publications identified were screened for their title and abstracts according to the eligibility criteria, and further shortlisted by full-text screening. Three independent reviewers extracted data from these studies, and studies were assessed for potential risk of bias. Studies comprising non-overlapping patient populations, were included for qualitative and quantitative synthesis of results. Pooled prevalence with 95% confidence intervals were calculated for patient characteristics. Results: A total of 29 publications were selected after full-text review. This comprised of 18 case reports, three case series and eight cross-sectional studies on patients admitted from mid-December of 2019 to early February of 2020. A total of 533 adult patients with pooled median age of 56 (95% CI: 49\u201357) and a pooled prevalence of male of 60% (95% CI: 52\u201368%) were admitted to hospital at a pooled median of 7 days (95% CI: 7\u20137) post-onset of symptoms. The most common symptoms at admission were fever, cough and fatigue, with a pooled prevalence of 90% (95% CI: 81\u201397%), 58% (95% CI: 47\u201368%), and 50% (95% CI: 29\u201371%), respectively. Myalgia, shortness of breath, headache, diarrhea and sore throat were less common with pooled prevalence of 27% (95% CI: 20\u201336%), 25% (95% CI: 15\u201335%), 10% (95% CI: 7\u201313%), 8% (95% CI: 5\u201313%), and 7% (95% CI: 1\u201315%), respectively. ICU patients had a higher proportion of shortness of breath at presentation, as well as pre-existing hypertension, cardiovascular disease and COPD, compared to non-ICU patients in 2 studies (n = 179). Conclusion: This study highlights the key epidemiological and clinical features of COVID-19 cases during the early phase of the COVID-19 pandemic.", "qid": 26, "docid": "vdpaxj4e", "rank": 70, "score": 0.7404415607452393}, {"content": "Title: Potential neuroinvasive pathways of SARS-CoV-2: Deciphering the spectrum of neurological deficit seen in coronavirus disease-2019 (COVID-19) Content: Coronavirus disease-2019 (COVID-19) was declared a global pandemic on 11 March 2020. Scientists and clinicians must acknowledge that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential to attack the human body in multiple ways simultaneously and exploit any weaknesses of its host. A multipronged attack could potentially explain the severity and extensive variety of signs and symptoms observed in patients with COVID-19. Understanding the diverse tactics of this virus to infect the human body is both critical and incredibly complex. Although patients diagnosed with COVID-19 have primarily presented with pulmonary involvement, viral invasion, and injury to diverse end organs is also prevalent and well documented in these patients, but has been largely unheeded. Human organs known for angiotensin-converting enzyme 2 (ACE2) expression including the gastrointestinal tract, kidneys, heart, adrenals, brain, and testicles are examples of extra pulmonary tissues with confirmed invasion by SARS-CoV-2. Initial multiple organ involvement may present with vague signs and symptoms to alert health care professionals early in the course of COVID-19. Another example of an ongoing, yet neglected element of the syndromic features of COVID-19, are the reported findings of loss of smell, altered taste, ataxia, headache, dizziness, and loss of consciousness, which suggest a potential for neural involvement. In this review, we further deliberate on the neuroinvasive potential of SARS-CoV-2, the neurologic symptomology observed in COVID-19, the host-virus interaction, possible routes of SARS-CoV-2 to invade the central nervous system, other neurologic considerations for patients with COVID-19, and a collective call to action.", "qid": 26, "docid": "0a010br6", "rank": 71, "score": 0.740388035774231}, {"content": "Title: Cutaneous signs in COVID\u201019 patients: A review Content: Coronavirus disease (COVID\u201019) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) primarily affects the epithelium of the airways. With the increasing involvement of dermatologist in management of this crisis, cutaneous symptoms gained more and more attention. In this review, we will describe cutaneous symptoms of patients of all ages in association with COVID\u201019. We will focus on such disorders that are caused by direct action of SARS\u2010CoV\u20102 on tissues, complement, and coagulation system and on nonspecific eruption of the systemic viral infection. Drug\u2010induced reactions are only mentioned in the differential diagnoses. Although more systematic investigations are warranted, it becomes clear that some symptoms are clinical signs of a milder COVID\u201019 course, while others are a red flag for a more severe course. Knowledge of the cutaneous manifestations of COVID\u201019 may help in early diagnosis, triage of patients, and risk stratification.", "qid": 26, "docid": "fsr0gija", "rank": 72, "score": 0.7402797937393188}, {"content": "Title: Abdominal Pain: A Real Challenge in Novel COVID-19 Infection Content: COVID-19 (coronavirus disease 19) is an infectious disease caused by coronavirus 2019-nCoV. Since its detection in China at the end of 2019, the novel coronavirus has rapidly spread throughout the world and has caused an international public health emergency. The most common manifestation is flu-like symptoms. Mild infections usually improve within a few days, but COVID-19 can cause severe pneumonia with acute respiratory distress syndrome and death. Gastrointestinal symptoms are less common but possible and more difficult to recognize as part of a COVID-19 syndrome. In line with the current opinion of the WHO, we strongly believe that preventive measures and early diagnosis of COVID-19 are crucial to interrupt virus spread and avoid local outbreaks. We report the cases of COVID-19 patients admitted to our Emergency Department who complained of gastrointestinal symptoms at admission. LEARNING POINTS: The novel COVID-19 infection is a severe public health problem which is causing an increasing number of deaths worldwide. Although uncommon, there may be a relationship between gastrointestinal symptoms and COVID-19, as reported in recent studies. Early detection and isolation of patients with COVID-19 infection is the only way to control and limit the global spread of this virus.", "qid": 26, "docid": "gjigvjgv", "rank": 73, "score": 0.7400632500648499}, {"content": "Title: Clinico-radiological Presentation of COVID-19 Patients at a Tertiary Care Center at Bhilwara Rajasthan, India Content: Background: COVID-19 has now become a pandemic. From Wuhan, China, in December 2019 to European countries, USA and now it seems to gain a strong foothold in India. The objective of this work is to report the initial experience with demographic and clinical features, and management of COVID-19 patients admitted in medical college Bhilwara, India. Methods: This is a descriptive case series of first 26 COVID-19 patients. Demographical, clinical, laboratory, and radiological characteristics and treatment and outcomes data were obtained with data collection forms and history given by 26 COVID-19 patients. Results and Discussion: During this study 26 COVID-19 positive patients were admitted in MG Hospital, Bhilwara. Male patients were 61.54% and majority (88.46%) were below 60 years of age. Approximately 30.76 % patients were asymptomatic. Fever was the most common symptom (61.54%) followed by sore throat (53.84 %), cough (42.30%) myalgia (38.46%)and dyspnea(23.07%). Six patients (23.07%) of total 26 had comorbidities. Leucopenia was seen in in 9 (34.61%) and leukocytosis was seen in 2 patient. Ten patient (38.46%) out of 26 shown increased lymphocyte/neutrophil ratio. Chest X- ray was normal in 20 patients (76.92%). Abnormalities in chest CT were detected among 10 (38.46%) patients. Typical findings were bilateral multifocal patchy peripheral subsegmental areas of consolidation more towards middle and lower zones and bilateral ground glass opacities involving multiple segments. Oseltamivir and chloroquine were given to all 26 patients. Azithromycin was given in 24 patients. Mean duration of conversion of COVID-19 patients was 6.83 days. All discharged patients advised home quarantine for 14 days as per guidelines. Conclusion: Patients often present without fever, and many may not have abnormal radiologic findings. Patients with older age and associated comorbid conditions (COPD and diabetes) seem to have greater risk for lung injury.", "qid": 26, "docid": "xsjfjwou", "rank": 74, "score": 0.7397499680519104}, {"content": "Title: Headache as the Presenting Symptom in 2 Patients With COVID-19 and a History of Migraine: 2 Case Reports Content: The coronavirus disease 2019 (COVID-19) pandemic has now affected more than 5 million people globally. Typical symptoms include fever, cough, and shortness of breath. Patients with underlying medical comorbidities such as cardiovascular disease and diabetes are more likely to become severely ill. To date there is limited information on how COVID-19 affects patients with a history migraine. Here, we present the cases of 2 women with a history of migraine whose first symptom of COVID-19 was a severe persistent headache.", "qid": 26, "docid": "ahwnezdn", "rank": 75, "score": 0.7396458387374878}, {"content": "Title: Neurological manifestations of COVID-19: a review of what we know so far Content: Coronavirus disease 2019 (COVID-19) has become a pandemic disease globally. While it mostly presents with respiratory symptoms, it has already been found that it could manifest with a series of neurological symptoms as well, either at presentation or during the course of the disease. Symptoms vary from non-specific such as headache or dizziness to more specific such as convulsions and cerebrovascular disease (CVD). This study aims to give an overview of the neurological manifestations of COVID-19 and discuss the potential pathogenetic mechanisms of central nervous system (CNS) involvement. Clinicians and especially internists, neurologists, and infectious disease specialists should be aware of these symptoms and able to recognize them early. Prompt diagnosis and immediate management of the neurological manifestations of the novel coronavirus will not only improve the prognosis of COVID-19 patients but will also prevent the dissemination of the disease due to misdiagnosed cases.", "qid": 26, "docid": "rvo73h2l", "rank": 76, "score": 0.7394759654998779}, {"content": "Title: Neurological manifestations and complications of COVID-19: A literature review Content: The Coronavirus disease due to SARS-CoV-2 emerged in Wuhan city, China in December 2019 and rapidly spread to more than 200 countries as a global health pandemic. There are more than 3.5 million confirmed cases and around 165,000 to 243,000 fatalities. The primary manifestation is respiratory and cardiac but neurological features are also being reported in the literature as case reports and case series. The most common reported symptoms to include headache and dizziness followed by encephalopathy and delirium. Among the complications noted are Cerebrovascular accident, Guillian barre syndrome, acute transverse myelitis, and acute encephalitis. The most common peripheral manifestation was hyposmia. It is further noted that sometimes the neurological manifestations can precede the typical features like fever and cough and later on typical manifestations develop in these patients. Hence a high index of suspicion is required for timely diagnosis and isolation of cases to prevent the spread in neurology wards. We present a narrative review of the neurological manifestations and complications of COVID-19. Our aim is to update the neurologists and physicians working with suspected cases of COVID-19 about the possible neurological presentations and the probable neurological complications resulting from this novel virus infection.", "qid": 26, "docid": "lo705hfr", "rank": 77, "score": 0.7394543886184692}, {"content": "Title: Does this patient have COVID-19? A practical guide for the internist Content: Coronavirus disease 2019 (COVID-19) is currently causing a pandemic and will likely persist in endemic form in the foreseeable future. Physicians need to correctly approach this new disease, often representing a challenge in terms of differential diagnosis. Although COVID-19 lacks specific signs and symptoms, we believe internists should develop specific skills to recognize the disease, learning its 'semeiotic'. In this review article, we summarize the key clinical features that may guide in differentiating a COVID-19 case, requiring specific testing, from upper respiratory and/or influenza-like illnesses of other aetiology. We consider two different clinical settings, where availability of the different diagnostic strategies differs widely: outpatient and inpatient. Our reasoning highlights how challenging a balanced approach to a patient with fever and flu-like symptoms can be. At present, clinical workup of COVID-19 remains a hard task to accomplish. However, knowledge of the natural history of the disease may aid the internist in putting common and unspecific symptoms into the correct clinical context.", "qid": 26, "docid": "evv73ry1", "rank": 78, "score": 0.7393471002578735}, {"content": "Title: Using open-source intelligence to detect early signals of COVID-19 in China, Descriptive study. Content: BACKGROUND COVID-19 in China was first reported to the World Health Organization on December 31st 2019. The first cases were officially identified around December 8th 2019. The origin of COVID-19 is not confirmed, but half the early cases were linked to a seafood market in Wuhan. The first two documented cases did not attend the seafood market. News reports, social media and informal sources may contain information about outbreaks prior to formal notification. OBJECTIVE To identify early signals of pneumonia and/or severe acute respiratory illness (SARI) in China, prior to official recognition of the COVID 19 outbreak in December 2019, using open source data. METHODS In order to capture early reports we searched an open source epidemic observatory, Epiwatch from 1st October2019 in China, for severe acute respiratory illness (SARI) or pneumonia related illnesses. Google and Chinese search engine Baidu were used. RESULTS There was an increase in reports following the official notification of COVID 19 to WHO on December 31 2019, and a retracted report on December 26th 2019. A report of severe pneumonia was identified on November 22 2019 in Xiangyang, Index patient was retrospectively identified on 17 November. CONCLUSIONS The lack of reports of a SARI outbreaks prior to December 31st, with a retracted report on December 26th suggests media censorship, given formal reports that cases began on December 8th. However, the findings also support relatively recent origin of COVID-19 in November 2019. The case reported on November 22nd was transferred to Wuhan approximately 1 incubation period before the first reported cases on December 8th, and should be further investigated, as only half of the early cases had exposure to the seafood market. It has since been reported that another case of COVID 19 has been retrospectively identified in Hubei on November 17th, confirming that the infection was present prior to December. CLINICALTRIAL", "qid": 26, "docid": "w9yibx5o", "rank": 79, "score": 0.739276647567749}, {"content": "Title: Clinical characteristics of 80 hospitalized frontline medical workers infected with COVID-19 in Wuhan, China Content: Summary More than 1,000 medical workers have been infected with COVID-19 in China. The 80 hospitalized patients included 57 SARS-CoV-2 confirmed and 23 clinically diagnosed. The median age was 39 years, 49 (61.25%) were women, and one patient died. The most common symptoms at onset were fever (65, 81.25%), cough (47, 58.75%), fatigue (28, 35%), myalgia (19, 23.75%), expectoration (19, 23.75%), and diarrhea (15, 18.75%). Patients of frontline medical workers at a single-center hospital showed some unique clinical and laboratory findings compared with other patients in Wuhan and outside of Wuhan. This study provides our experience for other frontline medical workers.", "qid": 26, "docid": "0ejs05e8", "rank": 80, "score": 0.7390360832214355}, {"content": "Title: Does this patient have COVID-19? A practical guide for the internist Content: Coronavirus disease 2019 (COVID-19) is currently causing a pandemic and will likely persist in endemic form in the foreseeable future. Physicians need to correctly approach this new disease, often representing a challenge in terms of differential diagnosis. Although COVID-19 lacks specific signs and symptoms, we believe internists should develop specific skills to recognize the disease, learning its \u2018semeiotic\u2019. In this review article, we summarize the key clinical features that may guide in differentiating a COVID-19 case, requiring specific testing, from upper respiratory and/or influenza-like illnesses of other aetiology. We consider two different clinical settings, where availability of the different diagnostic strategies differs widely: outpatient and inpatient. Our reasoning highlights how challenging a balanced approach to a patient with fever and flu-like symptoms can be. At present, clinical workup of COVID-19 remains a hard task to accomplish. However, knowledge of the natural history of the disease may aid the internist in putting common and unspecific symptoms into the correct clinical context.", "qid": 26, "docid": "t98ctnc2", "rank": 81, "score": 0.7388713359832764}, {"content": "Title: Experiencia COVID-19 en un sanatorio privado de Buenos Aires durante el primer mes de la pandemia: 26 casos./ [COVID-19 experience in a private institution in Buenos Aires during the first month of the pandemic: 26 cases] Content: The first case of coronavirus (COVID-19) infection in Argentina was reported in Buenos Aires on March 3rd, 2020, in a patient who arrived from Milan. The aim of this study is to describe the clinical characteristics and course of illness of patients infected with Covid-19 that were hospitalized in a private clinical setting during March 2020. Sixty three patients suspected of COVID-19 infection, were admitted to our hospital during March 2020. Twenty six of these subjects were diagnosed positive by the RT-PCR for SARS Cov-2 in a nasopharyngeal swab specimen. We recorded data about epidemiological characteristics, clinical signs and symptoms, in addition to comorbidities, laboratory and radiological studies were done. The median age was 40 years (SD \u00b1 15 years); there was an equal number of men and women; all the patients but one were coming from abroad; the most common symptom was fever (24/26 cases) and lymphopenia (n = 8). We found that there were patients in whom fever disappeared within the first 72h (n = 17) and another group in which the fever lasted six or more days (n = 7). One patient out of 26 died. The population of our study was young and almost all were imported cases, in alinement with the stage of the epidemic at the time when the study was conducted. We observed that there were two patterns in the fever curve but the persistence of it did not lead to a worse prognosis. Larger population studies are required in order to confirm these clinical findings.", "qid": 26, "docid": "vxo7vupg", "rank": 82, "score": 0.7388406991958618}, {"content": "Title: [COVID-19 experience in a private institution in Buenos Aires during the first month of the pandemic: 26 cases]. Content: The first case of coronavirus (COVID-19) infection in Argentina was reported in Buenos Aires on March 3rd, 2020, in a patient who arrived from Milan. The aim of this study is to describe the clinical characteristics and course of illness of patients infected with Covid-19 that were hospitalized in a private clinical setting during March 2020. Sixty three patients suspected of COVID-19 infection, were admitted to our hospital during March 2020. Twenty six of these subjects were diagnosed positive by the RT-PCR for SARS Cov-2 in a nasopharyngeal swab specimen. We recorded data about epidemiological characteristics, clinical signs and symptoms, in addition to comorbidities, laboratory and radiological studies were done. The median age was 40 years (SD \u00b1 15 years); there was an equal number of men and women; all the patients but one were coming from abroad; the most common symptom was fever (24/26 cases) and lymphopenia (n = 8). We found that there were patients in whom fever disappeared within the first 72h (n = 17) and another group in which the fever lasted six or more days (n = 7). One patient out of 26 died. The population of our study was young and almost all were imported cases, in alinement with the stage of the epidemic at the time when the study was conducted. We observed that there were two patterns in the fever curve but the persistence of it did not lead to a worse prognosis. Larger population studies are required in order to confirm these clinical findings.", "qid": 26, "docid": "a9ku6c7l", "rank": 83, "score": 0.7388406991958618}, {"content": "Title: [Diagnosis and treatment recommendation for pediatric COVID-19 (the second edition)] Content: The coronavirus disease 2019 (COVID-19) has caused a global pandemic. All people including children are generally susceptible to COVID-19, but the condition is relatively mild for children. The diagnosis of COVID-19 is largely based on the epidemiological evidence and clinical manifestations, and confirmed by positive detection of virus nucleic acid in respiratory samples. The main symptoms of COVID-19 in children are fever and cough; the total number of white blood cell count is usually normal or decreased; the chest imaging is characterized by interstitial pneumonia, which is similar to other respiratory virus infections and Mycoplasma pneumoniae infections. Early identification, early isolation, early diagnosis and early treatment are important for clinical management. The treatment of mild or moderate type of child COVID-19 is mainly symptomatic. For severe and critical ill cases, the oxygen therapy, antiviral drugs, antibacterial drugs, glucocorticoids, mechanical ventilation or even extracorporeal membrane oxygenation (ECMO) may be adopted, and the treatment plan should be adjusted timely through multi-disciplinary cooperation.", "qid": 26, "docid": "14dzd7h5", "rank": 84, "score": 0.7388324737548828}, {"content": "Title: [Diagnosis and treatment recommendation for pediatric COVID-19 (the second edition)]. Content: The coronavirus disease 2019 (COVID-19) has caused a global pandemic. All people including children are generally susceptible to COVID-19, but the condition is relatively mild for children. The diagnosis of COVID-19 is largely based on the epidemiological evidence and clinical manifestations, and confirmed by positive detection of virus nucleic acid in respiratory samples. The main symptoms of COVID-19 in children are fever and cough; the total number of white blood cell count is usually normal or decreased; the chest imaging is characterized by interstitial pneumonia, which is similar to other respiratory virus infections and Mycoplasma pneumoniae infections. Early identification, early isolation, early diagnosis and early treatment are important for clinical management. The treatment of mild or moderate type of child COVID-19 is mainly symptomatic. For severe and critical ill cases, the oxygen therapy, antiviral drugs, antibacterial drugs, glucocorticoids, mechanical ventilation or even extracorporeal membrane oxygenation (ECMO) may be adopted, and the treatment plan should be adjusted timely through multi-disciplinary cooperation.", "qid": 26, "docid": "zwv5e1kl", "rank": 85, "score": 0.7388324737548828}, {"content": "Title: Olfactory and Oral Manifestations of COVID-19: Sex-Related Symptoms\u2014A Potential Pathway to Early Diagnosis Content: OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic poses a threat to global health. Early diagnosis is an essential key to limit the outbreak of the virus. STUDY DESIGN: Case series, study conducted between March 25, 2020, and April 15, 2020. SETTING: Ambulatory, nonhospitalized patients who were quarantined in a designated hotel for COVID-19 patients and were recruited by an advertisement at the hotel. SUBJECTS AND METHODS: In total, 140 patients participated in a web-based questionnaire assessing initial symptoms of common viral diseases, olfactory and taste functions, xerostomia, and orofacial pain. RESULTS: A total of 58 men and 70 women participated. Initial symptoms were cough (59.4%), weakness (47.7%), myalgia (46.9%), fever (42.2%), headache (40.6%), impaired sense of smell (38.3%), impaired sense of taste (32.8%), sore throat (26.6%), runny nose (26.6%), and nasal congestion (22.7%). All symptoms were more frequent among women; however, only runny nose was statistically significant (P = .018). The most common combination of symptoms was cough and weakness (37.5%). A total of 25.8% reported olfactory and taste dysfunctions in the absence of other symptoms. In a comparison between the sexes, cough and runny nose were the most common combination in women (P = .018). A total of 38.3% of patients reported olfactory dysfunction as an initial symptom. Anosmia and facial pain were more common among women (P < .001 and P = .01, respectively), and 56% of patients reported xerostomia. CONCLUSION: A considerable number of patients presented with olfactory and oral disorders. Interestingly, women presented with a different cluster of symptoms than men, which may suggest a new clinical approach to diagnosing COVID-19 disease.", "qid": 26, "docid": "zv45usvu", "rank": 86, "score": 0.7388160228729248}, {"content": "Title: Olfactory and Oral Manifestations of COVID-19: Sex-Related Symptoms-A Potential Pathway to Early Diagnosis Content: OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic poses a threat to global health. Early diagnosis is an essential key to limit the outbreak of the virus. STUDY DESIGN: Case series, study conducted between March 25, 2020, and April 15, 2020. SETTING: Ambulatory, nonhospitalized patients who were quarantined in a designated hotel for COVID-19 patients and were recruited by an advertisement at the hotel. SUBJECTS AND METHODS: In total, 140 patients participated in a web-based questionnaire assessing initial symptoms of common viral diseases, olfactory and taste functions, xerostomia, and orofacial pain. RESULTS: A total of 58 men and 70 women participated. Initial symptoms were cough (59.4%), weakness (47.7%), myalgia (46.9%), fever (42.2%), headache (40.6%), impaired sense of smell (38.3%), impaired sense of taste (32.8%), sore throat (26.6%), runny nose (26.6%), and nasal congestion (22.7%). All symptoms were more frequent among women; however, only runny nose was statistically significant (P = .018). The most common combination of symptoms was cough and weakness (37.5%). A total of 25.8% reported olfactory and taste dysfunctions in the absence of other symptoms. In a comparison between the sexes, cough and runny nose were the most common combination in women (P = .018). A total of 38.3% of patients reported olfactory dysfunction as an initial symptom. Anosmia and facial pain were more common among women (P < .001 and P = .01, respectively), and 56% of patients reported xerostomia. CONCLUSION: A considerable number of patients presented with olfactory and oral disorders. Interestingly, women presented with a different cluster of symptoms than men, which may suggest a new clinical approach to diagnosing COVID-19 disease.", "qid": 26, "docid": "epk4uksu", "rank": 87, "score": 0.7388160228729248}, {"content": "Title: Altered Mental Status as a Novel Initial Clinical Presentation for COVID-19 Infection in the Elderly Content: The coronavirus disease of 2019 or COVID-19 was first identified in Hubei Province in China in November of 2019 and quickly spread to become a global pandemic. The virus, SARS-Coronavirus-2 (2-SARS-CoV-2), is particularly virulent in the elderly who can develop symptoms and become mortally ill within days of contracting the virus. The virus is easily transmitted by droplets (e.g., sneezing, coughing) and communal living settings such as personal care homes can be vulnerable to the spread of the virus. Identifying patients early in the disease process is important to providing appropriate medical interventions. To date, most of the medical literature, including Center for Disease Control guidelines, has relied on three necessary symptoms in making the diagnosis of COVID-19: fever, cough and shortness of breath. We present four cases of elderly patients who developed altered mental status as their presenting symptom without associated fever or respiratory symptoms.", "qid": 26, "docid": "78rv366w", "rank": 88, "score": 0.7388026714324951}, {"content": "Title: COVID-19 versus non-COVID-19 pneumonia: A retrospective cohort study Content: Background and Objective: Since the outbreak of coronavirus disease 2019 (COVID-19) in December 2019 in Wuhan, Hubei Province, China, it has spread around the world and become a global public health emergency. It is important to distinguish COVID-19 from other viral pneumonias in order to properly screen and diagnose patients, reduce nosocomial infections, and complement the inadequacy of nucleic acid testing. In this study, we retrospectively analysed the clinical data of COVID-19 versus non-COVID-19 patients treated at our hospital between January 17 and February 27, 2020 in order to summarize our clinical experience in the differential diagnosis of COVID-19. Methods: In this retrospective cohort study, 23 confirmed COVID-19 patients were consecutively enrolled from January 17 to February 27, 2020, while 29 confirmed non-COVID-19 patients were enrolled in West China Hospital of Sichuan University. We collected baseline data, epidemiological data, clinical characteristics, imaging findings, viral nucleic acid test results, and survival data. SPSS v22.0 was used for statistical analysis. Outcomes were followed up until March 25. Results: A total of 52 patients were included in this study, including 23 COVID-19 patients and 29 non-COVID-19 patients. No significant between-group difference was observed in age, sex, primary signs or symptoms, cellular immunity, or platelet count. Significant between-group differences were observed in clinical characteristics such as dry cough, contact with individuals from Wuhan, some underlying diseases, nucleated cell count, chest imaging findings, viral nucleic acid test result,28-day mortality, and 28-day survival. Conclusion: Epidemiological data, clinical symptoms, nucleic acid test results for COVID-19 and chest CT manifestation may help distinguish COVID-19 from non-COVID-19 cases, prevent imported cases and nosocomial infections.", "qid": 26, "docid": "ns4fskil", "rank": 89, "score": 0.7387944459915161}, {"content": "Title: Comment on \"Cutaneous manifestations in COVID-19: a first perspective \" by Recalcati S Content: Since the coronavirus disease 2019 (COVID 19) outbreak was first reported in the Chinese city of Wuhan on December 31, 2019, it has stricken more than 1,000,000 persons worldwide, of whom over 50,000 have died (1). Having been infected by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), patients with COVID-19 mainly present with fever and respiratory symptoms (2). Isolated sudden onset anosmia has also frequently been reported (3). Less frequently, rhinorrhea, diarrhoea and dysgeusia may be associated. While only a few reports have evoked cutaneous manifestations (4), we read with interest an initial study on the topic entitled \"Cutaneous manifestations in COVID-19: a first perspective \" by Recalcati S. (5).", "qid": 26, "docid": "5c3t4znm", "rank": 90, "score": 0.738784670829773}, {"content": "Title: Epidemiological and clinical characteristics of 333 confirmed cases with coronavirus disease 2019 in Shanghai, China Content: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease first identified in Wuhan City, Hubei Province, China. As of 19 February 2020, there had been 333 confirmed cases reported in Shanghai, China. This study elaborates on the epidemiological and clinical characteristics of COVID-19 based on a descriptive study of the 333 patients infected with COVID-19 in Shanghai for the purpose of probing into this new disease and providing reference. Among the 333 confirmed cases in Shanghai, 172 (51.7%) were males and 161 (48.3%) were females, with a median age of 50 years. 299 (89.8%) cases presented mild symptoms. 139 (41.7%) and 111 (33.3%) cases were infected in Wuhan and Shanghai, respectively. 148 (44.4%) cases once had contact with confirmed cases before onset, while 103 (30.9%) cases had never contacted confirmed cases but they had a sojourn history in Wuhan. The onset date of the first case in Shanghai was 28 December, with the peak appearing on 27 January. The median incubation period of COVID-19 was estimated to be 7.2 days. 207 (62.2%) cases had fever symptoms at the onset, whereas 273 (82.0%) cases experienced fever before hospitalization. 56 (18.6%) adults experienced a decrease in white blood cell and 84 (42.9%) had increased C-reactive protein after onset. Elderly, male and heart disease history were risk factors for severe or critical pneumonia. These findings suggest that most cases experienced fever symptoms and had mild pneumonia. Strengthening the health management of elderly men, especially those with underlying diseases, may help reduce the incidence of severe and critical pneumonia. Time intervals from onset to visit, hospitalization and diagnosis confirmed were all shortened after Shanghai's first-level public health emergency response. Shanghai's experience proves that COVID-19 can be controlled well in megacities.", "qid": 26, "docid": "zj3ftw1e", "rank": 91, "score": 0.738685667514801}, {"content": "Title: Longitudinal symptom dynamics of COVID-19 infection in primary care Content: Importance: Data regarding the clinical characteristics of COVID-19 infection is rapidly accumulating. However, most studies thus far are based on hospitalized patients and lack longitudinal follow up. As the majority of COVID-19 cases are not hospitalized, prospective studies of symptoms in the population presenting to primary care are needed. Objective: To assess the longitudinal dynamic of clinical symptoms in non-hospitalized individuals prior to and throughout the diagnosis of SARS-CoV-2 infection. Design, Setting, and Participants: From 1/3/2020 to 07/06/2020, information on symptoms from either surveys or primary care visits was available for 206,377 individuals, including 2,471 who tested positive for COVID-19. Data were extracted from electronic health records (EHR) of the second largest Health Maintenance Organization in Israel, consisting of both results of PCR tests and symptoms recorded by primary care physicians, and linked longitudinal self reported symptoms. Exposures: Diagnosis of COVID-19 disease was made by PCR testing for SARS-CoV-2 from nasopharyngeal swabs. Main Outcomes and Measures: Longitudinal prevalence of clinical symptoms Results: In adults, the most prevalent symptoms recorded in EHR were cough (11.6%), fever (10.3%), and myalgia (7.7%) and the most prevalent self-reported symptoms were cough (21%), fatigue (19%) and rhinorrhea and/or nasal congestion (17%). In children, the most prevalent symptoms recorded in the EHR were fever (7%), cough (5.5%) and abdominal pain (2.4%). Emotional disturbances were documented in 15.9% of the positive adults and 4.2% of the children. Loss of taste and smell, either self-reported or documented by a physician, 3 weeks prior to testing, were the most discriminative symptoms in adults (OR =11.18 and OR=5.47 respectively). Additional symptoms included self reported confusion (OR =4.02), and fatigue (OR = 1.73) and a documentation of syncope, rhinorrhea (OR = 2.09 for both ) and fever (OR= 1.62 ) by a physician. Mean time to recovery was 23.5 +- 9.9 days. Children had a significantly shorter disease duration (21.7 +- 8.8 days, p-value=0.01). Several symptoms, including fatigue, myalgia, runny nose and shortness of breath were reported weeks after recovery. Conclusions and Relevance: As the COVID-19 pandemic progresses rapidly worldwide, obtaining accurate information on symptoms and their progression is of essence. Our study shed light on the full clinical spectrum of symptoms experienced by infected individuals in primary care, and may alert physicians for the possibility of COVID-19 infection.", "qid": 26, "docid": "gg1qth9p", "rank": 92, "score": 0.7386839389801025}, {"content": "Title: [In-hospital treatment of COVID-19 patients]. Content: Covid-19 infection is now a pandemic disease. Most patients have mild symptoms without the need for hospitalization. On average, 5% of the COVID-19-positive patients have severe respiratory symptoms. We present 3 patients aged 45, 67 and 75 years, who were admitted to the ICU with severe respiratory symptoms. We describe the presentation of the COVID-19 patients on the emergency department, the development of the disease, and the treatment of these patients on the ICU.", "qid": 26, "docid": "v0nebaz1", "rank": 93, "score": 0.7385424375534058}, {"content": "Title: Clinical and virologic characteristics of the first 12 patients with coronavirus disease 2019 (COVID-19) in the United States Content: Data on the detailed clinical progression of COVID-19 in conjunction with epidemiological and virological characteristics are limited. In this case series, we describe the first 12 US patients confirmed to have COVID-19 from 20 January to 5 February 2020, including 4 patients described previously1-3. Respiratory, stool, serum and urine specimens were submitted for SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) testing, viral culture and whole genome sequencing. Median age was 53 years (range: 21-68); 8 patients were male. Common symptoms at illness onset were cough (n = 8) and fever (n = 7). Patients had mild to moderately severe illness; seven were hospitalized and demonstrated clinical or laboratory signs of worsening during the second week of illness. No patients required mechanical ventilation and all recovered. All had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset. Lowest real-time PCR with reverse transcription cycle threshold values in the upper respiratory tract were often detected in the first week and SARS-CoV-2 was cultured from early respiratory specimens. These data provide insight into the natural history of SARS-CoV-2. Although infectiousness is unclear, highest viral RNA levels were identified in the first week of illness. Clinicians should anticipate that some patients may worsen in the second week of illness.", "qid": 26, "docid": "15n0rny6", "rank": 94, "score": 0.738410472869873}, {"content": "Title: Clinical and virologic characteristics of the first 12 patients with coronavirus disease 2019 (COVID-19) in the United States. Content: Data on the detailed clinical progression of COVID-19 in conjunction with epidemiological and virological characteristics are limited. In this case series, we describe the first 12 US patients confirmed to have COVID-19 from 20 January to 5 February 2020, including 4 patients described previously1-3. Respiratory, stool, serum and urine specimens were submitted for SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) testing, viral culture and whole genome sequencing. Median age was 53 years (range: 21-68); 8 patients were male. Common symptoms at illness onset were cough (n = 8) and fever (n = 7). Patients had mild to moderately severe illness; seven were hospitalized and demonstrated clinical or laboratory signs of worsening during the second week of illness. No patients required mechanical ventilation and all recovered. All had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset. Lowest real-time PCR with reverse transcription cycle threshold values in the upper respiratory tract were often detected in the first week and SARS-CoV-2 was cultured from early respiratory specimens. These data provide insight into the natural history of SARS-CoV-2. Although infectiousness is unclear, highest viral RNA levels were identified in the first week of illness. Clinicians should anticipate that some patients may worsen in the second week of illness.", "qid": 26, "docid": "i0nppkp1", "rank": 95, "score": 0.738410472869873}, {"content": "Title: Clinico-radiological Presentation of COVID-19 Patients at a Tertiary Care Center at Bhilwara Rajasthan, India. Content: Background COVID-19 has now become a pandemic. From Wuhan, China, in December 2019 to European countries, USA and now it seems to gain a strong foothold in India. The objective of this work is to report the initial experience with demographic and clinical features, and management of COVID-19 patients admitted in medical college Bhilwara, India. Methods This is a descriptive case series of first 26 COVID-19 patients. Demographical, clinical, laboratory, and radiological characteristics and treatment and outcomes data were obtained with data collection forms and history given by 26 COVID-19 patients. Results and Discussion During this study 26 COVID-19 positive patients were admitted in MG Hospital, Bhilwara. Male patients were 61.54% and majority (88.46%) were below 60 years of age. Approximately 30.76 % patients were asymptomatic. Fever was the most common symptom (61.54%) followed by sore throat (53.84 %), cough (42.30%) myalgia (38.46%)and dyspnea(23.07%). Six patients (23.07%) of total 26 had comorbidities. Leucopenia was seen in in 9 (34.61%) and leukocytosis was seen in 2 patient. Ten patient (38.46%) out of 26 shown increased lymphocyte/neutrophil ratio. Chest X- ray was normal in 20 patients (76.92%). Abnormalities in chest CT were detected among 10 (38.46%) patients. Typical findings were bilateral multifocal patchy peripheral subsegmental areas of consolidation more towards middle and lower zones and bilateral ground glass opacities involving multiple segments. Oseltamivir and chloroquine were given to all 26 patients. Azithromycin was given in 24 patients. Mean duration of conversion of COVID-19 patients was 6.83 days. All discharged patients advised home quarantine for 14 days as per guidelines. Conclusion Patients often present without fever, and many may not have abnormal radiologic findings. Patients with older age and associated comorbid conditions (COPD and diabetes) seem to have greater risk for lung injury.", "qid": 26, "docid": "ismrzcbz", "rank": 96, "score": 0.7382454872131348}, {"content": "Title: Chest CT manifestations of new coronavirus disease 2019 (COVID-19): a pictorial review Content: Coronavirus disease 2019 (COVID-19) outbreak, first reported in Wuhan, China, has rapidly swept around the world just within a month, causing global public health emergency. In diagnosis, chest computed tomography (CT) manifestations can supplement parts of limitations of real-time reverse transcription polymerase chain reaction (RT-PCR) assay. Based on a comprehensive literature review and the experience in the frontline, we aim to review the typical and relatively atypical CT manifestations with representative COVID-19 cases at our hospital, and hope to strengthen the recognition of these features with radiologists and help them make a quick and accurate diagnosis. Key Points \u2022 Ground glass opacities, consolidation, reticular pattern, and crazy paving pattern are typical CT manifestations of COVID-19. \u2022 Emerging atypical CT manifestations, including airway changes, pleural changes, fibrosis, nodules, etc., were demonstrated in COVID-19 patients. \u2022 CT manifestations may associate with the progression and prognosis of COVID-19.", "qid": 26, "docid": "ef84i589", "rank": 97, "score": 0.738184928894043}, {"content": "Title: Clinical and imaging features of COVID-19 Content: Abstract Since December 2019, multiple cases of 2019 coronavirus disease (COVID-19) have been reported in Wuhan in China's Hubei Province, a disease which has subsequently spread rapidly across the entire country. Highly infectious, COVID-19 has numerous transmission channels and humans are highly susceptible to infection. The main clinical symptoms of COVID-19 are fever, fatigue, and a dry cough. Laboratory examination in the early stage of the disease shows a normal or decreased white blood cell count, and a decreased lymphocyte count. While CT examination serves as the screening and diagnostic basis for COVID-19, its accuracy is limited. The nucleic acid testing is the gold standard for the diagnosis of COVID-19, but has a low sensitivity is low. There is clearly a divide between the two means of examination. This paper reviews the published literature, guidelines and consensus, and summarizes the clinical and imaging characteristics of COVID-19, in order to provide a reliable basis for early diagnosis and treatment.", "qid": 26, "docid": "wap7lo05", "rank": 98, "score": 0.7381613254547119}, {"content": "Title: Gastrointestinal tract symptoms in coronavirus disease 2019: Analysis of clinical symptoms in adult patients Content: Objective: To investigate the clinical presentation of coronavirus disease 2019 (COVID-19), particularly the incidence of gastrointestinal tract symptoms. Design: We enrolled adult COVID-19 patients from a mobile cabin hospital in Wuhan with a definitive diagnosis by SARS-CoV-2 nucleic acid testing. Face-to-face interviews were conducted in which the patient selected COVID-19-related symptoms and report the time of onset and duration of symptoms. Results: A total of 212 adults were enrolled in this study, of which 127 (59.9%) were females, mean age was 48.50 (range: 17-79) years, and mean disease course was 26.78 (3-60) days. Fever and cough were the most common and earliest clinical symptoms of COVID-19. Diarrhoea occurred in 43.8% (93/212) of patients, of which 86.0% (80/93) had mushy stools. Nausea and vomiting were also common (20.7%). Diarrhoea lasted for 4.00(2.00-8.85) days and mostly occurred 5.00(0.25-11.00) days after the emergence of the first symptoms. Multiple logistic regression analysis found that diarrhoea was significantly correlated with fatigue [OR2.900,95%CI (1.629-5.164), p<0.0001]. Conclusions: Gastrointestinal tract symptoms are common in COVID-19 and most occur during the middle stage of the disease and lasts for a short period of time. Clinicians need to pay greater attention to gastrointestinal tract symptoms of COVID-19.", "qid": 26, "docid": "bu2w2ox6", "rank": 99, "score": 0.7376565337181091}, {"content": "Title: Differences in Clinical Characteristics of Covid-19 in Hispanic/Latino Population. Content: The Centers for Disease Control and Prevention (CDC) suggest several possible symptoms associated with coronavirus disease 2019 (COVID-19), including cough, shortness of breath (SOB), fever, chills, muscle pain, sore throats, new loss of taste or smell, nausea, vomiting, or diarrhea. (\"Centers for Disease Control and Prevention. Symptoms of Coronavirus.,\") The clinical characteristics from the study by Yu et al. published in Transboundary and Emerging Diseases and other Chinese studies were different from those we observe in the United States.", "qid": 26, "docid": "03z3wk6i", "rank": 100, "score": 0.7372042536735535}]}
{"query": "what is known about those infected with Covid-19 but are asymptomatic?", "hits": [{"content": "Title: There are asymptomatic and pre-symptomatic patients infected with COVID-19. So what? Pandemic response implications Content: Abstract Asymptomatic but infectious people have been reported in many infectious diseases. Asymptomatic and pre-symptomatic carriers would be a hidden reservoir of COVID-19. Aim This review identifies primary empirical evidence about the ability of asymptomatic carriers to infect others with COVID-19 pandemic and reflects on the implications for control measures. Methods A systematic review is followed by a narrative report and commentary inclusion criteria were: studies reporting primary data on asymptomatic or pre-symptomatic patients, who were considered to have passed on COVID-19 infection; and published in indexed journals or in peer review between January 1 and March 31, 2020. Results Nine articles reported on 83 asymptomatic or pre-symptomatic persons. Conclusions The evidence confirms COVID-19 transmission from people who were asymptomatic at the time. A series of implications for health service response are laid out. Keywords: Covid-19, Asymptomatic, Pre-symptomatic, Public Health", "qid": 27, "docid": "nadzy6lm", "rank": 1, "score": 0.8221811652183533}, {"content": "Title: Characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, China Content: Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is continuously and rapidly circulating at present. Asymptomatic patients have been proven to be contagious and thus pose a significant infection control challenge. Here we describe the characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, Shandong province, China. A total of 47 patients with confirmed COVID-19 were recruited. Among them, 11 patients were categorized as asymptomatic cases. We found that the asymptomatic patients in Jinan were relatively young and were mainly clustered cases. The laboratory indicators and lung lesion on chest CT were mild. No special factors were found accounting for the presence or absence of symptoms. The presence of asymptomatic patients increased the difficulty of screening. It is necessary to strengthen the identification of such patients in the future.", "qid": 27, "docid": "ffs350f2", "rank": 2, "score": 0.819778561592102}, {"content": "Title: Otolaryngology Providers Must Be Alert for Patients with Mild and Asymptomatic COVID-19 Content: More than half of COVID-19 patients are afebrile early in the disease course, yet mildly ill or asymptomatic patients can still spread SARS-CoV-2 with high efficiency. Atypically presenting patients may be seen in noninfectious disease settings such as otolaryngology, which is a specialty prone to occupational exposure. Otolaryngologists have been infected with COVID-19 at higher rates than other specialties in China and other countries. Otolaryngology providers should maintain high clinical suspicion for mild and asymptomatic COVID-19 patients. Protective strategies should be implemented including preappointment screening, triaging, restriction of nonurgent visits and surgeries, telemedicine, and appropriate personal protective equipment use.", "qid": 27, "docid": "yy7lhl9z", "rank": 3, "score": 0.817463755607605}, {"content": "Title: Otolaryngology Providers Must Be Alert for Patients with Mild and Asymptomatic COVID-19. Content: More than half of COVID-19 patients are afebrile early in the disease course, yet mildly ill or asymptomatic patients can still spread SARS-CoV-2 with high efficiency. Atypically presenting patients may be seen in noninfectious disease settings such as otolaryngology, which is a specialty prone to occupational exposure. Otolaryngologists have been infected with COVID-19 at higher rates than other specialties in China and other countries. Otolaryngology providers should maintain high clinical suspicion for mild and asymptomatic COVID-19 patients. Protective strategies should be implemented including preappointment screening, triaging, restriction of nonurgent visits and surgeries, telemedicine, and appropriate personal protective equipment use.", "qid": 27, "docid": "nhfjqdnh", "rank": 4, "score": 0.817463755607605}, {"content": "Title: Characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, China Content: Abstract Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is continuously and rapidly circulating at present. Asymptomatic patients have been proven to be contagious and thus pose a significant infection control challenge. Here we describe the characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, Shandong province, China. A total of 47 patients with confirmed COVID-19 were recruited. Among them, 11 patients were categorized as asymptomatic cases. We found that the asymptomatic patients in Jinan were relatively young and were mainly clustered cases. The laboratory indicators and lung lesion on chest CT were mild. No special factors were found accounting for the presence or absence of symptoms. The presence of asymptomatic patients increased the difficulty of screening. It is necessary to strengthen the identification of such patients in the future.", "qid": 27, "docid": "xwvtjm6s", "rank": 5, "score": 0.8131318092346191}, {"content": "Title: A systematic review of asymptomatic infections with COVID-19 Content: Since the outbreak of coronavirus disease 2019 (COVID-19) in late December 2019, it has brought significant harm and challenges to over 200 countries and regions around the world. However, there is increasing evidence that many patients with COVID-19 are asymptomatic or have only mild symptoms, but they are able to transmit the virus to others. There are difficulties in screening for asymptomatic infections, which makes it more difficult for national prevention and control of this epidemic. This article reviews the characteristics, treatment, and outcomes of asymptomatic infections with COVID-19, hoping it would be helpful for early prevention and control of this severe public health threat worldwide.", "qid": 27, "docid": "hv0cwf6d", "rank": 6, "score": 0.8110021948814392}, {"content": "Title: A Systematic Review of Asymptomatic Infections with COVID-19 Content: Since the outbreak of coronavirus disease 2019 (COVID-19) in late December 2019, it has brought significant harm and challenges to over 200 countries and regions around the world. However, there is increasing evidence that many patients with COVID-19 are asymptomatic or have only mild symptoms, but they are able to transmit the virus to others. There are difficulties in screening for asymptomatic infections, which makes it more difficult for national prevention and control of this epidemic. This article reviews the characteristics, treatment, and outcomes of asymptomatic infections with COVID-19, hoping it would be helpful for early prevention and control of this severe public health threat worldwide.", "qid": 27, "docid": "xz6pq0v3", "rank": 7, "score": 0.8110021948814392}, {"content": "Title: Delivery of infection from asymptomatic carriers of COVID-19 in a familial cluster Content: OBJECTIVES: With the ongoing outbreak of COVID-19 around the world, it has become a worldwide health concern. One previous study reported a family cluster with an asymptomatic transmission of COVID-19. Here, we report another series of cases and further demonstrate the repeatability of the transmission of COVID-19 by pre-symptomatic carriers. METHODS: A familial cluster of five patients associated with COVID-19 was enrolled in the hospital. We collected epidemiological and clinical characteristics, laboratory outcomes from electronic medical records, and also verified them with the patients and their families. RESULTS: Among them, three family members (Case 3/4/5) had returned from Wuhan. Additionally, two family members, those who had not traveled to Wuhan, also contracted COVID-19 after contacting with the other three family members. Case 1 developed severe pneumonia and was admitted to the ICU. Case 3 and Case 5 presented fever and cough on days two through three of hospitalization and had ground-glass opacity changes in their lungs. Case 4 presented with diarrhea and pharyngalgia after admission without radiographic abnormalities. Case 2 presented no clinical nor radiographic abnormalities. All five cases had an increasing level of C-reactive protein. CONCLUSIONS: Our findings indicate that COVID-19 can be transmitted by asymptomatic carriers during the incubation period.", "qid": 27, "docid": "bgoihr3t", "rank": 8, "score": 0.8099983334541321}, {"content": "Title: A study on infectivity of asymptomatic SARS-CoV-2 carriers Content: BACKGROUND: An ongoing outbreak of coronavirus disease 2019 (COVID-19) has spread around the world. It is debatable whether asymptomatic COVID-19 virus carriers are contagious. We report here a case of the asymptomatic patient and present clinical characteristics of 455 contacts, which aims to study the infectivity of asymptomatic carriers. MATERIAL AND METHODS: 455 contacts who were exposed to the asymptomatic COVID-19 virus carrier became the subjects of our research. They were divided into three groups: 35 patients, 196 family members and 224 hospital staffs. We extracted their epidemiological information, clinical records, auxiliary examination results and therapeutic schedules. RESULTS: The median contact time for patients was four days and that for family members was five days. Cardiovascular disease accounted for 25% among original diseases of patients. Apart from hospital staffs, both patients and family members were isolated medically. During the quarantine, seven patients plus one family member appeared new respiratory symptoms, where fever was the most common one. The blood counts in most contacts were within a normal range. All CT images showed no sign of COVID-19 infection. No severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections was detected in 455 contacts by nucleic acid test. CONCLUSION: In summary, all the 455 contacts were excluded from SARS-CoV-2 infection and we conclude that the infectivity of some asymptomatic SARS-CoV-2 carriers might be weak.", "qid": 27, "docid": "yz7goivp", "rank": 9, "score": 0.8094637393951416}, {"content": "Title: Prevalence of Asymptomatic SARS-CoV-2 Infection: A Narrative Review Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly throughout the world since the first cases of coronavirus disease 2019 (COVID-19) were observed in December 2019 in Wuhan, China. It has been suspected that infected persons who remain asymptomatic play a significant role in the ongoing pandemic, but their relative number and effect have been uncertain. The authors sought to review and synthesize the available evidence on asymptomatic SARS-CoV-2 infection. Asymptomatic persons seem to account for approximately 40% to 45% of SARS-CoV-2 infections, and they can transmit the virus to others for an extended period, perhaps longer than 14 days. Asymptomatic infection may be associated with subclinical lung abnormalities, as detected by computed tomography. Because of the high risk for silent spread by asymptomatic persons, it is imperative that testing programs include those without symptoms. To supplement conventional diagnostic testing, which is constrained by capacity, cost, and its one-off nature, innovative tactics for public health surveillance, such as crowdsourcing digital wearable data and monitoring sewage sludge, might be helpful.", "qid": 27, "docid": "1ay60wzs", "rank": 10, "score": 0.8089125752449036}, {"content": "Title: Challenges of managing the asymptomatic carriers of SARS-CoV-2 Content: After an outbreak in Wuhan, China, a growing number of countries are now suffering from an epidemic by SARS-CoV-2, which causes COVID-19. Undoubtedly, reports of the skyrocketing global spread of COVID-19 has shocked people globally, from Japan to the United States. Presently, the World Health Organization indicates that the fatality rate due to COVID-19 is about 2%, inferring that many positive subjects may potentially overcome the illness with mild influenza-like symptoms and no need for hospitalization at intensive-care units. Because COVID-19 is completely new to the human immune system, many throughout the world are likely vulnerable to becoming sick after their initial exposure to SARS-CoV-2. Besides hospitalized cases, many individuals are likely asymptomatic but potentially carry the virus. While our knowledge about carriers and their virus shedding is deficient, some studies modelling the viral transmission have considered the potential contribution of the asymptomatic carriers. Protocols for managing asymptomatic cases, for example for controlling them to restrict their contact with healthy people at public places or private residences, have not been established. In-house quarantine may as well be applicable to asymptomatic cases if they could be identified and diagnosed. Presumably now, the asymptomatic subjects potentially contribute to the transmission of COVID-19 without their knowledge, intention, or being diagnosed as carriers. Thus, managing the asymptomatic subjects, who can carry and likely transmit the virus, is a major healthcare challenge while the pandemic is looming.", "qid": 27, "docid": "27z0z409", "rank": 11, "score": 0.8086327314376831}, {"content": "Title: Characterization of an asymptomatic cohort of SARS-COV-2 infected individuals outside of Wuhan, China Content: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, resulting in the coronavirus disease COVID-19) is highly transmissible among people. Asymptomatic infections are also an important source of infection. Here, we aimed to further clarify the epidemiologic and clinical characteristics of asymptomatic SARS-CoV-2 infections. METHODS: We identified close contacts of confirmed COVID-19 cases in northeast Chongqing who were RT-PCR+ yet remained asymptomatic throughout their infections. We stratified this cohort by normal versus abnormal findings on chest CT, and compared the strata regarding comorbidities, demographics, laboratory findings, viral transmission and other factors. RESULTS: Between January and March, 2020, we identified and hospitalized 279 RT-PCR+ contacts of COVID-19 patients. Of these, 63 (23%) remained asymptomatic until discharge; 29 had abnormal and 34 had normal chest CT findings. The mean cohort age was 39.3 years, and 87.3% had no comorbidities. Mean time to diagnosis after close contact with a COVID-19 index patient was 16.0 days (range 1 to 29), and 13.4 days and 18.7 days for those with abnormal and normal CT findings, respectively (p < 0.05). Nine subjects (14.3%) transmitted the virus to others; 4 and 5 were in the abnormal and normal CT strata, respectively. The median length of nucleic acid turning negative in asymptomatic COVID-19 patients was 13 days, compared to 10.4 days in those with normal chest CT (p < 0.05). CONCLUSIONS: A portion of these asymptomatic individuals, with and without abnormal chest CT scans, were capable of transmitting the virus to others. Given the frequency and potential infectiousness of asymptomatic infections, testing of traced contacts is essential. Studies of the impact of treatment on asymptomatic RT-PCR+ individuals on disease progression and transmission should be undertaken.", "qid": 27, "docid": "we4kfb8u", "rank": 12, "score": 0.8080399632453918}, {"content": "Title: Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China Content: Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. As a result, none of the 24 asymptomatic cases presented any obvious symptoms while nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue, etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and 5 (20.8%) presented stripe shadowing in the lungs. The remaining 7 (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These 7 cases were younger (median age: 14.0 years; P=0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. Overall, the asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-020-1661-4 and is accessible for authorized users.", "qid": 27, "docid": "iff8cuum", "rank": 13, "score": 0.8072001338005066}, {"content": "Title: A study on infectivity of asymptomatic SARS-CoV-2 carriers. Content: BACKGROUND An ongoing outbreak of coronavirus disease 2019 (COVID-19) has spread around the world. It is debatable whether asymptomatic COVID-19 virus carriers are contagious. We report here a case of the asymptomatic patient and present clinical characteristics of 455 contacts, which aims to study the infectivity of asymptomatic carriers. MATERIAL AND METHODS 455 contacts who were exposed to the asymptomatic COVID-19 virus carrier became the subjects of our research. They were divided into three groups: 35 patients, 196 family members and 224 hospital staffs. We extracted their epidemiological information, clinical records, auxiliary examination results and therapeutic schedules. RESULTS The median contact time for patients was four days and that for family members was five days. Cardiovascular disease accounted for 25% among original diseases of patients. Apart from hospital staffs, both patients and family members were isolated medically. During the quarantine, seven patients plus one family member appeared new respiratory symptoms, where fever was the most common one. The blood counts in most contacts were within a normal range. All CT images showed no sign of COVID-19 infection. No severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections was detected in 455 contacts by nucleic acid test. CONCLUSION In summary, all the 455 contacts were excluded from SARS-CoV-2 infection and we conclude that the infectivity of some asymptomatic SARS-CoV-2 carriers might be weak.", "qid": 27, "docid": "7xb7hj9u", "rank": 14, "score": 0.8067675828933716}, {"content": "Title: Delivery of infection from asymptomatic carriers of COVID-19 in a familial cluster Content: Abstract Objectives With the ongoing outbreak of COVID-19 around the world, it has become a worldwide health concern. One previous study reported a family cluster with asymptomatic transmission of COVID-19. Here, we report another series of cases and further demonstrate the repeatability of the transmission of COVID-19 by pre-symptomatic carriers. Methods A familial cluster of five patients associated with COVID-19 was enrolled in the hospital. We collected epidemiological and clinical characteristics, laboratory outcomes from electronic medical records, and also affirmed them with the patients and their families. Results Among them, three family members (Case 3/4/5) had returned from Wuhan. Additionally, two family members, those who had not travelled to Wuhan, also contracted COVID-19 after contacting with the other three family members. Case 1 developed severe pneumonia and was admitted to the ICU. Case 3 and Case 5 presented fever and cough on days 2 through 3 of hospitalization and had ground-glass opacity changes in their lungs. Case 4 presented with diarrhoea and pharyngalgia after admission without radiographic abnormalities. Case 2 presented no clinical or radiographic abnormalities. All the cases had an increasing level of C-reactive protein. Conclusions Our findings indicate that COVID-19 can be transmitted by asymptomatic carriers during the incubation period.", "qid": 27, "docid": "pgtvx6wb", "rank": 15, "score": 0.8065034747123718}, {"content": "Title: Clinical characteristics of asymptomatic and symptomatic patients with mild COVID-19 Content: OBJECTIVES: Detailed knowledge on the prevalence of asymptomatic cases of coronavirus disease 2019 (COVID-19) and the clinical characteristics of mild COVID-19 is essential for effective control of the COVID-19 pandemic. We determined the prevalence of asymptomatic cases of COVID-19 and characterized the symptoms of patients with mild COVID-19. METHODS: Study participants were recruited from a community facility designated for the isolation of patients without moderate-to-severe symptoms of COVID-19 in South Korea. The prevalence of asymptomatic patients at admission and the detailed symptoms of mild COVID-19 were evaluated through a questionnaire-based survey. Diagnosis of COVID-19 was confirmed by real-time RT-PCR. RESULTS: Of the 213 individuals with COVID-19, 41 (19.2%) were asymptomatic until admission. Among the remaining patients with mild COVID-19, the most common symptom was cough (40.1%; 69/172), followed by hyposmia (39.5%; 68/172) and sputum (39.5%; 68/172). Of the 68 individuals with hyposmia, 61 (90%) had accompanying symptoms such as hypogeusia, nasal congestion or rhinorrhoea. Fever (>37.5\u00b0C) was only observed in 20 (11.6%) individuals. CONCLUSIONS: As much as one-fifth of individuals with COVID-19 remained asymptomatic from exposure to admission. Hyposmia was quite frequent among individuals with mild COVID-19, but fever was not. Social distancing should be strongly implemented to prevent disease transmission from asymptomatic individuals or those with mild and inconspicuous symptoms.", "qid": 27, "docid": "p76gscn5", "rank": 16, "score": 0.80643630027771}, {"content": "Title: Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China Content: Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. As a result, none of the 24 asymptomatic cases presented any obvious symptoms while nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue, etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and 5 (20.8%) presented stripe shadowing in the lungs. The remaining 7 (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These 7 cases were younger (median age: 14.0 years; P=0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. Overall, the asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged.", "qid": 27, "docid": "nubzfw13", "rank": 17, "score": 0.8060189485549927}, {"content": "Title: Transmission and clinical characteristics of asymptomatic patients with SARS-CoV-2 infection Content: The 2019 novel coronavirus disease, SARS-CoV-2, is now spreading globally and is characterized by person-to-person transmission. However, it has recently been found that individuals infected with SARS-CoV-2 can be asymptomatic, and simultaneously a source of infection in others. The viral load detected in nasopharyngeal swabs of asymptomatic carriers is relatively high, with a great potential for transmission. More attention should be paid to the insidious spread of disease and harm contributed by asymptomatic SARS-CoV-2 carriers. To provide a theoretical basis for the accurate and early clinical identification of asymptomatic patients, this review objectively summarizes the epidemic status, transmission characteristics and clinical features of asymptomatic patients with SARS-CoV-2 infection.", "qid": 27, "docid": "m9xifjth", "rank": 18, "score": 0.8054405450820923}, {"content": "Title: [Advances on presymptomatic or asymptomatic carrier transmission of COVID-19] Content: COVID-19 is rapidly spreading. Patients in incubation period and healthy carriers are possible sources for transmission. However, such sources of infection cannot be effectively identified due to the symptoms absent. The research evidence is very lacking so far, although there are a few studies suggesting that presymptomatic or asymptomatic carrier may cause COVID-19 transmission. Nearly half of the literature is in the state of preprint without peer review. The question of \"the degree to which presymptomatic or asymptomatic infections can transmit\" is not fully understood. There is an urgent need to screen infected carriers in larger close contacts or in the general population, and assess their risk for transmission.", "qid": 27, "docid": "3fd81ovn", "rank": 19, "score": 0.8046388626098633}, {"content": "Title: [Advances on presymptomatic or asymptomatic carrier transmission of COVID-19]. Content: COVID-19 is rapidly spreading. Patients in incubation period and healthy carriers are possible sources for transmission. However, such sources of infection cannot be effectively identified due to the symptoms absent. The research evidence is very lacking so far, although there are a few studies suggesting that presymptomatic or asymptomatic carrier may cause COVID-19 transmission. Nearly half of the literature is in the state of preprint without peer review. The question of \"the degree to which presymptomatic or asymptomatic infections can transmit\" is not fully understood. There is an urgent need to screen infected carriers in larger close contacts or in the general population, and assess their risk for transmission.", "qid": 27, "docid": "xbv0b96w", "rank": 20, "score": 0.8046388626098633}, {"content": "Title: Comparison of clinical and epidemiological characteristics of asymptomatic and symptomatic SARS-CoV-2 infection: A multi-center study in Sichuan Province, China Content: OBJECTIVES: Asymptomatic infection of SARS-CoV-2 has become a concern worldwide. This study aims to compare the epidemiology and the clinical characteristics of SARS-CoV-2 infection in asymptomatic and symptomatic individuals. METHODS: A total of 511 confirmed SARS-CoV-2 infection cases, including 100 asymptomatic (by the time of the pathogenic tests) and 411 symptomatic individuals were consecutively enrolled from January 25 to February 20, 2020 from hospitals in 21 cities and 47 counties or districts in Sichuan Province. Epidemiological and clinical characteristics were compared. RESULTS: Compared to the symptomatic patients, the asymptomatic cases were younger (P < 0.001), had similar co-morbidity percentages (P = 0.609), and came from higher altitude areas with lower population mobility (P < 0.001) with better defined epidemiological history (P < 0.001). 27.4% of well-documented asymptomatic cases developed delayed symptoms after the pathogenic diagnosis. 60% of asymptomatic cases demonstrated findings of pneumonia on the initial chest CT, including well-recognized features of coronavirus disease-19. None of the asymptomatic individuals died. Two elderly individuals with initially asymptomatic infection developed severe symptoms during hospitalization. One case of possible virus transmission by a patient during the incubation period was highly suspected. CONCLUSIONS: The epidemiological and clinical findings highlight the significance of asymptomatic infection with SARS-CoV-2. Inspecting the epidemiological history would facilitate the identification of asymptomatic cases. Evidence supports the chest CT scans for confirmed asymptomatic cases to evaluate the extent of lung involvement.", "qid": 27, "docid": "h3fnztro", "rank": 21, "score": 0.8046040534973145}, {"content": "Title: Follow up investigation of asymptomatic COVID-19 cases at diagnosis in Busan, Korea. Content: Objectives The objective of the study was to conduct a follow-up investigation of 10 asymptomatic patients at diagnosis among the 98 confirmed COVID-19 cases reported in Busan between February 21 and March 13, 2020 to determine whether asymptomatic infection and transmission during asymptomatic period are possible. Methods The study analyzed 10 asymptomatic, confirmed COVID-19 cases to determine whether asymptomatic infection is possible. We conducted in-depth interviews with patients and guardians; interviews with primary physicians; review of medical records and drug utilization review (DUR) reports; and base station-based location tracking. Results Among the 98, confirmed COVID-19 cases reported in Busan, the study analyzed 10 (10.2%) asymptomatic patients at diagnosis. The Results confirmed that two (2.0%) patients reported to be asymptomatic during the initial epidemiological investigation, but turned symptomatic before diagnosis as per the in-depth interview results. Four cases (4.0%) of early detection led to confirmed diagnosis during the incubation period and presentation of symptoms after diagnosis. In addition, the remaining four patients (4.0%), having no subjective symptoms nor specific findings on chest radiography and Computed Tomography, remained asymptomatic until the isolation order was lifted. With regard to whether transmission during the asymptomatic period is possible, it was found that one out of 23 household contacts of the confirmed patients was identified as an additional confirmed case after coming in close contact with an index patient during the presymptomatic period. Conclusion Among the 98 confirmed cases, asymptomatic infection was confirmed in four cases (4.0%). In addition, there was one additional confirmed case in which the patient was a family member who came in close contact with an index patient during the incubation period, thereby confirming that transmission during the asymptomatic period is possible. The possibility of transmission during the asymptomatic period has been confirmed; therefore, it is necessary to review the measures for expanding contact tracing that is currently being applied starting one day prior to the onset of symptoms.", "qid": 27, "docid": "8zw79b2f", "rank": 22, "score": 0.8046011924743652}, {"content": "Title: Follow up investigation of asymptomatic COVID-19 cases at diagnosis in Busan, Korea Content: Objectives: The objective of the study was to conduct a follow-up investigation of 10 asymptomatic patients at diagnosis among the 98 confirmed COVID-19 cases reported in Busan between February 21 and March 13, 2020 to determine whether asymptomatic infection and transmission during asymptomatic period are possible. Methods: The study analyzed 10 asymptomatic, confirmed COVID-19 cases to determine whether asymptomatic infection is possible. We conducted in-depth interviews with patients and guardians; interviews with primary physicians; review of medical records and drug utilization review (DUR) reports; and base station-based location tracking. Results: Among the 98, confirmed COVID-19 cases reported in Busan, the study analyzed 10 (10.2%) asymptomatic patients at diagnosis. The Results confirmed that two (2.0%) patients reported to be asymptomatic during the initial epidemiological investigation, but turned symptomatic before diagnosis as per the in-depth interview results. Four cases (4.0%) of early detection led to confirmed diagnosis during the incubation period and presentation of symptoms after diagnosis. In addition, the remaining four patients (4.0%), having no subjective symptoms nor specific findings on chest radiography and Computed Tomography, remained asymptomatic until the isolation order was lifted. With regard to whether transmission during the asymptomatic period is possible, it was found that one out of 23 household contacts of the confirmed patients was identified as an additional confirmed case after coming in close contact with an index patient during the presymptomatic period. Conclusion: Among the 98 confirmed cases, asymptomatic infection was confirmed in four cases (4.0%). In addition, there was one additional confirmed case in which the patient was a family member who came in close contact with an index patient during the incubation period, thereby confirming that transmission during the asymptomatic period is possible. The possibility of transmission during the asymptomatic period has been confirmed; therefore, it is necessary to review the measures for expanding contact tracing that is currently being applied starting one day prior to the onset of symptoms.", "qid": 27, "docid": "op7ohlv3", "rank": 23, "score": 0.8027917146682739}, {"content": "Title: Asymptomatic patients as a source of COVID-19 infections: A systematic review and meta-analysis. Content: BACKGROUND Coronavirus Disease 2019 (COVID-19) is characterised by an unpredictable disease course, ranging from asymptomatic infections to severe, life-threating manifestations. Asymptomatic COVID-19 infections have been described, and the aim of this systematic review was to summarise their presentation form. METHODS We searched PubMed\u00ae and Google\u00ae (1 December 2019 to 29 March 2020) and extracted age, laboratory findings, and computed tomography (CT) investigations. Pooled incidence rates of clinical characteristics were analysed using random effects models. RESULTS In total, 506 patients from 34 studies (68 single cases and 438 from case series) with an asymptomatic course were identified. Patients with normal radiology were younger (19.59 \u00b1 17.17 years) than patients with abnormal radiology (39.14 \u00b1 26.70 years) (p value = 0.013). Despite being asymptomatic, CT investigations revealed abnormalities in 62.2% of the cases and ground glass opacities were most frequently observed (43.09% by meta-analysis). Most studies reported normal laboratory findings (61.74% by meta-analysis). CONCLUSIONS More than half of patients without any symptoms present with CT abnormalities. Asymptomatic patients may be contagious and thus a potential source of transmission of COVID-19.", "qid": 27, "docid": "szzd7acz", "rank": 24, "score": 0.8025879859924316}, {"content": "Title: Asymptomatic patients as a source of COVID-19 infections: A systematic review and meta-analysis Content: BACKGROUND: Coronavirus Disease 2019 (COVID-19) is characterised by an unpredictable disease course, ranging from asymptomatic infections to severe, life-threating manifestations. Asymptomatic COVID-19 infections have been described, and the aim of this systematic review was to summarise their presentation form. METHODS: We searched PubMed\u00ae and Google\u00ae (1 December 2019 to 29 March 2020) and extracted age, laboratory findings, and computed tomography (CT) investigations. Pooled incidence rates of clinical characteristics were analysed using random effects models. RESULTS: In total, 506 patients from 34 studies (68 single cases and 438 from case series) with an asymptomatic course were identified. Patients with normal radiology were younger (19.59 \u00b1 17.17 years) than patients with abnormal radiology (39.14 \u00b1 26.70 years) (p value = 0.013). Despite being asymptomatic, CT investigations revealed abnormalities in 62.2% of the cases and ground glass opacities were most frequently observed (43.09% by meta-analysis). Most studies reported normal laboratory findings (61.74% by meta-analysis). CONCLUSIONS: More than half of patients without any symptoms present with CT abnormalities. Asymptomatic patients may be contagious and thus a potential source of transmission of COVID-19.", "qid": 27, "docid": "59a0v3sg", "rank": 25, "score": 0.8016149401664734}, {"content": "Title: Comparison of clinical and epidemiological characteristics of asymptomatic and symptomatic SARS-CoV-2 infection: A multi-center study in Sichuan Province, China. Content: OBJECTIVES Asymptomatic infection of SARS-CoV-2 has become a concern worldwide. This study aims to compare the epidemiology and the clinical characteristics of SARS-CoV-2 infection in asymptomatic and symptomatic individuals. METHODS A total of 511 confirmed SARS-CoV-2 infection cases, including 100 asymptomatic (by the time of the pathogenic tests) and 411 symptomatic individuals were consecutively enrolled from January 25 to February 20, 2020 from hospitals in 21 cities and 47 counties or districts in Sichuan Province. Epidemiological and clinical characteristics were compared. RESULTS Compared to the symptomatic patients, the asymptomatic cases were younger (P < 0.001), had similar co-morbidity percentages (P = 0.609), and came from higher altitude areas with lower population mobility (P < 0.001) with better defined epidemiological history (P < 0.001). 27.4% of well-documented asymptomatic cases developed delayed symptoms after the pathogenic diagnosis. 60% of asymptomatic cases demonstrated findings of pneumonia on the initial chest CT, including well-recognized features of coronavirus disease-19. None of the asymptomatic individuals died. Two elderly individuals with initially asymptomatic infection developed severe symptoms during hospitalization. One case of possible virus transmission by a patient during the incubation period was highly suspected. CONCLUSIONS The epidemiological and clinical findings highlight the significance of asymptomatic infection with SARS-CoV-2. Inspecting the epidemiological history would facilitate the identification of asymptomatic cases. Evidence supports the chest CT scans for confirmed asymptomatic cases to evaluate the extent of lung involvement.", "qid": 27, "docid": "gqb0rr5t", "rank": 26, "score": 0.7996755838394165}, {"content": "Title: How the asymptomatic population is influencing the COVID-19 outbreak in India? Content: According to the current perception, symptomatic, presymptomatic, and asymptomatic infectious persons can infect the healthy population susceptible to the SARS-Cov-2. More importantly, various reports indicate that the number of asymptomatic cases can be several-fold higher than the reported symptomatic cases. In this article, we take the reported cases in India and various states within the country as the specimen to understand the progression of the COVID-19. Employing a modified SEIRD model, we predict the spread of COVID-19 by the symptomatic as well as asymptomatic infectious population. Considering reported infection primarily due to symptomatic we compare the model predicted results with the available data to estimate the dynamics of the asymptomatically infected population. Our data indicate that in the absence of the asymptomatic infectious population, the number of symptomatic cases would have been much less. Therefore, the current progress of the symptomatic infection can be reduced by quarantining the asymptomatically infectious population via extensive or random testing. This study is motivated strictly towards academic pursuit; this theoretical investigation is not meant for influencing policy decisions or public health practices.", "qid": 27, "docid": "2ohq74mq", "rank": 27, "score": 0.7977309226989746}, {"content": "Title: Challenges of managing the asymptomatic carriers of SARS-CoV-2 Content: Abstract After an outbreak in Wuhan, China, a growing number of countries are now suffering from an epidemic by SARS-CoV-2, which causes COVID-19. Undoubtedly, reports of the skyrocketing global spread of COVID-19 has shocked people globally, from Japan to the United States.Presently, the World Health Organization indicates that fatality due to COVID-19 is about 2%, inferring that many positive subjects may potentially overcome the illness with mild influenza-like symptoms and no need for hospitalization at intensive-care units. Because COVID-19 is completely new to the human immune system, many throughout the world are likely vulnerable to becoming sick after their initial exposure to SARSCoV-2. Besides hospitalized cases, many individuals are likely asymptomatic but potentially carry the virus. While our knowledge about carriers and their virus shedding is deficient, some studies modelling the viral transmission have considered the potential contribution of the asymptomatic carriers. Protocols for managing asymptomatic cases, for example for controlling them to restrict their contact with healthy people at public places or private residences, have not been established.In-house quarantine may as well be applicable to asymptomatic cases if they could be identified and diagnosed. Presumably now, the asymptomatic subjects potentially contribute to the transmission of COVID-19 without their knowledge, intention or being diagnosed as carriers. Thus, managing the asymptomatic cases, who can carry and likely transmit the virus, is a major healthcare challenge while a pandemic is looming.", "qid": 27, "docid": "c5q7l7en", "rank": 28, "score": 0.7975742816925049}, {"content": "Title: Clinical Characteristics of 24 Asymptomatic Infections with COVID-19 Screened among Close Contacts in Nanjing, China Content: Background: Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Methods: Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. Findings: None of the 24 asymptomatic cases presented any obvious symptoms before nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue and etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and five (20.8%) presented stripe shadowing in the lungs. The remaining seven (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These seven cases were younger (median age: 14.0 years; P = 0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. Interpretation: The asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged.", "qid": 27, "docid": "ofoqk100", "rank": 29, "score": 0.7974827289581299}, {"content": "Title: The incidence of the novel coronavirus SARS-CoV-2 among asymptomatic patients: a systematic review Content: BACKGROUND: the recent outbreak of the coronavirus disease 2019 (COVID-19) has quickly spread globally since its discovery in Wuhan, China, in December 2019. A comprehensive strategy, including surveillance, diagnostics, research, and clinical treatment is urgently needed to win the battle against COVID-19. Recently, numerous studies reported the incidence of SARS-CoV-2 in asymptomatic patients. Yet, the incidence and viral transmission from the asymptomatic cases are not apparent yet. AIM: this study aims to systematically review the published literature on SARS-CoV-2 in the asymptomatic patients to estimate the incidence of COVID-19 among asymptomatic cases, as well as describe its epidemiological and clinical significance. METHOD: the literature was searched through four scientific databases: PubMed, Web of Science, Scopus, and Science Direct. RESULTS: a total of 63 studies satisfied the inclusion criteria where the majority of the reported studies were from China. However, there was a lack of SARS-CoV-2 epidemiological studies from several countries worldwide, tracing the actual incidence of COVID-19, especially in asymptomatic patients. Studies with a large sample size (n>1000) estimated that percentage of people contracting SARS-CoV-2 and are likely to be asymptomatic ranges from 1.2-12.9%. However, the other studies with a smaller sample size reported a much higher incidence and indicated that up to 87.9% of COVID-19 infected individuals could be asymptomatic. Most of these studies indicated that asymptopatics are a potential source of infection to the community. CONCLUSION: this review highlighted the need for more robust and well-designed studies to better estimate COVID-19 incidence among asymptomatic patients worldwide. The early identification of the asymptomatic cases, as well as monitoring and tracing close contact, could help in mitigating the spread of COVID-19.", "qid": 27, "docid": "6sf5xepa", "rank": 30, "score": 0.7966833710670471}, {"content": "Title: The contribution of asymptomatic SARS-CoV-2 infections to transmission - a model-based analysis of the Diamond Princess outbreak Content: Background: Some key gaps in the understanding of SARS-CoV-2 infection remain. One of them is the contribution to transmission from individuals experiencing asymptomatic infections. We aimed to characterise the proportion and infectiousness of asymptomatic infections using data from the outbreak on the Diamond Princess cruise ship. Methods: We used a transmission model of COVID-19 with asymptomatic and presymptomatic states calibrated to outbreak data from the Diamond Princess, to quantify the contribution of asymptomatic infections to transmission. Data available included the date of symptom onset for symptomatic disease for passengers and crew, the number of symptom agnostic tests done each day, and date of positive test for asymptomatic and presymptomatic individuals. Findings: On the Diamond Princess 74% (70-78%) of infections proceeded asymptomatically, i.e. a 1:3.8 case-to-infection ratio. Despite the intense testing 53%, (51-56%) of infections remained undetected, most of them asymptomatic. Asymptomatic individuals were the source for 69% (20-85%) of all infections. While the data did not allow identification of the infectiousness of asymptomatic infections, assuming no or low infectiousness resulted in posterior estimates for the net reproduction number of an individual progressing through presymptomatic and symptomatic stages in excess of 15. Interpretation: Asymptomatic SARS-CoV-2 infections may contribute substantially to transmission. This is essential to consider for countries when assessing the potential effectiveness of ongoing control measures to contain COVID-19.", "qid": 27, "docid": "eerqrqwk", "rank": 31, "score": 0.796660304069519}, {"content": "Title: Testing Asymptomatic Emergency Department Patients for Coronavirus of 2019 (COVID\u201019) in a Low Prevalence Region Content: The first cases of Coronavirus of 2019 (COVID\u201019) were reported in Wuhan, China in December 2019(1). The literature demonstrates geographical variation with regards to estimates of infection incidence, suggesting that COVID\u201019 has been underdiagnosed in certain regions(2,3). The rate of asymptomatic infection has been estimated to be as high as 30.8%, which may help explain variation in incidence, particularly in regions with differing screening practices (3). Transmission of COVID\u201019 by asymptomatic carriers has been reported in multiple family units, indicating that this mode of infection is important in understanding disease epidemiology and population risk(4,5).", "qid": 27, "docid": "wzb6qv7y", "rank": 32, "score": 0.7964389324188232}, {"content": "Title: Identification of RT-PCR-Negative Asymptomatic COVID-19 Patients via Serological Testing Content: Asymptomatic individuals with coronavirus disease (COVID-19) have been identified via nucleic acid testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, the epidemiologic characteristics and viral shedding pattern of asymptomatic patients remain largely unknown. In this study, serological testing was applied when identifying nine asymptomatic cases of COVID-19 who showed persistent negative RT-PCR test results for SARS-CoV-2 nucleic acid and no symptoms of COVID-19. Two asymptomatic cases were presumed to be index patients who had cleared the virus when their close contacts developed symptoms of COVID-19. Three of the asymptomatic cases were local individuals who spontaneously recovered before their presumed index patients developed symptoms of COVID-19. This report presents the epidemiologic and clinical characteristics of asymptomatic individuals with SARS-CoV-2 infection that were undetected on RT-PCR tests in previous epidemiologic investigations probably due to the transient viral shedding duration.", "qid": 27, "docid": "mu2v9o1p", "rank": 33, "score": 0.794546365737915}, {"content": "Title: The incidence of the novel coronavirus SARS-CoV-2 among asymptomatic patients: a systematic review Content: BACKGROUND: the recent outbreak of the coronavirus disease 2019 (COVID\u201019) has quickly spread globally since its discovery in Wuhan, China, in December 2019. A comprehensive strategy, including surveillance, diagnostics, research, and clinical treatment is urgently needed to win the battle against COVID-19. Recently, numerous studies reported the incidence of SARS-CoV-2 in asymptomatic patients. Yet, the incidence and viral transmission from the asymptomatic cases are not apparent yet. AIM: this study aims to systematically review the published literature on SARS-CoV-2 in the asymptomatic patients to estimate the incidence of COVID-19 among asymptomatic cases, as well as describe its epidemiological and clinical significance. METHOD: the literature was searched through four scientific databases: PubMed, Web of Science, Scopus, and Science Direct. RESULTS: a total of 63 studies satisfied the inclusion criteria where the majority of the reported studies were from China. However, there was a lack of SARS-CoV-2 epidemiological studies from several countries worldwide, tracing the actual incidence of COVID-19, especially in asymptomatic patients. Studies with a large sample size (n>1000) estimated that percentage of people contracting SARS-CoV-2 and are likely to be asymptomatic ranges from 1.2-12.9%. However, the other studies with a smaller sample size reported a much higher incidence and indicated that up to 87.9% of COVID-19 infected individuals could be asymptomatic. Most of these studies indicated that asymptopatics are a potential source of infection to the community. CONCLUSION: this review highlighted the need for more robust and well-designed studies to better estimate COVID-19 incidence among asymptomatic patients worldwide. The early identification of the asymptomatic cases, as well as monitoring and tracing close contact, could help in mitigating the spread of COVID-19.", "qid": 27, "docid": "lgze4zex", "rank": 34, "score": 0.7941283583641052}, {"content": "Title: COVID-19 Pneumonia in Asymptomatic Trauma Patients;Report of 8 Cases Content: We are currently involved in the novel coronavirus 2019 (COVID-19) pandemic A considerable number of COVID-19 infected cases are asymptomatic but they can transmit the disease to others, especially healthcare workers In this study, we reported 8 incidentally detected cases of COVID-19 pneumonia in chest computed tomography (CT) scan of patients referred to emergency department following multiple trauma without any respiratory symptoms", "qid": 27, "docid": "ux2a4pi3", "rank": 35, "score": 0.7937697172164917}, {"content": "Title: Clinical Outcomes in 55 Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Who Were Asymptomatic at Hospital Admission in Shenzhen, China Content: An epidemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread unexpectedly in Wuhan, Hubei Province, China, since December 2019. There are few reports about asymptomatic contacts of infected patients identified as positive for SARS-CoV-2 through screening. We studied the epidemiological and clinical outcomes in 55 asymptomatic carriers who were laboratory confirmed to be positive for SARS-CoV-2 through nucleic acid testing of pharyngeal swab samples. The asymptomatic carriers seldom occurred among young people (aged 18\u201329 years) who had close contact with infected family members. In the majority of patients, the outcome was mild or ordinary 2019 novel coronavirus disease during hospitalization.", "qid": 27, "docid": "fjnhoai4", "rank": 36, "score": 0.7923001050949097}, {"content": "Title: Clinical Outcomes in 55 Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Who Were Asymptomatic at Hospital Admission in Shenzhen, China Content: An epidemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread unexpectedly in Wuhan, Hubei Province, China, since December 2019. There are few reports about asymptomatic contacts of infected patients identified as positive for SARS-CoV-2 through screening. We studied the epidemiological and clinical outcomes in 55 asymptomatic carriers who were laboratory confirmed to be positive for SARS-CoV-2 through nucleic acid testing of pharyngeal swab samples. The asymptomatic carriers seldom occurred among young people (aged 18-29 years) who had close contact with infected family members. In the majority of patients, the outcome was mild or ordinary 2019 novel coronavirus disease during hospitalization.", "qid": 27, "docid": "tj5pv57m", "rank": 37, "score": 0.7922754883766174}, {"content": "Title: Estimating the extent of true asymptomatic COVID-19 and its potential for community transmission: systematic review and meta-analysis Content: Background: The prevalence of true asymptomatic COVID-19 cases is critical to policy makers considering the effectiveness of mitigation measures against the SARS-CoV-2 pandemic. We aimed to synthesize all available research on the asymptomatic rates and transmission rates where possible. Methods: We searched PubMed, Embase, Cochrane COVID-19 trials, and European PMC for pre-print platforms such as MedRxiv. We included primary studies reporting on asymptomatic prevalence where: (a) the sample frame includes at-risk population, and (b) there was sufficiently long follow up to identify pre-symptomatic cases. Meta-analysis used fixed effect and random effects models. Results: We screened 571 articles and included five low risk-of-bias studies from three countries (China (2), USA (2), Italy (1)) that tested 9,242 at-risk people, of which 413 were positive and 65 were asymptomatic. Diagnosis in all studies was confirmed using a RT-qPCR test. The proportion of asymptomatic cases ranged from 6% to 41%. Meta-analysis (fixed effect) found that the proportion of asymptomatic cases was 16% (95% CI: 12% - 20%) overall; higher in non-aged care 19% (15% - 24%), and lower in long-term aged care 8% (4% - 14%). Two studies provided direct evidence of forward transmission of the infection by asymptomatic cases but suggested lower rates than symptomatic cases. Conclusion: Our estimates of the prevalence of asymptomatic COVID-19 cases are lower than many highly publicized studies, but still substantial. Further robust epidemiological evidence is urgently needed, including in sub-populations such as children, to better understand the importance of asymptomatic cases for driving spread of the pandemic.", "qid": 27, "docid": "li8kvzdh", "rank": 38, "score": 0.789986252784729}, {"content": "Title: Viral dynamics in asymptomatic patients with COVID-19 Content: Abstract Data are limited on the viral load, viral shedding patterns and potential infectivity of asymptomatic patients (APs) with coronavirus disease 2019 (COVID-19). We included 31 adult patients who were virologically confirmed to have COVID-19 but were asymptomatic on admission. Among these 31 patients, 22 presented symptoms after admission and were defined as asymptomatic patients in incubation period (APIs); the other 9 patients remained asymptomatic during hospitalization and were defined as asymptomatic patients (APs). The cycle threshold (Ct) values of APs (39.0, IQR 37.5-39.5) was significantly higher than those of APIs (34.5, IQR 32.2-37.0), which indicated a lower viral load in APs, but the duration of viral shedding remained similar between the two groups (7 days IQR 5-14 vs. 8 days IQR 5-16). The study findings demonstrated that although they have a lower viral load, APs with COVID-19 still have certain period of viral shedding, which suggests the possibility of transmission during their asymptomatic period. Further longitudinal surveillance of these asymptomatic cases via virus nucleic acid tests are warranted.", "qid": 27, "docid": "bi3bl5qt", "rank": 39, "score": 0.7887566685676575}, {"content": "Title: [Asymptomatic and pre-symptomatic cases of COVID-19 contribution to spreading the epidemic and need for targeted control strategies]. Content: The asymptomatic carrier state of COVID-19 has become a topic of concern for preventing a possible epidemic rebound. This review describes and defines the COVID-19 asymptomatic carrier state and outlines methods for identifying counting and reporting these cases. The author elaborates that the asymptomatic carrier state can be further divided into asymptomatic infection and pre-symptomatic infection after extended follow-up based on the nature of disease progression. The author presents the limited available data about infectiousness of asymptomatic and pre-symptomatic cases and their possible contributions to the overall epidemic of COVID-19 observed so far in China. Challenges of a possible second epidemic wave of COVID-19 caused by asymptomatic and pre-symptomatic cases are discussed and suggestions for control strategies and scientific research are provided.", "qid": 27, "docid": "ghasrwqc", "rank": 40, "score": 0.788183867931366}, {"content": "Title: Risk factors for disease progression in COVID-19 patients Content: BACKGROUND: Coronavirus disease (COVID-19) is rapidly spreading worldwide. Although 10-20% of patients with COVID-19 have severe symptoms, little is known about the risk factors related to the aggravation of COVID-19 symptoms from asymptomatic or mild to severe disease states. METHODS: This retrospective study included 211 patients who were asymptomatic or with mild presentations of COVID-19. We evaluated the differences in demographic and clinical data between the cured (discharged to home) and transferred (aggravated to severe-stage COVID-19) groups. RESULTS: A multivariate logistic analysis showed that body temperature, chills, initial chest X-ray findings, and the presence of diabetes were significantly associated with predicting the progression to severe stage of COVID-19 (p < 0.05). The odds ratio of transfer in patients with COVID-19 increased by 12.7-fold for abnormal findings such as haziness or consolidation in initial chest X-ray, 6.32-fold for initial symptom of chills, and 64.1-fold for diabetes. CONCLUSIONS: Even if patients are asymptomatic or have mild symptoms, clinicians should closely observe patients with COVID-19 presenting with chills, body temperature > 37.5 \u00b0C, findings of pneumonia in chest X-ray, or diabetes.", "qid": 27, "docid": "88n6hwyo", "rank": 41, "score": 0.7875621318817139}, {"content": "Title: Risk factors for disease progression in COVID-19 patients Content: BACKGROUND: Coronavirus disease (COVID-19) is rapidly spreading worldwide. Although 10\u201320% of patients with COVID-19 have severe symptoms, little is known about the risk factors related to the aggravation of COVID-19 symptoms from asymptomatic or mild to severe disease states. METHODS: This retrospective study included 211 patients who were asymptomatic or with mild presentations of COVID-19. We evaluated the differences in demographic and clinical data between the cured (discharged to home) and transferred (aggravated to severe-stage COVID-19) groups. RESULTS: A multivariate logistic analysis showed that body temperature, chills, initial chest X-ray findings, and the presence of diabetes were significantly associated with predicting the progression to severe stage of COVID-19 (p < 0.05). The odds ratio of transfer in patients with COVID-19 increased by 12.7-fold for abnormal findings such as haziness or consolidation in initial chest X-ray, 6.32-fold for initial symptom of chills, and 64.1-fold for diabetes. CONCLUSIONS: Even if patients are asymptomatic or have mild symptoms, clinicians should closely observe patients with COVID-19 presenting with chills, body temperature > 37.5 \u00b0C, findings of pneumonia in chest X-ray, or diabetes.", "qid": 27, "docid": "2ootfjhk", "rank": 42, "score": 0.7875353097915649}, {"content": "Title: Chest Computed Tomography Findings in Asymptomatic Patients with COVID-19 Content: Background: Little is known about the damage to the respiratory system in asymptomatic patients with coronavirus disease (COVID-19). Objective: Herein, we evaluated the findings of chest computed tomography (CT) and radiography in patients with COVID-19 who were asymptomatic. Methods: We retrospectively investigated patients with a confirmed diagnosis of COVID-19 but who did not show any symptoms. Among the 139 patients with COVID-19 who were hospitalized, 10 (7.2%) were asymptomatic. Their chest CT and radiographic findings were analyzed. Results: In the results, all patients (100%) had ground glass opacity (GGO) on chest CT. Further, the GGO lesions were predominantly distributed peripherally and posteriorly in all patients. In 9 (90%) patients, the GGO lesions were combined with reticular opacity. Air-bronchogram due to bronchiolectasis surrounded by GGO was observed in 8 patients (80%). Additionally, the lung lesions were dominant on the right side in all patients. Conclusions: In conclusion, considering our results that the lung is affected in asymptomatic patients, it will be necessary to extend the indications of COVID-19 testing for effective management of COVID-19 during the pandemic.", "qid": 27, "docid": "4hfmst53", "rank": 43, "score": 0.7859755754470825}, {"content": "Title: Transmission potential of asymptomatic and paucisymptomatic SARS-CoV-2 infections: a three-family cluster study in China Content: Data concerning the transmission of SARS-CoV-2 in asymptomatic and paucisymptomatic patients are lacking. We report a three-family cluster of infections involving asymptomatic and paucisymptomatic transmission. Eight (53%) of 15 members from three families were confirmed with SARS-CoV-2 infection. Of eight patients, three were asymptomatic and one was paucisymptomatic. An asymptomatic mother transmitted the virus to her son, and a paucisymptomatic father transmitted the virus to his three-month-old daughter. SARS-CoV-2 was detected in the environment of one household. The complete genomes of SARS-CoV-2 from the patients were >99.9% identical and were clustered with other SARS-CoV-2 sequences reported from China and other countries.", "qid": 27, "docid": "uofy7jyx", "rank": 44, "score": 0.7859072685241699}, {"content": "Title: A retrospective analysis of the epidemiology, clinical manifestations, and imaging characteristics of familial cluster-onset COVID-19. Content: Background The coronavirus disease 2019 (COVID-19) virus has a high incidence rate and strong infectivity. The diagnosis and evaluation of familial outbreaks requires a collective consideration of epidemiological history, molecular detection methods, chest computed tomography (CT), and clinical symptoms. Methods A group of family patients with COVID-19 diagnosed in Guizhou, China, in February 2020, was retrospectively analyzed. As of March 1, all patients in the group have been discharged from hospital. This study tracked all patients in the group. We report the epidemiology, radiological characteristics, treatment, and clinical outcomes of these patients. Results We collected a group of 8 clustered cases (3 men and 5 women) from a family with confirmed COVID-19 infection. In the first admission diagnosis, according to the degree of clinical symptoms, the 8 patients were defined as mild type (4/8) or moderate type (4/8). They were also divided according to the CT findings into early period (1/8), progressive period (3/8), and negative on CT scan (4/8); for the first 4 patients, the corresponding CT image scores were 1, 4, 5, and 5 respectively. In this group of COVID-19 patients, half of the patients showed occult clinical manifestations and negative CT performance. We defined these patients as COVID-19-infected patients, or asymptomatic carriers. Conclusions The family cluster analysis indicated that COVID-19-infected patients (asymptomatic carriers) and symptomatic COVID-19 patients are distinct but coexistent. This may indicate that the infectivity and virulence of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has decreased. In order to block the transmission pathway of this virus before it spreads, we need to identify the presence of asymptomatic carriers as early as possible.", "qid": 27, "docid": "gukvgvce", "rank": 45, "score": 0.7857910394668579}, {"content": "Title: The prevalence of antibodies to SARS-CoV-2 in asymptomatic healthcare workers with intensive exposure to COVID-19 Content: The prevalence of asymptomatic SARS-CoV-2 infection in healthcare workers with intensive exposure to COVID-19 is unclear. In this study, we investigated the seroprevalence of SARS-CoV-2 in 797 asymptomatic healthcare workers with intensive exposure to COVID-19 patients in Wuhan, China. Positive IgG was detected from 35 asymptomatic healthcare workers, and the prevalence of antibodies to SARS-CoV-2 in asymptomatic healthcare workers was 4.39% (35/797). None of them developed COVID-19 until May 15. 33 of them have performed at least one chest CT scan showing no viral pneumonia features, and 16 have finished at least one-time SARS-CoV-2 RNA detection with negative results. When contacting with the patients, 15 of them dressed with full personal protective equipment (PPE), and 16 worn N95 mask and gown. To the best of our knowledge, this is the first investigation reported that the seroprevalence of SARS-CoV-2 was 4.39% in asymptomatic healthcare workers with applied PPE in a high epidemic area, which may provide useful information of estimating asymptomatic infection rate in general population.", "qid": 27, "docid": "9e8ra3sa", "rank": 46, "score": 0.7849855422973633}, {"content": "Title: The natural history and transmission potential of asymptomatic SARS-CoV-2 infection Content: BACKGROUND: Little is known about the natural history of asymptomatic SARS-CoV-2 infection or its contribution to infection transmission. METHODS: We conducted a prospective study at a quarantine center for COVID-19 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with RT-PCR-confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrolment and daily nasopharyngeal throat swabs (NTS) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals. RESULTS: Between March 10(th) and April 4(th), 2020, 14,000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13(43%) never had symptoms and 17(57%) were symptomatic. 17(57%) participants acquired their infection outside Vietnam. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS samples collected at enrolment (8/13 (62%) vs. 17/17 (100%) P=0.02). SARS-CoV-2 RNA was detected in 20/27 (74%) available saliva; 7/11 (64%) in the asymptomatic and 13/16 (81%) in the symptomatic group (P=0.56). Analysis of the probability of RT-PCR positivity showed asymptomatic participants had faster viral clearance than symptomatic participants (P<0.001 for difference over first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit the infection to up to four contacts. CONCLUSIONS: Asymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTS. NTS viral loads fall faster in asymptomatic individuals, but they appear able to transmit the virus to others.", "qid": 27, "docid": "bfe8e0wu", "rank": 47, "score": 0.7848775386810303}, {"content": "Title: Clinical characteristics of COVID-19 in 104 people with SARS-CoV-2 infection on the Diamond Princess cruise ship: a retrospective analysis Content: BACKGROUND: The ongoing COVID-19 pandemic is a global threat. Identification of markers for symptom onset and disease progression is a pressing issue. We described the clinical features of people infected on board the Diamond Princess cruise ship who were diagnosed with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or mild or severe COVID-19, on admission to the Self-Defense Forces Central Hospital (Tokyo, Japan) and at the end of observation. METHODS: This retrospective, single-centre study included participants with laboratory-detected SARS-CoV-2 infection who were admitted to the Self-Defense Forces Central Hospital from Feb 11 to Feb 25, 2020. Clinical records, laboratory data, and radiological findings were analysed. Clinical outcomes were followed up until discharge or Feb 26, 2020, whichever came first. We defined asymptomatic infection as SARS-CoV-2 infection with no history of clinical signs and symptoms, severe COVID-19 as clinical symptoms of pneumonia (dyspnoea, tachypnoea, peripheral capillary oxygen saturation <93%, and need for oxygen therapy), and mild COVID-19 as all other symptoms. Clinical features on admission were compared among patients with different disease severity, including asymptomatic infection, at the end of observation. We used univariable analysis to identify factors associated with symptomatic illness among asymptomatic people infected with SARS-CoV-2 and disease progression in patients with COVID-19. FINDINGS: Among the 104 participants included in the final analysis, the median age was 68 years (IQR 47-75) and 54 (52%) were male. On admission, 43 (41%) participants were classified as asymptomatic, 41 (39%) as having mild COVID-10, and 20 (19%) as having severe COVID-19. At the end of observation, 33 (32%) participants were confirmed as being asymptomatic, 43 (41%) as having mild COVID-19, and 28 (27%) as having severe COVID-19. Serum lactate hydrogenase concentrations were significantly higher in the ten participants who were asymptomatic on admission but developed symptomatic COVID-19 compared with the 33 participants who remained asymptomatic throughout the observation period (five [50%] vs four [12%] participants; odds ratio 7\u00b725, 95% CI 1\u00b743-36\u00b770; p=0\u00b7020). Compared with patients with mild disease at the end of observation, patients with severe COVID-19 were older (median age 73 years [IQR 55-77] vs 60 years [40-71]; p=0\u00b7028) and had more frequent consolidation on chest CT (13 [46%] of 28 vs nine [21%] of 43; p=0\u00b7035) and lymphopenia (16 [57%] vs ten [23%]; p=0\u00b70055) on admission. INTERPRETATION: Older age, consolidation on chest CT images, and lymphopenia might be risk factors for disease progression of COVID-19 and contribute to improved clinical management. FUNDING: None.", "qid": 27, "docid": "2i1q54nd", "rank": 48, "score": 0.784060001373291}, {"content": "Title: Clinical characteristics of COVID-19 in 104 people with SARS-CoV-2 infection on the Diamond Princess cruise ship: a retrospective analysis Content: BACKGROUND: The ongoing COVID-19 pandemic is a global threat. Identification of markers for symptom onset and disease progression is a pressing issue. We described the clinical features of people infected on board the Diamond Princess cruise ship who were diagnosed with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or mild or severe COVID-19, on admission to the Self-Defense Forces Central Hospital (Tokyo, Japan) and at the end of observation. METHODS: This retrospective, single-centre study included participants with laboratory-detected SARS-CoV-2 infection who were admitted to the Self-Defense Forces Central Hospital from Feb 11 to Feb 25, 2020. Clinical records, laboratory data, and radiological findings were analysed. Clinical outcomes were followed up until discharge or Feb 26, 2020, whichever came first. We defined asymptomatic infection as SARS-CoV-2 infection with no history of clinical signs and symptoms, severe COVID-19 as clinical symptoms of pneumonia (dyspnoea, tachypnoea, peripheral capillary oxygen saturation <93%, and need for oxygen therapy), and mild COVID-19 as all other symptoms. Clinical features on admission were compared among patients with different disease severity, including asymptomatic infection, at the end of observation. We used univariable analysis to identify factors associated with symptomatic illness among asymptomatic people infected with SARS-CoV-2 and disease progression in patients with COVID-19. FINDINGS: Among the 104 participants included in the final analysis, the median age was 68 years (IQR 47\u201375) and 54 (52%) were male. On admission, 43 (41%) participants were classified as asymptomatic, 41 (39%) as having mild COVID-10, and 20 (19%) as having severe COVID-19. At the end of observation, 33 (32%) participants were confirmed as being asymptomatic, 43 (41%) as having mild COVID-19, and 28 (27%) as having severe COVID-19. Serum lactate hydrogenase concentrations were significantly higher in the ten participants who were asymptomatic on admission but developed symptomatic COVID-19 compared with the 33 participants who remained asymptomatic throughout the observation period (five [50%] vs four [12%] participants; odds ratio 7\u00b725, 95% CI 1\u00b743\u201336\u00b770; p=0\u00b7020). Compared with patients with mild disease at the end of observation, patients with severe COVID-19 were older (median age 73 years [IQR 55\u201377] vs 60 years [40\u201371]; p=0\u00b7028) and had more frequent consolidation on chest CT (13 [46%] of 28 vs nine [21%] of 43; p=0\u00b7035) and lymphopenia (16 [57%] vs ten [23%]; p=0\u00b70055) on admission. INTERPRETATION: Older age, consolidation on chest CT images, and lymphopenia might be risk factors for disease progression of COVID-19 and contribute to improved clinical management. FUNDING: None.", "qid": 27, "docid": "11rd64fp", "rank": 49, "score": 0.7839915156364441}, {"content": "Title: Asymptomatic COVID-19 Have Longer Treatment Cycle Than Moderate Type of Confirmed Patients Content: IMPORTANCE A kind of pneumonia caused by unknown causes that occurred in Wuhan, Hubei, China in December 2019, was reported as a result of novel coronavirus infection on January 7, 2020, and then WHO named it \"COVID-19\". The comparison of epidemiological and clinical characteristics for those patients between asymptomatic COVID-19 infections and moderate type of confirmed cases is limited. OBJECTIVE To compare the difference of epidemiology and clinical characteristics between asymptomatic COVID-19 infections and moderate type of confirmed cases. DESIGN, SETTING, AND PARTICIPANTS Retrospective, single-center cohort study of COVID-19 involving 52 infections of both 26 asymptomatic and 26 moderate type of confirmed cases in the recovery stage at Guizhou Provincial Staff Hospital in Guiyang, China, from January 29, to March 31, 2020; final date of follow-up was April 22. This study was registered in Chinese Clinical Trial Registry Center. EXPOSURES Documented the asymptomatic COVID-19 infections and moderate type of confirmed cases. MAIN OUTCOMES AND MEASURES Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Epidemiological and clinical characteristics of asymptomatic COVID-19 infections and moderate type of confirmed cases were compared. RESULTS The median treatment cycle of asymptomatic COVID-19 infections was 16 days (interquartile range, 11-20 days) and longer than 13 days (interquartile range, 10-15 days) of moderate type of confirmed cases (p=0.049). The median incubation period of asymptomatic COVID-19 infections was 10 days (interquartile range, 0-21 days), while the control group was 7 days (interquartile range, 1-15 days) (p=0.27). On the initial chest computerized tomography (CT) check, 18 (69.2%, 18/26) asymptomatic COVID-19 infections were no imaging changes, which was of no significance compared with 12 (46.2%, 12/26) patients with moderate type of confirmed patients (p=0.092). CONCLUSIONS AND RELEVANCE In this single-center study, we found that asymptomatic COVID-19 infections have longer treatment cycle than those moderate type of confirmed cases.", "qid": 27, "docid": "6vxc7wv0", "rank": 50, "score": 0.7838696837425232}, {"content": "Title: Transmission Potential of Asymptomatic and Paucisymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infections: A 3-Family Cluster Study in China Content: Data concerning the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic and paucisymptomatic patients are lacking. We report a 3-family cluster of infections involving asymptomatic and paucisymptomatic transmission. Eight of 15 (53%) members from 3 families were confirmed with SARS-CoV-2 infection. Of 8 patients, 3 were asymptomatic and 1 was paucisymptomatic. An asymptomatic mother transmitted the virus to her son, and a paucisymptomatic father transmitted the virus to his 3-month-old daughter. SARS-CoV-2 was detected in the environment of 1 household. The complete genomes of SARS-CoV-2 from the patients were > 99.9% identical and were clustered with other SARS-CoV-2 sequences reported from China and other countries.", "qid": 27, "docid": "uq1801p1", "rank": 51, "score": 0.7835155725479126}, {"content": "Title: COVID-19 Pneumonia in Asymptomatic Trauma Patients; Report of 8 Cases. Content: We are currently involved in the novel coronavirus 2019 (COVID-19) pandemic. A considerable number of COVID-19 infected cases are asymptomatic but they can transmit the disease to others, especially healthcare workers. In this study, we reported 8 incidentally detected cases of COVID-19 pneumonia in chest computed tomography (CT) scan of patients referred to emergency department following multiple trauma without any respiratory symptoms.", "qid": 27, "docid": "ldamulbe", "rank": 52, "score": 0.7828434705734253}, {"content": "Title: COVID-19 Pneumonia in Asymptomatic Trauma Patients; Report of 8 Cases Content: We are currently involved in the novel coronavirus 2019 (COVID-19) pandemic. A considerable number of COVID-19 infected cases are asymptomatic but they can transmit the disease to others, especially healthcare workers. In this study, we reported 8 incidentally detected cases of COVID-19 pneumonia in chest computed tomography (CT) scan of patients referred to emergency department following multiple trauma without any respiratory symptoms.", "qid": 27, "docid": "54260tth", "rank": 53, "score": 0.7828434705734253}, {"content": "Title: Clinical outcome of 55 asymptomatic cases at the time of hospital admission infected with SARS-Coronavirus-2 in Shenzhen, China ;The Journal of Infectious Diseases ;Oxford Academic Content: Abstract An epidemic caused by SARS-Coronavirus-2 infection has spread unexpectedly in Wuhan, Hubei Province, China since December 2019 It is rarely reported about asymptomatic cases screened from close contacts We study epidemiological and clinical outcome of 55 asymptomatic carriers who were laboratory-confirmed positive for the SARS-Coronavirus-2 by testing the nucleic acid of the pharyngeal swab samples The evidence showed that asymptomatic carriers occurred more often in middle aged people who had close contact with infected family members The majority of the cases developed to be mild and ordinary COVID-19 during hospital", "qid": 27, "docid": "qrf7n7dr", "rank": 54, "score": 0.7825710773468018}, {"content": "Title: Epidemiological and clinical features of asymptomatic patients with SARS-CoV-2 infection Content: Few studies reported the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients with completely asymptomatic throughout the disease course. We investigated the epidemiological and clinical features of patients infected by SARS-CoV-2 without any symptoms. Patients with confirmed SARS-CoV-2 infection were retrospectively recruited. The demographic characteristics, clinical data, treatment, and outcomes of SARS-CoV-2 infected patients without any symptoms were analyzed. Fifteen (4.4%) of 342 SARS-CoV-2 infected patients did not develop any symptom during the course of the disease. The median time from exposure to diagnosis was 7.0 days (interquartile range [IQR]: 1.0-15.0 days). Of the 15 patients, 14 patients were diagnosed by tested positive for SARS-CoV-2 in throat swabs, while one patient was only tested positive for SARS-CoV-2 in anal swabs. During hospitalization, only 1 (6.7%) patient developed lymphopenia. Abnormalities of chest computed tomography examinations were detected in 8 (53.4%) patients on admission. As of 8 March 2020, all patients have been discharged. The median time of SARS-CoV-2 tested negative from admission was 7.0 days (IQR: 4.0-9.0 days). Patients without any symptoms but with SARS-CoV-2 exposure should be closely monitored and tested for SARS-CoV-2 both in anal and throat swabs to excluded the infection. Asymptomatic patients infected by SARS-CoV-2 have favorable outcomes.", "qid": 27, "docid": "dud6dzp6", "rank": 55, "score": 0.782219648361206}, {"content": "Title: High incidence of asymptomatic SARS-CoV-2 infection, Chongqing, China Content: Background: SARS-CoV-2 has been a global pandemic, but the emergence of asymptomatic patients has caused difficulties in the prevention of the epidemic. Therefore, it is significant to understand the epidemiological characteristics of asymptomatic patients with SARS-CoV-2 infection. Methods: In this single-center, retrospective and observational study, we collected data from 167 patients with SARS-CoV-2 infection treated in Chongqing Public Health Medical Center (Chongqing, China) from January to March 2020. The epidemiological characteristics and variable of these patients were collected and analyzed. Findings: 82.04% of the SARS-CoV-2 infected patients had a travel history in Wuhan or a history of contact with returnees from Wuhan, showing typical characteristics of imported cases, and the proportion of severe Covid-19 patients was 13.2%, of which 59% were imported from Wuhan. For the patients who was returnees from Wuhan, 18.1% was asymptomatic patients. In different infection periods, compared with the proportion after 1/31/2020, the proportion of asymptomatic patient among SARS-CoV-2 infected patient was higher(19% VS 1.5%). In different age groups, the proportion of asymptomatic patient was the highest(28.6%) in children group under 14, next in elder group over 70 (27.3%). Compared with mild and common Covid-19 patients, the mean latency of asymptomatic was longer (11.25 days VS 8.86 days), but the hospital length of stay was shorter (14.3 days VS 16.96 days) . Conclusion: The SARS-CoV-2 prevention needs to focus on the screening of asymptomatic patients in the community with a history of contact with the imported population, especially for children and the elderly population.", "qid": 27, "docid": "7w1bhaz6", "rank": 56, "score": 0.7818744778633118}, {"content": "Title: Asymptomatic patients and asymptomatic phases of Coronavirus Disease 2019 (COVID-19): a population-based surveillance study Content: In this population-based study, we identified 307 confirmed COVID-19 cases from massive surveillance, including 129,551 individuals screened at fever clinics or returning from Hubei and 3710 close contacts of confirmed COVID-19 patients. Among them, 17 patients were asymptomatic at initial clinical assessment. These asymptomatic patients on admission accounted for a small proportion of all patients (5.54%) with relatively weak transmissibility, and the detection rate was 0.35 per 100 close contacts. Moreover, the dynamics of symptoms of the 307 patients showed that the interval from symptom remission to the final negativity of viral nucleic acid was 5.0 days (IQR 2.0 to 11.0 days), with 14 patients (4.56%) having re-detectable viral RNA after discharge. Together, our findings suggested asymptomatic carriers and presymptomatic patients only accounted for a small proportion of COVID-19. Also, the asymptomatic phase in during recovery of COVID-19 urged that negativity in viral RNA is necessary as de-isolation criteria and follow-up is recommended.", "qid": 27, "docid": "l4n9hwcx", "rank": 57, "score": 0.7813324928283691}, {"content": "Title: A considerable proportion of individuals with asymptomatic SARS-CoV-2 infection in Tibetan population Content: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) quickly became a major epidemic threat in the whole China. We analysed SARS-Cov-2 infected cases from Tibetan Autonomous Prefecture, and noted divergent characteristics of these Tibetans infected cases compared to Han Chinese, characterizing by a considerable proportion of asymptomatic carriers (21.7%), and few symptomatic patients with initial symptom of fever (7.7%). Here, we did a descriptive study on clinical characteristics of 18 asymptomatic individuals with SARS-CoV-2 infection. The median age of these asymptomatic carriers was 31 years and one third of them were students, aged under 20 years. Notably, some of asymptomatic carriers had recognizable changes in radiological and laboratory indexes. Our finding indicates a potentially big number of SARS-CoV-2 asymptomatic carriers in prevalent area, highlighting a necessity of screening individuals with close contact of infected patients, for a better control on the spread of SARS-CoV-2 infection.", "qid": 27, "docid": "bmsmegbs", "rank": 58, "score": 0.7812708616256714}, {"content": "Title: The natural history and transmission potential of asymptomatic SARS-CoV-2 infection Content: Background: Little is known about the natural history of asymptomatic SARS-CoV-2 infection or its contribution to infection transmission. Methods: We conducted a prospective study at a quarantine centre for COVID-19 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with RT-PCR-confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrolment and daily nasopharyngeal throat swabs (NTS) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals. Results: Between March 10th and April 4th, 2020, 14,000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13(43%) never had symptoms and 17(57%) were symptomatic. 17(57%) participants acquired their infection outside Vietnam. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS samples collected at enrolment (8/13 (62%) vs. 17/17 (100%) P=0.02). SARS-CoV-2 RNA was detected in 20/27 (74%) available saliva; 7/11 (64%) in the asymptomatic and 13/16 (81%) in the symptomatic group (P=0.56). Analysis of the probability of RT-PCR positivity showed asymptomatic participants had faster viral clearance than symptomatic participants (P<0.001 for difference over first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit the infection to up to four contacts. Conclusions: Asymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTS. NTS viral loads fall faster in asymptomatic individuals, but they appear able to transmit the virus to others.", "qid": 27, "docid": "js5my502", "rank": 59, "score": 0.7812528610229492}, {"content": "Title: The natural history and transmission potential of asymptomatic SARS-CoV-2 infection Content: BACKGROUND: Little is known about the natural history of asymptomatic SARS-CoV-2 infection or its contribution to infection transmission. METHODS: We conducted a prospective study at a quarantine center for COVID-19 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with RT-PCR-confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrolment and daily nasopharyngeal throat swabs (NTS) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals. RESULTS: Between March 10th and April 4th, 2020, 14,000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13(43%) never had symptoms and 17(57%) were symptomatic. 17(57%) participants acquired their infection outside Vietnam. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS samples collected at enrolment (8/13 (62%) vs. 17/17 (100%) P=0.02). SARS-CoV-2 RNA was detected in 20/27 (74%) available saliva; 7/11 (64%) in the asymptomatic and 13/16 (81%) in the symptomatic group (P=0.56). Analysis of the probability of RT-PCR positivity showed asymptomatic participants had faster viral clearance than symptomatic participants (P<0.001 for difference over first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit the infection to up to four contacts. CONCLUSIONS: Asymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTS. NTS viral loads fall faster in asymptomatic individuals, but they appear able to transmit the virus to others.", "qid": 27, "docid": "pf2pj6mo", "rank": 60, "score": 0.7809725999832153}, {"content": "Title: COVID\u201019 suspicion and diagnosis: are we still chasing epidemiological criteria? Content: Italy was the second nation after China to be most involved into the COVID\u201019 outbreak. From the beginning, much attention has been attributed to the importance of epidemiological criteria (such as previous contact with confirmed COVID\u201019 cases, recent journey across China or the northern Italian regions) in order to assess a suspected patient for SARS\u2010CoV\u20102 infection. Despite this, by now evidences do exist about the possibly huge reservoir of asymptomatic patients and its underestimated ability to spread the infection. Thus, we do believe that when an infectious disease has a big ratio of asymptomatic cases, as for COVID\u201019, it is simply not safe to rely on epidemiological criteria and we briefly discuss this issue throughout the few new evidences there are about. This article is protected by copyright. All rights reserved.", "qid": 27, "docid": "p4ef9l3p", "rank": 61, "score": 0.7803099155426025}, {"content": "Title: Prevention of COVID-19 infection in the medical population: a possible help from anosmia? Content: COVID-19 asymptomatic cases increases the risks of disease dissemination with even greater risk for physicians given the shortage of personal protective equipment. Here we report on the consistent finding of frequent presentation of anosmia or hyposmia in COVID-19 patients, even in the absence of other symptoms and without other olfactory or nasal findings. In the uncertainty of the clinical characteristics of these patients, this symptom can be a tool to reduce the spread of the infection between medical population.", "qid": 27, "docid": "dgvizk1z", "rank": 62, "score": 0.7800829410552979}, {"content": "Title: Prevention of COVID-19 infection in the medical population: a possible help from anosmia?. Content: COVID-19 asymptomatic cases increases the risks of disease dissemination with even greater risk for physicians given the shortage of personal protective equipment. Here we report on the consistent finding of frequent presentation of anosmia or hyposmia in COVID-19 patients, even in the absence of other symptoms and without other olfactory or nasal findings. In the uncertainty of the clinical characteristics of these patients, this symptom can be a tool to reduce the spread of the infection between medical population.", "qid": 27, "docid": "lln8japc", "rank": 63, "score": 0.7800829410552979}, {"content": "Title: COVID-19: asymptomatic carrier transmission is an underestimated problem Content: At the present time, COVID-19 is spreading rapidly [1]. The global prevention and control of COVID-19 is focused on the estimation of the relevant incubation period, basic reproduction number (R0), effective reproduction number (Rt) and death risk. Although the prevention and control of COVID-19 requires a reliable estimation of the relevant incubation period, R0, Rt and death risk. Another key epidemiological parameter-asymptomatic ratio that provides strength and range for social alienation strategies of COVID-19, which is widely defined as the proportion of asymptomatic infections among all disease infections. In fact, the ratio of asymptomatic infection is a useful indicator of the burden of disease and a better measurement of the transmissibility of the virus. So far, people have not paid enough attention to asymptomatic carriers. The asymptomatic carriers discussed in this study are recessive infections, that is, those who have never shown symptoms after onset of infection. We will discuss three aspects: detection, infectivity and proportion of healthy carriers.", "qid": 27, "docid": "32jaz3vz", "rank": 64, "score": 0.7800375819206238}, {"content": "Title: Intraoperative Diagnosis of Coronavirus Disease 2019 in an Asymptomatic Patient: A Case Report Content: Patients with coronavirus disease 2019 (COVID-19) with variable clinical presentations are encountered in the perioperative setting. While some have already been diagnosed and are symptomatic, others have undiagnosed, asymptomatic COVID-19. The latter group poses the greatest risk of transmission. Given limited capacities in most health care systems, diagnostic testing is mainly performed in symptomatic patients or those with relevant exposure. We report an intraoperative diagnosis of COVID-19 in an asymptomatic patient, prompted by clinical signs. To control a pandemic such as COVID-19, a high index of suspicion is pivotal when caring for asymptomatic patients in the perioperative setting.", "qid": 27, "docid": "d06wt817", "rank": 65, "score": 0.7797796726226807}, {"content": "Title: Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19 disease. Content: BACKGROUND Some people with SARS-CoV-2 infection remain asymptomatic, whilst in others the infection can cause mild to moderate COVID-19 disease and COVID-19 pneumonia, leading some patients to require intensive care support and, in some cases, to death, especially in older adults. Symptoms such as fever or cough, and signs such as oxygen saturation or lung auscultation findings, are the first and most readily available diagnostic information. Such information could be used to either rule out COVID-19 disease, or select patients for further diagnostic testing. OBJECTIVES To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID-19 clinics, has COVID-19 disease or COVID-19 pneumonia. SEARCH METHODS On 27 April 2020, we undertook electronic searches in the Cochrane COVID-19 Study Register and the University of Bern living search database, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. SELECTION CRITERIA Studies were eligible if they included patients with suspected COVID-19 disease, or if they recruited known cases with COVID-19 disease and controls without COVID-19. Studies were eligible when they recruited patients presenting to primary care or hospital outpatient settings. Studies including patients who contracted SARS-CoV-2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards including reverse transcription polymerase chain reaction (RT-PCR), clinical expertise, imaging, serology tests and World Health Organization (WHO) or other definitions of COVID-19. DATA COLLECTION AND ANALYSIS Pairs of review authors independently selected all studies, at both title and abstract stage and full-text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and resolved disagreements by discussion with a third review author. Two review authors independently assessed risk of bias using the QUADAS-2 checklist. Analyses were descriptive, presenting sensitivity and specificity in paired forest plots, in ROC (receiver operating characteristic) space and in dumbbell plots. We did not attempt meta-analysis due to the small number of studies, heterogeneity across studies and the high risk of bias. MAIN RESULTS We identified 16 studies including 7706 participants in total. Prevalence of COVID-19 disease varied from 5% to 38% with a median of 17%. There were no studies from primary care settings, although we did find seven studies in outpatient clinics (2172 participants), and four studies in the emergency department (1401 participants). We found data on 27 signs and symptoms, which fall into four different categories: systemic, respiratory, gastrointestinal and cardiovascular. No studies assessed combinations of different signs and symptoms and results were highly variable across studies. Most had very low sensitivity and high specificity; only six symptoms had a sensitivity of at least 50% in at least one study: cough, sore throat, fever, myalgia or arthralgia, fatigue, and headache. Of these, fever, myalgia or arthralgia, fatigue, and headache could be considered red flags (defined as having a positive likelihood ratio of at least 5) for COVID-19 as their specificity was above 90%, meaning that they substantially increase the likelihood of COVID-19 disease when present. Seven studies carried a high risk of bias for selection of participants because inclusion in the studies depended on the applicable testing and referral protocols, which included many of the signs and symptoms under study in this review. Five studies only included participants with pneumonia on imaging, suggesting that this is a highly selected population. In an additional four studies, we were unable to assess the risk for selection bias. These factors make it very difficult to determine the diagnostic properties of these signs and symptoms from the included studies. We also had concerns about the applicability of these results, since most studies included participants who were already admitted to hospital or presenting to hospital settings. This makes these findings less applicable to people presenting to primary care, who may have less severe illness and a lower prevalence of COVID-19 disease. None of the studies included any data on children, and only one focused specifically on older adults. We hope that future updates of this review will be able to provide more information about the diagnostic properties of signs and symptoms in different settings and age groups. AUTHORS' CONCLUSIONS The individual signs and symptoms included in this review appear to have very poor diagnostic properties, although this should be interpreted in the context of selection bias and heterogeneity between studies. Based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out disease. Prospective studies in an unselected population presenting to primary care or hospital outpatient settings, examining combinations of signs and symptoms to evaluate the syndromic presentation of COVID-19 disease, are urgently needed. Results from such studies could inform subsequent management decisions such as self-isolation or selecting patients for further diagnostic testing. We also need data on potentially more specific symptoms such as loss of sense of smell. Studies in older adults are especially important.", "qid": 27, "docid": "3062h5on", "rank": 66, "score": 0.7797439098358154}, {"content": "Title: CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia at admission in Wuhan, China Content: PURPOSE: Aimed to characterize the CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia. METHODS: Asymptomatic cases with COVID-19 pneumonia confirmed by SARS-COV-2 nucleic acid testing in Renmin Hospital of Wuhan University were retrospectively enrolled. The characteristics of CT imaging and clinical feature were collected and analyzed. RESULTS: 58 asymptomatic cases with COVID-19 pneumonia admitted to our hospital between Jan 1, 2020 and Feb 23, 2020 were enrolled. All patients had history of exposure to SARS-CoV-2. On admission, patients had no symptoms and laboratory findings were normal. The predominant feature of CT findings in this cohort was ground glass opacity (GGO) (55, 94.8%) with peripheral (44, 75.9%) distribution, unilateral location (34, 58.6%) and mostly involving one or two lobes (38, 65.5%), often accompanied by characteristic signs. After short-term follow-up, 16 patients (27.6%) presented symptoms with lower lymphocyte count and higher CRP, mainly including fever, cough and fatigue. The evolution of lesions on CT imaging were observed in 10 patients (17.2%). The average days of hospitalization was19.80\u00b110.82 days, and was significantly longer in progression patients (28.60\u00b17.55 day). CONCLUSION: CT imaging of asymptomatic cases with COVID-19 pneumonia has definite characteristics. Since asymptomatic infections as \"covert transmitter\", and some patients can progress rapidly in the short term. It is essential to pay attention to the surveillance of asymptomatic patients with COVID-19. CT scan has great value in screening and detecting patients with COVID-19 pneumonia, especially in the highly suspicious, asymptomatic cases with negative nucleic acid testing.", "qid": 27, "docid": "5daqr7ff", "rank": 67, "score": 0.7797211408615112}, {"content": "Title: Asymptomatic transmission during the COVID-19 pandemic and implications for public health strategies Content: SARS-CoV-2 spread rapidly within months despite global public health strategies to curb transmission by testing symptomatic patients and encouraging social distancing. Here, we summarize rapidly emerging evidence highlighting transmission by asymptomatic and pre-symptomatic individuals. Viral load of asymptomatic carriers is comparable to symptomatic patients, viral shedding is highest before symptom onset suggesting high transmissibility before symptoms. Within universally tested subgroups, surprisingly high percentages of COVID-19 positive asymptomatic individuals were found. Asymptomatic transmission was reported in several clusters. A Wuhan study showed an alarming rate of intrahospital transmission, and several countries reported higher prevalence among healthcare workers than the general population. This raises concern that health workers could act as silent disease vectors. Therefore, current public health strategies relying solely on 'symptom onset' for infection identification need urgent reassessment. Extensive universal testing irrespective of symptoms may be considered with priority placed on groups with high frequency exposure to positive patients.", "qid": 27, "docid": "6ua5txjc", "rank": 68, "score": 0.7791552543640137}, {"content": "Title: Presumed pulmonary COVID-19 infection detected incidentally on breast MR Content: COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A global pandemic was declared by the World Health Organisation on 11 March 2020. Approximately 30% of infected individuals are asymptomatic.(1) We present the case of a 68-year-old female who underwent outpatient breast magnetic resonance (MR) imaging for assessment of a right breast mass. The study demonstrated abnormal subpleural high T2 signal intensity change within in the partially visualised lungs, which showed enhancement following administration of contrast. Concern was raised that the pulmonary changes may represent COVID-19 infection. The patient was urgently contacted and denied any current symptoms but reported suffering mild upper respiratory tract symptoms two weeks earlier. An outpatient chest radiograph demonstrated changes consistent with COVID-19 infection and the patient was treated as COVID-19 positive and advised to self-isolate for seven days as per Public Health England guidance.(2) Due to increasing breathlessness the patient presented to our Emergency Department the next day and underwent a CT pulmonary angiogram which demonstrated segmental pulmonary emboli and subpleural consolidation in keeping with COVID-19 infection. This represents the first case of COVID-19 identified on breast MR imaging that the authors have seen and highlights the importance of prompt identification and flagging of incidental pulmonary findings to minimise further transmission of the virus in asymptomatic carriers.", "qid": 27, "docid": "mots5f94", "rank": 69, "score": 0.77845299243927}, {"content": "Title: Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19 disease Content: BACKGROUND: Some people with SARS-CoV-2 infection remain asymptomatic, whilst in others the infection can cause mild to moderate COVID-19 disease and COVID-19 pneumonia, leading some patients to require intensive care support and, in some cases, to death, especially in older adults. Symptoms such as fever or cough, and signs such as oxygen saturation or lung auscultation findings, are the first and most readily available diagnostic information. Such information could be used to either rule out COVID-19 disease, or select patients for further diagnostic testing. OBJECTIVES: To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID-19 clinics, has COVID-19 disease or COVID-19 pneumonia. SEARCH METHODS: On 27 April 2020, we undertook electronic searches in the Cochrane COVID-19 Study Register and the University of Bern living search database, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. SELECTION CRITERIA: Studies were eligible if they included patients with suspected COVID-19 disease, or if they recruited known cases with COVID-19 disease and controls without COVID-19. Studies were eligible when they recruited patients presenting to primary care or hospital outpatient settings. Studies including patients who contracted SARS-CoV-2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards including reverse transcription polymerase chain reaction (RT-PCR), clinical expertise, imaging, serology tests and World Health Organization (WHO) or other definitions of COVID-19. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently selected all studies, at both title and abstract stage and full-text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and resolved disagreements by discussion with a third review author. Two review authors independently assessed risk of bias using the QUADAS-2 checklist. Analyses were descriptive, presenting sensitivity and specificity in paired forest plots, in ROC (receiver operating characteristic) space and in dumbbell plots. We did not attempt meta-analysis due to the small number of studies, heterogeneity across studies and the high risk of bias. MAIN RESULTS: We identified 16 studies including 7706 participants in total. Prevalence of COVID-19 disease varied from 5% to 38% with a median of 17%. There were no studies from primary care settings, although we did find seven studies in outpatient clinics (2172 participants), and four studies in the emergency department (1401 participants). We found data on 27 signs and symptoms, which fall into four different categories: systemic, respiratory, gastrointestinal and cardiovascular. No studies assessed combinations of different signs and symptoms and results were highly variable across studies. Most had very low sensitivity and high specificity; only six symptoms had a sensitivity of at least 50% in at least one study: cough, sore throat, fever, myalgia or arthralgia, fatigue, and headache. Of these, fever, myalgia or arthralgia, fatigue, and headache could be considered red flags (defined as having a positive likelihood ratio of at least 5) for COVID-19 as their specificity was above 90%, meaning that they substantially increase the likelihood of COVID-19 disease when present. Seven studies carried a high risk of bias for selection of participants because inclusion in the studies depended on the applicable testing and referral protocols, which included many of the signs and symptoms under study in this review. Five studies only included participants with pneumonia on imaging, suggesting that this is a highly selected population. In an additional four studies, we were unable to assess the risk for selection bias. These factors make it very difficult to determine the diagnostic properties of these signs and symptoms from the included studies. We also had concerns about the applicability of these results, since most studies included participants who were already admitted to hospital or presenting to hospital settings. This makes these findings less applicable to people presenting to primary care, who may have less severe illness and a lower prevalence of COVID-19 disease. None of the studies included any data on children, and only one focused specifically on older adults. We hope that future updates of this review will be able to provide more information about the diagnostic properties of signs and symptoms in different settings and age groups. AUTHORS' CONCLUSIONS: The individual signs and symptoms included in this review appear to have very poor diagnostic properties, although this should be interpreted in the context of selection bias and heterogeneity between studies. Based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out disease. Prospective studies in an unselected population presenting to primary care or hospital outpatient settings, examining combinations of signs and symptoms to evaluate the syndromic presentation of COVID-19 disease, are urgently needed. Results from such studies could inform subsequent management decisions such as self-isolation or selecting patients for further diagnostic testing. We also need data on potentially more specific symptoms such as loss of sense of smell. Studies in older adults are especially important.", "qid": 27, "docid": "83z84cts", "rank": 70, "score": 0.7783596515655518}, {"content": "Title: Asymptomatic transmission and the infection fatality risk for COVID-19: Implications for school reopening Content: Asymptomatic infection occurs for numerous respiratory viral diseases, including influenza and COVID-19. We seek to clarify confusion in three areas: age-specific risks of transmission and/or disease; various definitions for the COVID-19 \u201cmortality rate\u201d, each useful for specific purposes; and implications for student return strategies from pre-school through university settings.", "qid": 27, "docid": "e995ev2w", "rank": 71, "score": 0.7779974937438965}, {"content": "Title: Low Transmission Risk of 9 Asymptomatic Carriers Tested Positive for both SARS-CoV-2 Nucleic Acid and Serum IgG Content: \u2022 Asymptomatic carriers (RT-PCR+ and serum IgG+) are unable to transmit virus. \u2022 Such a low transmission risk might be partly associated with high Ct values. \u2022 A new pattern in SARS-CoV-2 infected patients might have emerged.", "qid": 27, "docid": "ajzhlsp3", "rank": 72, "score": 0.7778511643409729}, {"content": "Title: Asymptomatic transmission and the infection fatality risk for COVID-19: Implications for school reopening Content: Asymptomatic infection occurs for numerous respiratory viral diseases, including influenza and COVID-19. We seek to clarify confusion in three areas: age-specific risks of transmission and/or disease; various definitions for the COVID-19 \"mortality rate\", each useful for specific purposes; and implications for student return strategies from pre-school through university settings.", "qid": 27, "docid": "401kxcmi", "rank": 73, "score": 0.7776569128036499}, {"content": "Title: Asymptomatic transmission during the COVID-19 pandemic and implications for public health strategies Content: SARS-CoV-2 spread rapidly within months despite global public health strategies to curb transmission by testing symptomatic patients and encouraging social distancing. Here, we summarize rapidly emerging evidence highlighting transmission by asymptomatic and pre-symptomatic individuals. Viral load of asymptomatic carriers is comparable to symptomatic patients, viral shedding is highest before symptom onset suggesting high transmissibility before symptoms. Within universally tested subgroups, surprisingly high percentages of COVID-19 positive asymptomatic individuals were found. Asymptomatic transmission was reported in several clusters. A Wuhan study showed an alarming rate of intrahospital transmission, and several countries reported higher prevalence among healthcare workers than the general population. This raises concern that health workers could act as silent disease vectors. Therefore, current public health strategies relying solely on \u2018symptom onset\u2019 for infection identification need urgent reassessment. Extensive universal testing irrespective of symptoms may be considered with priority placed on groups with high frequency exposure to positive patients.", "qid": 27, "docid": "f99itvu9", "rank": 74, "score": 0.7774931192398071}, {"content": "Title: Epidemiological characterization of asymptomatic carriers of COVID-19 in Colombia Content: Objective: Asymptomatic carriers (AC) of the new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) represent an important source of spread for Coronavirus Disease 2019 (COVID-19). Early diagnosis of these cases is a powerful tool to control the pandemic. Our objective was to characterize patients with AC status and identify associated sociodemographic factors. Methods: Using a cross-sectional design and the national database of daily occurrence of COVID-19, we characterized both socially and demographically all ACs. Additional Correspondence Analysis and Logistic Regression Model were performed to identify characteristics associated with AC state (OR, 95% CI). Results: 2338 ACs (11.8%; 95% CI, 11.3-12.2%) were identified, mainly in epidemiological week 18 [EW] (3.98; 3.24-4.90). Age [\u2264]39 years (1.56; 1.42-1.72). Male sex (1.39; 1.26-1.53), cases imported from Argentina, Spain, Peru, Brazil, Costa Rica or Mexico (3.37; 1.47-7.71) and autochthonous cases (4.35 ; 2.12-8.93) increased the risk of identifying AC. We also identified groups of departments with moderate (3.68; 3.13-4.33) and strong (8.31; 6.10-7.46) association with AC. Discussion: Sociodemographic characteristics strongly associated with AC were identified, which may explain its epidemiological relevance and usefulness to optimize mass screening strategies and prevent person-to-person transmission.", "qid": 27, "docid": "4oet4pa5", "rank": 75, "score": 0.7768099904060364}, {"content": "Title: Prevalence of positive COVID-19 among asymptomatic health care workers who care patients infected with the novel coronavirus: A retrospective study Content: BACKGROUND: Limited information is available about COVID-19 infections among health care workers. Sensitive detection of COVID-19 cases in health care workers is crucial for hospital infection prevention policy, particularly for those who work with vulnerable patients. The aim of this study is to describe the prevalence of positive COVID-19 among asymptomatic health care workers who took care of patients with COVID-19 during the pandemic. METHODS: This retrospective study included all health care workers at King Abdullah University Hospital who take care of patients infected with COVID-19 patients from March 18, 2020 to April 29, 2020. They were tested for COVID-19 infection by use of real-time reverse-transcriptase rRT-PCR on samples from nasopharyngeal swabs. RESULTS: A total number of 370 health care workers were screened. The majority were nurses followed by physicians and other personnel. This study showed that all asymptomatic health care workers were tested negative for COVID-19Q. CONCLUSION: Unexpectedly, the prevalence of positive COVID-19 among asymptomatic health care workers who take care of patients infected with the novel coronavirus was 0%. This result must be cautiously interpreted. Further studies are needed in order to find effective strategy of screening health care workers to insure a safe working environment.", "qid": 27, "docid": "hvo5smwx", "rank": 76, "score": 0.7767354846000671}, {"content": "Title: The relative transmissibility of asymptomatic COVID-19 infections among close contacts Content: Asymptomatic transmission of the coronavirus disease 2019 is an important topic. A recent study in China showed that transmissibility of the asymptomatic cases is comparable to that of symptomatic cases. Here, we discuss that the conclusion may depend on how we interpret the data. To the best of our knowledge, this is the first time the relative transmissibility of asymptomatic COVID-19 infections is quantified.", "qid": 27, "docid": "cca7gzjq", "rank": 77, "score": 0.7766305208206177}, {"content": "Title: Epidemiological and clinical features of asymptomatic patients with SARS\u2010CoV\u20102 infection Content: Few studies reported the severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) infected patients with completely asymptomatic throughout the disease course. We investigated the epidemiological and clinical features of patients infected by SARS\u2010CoV\u20102 without any symptoms. Patients with confirmed SARS\u2010CoV\u20102 infection were retrospectively recruited. The demographic characteristics, clinical data, treatment, and outcomes of SARS\u2010CoV\u20102 infected patients without any symptoms were analyzed. Fifteen (4.4%) of 342 SARS\u2010CoV\u20102 infected patients did not develop any symptom during the course of the disease. The median time from exposure to diagnosis was 7.0 days (interquartile range [IQR]: 1.0\u201015.0 days). Of the 15 patients, 14 patients were diagnosed by tested positive for SARS\u2010CoV\u20102 in throat swabs, while one patient was only tested positive for SARS\u2010CoV\u20102 in anal swabs. During hospitalization, only 1 (6.7%) patient developed lymphopenia. Abnormalities of chest computed tomography examinations were detected in 8 (53.4%) patients on admission. As of 8 March 2020, all patients have been discharged. The median time of SARS\u2010CoV\u20102 tested negative from admission was 7.0 days (IQR: 4.0\u20109.0 days). Patients without any symptoms but with SARS\u2010CoV\u20102 exposure should be closely monitored and tested for SARS\u2010CoV\u20102 both in anal and throat swabs to excluded the infection. Asymptomatic patients infected by SARS\u2010CoV\u20102 have favorable outcomes.", "qid": 27, "docid": "4ki5st9h", "rank": 78, "score": 0.7765111923217773}, {"content": "Title: Asymptomatic COVID-19: What the Neuroradiologist Needs to Know about Pulmonary Manifestations Content: Coronavirus disease 2019 (COVID-19) is an infectious disease with a high asymptomatic incidence. Asymptomatic infections within a population will inevitably lead to diagnosis via unrelated medical imaging. We report the case of an asymptomatic patient undergoing a spine CT examination for trauma who was incidentally found to have lung abnormalities later confirmed to be COVID-19. We aim to familiarize neuroradiologists with the spectrum of COVID-19 pulmonary manifestations that are likely to be observed on neck and spine CT imaging.", "qid": 27, "docid": "5j6uu16i", "rank": 79, "score": 0.7757358551025391}, {"content": "Title: Asymptomatic COVID-19: What the Neuroradiologist Needs to Know about Pulmonary Manifestations. Content: Coronavirus disease 2019 (COVID-19) is an infectious disease with a high asymptomatic incidence. Asymptomatic infections within a population will inevitably lead to diagnosis via unrelated medical imaging. We report the case of an asymptomatic patient undergoing a spine CT examination for trauma who was incidentally found to have lung abnormalities later confirmed to be COVID-19. We aim to familiarize neuroradiologists with the spectrum of COVID-19 pulmonary manifestations that are likely to be observed on neck and spine CT imaging.", "qid": 27, "docid": "t0mqh9m0", "rank": 80, "score": 0.7757358551025391}, {"content": "Title: Viral dynamics in asymptomatic patients with COVID-19 Content: Data are limited on the viral load, viral shedding patterns, and potential infectivity of asymptomatic patients (APs) with coronavirus disease 2019 (COVID-19). This study included 31 adult patients who were virologically confirmed to have COVID-19 but were asymptomatic on admission. Among these 31 patients, 22 presented symptoms after admission and were defined as asymptomatic patients in the incubation period (APIs); the other nine patients remained asymptomatic during hospitalization and were defined as asymptomatic patients (APs). The median cycle threshold (Ct) value of APs (39.0, interquartile range (IQR) 37.5-39.5) was significantly higher than that of APIs (34.5, IQR 32.2-37.0), indicating a lower viral load in APs. However, the duration of viral shedding remained similar in the two groups (7 days, IQR 5-14 days vs. 8 days, IQR 5-16 days). The study findings demonstrated that although APs with COVID-19 have a lower viral load, they still have certain period of viral shedding, which suggests the possibility of transmission during their asymptomatic period. Further longitudinal surveillance of these asymptomatic cases via virus nucleic acid testing are warranted.", "qid": 27, "docid": "thftzde3", "rank": 81, "score": 0.7753568887710571}, {"content": "Title: COVID-19 \u2013 What does a paediatrician need to know? Content: COVID-19 is a coronavirus responsible for a global pandemic that started in China in December 2019 and has quickly spread to almost all countries. Approximately 2% of cases are diagnosed in children. There is increasing evidence for transmission by asymptomatic or presymptomatic adults and children. The clinical features do not differ from those of other respiratory viral infections, although rare cases manifest an unusual rash involving the digits. Disease is generally mild in children but deaths have been reported. Risk groups for severe disease in children are yet to be delineated. All treatments remain experimental.", "qid": 27, "docid": "828ubhzi", "rank": 82, "score": 0.7745682001113892}, {"content": "Title: CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia at admission in Wuhan, China Content: Abstract Purpose Aimed to characterize the CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia. Methods Asymptomatic cases with COVID-19 pneumonia confirmed by SARS-COV-2 nucleic acid testing in Renmin Hospital of Wuhan University were retrospectively enrolled. The characteristics of CT imaging and clinical feature were collected and analyzed. Results 58 asymptomatic cases with COVID-19 pneumonia admitted to our hospital between Jan 1, 2020 and Feb 23, 2020 were enrolled. All patients had history of exposure to SARS-CoV-2. On admission, patients had no symptoms and laboratory findings were normal. The predominant feature of CT findings in this cohort was ground glass opacity (GGO) (55, 94.8%) with peripheral (44, 75.9%) distribution, unilateral location (34, 58.6%) and mostly involving one or two lobes (38, 65.5%), often accompanied by characteristic signs. After short-term follow-up, 16 patients (27.6%) presented symptoms with lower lymphocyte count and higher CRP, mainly including fever, cough and fatigue. The evolution of lesions on CT imaging were observed in 10 patients (17.2%). The average days of hospitalization was19.80\u00b110.82 days, and was significantly longer in progression patients (28.60\u00b17.55 day). Conclusion CT imaging of asymptomatic cases with COVID-19 pneumonia has definite characteristics. Since asymptomatic infections as \u201ccovert transmitter\u201d, and some patients can progress rapidly in the short term. It is essential to pay attention to the surveillance of asymptomatic patients with COVID-19. CT scan has great value in screening and detecting patients with COVID-19 pneumonia, especially in the highly suspicious, asymptomatic cases with negative nucleic acid testing.", "qid": 27, "docid": "zbzrxuoh", "rank": 83, "score": 0.7745233774185181}, {"content": "Title: COVID-19: asymptomatic carrier transmission is an underestimated problem Content: At the present time, COVID-19 is spreading rapidly [1]. The global prevention and control of COVID-19 is focused on the estimation of the relevant incubation period, basic reproduction number (R(0)), effective reproduction number (R(t)) and death risk. Although the prevention and control of COVID-19 requires a reliable estimation of the relevant incubation period, R(0), R(t) and death risk. Another key epidemiological parameter-asymptomatic ratio that provides strength and range for social alienation strategies of COVID-19, which is widely defined as the proportion of asymptomatic infections among all disease infections. In fact, the ratio of asymptomatic infection is a useful indicator of the burden of disease and a better measurement of the transmissibility of the virus. So far, people have not paid enough attention to asymptomatic carriers. The asymptomatic carriers discussed in this study are recessive infections, that is, those who have never shown symptoms after onset of infection. We will discuss three aspects: detection, infectivity and proportion of healthy carriers.", "qid": 27, "docid": "c93j35fl", "rank": 84, "score": 0.7741522789001465}, {"content": "Title: Lung Involvement Found on Chest CT Scan in a Pre-Symptomatic Person with SARS-CoV-2 Infection: A Case Report Content: The novel coronavirus SARS-CoV-2 infection is spreading worldwide, and there are many reports of acute respiratory distress syndrome caused by this infection. However, asymptomatic lung involvement has not been reported. We hereby present the case of a 44-year-old health-care worker, who was found to be infected with the SARS-CoV-2 virus after a CT-scan performed for an unrelated condition revealed a lesion in the lung field compatible with COVID-19 infection. His condition deteriorated initially, but eventually improved with supportive treatment and the compassionate use of antivirals and antimalarials and is now in a stable condition.", "qid": 27, "docid": "rymfx50v", "rank": 85, "score": 0.7738629579544067}, {"content": "Title: Diagn\u00f3stico De Neumon\u00eda Covid 19 En Pacientes Asintom\u00e1ticos Tras La Realizaci\u00f3n De Un Pet-tc Oncol\u00f3gico Content: INTRODUCTION: On January 30, 2020, the World Health Organization (WHO) declared an international emergency due to the pandemic caused by a new coronavirus. There are some oncological indications that have special priority and studies are still being carried out despite the current situation. In these studies we have found suspicious findings of COVID-19 pneumonia in asymptomatic patients. The objective of this work is to assess the incidence of these findings, describe their characteristics and the evolution of suspected patients. MATERIAL AND METHODS: Oncological PET studies carried out in asymptomatic patients between March 18 and April 8, 2020 have been reviewed. Patients who presented findings suggestive of corresponding to an pulmonary infectious process were selected. Clinical findings have been reviewed to confirm or rule out SARS-CoV2 infection. RESULTS: During the specified period, a total of 129 PET-CT studies were performed. Of these, 11 (8.5%) found suspicious findings of a pulmonary infectious process. These were 8 men and 3 women aged between 30 and 79 years (mean 62.2). CONCLUSIONS: Patients with COVID 19 can present few symptoms of the disease, and in PET-CT studies both presymptomatic and almost asymptomatic patients can be detected, so nuclear medicine physicians should take special attention to the pulmonary evaluation of PET-CT studies.", "qid": 27, "docid": "jjslw3lu", "rank": 86, "score": 0.7736973762512207}, {"content": "Title: Rapid asymptomatic transmission of COVID-19 during the incubation period demonstrating strong infectivity in a cluster of youngsters aged 16-23 years outside Wuhan and characteristics of young patients with COVID-19: A prospective contact-tracing study Content: Summary Background The outbreak of coronavirus-disease-2019 (COVID-19) has rapidly spread to many places outside Wuhan. Previous studies on COVID-19 mostly included older hospitalized-adults. Little information on infectivity among and characteristics of youngsters with COVID-19 is available. Methods A cluster of 22 close-contacts of a 22-year-old male (Patient-Index) including youngsters with laboratory-confirmed COVID-19 and hospitalized close-contacts testing negative for severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) in Anhui Province, China was prospectively-traced. Results Since January 23, 2020, we enrolled a cluster of eight youngsters with COVID-19 (median age [range], 22 [16\u201323] years; six males) originating from Patient-Index returning from Wuhan to Hefei on January 19. Patient-Index visited his 16-year-old female cousin in the evening on his return, and met 15 previous classmates in a get-together on January 21. He reported being totally asymptomatic and were described by all his contacts as healthy on January 19-21. His very first symptoms were itchy eyes and fever developed at noon and in the afternoon on January 22, respectively. Seven youngsters (his cousin and six classmates) became infected with COVID-19 after a-few-hour-contact with Patient-Index. None of the patients and contacts had visited Wuhan (except Patient-Index), or had any exposure to wet-markets, wild-animals, or medical-institutes within three months. For affected youngsters, the median incubation-period was 2 days (range, 1\u20134). The median serial-interval was 1 day (range, 0\u20134). Half or more of the eight COVID-19-infected youngsters had fever, cough, sputum production, nasal congestion, and fatigue on admission. All patients had mild conditions. Six patients developed pneumonia (all mild; one bilateral) on admission. As of February 20, four patients were discharged. Conclusions SARS-CoV-2-infection presented strong infectivity during the incubation-period with rapid transmission in this cluster of youngsters outside Wuhan. COVID-19 developed in these youngsters had fast onset and various nonspecific atypical manifestations, and were much milder than in older patients as previously reported.", "qid": 27, "docid": "8rfhwqp5", "rank": 87, "score": 0.7720495462417603}, {"content": "Title: DIAGN\u00d3STICO DE NEUMON\u00cdA COVID 19 EN PACIENTES ASINTOM\u00c1TICOS TRAS LA REALIZACI\u00d3N DE UN PET-TC ONCOL\u00d3GICO Content: ABSTRACT INTRODUCTION: On January 30, 2020, the World Health Organization (WHO) declared an international emergency due to the pandemic caused by a new coronavirus. There are some oncological indications that have special priority and studies are still being carried out despite the current situation. In these studies we have found suspicious findings of COVID-19 pneumonia in asymptomatic patients. The objective of this work is to assess the incidence of these findings, describe their characteristics and the evolution of suspected patients. MATERIAL AND METHODS: Oncological PET studies carried out in asymptomatic patients between March 18 and April 8, 2020 have been reviewed. Patients who presented findings suggestive of corresponding to an pulmonary infectious process were selected. Clinical findings have been reviewed to confirm or rule out SARS-CoV2 infection. RESULTS: During the specified period, a total of 129 PET-CT studies were performed. Of these, 11 (8.5%) found suspicious findings of a pulmonary infectious process. These were 8 men and 3 women aged between 30 and 79 years (mean 62.2). CONCLUSIONS: Patients with COVID 19 can present few symptoms of the disease, and in PET-CT studies both presymptomatic and almost asymptomatic patients can be detected, so nuclear medicine physicians should take special attention to the pulmonary evaluation of PET-CT studies.", "qid": 27, "docid": "zjoyxioy", "rank": 88, "score": 0.7720116376876831}, {"content": "Title: Early viral clearance and antibody kinetics of COVID-19 among asymptomatic carriers Content: Background Asymptomatic carriers contribute to the spread of Coronavirus Disease 2019 (COVID-19), but their clinical characteristics, viral kinetics, and antibody responses remain unclear. Methods A total of 56 COVID-19 patients without symptoms at admission and 19 age-matched symptomatic patients were enrolled. RNA of SARS-CoV-2 was tested using transcriptase quantitative PCR, and the total antibodies (Ab), IgG, IgA and IgM against the SARS-CoV-2 were tested using Chemiluminescence Microparticle Immuno Assay. Results Among 56 patients without symptoms at admission, 33 cases displayed symptoms and 23 remained asymptomatic throughout the follow-up period. 43.8% of the asymptomatic carriers were children and none of the asymptomatic cases had recognizable changes in C-reactive protein or interleukin-6, except one 64-year-old patient. The initial threshold cycle value of nasopharyngeal SARS-CoV-2 in asymptomatic carriers was similar to that in pre-symptomatic and symptomatic patients, but the communicable period of asymptomatic carriers (9.63 days) was shorter than pre-symptomatic patients (13.6 days). There was no obvious differences of the seropositive conversion rate of total Ab, IgG, and IgA among the three groups, though the rates of IgM varied largely. The average peak IgG and IgM COI of asymptomatic cases was 3.5 and 0.8, respectively, which is also lower than those in symptomatic patients with peaked IgG and IgM COI of 4.5 and 2.4 (p <0.05). Conclusion Young COVID-19 patients seem to be asymptomatic cases with early clearance of SARS-CoV-2 and low levels of IgM generation but high total Ab, IgG and IgA. Our findings provide empirical information for viral clearance and antibody kinetics of asymptomatic COVID-19 patients.", "qid": 27, "docid": "c6um6puc", "rank": 89, "score": 0.771941602230072}, {"content": "Title: Prevalence of SARS-CoV-2 infection among asymptomatic healthcare workers in greater Houston: a cross-sectional analysis of surveillance data from a large healthcare system Content: Objective: To determine the prevalence of SARS-CoV-2 infection among asymptomatic COVID-19 facing and non-COVID-19 facing Healthcare Workers (HCWs), with varying job categories across different hospitals. Design: Cross-sectional analysis of a healthcare system surveillance program that included asymptomatic clinical (COVID-19 facing and non-COVID-19 facing), and non-clinical HCWs. A convenience sample of asymptomatic community residents (CR) was also tested. Proportions and 95% confidence intervals (CI) of SARS-CoV-2 positive HCWs are reported. Proportional trend across HCW categories was tested using Chi Square trend test. Logistic regression model-based likelihood estimates of SARS-CoV-2 prevalence among HCWs with varying job functions and across different hospitals are reported as adjusted odds ratios (aOR) and CI. Setting: Healthcare system comprising one tertiary care academic medical center and six large community hospitals across Greater Houston and a community sample. Participants: 2,872 self-reported asymptomatic adult (> 18 years) HCWs and CRs. Exposure: Clinical HCWs in COVID-19 and non-COVID-19 units, non-Clinical HCWs, and CRs. Job categories of Nursing, Providers, Allied Health, Support, and Administration / Research. Seven hospitals in the healthcare system. Main Outcomes: Positive reverse transcriptase polymerized chain reaction (RT-PCR) test for SARS-CoV-2 Results: Among 2,872 asymptomatic HCWs and CRs, 3.9% (CI: 3.2 - 4.7) tested positive for SARS-CoV-2. Mean (SD) age was 40.9 (11.7) years and 73% were females. Among COVID-19 facing HCWs 5.4% (CI: 4.5 - 6.5) were positive, whereas 0.6% (CI: 0.2 - 1.7%) of non COVID-19 facing HCWs and none of the non-clinical HCWs or CRs were positive (Ptrend < 0.001). Among COVID-19 facing HCWs, SARS-CoV-2 positivity was similar for all job categories (p = 0.74). However, significant differences in positivity were observed across hospitals. Conclusions and Relevance: Asymptomatic HCWs with COVID-19 patient exposure had a higher rate of SARS-CoV-2 positive testing than those not routinely exposed to COVID-19 patients and those not engaged in patient care. Among HCWs with routine COVID-19 exposure, all job types had relatively similar infection rates. These data can inform hospital surveillance and infection control practices for patient-facing job classifications and suggest that general environmental exposure within hospitals is not a significant source of asymptomatic SARS-CoV-2 infection.", "qid": 27, "docid": "cib1oivu", "rank": 90, "score": 0.7718737721443176}, {"content": "Title: Estimating the Asymptomatic Proportion of 2019 Novel Coronavirus onboard the Princess Cruises Ship, 2020 Content: The potential infectiousness of asymptomatic COVID-19 cases together with a substantial fraction of asymptomatic infections among all infections, have been highlighted in clinical studies. We conducted statistical modeling analysis to derive the delay-adjusted asymptomatic proportion of the positive COVID-19 infections onboard the Princess Cruises ship along with the timeline of infections. We estimated the asymptomatic proportion at 17.9% (95% CrI: 15.5%-20.2%), with most of the infections occurring before the start of the 2-week quarantine.", "qid": 27, "docid": "atnz63pk", "rank": 91, "score": 0.7718557119369507}, {"content": "Title: The proportion of COVID-19 cases that are asymptomatic in South Korea: Comment on Nishiura et al Content: The Korean Centers for Disease Control & Prevention reports the asymptomatic case proportion for COVID-19 is 33.3%. The asymptomatic case proportion in South Korea closely approximates the rate of 30.8% reported by Nishiura et al. (2020) among Japanese nationals returning from abroad.", "qid": 27, "docid": "hzez9mj4", "rank": 92, "score": 0.771474301815033}, {"content": "Title: Asymptomatic cases with SARS-CoV-2 infection Content: On 31 March 2020, Chinese Health Authorization announced that numbers of asymptomatic cases with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection will be made to the public daily. This was a very important step since different counties have different capacities for the detection of SARS-CoV-2 infection and control strategy for the Coronavirus Disease 2019 outbreak. We summarized the characteristics of asymptomatic SARS-CoV-2 infections and the transmission potential of asymptomatic cases. Then we provided guidelines for the management of asymptomatic cases through quarantine and nucleic acid/serology tests.", "qid": 27, "docid": "0r8vo1fa", "rank": 93, "score": 0.7706629037857056}, {"content": "Title: A COVID-19 Transmission within a family cluster by presymptomatic infectors in China Content: We report a COVID-19 family cluster caused by a presymptomatic case. There were 9 family members, including 8 laboratory-confirmed with COVID-19, and a 6-year-old child had no evidence of infection. Amongst the 8 patients, one adult and one 13-month-old infant were asymptomatic, one adult was diagnosed as having severe pneumonia.", "qid": 27, "docid": "scb7yot1", "rank": 94, "score": 0.7702001333236694}, {"content": "Title: Clinical features of covid-19 in children Content: In early December, pneumonia cases of unknown origin started to appear and, on the 7thof January 2020, these cases were declared to be caused by a novel beta-coronavirus according to viral genome sequencing on the 11thof February, 2020. Coronaviruses are enveloped, single strand RNA viruses that have been known to have the ability to mutate rapidly, alter tissue tropism and adjust to different epidemiological situations. As of the end of April 2020, 122,392 laboratory-confirmed cases of COVID-19 had been detected in Turkey, of whom 3,258 died. From the beginning of the COVID-19 epidemic, children seem to be less affected than adults. Therefore, there are limited data regarding the clinical features of COVID-19 in children. The majority of children with confirmed COVID-19 had a history of household contact. The most common symptoms were fever and cough. Previous data suggest that nearly half of patients are afebrile at the onset of the disease. Hospitalization and PICU admission rates for children were lower than for adults. However, PICU admission can be necessitated in children with severe disease. Infants, particularly under the age of 12 months, were more likely to develop severe disease. In children, milder and asymptomatic cases can be challenging and can play a role in transmission. In particular, clinicians should test those children who have a history of family cluster even though they are asymptomatic or present with mild symptoms.", "qid": 27, "docid": "34ytd87a", "rank": 95, "score": 0.7698282599449158}, {"content": "Title: SARS-CoV-2 infection in two patients following recent lung transplantation Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes Coronavirus disease 2019 (COVID-19) has become a world spreading health problem with pandemic character. Lung transplant recipients may be particularly at risk due to the high degree of immunosupression and the lung being the organ primarily affected by COVID-19. We describe a 16-year old male and a 64-year old female recently lung transplanted patients with COVID-19 during inpatient rehabilitation. Both patients were on triple immunosuppressive therapy and had no signs of allograft dysfunction. Both patients had close contact to a person who developed COVID-19 and were tested positive for SARS-CoV-2. Subsequently, both patients underwent systematic screening and SARS-CoV-2 was detected ultimately. While the 16-year old boy was completely asymptomatic, the 64-year old woman developed only mild COVID-19. Immunosuppressive therapy was unchanged and no experimental treatment was initiated. No signs of graft involvement or dysfunction were noticed. In conclusion, our report of patients with asymptomatic SARS-CoV-2 infection and mild COVID-19 respectively, may indicate that lung transplant recipients are not per se at risk for severe COVID-19. Further observations and controlled trials are urgently needed to study SARS-CoV-2 infection in lung transplant recipients.", "qid": 27, "docid": "lli6pgkv", "rank": 96, "score": 0.7694050073623657}, {"content": "Title: The role of asymptomatic SARS-CoV-2 infections: rapid living systematic review and meta-analysis Content: Background: There is substantial disagreement about the level of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a population. The disagreement results, in part, from the interpretation of studies that report a proportion of asymptomatic people with SARS-CoV-2 detected at a single point. Review questions: 1. Amongst people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? 2. Amongst people with SARS-CoV-2 infection who are asymptomatic when diagnosed, what proportion will develop symptoms later? 3. What proportion of SARS-CoV-2 transmission is accounted for by people who are either asymptomatic throughout infection, or pre-symptomatic? Methods: Rapid living systematic review (protocol https://osf.io/9ewys/). We searched Pubmed, Embase, bioRxiv and medRxiv using a living evidence database of SARS-CoV-2 literature on 25.03.2020. We included studies of people with SARS-CoV-2 diagnosed by reverse transcriptase PCR (RT-PCR) that documented follow-up and symptom status at the beginning and end of follow-up and modelling studies. Study selection, data extraction and bias assessment were done by one reviewer and verified by a second, with disagreement resolved by discussion or a third reviewer. We used a common-effect model to synthesise proportions from comparable studies. Results: We screened 89 studies and included 11. We estimated an upper bound for the proportion of asymptomatic SARS-CoV-2 infections of 29% (95% confidence interval 23 to 37%) in eight studies. Selection bias and likely publication bias affected the family case investigation studies. One statistical modelling study estimated the true proportion of asymptomatic infections at 18% (95% credibility interval 16 to 20%). Estimates of the proportions of pre-symptomatic individual in four studies were too heterogeneous to combine. In modelling studies, 40-60% of all SARS-CoV-2 infections are the result of transmission from pre-symptomatic individuals, with a smaller contribution from asymptomatic individuals. Conclusions: An intermediate contribution of pre-symptomatic and asymptomatic infections to overall SARS-CoV-2 transmission means that combination prevention, with enhanced hand and respiratory hygiene, testing tracing and isolation strategies and social distancing, will continue to be needed. The findings of this systematic review of publications early in the pandemic suggests that most SARS-CoV-2 infections are not asymptomatic throughout the course of infection.", "qid": 27, "docid": "c5be70t6", "rank": 97, "score": 0.7692136764526367}, {"content": "Title: A Well Infant with Coronavirus Disease 2019 (COVID-19) with High Viral Load Content: A well 6-month-old infant with coronavirus disease 2019 (COVID-19) had persistently positive nasopharyngeal swabs to day 16 of admission. This case highlights the difficulties in establishing the true incidence of COVID-19 as asymptomatic individuals can excrete the virus. These patients may play important roles in human-to-human transmission in the community.", "qid": 27, "docid": "blcozxq3", "rank": 98, "score": 0.7690948247909546}, {"content": "Title: Flash survey on severe acute respiratory syndrome coronavirus-2 infections in paediatric patients on anticancer treatment Content: INTRODUCTION: Since the beginning of COVID-19 pandemic, it is known that the severe course of the disease occurs mostly among the elderly, whereas it is rare among children and young adults. Comorbidities, in particular, diabetes and hypertension, clearly associated with age, besides obesity and smoke, are strongly associated with the need for intensive treatment and a dismal outcome. A weaker immunity of the elderly has been proposed as a possible explanation of this uneven age distribution. Thus, there is concern that children treated for cancer may allso be at risk for an unfavourable course of infection. Along the same line, anecdotal information from Wuhan, China, mentioned a severe course of COVID-19 in a child treated for leukaemia. AIM AND METHODS: We made a flash survey on COVID-19 incidence and severity among children on anticancer treatment. Respondents were asked by email to fill in a short Web-based survey. RESULTS: We received reports from 25 countries, where approximately 10,000 patients at risk are followed up. At the time of the survey, more than 200 of these children were tested, nine of whom were positive for COVID-19. Eight of the nine cases had asymptomatic to mild disease, and one was just diagnosed with COVID-19. We also discuss preventive measures that are in place or should be taken and treatment options in immunocompromised children with COVID-19. CONCLUSION: Thus, even children receiving anticancer chemotherapy may have a mild or asymptomatic course of COVID-19. While we should not underestimate the risk of developing a more severe course of COVID-19 than that observed here, the intensity of preventive measures should not cause delays or obstructions in oncological treatment.", "qid": 27, "docid": "vz4c270q", "rank": 99, "score": 0.7690533399581909}, {"content": "Title: Comparison of transmissibility of coronavirus between symptomatic and asymptomatic patients: Reanalysis of the Ningbo Covid-19 data Content: We investigate the transmissibility of coronavirus for symptomatic and asymptomatic patients using the Ningbo Covid-19 data1. Through more in-depth and comprehensive statistical analysis, we conclude that there is no difference in the transmission rates of coronavirus between the symptomatic and asymptomatic patients, which is consistent with the original findings in Chen et al.1", "qid": 27, "docid": "nlzdto1h", "rank": 100, "score": 0.768416166305542}]}
{"query": "what evidence is there for the value of hydroxychloroquine in treating Covid-19?", "hits": [{"content": "Title: Chloroquine and hydroxychloroquine in the management of COVID-19: much kerfuffle but little evidence Content: Summary Chloroquine and hydroxychloroquine are drugs that have shown in vitro activity on the replication of certain coronaviruses. In the context of the SARS-Cov-2 epidemic, the virus responsible for the novel coronavirus disease (COVID-19), these two drugs have been proposed as possible treatments. The results of the first clinical studies evaluating the effect of hydroxychloroquine do not support any efficacy of this drug in patients with COVID-19, due to major methodological weaknesses. Yet, these preliminary studies have aroused considerable media interest, raising fears of massive and uncontrolled use. In the absence of evidence of clinical benefits, the main risk is of exposing patients unnecessarily to the well-known adverse effects of hydroxychloroquine, with a possibly increased risk in the specific setting of COVID-19. In addition, widespread use outside of any recommendation risks compromising the completion of good quality clinical trials. The chloroquine hype, fueled by low-quality studies and media announcements, has yielded to the implementation of more than 150 studies worldwide. This represents a waste of resources and a loss of opportunity for other drugs to be properly evaluated. In the context of emergency, rigorous trials are more than ever needed in order to have, as soon as possible, reliable data on drugs that are possibly effective against the disease. Meanwhile, serious adverse drug reactions have been reported in patients with COVID-19 receiving hydroxychloroquine, justifying to limit its prescription, and to perform suitable cardiac and therapeutic drug monitoring.", "qid": 28, "docid": "pdvqdgsw", "rank": 1, "score": 0.8493238687515259}, {"content": "Title: Chloroquine and hydroxychloroquine in the management of COVID-19: Much kerfuffle but little evidence Content: Chloroquine and hydroxychloroquine are drugs that have shown in vitro activity on the replication of certain coronaviruses. In the context of the SARS-Cov-2 epidemic, the virus responsible for the novel coronavirus disease (COVID-19), these two drugs have been proposed as possible treatments. The results of the first clinical studies evaluating the effect of hydroxychloroquine do not support any efficacy of this drug in patients with COVID-19, due to major methodological weaknesses. Yet, these preliminary studies have aroused considerable media interest, raising fears of massive and uncontrolled use. In the absence of evidence of clinical benefits, the main risk is of exposing patients unnecessarily to the well-known adverse effects of hydroxychloroquine, with a possibly increased risk in the specific setting of COVID-19. In addition, widespread use outside of any recommendation risks compromising the completion of good quality clinical trials. The chloroquine hype, fueled by low-quality studies and media announcements, has yielded to the implementation of more than 150 studies worldwide. This represents a waste of resources and a loss of opportunity for other drugs to be properly evaluated. In the context of emergency, rigorous trials are more than ever needed in order to have, as soon as possible, reliable data on drugs that are possibly effective against the disease. Meanwhile, serious adverse drug reactions have been reported in patients with COVID-19 receiving hydroxychloroquine, justifying to limit its prescription, and to perform suitable cardiac and therapeutic drug monitoring.", "qid": 28, "docid": "gjmvw8l2", "rank": 2, "score": 0.8474178314208984}, {"content": "Title: [Lack of clinical evidence for the use of hydroxychloroquine to treat SARS-CoV-2 infection] Content: The severity of COVID-19 disease has led to an urgent need for the discovery of new treatments. Thus, global stocks of hydroxychloroquine (HCQ) have been put under pressure with a study of 26 patients treated with HCQ during their infection with SARS-CoV-2. Despite the study's lack of quality, several countries' medicines agencies subsequently issued guidelines for the use of HCQ for COVID-19. This review aims to elucidate potential mechanisms, which make HCQ treatment interesting in the fight against SARS-CoV-2 infection, as well as the current evidence for clinical use of HCQ to treat COVID-19.", "qid": 28, "docid": "v5qhqn9o", "rank": 3, "score": 0.8434442281723022}, {"content": "Title: [Lack of clinical evidence for the use of hydroxychloroquine to treat SARS-CoV-2 infection]. Content: The severity of COVID-19 disease has led to an urgent need for the discovery of new treatments. Thus, global stocks of hydroxychloroquine (HCQ) have been put under pressure with a study of 26 patients treated with HCQ during their infection with SARS-CoV-2. Despite the study's lack of quality, several countries' medicines agencies subsequently issued guidelines for the use of HCQ for COVID-19. This review aims to elucidate potential mechanisms, which make HCQ treatment interesting in the fight against SARS-CoV-2 infection, as well as the current evidence for clinical use of HCQ to treat COVID-19.", "qid": 28, "docid": "hjl6vdwy", "rank": 4, "score": 0.8434442281723022}, {"content": "Title: Chloroquine and hydroxychloroquine effectiveness in human subjects during coronavirus: a systematic review Content: In a search to find effective treatments for COVID-19, chloroquine and hydroxychloroquine have gained attention. We aim to provide evidence to support clinical decision-making regarding medication for the treatment of COVID-19 by carrying out a systematic review of the literature. The electronic databases MEDLINE, EMBASE, Global Health, and HMIC were searched up to April 2020. Eligible study outcomes included: extubation or patient recovery. Relevant data were extracted and analysed by narrative synthesis. Our results included six studies in the review of which four studies were of good or fair quality. All eligible studies included were for coronavirus involving the use of either chloroquine or hydroxychloroquine to treat common symptoms such as fever, cough, shortness of breath and fatigue. Outcomes most commonly reported were improved lung function, viral clearance, and hospital discharge. Strong evidence to support the use of chloroquine and hydroxychloroquine in the treatment of COVID-19 is lacking. Fast track trials are riddled with bias and may not conform to rigorous guidelines which may lead to inadequate data being reported. The use of these drugs in combination with other medications may be useful but without knowing which groups they are suited for and when they may cause more harm than good.", "qid": 28, "docid": "w1au4pyl", "rank": 5, "score": 0.8419474363327026}, {"content": "Title: Hydroxychloroquine for the management of COVID-19: Hope or Hype? A Systematic review of the current evidence Content: Purpose: The COVID-19 Pandemic has literally left the world breathless in the chase for Pharmacotherapy. With the vaccine approval likely more than a year away and novel drugs in early clinical trials, repurposing of existing drugs takes the center stage. A potential drug discussed both in geopolitical and global scientific community is hydroxychloroquine (HCQ). We intend to systematically weigh and analyze the existing evidence of HCQ in the light of published and pre-print data available so far. Methods: PubMed Ovid MEDLINE, EMBASE, Google scholar databases and official clinical trial Registries of the United States, China, WHO ICTRP were electronically searched for studies for the use of HCQ in patients with COVID-19. Pre-proof article repositories like MedRxiv, BioRxiv, and ChemRxiv were also included in the search. The literature was critically appraised. Results: Total 71 articles were available as of 15 th April of which articles of relevance (three invitro studies, two open label non-randomized trials, two open label randomized control trials, one follow-up study, three reviews, ten short communications) and 88 clinical trials registered in three clinical trial registries were analyzed. HCQ seems to be efficient in inhibiting of SARS CoV-2 in in-vitro cell lines; there is lack of strong evidence from human studies. Conclusions: The in-vitro cell culture based data of viral inhibition does not suffice for the use of hydroxychloroquine in the patients with COVID-19. Currently literature shows inadequate, low level evidence in human studies. Scarcity of safety and efficacy data warrants medical communities, health care agencies and governments across the world against the widespread use of HCQ in COVID-19 prophylaxis and treatment, until robust evidence becomes available. Keywords: Hydroxychloroquine, SARS-CoV-2, COVID-19, Corona virus, nCov2, systematic review", "qid": 28, "docid": "0u4ar3b5", "rank": 6, "score": 0.8413219451904297}, {"content": "Title: Off-label prescribing in the midst of a pandemic: The case of hydroxychloroquine Content: There is currently no robust evidence to support prescribing hydroxychloroquine as a treatment or prophylaxis for COVID-19.", "qid": 28, "docid": "lh5g8vl7", "rank": 7, "score": 0.8351137042045593}, {"content": "Title: Off-label prescribing in the midst of a pandemic: The case of hydroxychloroquine. Content: There is currently no robust evidence to support prescribing hydroxychloroquine as a treatment or prophylaxis for COVID-19.", "qid": 28, "docid": "0eizsamh", "rank": 8, "score": 0.8351137042045593}, {"content": "Title: A Rush to Judgment? Rapid Reporting and Dissemination of Results and Its Consequences Regarding the Use of Hydroxychloroquine for COVID-19 Content: Hydroxychloroquine, an essential treatment for many patients with rheumatologic conditions, has recently garnered widespread attention as a potential treatment for COVID-19 infection. The authors appraise the study generating this interest and highlight the potential consequences of rapid dissemination of overinterpreted data, particularly for people with conditions for which hydroxychloroquine has demonstrated benefits in preventing organ damage and life-threatening disease flares.", "qid": 28, "docid": "amhj8ljl", "rank": 9, "score": 0.8333662152290344}, {"content": "Title: The ICMR bulletin on targeted hydroxychloroquine prophylaxis for Covid-19: Need to interpret with caution Content: The National Task Force for Covid-19 of the Indian Council of Medical Research (ICMR) in a bulletin dated March 21, 2020 recommended the use of hydroxychloroquine for prophylaxis in asymptomatic health care workers caring for suspected or confirmed patients and household contacts of confirmed patients. This is cause for concern with regard to bioethics and good clinical practice. The evidence for the efficacy of chloroquine and hydroxychloroquine is currently derived from open label trials and cell culture studies with no conclusive evidence available from randomised clinical trials. Hydroxychloroquine also carries contraindications in the case of conditions such as maculopathy, retinopathy and QTc prolongation and should be used with caution in vulnerable populations such as children, pregnancy, lactation and the elderly. Despite this, there has been a rush to procure and self-medicate with hydroxychloroquine, which has been addressed by the National Task Force. The WHO and the FDA have not found adequate evidence to recommend any specific medication for the treatment of Covid-19. While further evidence is awaited, including from trials registered with the FDA and the ICMR, it is recommended that the administration of hydroxychloroquine for chemo-prophylaxis be considered on a case by case basis with monitoring by a registered medical practitioner including electrocardiography (ECG). The potential for retinal and cardiac toxicity must also be borne in mind. It is further recommended that a public advisory regarding the need for caution in chemo-prophylaxis be made available in the public domain. Keywords: Coronavirus, Covid-19, SARS-CoV-2, hydroxychloroquine, chloroquine, chemoprophylaxis, bioethics, evidence- based medicine.", "qid": 28, "docid": "98zpr960", "rank": 10, "score": 0.8329834938049316}, {"content": "Title: The ICMR bulletin on targeted hydroxychloroquine prophylaxis for Covid-19: Need to interpret with caution. Content: The National Task Force for Covid-19 of the Indian Council of Medical Research (ICMR) in a bulletin dated March 21, 2020 recommended the use of hydroxychloroquine for prophylaxis in asymptomatic health care workers caring for suspected or confirmed patients and household contacts of confirmed patients. This is cause for concern with regard to bioethics and good clinical practice. The evidence for the efficacy of chloroquine and hydroxychloroquine is currently derived from open label trials and cell culture studies with no conclusive evidence available from randomised clinical trials. Hydroxychloroquine also carries contraindications in the case of conditions such as maculopathy, retinopathy and QTc prolongation and should be used with caution in vulnerable populations such as children, pregnancy, lactation and the elderly. Despite this, there has been a rush to procure and self-medicate with hydroxychloroquine, which has been addressed by the National Task Force. The WHO and the FDA have not found adequate evidence to recommend any specific medication for the treatment of Covid-19. While further evidence is awaited, including from trials registered with the FDA and the ICMR, it is recommended that the administration of hydroxychloroquine for chemo-prophylaxis be considered on a case by case basis with monitoring by a registered medical practitioner including electrocardiography (ECG). The potential for retinal and cardiac toxicity must also be borne in mind. It is further recommended that a public advisory regarding the need for caution in chemo-prophylaxis be made available in the public domain. Keywords: Coronavirus, Covid-19, SARS-CoV-2, hydroxychloroquine, chloroquine, chemoprophylaxis, bioethics, evidence- based medicine.", "qid": 28, "docid": "opbozg55", "rank": 11, "score": 0.8329834938049316}, {"content": "Title: Hydroxychloroquine for COVID-19: What is our Current State of Knowledge? Content: Chloroquine and Hydroxychloroquine are drugs which have been widely used in malaria and rheumatoid arthritis respectively for over 50 years. There was anecdotal evidence of their efficacy in the earlier SARS outbreak in 2003. This prompted physicians from across the world to use them in the present SARS-CoV- 2 pandemic that is currently sweeping the globe, with 5 million people already infected to date. These drugs are already in widespread use for the treatment of COVID-19 in India, mainly because they are cheap and easily available, and because of the absence of any readily available alternative therapy. This timely review discusses the pre-clinical evidence, and data from the eight available clinical trials. We emphasise that careful monitoring for cardiac toxicity is required when these drugs are used. Finally, we conclude that current data does not allow us to recommend for or against the use of these drugs. Results of two large RCTs, one from the NIH and the other from WHO (Solidarity) are eagerly awaited before the role of these drugs in COVID-19 can be definitively established.", "qid": 28, "docid": "b6aeu1ph", "rank": 12, "score": 0.831878125667572}, {"content": "Title: Chloroquine and hydroxychloroquine for the treatment of COVID-19: A living systematic review protocol Content: OBJECTIVE: To determine the relative impact of the use of chloroquine and hydroxychloroquine on outcomes important to patients with COVID 19. DESIGN: This is the protocol of a living systematic review. DATA SOURCES: We will conduct searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), trial registries, grey literature and in a centralised repository in L-OVE (Living OVerview of Evidence). L-OVE is a platform that maps PICO questions to evidence from Epistemonikos database. In response to the COVID-19 emergency, L-OVE was adapted to expand the range of evidence it covers and customised to group all COVID-19 evidence in one place. The search will cover the period until the day before submission to a journal. ELIGIBILITY CRITERIA FOR SELECTING STUDIES AND METHODS: We will follow a common protocol for multiple parallel systematic reviews, already published and submitted to PROSPERO (awaiting ID allocation). We will include randomised controlled trials evaluating the effect of chloroquine and hydroxychloroquine - as monotherapy or in combination with other drugs - versus placebo or no treatment in patients with COVID-19. Randomised trials evaluating chloroquine and hydroxychloroquine in infections caused by other coronaviruses, such as MERS-CoV and SARS-CoV, and non-randomised studies in COVID-19 will be searched in case no direct evidence from randomised trials is found, or if the direct evidence provides low- or very low-certainty for critical outcomes. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will perform random-effects meta-analyses and use GRADE to assess the certainty of the evidence for each outcome. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it if the conclusions change or there are substantial updates. ETHICS AND DISSEMINATION: No ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media.", "qid": 28, "docid": "fckn8ld4", "rank": 13, "score": 0.8310688734054565}, {"content": "Title: Swinging the pendulum: lessons learned from public discourse concerning hydroxychloroquine and COVID-19. Content: INTRODUCTION Several months into the COVID-19 pandemic, safe and effective treatments against this global health disaster have yet to be identified. Clinical research trials around the world are underway testing a wide array of possible medications. In particular, the off-label use of hydroxychloroquine for COVID-19 prophylaxis and treatment has created many unprecedented challenges for the scientific community and the public. AREAS COVERED We critically assessed major events from February - May 2020 that contributed to widespread use of hydroxychloroquine for the treatment and prophylaxis of COVID-19. We aimed to explore how opinions towards hydroxychloroquine may shift from early enthusiasm (based on in vitro and preliminary clinical data) to the hope for a miracle cure (through communication and promotion of questionable results) and, finally, to a rise of skepticism as more in-depth analyses are emerging. EXPERT OPINION Mindful and rigorous acquisition of data, as well as its interpretation, are essential to an effective pandemic response. The rapid and premature promotion of results has had major implications for global crisis management, even creating distrust among the public. It is crucial for the medical and scientific community to incorporate the lessons learned from this situation.", "qid": 28, "docid": "ilu5oskk", "rank": 14, "score": 0.8268388509750366}, {"content": "Title: Chloroquine, hydroxychloroquine, and COVID-19: systematic review and narrative synthesis of efficacy and safety Content: Background: The COVID-19 pandemic has required clinicians to urgently identify new treatment options or the repurposing of existing drugs. Several drugs are now being repurposed with the aim of identifying if these drugs provide some level of disease resolution. Of particular interest are chloroquine (CQ) and hydroxychloroquine (HCQ), first developed as an antimalarial therapy. There is increasing concern with regards to the efficacy and safety of these agents. The aims of this review are to systematically identify and collate studies describing the use of CQ and HCQ in human clinical trials and provide a detailed synthesis of evidence of its efficacy and safety. Methods and Findings: Searches for (COVID AND chloroquine [title/abstract] AND outcomes[full text]) and two (COVID AND hydroxychloroquine[title/abstract] AND outcomes[full text]) yielded 272 unique articles. Unique articles were manually checked for inclusion and exclusion criteria and also subjected to a quality appraisal assessment. A total of 19 articles were included in the systematic review. Seventy-five percent of observational studies employing an endpoint specific to efficacy recorded no significant difference in the attainment of outcomes, between COVID-19 patients given a range of CQ and/or HCQ doses, and the control groups. All clinical trials and 82% of observational studies examining an indicator unique to drug safety discovered a higher probability of adverse events in those treated patients suspected of, and diagnosed with, COVID-19. Seventy-five percent of the total papers focusing on cardiac side-effects found a greater incidence among patients administered a wide range of CQ and/or HCQ doses, with QTc prolongation the most common finding, in addition to its consequences of VT and cardiac arrest. Of the total studies using mortality rate as an end-point, 60% reported no significant change in the risk of death, while 30% showed an elevation, and 10% a depression, in treated relative to control patients. Conclusion: The strongest available evidence suggests that, relative to standard in-hospital management of symptoms, the use of CQ and HCQ to treat hospitalised COVID-19 patients has likely been unsafe. At the very least, the poor quality of data failing to find any significant changes in the risk of VT should preclude definitive judgment on drug safety until the completion of high-quality randomised clinical trials.", "qid": 28, "docid": "srr2n28u", "rank": 15, "score": 0.8267763257026672}, {"content": "Title: A pharmacological perspective of Chloroquine in SARS-CoV-2 infection Content: The pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is having serious consequences on health and the economy worldwide. All evidence-based treatment strategies need to be considered to combat this new virus. Drugs need to be considered on scientific grounds of efficacy, safety and cost. Chloroquine (CQ) and hydroxychloroquine (HCQ) are old drugs used in the treatment of malaria; in addition, their antiviral properties have been previously studied, including in coronaviruses, where evidence of efficacy has been found. The safety of CQ and HCQ has been studied for over 50 years. In the current race against time triggered by the SARS-CoV-2 pandemic, the search for new antivirals is very important. However, consideration should be given to old drugs with known anti-coronavirus activity, such as CQ and HCQ; these could be integrated into current treatment strategies while novel treatments are awaited, also in light of the fact that they display an anticoagulant effect that facilitates the activity of low MW heparin, aimed at preventing ARDS-associated thrombotic events. The safety of CQ and HCQ has been studied for over 50 years, however, recently published data raise concerns for cardiac toxicity of CQ/HCQ in patients with COVID-19. The review that we here provide also reexamines the real information provided by some of the published alarming reports although concluding that cardiac toxicity should in any case be stringently monitored with patients with CQ/HCQ.", "qid": 28, "docid": "wgm26pla", "rank": 16, "score": 0.8256015777587891}, {"content": "Title: Therapeutic use of chloroquine and hydroxychloroquine in COVID-19 and other viral infections: A narrative review Content: The rapidly spreading Coronavirus Disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), represents an unprecedented serious challenge to the global public health community. The extremely rapid international spread of the disease with significant morbidity and mortality made finding possible therapeutic interventions a global priority. While approved specific antiviral drugs against SARS-CoV-2 are still lacking, a large number of existing drugs are being explored as a possible treatment for COVID-19 infected patients. Recent publications have re-examined the use of Chloroquine (CQ) and/or Hydroxychloroquine (HCQ) as a potential therapeutic option for these patients. In an attempt to explore the evidence that supports their use in COVID-19 patients, we comprehensively reviewed the previous studies which used CQ or HCQ as an antiviral treatment. Both CQ and HCQ demonstrated promising in vitro results, however, such data have not yet been translated into meaningful in vivo studies. While few clinical trials have suggested some beneficial effects of CQ and HCQ in COVID-19 patients, most of the reported data are still preliminary. Given the current uncertainty, it is worth being mindful of the potential risks and strictly rationalise the use of these drugs in COVID-19 patients until further high quality randomized clinical trials are available to clarify their role in the treatment or prevention of COVID-19.", "qid": 28, "docid": "7habtj4m", "rank": 17, "score": 0.8245195150375366}, {"content": "Title: Does pandemic justify the use of Hydroxychloroquine for treatment and prevention of COVID\u201019 in India? Content: The Indian Council of Medical Research (ICMR), recommended the use of hydroxychloroquine (HCQ) as a prophylactic against COVID\u201019 among health care workers and asymptomatic contacts of laboratory confirmed cases of COVID. This is widely criticised as a hastily taken step with political inclination and minimal evidence backing. In the current scenario, where there is mass fear against COVID\u201019, this recommendation has made the people to believe that it will kill the viruses. This has important public health implications which are discussed below. Better communication should have been planned to ensure everyone does not go out and buy it. However, as a nation of 1.3 billion, we need to capitalize on this opportunity to generate data and valuable evidence on the use of HCQ to beat this pandemic. All health care workers taking this drug should volunteer themselves to be part of a trial/observational study and get registered online to generate useful data related to its safety and efficacy and guide future recommendations. The other risk group which includes asymptomatic contacts of laboratory confirmed COVID\u201019 patients are under surveillance by the state and local health authorities and could also be roped into this study to generate robust evidence. Of course, pandemic does not just justify the use of HCQ, but pandemic is the time to innovate, think out of box and generate evidence to prove the same so that we can lives. This article is protected by copyright. All rights reserved.", "qid": 28, "docid": "vtiwj788", "rank": 18, "score": 0.8244963884353638}, {"content": "Title: Should chloroquine and hydroxychloroquine be used to treat COVID-19? A rapid review Content: BACKGROUND: On the 11 March 2020, the World Health Organization (WHO) declared that COVID-19 was a pandemic. To date, there are no medical treatments for COVID-19 with proven effectiveness. Novel treatments and/or vaccines will take time to be developed and distributed to patients. In light of this, there has been growing interest in the use of existing medications, such as chloroquine (CQ) and hydroxychloroquine (HCQ), as potential treatments of this disease. AIM: To establish the current evidence for the effectiveness of CQ and HCQ in treating COVID-19. DESIGN & SETTING: A rapid review of the literature was conducted. METHOD: Electronic searches in PubMed and Google Scholar were conducted on 21 March 2020. A further search was conducted in Google for relevant literature on 28 March 2020. RESULTS: There is limited evidence of in vitro activity of CQ/HCQ against SARS-CoV-2. A number of in vivo clinical trials are underway. The empirical data available from two of these trials reveal conflicting results. Both trials are characterised by small numbers of participants (n = 30 and n = 36) and suffer methodological limitations. No medium or long-term follow-up data is available. CONCLUSION: At present, there is insufficient evidence to determine whether CQ/HCQ are safe and effective treatments for COVID-19. High quality, adequately powered randomised clinical trials in primary and secondary care settings are urgently required to guide policymakers and clinicians. These studies should report medium- and long-term follow-up results, and safety data.", "qid": 28, "docid": "86h5ptxm", "rank": 19, "score": 0.8243564367294312}, {"content": "Title: Risk of using hydroxychloroquine as a treatment of COVID-19 Content: The emerging COVID-19 pandemic poses a threat to the global health care system. Given the lack of antiviral therapies or vaccines for the disease, the antimalarial drug hydroxychloroquine (HCQ) obtained much attention as a treatment for COVID-19. However, there are limited and uncertain clinical data to support the beneficial effect of this drug in COVID-19 treatment. HCQ has several side effects and warnings, including blindness, heart failure, and renal toxicity, even with recommended doses. For severe cases of COVID-19 or in patients with preexisting conditions, administering such a drug could be fatal, particularly when taken at high doses or in combination with other antibiotics. However, further well-designed studies that would address the optimal dose, duration of treatment, possible side effects, and long-term usage outcomes are needed to make the final decision. In this paper, we aim to discuss the risk of using HCQ in treating COVID-19 patients, including its possible side effects.", "qid": 28, "docid": "xv6g05zk", "rank": 20, "score": 0.8242731094360352}, {"content": "Title: Risk of using hydroxychloroquine as a treatment of COVID-19. Content: The emerging COVID-19 pandemic poses a threat to the global health care system. Given the lack of antiviral therapies or vaccines for the disease, the antimalarial drug hydroxychloroquine (HCQ) obtained much attention as a treatment for COVID-19. However, there are limited and uncertain clinical data to support the beneficial effect of this drug in COVID-19 treatment. HCQ has several side effects and warnings, including blindness, heart failure, and renal toxicity, even with recommended doses. For severe cases of COVID-19 or in patients with preexisting conditions, administering such a drug could be fatal, particularly when taken at high doses or in combination with other antibiotics. However, further well-designed studies that would address the optimal dose, duration of treatment, possible side effects, and long-term usage outcomes are needed to make the final decision. In this paper, we aim to discuss the risk of using HCQ in treating COVID-19 patients, including its possible side effects.", "qid": 28, "docid": "p88auycu", "rank": 21, "score": 0.8242731094360352}, {"content": "Title: Review: Hydroxychloroquine and Chloroquine for Treatment of SARS-CoV-2 (COVID-19) Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging viral infection causing coronavirus disease 2019 (COVID-19). Hydroxychloroquine and chloroquine have garnered unprecedented attention as potential therapeutic agents against COVID-19 following several small clinical trials, uncontrolled case series, and public figure endorsements. While there is a growing body of scientific data, there is also concern for harm, particularly QTc prolongation and cardiac arrhythmias. Here, we perform a rapid narrative review and discuss the strengths and limitations of existing in vitro and clinical studies. We call for additional randomized controlled trial evidence prior to the widespread incorporation of hydroxychloroquine and chloroquine into national and international treatment guidelines.", "qid": 28, "docid": "wmpjfc02", "rank": 22, "score": 0.8237764239311218}, {"content": "Title: Swinging the pendulum: lessons learned from public discourse concerning hydroxychloroquine and COVID-19 Content: INTRODUCTION: Several months into the COVID-19 pandemic, safe and effective treatments against this global health disaster have yet to be identified. Clinical research trials around the world are underway testing a wide array of possible medications. In particular, the off-label use of hydroxychloroquine for COVID-19 prophylaxis and treatment has created many unprecedented challenges for the scientific community and the public. AREAS COVERED: We critically assessed major events from February - May 2020 that contributed to widespread use of hydroxychloroquine for the treatment and prophylaxis of COVID-19. We aimed to explore how opinions towards hydroxychloroquine may shift from early enthusiasm (based on in vitro and preliminary clinical data) to the hope for a miracle cure (through communication and promotion of questionable results) and, finally, to a rise of skepticism as more in-depth analyses are emerging. EXPERT OPINION: Mindful and rigorous acquisition of data, as well as its interpretation, are essential to an effective pandemic response. The rapid and premature promotion of results has had major implications for global crisis management, even creating distrust among the public. It is crucial for the medical and scientific community to incorporate the lessons learned from this situation.", "qid": 28, "docid": "salxq8ir", "rank": 23, "score": 0.8234752416610718}, {"content": "Title: Rethinking the role of hydroxychloroquine in the treatment of COVID-19 Content: There are currently no proven or approved treatments for coronavirus disease 2019 (COVID-19). Early anecdotal reports and limited in vitro data led to the significant uptake of hydroxychloroquine (HCQ), and to lesser extent chloroquine (CQ), for many patients with this disease. As an increasing number of patients with COVID-19 are treated with these agents and more evidence accumulates, there continues to be no high-quality clinical data showing a clear benefit of these agents for this disease. Moreover, these agents have the potential to cause harm, including a broad range of adverse events including serious cardiac side effects when combined with other agents. In addition, the known and potent immunomodulatory effects of these agents which support their use in the treatment of auto-immune conditions, and provided a component in the original rationale for their use in patients with COVID-19, may, in fact, undermine their utility in the context of the treatment of this respiratory viral infection. Specifically, the impact of HCQ on cytokine production and suppression of antigen presentation may have immunologic consequences that hamper innate and adaptive antiviral immune responses for patients with COVID-19. Similarly, the reported in vitro inhibition of viral proliferation is largely derived from the blockade of viral fusion that initiates infection rather than the direct inhibition of viral replication as seen with nucleoside/tide analogs in other viral infections. Given these facts and the growing uncertainty about these agents for the treatment of COVID-19, it is clear that at the very least thoughtful planning and data collection from randomized clinical trials are needed to understand what if any role these agents may have in this disease. In this article, we review the datasets that support or detract from the use of these agents for the treatment of COVID-19 and render a data informed opinion that they should only be used with caution and in the context of carefully thought out clinical trials, or on a case-by-case basis after rigorous consideration of the risks and benefits of this therapeutic approach.", "qid": 28, "docid": "87uhx3pt", "rank": 24, "score": 0.8229915499687195}, {"content": "Title: Commentary on \u201cHydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open label non-randomized clinical trial\u201d by Gautret et al Content: The results of a clinical trial comparing hydroxychloroquine with or without azithromycin to the standard of care for the treatment of COVID-19 were recently published by Philippe Gautret et al. This study provides outstanding results for the combination of hydroxychloroquine and azithromycin over the standard of care, but the evidence was deemed insufficiently robust to warrant a public health decision to widen the use of hydroxychloroquine for the treatment of COVID-19. We provide a scientific critical review of the Gautret et al. publication, put the results in the context of the current knowledge, provide an evaluation of the validity of the results (from a methodologic perspective), and discuss public health implications. The study has a number of limitations, including small sample size, lack of comparability between patients in active treatment and control arms, lack of blinding, use of interim analyses without controlling for the risk of type 1 error, use of analysis in the per-protocol population instead of the intention-to-treat population, and inconsistencies between the study protocol and article. However, none of these observations is of a nature to reverse the conclusions. The study brings useful knowledge consistent with available evidence and clinical practice from China and South Korea, which could have prompted quicker policy decision-making.", "qid": 28, "docid": "gg706q8s", "rank": 25, "score": 0.8228152990341187}, {"content": "Title: Rethinking the role of hydroxychloroquine in the treatment of COVID\u201019 Content: There are currently no proven or approved treatments for coronavirus disease 2019 (COVID\u201019). Early anecdotal reports and limited in vitro data led to the significant uptake of hydroxychloroquine (HCQ), and to lesser extent chloroquine (CQ), for many patients with this disease. As an increasing number of patients with COVID\u201019 are treated with these agents and more evidence accumulates, there continues to be no high\u2010quality clinical data showing a clear benefit of these agents for this disease. Moreover, these agents have the potential to cause harm, including a broad range of adverse events including serious cardiac side effects when combined with other agents. In addition, the known and potent immunomodulatory effects of these agents which support their use in the treatment of auto\u2010immune conditions, and provided a component in the original rationale for their use in patients with COVID\u201019, may, in fact, undermine their utility in the context of the treatment of this respiratory viral infection. Specifically, the impact of HCQ on cytokine production and suppression of antigen presentation may have immunologic consequences that hamper innate and adaptive antiviral immune responses for patients with COVID\u201019. Similarly, the reported in vitro inhibition of viral proliferation is largely derived from the blockade of viral fusion that initiates infection rather than the direct inhibition of viral replication as seen with nucleoside/tide analogs in other viral infections. Given these facts and the growing uncertainty about these agents for the treatment of COVID\u201019, it is clear that at the very least thoughtful planning and data collection from randomized clinical trials are needed to understand what if any role these agents may have in this disease. In this article, we review the datasets that support or detract from the use of these agents for the treatment of COVID\u201019 and render a data informed opinion that they should only be used with caution and in the context of carefully thought out clinical trials, or on a case\u2010by\u2010case basis after rigorous consideration of the risks and benefits of this therapeutic approach.", "qid": 28, "docid": "75vvix5o", "rank": 26, "score": 0.8220670223236084}, {"content": "Title: Therapeutic use of chloroquine and hydroxychloroquine in COVID-19 and other viral infections: A narrative review Content: Abstract The rapidly spreading Coronavirus Disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), represents an unprecedented serious challenge to the global public health community. The extremely rapid international spread of the disease with significant morbidity and mortality made finding possible therapeutic interventions a global priority. While approved specific antiviral drugs against SARS-CoV-2 are still lacking, a large number of existing drugs are being explored as a possible treatment for COVID-19 infected patients. Recent publications have re-examined the use of Chloroquine (CQ) and/or Hydroxychloroquine (HCQ) as a potential therapeutic option for these patients. In an attempt to explore the evidence that supports their use in COVID-19 patients, we comprehensively reviewed the previous studies which used CQ or HCQ as an antiviral treatment. Both CQ and HCQ demonstrated promising in vitro results, however, such data have not yet been translated into meaningful in vivo studies. While few clinical trials have suggested some beneficial effects of CQ and HCQ in COVID-19 patients, most of the reported data are still preliminary. Given the current uncertainty, it is worth being mindful of the potential risks and strictly rational the use of these drugs in COVID-19 patients until further high quality randomized clinical trials are available to clarify their role in the treatment or prevention of COVID-19.", "qid": 28, "docid": "5yvjbr5q", "rank": 27, "score": 0.8189564943313599}, {"content": "Title: Chloroquine and Hydroxychloroquine for the treatment of COVID-19: A Systematic Review and Meta-analysis Content: Background: There is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain. Objective: We performed a systematic review to synthesize the available data on the efficacy and safety of CQ and HCQ for the treatment of COVID-19. Methods: Two reviewers searched for published and pre-published relevant articles between December 2019 to 8th June 2020. The data from the selected studies were abstracted and analyzed for efficacy and safety outcomes. Critical appraisal of the evidence was done by Cochrane risk of bias tool and Newcastle Ottawa scale. The quality of evidence was graded as per the GRADE approach. Results: We reviewed 12 observational and 3 randomized trials which included 10659 patients of whom 5713 received CQ/HCQ and 4966 received only standard of care. The efficacy of CQ/HCQ for COVID-19 was inconsistent across the studies. Meta-analysis of included studies revealed no significant reduction in mortality with HCQ use [RR 0.98 95% CI 0.66-1.46] , time to fever resolution [mean difference -0.54 days (-1.19-011)] or clinical deterioration/development of ARDS with HCQ [RR 0.90 95% CI 0.47-1.71]. There was a higher risk of ECG abnormalities/arrhythmia with HCQ/CQ [RR 1.46 95% CI 1.04 to 2.06]. The quality of evidence was graded as very low for these outcomes. Conclusions: The available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID-19.", "qid": 28, "docid": "uf32cq68", "rank": 28, "score": 0.8181905746459961}, {"content": "Title: Primum non nocere \u2013 Are chloroquine and hydroxychloroquine safe prophylactic/treatment options for SARS-CoV-2 (covid-19)? Content: Chloroquine (CQ) and its analog hydroxychloroquine (HCQ) were recently included in several clinical trials as potential prophylactic and therapeutic options for SARS-COV-2 infection/covid-19. However, drug effectiveness in preventing, treating, or slowing the progression of the disease is still unknown. Despite some initial promising in vitro results, rigorous pre-clinical animal studies and randomized clinical trials have not been performed yet. On the other hand, while the potential effectiveness of CQ/HCQ is, at best, hypothetical, their side effects are factual and most worrisome, particularly when considering vulnerable groups of patients being treated with these drugs. in this comment, we briefly explain the possible mechanisms of action of CQ/HCQ for treating other diseases, possible actions against covid-19, and their potent side effects, in order to reinforce the necessity of evaluating the benefit-risk balance when widely prescribing these drugs for SARS-COV-2 infection/covid-19. We conclude by strongly recommending against their indiscriminate use.", "qid": 28, "docid": "u87lx38h", "rank": 29, "score": 0.8179612159729004}, {"content": "Title: Hydroxychloroquine Versus COVID-19: A Rapid Systematic Review and Meta-Analysis Content: Background: Coronavirus Disease 2019 (COVID-19) has become a major global issue with rising the number of infected individuals and mortality in recent months. Among all therapeutic approaches, arguments have raised about hydroxychloroquine efficacy in treatment of COVID-19. We aimed to overcome the controversies regarding effectiveness of hydroxychloroquine in treatment of COVID-19, using a systematic review and meta-analysis. Methods: A systematic search was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, Google Scholar and medRxiv pre-print database using all available MeSH terms for COVID-19 and hydroxychloroquine. Two authors selected and assessed the quality of studies independently using related checklists. Data have been extracted from included studies and analyzed using CMA v. 2.2.064. heterogeneity was also assessed using I-squared test. Results: Seven studies including four clinical trials and three observational studies have entered into the study. The results of meta-analysis of clinical trials showed that there were no significant differences between patients who received the standard treatment with HCQ regimen and the patients that received the standard treatment without HCQ (RR: 1.44, 95% CI, 0.80-2.59). CT-Scan findings improved in 59% (95% CI 0.15-0.92) and nasopharyngeal culture following RT-PCR resulted negative in 76% (95% CI 0.56-0.89) of patients received hydroxychloroquine. Meta-analysis of observational studies showed 75% (95% CI, 0.54-0.88) of patients were discharged from the hospital, 34% (95% CI, 0.07-0.14) admitted to intensive care unit and 1.5% (95% CI, 0.03-0.83) have expired. Conclusion: This study indicated no clinical benefits regarding HCQ for treatment of COVID-19 patients. However, further large clinical trials should be taken into account in order to achieve more reliable findings.", "qid": 28, "docid": "ujomta30", "rank": 30, "score": 0.8178362250328064}, {"content": "Title: Repositioned chloroquine and hydroxychloroquine as antiviral prophylaxis for COVID-19: A protocol for rapid systematic review of randomized controlled trials Content: Since the SARS-CoV-2 outbreak rapidly evolved into a pandemic, there is an urgent need for rapid development, identification and confirmation of efficacious antiviral prophylaxis. In this setting, the existing drugs chloroquine (CQ) and hydroxychloroquine (HCQ) which has suggestive evidence of efficacy against SARS-CoV-2 infection and COVID-19 disease has become prime candidates to be repositioned as therapeutic and preventative agents, and a growing number of clinical trials have been registered to study their preventative potential for at-risk populations using a range of dosing schemes and outcome measures. This rapid systematic review protocol aims to provide streamlined and timely synthesis on methodologies and results of randomized controlled trials assessing the efficacy of CQ and HCQ in hopes that this will constructively inform further research as well as public health policy.", "qid": 28, "docid": "ehidj2ev", "rank": 31, "score": 0.8161910176277161}, {"content": "Title: Chloroquine and hydroxychloroquine in the context of COVID-19 Content: Chloroquine and closely related structural analogs, employed initially for the treatment of malaria, are now gaining worldwide attention due to the rapidly spreading pandemic caused by severe acute respiratory syndrome-coronavirus-2, named coronavirus disease (COVID) of 2019 (COVID-19). Although much of this attention has a mechanistic basis, the hard efficacy data for chloroquine/hydroxychloroquine in the management of the clinical syndrome of COVID-19 have been limited thus far. This review aims to present the available in vitro and clinical data for the role of chloroquine/hydroxychloroquine in COVID-19 and attempts to put them into perspective, especially in relation to the different risks/benefits particular to each patient who may require treatment.", "qid": 28, "docid": "tkqmu1va", "rank": 32, "score": 0.815744936466217}, {"content": "Title: A Rapid Systematic Review of Clinical Trials Utilizing Chloroquine and Hydroxychloroquine as a Treatment for COVID-19 Content: OBJECTIVES: The emergence of SARS-CoV-2 has presented clinicians with a difficult therapeutic dilemma. With supportive care as the current mainstay of treatment, the fatality rate of COVID-19 is 6.9%. There are currently several trials assessing the efficacy of different antivirals as treatment. Of these, chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have garnered the most attention. METHODS: In this study, the literature currently available on CQ and HCQ as treatment of COVID-19 was surveyed using EMBASE, PubMed, Cochrane Library, MedRxiv, and one clinical trial registry. Upon gathering published and preprint trials, risk of bias was assessed using Cochrane Risk of Bias Tool 2.0. RESULTS: There are currently seven completed clinical trials and 29 registered clinical trials focusing on HCQ or CQ as a therapeutic avenue for COVID-19. Of these, five of seven trials have shown favorable outcomes for patients using CQ or HCQ and two of seven have shown no change compared to control. However, all seven trials carried varying degrees of bias and poor study design. CONCLUSION: There are currently not enough data available to support the routine use of HCQ and CQ as therapies for COVID-19. Pending further results from more extensive studies with more stringent study parameters, clinicians should defer from routine use of HCQ and CQ. There are several clinical trials currently under way with results expected soon.", "qid": 28, "docid": "bfui91w7", "rank": 33, "score": 0.8144960403442383}, {"content": "Title: \u201cHydroxychloroquine in patients with COVID-19: A Systematic Review and meta-analysis.\u201d Content: BACKGROUNDS AND AIMS: The role of hydroxychloroquine (HCQ) in the treatment of COVID-19 is not fully known. We studied the efficacy of HCQ compared to the control in COVID-19 subjects on a. viral clearance measured by reverse transcriptase polymerase chain reaction (RT-PCR) and, b. death due to all cause. METHODS: PubMed, Scopus, Cochrane and MedRxiv database were searched using the specific keywords up to April 30, 2020. Studies that met our objectives were assessed for the risk of bias applying various tools as indicated. Three studies each that reported the outcome of viral clearance by RT-PCR and death due to all cause, were meta-analyzed by applying inverse variance-weighted averages of logarithmic risk ratio (RR) using a random effects model. Heterogeneity and publication bias were assessed using the I(2) statistic and funnel plots, respectively. RESULTS: Meta-analysis of 3 studies (n = 210) on viral clearance assessed by RT-PCR showed no benefit (RR, 1.05; 95% CI, 0.79 to 1.38; p = 0.74), although with a moderate heterogeneity (I(2) = 61.7%, p = 0.07). While meta-analysis of 3 studies (n = 474) showed a significant increase in death with HCQ, compared to the control (RR, 2.17; 95% 1.32 to 3.57; p = 0.002), without any heterogeneity (I(2) = 0.0%, p = 0.43). CONCLUSIONS: No benefit on viral clearance but a significant increase in mortality was observed with HCQ compared to control in patients with COVID-19.", "qid": 28, "docid": "95zrth5d", "rank": 34, "score": 0.8142855167388916}, {"content": "Title: The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis? Content: The anti-malarial drugs chloroquine (CQ) and primarily the less toxic hydroxychloroquine (HCQ) are currently used to treat autoimmune diseases for their immunomodulatory and anti-thrombotic properties. They have also been proposed for the treatment of several viral infections, due to their anti-viral effects in cell cultures and animal models, and, currently, for the treatment of coronavirus disease 2019 (COVID-19), the pandemic severe acute respiratory syndrome caused by coronavirus 2 (Sars-Cov-2) infection that is spreading all over the world. Although in some recent studies a clinical improvement in COVID-19 patients has been observed, the clinical efficacy of CQ and HCQ in COVID-19 has yet to be proven with randomized controlled studies, many of which are currently ongoing, also considering pharmacokinetics, optimal dosing regimen, therapeutic level and duration of treatment and taking into account patients with different severity degrees of disease. Here we review what is currently known on the mechanisms of action of CQ and HCQ as anti-viral, anti-inflammatory and anti-thrombotic drugs and discuss the up-to-date experimental evidence on the potential mechanisms of action of CQ/HCQ in Sars-Cov2 infection and the current clinical knowledge on their efficacy in the treatment of COVID-19 patients. Given the role of iron in several human viral infections, we also propose a different insight into a number of CQ and HCQ pharmacological effects, suggesting a potential involvement of iron homeostasis in Sars-Cov-2 infection and COVID-19 clinical course.", "qid": 28, "docid": "l6l24pco", "rank": 35, "score": 0.8135237693786621}, {"content": "Title: COVID-19 in Patient with Sarcoidosis Receiving Long-Term Hydroxychloroquine Treatment, France, 2020 Content: Because of in vitro studies, hydroxychloroquine is under evaluation as a preexposure or postexposure prophylaxis for coronavirus disease (COVID-19) and as a possible COVID-19 curative treatment. We report a case of COVID-19 in a patient with sarcoidosis who was receiving long-term hydroxychloroquine treatment, despite adequate plasma concentrations.", "qid": 28, "docid": "d612wsh3", "rank": 36, "score": 0.8133524656295776}, {"content": "Title: COVID-19 in Patient with Sarcoidosis Receiving Long-Term Hydroxychloroquine Treatment, France, 2020. Content: Because of in vitro studies, hydroxychloroquine is under evaluation as a preexposure or postexposure prophylaxis for coronavirus disease (COVID-19) and as a possible COVID-19 curative treatment. We report a case of COVID-19 in a patient with sarcoidosis who was receiving long-term hydroxychloroquine treatment, despite adequate plasma concentrations.", "qid": 28, "docid": "5moean7z", "rank": 37, "score": 0.8133524656295776}, {"content": "Title: Reply to Gautret et al: hydroxychloroquine sulfate and azithromycin for COVID-19: what is the evidence and what are the risks? Content: The severity of COVID-19 has resulted in a global rush to find the right antiviral treatment to conquer the pandemic and to treat patients. This requires reliable studies to support treatment. In a recently published study by Gautret et al. the authors concluded that hydroxychloroquine monotherapy and hydroxychloroquine in combination with azithromycin reduced viral load. However, this trial has several major methodological issues, including the design, outcome measure and the statistical analyses. In this paper we discuss the background, clinical evidence, pharmacology and methodological issues related to this clinical trial. We understand the rush to release results, however in case conclusions are far reaching the evidence needs to be robust.", "qid": 28, "docid": "wnb4cltt", "rank": 38, "score": 0.8130641579627991}, {"content": "Title: Challenges and cares to promote rational use of chloroquine and hydroxychloroquine in the management of coronavirus disease 2019 (COVID-19) pandemic: a timely review Content: As a result of the 2019 coronavirus disease pandemic (COVID-19), there has been an urgent worldwide demand for treatments. Due to factors such as history of prescription for other infectious diseases, availability, and relatively low cost, the use of chloroquine (CQ) and hydroxychloroquine (HCQ) has been tested in vivo and in vitro for the ability to inhibit the causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, even though investigators noted the therapeutic potential of these drugs, it is important to consider the toxicological risks and necessary care for rational use of CQ and HCQ. This study provides information on the main toxicological and epidemiological aspects to be considered for prophylaxis or treatment of COVID-19 using CQ but mainly HCQ, which is a less toxic derivative than CQ, and was shown to produce better results in inhibiting proliferation of SARS-CoV-2 based upon preliminary tests.", "qid": 28, "docid": "msz9d6cr", "rank": 39, "score": 0.8127866983413696}, {"content": "Title: \"Hydroxychloroquine in patients with COVID-19: A Systematic Review and meta-analysis.\" Content: BACKGROUNDS AND AIMS: The role of hydroxychloroquine (HCQ) in the treatment of COVID-19 is not fully known. We studied the efficacy of HCQ compared to the control in COVID-19 subjects on - a. viral clearance measured by reverse transcriptase polymerase chain reaction (RT-PCR) and, b. death due to all cause. METHODS: PubMed, Scopus, Cochrane and MedRxiv database were searched using the specific keywords up to April 30, 2020. Studies that met our objectives were assessed for the risk of bias applying various tools as indicated. Three studies each that reported the outcome of viral clearance by RT-PCR and death due to all cause, were meta-analyzed by applying inverse variance-weighted averages of logarithmic risk ratio (RR) using a random effects model. Heterogeneity and publication bias were assessed using the I2 statistic and funnel plots, respectively. RESULTS: Meta-analysis of 3 studies (n = 210) on viral clearance assessed by RT-PCR showed no benefit (RR, 1.05; 95% CI, 0.79 to 1.38; p = 0.74), although with a moderate heterogeneity (I2 = 61.7%, p = 0.07). While meta-analysis of 3 studies (n = 474) showed a significant increase in death with HCQ, compared to the control (RR, 2.17; 95% 1.32 to 3.57; p = 0.002), without any heterogeneity (I2 = 0.0%, p = 0.43). CONCLUSIONS: No benefit on viral clearance but a significant increase in mortality was observed with HCQ compared to control in patients with COVID-19.", "qid": 28, "docid": "dapkxiyy", "rank": 40, "score": 0.812685489654541}, {"content": "Title: Hydroxychloroquine use in the COVID-19 patient Content: Hydroxychloroquine (HCQ) has multiple potential antiviral mechanisms of action that differ according to the pathogen studied (eg, Chikungunya, Dengue virus, human immunodeficiency virus, poliovirus, Zika virus). Data on HCQ for treatment of coronavirus disease 2019 (COVID-19) are rapidly evolving. To date, there is no evidence from randomized controlled trials that HCQ, or any single therapy, improves outcomes in patients infected with COVID-19. There are also no clinical trial data supporting prophylactic HCQ therapy in COVID-19. Use of HCQ in patients with COVID-19 is being investigated for prophylaxis, postexposure prophylaxis, and treatment.", "qid": 28, "docid": "1x9vqepb", "rank": 41, "score": 0.8125794529914856}, {"content": "Title: An Updated Systematic Review of the Therapeutic Role of Hydroxychloroquine in Coronavirus Disease-19 (COVID-19) Content: BACKGROUND AND OBJECTIVE: The world is currently experiencing the Coronavirus Disease-19 (COVID-19) pandemic. There is no approved drug for the definitive treatment of the disease. Various drugs are being tried for the treatment of COVID-19, including hydroxychloroquine (HCQ). This study was performed to systematically review the therapeutic role of HCQ in COVID-19 from the available literature. METHODS: PubMed, Embase, ClinicalTrials.gov, ICTRP (WHO), Cochrane Library databases, and two pre-print servers (medRxiv.org and Research Square) were searched for clinical studies that evaluated the therapeutic role of HCQ on COVID-19 until 10 May 2020. The available studies were critically analyzed and the data were extracted. RESULTS: A total of 663 articles were screened and 12 clinical studies (seven peer-reviewed and published studies and five non-peer-reviewed studies from pre-print servers) with a total sample size of 3543 patients were included. Some of the clinical studies demonstrated good virological and clinical outcomes with HCQ alone or in combination with azithromycin in COVID-19 patients, although the studies had major methodological limitations. Some of the other studies showed negative results with HCQ therapy along with the risk of adverse reactions. CONCLUSION: The results of efficacy and safety of HCQ in COVID-19, as obtained from the clinical studies, are not satisfactory, although many of these studies had major methodological limitations. Stronger evidence from well-designed robust randomized clinical trials is required before conclusively determining the role of HCQ in the treatment of COVID-19. Clinical prudence is required in advocating HCQ as a therapeutic armamentarium in COVID-19. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40261-020-00927-1) contains supplementary material, which is available to authorized users.", "qid": 28, "docid": "ne8k1vez", "rank": 42, "score": 0.8123557567596436}, {"content": "Title: Systematic Review and Meta-analysis of the Effectiveness and Safety of Hydroxychloroquine in COVID-19. Content: Backgrounds. Since COVID-19 outbreak, various agents have been tested but no proven effective therapies have been identified. This has led to a lot of controversies among associated researches. Hence, in order to address the issue of using hydroxychloroquine in treating COVID-19 patients, we conducted a systematic review and meta-analysis. Methods. A thorough search was carried out to find relevant studies in MEDLINE, medRxiv, PubMed, Cochrane Database, China Academic Journals Full-text Database and Web of Science. Two investigators independently reviewed 274 abstracts and 23 articles. The trials which evaluated hydroxychloroquine for treatment of COVID-19 were included for this systematic review. Two investigators assessed quality of the studies and data extraction was done by one reviewer and cross checked by the other. Results. Five trials involving 677 patients were included while conducting the meta-analysis. Compared with the control group, hydroxychloroquine with or without azithromycin showed benefits in positive-to-negative conversion of SARS-CoV-2 (odds ratio [OR], 1.95 [95% CI,0.19 to 19.73] and a reduction in progression rate (OR, 0.89 [95% CI, 0.58 to 1.37]), but without demonstrating any statistical significance. This systematic review has also suggested a possible synergistic effect of the combination therapy which included hydroxychloroquine and azithromycin. However, the use of hydroxychloroquine alone was associated with increased mortality in COVID-19 patients. Conclusion. The use of hydroxychloroquine with or without azithromycin for treatment of COVID-19 patients, seems to be effective. The combination of hydroxychloroquine and azithromycin has shown synergic effects. However, mortality rate was increased when the treatment was conducted with hydroxychloroquine.", "qid": 28, "docid": "2f6nj4to", "rank": 43, "score": 0.8123332262039185}, {"content": "Title: A Rapid Systematic Review of Clinical Trials Utilizing Chloroquine and Hydroxychloroquine as a Treatment for COVID\u201019 Content: OBJECTIVES: The emergence of SARS\u2010CoV\u20102 has presented clinicians with a difficult therapeutic dilemma. With supportive care as the current mainstay of treatment, the fatality rate of COVID\u201019 is 6.9%. There are currently several trials assessing the efficacy of different antivirals as treatment. Of these, chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have garnered the most attention. METHODS: In this study, the literature currently available on CQ and HCQ as treatment of COVID\u201019 was surveyed using EMBASE, PubMed, Cochrane Library, MedRxiv, and one clinical trial registry. Upon gathering published and preprint trials, risk of bias was assessed using Cochrane Risk of Bias Tool 2.0. RESULTS: There are currently seven completed clinical trials and 29 registered clinical trials focusing on HCQ or CQ as a therapeutic avenue for COVID\u201019. Of these, five of seven trials have shown favorable outcomes for patients using CQ or HCQ and two of seven have shown no change compared to control. However, all seven trials carried varying degrees of bias and poor study design. CONCLUSION: There are currently not enough data available to support the routine use of HCQ and CQ as therapies for COVID\u201019. Pending further results from more extensive studies with more stringent study parameters, clinicians should defer from routine use of HCQ and CQ. There are several clinical trials currently under way with results expected soon.", "qid": 28, "docid": "4stz2t7s", "rank": 44, "score": 0.8116996884346008}, {"content": "Title: When there is a pandemic there is no time to waste: should we have hydroxychloroquine in our armoury against COVID-19 infected patients? Content: The current use of chloroquine and/or hydroxychloroquine, a drug currently used to treat autoimmune rheumatic diseases, in treating severe acute respiratory syndrome caused by coronavirus 2 (SARSCoV-2) or COVID-19-infected patients with pneumonia is a matter of intense consideration. We wish to enter the ongoing debate as to whether this well-known drug must be given to Greek COVID-19-infected patients, especially those with pneumonia. Our arguments are based on the existing data and the capacity of the Greek health system to afford potent anti-viral treatments, which are under immense investigation. We propose several suggestions related to treatment of COVID-19 pneumonia with chloroquine/hydroxychloroquine that we think must be taken into consideration to fit the evolving situation of the pandemic in Greece.", "qid": 28, "docid": "vvexfg1c", "rank": 45, "score": 0.8115557432174683}, {"content": "Title: Smooth or Risky Revisit of an Old Malaria Drug for COVID-19? Content: Hydroxychloroquine (HCQ) is an old medication for malaria. In addition to handling this parasitic disease, HCQ is also used to treat a number of autoimmune disorders including rheumatoid arthritis and systemic lupus erythematosus when other medications are not effective. Recently a new viral infection (COVID-19) is rocking the entire world so much that it has already taken more than 200,000 lives throughout the world within the last two months and the World Health Organization was forced to declare it as a pandemic on March 11, 2020. Interestingly, some reports indicate that this wonder drug may be also beneficial for COVID-19 and accordingly, many clinical trials have begun. Here, we discuss different modes of action (anti-inflammatory, antioxidant, inhibition of endosomal acidification, suppression of angiotensin-converting enzyme 2 or ACE2 glycosylation, etc.) of HCQ that might be responsible for its possible anti-COVID-19 effect. On the other hand, this review also makes an honest attempt to delineate mechanisms (increase in vasoconstriction, inhibition of autophagy, depletion of T cells, etc.) indicating how it may aggravate certain conditions and why caution should be taken before granting widespread repurposing of HCQ for COVID-19. Graphical Abstract.", "qid": 28, "docid": "kmic4j3q", "rank": 46, "score": 0.8111553192138672}, {"content": "Title: Systematic benefit-risk assessment for the use of chloroquine or hydroxychloroquine as a treatment for COVID-19: Establishing a framework for rapid decision-making Content: Objectives: Given the current pandemic, there is an urgent need to identify effective, safe treatments for COVID-19 (coronavirus disease). A systematic benefit-risk assessment was designed and conducted to strengthen the ongoing monitoring of the benefit-risk balance for chloroquine and hydroxychloroquine in COVID-19 treatment. Methods: The overall benefit-risk of the use of chloroquine or hydroxychloroquine as a treatment for COVID-19 compared to standard of care, placebo or other treatments was assessed using the Benefit-Risk Action Team (BRAT) framework. We searched PubMed and Google Scholar to identify literature reporting clinical outcomes in patients taking chloroquine or hydroxychloroquine for COVID-19. A value tree was constructed and key benefits and risks were ranked by two clinicians in order of considered importance. Results: Several potential key benefits and risks were identified for use of hydroxychloroquine or chloroquine in COVID-19 treatment. For the benefit of virological clearance, three studies were identified. A significant risk difference (RD) between hydroxychloroquine and the comparator group (standard of care) was found for only one study (RD=0.58, 95% CI: 0.17, 0.98). The risk difference was not significant for the other two studies (RD=-0.07, 95% CI:-0.75, 0.61 and RD=0.08, 95% CI:-0.74, 0.91). In addition, no significant risk difference between hydroxychloroquine and the comparator group (standard of care) was identified for the risk of abnormal liver function tests (LFTs) (RD=0.07, 95% CI: -0.28, 0.41). Conclusions: Overall, no conclusion can be made on the benefit-risk profile of hydroxychloroquine or chloroquine in the treatment of COVID-19 compared to standard of care, placebo or other treatments at this time. Whilst the availability of comparative data are limited, the current framework summarises the key anticipated benefits and risks. As further data from clinical trials and real world use on these benefits and risks becomes available, this can be incorporated into the framework for an ongoing benefit-risk assessment.", "qid": 28, "docid": "zhfrgaxf", "rank": 47, "score": 0.8110246658325195}, {"content": "Title: An Updated Systematic Review of the Therapeutic Role of Hydroxychloroquine in Coronavirus Disease-19 (COVID-19) Content: BACKGROUND AND OBJECTIVE: The world is currently experiencing the Coronavirus Disease-19 (COVID-19) pandemic. There is no approved drug for the definitive treatment of the disease. Various drugs are being tried for the treatment of COVID-19, including hydroxychloroquine (HCQ). This study was performed to systematically review the therapeutic role of HCQ in COVID-19 from the available literature. METHODS: PubMed, Embase, ClinicalTrials.gov, ICTRP (WHO), Cochrane Library databases, and two pre-print servers (medRxiv.org and Research Square) were searched for clinical studies that evaluated the therapeutic role of HCQ on COVID-19 until 10 May 2020. The available studies were critically analyzed and the data were extracted. RESULTS: A total of 663 articles were screened and 12 clinical studies (seven peer-reviewed and published studies and five non-peer-reviewed studies from pre-print servers) with a total sample size of 3543 patients were included. Some of the clinical studies demonstrated good virological and clinical outcomes with HCQ alone or in combination with azithromycin in COVID-19 patients, although the studies had major methodological limitations. Some of the other studies showed negative results with HCQ therapy along with the risk of adverse reactions. CONCLUSION: The results of efficacy and safety of HCQ in COVID-19, as obtained from the clinical studies, are not satisfactory, although many of these studies had major methodological limitations. Stronger evidence from well-designed robust randomized clinical trials is required before conclusively determining the role of HCQ in the treatment of COVID-19. Clinical prudence is required in advocating HCQ as a therapeutic armamentarium in COVID-19.", "qid": 28, "docid": "5gvdddeh", "rank": 48, "score": 0.8106961846351624}, {"content": "Title: Hydroxychloroquine against COVID-19: A critical appraisal of the existing evidence Content: Hydroxychloroquine (HCQ) has sparked much interest in the therapeutics of the Coronavirus Disease 2019 (COVID-19) pandemic. Its antiviral properties have been studied for years; regarding the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2), it has been shown that HCQ may act at multiple levels. These extend from the initial attachment of the virus to the respiratory epithelium to the inhibition of its replication by the alkalinisation of the phagolysosome's microenvironment and the post-translational modification of certain viral proteins. Preliminary clinical evidence from China and France showed significant virological and clinical benefit in HCQ-treated patients, while other studies, mostly including critically ill patients, did not show favorable results. In this review, we critically appraise the existing evidence on HCQ against SARS-CoV-2 with particular emphasis on its protective and therapeutic role. Safety concerns that are relevant to the short-term HCQ use are also discussed. In the context of the rapid evolution of the COVID-19 pandemic that strains the health care systems worldwide and considering limited population-wide testing rates in most of the vulnerable countries, early empiric short-term administration of HCQ in symptomatic individuals, may be a promising, safe and low-cost strategy.", "qid": 28, "docid": "5jafu8tw", "rank": 49, "score": 0.8106141090393066}, {"content": "Title: Hydroxychloroquine against COVID-19: A critical appraisal of the existing evidence. Content: Hydroxychloroquine (HCQ) has sparked much interest in the therapeutics of the Coronavirus Disease 2019 (COVID-19) pandemic. Its antiviral properties have been studied for years; regarding the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2), it has been shown that HCQ may act at multiple levels. These extend from the initial attachment of the virus to the respiratory epithelium to the inhibition of its replication by the alkalinisation of the phagolysosome's microenvironment and the post-translational modification of certain viral proteins. Preliminary clinical evidence from China and France showed significant virological and clinical benefit in HCQ-treated patients, while other studies, mostly including critically ill patients, did not show favorable results. In this review, we critically appraise the existing evidence on HCQ against SARS-CoV-2 with particular emphasis on its protective and therapeutic role. Safety concerns that are relevant to the short-term HCQ use are also discussed. In the context of the rapid evolution of the COVID-19 pandemic that strains the health care systems worldwide and considering limited population-wide testing rates in most of the vulnerable countries, early empiric short-term administration of HCQ in symptomatic individuals, may be a promising, safe and low-cost strategy.", "qid": 28, "docid": "an28gfe4", "rank": 50, "score": 0.8106140494346619}, {"content": "Title: Rheumotologitsts\u2019 view on the use of hydroxychloroquine to treat COVID-19 Content: The current pandemic coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) calls urgently for effective therapies. Anti-malarial medicine chloroquine (CQ) and particularly its chemical analogue hydroxychloroquine (HCQ) have been recommended as promising candidate therapeutics that are now under either compassionate off-label use or clinical trials for the treatment of COVID-19 patients. However, there are public concerns and disputes about both the safety and efficacy of CQ and HCQ for this new application. Given the fact that for decades HCQ has been approved as an immunomodulatory drug for the long term treatment of chronic rheumatic diseases, as experienced rheumatologists, we would like to share our thoughts in this regard and trigger a brainstorm among clinical care providers for exchanging their diverse opinions on this urgent topic.", "qid": 28, "docid": "isxasd9b", "rank": 51, "score": 0.8094373941421509}, {"content": "Title: Rheumotologitsts' view on the use of hydroxychloroquine to treat COVID-19 Content: The current pandemic coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) calls urgently for effective therapies. Anti-malarial medicine chloroquine (CQ) and particularly its chemical analogue hydroxychloroquine (HCQ) have been recommended as promising candidate therapeutics that are now under either compassionate off-label use or clinical trials for the treatment of COVID-19 patients. However, there are public concerns and disputes about both the safety and efficacy of CQ and HCQ for this new application. Given the fact that for decades HCQ has been approved as an immunomodulatory drug for the long term treatment of chronic rheumatic diseases, as experienced rheumatologists, we would like to share our thoughts in this regard and trigger a brainstorm among clinical care providers for exchanging their diverse opinions on this urgent topic.", "qid": 28, "docid": "f3mebese", "rank": 52, "score": 0.8094373941421509}, {"content": "Title: Hydroxychloroquine use in the COVID-19 patient. Content: Hydroxychloroquine (HCQ) has multiple potential antiviral mechanisms of action that differ according to the pathogen studied (eg, Chikungunya, Dengue virus, human immunodeficiency virus, poliovirus, Zika virus). Data on HCQ for treatment of coronavirus disease 2019 (COVID-19) are rapidly evolving. To date there is no evidence from randomized controlled trials that any single therapy improves outcomes in patients infected with COVID-19. There are also no clinical trial data supporting prophylactic HCQ therapy in COVID-19. Hydroxychloroquine (HCQ) use in patients with COVID-19 is being investigated examining prophylaxis, postexposure prophylaxis, and treatment regimens.", "qid": 28, "docid": "7ttesiuu", "rank": 53, "score": 0.8092166185379028}, {"content": "Title: Hydroxychloroquine for Treatment of SARS\u2010CoV\u20102 Infection? Improving Our Confidence in a Model\u2010Based Approach to Dose Selection Content: In less than six months, COVID-19 has spread from a marketplace in Wuhan, China to over 150 countries and territories of the world. Therapeutics are desperately needed to reduce the morbidity and mortality of this pandemic disease. It has been reported that hydroxychloroquine (HCQ) is active against SARS-CoV-2 in vitro, and this finding was quickly supported by an open label non-randomized clinical trial that provided the first published clinical evidence HCQ may be a treatment option.", "qid": 28, "docid": "248de4cj", "rank": 54, "score": 0.8091937303543091}, {"content": "Title: A case report of serious haemolysis in a glucose-6-phosphate dehydrogenase-deficient COVID-19 patient receiving hydroxychloroquine Content: While the COVID-19 epidemic occurred since December 2019, as of end April 2020, no treatment has been validated or invalidated by accurate clinical trials. Use of hydroxychloroquine has been popularised on mass media and put forward as a valid treatment option without strong evidence of efficacy. Hydroxychloroquine (HCQ) has its own side effects, some of which are very serious like acute haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. Side effects may be worse than the disease itself. Belgian national treatment guidelines recommend the use of HCQ in mild to severe COVID-19 disease. As opinions, politics, media and beliefs are governing COVID-19 therapy, performance of randomised controlled blinded clinical trials became difficult. Results of sound clinical trials are eagerly awaited. We report a case of acute haemolysis leading to admission in intensive care unit and renal failure in a patient with uncovered G6PD deficiency.", "qid": 28, "docid": "fnbuagwg", "rank": 55, "score": 0.8091161251068115}, {"content": "Title: Chloroquine as prophylactic agent against COVID-19? Content: \u2022 Efficacy of hydroxychloroquine and chloroquine in COVID-19 treatment; \u2022 Use of hydroxychloroquine or chloroquine in COVID-19 prophylaxis.", "qid": 28, "docid": "03eifdr1", "rank": 56, "score": 0.8089922070503235}, {"content": "Title: Efficacy and safety of chloroquine or hydroxychloroquine in moderate type of COVID-19: a prospective open-label randomized controlled study Content: The outbreak of novel coronavirus disease 2019 (COVID-19) has become a pandemic. Drug repurposing may represent a rapid way to fill the urgent need for effective treatment. We evaluated the clinical utility of chloroquine and hydroxychloroquine in treating COVID-19. Forty-eight patients with moderate COVID-19 were randomized to oral treatment with chloroquine (1000 mg QD on Day 1, then 500 mg QD for 9 days; n=18), hydroxychloroquine (200 mg BID for 10 days; n=18), or control treatment (n=12). Adverse events were mild, except for one case of Grade 2 ALT elevation. Adverse events were more commonly observed in the chloroquine group (44.44%) and the hydroxychloroquine group (50.00%) than in the control group (16.67%). The chloroquine group achieved shorter time to clinical recovery (TTCR) than the control group (P=0.019). There was a trend toward reduced TTCR in the hydroxychloroquine group (P=0.049). The time to reach viral RNA negativity was significantly faster in the chloroquine group and the hydroxychloroquine group than in the control group (P=0.006 and P=0.010, respectively). The median numbers of days to reach RNA negativity in the chloroquine, hydroxychloroquine, and control groups was 2.5 (IQR: 2.0-3.8) days, 2.0 (IQR: 2.0-3.5) days, and 7.0 (IQR: 3.0-10.0) days, respectively. The chloroquine and hydroxychloroquine groups also showed trends toward improvement in the duration of hospitalization and findings on lung computerized tomography (CT). This study provides evidence that (hydroxy)chloroquine may be used effectively in treating moderate COVID-19 and supports larger trials.", "qid": 28, "docid": "t1vom8f3", "rank": 57, "score": 0.8087176084518433}, {"content": "Title: Hydroxychloroquine Proves Ineffective in Hamsters and Macaques Infected with SARS-CoV-2 Content: We remain largely without effective prophylactic/therapeutic interventions for COVID-19. Although many human clinical trials are ongoing, there remains a deficiency of supportive preclinical drug efficacy studies. Here we assessed the prophylactic/therapeutic efficacy of hydroxychloroquine (HCQ), a drug of interest for COVID-19 management, in two animal models. When used for prophylaxis or treatment neither the standard human malaria dose (6.5 mg/kg) nor a high dose (50 mg/kg) of HCQ had any beneficial effect on clinical disease or SARS-CoV-2 kinetics (replication/shedding) in the Syrian hamster disease model. Similarly, HCQ prophylaxis/treatment (6.5 mg/kg) did not significantly benefit clinical outcome nor reduce SARS-CoV-2 replication/shedding in the upper and lower respiratory tract in the rhesus macaque disease model. In conclusion, our preclinical animal studies do not support the use of HCQ in prophylaxis/treatment of COVID-19.", "qid": 28, "docid": "y5cbp2yz", "rank": 58, "score": 0.8083546161651611}, {"content": "Title: Pharmacokinetic bases of the hydroxychloroquine response in COVID-19: implications for therapy and prevention Content: Chloroquine/hydroxychloroquine has recently been the subject of intense debate in regard to its potential antiviral activity against SARS-Cov-2, the etiological agent of COVID-19. Some report possible curative effects, others do not. In order to shed some light on this rather controversial topic, we used mathematical modelling to simulate possible scenarios of response to hydroxychloroquine in COVID-19 patients. Our computer-aided simulations show that hydroxychloroquine may have an impact on the amplitude of the viral load peak but that viral clearance is not significantly accelerated if the drug is not administered early enough (i.e. when viral loads range from 1 to 1,000 copies/mL). Although some authors had used the trough plasma concentrations or the theoretical drug distribution in the lung to model the effect of chloroquine/hydroxychloroquine on COVID-19, the theoretical drug response based on the trough whole blood concentrations of the drug agreed well with the results of the clinical trials so far reported. Moreover, the effects of chloroquine/hydroxychloroquine could be fully explained when taking into account also the capacity of this drug to raise cell-mediated responses against the productively SARS-Cov-2-infected cells. On the whole, the present study suggests that chloroquine/hydroxychloroquine has a narrow therapeutic window, which overlaps with the highest tolerated doses. These considerations may have implications for development of anti-COVID-19 combination therapies and prevention strategies.", "qid": 28, "docid": "gpofwyux", "rank": 59, "score": 0.8083398342132568}, {"content": "Title: Smooth or Risky Revisit of an Old Malaria Drug for COVID-19? Content: Hydroxychloroquine (HCQ) is an old medication for malaria. In addition to handling this parasitic disease, HCQ is also used to treat a number of autoimmune disorders including rheumatoid arthritis and systemic lupus erythematosus when other medications are not effective. Recently a new viral infection (COVID-19) is rocking the entire world so much that it has already taken more than 200,000 lives throughout the world within the last two months and the World Health Organization was forced to declare it as a pandemic on March 11, 2020. Interestingly, some reports indicate that this wonder drug may be also beneficial for COVID-19 and accordingly, many clinical trials have begun. Here, we discuss different modes of action (anti-inflammatory, antioxidant, inhibition of endosomal acidification, suppression of angiotensin-converting enzyme 2 or ACE2 glycosylation, etc.) of HCQ that might be responsible for its possible anti-COVID-19 effect. On the other hand, this review also makes an honest attempt to delineate mechanisms (increase in vasoconstriction, inhibition of autophagy, depletion of T cells, etc.) indicating how it may aggravate certain conditions and why caution should be taken before granting widespread repurposing of HCQ for COVID-19. [Figure: see text]", "qid": 28, "docid": "pnpsn6dr", "rank": 60, "score": 0.8080312013626099}, {"content": "Title: Serious Adverse Events Associated With Hydroxychloroquine Amidst COVID-19 Pandemic: Case Series and Literature Review Content: COVID-19 represents a global health crisis. Several studies are evaluating potential therapies including hydroxychloroquine (HCQ) which is given to patients based on limited observational evidence. However, it can cause serious adverse events. Moreover, recent studies showed no benefits due to HCQ. We present two COVID-19 patients treated with HCQ and had adverse events.", "qid": 28, "docid": "q1akwoo1", "rank": 61, "score": 0.8078977465629578}, {"content": "Title: Perspectives on repositioning chloroquine and hydroxychloroquine for the treatment of Covid-19 Content: Coronavirus disease 2019 (COVID-19) is now spreading as a pandemic ravaging the whole world In the absence of a vaccine and an effective antiviral chemotherapy, there is currently an intense global interest in repositioning chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) to combat the pandemic CQ has been used for decades for the treatment and prophylaxis against malaria in endemic countries It is readily available and has also been manufactured in these countries CQ is cheap, stable under field conditions and has been well tolerated as an antimalarial This experience could be adapted to deploy CQ or HCQ for prophylaxis or treatment of COVID19 if strong evidence could be generated for these uses We believe that well-designed drug trials should be initiated in malaria-endemic countries, taking into account the local context of the epidemic and the capacity of the health system in combating it In this paper, we are presenting the current status of evidence for using CQ and HCQ against COVID19", "qid": 28, "docid": "85g1tp38", "rank": 62, "score": 0.8071030974388123}, {"content": "Title: Chloroquine als mogelijke behandeling van COVID-19./ [Chloroquine as a possible treatment for COVID-19] Content: Since the outbreak of COVID-19, chloroquine has been mentioned as a possible treatment. In vitro studies have shown anti-viral activity of chloroquine against SARS-CoV-2. Recently, the Dutch National Institute for Public Health and the Environment published treatment options for antiviral treatment for COVID-19 where chloroquine was suggested as first choice for off-label treatment, beside remdesivir en lopinavir/ritonavir. In this commentary, we provide a background and history of chloroquine, the evidence for antiviral efficacy of chloroquine and the arguments for off-label use of chloroquine in COVID-19.", "qid": 28, "docid": "0pboygd7", "rank": 63, "score": 0.8067281246185303}, {"content": "Title: [Chloroquine as a possible treatment for COVID-19]. Content: Since the outbreak of COVID-19, chloroquine has been mentioned as a possible treatment. In vitro studies have shown anti-viral activity of chloroquine against SARS-CoV-2. Recently, the Dutch National Institute for Public Health and the Environment published treatment options for antiviral treatment for COVID-19 where chloroquine was suggested as first choice for off-label treatment, beside remdesivir en lopinavir/ritonavir. In this commentary, we provide a background and history of chloroquine, the evidence for antiviral efficacy of chloroquine and the arguments for off-label use of chloroquine in COVID-19.", "qid": 28, "docid": "mgsvg5gu", "rank": 64, "score": 0.8067281246185303}, {"content": "Title: Hydroxychloroquine treatment in COVID\u201019: a descriptive observational analysis of 30 cases from a single center in Wuhan, China Content: Hydroxychloroquine (HCQ) garnered scientific attention in early February following publication of reports showing in vitro activity of chloroquine (CQ) against COVID\u201019. While studies are mixed on this topic, the therapeutic effect of HCQ or CQ still need more valid clinical evidence. In this descriptive observational study, we aimed to discuss the treatment response of HCQ in COVID\u201019 infected patients and 30 cases were included. The demographic, treatment, laboratory parameters of C\u2010reactive protein (CRP) and interleukin\u20106 (IL\u20106) before and after HCQ therapy and clinical outcome in the 30 COVID\u201019 patients were assessed. In order to evaluate the effect of mediation time point, we also divided these cases into two groups, patients began administrated with HCQ within 7 days hospital (defined as early delivery group) and 7 days after hospital (defined as later delivery group). We found that, the elevated IL\u20106, a risk factor in severe patients were reduced to normal level after HCQ treatment. More importantly, patients treated with HCQ at the time of early hospital recovered faster than those who treated later or taken as second line choose for their obvious shorter hospitalization time. In summary, early use of HCQ was better than later use and the effect of IL\u20106 and CRP level can not be ruled out. This article is protected by copyright. All rights reserved.", "qid": 28, "docid": "hd5yvs5x", "rank": 65, "score": 0.8064291477203369}, {"content": "Title: Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review. Content: BACKGROUND Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). PURPOSE To summarize evidence about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19). DATA SOURCES PubMed (via MEDLINE), EMBASE (via Ovid), Scopus, Web of Science, Cochrane Library, bioRxiv, Preprints, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry from 1 December 2019 until 8 May 2020. STUDY SELECTION Studies in any language reporting efficacy or safety outcomes from hydroxychloroquine or chloroquine use in any setting in adults or children with suspected COVID-19 or at risk for SARS-CoV-2 infection. DATA EXTRACTION Independent, dually performed data extraction and quality assessments. DATA SYNTHESIS Four randomized controlled trials, 10 cohort studies, and 9 case series assessed treatment effects of the medications, but no studies evaluated prophylaxis. Evidence was conflicting and insufficient regarding the effect of hydroxychloroquine on such outcomes as all-cause mortality, progression to severe disease, clinical symptoms, and upper respiratory virologic clearance with antigen testing. Several studies found that patients receiving hydroxychloroquine developed a QTc interval of 500 ms or greater, but the proportion of patients with this finding varied among the studies. Two studies assessed the efficacy of chloroquine; 1 trial, which compared higher-dose (600 mg twice daily for 10 days) with lower-dose (450 mg twice daily on day 1 and once daily for 4 days) therapy, was stopped owing to concern that the higher dose therapy increased lethality and QTc interval prolongation. An observational study that compared adults with COVID-19 receiving chloroquine phosphate 500 mg once or twice daily with patients not receiving chloroquine found minor fever resolution and virologic clearance benefits with chloroquine. LIMITATION There were few controlled studies, and control for confounding was inadequate in observational studies. CONCLUSION Evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19 is very weak and conflicting. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.", "qid": 28, "docid": "fanupn22", "rank": 66, "score": 0.8064112663269043}, {"content": "Title: Are hydroxychloroquine and chloroquine effective in the treatment of SARS-COV-2 (COVID-19)? Content: Data sources The authors of this rapid review did not disclose which electronic databases were included in their literature search. The inclusion and exclusion criteria for the data sources are not reported in the manuscript. Study selection The authors included six studies on the effectiveness of hydroxychloroquine or chloroquine for the prevention and treatment of COVID-19 in humans. Studies comprised of two randomised controlled trials, two non-randomised trials both of which were non-blinded and open-label and one that was uncontrolled, a prospective cohort study and an interim report. The authors did not report details of any studies that were excluded. Data extraction and synthesis The data extraction methodology was not reported and it is unclear if the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were followed. Treatment regimens and the study outcomes were extracted where available and overall findings were presented in a table. There were no comparable outcome measures; therefore, results were deemed unsuitable to combine and no statistical analyses were carried out. A narrative synthesis of each study is presented. Results The results of the studies in this rapid review are difficult to quantify as each study had different outcome parameters. Due to the heterogeneity of the studies, results were not combined, and no statistical analysis was carried out. Narrative synthesis of each of the included studies identified important and significant limitations, precluding the studies from demonstrating a statistically significant difference in outcomes. Conclusions This review highlights the urgent need for more high quality evidence on the use of hydroxychloroquine and chloroquine in the prevention and treatment of COVID-19. The results of the studies included should be interpreted with caution due to the weak supporting data and numerous methodological limitations. The authors suggested that the studies be viewed as hypothesis-generating and should not be used in decision making around the recommendations and guidelines in the prevention and treatment of COVID-19. There are currently several ongoing randomised controlled trials looking at the effectiveness and efficacy of these drugs on COVID-19. It is hoped the outcome of these studies can help guide future recommendations and national guidelines.", "qid": 28, "docid": "vn7nvsse", "rank": 67, "score": 0.8062609434127808}, {"content": "Title: Are hydroxychloroquine and chloroquine effective in the treatment of SARS-COV-2 (COVID-19)? Content: Data sources The authors of this rapid review did not disclose which electronic databases were included in their literature search. The inclusion and exclusion criteria for the data sources are not reported in the manuscript.Study selection The authors included six studies on the effectiveness of hydroxychloroquine or chloroquine for the prevention and treatment of COVID-19 in humans. Studies comprised of two randomised controlled trials, two non-randomised trials both of which were non-blinded and open-label and one that was uncontrolled, a prospective cohort study and an interim report. The authors did not report details of any studies that were excluded.Data extraction and synthesis The data extraction methodology was not reported and it is unclear if the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were followed. Treatment regimens and the study outcomes were extracted where available and overall findings were presented in a table. There were no comparable outcome measures; therefore, results were deemed unsuitable to combine and no statistical analyses were carried out. A narrative synthesis of each study is presented.Results The results of the studies in this rapid review are difficult to quantify as each study had different outcome parameters. Due to the heterogeneity of the studies, results were not combined, and no statistical analysis was carried out. Narrative synthesis of each of the included studies identified important and significant limitations, precluding the studies from demonstrating a statistically significant difference in outcomes.Conclusions This review highlights the urgent need for more high quality evidence on the use of hydroxychloroquine and chloroquine in the prevention and treatment of COVID-19. The results of the studies included should be interpreted with caution due to the weak supporting data and numerous methodological limitations. The authors suggested that the studies be viewed as hypothesis-generating and should not be used in decision making around the recommendations and guidelines in the prevention and treatment of COVID-19. There are currently several ongoing randomised controlled trials looking at the effectiveness and efficacy of these drugs on COVID-19. It is hoped the outcome of these studies can help guide future recommendations and national guidelines.", "qid": 28, "docid": "znv6yru8", "rank": 68, "score": 0.8062609434127808}, {"content": "Title: Hydroxychloroquine as prophylaxis or treatment for COVID-19: What does the evidence say? Content: Hydroxychloroquine (HCQ), an antimalarial has been proposed as possible treatment for coronavirus disease-2019 (COVID-19). India has approved the use of HCQ for prophylaxis of asymptomatic health workers treating suspected or confirmed COVID-19 cases, and asymptomatic household contacts of confirmed patients. The U.S. Food and Drug Administration has issued Emergency Use Authorization for the use of HCQ to treat COVID-19 in adolescents and adults. In this review, we go over the available evidence for and against HCQ's use as prophylaxis or treatment for COVID-19, especially in the Indian context.", "qid": 28, "docid": "9eo0leey", "rank": 69, "score": 0.8058508634567261}, {"content": "Title: Rapid systematic review on clinical evidence of chloroquine and hydroxychloroquine in COVID-19: critical assessment and recommendation for future clinical trials Content: Purpose: This study aims to critically assess the published studies of Chloroquine (CQ) and hydroxychloroquine (HCQ) for the treatment of COVID-19 and provide recommendations for future clinical trials for the COVID-19 pandemic. Method: A rapid systematic review was conducted by searching the PubMed, Embase, and China National Knowledge Infrastructure databases on April 13, 2020. Three clinical trial registry platforms, including ClinicalTrials.gov, the EU Clinical Trials Register, and the Chinese Clinical Trial Register were also complementarily searched. Results: A total of 10 clinical studies were identified, including 3 randomized controlled trials (RCTs), 1 comparative nonrandomized trial, 5 single-arm trials, and 1 interim analysis. The heterogeneity among studies of the baseline disease severity and reported endpoints made a pooled analysis impossible. CQ and HCQ (with or without azithromycin) showed significant therapeutic benefit in terms of virologic clearance rate, improvement in symptoms and imaging findings, time to clinical recovery, and length of hospital stay in 1 RCT, 4 single-arm trials, and the interim analysis, whereas no treatment benefit of CQ or HCQ was observed in the remaining 4 studies. Limitations of the included studies ranged from small sample size, to insufficient information concerning baseline patient characteristics, to potential for selection bias without detailing the rationale for exclusion, and presence of confounding factors. Conclusion: Based on the studies evaluated, there still lacked solid evidence supporting the efficacy and safety of HCQ and CQ as a treatment for COVID-19 with or without azithromycin. This emphasized the importance of robust RCTs investing HCQ/CQ to address the evidence uncertainties. Keywords: COVID-19, Systematic review, Clinical trial, Chloroquine, Hydroxychloroquine", "qid": 28, "docid": "y9wuszu5", "rank": 70, "score": 0.8056310415267944}, {"content": "Title: A systematic review protocol of the antiviral activity of chloroquine and hydroxychloroquine against COVID-19. Content: Introduction: The recent outbreak of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), or COVID-19 with no approved medicines has led to global health threat. Currently, repositioning of old medicines seems the most responsible strategy for potential cure and prevention COVID-19. Hydroxychloroquine and chloroquine have shown promising efficacy against COVID-19 related pneumonia in clinical studies. However, the mode of drug action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection is not clear. This review aims to gather evidence on antiviral activity and possible mechanism of drug action of chloroquine and hydroxychloroquine on SARS-CoV-2, including in-vitro, animal studies, and studies in humans. Method: A structured search of five bibliographic databases namely; Medline, Web of Science, PubMed, Cochrane CENTRAL, and Google Scholar will be undertaken to retrieve studies that describe the antiviral activity and possible mechanism of drug action of chloroquine and hydroxychloroquine on SARS-CoV-2. No restrictions will be placed on publication date, but studies will be limited to only publications in English. Duplication of studies will be removed using EndNote reference manager. Three authors will screen the citations independently based on inclusion criteria. Data extraction and assessment of risk of bias will be done independently. Meta-analysis of selected studies will be done wherever suitable. Ethics and dissemination: Primary data collection will not be involved in this study, hence no need for formal ethical clearance. Findings from the study will be disseminated through a peer-reviewed publication and conference meeting. Trial registration number: https://doi.org/10.17605/OSF.IO/7DJMU", "qid": 28, "docid": "em98mikz", "rank": 71, "score": 0.8055201172828674}, {"content": "Title: A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19 Content: PURPOSE: COVID-19 (coronavirus disease 2019) is a public health emergency of international concern. As of this time, there is no known effective pharmaceutical treatment, although it is much needed for patient contracting the severe form of the disease. The aim of this systematic review was to summarize the evidence regarding chloroquine for the treatment of COVID-19. METHODS: PubMed, EMBASE, and three trial Registries were searched for studies on the use of chloroquine in patients with COVID-19. RESULTS: We included six articles (one narrative letter, one in-vitro study, one editorial, expert consensus paper, two national guideline documents) and 23 ongoing clinical trials in China. Chloroquine seems to be effective in limiting the replication of SARS-CoV-2 (virus causing COVID-19) in vitro. CONCLUSIONS: There is rationale, pre-clinical evidence of effectiveness and evidence of safety from long-time clinical use for other indications to justify clinical research on chloroquine in patients with COVID-19. However, clinical use should either adhere to the Monitored Emergency Use of Unregistered Interventions (MEURI) framework or be ethically approved as a trial as stated by the World Health Organization. Safety data and data from high-quality clinical trials are urgently needed.", "qid": 28, "docid": "m7sawt31", "rank": 72, "score": 0.8051142692565918}, {"content": "Title: Ethical issues related to the hydroxychloroquine treatment prescription for Covid-19 Content: Abstract The 2019-20 coronavirus pandemic (COVID-19), has led to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, no drugs have demonstrated safety and efficacy in randomized controlled trials for patients with COVID-19. Although the association between Hydroxychloroquine and Azithromycin efficacy lack of solid evidence-base, several governments have adopted it for all virology confirmed Covid-19 cases even for those who are asymptomatic. In the following, we aim to discuss some of the ethical issues associated with the use of this treatment association. We mainly tried to discuss the following controversial questions: Is it ethical not to treat a patient while a treatment exists and is used for other indications than Covid-19 for which it\u2019s not proven yet? If yes, is a randomized controlled trial to prove the hydroxychloroquine for the Covid-19 treatment, necessary, in the context of covid-19 pandemic? If No, is it the government\u2019s right to decide the hydroxychloroquine treatment for all covid-19 patients? and what should be the physicians\u2019 attitudes? Finally, what are the government, physicians, and patient\u2019s rights and responsibilities? The paper conclude that, since health authorities in some countries recommended this off-label use treatment, physicians are challenged by the requirement of veracity while providing care to their patients and the implications of such a requirement; they are facing the challenge of balancing this guideline and their own conviction. Furthermore, the fundamental principles of beneficence and non-maleficence, and respect for persons should underlie any reflection process to address this dilemma. In addition, in a pandemic context, the limits between the government\u2019s, practitioner\u2019s and patient\u2019s rights and obligations are not clear which could significantly endanger the universal ethical principles in clinical practice. It could also undermine any attempt to develop serious clinical trials to prove the considered off-label drug.", "qid": 28, "docid": "rffp6qe2", "rank": 73, "score": 0.8051010966300964}, {"content": "Title: Hydroxychloroquine in COVID-19: A systematic review and meta-analysis Content: Abstract Background Hydroxychloroquine is being administered among patients with COVID19 infection in many healthcare systems across the world considering its in vitro effect against the SARS CoV 2 virus. In spite of several observational studies and a few randomized controlled trials, the effect of hydroxychloroquine on patients with COVID 19 infection remains unclear. We undertook this systematic review with meta-analysis to evaluate the efficacy and safety of hydroxychloroquine among patients with COVID 19 infection. Methods We searched PubMed, Embase, the Cochrane Library, Web of Science, medRxiv, and other relevant resources until May 13, 2020. We included randomized controlled trials and observational studies in which hydroxychloroquine was adminstered and compared to a control group. Data were extracted, and quality assessment of the studies was carried out. We evaluated symptomatic progression, mortality, viral clearance, the evolution of changes on chest CT imaging, and adverse events. A fixed or random-effects model was used depending on outcome heterogeneity. Results We included eleven studies including, three randomized controlled trials and eight observational studies. Among these, 2354 patients received hydroxychloroquine alone or in combination, while 1952 did not. Mortality was reported at different points of time. The overall mortality was not significantly different among patients who received hydroxychloroquine compared to the control group (OR: 1.41, 95% CI: 0.76 to 2.62; p = 0.28). Clinical worsening or lack of symptomatic improvement did not differ between patients who received hydroxychloroquine compared to those who did not (OR 1.1, 95% CI: 0.6 to 2.02; p = 0.76). Viral clearance, assessed by RT-PCR, did not differ significantly between the hydroxychloroquine and the control groups (OR: 1.13, CI: 0.26 to 5.01; p = 0.87). The evolution of changes on chest CT imaging was reported only in two studies; a more pronounced improvement was observed with the use of hydroxychloroquine compared to standard care (OR: 2.68, CI: 1.1 to 6.6; P = 0.03). The incidence of adverse events was significantly higher with hydroxychloroquine (OR: 4.1, CI: 1.42 to 11.88; p = 0.009). Conclusions Our meta-analysis does not suggest improvement in clinical progression, mortality, or viral clearance by RT PCR among patients with COVID 19 infection who are treated with hydroxychloroquine. There was a significantly higher incidence of adverse events with hydroxychloroquine use.", "qid": 28, "docid": "qxgpehuy", "rank": 74, "score": 0.8047231435775757}, {"content": "Title: Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries Content: BACKGROUND AND AIMS: No drugs are currently approved for Coronavirus Disease-2019 (COVID-19), although some have been tried. In view of recent studies and discussion on chloroquine and hydroxychloroquine (HCQ), we aimed to review existing literature and relevant websites regarding these drugs and COVID-19, adverse effects related to drugs, and related guidelines. AIMS AND METHODS: We systematically searched the PubMed database up till March 21, 2020 and retrieved all the articles published on chloroquine and HCQ and COVID-19. RESULTS: Two small human studies have been conducted with both these drugs in COVID-19, and have shown significant improvement in some parameters in patients with COVID-19. CONCLUSION: Considering minimal risk upon use, a long experience of use in other diseases, cost-effectiveness and easy availability across India, we propose that both these drugs are worthy of fast track clinical trial for treatment, and may be carefully considered for clinical use as experimental drugs. Since HCQ has been approved for treatment of diabetes in India, it should be further researched in diabetes and COVID-19, a subgroup where significant mortality has been shown.", "qid": 28, "docid": "mn52exdm", "rank": 75, "score": 0.8046222925186157}, {"content": "Title: Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries Content: Abstract Background and aims No drugs are currently approved for Coronavirus Disease-2019 (COVID-19), although some have been tried. In view of recent studies and discussion on chloroquine and hydroxychloroquine (HCQ), we aimed to review existing literature and relevant websites regarding these drugs and COVID-19, adverse effects related to drugs, and related guidelines. Aims and methods We systematically searched the PubMed database up till March 21, 2020 and retrieved all the articles published on chloroquine and HCQ and COVID-19. Results Two small human studies have been conducted with both these drugs in COVID-19, and have shown significant improvement in some parameters in patients with COVID-19. Conclusion Considering minimal risk upon use, a long experience of use in other diseases, cost-effectiveness and easy availability across India, we propose that both these drugs are worthy of fast track clinical trial for treatment, and may be carefully considered for clinical use as experimental drugs. Since HCQ has been approved for treatment of diabetes in India, it should be further researched in diabetes and COVID-19, a subgroup where significant mortality has been shown.", "qid": 28, "docid": "41jqgsv0", "rank": 76, "score": 0.8043110370635986}, {"content": "Title: COVID-19 coronavirus research has overall low methodological quality thus far: case in point for chloroquine/hydroxychloroquine Content: OBJECTIVES/BACKGROUND AND OBJECTIVES: Prior epidemics of high-mortality human coronaviruses, such as the acute respiratory syndrome coronavirus (SARS-CoV or SARS-1) in 2003, have driven the characterization of compounds that could be possibly active against the currently emerging novel coronavirus SARS-CoV-2 (COVID-19). Presently, no approved treatment or prophylaxis is available for COVID-19. We comment on the existing COVID-19 research methodologies in general and the published reporting. Given the media attention and claims of effectiveness, we chose chloroquine and hydroxychloroquine, in combination with azithromycin, as an area of COVID-19 research to examine. METHODS/STUDY DESIGN AND SETTING: MEDLINE and EMBASE electronic databases were searched from 2019 to present (April 3rd, 2020) using a mix of keywords such as COVID-19 and chloroquine and hydroxychloroquine. We also searched the largest clinical medicine preprint repository, medRxiv.org. RESULTS: We found 6 studies, 3 randomized control trials and 3 observational studies, focusing on chloroquine and hydroxychloroquine (with azithromycin). We critically appraised the evidence. CONCLUSION: We found that the COVID-19 research methodology is very poor in the area of chloroquine/hydroxychloroquine research. In screening the literature, we observed the same across COVID-19 research in relation to potential treatments. The reporting is very poor and sparse, and patient-important outcomes needed to discern decision-making priorities are not reported. We do understand the barriers to perform rigorous research in health care settings overwhelmed by a novel deadly disease. However, this emergency pandemic situation does not transform flawed methods and data into credible results. The adequately powered, comparative, and robust clinical research that is needed for optimal evidence-informed decision-making remains absent in COVID-19.", "qid": 28, "docid": "5w1q57v2", "rank": 77, "score": 0.8036164045333862}, {"content": "Title: Behandling med 4-aminokinoliner vid covid-19 kan ge allvarliga biverkningar./ [Potential harms associated with 4-aminoquinoline treatment] Content: Hydroxychloroquine and chloroquine are currently being evaluated as treatment against COVID-19. These drugs are associated with some potential harms, including QTc-interval prolongation, hypoglycaemia, severe skin reactions and psychiatric effects. Use of hydroxychloroquine or chloroquine should be reserved to current indications or clinical trials, as recommended by several governmental medical products agencies.", "qid": 28, "docid": "x09n56na", "rank": 78, "score": 0.8034845590591431}, {"content": "Title: [Potential harms associated with 4-aminoquinoline treatment]. Content: Hydroxychloroquine and chloroquine are currently being evaluated as treatment against COVID-19. These drugs are associated with some potential harms, including QTc-interval prolongation, hypoglycaemia, severe skin reactions and psychiatric effects. Use of hydroxychloroquine or chloroquine should be reserved to current indications or clinical trials, as recommended by several governmental medical products agencies.", "qid": 28, "docid": "8wgg86qc", "rank": 79, "score": 0.8034845590591431}, {"content": "Title: Hydroxychloroquine plus standard care compared with the standard care alone in COVID-19: a meta-analysis of randomized controlled trials Content: Background & Objective: The efficacy and safety of Hydroxychloroquine (HCQ) in treating coronavirus disease COVID-19 pandemic is disputed. This study aimed to examine the efficacy and safety of HCQ plus standard of care in COVID-19 patients. Methods: PubMed, The Cochrane Library, Embase, and web of sciences were searched up to June 1, 2020. The references list of the key studies was reviewed for additional relevant resources. Clinical studies registry databases were searched for identifying potential clinical trials. The quality of the included studies was evaluated using the Cochrane Collaborations tool. Meta-analysis was performed using RevMan software (version 5.3). Results: Three randomized controlled trials with total number of 242 patients were identified eligible for meta-analysis. No significant differences were observed between HCQ and standard care in terms of viral clearance (Risk ratio [RR] = 1.03; 95% confidence interval [CI] = 0.91, 1.16; P= 0.68), disease progression (RR=0.92; 95% CI= 0.10, 0.81; P=0.94), Chest CT (RR=1.40; 95% CI= 1.03, 1.91; P=0.03). There is a significant difference between HCQ and standard care for adverse events (RR=2.88; 95% CI= 1.50, 5.54; P=0.002). Conclusion: Although the current meta-analysis failed to confirm the efficacy and safety of HCQ in the treatment of COVID-19 patients, further rigorous randomized clinical trials are necessary to evaluate conclusively the efficacy and safety of HCQ against COVID-19. Keyword: Coronavirus Disease; COVID-19; SARS-CoV-2; Hydroxychloroquine; Efficacy; Safety", "qid": 28, "docid": "n288cnap", "rank": 80, "score": 0.8034682869911194}, {"content": "Title: Hydroxychloroquine and mortality risk of patients with COVID-19: a systematic review and meta-analysis of human comparative studies Content: Background: Global COVID-19 deaths reached at least 400,000 fatalities. Hydroxychloroquine is an antimalarial drug that elicit immunomodulatory effects and had shown in vitro antiviral effects against SRAS-CoV-2. This drug divided opinion worldwide in the medical community but also in the press, the general public and in public health policies. The aim of this systematic review and this meta-analysis was to bring a new overview on this controversial drug and to assess whether hydroxychloroquine could reduce COVID-19 mortality risk in hospitalized patients. Methods and Findings: Pubmed, Web of Science, Cochrane Library, MedRxiv and grey literature were searched until 10 June 2020. Only studies of COVID-19 patients treated with hydroxychloroquine (with or without azithromycin) compared with a comparative standard care group and with full-text articles in English were included. Studies reporting effect sizes as Odds Ratios, Hazard Ratio and Relative Risk for mortality risk and the number of deaths per groups were included. This meta-analysis was conducted following PRISMA guidelines and registered on PROSPERO (Registration number: CRD42020190801). Independent extraction has been performed by two independent reviewers. Effect sizes were pooled using a random-effects model. The initial search leaded to 112 articles, from which 16 articles met our inclusion criteria. 15 studies were retained for association between hydroxychloroquine and COVID-19 survival including 15,081 patients (8,072 patients in the hydroxychloroquine arm and 7,009 patients in the standard care arm with respectively, 1,578 deaths and 1,423 deaths). 6 studies were retained for hydroxychloroquine with azithromycin. Hydroxychloroquine was not significantly associated with mortality risk (pooled Relative Risk RR=0.82 (95% Confidence Interval: 0.62-1.07, I2=82, Pheterogeneity<0.01, n=15)) within hospitalized patients, nor in association with azithromycin (pooled Relative Risk RR=1.33 (95% CI: 0.92-1.92, I2=75%, Pheterogeneity<0.01, n=6)), nor in the numerous subgroup analysis by study design, median age population, published studies (vs unpublished articles), level of bias risk. However, stratified analysis by continents, we found a significant decreased risk of mortality associated with hydroxychlroquine alone but not with azithromycin among European (RR= 0.62 (95%CI: 0.41-0.93, n=7)) and Asian studies (RR=0.36 (95%CI:0.18-0.73, n=1)), with heterogeneity detected across continent (Pheterogeneity between=0.003). These finding should be interpreted with caution since several included studies had a low quality of evidence with a small sample size, a lack of adjustment on potential confounders or selection and intervention biases. Conclusion: Our meta-analysis does not support the use of hydroxychloroquine with or without azithromycin to reduce COVID-19 mortality in hospitalized patients. It raises the question of the hydroxychloroquine use outside of clinical trial. Additional results from larger randomised controlled trials are needed", "qid": 28, "docid": "tsmqssjm", "rank": 81, "score": 0.8032566905021667}, {"content": "Title: Efficacy and Safety of Hydroxychloroquine and Chloroquine for COVID-19: A systematic review Content: BACKGROUND: Hydroxychloroquine and chloroquine are widely used to treat hospitalized COVID-19 patients primarily based on antiviral activity in in vitro studies. Our objective was to systematically evaluate their efficacy and safety in hospitalized patients with COVID-19. METHODS: We systematically reviewed PubMed, ClinicalTrials.gov, and Medrxviv for studies of hydroxychloroquine and chloroquine in COVID-19 hospitalized patients on April 26, 2020. We evaluated the quality of trials and observational studies using the Jadad criteria and Newcastle Ottawa Scale, respectively. RESULTS: After a review of 175 citations, we included 5 clinical trials (total of 345 patients), 9 observational studies (n = 2529), and 6 additional studies (n = 775) reporting on the QT interval. Three studies reported treatment benefits including two studies reporting benefit on virologic outcomes, which was statistically significant in one study, and another reported significant improvement on cough symptoms. Three studies reported that treatment was potentially harmful, including an significantly increased risk of mortality in two studies and increased need for respiratory support in another. Eight studies were unable to detect improvements on virologic outcomes (n = 3) or pneumonia or transfer to ICU/death (n = 5). The proportion of participants with critical QTc intervals of [\u2265] 500 ms or an increase of [\u2265] 60 ms from baseline ranged from 8.3% to 36% (n = 8). One clinical trial and six observational studies were of good quality. The remaining studies were of poor quality. CONCLUSIONS: Our systematic review of reported clinical studies did not identify substantial evidence to support the efficacy of hydroxychloroquine or chloroquine in hospitalized COVID-19 patients and raises questions about potential harm from QT prolongation and increased mortality.", "qid": 28, "docid": "2txzi7kb", "rank": 82, "score": 0.8027888536453247}, {"content": "Title: Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review Content: BACKGROUND: Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). PURPOSE: To summarize evidence about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19). DATA SOURCES: PubMed (via MEDLINE), EMBASE (via Ovid), Scopus, Web of Science, Cochrane Library, bioRxiv, Preprints, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry from 1 December 2019 until 8 May 2020. STUDY SELECTION: Studies in any language reporting efficacy or safety outcomes from hydroxychloroquine or chloroquine use in any setting in adults or children with suspected COVID-19 or at risk for SARS-CoV-2 infection. DATA EXTRACTION: Independent, dually performed data extraction and quality assessments. DATA SYNTHESIS: Four randomized controlled trials, 10 cohort studies, and 9 case series assessed treatment effects of the medications, but no studies evaluated prophylaxis. Evidence was conflicting and insufficient regarding the effect of hydroxychloroquine on such outcomes as all-cause mortality, progression to severe disease, clinical symptoms, and upper respiratory virologic clearance with antigen testing. Several studies found that patients receiving hydroxychloroquine developed a QTc interval of 500 ms or greater, but the proportion of patients with this finding varied among the studies. Two studies assessed the efficacy of chloroquine; 1 trial, which compared higher-dose (600 mg twice daily for 10 days) with lower-dose (450 mg twice daily on day 1 and once daily for 4 days) therapy, was stopped owing to concern that the higher dose therapy increased lethality and QTc interval prolongation. An observational study that compared adults with COVID-19 receiving chloroquine phosphate 500 mg once or twice daily with patients not receiving chloroquine found minor fever resolution and virologic clearance benefits with chloroquine. LIMITATION: There were few controlled studies, and control for confounding was inadequate in observational studies. CONCLUSION: Evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19 is very weak and conflicting. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.", "qid": 28, "docid": "fs8r5ze0", "rank": 83, "score": 0.8026893734931946}, {"content": "Title: Towards Optimization of Hydroxychloroquine Dosing in Intensive Care Unit COVID-19 Patients Content: Hydroxychloroquine (HCQ) appears to be a promising treatment for COVID-19. However, all ongoing clinical trials with HCQ use different dosing regimens, resulting on various concentrations PK studies are therefore needed to define the optimal dosing regimen.", "qid": 28, "docid": "onqy21w5", "rank": 84, "score": 0.8019733428955078}, {"content": "Title: Pharmacotherapy in COVID-19; A narrative review for emergency providers Content: INTRODUCTION: The COVID-19 pandemic has been particularly challenging due to a lack of established therapies and treatment guidelines. With the rapid transmission of disease, even the off-label use of available therapies has been impeded by limited availability. Several antivirals, antimalarials, and biologics are being considered for treatment at this time. The purpose of this literature review is to synthesize the available information regarding treatment options for COVID-19 and serve as a resource for health care professionals. OBJECTIVES: This narrative review was conducted to summarize the effectiveness of current therapy options for COVID-19 and address the controversial use of non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs). PubMed and SCOPUS were queried using a combination of the keywords \"COVID 19,\" \"SARS-CoV-2,\" and \"treatment.\" All types of studies were evaluated including systematic reviews, case-studies, and clinical guidelines. DISCUSSION: There are currently no therapeutic drugs available that are directly active against SARS-CoV-2; however, several antivirals (remdesivir, favipiravir) and antimalarials (chloroquine, hydroxychloroquine) have emerged as potential therapies. Current guidelines recommend combination treatment with hydroxychloroquine/azithromycin or chloroquine, if hydroxychloroquine is unavailable, in patients with moderate disease, although these recommendations are based on limited evidence. Remdesivir and convalescent plasma may be considered in critical patients with respiratory failure; however, access to these therapies may be limited. Interleukin-6 (IL-6) antagonists may be used in patients who develop evidence of cytokine release syndrome (CRS). Corticosteroids should be avoided unless there is evidence of refractory septic shock, acute respiratory distress syndrome (ARDS), or another compelling indication for their use. ACE inhibitors and ARBs should not be discontinued at this time and ibuprofen may be used for fever. CONCLUSION: There are several ongoing clinical trials that are testing the efficacy of single and combination treatments with the drugs mentioned in this review and new agents are under development. Until the results of these trials become available, we must use the best available evidence for the prevention and treatment of COVID-19. Additionally, we can learn from the experiences of healthcare providers around the world to combat this pandemic.", "qid": 28, "docid": "4ehhtkfn", "rank": 85, "score": 0.8012102842330933}, {"content": "Title: Chloroquine and COVID-19 - a potential game changer? Content: The novel coronavirus SARS-CoV-2, causing the disease COVID-19, first emerged in Wuhan, China in December 2019 and has now spread to 203 countries or territories, infected over 2 million people and caused over 133,000 deaths. There is an urgent need for specific treatments. One potential treatment is chloroquine and its derivatives, including hydroxychloroquine, which have both antiviral and anti-inflammatory effects. These compounds are effective against SARS-CoV-2 in vitro, but in vivo data are lacking. Although some encouraging outcomes have been reported, and these results have been received enthusiastically, we recommend careful and critical evaluation of current evidence only when all methods and data are available for peer review. Chloroquine is safe and cheap. However, further evidence from coordinated multicentre trials is required before it can be confidently said whether it is effective against the current pandemic.", "qid": 28, "docid": "zrx4x5sa", "rank": 86, "score": 0.8004612326622009}, {"content": "Title: Chloroquine paradox may cause more damage than help fight COVID-19 Content: Abstract Novel coronavirus disease 2019 (COVID-19) pandemic is the most recent health care crisis without specific prophylactic or therapeutic drugs. Antimalarial drug chloroquine (CHL) and its safer derivative hydroxychloroquine (HCHL) have been proposed to be repurposed to treat SARS coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. CHL/HCHL have anti-inflammatory activity and are used to treat rheumatoid arthritis, osteoarthritis and lupus. Although, CHL/HCHL have an anti-viral activity against several viruses in cell-cultures, the anti-viral activity in-vivo is questionable. Repurposing of CHL/HCHL to treat SARS-CoV-2 infection is appealing. However, there is empirical evidence from animal studies with other viruses suggesting that CHL/HCHL may have an untoward paradoxical effect. One thus cannot exclude the possibility that CHL may increase the severity of the disease and prove deleterious both for the patients and public health efforts to contain the highly contagious and explosive spread of SARS-CoV-2.", "qid": 28, "docid": "j9vmsfjw", "rank": 87, "score": 0.8001247048377991}, {"content": "Title: Clinical and biological data on the use of hydroxychloroquine against SARS\u2010CoV\u20102 could support the role of the NLRP3 inflammasome in the pathogenesis of respiratory disease Content: The use of hydroxychloroquine (HCL) has been very common in countries with a rapid spread of coronavirus disease 2019 (COVID-19), although controversial and the subject of heated scientific discussions with implications for the whole society. This article is protected by copyright. All rights reserved.", "qid": 28, "docid": "f2ic7vow", "rank": 88, "score": 0.7994151711463928}, {"content": "Title: Update on use of chloroquine/hydroxychloroquine to treat coronavirus disease 2019 (COVID-19) Content: Drugs that are specifically efficacious against SARS-CoV-2 have yet to be established. Chloroquine and hydroxychloroquine have garnered considerable attention for their potential to treat coronavirus disease 2019 (COVID-19). Increasing evidence obtained from completed clinical studies indicates the prospects for chloroquine/hydroxychloroquine to treat COVID-19. More randomized control clinical studies are warranted to determine the feasibility of these two drugs in treating COVID-19.", "qid": 28, "docid": "n3cg3w9v", "rank": 89, "score": 0.7988682389259338}, {"content": "Title: Update on use of chloroquine/hydroxychloroquine to treat coronavirus disease 2019 (COVID-19). Content: Drugs that are specifically efficacious against SARS-CoV-2 have yet to be established. Chloroquine and hydroxychloroquine have garnered considerable attention for their potential to treat coronavirus disease 2019 (COVID-19). Increasing evidence obtained from completed clinical studies indicates the prospects for chloroquine/hydroxychloroquine to treat COVID-19. More randomized control clinical studies are warranted to determine the feasibility of these two drugs in treating COVID-19.", "qid": 28, "docid": "px2o98cv", "rank": 90, "score": 0.7988682389259338}, {"content": "Title: The Cardiac Toxicity of Chloroquine or Hydroxychloroquine in COVID-19 Patients: A Systematic Review and Meta-regression Analysis Content: Abstract Importance The antimalarial agents chloroquine (CQ) and hydroxychloroquine (HCQ) have been proposed as a potential treatment for COVID-19 due their effect on several cellular processes that impact viral replication. Although more than 100 ongoing trials are testing their efficacy, CQ and HCQ are being used widely in clinical practice, exposing COVID-19 patients to potentially significant cardiac adverse effects. Objective To systematically review the literature and estimate the risk of cardiac toxicity in patients receiving CQ or HCQ for COVID-19. Data Sources A systematic search was conducted on May 27, 2020 of Ovid EBM Reviews, Ovid Embase (1974+), Ovid Medline (1946+ including epub ahead of print, in-process & other non-indexed citations), Scopus (1970+) and Web of Science (1975+) and preprint servers (Medrvix and ResearchSquare) and manual search of references lists. Study Selection Studies that included COVID-19 patients treated with CQ or HCQ, with or without azithromycin, were included as follows: (1) COVID-19 patient population, (2) the study included more than 10 patients receiving either one of the medications, (3) reported electrocardiographic changes and/or cardiac arrhythmias. Data Extraction and Synthesis Study characteristics and endpoints incidence were extracted. Due to the very low incidence of torsades de pointes (TdP) and other endpoints (rare events), the arcsine transformation was used to obtain a pooled estimate of the different incidences using a random-effects meta-analysis. Meta-regression analyses were used to assess whether the incidence of different endpoints significantly varied by multiple study-level variables specified a priori. Main Outcomes and Measures Pooled Incidence of: (1) change in QTc value from baseline [\u2265] 60 ms, (2) QTc [\u2265] 500 ms, (3) the composite of endpoint 1 and 2, (4) TdP arrhythmia or ventricular tachycardia (VT) or cardiac arrest, (5) discontinuation of treatment due to drug-induced QT prolongation or arrhythmias. Results A total of 19 studies with a total of 5652 patients were included. All included studies were of high methodological quality in terms of exposure ascertainment or outcome assessment. Among 2719 patients treated with CQ or HCQ, only two episodes of TdP were reported; the pooled incidence of TdP arrhythmia or VT or cardiac arrest was 3 per 1000, 95% CI (0-21), I2=96%, 18 studies with 3725 patients. Among 13 studies of 4334 patients, the pooled incidence of discontinuation of CQ or HCQ due to prolonged QTc or arrhythmias was 5%, 95% CI (1-11), I2=98%. The pooled incidence of change in QTc from baseline of [\u2265] 60 ms was 7%, 95% CI (3-14), I2=94% (12 studies of 2008 patients). The pooled incidence of QTc [\u2265] 500 ms was 6%, 95% CI (2-12), I2=95% (16 studies of 2317 patients). Among 11 studies of 3127 patients, the pooled incidence of change in QTc from baseline of [\u2265] 60 ms or QTc [\u2265] 500 ms was 9%, 95% CI (3-17), I2=97%. Mean/median age, coronary artery disease, hypertension, diabetes, concomitant QT prolonging medications, ICU care, and severity of illness in the study populations explained between-studies heterogeneity. Conclusions and Relevance Treatment of COVID-19 patients with CQ or HCQ is associated with a significant risk of drug-induced QT prolongation, which is a harbinger for drug-induced TdP/VT or cardiac arrest. CQ/HCQ use resulted in a relatively higher incidence of TdP as compared to drugs withdrawn from the market for this particular adverse effect. Therefore, these agents should be used only in the context of randomized clinical trials, in patients at low risk for drug-induced QT prolongation, with adequate safety monitoring.", "qid": 28, "docid": "62j81bq3", "rank": 91, "score": 0.7982137799263}, {"content": "Title: Safety considerations of chloroquine and hydroxychloroquine in treatment of COVID-19 Content: Chloroquine and hydroxychloroquine are both used to treat COVID-19. Safety data in this specific population is largely unknown. In particular, cardiologic, gastro-intestinal and neuropsychiatric side-effects of (hydroxychloroquine) needs special attention in COVID-19 patients.", "qid": 28, "docid": "b5fel2d3", "rank": 92, "score": 0.7980339527130127}, {"content": "Title: Role of Chloroquine and Hydroxychloroquine in the Treatment of COVID-19 Infection- A Systematic Literature Review Content: Background: Coronavirus pandemic is currently a global public health emergency. At present, no pharmacological treatment is known to treat this condition, and there is a need to review the available treatments. Objective: While there have been studies to describe the role of chloroquine and hydroxychloroquine in various viral conditions, there is limited information about the use of them in COVID-19. This systematic review aims to summarize the available evidence regarding the role of chloroquine in treating coronavirus infection. Methods: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used for this review. A literature search was performed using PUBMED & Google Scholar to find articles about the role of CQ in COVID-19 patients. Results: We included 19 publications (Five published articles, three letters/correspondence, one commentary, five pre-proofs of accepted articles, one abstract of yet to be published article, and four were pre-prints (not yet peer-reviewed) articles) in this systematic review. All the articles mentioned about the role of chloroquine and /or hydroxychloroquine in limiting the infection with SARS-CoV-2 (the virus causing COVID-19). Conclusions: There is theoretical, experimental, preclinical and clinical evidence of the effectiveness of chloroquine in patients affected with COVID-19. There is adequate evidence of drug safety from the long-time clinical use of chloroquine and hydroxychloroquine in other indications. More data from ongoing and future trials will add more insight into the role of chloroquine and hydroxychloroquine in COVID-19 infection.", "qid": 28, "docid": "0lk8eujq", "rank": 93, "score": 0.796826183795929}, {"content": "Title: Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial Content: Aims: Studies have indicated that chloroquine (CQ) shows antagonism against COVID-19 in vitro. However, evidence regarding its effects in patients is limited. This study aims to evaluate the efficacy of hydroxychloroquine (HCQ) in the treatment of patients with COVID-19. Main methods: From February 4 to February 28, 2020, 62 patients suffering from COVID-19 were diagnosed and admitted to Renmin Hospital of Wuhan University. All participants were randomized in a parallel-group trial, 31 patients were assigned to receive an additional 5-day HCQ (400 mg/d) treatment, Time to clinical recovery (TTCR), clinical characteristics, and radiological results were assessed at baseline and 5 days after treatment to evaluate the effect of HCQ. Key findings: For the 62 COVID-19 patients, 46.8% (29 of 62) were male and 53.2% (33 of 62) were female, the mean age was 44.7 (15.3) years. No difference in the age and sex distribution between the control group and the HCQ group. But for TTCR, the body temperature recovery time and the cough remission time were significantly shortened in the HCQ treatment group. Besides, a larger proportion of patients with improved pneumonia in the HCQ treatment group (80.6%, 25 of 31) compared with the control group (54.8%, 17 of 31). Notably, all 4 patients progressed to severe illness that occurred in the control group. However, there were 2 patients with mild adverse reactions in the HCQ treatment group. Significance: Among patients with COVID-19, the use of HCQ could significantly shorten TTCR and promote the absorption of pneumonia.", "qid": 28, "docid": "q8l3ra55", "rank": 94, "score": 0.7966960668563843}, {"content": "Title: Of chloroquine and COVID-19 Content: Abstract Recent publications have brought attention to the possible benefit of chloroquine, a broadly used antimalarial drug, in the treatment of patients infected by the novel emerged coronavirus (SARS-CoV-2). The scientific community should consider this information in light of previous experiments with chloroquine in the field of antiviral research.", "qid": 28, "docid": "y7lrp0gc", "rank": 95, "score": 0.7966055870056152}, {"content": "Title: Potential negative effects of the free use of chloroquine to manage COVID\u201019 in Colombia Content: Coronavirus disease 2019 (COVID-19) pandemic has challenged healthcare systems around the world. Unfortunately, failure has ensued: high-income countries have succumbed to the global emergency despite highly prepared human and technological assets. There is no current consensus on pharmacological management of COVID-19, but chloroquine phosphate (CQ) has emerged as a possible therapeutical candidate. However, no conclusive evidence has been published on the efficacy of CQ against SARS-CoV-2 infection. The Colombian government has approved the use of CQ for COVID-19, a measure that could negatively impact a large number of patients who depend on this drug for the treatment of other life-threatening diseases such as malaria and rheumatic autoimmune diseases. Careful consideration should be taken by Colombian authorities regarding the use of CQ in context of the ongoing pandemic. This article is protected by copyright. All rights reserved.", "qid": 28, "docid": "0fq2ngcb", "rank": 96, "score": 0.7963589429855347}, {"content": "Title: Hydroxychloroquine and COVID-19: critiquing the impact of disease public profile on policy and clinical decision-making Content: The controversy surrounding the use of hydroxychloroquine (HCQ), an antimalarial drug, for COVID-19 has raised numerous ethical and policy problems. Since the suggestion that HCQ has potential for COVID-19, there have been varying responses from clinicians and healthcare institutions, ranging from adoption of protocols using HCQ for routine care to the conduct of randomised controlled trials to an effective system-wide prohibition on its use for COVID-19. In this article, we argue that the concept of 'disease public profile' has become a prominent, if not the sole, determinant in decision-making across various healthcare responses to the pandemic. In the case of COVID-19, the disease's public profile is based on clinical and non-clinical factors that include contagiousness, clinical presentation and media coverage. In particular, we briefly examine the dangers of a heightened public profile in magnifying the inequality of diseases and undermining three key ethical concepts, namely (1) evidence-based practice, (2) sustainable allocation and (3) meaningful consent.", "qid": 28, "docid": "m7z23lps", "rank": 97, "score": 0.795461893081665}, {"content": "Title: Hydroxychloroquine and COVID-19: critiquing the impact of disease public profile on policy and clinical decision-making. Content: The controversy surrounding the use of hydroxychloroquine (HCQ), an antimalarial drug, for COVID-19 has raised numerous ethical and policy problems. Since the suggestion that HCQ has potential for COVID-19, there have been varying responses from clinicians and healthcare institutions, ranging from adoption of protocols using HCQ for routine care to the conduct of randomised controlled trials to an effective system-wide prohibition on its use for COVID-19. In this article, we argue that the concept of 'disease public profile' has become a prominent, if not the sole, determinant in decision-making across various healthcare responses to the pandemic. In the case of COVID-19, the disease's public profile is based on clinical and non-clinical factors that include contagiousness, clinical presentation and media coverage. In particular, we briefly examine the dangers of a heightened public profile in magnifying the inequality of diseases and undermining three key ethical concepts, namely (1) evidence-based practice, (2) sustainable allocation and (3) meaningful consent.", "qid": 28, "docid": "8m4930bc", "rank": 98, "score": 0.795461893081665}, {"content": "Title: Contentious issues and evolving concepts in the clinical presentation and management of patients with COVID-19 infectionwith reference to use of therapeutic and other drugs used in Co-morbid diseases (Hypertension, diabetes etc) Content: BACKGROUND AND AIMS: Multiple issues in management of COVID have emerged, but confusion persists regarding rational interpretation. Aim of this brief review is to review these issues based on current literature. METHODS: This is a narrative review with Pubmed and Google Scholar search till 23 March 2020. Search terms were, COVID-19, treatment of coronavirus, COVID 19 and following terms; chloroquine, hydroxychloroquine, ibuprofen, ACE-inhibitors or angiotensin receptor blockers, cardiovascular disease, diarrhoea, liver, testis and gastrointestinal disease. RESULTS: We discuss evidence regarding role of chloroquine and hydroxychloroquine in treatment and prophylaxis, use of inhibitors of the renin angiotensin system, safety of ibuprofen, unusual clinical features like gastrointestinal symptoms and interpretation of tests for cardiac enzymes and biomarkers. CONCLUSIONS: While our conclusions on management of COVID-19 patients with co-morbidities are based on current evidence, however, data is limited and there is immediate need for fast track research.", "qid": 28, "docid": "sngnrrp5", "rank": 99, "score": 0.795246958732605}, {"content": "Title: Does Adding of Hydroxychloroquine to the Standard Care Provide any Benefit in Reducing the Mortality among COVID-19 Patients?: a Systematic Review Content: Hydroxychloroquine has been promoted for its use in treatment of COVID-19 patients based on in-vitro evidences. We searched the databases to include randomized and observational studies evaluating the effect of Hydroxychloroquine on mortality in COVID-19 patients. The outcome was summarized as odds ratios (OR) with a 95% confidence interval (CI).We used the inverse-variance method with a random effect model and assessed the heterogeneity using I2 test. We used ROBINS-I tool to assess methodological quality of the included studies. We performed the meta-analysis using 'Review manager software version 5.3'. We identified 6 observationalstudies satisfying the selection criteria. In all studies, Hydroxychloroquine was given as add on to the standard care and effect was compared with the standard care alone. A pooled analysis observed 251 deaths in 1331 participants of the Hydroxychloroquine arm and 363 deaths in 1577 participants of the control arm. There was no difference in odds of mortality events amongst Hydroxychloroquine and supportive care arm [1.25 (95% CI: 0.65, 2.38); I2 = 80%]. A similar trend was observed with moderate risk of bias studies [0.95 (95% CI: 0.44, 2.06); I2 = 85%]. The odds of mortality were significantly higher in patients treated with Hydroxychloroquine + Azithromycin than supportive care alone [2.34 (95% CI: 1.63, 3.34); I2 = 0%]. A pooled analysis of recently published studies suggests no additional benefit for reducing mortality in COVID-19 patients when Hydroxychloroquine is given as add-on to the standard care. Graphical Abstract.", "qid": 28, "docid": "wuv1kafa", "rank": 100, "score": 0.7950445413589478}]}
{"query": "which SARS-CoV-2 proteins-human proteins interactions indicate potential for drug targets. Are there approved drugs that can be repurposed based on this information?", "hits": [{"content": "Title: A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Content: The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.", "qid": 29, "docid": "eje3i558", "rank": 1, "score": 0.8251388072967529}, {"content": "Title: The Landscape of Human Cancer Proteins Targeted by SARS-CoV-2 Content: The mapping of SARS-CoV-2 human protein\u2013protein interactions by Gordon and colleagues revealed druggable targets that are hijacked by the virus. Here, we highlight several oncogenic pathways identified at the host\u2013virus interface of SARS-CoV-2 to enable cancer biologists to apply their knowledge for rapid drug repurposing to treat COVID-19, and help inform the response to potential long-term complications of the disease.", "qid": 29, "docid": "uuy94dwa", "rank": 2, "score": 0.8244900703430176}, {"content": "Title: The Landscape of Human Cancer Proteins Targeted by SARS-CoV-2 Content: The mapping of SARS-CoV-2 human protein-protein interactions by Gordon and colleagues revealed druggable targets that are hijacked by the virus. Here, we highlight several oncogenic pathways identified at the host-virus interface of SARS-CoV-2 to enable cancer biologists to apply their knowledge for rapid drug repurposing to treat COVID-19, and help inform the response to potential long-term complications of the disease.", "qid": 29, "docid": "2cvvkrx9", "rank": 3, "score": 0.823745846748352}, {"content": "Title: A SARS-CoV-2 protein interaction map reveals targets for drug repurposing Content: A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption1,2. There are no antiviral drugs with proven clinical efficacy for the treatment of COVID-19, nor are there any vaccines that prevent infection with SARS-CoV-2, and efforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells. Here we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins that physically associated with each of the SARS-CoV-2 proteins using affinity-purification mass spectrometry, identifying 332 high-confidence protein-protein interactions between SARS-CoV-2 and human proteins. Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (of which, 29 drugs are approved by the US Food and Drug Administration, 12 are in clinical trials and 28 are preclinical compounds). We screened a subset of these in multiple viral assays and found two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the sigma-1 and sigma-2 receptors. Further studies of these host-factor-targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.", "qid": 29, "docid": "7qd8z5e7", "rank": 4, "score": 0.8144780993461609}, {"content": "Title: Potentially repurposable drugs for COVID-19 identified from SARS-CoV-2 Host Protein Interactome Content: We previously presented the protein-protein interaction network - the \u2018HoP\u2019 or the host protein interactome - of 332 host proteins that were identified to interact with 27 nCoV19 viral proteins by Gordon et al. Here, we studied drugs targeting the proteins in this interactome to identify whether any of them may potentially be repurposable against SARS-CoV-2. We studied each of the drugs using the BaseSpace Correlation Engine and identified those that induce gene expression profiles negatively correlated with SARS-associated expression profile. This analysis resulted in 20 drugs whose differential gene expression (drug versus normal) had an anti-correlation with differential expression for SARS (viral infection versus normal). These included drugs that were already being tested for their clinical activity against SARS-CoV-2, those with proven activity against SARS-CoV/MERS-CoV, broad-spectrum antiviral drugs, and those identified/prioritized by other computational re-purposing studies. In summary, our integrated computational analysis of the HoP interactome in conjunction with drug-induced transcriptomic data resulted in drugs that may be repurposable for COVID-19.", "qid": 29, "docid": "yv2gjjzg", "rank": 5, "score": 0.8131853342056274}, {"content": "Title: Computational Prediction of the Comprehensive SARS-CoV-2 vs. Human Interactome to Guide the Design of Therapeutics Content: Understanding the disease pathogenesis of the novel coronavirus, denoted SARS-CoV-2, is critical to the development of anti-SARS-CoV-2 therapeutics. The global propagation of the viral disease, denoted COVID-19 (\u201ccoronavirus disease 2019\u201d), has unified the scientific community in searching for possible inhibitory small molecules or polypeptides. Given the known interaction between the human ACE2 (\u201cAngiotensin-converting enzyme 2\u201d) protein and the SARS-CoV virus (responsible for the coronavirus outbreak circa. 2003), considerable focus has been directed towards the putative interaction between the SARS-CoV-2 Spike protein and ACE2. However, a more holistic understanding of the SARS-CoV-2 vs. human inter-species interactome promises additional putative protein-protein interactions (PPI) that may be considered targets for the development of inhibitory therapeutics. To that end, we leverage two state-of-the-art, sequence-based PPI predictors (PIPE4 & SPRINT) capable of generating the comprehensive SARS-CoV-2 vs. human interactome, comprising approximately 285,000 pairwise predictions. Of these, we identify the high-scoring subset of human proteins predicted to interact with each of the 14 SARS-CoV-2 proteins by both methods, comprising 279 high-confidence putative interactions involving 225 human proteins. Notably, the Spike-ACE2 interaction was the highest ranked for both the PIPE4 and SPRINT predictors, corroborating existing evidence for this PPI. Furthermore, the PIPE-Sites algorithm was used to predict the putative subsequence that might mediate each interaction and thereby inform the design of inhibitory polypeptides intended to disrupt the corresponding host-pathogen interactions. We hereby publicly release the comprehensive set of PPI predictions and their corresponding PIPE-Sites landscapes in the following DataVerse repository: 10.5683/SP2/JZ77XA. All data and metadata are released under a CC-BY 4.0 licence. The information provided represents theoretical modeling only and caution should be exercised in its use. It is intended as a resource for the scientific community at large in furthering our understanding of SARS-CoV-2.", "qid": 29, "docid": "dxabs45r", "rank": 6, "score": 0.8119158148765564}, {"content": "Title: Tackling SARS-CoV-2: proposed targets and repurposed drugs Content: The SARS-CoV-2 pandemic, declared as a global health emergency by the WHO in February 2020, has currently infected more than 6 million people with fatalities near 371,000 and increasing exponentially, in absence of vaccines and drugs. The pathogenesis of SARS-CoV-2 is still being elucidated. Identifying potential targets and repurposing drugs as therapeutic options is the need of the hour. In this review, we focus on potential druggable targets and suitable therapeutics, currently being explored in clinical trials, to treat SARS-CoV-2 infection. A brief understanding of the complex interactions of both viral as well as host targets, and the possible repurposed drug candidates are described with an emphasis on understanding the mechanisms at the molecular level.", "qid": 29, "docid": "4tis2he4", "rank": 7, "score": 0.8104881048202515}, {"content": "Title: A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing Content: An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption(1,2). There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To illuminate this, we cloned, tagged and expressed 26 of the 29 viral proteins in human cells and identified the human proteins physically associated with each using affinity- purification mass spectrometry (AP-MS), which identified 332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains.", "qid": 29, "docid": "38d6gb7o", "rank": 8, "score": 0.8031163215637207}, {"content": "Title: Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods Content: SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further in vitro and in vivo studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.", "qid": 29, "docid": "i1lyno9g", "rank": 9, "score": 0.7995169162750244}, {"content": "Title: Identifying Human Interactors of SARS-CoV-2 Proteins and Drug Targets for COVID-19 using Network-Based Label Propagation Content: Motivated by the critical need to identify new treatments for COVID-19, we present a genome-scale, systems-level computational approach to prioritize drug targets based on their potential to regulate host-virus interactions or their downstream signaling targets. We adapt and specialize network label propagation methods to this end. We demonstrate that these techniques can predict human-SARS-CoV-2 protein interactors with high accuracy. The top-ranked proteins that we identify are enriched in host biological processes that are potentially coopted by the virus. We present cases where our methodology generates promising insights such as the potential role of HSPA5 in viral entry. We highlight the connection between endoplasmic reticulum stress, HSPA5, and anti-clotting agents. We identify tubulin proteins involved in ciliary assembly that are targeted by anti-mitotic drugs. Drugs that we discuss are already undergoing clinical trials to test their efficacy against COVID-19. Our prioritized list of human proteins and drug targets is available as a general resource for biological and clinical researchers who are repositioning existing and approved drugs or developing novel therapeutics as anti-COVID-19 agents.", "qid": 29, "docid": "qrfx165d", "rank": 10, "score": 0.7992713451385498}, {"content": "Title: Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2 Content: Human coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and 2019 novel coronavirus (2019-nCoV, also known as SARS-CoV-2), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV/SARS-CoV-2. Drug repurposing, representing as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV\u2013host interactome and drug targets in the human protein\u2013protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV/SARS-CoV-2 shares the highest nucleotide sequence identity with SARS-CoV (79.7%). Specifically, the envelope and nucleocapsid proteins of 2019-nCoV/SARS-CoV-2 are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. Using network proximity analyses of drug targets and HCoV\u2013host interactions in the human interactome, we prioritize 16 potential anti-HCoV repurposable drugs (e.g., melatonin, mercaptopurine, and sirolimus) that are further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. We further identify three potential drug combinations (e.g., sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the \u201cComplementary Exposure\u201d pattern: the targets of the drugs both hit the HCoV\u2013host subnetwork, but target separate neighborhoods in the human interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations targeting 2019-nCoV/SARS-CoV-2.", "qid": 29, "docid": "4yuw7jo3", "rank": 11, "score": 0.7967931032180786}, {"content": "Title: Genetic architecture of host proteins interacting with SARS-CoV-2 Content: Strategies to develop therapeutics for SARS-CoV-2 infection may be informed by experimental identification of viral-host protein interactions in cellular assays and measurement of host response proteins in COVID-19 patients. Identification of genetic variants that influence the level or activity of these proteins in the host could enable rapid \u2018in silico\u2019 assessment in human genetic studies of their causal relevance as molecular targets for new or repurposed drugs to treat COVID-19. We integrated large-scale genomic and aptamer-based plasma proteomic data from 10,708 individuals to characterize the genetic architecture of 179 host proteins reported to interact with SARS-CoV-2 proteins or to participate in the host response to COVID-19. We identified 220 host DNA sequence variants acting in cis (MAF 0.01\u201349.9%) and explaining 0.3\u201370.9% of the variance of 97 of these proteins, including 45 with no previously known protein quantitative trait loci (pQTL) and 38 encoding current drug targets. Systematic characterization of pQTLs across the phenome identified protein-drug-disease links, evidence that putative viral interaction partners such as MARK3 affect immune response, and establish the first link between a recently reported variant for respiratory failure of COVID-19 patients at the ABO locus and hypercoagulation, i.e. maladaptive host response. Our results accelerate the evaluation and prioritization of new drug development programmes and repurposing of trials to prevent, treat or reduce adverse outcomes. Rapid sharing and dynamic and detailed interrogation of results is facilitated through an interactive webserver (https://omicscience.org/apps/covidpgwas/).", "qid": 29, "docid": "k0dzrgtx", "rank": 12, "score": 0.7941079139709473}, {"content": "Title: Recognition of potential Covid-19 drug treatments through the study of existing protein-drug and protein-protein structures: an analysis of kinetically active residues Content: We report results of our study of approved drugs as potential treatments for COVID 19, based on the application of various bioinformatics predictive methods. The drugs studied include Chloroquine, Ivermectin, Remdesivir and alpha-difluoromethylornithine (DMFO). Our results indicate that these small drug molecules selectively bind to stable, kinetically active residues and residues adjoining them on the surface of proteins and inside protein pockets, and that some prefer hydrophobic over other active sites. Our approach is not restricted to viruses and can facilitate rational drug design, as well as improve our understanding of molecular interactions, in general.", "qid": 29, "docid": "khxdk8t8", "rank": 13, "score": 0.7932873964309692}, {"content": "Title: Computational modeling of Human-nCoV protein-protein interaction network Content: COVID-19 has created a global pandemic with high morbidity and mortality in 2020. Novel coronavirus (nCoV), also known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), is responsible for this deadly disease. International Committee on Taxonomy of Viruses (ICTV) has declared that nCoV is highly genetically similar to SARS-CoV epidemic in 2003 (89% similarity). Limited number of clinically validated Human-nCoV protein interaction data is available in the literature. With this hypothesis, the present work focuses on developing a computational model for nCoV-Human protein interaction network, using the experimentally validated SARS-CoV-Human protein interactions. Initially, level-1 and level-2 human spreader proteins are identified in SARS-CoV-Human interaction network, using Susceptible-Infected-Susceptible (SIS) model. These proteins are considered as potential human targets for nCoV bait proteins. A gene-ontology based fuzzy affinity function has been used to construct the nCoV-Human protein interaction network at 99.98% specificity threshold. This also identifies the level-1 human spreaders for COVID-19 in human protein-interaction network. Level-2 human spreaders are subsequently identified using the SIS model. The derived host-pathogen interaction network is finally validated using 7 potential FDA listed drugs for COVID-19 with significant overlap between the known drug target proteins and the identified spreader proteins.", "qid": 29, "docid": "k4f79dr4", "rank": 14, "score": 0.7905713319778442}, {"content": "Title: Identification of potential inhibitors of three key enzymes of SARS-CoV2 using computational approach Content: The recent outbreak of coronavirus disease-19 (COVID-19) continues to drastically affect healthcare throughout the world. To date, no approved treatment regimen or vaccine is available to effectively attenuate or prevent the infection. Therefore, collective and multidisciplinary efforts are needed to identify new therapeutics or to explore effectiveness of existing drugs and drug-like small molecules against SARS-CoV-2 for lead identification and repurposing prospects. This study addresses the identification of small molecules that specifically bind to any of the three essential proteins (RdRp, 3CL-protease and helicase) of SARS-CoV-2. By applying computational approaches we screened a library of 4574 compounds also containing FDA-approved drugs against these viral proteins. Shortlisted hits from initial screening were subjected to iterative docking with the respective proteins. Ranking score on the basis of binding energy, clustering score, shape complementarity and functional significance of the binding pocket was applied to identify the binding compounds. Finally, to minimize chances of false positives, we performed docking of the identified molecules with 100 irrelevant proteins of diverse classes thereby ruling out the non-specific binding. Three FDA-approved drugs showed binding to 3CL-protease either at the catalytic pocket or at an allosteric site related to functionally important dimer formation. A drug-like molecule showed binding to RdRp in its catalytic pocket blocking the key catalytic residues. Two other drug-like molecules showed specific interactions with helicase at a key domain involved in catalysis. This study provides lead drugs or drug-like molecules for further in vitro and clinical investigation for drug repurposing and new drug development prospects.", "qid": 29, "docid": "eja8fkwv", "rank": 15, "score": 0.7872254252433777}, {"content": "Title: Virtual screening of approved drugs as potential SARS-CoV-2 main protease inhibitors Content: The global emergency caused by COVID-19 makes the discovery of drugs capable of inhibiting SARS-CoV-2 a priority, to reduce the mortality and morbidity of this disease. Repurposing approved drugs can provide therapeutic alternatives that promise rapid and ample coverage because they have a documented safety record, as well as infrastructure for large-scale production. The main protease of SARS-CoV-2 (Mpro) is an excellent therapeutic target because it is critical for viral replication; however, Mpro has a highly flexible active site that must be considered when performing computer-assisted drug discovery. In this work, potential inhibitors of the main protease (Mpro) of SARS-Cov-2 were identified through a docking-assisted virtual screening procedure. A total of 4384 drugs, all approved for human use, were screened against three conformers of Mpro. The ligands were further studied through molecular dynamics simulations and binding free energy analysis. A total of nine currently approved molecules are proposed as potential inhibitors of SARS-CoV-2. These molecules can be further tested to speed the development of therapeutics against COVID-19.", "qid": 29, "docid": "jnw0pnfu", "rank": 16, "score": 0.7870070934295654}, {"content": "Title: Discovering small-molecule therapeutics against SARS-CoV-2 Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global health pandemic. The lack of effective treatments, coupled with its etiology, has resulted in more than 400,000 deaths at the time of writing. The SARS-CoV-2 genome is highly homologous to that of SARS-CoV, the causative agent behind the 2003 SARS outbreak. Based on prior reports, clinicians have pursued the off-label use of several antiviral drugs, while the scientific community has responded by seeking agents against traditional targets, especially viral proteases. However, several avenues remain unexplored, including disrupting E and M protein oligomerization, outcompeting host glycan-virus interactions, interfering with the heparan sulfate proteoglycans-virus interaction, and others. In this review, we highlight some of these opportunities while summarizing the drugs currently in use against coronavirus 2019 (COVID-19).", "qid": 29, "docid": "cpg4q29v", "rank": 17, "score": 0.7867445349693298}, {"content": "Title: Discovering small-molecule therapeutics against SARS-CoV-2 Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global health pandemic. The lack of effective treatments, coupled with its etiology, has resulted in more than 400,000 deaths at the time of writing. The SARS-CoV-2 genome is highly homologous to that of SARS-CoV, the causative agent behind the 2003 SARS outbreak. Based on prior reports, clinicians have pursued the off-label use of several antiviral drugs, while the scientific community has responded by seeking agents against traditional targets, especially viral proteases. However, several avenues remain unexplored, including disrupting E and M protein oligomerization, outcompeting host glycan\u2013virus interactions, interfering with the heparan sulfate proteoglycans\u2013virus interaction, and others. In this review, we highlight some of these opportunities while summarizing the drugs current in use against coronavirus 2019 (COVID-19).", "qid": 29, "docid": "043w3zgy", "rank": 18, "score": 0.7862992286682129}, {"content": "Title: COVID-19: Drug Targets and Potential Treatments Content: Currently, humans are immersed in a pandemic caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which threatens public health worldwide. To date, no drug or vaccine has been approved to treat the severe disease caused by this coronavirus, COVID-19. In this paper, we will focus on the main virus-based and host-based targets that can guide efforts in medicinal chemistry to discover new drugs for this devastating disease. In principle, all CoV enzymes and proteins involved in viral replication and the control of host cellular machineries are potentially druggable targets in the search for therapeutic options for SARS-CoV-2. This Perspective provides an overview of the main targets from a structural point of view, together with reported therapeutic compounds with activity against SARS-CoV-2 and/or other CoVs. Also, the role of innate immune response to coronavirus infection and the related therapeutic options will be presented.", "qid": 29, "docid": "f6xhrpi8", "rank": 19, "score": 0.7848995923995972}, {"content": "Title: Structural Basis of the SARS-CoV-2/SARS-CoV Receptor Binding and Small-Molecule Blockers as Potential Therapeutics Content: Over the past two decades, deadly coronaviruses have caused major challenges to public health, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2, 2019) pandemic. The path for virus invasion into humans and other hosts is mediated by \"host-pathogen\" interactions, specifically, virus-receptor binding. An in-depth understanding of the virus-receptor binding mechanism is a prerequisite for the discovery of vaccines, antibodies, and/or small-molecule inhibitors that can interrupt this interaction and prevent or cure infection. In this review, we discuss the viral entry mechanism, the known structural aspects of virus-receptor interactions (SARS-CoV-2 S/humanACE2, SARS-CoV S/humanACE2, and MERS-CoV S/humanDPP4), the key protein domains and amino acid residues involved in binding, and the small-molecule inhibitors and other drugs that have (as of June, 2020) exhibited therapeutic potential. Specifically, we review the potential clinical utility of two transmembrane serine protease 2 (TMPRSS2)-targeting protease inhibitors, nafamostat mesylate and camostat mesylate, as well as two novel potent fusion inhibitors and the repurposed Ebola drug, remdesivir, which is specific to RdRp, against human coronaviruses, including SARS-CoV-2. This article has been accepted for publication on June 23, 2020. Changes may still occur before final publication. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 61 is January 8, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.", "qid": 29, "docid": "nbc07tf7", "rank": 20, "score": 0.7847791910171509}, {"content": "Title: Structural Basis of the SARS-CoV-2/SARS-CoV Receptor Binding and Small-Molecule Blockers as Potential Therapeutics. Content: Over the past two decades, deadly coronaviruses have caused major challenges to public health, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2, 2019) pandemic. The path for virus invasion into humans and other hosts is mediated by \"host-pathogen\" interactions, specifically, virus-receptor binding. An in-depth understanding of the virus-receptor binding mechanism is a prerequisite for the discovery of vaccines, antibodies, and/or small-molecule inhibitors that can interrupt this interaction and prevent or cure infection. In this review, we discuss the viral entry mechanism, the known structural aspects of virus-receptor interactions (SARS-CoV-2 S/humanACE2, SARS-CoV S/humanACE2, and MERS-CoV S/humanDPP4), the key protein domains and amino acid residues involved in binding, and the small-molecule inhibitors and other drugs that have (as of June, 2020) exhibited therapeutic potential. Specifically, we review the potential clinical utility of two transmembrane serine protease 2 (TMPRSS2)-targeting protease inhibitors, nafamostat mesylate and camostat mesylate, as well as two novel potent fusion inhibitors and the repurposed Ebola drug, remdesivir, which is specific to RdRp, against human coronaviruses, including SARS-CoV-2. This article has been accepted for publication on June 23, 2020. Changes may still occur before final publication. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 61 is January 8, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.", "qid": 29, "docid": "tw2nls29", "rank": 21, "score": 0.7847791910171509}, {"content": "Title: Multi-level proteomics reveals host-perturbation strategies of SARS-CoV-2 and SARS-CoV Content: The sudden global emergence of SARS-CoV-2 urgently requires an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several omics studies have extended our knowledge of COVID-19 pathophysiology, including some focused on proteomic aspects1\u20133. To understand how SARS-CoV-2 and related coronaviruses manipulate the host we here characterized interactome, proteome and signaling processes in a systems-wide manner. This identified connections between the corresponding cellular events, revealed functional effects of the individual viral proteins and put these findings into the context of host signaling pathways. We investigated the closely related SARS-CoV-2 and SARS-CoV viruses as well as the influence of SARS-CoV-2 on transcriptome, proteome, ubiquitinome and phosphoproteome of a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed relationships between the perturbations taking place upon SARS-CoV-2 infection at different layers and identified unique and common molecular mechanisms of SARS coronaviruses. The results highlight the functionality of individual proteins as well as vulnerability hotspots of SARS-CoV-2, which we targeted with clinically approved drugs. We exemplify this by identification of kinase inhibitors as well as MMPase inhibitors with significant antiviral effects against SARS-CoV-2.", "qid": 29, "docid": "zf096duh", "rank": 22, "score": 0.7836892604827881}, {"content": "Title: Potential targets for anti-SARS drugs in the structural proteins from SARS related coronavirus Content: This is a further study on the severe acute respiratory syndrome (SARS) using the probabilistic models. The purpose was to define the potential targets for anti-SARS drugs in the structural proteins from human SARS related coronavirus (SARS-CoV) while knowing little about the functional sites and possible mutations in these proteins. From a probabilistic viewpoint, we can theoretically select the amino acid pairs as potential candidates for anti-SARS drugs. These candidates have a greater chance of colliding with anti-SARS drugs, are more likely to link with the protein functions and are less vulnerable to mutations.", "qid": 29, "docid": "amzmyqys", "rank": 23, "score": 0.7819141149520874}, {"content": "Title: Predicting potential drug targets and repurposable drugs for COVID-19 via a deep generative model for graphs Content: Coronavirus Disease 2019 (COVID-19) has been creating a worldwide pandemic situation. Repurposing drugs, already shown to be free of harmful side effects, for the treatment of COVID-19 patients is an important option in launching novel therapeutic strategies. Therefore, reliable molecule interaction data are a crucial basis, where drug-/protein-protein interaction networks establish invaluable, year-long carefully curated data resources. However, these resources have not yet been systematically exploited using high-performance artificial intelligence approaches. Here, we combine three networks, two of which are year-long curated, and one of which, on SARS-CoV-2-human host-virus protein interactions, was published only most recently (30th of April 2020), raising a novel network that puts drugs, human and virus proteins into mutual context. We apply Variational Graph AutoEncoders (VGAEs), representing most advanced deep learning based methodology for the analysis of data that are subject to network constraints. Reliable simulations confirm that we operate at utmost accuracy in terms of predicting missing links. We then predict hitherto unknown links between drugs and human proteins against which virus proteins preferably bind. The corresponding therapeutic agents present splendid starting points for exploring novel host-directed therapy (HDT) options.", "qid": 29, "docid": "2lmwnfda", "rank": 24, "score": 0.7818838953971863}, {"content": "Title: COVID-19: Drug Targets and Potential Treatments Content: [Image: see text] Currently, humans are immersed in a pandemic caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which threatens public health worldwide. To date, no drug or vaccine has been approved to treat the severe disease caused by this coronavirus, COVID-19. In this paper, we will focus on the main virus-based and host-based targets that can guide efforts in medicinal chemistry to discover new drugs for this devastating disease. In principle, all CoV enzymes and proteins involved in viral replication and the control of host cellular machineries are potentially druggable targets in the search for therapeutic options for SARS-CoV-2. This Perspective provides an overview of the main targets from a structural point of view, together with reported therapeutic compounds with activity against SARS-CoV-2 and/or other CoVs. Also, the role of innate immune response to coronavirus infection and the related therapeutic options will be presented.", "qid": 29, "docid": "2kfmgr7k", "rank": 25, "score": 0.781386137008667}, {"content": "Title: Coagulation modifiers targeting SARS-CoV-2 main protease Mpro for COVID-19 treatment: an in silico approach Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection depends on viral polyprotein processing, catalysed by the main proteinase (Mpro). The solution of the SARS-CoV-2 Mpro structure allowed the investigation of potential inhibitors. This work aims to provide first evidences of the applicability of commercially approved drugs to treat coronavirus disease-19 (COVID-19). We screened 4,334 compounds to found potential inhibitors of SARS-CoV-2 replication using an in silico approach. Our results evidenced the potential use of coagulation modifiers in COVID-19 treatment due to the structural similarity of SARS-CoV-2 Mpro and human coagulation factors thrombin and Factor Xa. Further in vitro and in vivo analysis are needed to corroborate these results.", "qid": 29, "docid": "jxha9b65", "rank": 26, "score": 0.7802001237869263}, {"content": "Title: Drug repurposing against SARS-CoV-2 using E-pharmacophore based virtual screening, molecular docking and molecular dynamics with main protease as the target Content: Since its first report in December 2019 from China, the COVID-19 pandemic caused by the beta-coronavirus SARS-CoV-2 has spread at an alarming pace infecting about 5.59 million, and claiming the lives of more than 0.35 million individuals across the globe. The lack of a clinically approved vaccine or drug remains the biggest bottleneck in combating the pandemic. Drug repurposing can expedite the process of drug development by identifying known drugs which are effective against SARS-CoV-2. The SARS-CoV-2 main protease is a promising drug target due to its indispensable role in viral multiplication inside the host. In the present study an E-pharmacophore hypothesis was generated using a crystal structure of the viral protease in complex with an imidazole carbaximide inhibitor. Drugs available in the superDRUG2 database were used to identify candidate drugs for repurposing. The hits obtained from the pharmacophore based screening were further screened using a structure based approach involving molecular docking at different precisions. The binding energies of the most promising compounds were estimated using MM-GBSA. The stability of the interactions between the selected drugs and the target were further explored using molecular dynamics simulation at 100 ns. The results showed that the drugs Binifibrate and Bamifylline bind strongly to the enzyme active site and hence they can be repurposed against SARS-CoV-2. However, U.S Food and Drug Administration have withdrawn Binifibrate from the market as it was having some adverse health effects on patients. Communicated by Ramaswamy H. Sarma", "qid": 29, "docid": "hg9i6v26", "rank": 27, "score": 0.7797269225120544}, {"content": "Title: Hypothetical targets and plausible drugs of Coronavirus infection caused by SARS-CoV-2. Content: The world is confronting a dire situation due to the recent pandemic of the novel coronavirus disease (SARS-CoV-2) with the mortality rate passed over 470,000. Attaining efficient drugs evolve in parallel to the understanding of the SARS-CoV-2 pathogenesis. The current drugs in the pipeline and some plausible drugs are overviewed in this paper. Although different types of antiviral targets are applicable for SARS-CoV-2 drug screenings, the more promising targets can be considered as 3C-like main protease (3CL protease) and RNA polymerase. The remdesivir could be considered the closest bifunctional drug to the provisional clinical administration for SARS-CoV-2. The known molecular targets of the SARS-CoV-2 include fourteen targets while four molecules of angiotensin-converting enzyme 2 (ACE2), cathepsin L, 3CL protease and RNA-dependent RNA polymerase (RdRp) are suggested as more promising potential targets. Accordingly, dual-acting drugs as an encouraging solution in drug discovery are suggested. Emphasizing the potential route of SARS-CoV-2 infection and virus entry related factors like integrins, cathepsin and ACE2 seems valuable. The potential molecular targets of each phase of the SARS-CoV-2 life cycle are discussed and highlighted in this paper. Much progress in understanding the SARS-CoV-2 and molecular details of its life cycle followed by the identification of new therapeutic targets are needed to lead us to an efficient approach in anti-SARS-CoV-2 drug discovery.", "qid": 29, "docid": "bq0hm89l", "rank": 28, "score": 0.7783788442611694}, {"content": "Title: Potential inhibitors of the interaction between ACE2 and SARS-CoV-2 (RBD), to develop a drug Content: AIMS: The COVID-19 disease caused by the SARS-CoV-2 has become a pandemic and there are no effective treatments that reduce the contagion. It is urgent to propose new treatment options, which are more effective in the interaction between viruses and cells. In this study was to develop a search for new pharmacological compounds against the angiotensin-converting enzyme 2 (ACE2), to inhibit the interaction with SARS-CoV-2. MATERIALS AND METHODS: Docking, virtual screening using almost 500,000 compounds directed to interact in the region between the residues (Gln24, Asp30, His34, Tyr41, Gln42, Met82, Lys353, and Arg357) in ACE2. The average of \u0394G(binding), the standard deviation value and the theoretical toxicity from compounds were analyzed. KEY FINDINGS: 20 best compounds directed to interact in ACE2 with a high probability to be safe in humans, validated by web servers of prediction of ADME and toxicity (ProTox-II and PreADMET), to difficult the interaction between ACE2 and region binding domain (RBD) of SARS-CoV-2. SIGNIFICANCE: In this study, 20 compounds were determined by docking focused on the region of interaction between ACE2 and RBD of SARS-CoV-2 was carried out. The compounds are publicly available to validate the effect in in vitro tests.", "qid": 29, "docid": "1c4vqaqr", "rank": 29, "score": 0.7783781886100769}, {"content": "Title: Machine-Learning Driven Drug Repurposing for COVID-19 Content: The integration of machine learning methods into bioinformatics provides particular benefits in identifying how therapeutics effective in one context might have utility in an unknown clinical context or against a novel pathology. We aim to discover the underlying associations between viral proteins and antiviral therapeutics that are effective against them by employing neural network models. Using the National Center for Biotechnology Information virus protein database and the DrugVirus database, which provides a comprehensive report of broad-spectrum antiviral agents (BSAAs) and viruses they inhibit, we trained ANN models with virus protein sequences as inputs and antiviral agents deemed safe-in-humans as outputs. Model training excluded SARS-CoV-2 proteins and included only Phases II, III, IV and Approved level drugs. Using sequences for SARS-CoV-2 (the coronavirus that causes COVID-19) as inputs to the trained models produces outputs of tentative safe-in-human antiviral candidates for treating COVID-19. Our results suggest multiple drug candidates, some of which complement recent findings from noteworthy clinical studies. Our in-silico approach to drug repurposing has promise in identifying new drug candidates and treatments for other viruses.", "qid": 29, "docid": "1nnqx1g9", "rank": 30, "score": 0.7779521942138672}, {"content": "Title: Identification of Repurposal Drugs and Adverse Drug Reactions for Various Courses of Coronavirus Disease 2019 (COVID-19) Based on Single-cell RNA Sequencing Data Content: With more than 3.8 million people infected Coronavirus Disease 2019 (COVID-19), caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a critical threat to human health. There is no proven vaccine or specific drug to date, which highlights the urgent need for rapid development of therapeutics for COVID-19. To identify potentially repurposable drugs, we employed a systematic approach to mine candidates from U.S. FDA approved drugs and pre-clinical small-molecule compounds by integrating the gene expression perturbation data by chemicals from the Library of Integrated Network-Based Cellular Signatures (LINCS) project with publically available single-cell RNA sequencing dataset from mild and severe COVID-19 patients. We identified 281 FDA approved drugs that have the potential to be effective against SARS-CoV-2 infection, 10 of which are currently undergoing clinical trials to evaluate their efficacy against COVID-19. In conclusion, we have identified a list of repurposable anti-SARS- CoV-2 drugs using a systems biology approach.", "qid": 29, "docid": "7ftg6bfx", "rank": 31, "score": 0.7770999670028687}, {"content": "Title: Drug repurposing against SARS-CoV-2 using E-pharmacophore based virtual screening, molecular docking and molecular dynamics with main protease as the target Content: Since its first report in December 2019 from China, the COVID-19 pandemic caused by the beta-coronavirus SARS-CoV-2 has spread at an alarming pace infecting about 5.59 million, and claiming the lives of more than 0.35 million individuals across the globe. The lack of a clinically approved vaccine or drug remains the biggest bottleneck in combating the pandemic. Drug repurposing can expedite the process of drug development by identifying known drugs which are effective against SARS-CoV-2. The SARS-CoV-2 main protease is a promising drug target due to its indispensable role in viral multiplication inside the host. In the present study an E-pharmacophore hypothesis was generated using a crystal structure of the viral protease in complex with an imidazole carbaximide inhibitor. Drugs available in the superDRUG2 database were used to identify candidate drugs for repurposing. The hits obtained from the pharmacophore based screening were further screened using a structure based approach involving molecular docking at different precisions. The binding energies of the most promising compounds were estimated using MM-GBSA. The stability of the interactions between the selected drugs and the target were further explored using molecular dynamics simulation at 100 ns. The results showed that the drugs Binifibrate and Bamifylline bind strongly to the enzyme active site and hence they can be repurposed against SARS-CoV-2. However, U.S Food and Drug Administration have withdrawn Binifibrate from the market as it was having some adverse health effects on patients.Communicated by Ramaswamy H. Sarma.", "qid": 29, "docid": "rvzgut4w", "rank": 32, "score": 0.7768269777297974}, {"content": "Title: Potential inhibitors of the interaction between ACE2 and SARS-CoV-2 (RBD), to develop a drug Content: AIMS: The COVID-19 disease caused by the SARS-CoV-2 has become a pandemic and there are no effective treatments that reduce the contagion. It is urgent to propose new treatment options, which are more effective in the interaction between viruses and cells. In this study was to develop a search for new pharmacological compounds against the angiotensin-converting enzyme 2 (ACE2), to inhibit the interaction with SARS-CoV-2. MATERIALS AND METHODS: Docking, virtual screening using almost 500,000 compounds directed to interact in the region between the residues (Gln24, Asp30, His34, Tyr41, Gln42, Met82, Lys353, and Arg357) in ACE2. The average of &#916;Gbinding, the standard deviation value and the theoretical toxicity from compounds were analyzed. KEY FINDINGS: 20 best compounds directed to interact in ACE2 with a high probability to be safe in humans, validated by web servers of prediction of ADME and toxicity (ProTox-II and PreADMET), to difficult the interaction between ACE2 and region binding domain (RBD) of SARS-CoV-2. SIGNIFICANCE: In this study, 20 compounds were determined by docking focused on the region of interaction between ACE2 and RBD of SARS-CoV-2 was carried out. The compounds are publicly available to validate the effect in in vitro tests.", "qid": 29, "docid": "qotug475", "rank": 33, "score": 0.7767140865325928}, {"content": "Title: Network-based Drug Repurposing for Human Coronavirus Content: Human Coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle east respiratory syndrome coronavirus (MERS-CoV), and 2019 novel coronavirus (2019-nCoV), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV. Drug repurposing, represented as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV-host interactome and drug targets in the human protein-protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV has the highest nucleotide sequence identity with SARS-CoV (79.7%) among the six other known pathogenic HCoVs. Specifically, the envelope and nucleocapsid proteins of 2019-nCoV are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. Using network proximity analyses of drug targets and known HCoV-host interactions in the human protein-protein interactome, we computationally identified 135 putative repurposable drugs for the potential prevention and treatment of HCoVs. In addition, we prioritized 16 potential anti-HCoV repurposable drugs (including melatonin, mercaptopurine, and sirolimus) that were further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. Finally, we showcased three potential drug combinations (including sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the Complementary Exposure pattern: the targets of the drugs both hit the HCoV-host subnetwork, but target separate neighborhoods in the human protein-protein interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations toward future clinical trials for HCoVs.", "qid": 29, "docid": "b4mdiont", "rank": 34, "score": 0.77651447057724}, {"content": "Title: Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells Content: Current guidelines for COVID-19 management recommend the utilization of various repurposed drugs. Despite ongoing research toward the development of a vaccine against SARS-CoV-2, such a vaccine will not be available in time to contribute to the containment of the ongoing pandemic. Therefore, there is an urgent need to develop a framework for the rapid identification of novel targets for diagnostic and therapeutic interventions. We analyzed publicly available transcriptomic datasets of SARS-CoV infected humans and mammals to identify consistent differentially expressed genes then validated in SARS-CoV-2 infected epithelial cells transcriptomic datasets. Comprehensive toxicogenomic analysis of the identified genes to identify possible interactions with clinically proven drugs was carried out. We identified IFITM3 as an early upregulated gene, and valproic acid was found to enhance its mRNA expression as well as induce its antiviral action. These findings indicate that analysis of publicly available transcriptomic and toxicogenomic data represents a rapid approach for the identification of novel targets and molecules that can modify the action of such targets during the early phases of emerging infections like COVID-19.", "qid": 29, "docid": "cmfo60z0", "rank": 35, "score": 0.7764725685119629}, {"content": "Title: Blocking Coronavirus 19 Infection via the SARS-CoV-2 Spike Protein: Initial Steps Content: [Image: see text] Recent crystal structure data for protein\u2013protein interactions featuring the SARS-CoV-2 spike protein will inevitably trigger a new wave of research in this area that was not possible before. This Viewpoint outlines a few of the ways that it is already happening.", "qid": 29, "docid": "908d8bax", "rank": 36, "score": 0.7762693166732788}, {"content": "Title: Ligand\u2010centered assessment of SARS\u2010CoV\u20102 drug target models in the Protein Data Bank Content: A bright spot in the SARS\u2010CoV\u20102 (CoV\u20102) coronavirus pandemic has been the immediate mobilization of the biomedical community, working to develop treatments and vaccines for COVID\u201019. Rational drug design against emerging threats depends on well\u2010established methodology, mainly utilizing X\u2010ray crystallography, to provide accurate structure models of the macromolecular drug targets and of their complexes with candidates for drug development. In the current crisis the structural biological community has responded by presenting structure models of CoV\u20102 proteins and depositing them in the Protein Data Bank (PDB), usually without time embargo and before publication. Since the structures from the first\u2010line research are produced in an accelerated mode, there is an elevated chance of mistakes and errors, with the ultimate risk of hindering, rather than speeding\u2010up, drug development. In the present work, we have used model\u2010validation metrics and examined the electron density maps for the deposited models of CoV\u20102 proteins and a sample of related proteins available in the PDB as of 1 April 2020. We present these results with the aim of helping the biomedical community establish a better\u2010validated pool of data. The proteins are divided into groups according to their structure and function. In most cases, no major corrections were necessary. However, in several cases significant revisions in the functionally sensitive area of protein\u2010inhibitor complexes or for bound ions justified correction, re\u2010refinement, and eventually re\u2010versioning in the PDB. The re\u2010refined coordinate files and a tool for facilitating model comparisons are available at https://covid-19.bioreproducibility.org.", "qid": 29, "docid": "0eqn7m73", "rank": 37, "score": 0.7756678462028503}, {"content": "Title: Predicting commercially available antiviral drugs that may act on the novel coronavirus (SARS-CoV-2) through a drug-target interaction deep learning model Content: Abstract The infection of a novel coronavirus found in Wuhan of China (SARS-CoV-2) is rapidly spreading, and the incidence rate is increasing worldwide. Due to the lack of effective treatment options for SARS-CoV-2, various strategies are being tested in China, including drug repurposing. In this study, we used our pre-trained deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI) to identify commercially available drugs that could act on viral proteins of SARS-CoV-2. The result showed that atazanavir, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), is the best chemical compound, showing an inhibitory potency with Kd of 94.94 nM against the SARS-CoV-2 3C-like proteinase, followed by remdesivir (113.13 nM), efavirenz (199.17 nM), ritonavir (204.05 nM), and dolutegravir (336.91 nM). Interestingly, lopinavir, ritonavir, and darunavir are all designed to target viral proteinases. However, in our prediction, they may also bind to the replication complex components of SARS-CoV-2 with an inhibitory potency with Kd < 1,000 nM. In addition, we also found that several antiviral agents, such as Kaletra (lopinavir/ritonavir), could be used for the treatment of SARS-CoV-2. Overall, we suggest that the list of antiviral drugs identified by the MT-DTI model should be considered, when establishing effective treatment strategies for SARS-CoV-2.", "qid": 29, "docid": "zb434ve3", "rank": 38, "score": 0.7755308747291565}, {"content": "Title: In silico Study of Pharmacological Treatments against SARS-CoV2 Main Protease Content: The COVID-19 caused by a new type of coronavirus has emerged from China and led to thousands of death globally Despite the efforts engaged in studying this newly emerged virus and searching for its treatment, the understanding of the COVID-19 drug and target protein interactions still represent a key challenge Several molecules have demonstrated In-Vitro activity against the SARS-CoV-2 virus and/or potential clinical benefit in observational and non-randomized studies Randomized clinical trials of an appropriate size are currently ongoing to establish the efficacy of these therapeutic proposals Herein, concerning these diverse guidelines and therapeutic suggestions of different approaches to the treatment, this research aims to provide a molecular analysis of the interaction between the principal molecules cited in bibliography and the active protease site of the virus", "qid": 29, "docid": "krtcols6", "rank": 39, "score": 0.7753192186355591}, {"content": "Title: Matrix metallopeptidase 9 as a host protein target of chloroquine and melatonin for immunoregulation in COVID-19: A network-based meta-analysis Content: AIMS: The molecular pathogenesis of COVID-19 is similar to other coronavirus (CoV) infections viz. severe acute respiratory syndrome (SARS) in human. Due to scarcity of the suitable treatment strategy, the present study was undertaken to explore host protein(s) targeted by potent repurposed drug(s) in COVID-19. MATERIALS AND METHODS: The differentially expressed genes (DEGs) were identified from microarray data repository of SARS-CoV patient blood. The repurposed drugs for COVID-19 were selected from available literature. Using DEGs and drugs, the protein-protein interaction (PPI) and chemo-protein interaction (CPI) networks were constructed and combined to develop an interactome model of PPI-CPI network. The top-ranked sub-network with its hub-bottleneck nodes were evaluated with their functional annotations. KEY FINDINGS: A total of 120 DEGs and 65 drugs were identified. The PPI-CPI network (118 nodes and 293 edges) exhibited a top-ranked sub-network (35 nodes and 174 connectivities) with 12 hub-bottleneck nodes having two drugs chloroquine and melatonin in association with 10 proteins corresponding to six upregulated and four downregulated genes. Two drugs interacted directly with the hub-bottleneck node i.e. matrix metallopeptidase 9 (MMP9), a host protein corresponding to its upregulated gene. MMP9 showed functional annotations associated with neutrophil mediated immunoinflammation. Moreover, literature survey revealed that angiotensin converting enzyme 2, a membrane receptor of SARS-CoV-2 virus, might have functional cooperativity with MMP9 and a possible interaction with both drugs. SIGNIFICANCE: The present study reveals that between chloroquine and melatonin, melatonin appears to be more promising repurposed drug against MMP9 for better immunocompromisation in COVID-19.", "qid": 29, "docid": "0sdjy80s", "rank": 40, "score": 0.774427056312561}, {"content": "Title: Ligand-centered assessment of SARS-CoV-2 drug target models in the Protein Data Bank Content: A bright spot in the SARS-CoV-2 (CoV-2) coronavirus pandemic has been the immediate mobilization of the biomedical community, working to develop treatments and vaccines for COVID-19. Rational drug design against emerging threats depends on well-established methodology, mainly utilizing X-ray crystallography, to provide accurate structure models of the macromolecular drug targets and of their complexes with candidates for drug development. In the current crisis, the structural biological community has responded by presenting structure models of CoV-2 proteins and depositing them in the Protein Data Bank (PDB), usually without time embargo and before publication. Since the structures from the first-line research are produced in an accelerated mode, there is an elevated chance of mistakes and errors, with the ultimate risk of hindering, rather than speeding up, drug development. In the present work, we have used model-validation metrics and examined the electron density maps for the deposited models of CoV-2 proteins and a sample of related proteins available in the PDB as of April 1, 2020. We present these results with the aim of helping the biomedical community establish a better-validated pool of data. The proteins are divided into groups according to their structure and function. In most cases, no major corrections were necessary. However, in several cases significant revisions in the functionally sensitive area of protein-inhibitor complexes or for bound ions justified correction, re-refinement, and eventually reversioning in the PDB. The re-refined coordinate files and a tool for facilitating model comparisons are available at https://covid-19.bioreproducibility.org. DATABASE: Validated models of CoV-2 proteins are available in a dedicated, publicly accessible web service https://covid-19.bioreproducibility.org.", "qid": 29, "docid": "jt989p2x", "rank": 41, "score": 0.7744141817092896}, {"content": "Title: Repurposing cefuroxime for treatment of COVID-19: a scoping review of in silico studies Content: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 19 (COVID-19), is a novel human Coronavirus that is responsible for about 300,000 deaths worldwide. To date, there is no confirmed treatment or vaccine prevention strategy against COVID-19. Due to the urgent need for effective treatment, drug repurposing is regarded as the immediate option. Potential drugs can often be identified via in silico drug screening experiments. Consequently, there has been an explosion of in silico experiments to find drug candidates or investigate anecdotal claims. One drug with several anecdotal accounts of benefit is Cefuroxime. The aim of this study was to identify and summarize in silico evidence for possible activity of Cefuroxime against SARS-CoV-2.To this end, we performed a scoping review of literature of in silico drug repurposing experiments for SARS-CoV-2 using PRISMA-ScR. We searched Medline, Embase, Scopus, Web of Knowledge, and Google Scholar for original studies published between 1st Feb, 2020 and 15th May, 2020 that screened drug libraries, and identified Cefuroxime as a top-ranked potential inhibitor drug against SARS-CoV-2 proteins. Six studies were identified. These studies reported Cefuroxime as a potential inhibitor of 3 key SARS-CoV-2 proteins; main protease, RNA dependent RNA polymerase, and ACE2-Spike complex. We provided a summary of the methodology and findings of the identified studies. Our scoping review identified significant in silico evidence that Cefuroxime may be a potential multi-target inhibitor of SARS-CoV-2. Further in vitro and in vivo studies are required to evaluate the potential of Cefuroxime for COVID-19.Communicated by Ramaswamy H. Sarma.", "qid": 29, "docid": "xui8cfzv", "rank": 42, "score": 0.7742651700973511}, {"content": "Title: The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor Content: The COVID-19 disease has plagued over 110 countries and has resulted in over 4,000 deaths within 10 weeks. We compare the interaction between the human ACE2 receptor and the SARS-CoV-2 spike protein with that of other pathogenic coronaviruses using molecular dynamics simulations. SARS-CoV, SARS-CoV-2, and HCoV-NL63 recognize ACE2 as the natural receptor but present a distinct binding interface to ACE2 and a different network of residue-residue contacts. SARS-CoV and SARS-CoV-2 have comparable binding affinities achieved by balancing energetics and dynamics. The SARS-CoV-2\u2013ACE2 complex contains a higher number of contacts, a larger interface area, and decreased interface residue fluctuations relative to SARS-CoV. These findings expose an exceptional evolutionary exploration exerted by coronaviruses toward host recognition. We postulate that the versatility of cell receptor binding strategies has immediate implications on therapeutic strategies. One Sentence Summary Molecular dynamics simulations reveal a temporal dimension of coronaviruses interactions with the host receptor.", "qid": 29, "docid": "jpkxjn6e", "rank": 43, "score": 0.7739901542663574}, {"content": "Title: SAveRUNNER: a network-based algorithm for drug repurposing and its application to COVID-19 Content: The novelty of new human coronavirus COVID-19/SARS-CoV-2 and the lack of effective drugs and vaccines gave rise to a wide variety of strategies employed to fight this worldwide pandemic. Many of these strategies rely on the repositioning of existing drugs that could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we presented a new network-based algorithm for drug repositioning, called SAveRUNNER (Searching off-lAbel dRUg aNd NEtwoRk), which predicts drug-disease associations by quantifying the interplay between the drug targets and the disease-specific proteins in the human interactome via a novel network-based similarity measure that prioritizes associations between drugs and diseases locating in the same network neighborhoods. Specifically, we applied SAveRUNNER on a panel of 14 selected diseases with a consolidated knowledge about their disease-causing genes and that have been found to be related to COVID-19 for genetic similarity, comorbidity, or for their association to drugs tentatively repurposed to treat COVID-19. Focusing specifically on SARS subnetwork, we identified 282 repurposable drugs, including some the most rumored off-label drugs for COVID-19 treatments, as well as a new combination therapy of 5 drugs, actually used in clinical practice. Furthermore, to maximize the efficiency of putative downstream validation experiments, we prioritized 24 potential anti-SARS-CoV repurposable drugs based on their network-based similarity values. These top-ranked drugs include ACE-inhibitors, monoclonal antibodies, and thrombin inhibitors. Finally, our findings were in-silico validated by performing a gene set enrichment analysis, which confirmed that most of the network-predicted repurposable drugs may have a potential treatment effect against human coronavirus infections.", "qid": 29, "docid": "jozd45ch", "rank": 44, "score": 0.7731759548187256}, {"content": "Title: Repurposing cefuroxime for treatment of COVID-19: a scoping review of in silico studies Content: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 19 (COVID-19), is a novel human Coronavirus that is responsible for about 300,000 deaths worldwide. To date, there is no confirmed treatment or vaccine prevention strategy against COVID-19. Due to the urgent need for effective treatment, drug repurposing is regarded as the immediate option. Potential drugs can often be identified via in silico drug screening experiments. Consequently, there has been an explosion of in silico experiments to find drug candidates or investigate anecdotal claims. One drug with several anecdotal accounts of benefit is Cefuroxime. The aim of this study was to identify and summarize in silico evidence for possible activity of Cefuroxime against SARS-CoV-2.To this end, we performed a scoping review of literature of in silico drug repurposing experiments for SARS-CoV-2 using PRISMA-ScR. We searched Medline, Embase, Scopus, Web of Knowledge, and Google Scholar for original studies published between 1st Feb, 2020 and 15th May, 2020 that screened drug libraries, and identified Cefuroxime as a top-ranked potential inhibitor drug against SARS-CoV-2 proteins. Six studies were identified. These studies reported Cefuroxime as a potential inhibitor of 3 key SARS-CoV-2 proteins; main protease, RNA dependent RNA polymerase, and ACE2-Spike complex. We provided a summary of the methodology and findings of the identified studies. Our scoping review identified significant in silico evidence that Cefuroxime may be a potential multi-target inhibitor of SARS-CoV-2. Further in vitro and in vivo studies are required to evaluate the potential of Cefuroxime for COVID-19. Communicated by Ramaswamy H. Sarma", "qid": 29, "docid": "aqge7xuu", "rank": 45, "score": 0.7725127935409546}, {"content": "Title: SARS-CoV-2 and SARS-CoV differ in their cell tropism and drug sensitivity profiles Content: SARS-CoV-2 is a novel coronavirus currently causing a pandemic. We show that the majority of amino acid positions, which differ between SARS-CoV-2 and the closely related SARS-CoV, are differentially conserved suggesting differences in biological behaviour. In agreement, novel cell culture models revealed differences between the tropism of SARS-CoV-2 and SARS-CoV. Moreover, cellular ACE2 (SARS-CoV-2 receptor) and TMPRSS2 (enables virus entry via S protein cleavage) levels did not reliably indicate cell susceptibility to SARS-CoV-2. SARS-CoV-2 and SARS-CoV further differed in their drug sensitivity profiles. Thus, only drug testing using SARS-CoV-2 reliably identifies therapy candidates. Therapeutic concentrations of the approved protease inhibitor aprotinin displayed anti-SARS-CoV-2 activity. The efficacy of aprotinin and of remdesivir (currently under clinical investigation against SARS-CoV-2) were further enhanced by therapeutic concentrations of the proton pump inhibitor omeprazole (aprotinin 2.7-fold, remdesivir 10-fold). Hence, our study has also identified anti-SARS-CoV-2 therapy candidates that can be readily tested in patients.", "qid": 29, "docid": "gpr86lxe", "rank": 46, "score": 0.7719959020614624}, {"content": "Title: Therapeutic dilemma in the repression of severe acute respiratory syndrome coronavirus-2 proteome. Content: Currently, the pandemic coronavirus disease 2019 (COVID-19) has unprecedentedly captivated its human hosts by causing respiratory illnesses because of evolution of the genetic makeup of novel coronavirus (CoV) known as severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). As much as the researchers are inundated for the quest of effective treatments from available drugs, the discovery and trials of new experimental drugs are also at a threshold for clinical trials. There has been much concern regarding the new and targeted drugs considering the comprehensive ambiguity regarding the mechanism and pathway of the drug action with respect to the new and unpredictable structural and nonstructural proteins (NSPs) of SARS CoV-2. This study was aimed to discuss functional pathways related to NSPs in CoVs with updated knowledge regarding SARS CoV-2, mechanisms of action of certain approved and investigational drugs for correct orientation regarding the treatment strategies, including nucleotide analog mechanism, receptor analog mechanism, and peptide-peptide interactions, along with the impact of COVID-19 on a global scale. Although there is a dire need for targeted drugs against SARS CoV-2, the practical achievement of its cure is possible by only using effective drugs with appropriate mechanisms to eliminate the disease.", "qid": 29, "docid": "btk6u9j4", "rank": 47, "score": 0.7711975574493408}, {"content": "Title: Potential Inhibitors for Novel Coronavirus Protease Identified by Virtual Screening of 606 Million Compounds Content: The rapid outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China followed by its spread around the world poses a serious global concern for public health. To this date, no specific drugs or vaccines are available to treat SARS-CoV-2 despite its close relation to the SARS-CoV virus that caused a similar epidemic in 2003. Thus, there remains an urgent need for the identification and development of specific antiviral therapeutics against SARS-CoV-2. To conquer viral infections, the inhibition of proteases essential for proteolytic processing of viral polyproteins is a conventional therapeutic strategy. In order to find novel inhibitors, we computationally screened a compound library of over 606 million compounds for binding at the recently solved crystal structure of the main protease (M(pro)) of SARS-CoV-2. A screening of such a vast chemical space for SARS-CoV-2 M(pro) inhibitors has not been reported before. After shape screening, two docking protocols were applied followed by the determination of molecular descriptors relevant for pharmacokinetics to narrow down the number of initial hits. Next, molecular dynamics simulations were conducted to validate the stability of docked binding modes and comprehensively quantify ligand binding energies. After evaluation of potential off-target binding, we report a list of 12 purchasable compounds, with binding affinity to the target protease that is predicted to be more favorable than that of the cocrystallized peptidomimetic compound. In order to quickly advise ongoing therapeutic intervention for patients, we evaluated approved antiviral drugs and other protease inhibitors to provide a list of nine compounds for drug repurposing. Furthermore, we identified the natural compounds (\u2212)-taxifolin and rhamnetin as potential inhibitors of M(pro). Rhamnetin is already commercially available in pharmacies.", "qid": 29, "docid": "7aulcwfa", "rank": 48, "score": 0.7708615660667419}, {"content": "Title: Potential Inhibitors for Novel Coronavirus Protease Identified by Virtual Screening of 606 Million Compounds Content: The rapid outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China followed by its spread around the world poses a serious global concern for public health. To this date, no specific drugs or vaccines are available to treat SARS-CoV-2 despite its close relation to the SARS-CoV virus that caused a similar epidemic in 2003. Thus, there remains an urgent need for the identification and development of specific antiviral therapeutics against SARS-CoV-2. To conquer viral infections, the inhibition of proteases essential for proteolytic processing of viral polyproteins is a conventional therapeutic strategy. In order to find novel inhibitors, we computationally screened a compound library of over 606 million compounds for binding at the recently solved crystal structure of the main protease (Mpro) of SARS-CoV-2. A screening of such a vast chemical space for SARS-CoV-2 Mpro inhibitors has not been reported before. After shape screening, two docking protocols were applied followed by the determination of molecular descriptors relevant for pharmacokinetics to narrow down the number of initial hits. Next, molecular dynamics simulations were conducted to validate the stability of docked binding modes and comprehensively quantify ligand binding energies. After evaluation of potential off-target binding, we report a list of 12 purchasable compounds, with binding affinity to the target protease that is predicted to be more favorable than that of the cocrystallized peptidomimetic compound. In order to quickly advise ongoing therapeutic intervention for patients, we evaluated approved antiviral drugs and other protease inhibitors to provide a list of nine compounds for drug repurposing. Furthermore, we identified the natural compounds (-)-taxifolin and rhamnetin as potential inhibitors of Mpro. Rhamnetin is already commercially available in pharmacies.", "qid": 29, "docid": "b7n8jadp", "rank": 49, "score": 0.770030677318573}, {"content": "Title: A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV-2 main protease Content: The SARS coronavirus type 2 (SARS-CoV-2) emerged in late 2019 as a zoonotic virus highly transmissible between humans that has caused the COVID-19 pandemic 1,2. This pandemic has the potential to disrupt healthcare globally and has already caused high levels of mortality, especially amongst the elderly. The overall case fatality rate for COVID-19 is estimated to be \u223c2.3% overall 3 and 32.3% in hospitalized patients age 70-79 years 4. Therapeutic options for treating the underlying viremia in COVID-19 are presently limited by a lack of effective SARS-CoV-2 antiviral drugs, although steroidal anti-inflammatory treatment can be helpful. A variety of potential antiviral targets for SARS-CoV-2 have been considered including the spike protein and replicase. Based upon previous successful antiviral drug development for HIV-1 and hepatitis C, the SARS-CoV-2 main protease (Mpro) appears an attractive target for drug development. Here we show the existing pharmacopeia contains many drugs with potential for therapeutic repurposing as selective and potent inhibitors of SARS-CoV-2 Mpro. We screened a collection of \u223c6,070 drugs with a previous history of use in humans for compounds that inhibit the activity of Mpro in vitro. In our primary screen we found \u223c50 compounds with activity against Mpro (overall hit rate <0.75%). Subsequent dose validation studies demonstrated 8 dose responsive hits with an IC50 \u2264 50 \u03bcM. Hits from our screen are enriched with hepatitis C NS3/4A protease targeting drugs including Boceprevir (IC50=0.95 \u03bcM), Ciluprevir (20.77\u03bcM). Narlaprevir (IC50=1.10\u03bcM), and Telaprevir (15.25\u03bcM). These results demonstrate that some existing approved drugs can inhibit SARS-CoV-2 Mpro and that screen saturation of all approved drugs is both feasible and warranted. Taken together this work suggests previous large-scale commercial drug development initiatives targeting hepatitis C NS3/4A viral protease should be revisited because some previous lead compounds may be more potent against SARS-CoV-2 Mpro than Boceprevir and suitable for rapid repurposing.", "qid": 29, "docid": "slouuryl", "rank": 50, "score": 0.7699284553527832}, {"content": "Title: Gene Expression Network Analysis Provides Potential Targets Against SARS-CoV-2 Content: BACKGROUND Cell entry of SARS-CoV-2, the novel coronavirus causing COVID-19, is facilitated by host cell angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). We aimed to identify and characterize genes that are co-expressed with ACE2 and TMPRSS2, and to further explore their biological functions and potential as druggable targets. METHODS Using the gene expression profiles of 1,038 lung tissue samples, we performed a weighted gene correlation network analysis (WGCNA) to identify modules of co-expressed genes. We explored the biology of co-expressed genes using bioinformatics databases, and identified known drug-gene interactions. RESULTS ACE2 was in a module of 681 co-expressed genes; 12 genes with moderate-high correlation with ACE2 (r>0.3, FDR<0.05) had known interactions with existing drug compounds. TMPRSS2 was in a module of 1,086 co-expressed genes; 15 of these genes were enriched in the gene ontology biologic process \u2018Entry into host cell\u2019, and 53 TMPRSS2-correlated genes had known interactions with drug compounds. CONCLUSION Dozens of genes are co-expressed with ACE2 and TMPRSS2, many of which have plausible links to COVID-19 pathophysiology. Many of the co-expressed genes are potentially targetable with existing drugs, which may help to fast-track the development of COVID-19 therapeutics.", "qid": 29, "docid": "par7lp1z", "rank": 51, "score": 0.7693909406661987}, {"content": "Title: En route to Peptide Therapeutics for COVID 19: Harnessing Potential Antigenic Mimicry Between Viral and Human Proteins Content: Molecular mimicry is a general strategy used by pathogens to infect the host cells. The emergence of SARS-CoV-2 virus has resulted in more than 6,700,000 infections and 390,000 deaths worldwide. Coronavirus disease (COVID-19) is an infectious disease caused by this virus. In this project concept, we aim to focus on the peptide-protein interaction analysis using two important drug targets in SARS-CoV-2 such as spike (S) protein and nucleocapsid (N) protein. These proteins play an important role in the virus entry and encapsidation of the viral particles. Motifs or functional regions in these two proteins must be sharing sequence homology with human protein (ACE2) which may be involved in the binding mechanism. The results will show a set of motif regions which can disrupt the viral infection. Once we identify these sets of antigenic determinant regions, antibody binding activity studies can be performed by in vitro methods. Our results from this study may suggest the existence of antigenic mimicry between SARS-CoV-2 and host proteins. The hit peptide components will have therapeutic applications to be developed into a wide variety of medicinal formulations against SARS-CoV-2 such as vaccine, intranasal and inhalation formulations. Also, the choice of conserved regions will lead to development of cross protective therapeutics against wide range of coronaviruses.", "qid": 29, "docid": "qj81xbn0", "rank": 52, "score": 0.7680668830871582}, {"content": "Title: SARS-CoV-2 E protein is a potential ion channel that can Be inhibited by Gliclazide and Memantine Content: COVID-19 is one of the most impactful pandemics in recorded history. As such, the identification of inhibitory drugs against its etiological agent, SARS-CoV-2, is of utmost importance, and in particular, repurposing may provide the fastest route to curb the disease. As the first step in this route, we sought to identify an attractive and viable target in the virus for pharmaceutical inhibition. Using three bacteria-based assays that were tested on known viroporins, we demonstrate that one of its essential components, the E protein, is a potential ion channel and, therefore, is an excellent drug target. Channel activity was demonstrated for E proteins in other coronaviruses, providing further emphasis on the importance of this functionally to the virus\u2019 pathogenicity. The results of a screening effort involving a repurposing drug library of ion channel blockers yielded two compounds that inhibit the E protein: Gliclazide and Memantine. In conclusion, as a route to curb viral virulence and abate COVID-19, we point to the E protein of SARS-CoV-2 as an attractive drug target and identify off-label compounds that inhibit it.", "qid": 29, "docid": "cjq0ep4f", "rank": 53, "score": 0.7680270075798035}, {"content": "Title: Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Content: Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors (VDR; GATA5; SFTPC; HIF1a) and activators (HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website.", "qid": 29, "docid": "24m4rh9w", "rank": 54, "score": 0.7679752707481384}, {"content": "Title: Host transcriptome-guided drug repurposing for COVID-19 treatment: a meta-analysis based approach Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a pandemic by the World Health Organization, and the identification of effective therapeutic strategy is a need of the hour to combat SARS-CoV-2 infection. In this scenario, the drug repurposing approach is widely used for the rapid identification of potential drugs against SARS-CoV-2, considering viral and host factors. METHODS: We adopted a host transcriptome-based drug repurposing strategy utilizing the publicly available high throughput gene expression data on SARS-CoV-2 and other respiratory infection viruses. Based on the consistency in expression status of host factors in different cell types and previous evidence reported in the literature, pro-viral factors of SARS-CoV-2 identified and subject to drug repurposing analysis based on DrugBank and Connectivity Map (CMap) using the web tool, CLUE. RESULTS: The upregulated pro-viral factors such as TYMP, PTGS2, C1S, CFB, IFI44, XAF1, CXCL2, and CXCL3 were identified in early infection models of SARS-CoV-2. By further analysis of the drug-perturbed expression profiles in the connectivity map, 27 drugs that can reverse the expression of pro-viral factors were identified, and importantly, twelve of them reported to have anti-viral activity. The direct inhibition of the PTGS2 gene product can be considered as another therapeutic strategy for SARS-CoV-2 infection and could suggest six approved PTGS2 inhibitor drugs for the treatment of COVID-19. The computational study could propose candidate repurposable drugs against COVID-19, and further experimental studies are required for validation.", "qid": 29, "docid": "qnccsstb", "rank": 55, "score": 0.767940878868103}, {"content": "Title: Oral drug repositioning candidates and synergistic remdesivir combinations for the prophylaxis and treatment of COVID-19 Content: The ongoing pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates strategies to identify prophylactic and therapeutic drug candidates for rapid clinical deployment. A high-throughput, high-content imaging assay of human HeLa cells expressing the SARS-CoV-2 receptor ACE2 was used to screen ReFRAME, a best-in-class drug repurposing library. From nearly 12,000 compounds, we identified 66 compounds capable of selectively inhibiting SARS-CoV-2 replication in human cells. Twenty-four of these drugs show additive activity in combination with the RNA-dependent RNA polymerase inhibitor remdesivir and may afford increased in vivo efficacy. We also identified synergistic interaction of the nucleoside analog riboprine and a folate antagonist 10-deazaaminopterin with remdesivir. Overall, seven clinically approved drugs (halofantrine, amiodarone, nelfinavir, simeprevir, manidipine, ozanimod, osimertinib) and 19 compounds in other stages of development may have the potential to be repurposed as SARS-CoV-2 oral therapeutics based on their potency, pharmacokinetic and human safety profiles.", "qid": 29, "docid": "9od553a6", "rank": 56, "score": 0.7675581574440002}, {"content": "Title: Screening of Chloroquine, Hydroxychloroquine and its derivatives for their binding affinity to multiple SARS-CoV-2 protein drug targets Content: Recently Chloroquine and its derivative Hydroxychloroquine have garnered enormous interest amongst the clinicians and health authorities\u2019 world over as a potential treatment to contain COVID-19 pandemic. The present research aims at investigating the therapeutic potential of Chloroquine and its potent derivative Hydroxychloroquine against SARS-CoV-2 viral proteins. At the same time screening was performed for some chemically synthesized derivatives of Chloroquine and compared their binding efficacy with chemically synthesized Chloroquine derivatives through in silico approaches. For the purpose of the study, some essential viral proteins and enzymes were selected that are implicated in SARS-CoV-2 replication and multiplication as putative drug targets. Chloroquine, Hydroxychloroquine, and some of their chemically synthesized derivatives, taken from earlier published studies were selected as drug molecules. We have conducted molecular docking and related studies between Chloroquine and its derivatives and SARS-CoV-2 viral proteins, and the findings show that both Chloroquine and Hydroxychloroquine can bind to specific structural and non-structural proteins implicated in the pathogenesis of SARS-CoV-2 infection with different efficiencies. Our current study also shows that some of the chemically synthesized Chloroquine derivatives can also potentially inhibit various SARS-CoV-2 viral proteins by binding to them and concomitantly effectively disrupting the active site of these proteins. These findings bring into light another possible mechanism of action of Chloroquine and Hydroxychloroquine and also pave the way for further drug repurposing and remodeling. Communicated by Ramaswamy H. Sarma", "qid": 29, "docid": "8g37xsys", "rank": 57, "score": 0.7675451636314392}, {"content": "Title: Screening of Chloroquine, Hydroxychloroquine and its derivatives for their binding affinity to multiple SARS-CoV-2 protein drug targets Content: Recently Chloroquine and its derivative Hydroxychloroquine have garnered enormous interest amongst the clinicians and health authorities' world over as a potential treatment to contain COVID-19 pandemic. The present research aims at investigating the therapeutic potential of Chloroquine and its potent derivative Hydroxychloroquine against SARS-CoV-2 viral proteins. At the same time screening was performed for some chemically synthesized derivatives of Chloroquine and compared their binding efficacy with chemically synthesized Chloroquine derivatives through in silico approaches. For the purpose of the study, some essential viral proteins and enzymes were selected that are implicated in SARS-CoV-2 replication and multiplication as putative drug targets. Chloroquine, Hydroxychloroquine, and some of their chemically synthesized derivatives, taken from earlier published studies were selected as drug molecules. We have conducted molecular docking and related studies between Chloroquine and its derivatives and SARS-CoV-2 viral proteins, and the findings show that both Chloroquine and Hydroxychloroquine can bind to specific structural and non-structural proteins implicated in the pathogenesis of SARS-CoV-2 infection with different efficiencies. Our current study also shows that some of the chemically synthesized Chloroquine derivatives can also potentially inhibit various SARS-CoV-2 viral proteins by binding to them and concomitantly effectively disrupting the active site of these proteins. These findings bring into light another possible mechanism of action of Chloroquine and Hydroxychloroquine and also pave the way for further drug repurposing and remodeling.Communicated by Ramaswamy H. Sarma.", "qid": 29, "docid": "juigdaib", "rank": 58, "score": 0.767332136631012}, {"content": "Title: Virtual Screening of Plant Metabolites against Main protease, RNA-dependent RNA polymerase and Spike protein of SARS-CoV-2: Therapeutics option of COVID-19 Content: Covid-19, a serious respiratory complications caused by SARS-CoV-2 has become one of the global threat to human healthcare system. The present study evaluated the possibility of plant originated approved 117 therapeutics against the main protease protein (MPP), RNA-dependent RNA polymerase (RdRp) and spike protein (S) of SARS-CoV-2 including drug surface analysis by using molecular docking through drug repurposing approaches. The molecular interaction study revealed that Rifampin (-16.3 kcal/mol) were topmost inhibitor of MPP where Azobechalcone were found most potent plant therapeutics for blocking the RdRp (-15.9 kcal /mol) and S (-14.4 kcal/mol) protein of SARS-CoV-2. After the comparative analysis of all docking results, Azobechalcone, Rifampin, Isolophirachalcone, Tetrandrine and Fangchinoline were exhibited as the most potential inhibitory plant compounds for targeting the key proteins of SARS-CoV-2. However, amino acid positions; H41, C145, and M165 of MPP played crucial roles for the drug surface interaction where F368, L371, L372, A375, W509, L514, Y515 were pivotal for RdRP. In addition, the drug interaction surface of S proteins also showed similar patterns with all of its maximum inhibitors. ADME analysis also strengthened the possibility of screened plant therapeutics as the potent drug candidates against SARS-C with the highest drug friendliness.", "qid": 29, "docid": "oyc2djxk", "rank": 59, "score": 0.766738772392273}, {"content": "Title: Interactome of SARS-CoV-2 / nCoV19 modulated host proteins with computationally predicted PPIs Content: World over, people are looking for solutions to tackle the pandemic coronavirus disease (COVID-19) caused by the virus SARS-CoV-2/nCoV-19. Notable contributions in biomedical field have been characterizing viral genomes, host transcriptomes and proteomes, repurposable drugs and vaccines. In one such study, 332 human proteins targeted by nCoV19 were identified. We expanded this set of host proteins by constructing their protein interactome, including in it not only the known protein-protein interactions (PPIs) but also novel, hitherto unknown PPIs predicted with our High-precision Protein-Protein Interaction Prediction (HiPPIP) model that was shown to be highly accurate. In fact, one of the earliest discoveries made possible by HiPPIP is related to activation of immunity upon viral infection. We found that several interactors of the host proteins are differentially expressed upon viral infection, are related to highly relevant pathways, and that the novel interaction of NUP98 with CHMP5 may activate an antiviral mechanism leading to disruption of viral budding. We are making the interactions available as downloadable files to facilitate future systems biology studies and also on a web-server at http://hagrid.dbmi.pitt.edu/corona that allows not only keyword search but also queries such as \u201cPPIs where one protein is associated with \u2018virus\u2019 and the interactors with \u2018pulmonary\u2019\u201d.", "qid": 29, "docid": "jk01nq02", "rank": 60, "score": 0.766337513923645}, {"content": "Title: Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies Content: The recent severe acute respiratory syndrome, known as Corona Virus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim we performed an in silico comparative modeling analysis, which allows to gain new insights about the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor binding domain (RBD), along interactions with human cells angiotensin converting enzyme 2 (ACE2) receptor, that favour human cell invasion. Furthermore, our analysis provides i) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, for preventing interactions with the human ACE2, and ii) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. The proposed antibodies show in silico a high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high affinity antibodies against present and future coronavirus able to invade human cells through interactions of their spike proteins with the human ACE2. More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD-ACE2 interactions for the development of new vaccines, diagnosis kits and other treatments based on the usage or the targeting of SARS-CoV-2 spike protein.", "qid": 29, "docid": "mswmkgl4", "rank": 61, "score": 0.7659177780151367}, {"content": "Title: Computational Models Identify Several FDA Approved or Experimental Drugs as Putative Agents Against SARS-CoV-2. Content: The outbreak of a novel human coronavirus (SARS-CoV-2) has evolved into global health emergency, infecting hundreds of thousands of people worldwide. We have identified experimental data on the inhibitory activity of compounds tested against closely related (96% sequence identity, 100% active site conservation) protease of SARS-CoV and employed this data to build QSAR models for this dataset. We employed these models for virtual screening of all drugs from DrugBank, including compounds in clinical trials. Molecular docking and similarity search approaches were explored in parallel with QSAR modeling, but molecular docking failed to correctly discriminate between experimentally active and inactive compounds. As a result of our studies, we recommended 41 approved, experimental, or investigational drugs as potential agents against SARS-CoV-2 acting as putative inhibitors of Mpro. Ten compounds with feasible prices were purchased and are awaiting the experimental validation..", "qid": 29, "docid": "hchioraj", "rank": 62, "score": 0.7657067775726318}, {"content": "Title: Molecular docking and binding mode analysis of selected FDA approved drugs against COVID-19 selected key protein targets: An effort towards drug repurposing to identify the combination therapy to combat COVID-19 Content: The emergence of COVID-19 has severely compromised the arsenal of antiviral and antibiotic drugs. Drug discovery is a multistep process with a high failure rate, high cost and it takes approximately 10-12 years for the development of new molecules into the clinical candidate. On the other side, drug repurposing also called old drugs for new uses, is an attractive alternative approach for a new application of marketed FDA approved or investigational drugs. In the current pandemic situation raised due to COVID-19, repurposing of existing FDA approved drugs are emerging as the first line of the treatment. The causative viral agent of this highly contagious disease and acute respiratory syndrome coronavirus (SARS-CoV) shares high nucleotide similarity. Therefore, many existing viral targets are structurally expected to be similar to SARS-CoV and likely to be inhibited by the same compounds. Here, we selected three viral key proteins based on their vital role in viral life cycle: ACE2 (helps in entry into the human host), viral nonstructural proteins RNA-dependent RNA polymerase (RdRp) NSP12, and NSP16 which helps in replication, and viral latency (invasion from immunity). The FDA approved drugs chloroquine (CQ), hydroxychloroquine (HCQ), remdesivir (RDV) and arbidol (ABD) are emerging as promising agents to combat COVID-19. Our hypothesis behind the docking studies is to determine the binding affinities of these drugs and identify the key amino acid residues playing a key role in their mechanism of action. The docking studies were carried out through Autodock and online COVID-19 docking server. Further studies on a broad range of FDA approved drugs including few more protein targets, molecular dynamics studies, in-vitro and in-vivo biological evaluation are required to identify the combination therapy targeting various stages of the viral life cycle.", "qid": 29, "docid": "vnn7lp8w", "rank": 63, "score": 0.7655760049819946}, {"content": "Title: Update on the target structures of SARS-CoV-2: A systematic review Content: Knowledge of structural details is very much essential from the drug-design perspective. In the systematic review, we systematically reviewed the structural basis of different target proteins of SARS-corona virus (CoV2) from a viral life cycle and from drug design perspective. We searched four literature (PubMed, EMBASE, NATURE, and Willey online library) databases and one structural database (RCSB.org) with appropriate keywords till April 18, and finally, 26 articles were included in the systematic review. The published literature mainly centered upon the structural details of \u201cspike protein,\u201d \u201cmain protease/M Pro/3CL pro,\u201d \u201cRNA-dependent RNA polymerase,\u201d and \u201cnonstructural protein 15 Endoribonuclease\u201d of SARS-CoV-2. However, inhibitor bound structures were very less. We need better structures elucidating the interactions between different targets and their inhibitors which will help us in understanding the atomic level importance of different amino acid residues in the functionality of the target structures. To summarize, we need structures with fine resolution, co-crystallized structures with biologically validated inhibitors, and functional characterization of different target proteins. Some other routes of entry of SARS-CoV-2 are also mentioned (e.g., CD147); however, these findings are not structurally validated. This review may pave way for better understanding of SARS-CoV-2 life cycle from structural biology perspective.", "qid": 29, "docid": "iyoem0p6", "rank": 64, "score": 0.7655282616615295}, {"content": "Title: Fragment tailoring strategy to design novel chemical entities as potential binders of novel corona virus main protease Content: The recent pandemic of severe acute respiratory syndrome\u2013coronavirus2 (SARS-CoV-2) infection (COVID-19) has put the world on serious alert. The main protease of SARS-CoV-2 (SARS-CoV-2-M(Pro)) cleaves the long polyprotein chains to release functional proteins required for replication of the virus and thus is a potential drug target to design new chemical entities in order to inhibit the viral replication in human cells. The current study employs state of art computational methods to design novel molecules by linking molecular fragments which specifically bind to different constituent sub-pockets of the SARS-CoV-2-M(Pro) binding site. A huge library of 191678 fragments was screened against the binding cavity of SARS-CoV-2-M(Pro) and high affinity fragments binding to adjacent sub-pockets were tailored to generate new molecules. These newly formed molecules were further subjected to molecular docking, ADMET filters and MM-GBSA binding energy calculations to select 17 best molecules (named as MP-In1 to MP-In17), which showed comparable binding affinities and interactions with the key binding site residues as the reference ligand. The complexes of these 17 molecules and the reference molecule with SARS-CoV-2-M(Pro), were subjected to molecular dynamics simulations, which assessed the stabilities of their binding with SARS-CoV-2-M(Pro). Fifteen molecules were found to form stable complexes with SARS-CoV-2-M(Pro). These novel chemical entities designed specifically according to the pharmacophoric requirements of SARS-CoV-2-M(Pro) binding pockets showed good synthetic feasibility and returned no exact match when searched against chemical databases. Considering their interactions, binding efficiencies and novel chemotypes, they can be further evaluated as potential starting points for SARS-CoV-2 drug discovery. [Image: see text] Communicated by Ramaswamy H. Sarma", "qid": 29, "docid": "lr3wj8we", "rank": 65, "score": 0.7652708888053894}, {"content": "Title: Update on the target structures of SARS-CoV-2: A systematic review Content: Knowledge of structural details is very much essential from the drug-design perspective. In the systematic review, we systematically reviewed the structural basis of different target proteins of SARS-corona virus (CoV2) from a viral life cycle and from drug design perspective. We searched four literature (PubMed, EMBASE, NATURE, and Willey online library) databases and one structural database (RCSB.org) with appropriate keywords till April 18, and finally, 26 articles were included in the systematic review. The published literature mainly centered upon the structural details of \"spike protein,\" \"main protease/M Pro/3CL pro,\" \"RNA-dependent RNA polymerase,\" and \"nonstructural protein 15 Endoribonuclease\" of SARS-CoV-2. However, inhibitor bound structures were very less. We need better structures elucidating the interactions between different targets and their inhibitors which will help us in understanding the atomic level importance of different amino acid residues in the functionality of the target structures. To summarize, we need structures with fine resolution, co-crystallized structures with biologically validated inhibitors, and functional characterization of different target proteins. Some other routes of entry of SARS-CoV-2 are also mentioned (e.g., CD147); however, these findings are not structurally validated. This review may pave way for better understanding of SARS-CoV-2 life cycle from structural biology perspective.", "qid": 29, "docid": "wak7ie3q", "rank": 66, "score": 0.7650319933891296}, {"content": "Title: In silico identification of clinically approved medicines against the main protease of SARS-CoV-2, causative agent of covid-19 Content: The COVID-19 pandemic triggered by SARS-CoV-2 is a worldwide health disaster. Main protease is an attractive drug target among coronaviruses, due to its vital role in processing the polyproteins that are translated from the viral RNA. There is presently no exact drug or treatment for this diseases caused by SARS-CoV-2. In the present study, we report the potential inhibitory activity of some FDA approved drugs against SARS-CoV-2 main protease by molecular docking study to investigate their binding affinity in protease active site. Docking studies revealed that drug Oseltamivir (anti-H1N1 drug), Rifampin (anti-TB drug), Maraviroc, Etravirine, Indinavir, Rilpivirine (anti-HIV drugs) and Atovaquone, Quinidine, Halofantrine, Amodiaquine, Tetracylcine, Azithromycin, hydroxycholoroquine (anti-malarial drugs) among others binds in the active site of the protease with similar or higher affinity. However, the in-silico abilities of the drug molecules tested in this study, further needs to be validated by carrying out in vitro and in vivo studies. Moreover, this study spreads the potential use of current drugs to be considered and used to comprise the fast expanding SARS-CoV-2 infection.", "qid": 29, "docid": "w9mij6c6", "rank": 67, "score": 0.7647244334220886}, {"content": "Title: Fragment tailoring strategy to design novel chemical entities as potential binders of novel corona virus main protease Content: The recent pandemic of severe acute respiratory syndrome-coronavirus2 (SARS-CoV-2) infection (COVID-19) has put the world on serious alert. The main protease of SARS-CoV-2 (SARS-CoV-2-MPro) cleaves the long polyprotein chains to release functional proteins required for replication of the virus and thus is a potential drug target to design new chemical entities in order to inhibit the viral replication in human cells. The current study employs state of art computational methods to design novel molecules by linking molecular fragments which specifically bind to different constituent sub-pockets of the SARS-CoV-2-MPro binding site. A huge library of 191678 fragments was screened against the binding cavity of SARS-CoV-2-MPro and high affinity fragments binding to adjacent sub-pockets were tailored to generate new molecules. These newly formed molecules were further subjected to molecular docking, ADMET filters and MM-GBSA binding energy calculations to select 17 best molecules (named as MP-In1 to MP-In17), which showed comparable binding affinities and interactions with the key binding site residues as the reference ligand. The complexes of these 17 molecules and the reference molecule with SARS-CoV-2-MPro, were subjected to molecular dynamics simulations, which assessed the stabilities of their binding with SARS-CoV-2-MPro. Fifteen molecules were found to form stable complexes with SARS-CoV-2-MPro. These novel chemical entities designed specifically according to the pharmacophoric requirements of SARS-CoV-2-MPro binding pockets showed good synthetic feasibility and returned no exact match when searched against chemical databases. Considering their interactions, binding efficiencies and novel chemotypes, they can be further evaluated as potential starting points for SARS-CoV-2 drug discovery. [Formula: see text]Communicated by Ramaswamy H. Sarma.", "qid": 29, "docid": "84h7nqbs", "rank": 68, "score": 0.7642807960510254}, {"content": "Title: State-of-the-art tools to identify druggable protein ligand of SARS-CoV-2 Content: INTRODUCTION: The SARS-CoV-2 (previously 2019-nCoV) outbreak in Wuhan, China and other parts of the world affects people and spreads coronavirus disease 2019 (COVID-19) through human-to-human contact, with a mortality rate of > 2%. There are no approved drugs or vaccines yet available against SARS-CoV-2. MATERIAL AND METHODS: State-of-the-art tools based on in-silico methods are a cost-effective initial approach for identifying appropriate ligands against SARS-CoV-2. The present study developed the 3D structure of the envelope and nucleocapsid phosphoprotein of SARS-CoV-2, and molecular docking analysis was done against various ligands. RESULTS: The highest log octanol/water partition coefficient, high number of hydrogen bond donors and acceptors, lowest non-bonded interaction energy between the receptor and the ligand, and high binding affinity were considered for the best ligand for the envelope (mycophenolic acid: log P = 3.00; DG = \u201310.2567 kcal/mol; pKi = 7.713 \u00b5M) and nucleocapsid phosphoprotein (1-[(2,4-dichlorophenyl)methyl]pyrazole-3,5-dicarboxylic acid: log P = 2.901; DG = \u201312.2112 kcal/mol; pKi = 7.885 \u00b5M) of SARS-CoV-2. CONCLUSIONS: The study identifies the most potent compounds against the SARS-CoV-2 envelope and nucleocapsid phosphoprotein through state-of-the-art tools based on an in-silico approach. A combination of these two ligands could be the best option to consider for further detailed studies to develop a drug for treating patients infected with SARS-CoV-2, COVID-19.", "qid": 29, "docid": "f9s46an9", "rank": 69, "score": 0.7642470598220825}, {"content": "Title: In silico approaches to drug repositioning for COVID-19 at AMED-BINDS Content: Abstract In silico prediction based on the protein structures of SARS-CoV2 is effective to find the putative drug candidates from the approved drugs, as drug repositioning The main protease, 3CL protease, of SARS-Cov2 is essential for proteolytic maturation of the virus, and inhibiting its function could prevent the COVID-19 spreading Here, recent activities in the in-silico unit of AMED-BINDS are introduced Hirokawa et al adopted an in silico docking-based screening approach, which combines molecular docking with a protein-ligand interaction fingerprint (PLIF) scoring method, utilizing the crystal structure of SARS-Cov2 3CL protease (PDB: 6LU7) and a database of known drugs (KEGG-Drug) Selected drugs have the binding modes similar to PLIF of the known active N3 inhibitors with favorable docking scores They identified one hundred and several dozen potentially candidate drugs for 3CL protease inhibitors, which are already approved as antiviral, HIV protease inhibitors, antibacterial or antineoplastic agents Sekijima et al analyzed the interactions between 3CL protease and the drug candidate compounds using molecular dynamics simulation Through this study, they aim to elucidate the interactions between 3CL protease and the drugs The chemical compound libraries in AMED-BINDS will also be available in the future assay studies", "qid": 29, "docid": "c7jdjjs7", "rank": 70, "score": 0.7642215490341187}, {"content": "Title: Current status of COVID-19 therapies and drug repositioning applications Content: Summary The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for treatment of COVID-19. Drug repositioning is an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. In addition, we describe computational approaches to be used in drug repurposing and highlight examples of in-silico studies of drug development efforts against SARS-CoV-2.", "qid": 29, "docid": "1t4ykc01", "rank": 71, "score": 0.7640680074691772}, {"content": "Title: Clinical trials of repurposed antivirals for SARS-CoV-2 Content: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prompted the repurposing of drugs on the basis of promising in vitro and therapeutic results with other human coronavirus diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). These repurposed drugs have mainly included remdesivir, favipiravir, lopinavir/ritonavir, ribavirin, interferons, and hydroxychloroquine. Unfortunately, the first open-label, randomized controlled trials are showing the poor efficacy of these repurposed drugs. These results highlight the necessity of identifying and characterizing specific and potent SARS-CoV-2 antivirals.", "qid": 29, "docid": "yvlcorrg", "rank": 72, "score": 0.7640016078948975}, {"content": "Title: Clinical trials of repurposed antivirals for SARS-CoV-2. Content: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prompted the repurposing of drugs on the basis of promising in vitro and therapeutic results with other human coronavirus diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). These repurposed drugs have mainly included remdesivir, favipiravir, lopinavir/ritonavir, ribavirin, interferons, and hydroxychloroquine. Unfortunately, the first open-label, randomized controlled trials are showing the poor efficacy of these repurposed drugs. These results highlight the necessity of identifying and characterizing specific and potent SARS-CoV-2 antivirals.", "qid": 29, "docid": "5q5mele8", "rank": 73, "score": 0.7640016078948975}, {"content": "Title: Homology Modeling of TMPRSS2 Yields Candidate Drugs That May Inhibit Entry of SARS-CoV-2 into Human Cells. Content: The most rapid path to discovering treatment options for the novel coronavirus SARS-CoV-2 is to find existing medications that are active against the virus. We have focused on identifying repurposing candidates for the transmembrane serine protease family member II (TMPRSS2), which is critical for entry of coronaviruses into cells. Using known 3D structures of close homologs, we created seven homology models. We also identified a set of serine protease inhibitor drugs, generated several conformations of each, and docked them into our models. We used three known chemical (non-drug) inhibitors and one validated inhibitor of TMPRSS2 in MERS as benchmark compounds and found six compounds with predicted high binding affinity in the range of the known inhibitors. We also showed that a previously published weak inhibitor, Camostat, had a significantly lower binding score than our six compounds. All six compounds are anticoagulants with significant and potentially dangerous clinical effects and side effects. Nonetheless, if these compounds significantly inhibit SARS-CoV-2 infection, they could represent a potentially useful clinical tool.", "qid": 29, "docid": "97l3r5tv", "rank": 74, "score": 0.7638736963272095}, {"content": "Title: Current Status of COVID-19 Therapies and Drug Repositioning Applications Content: The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Drug repositioning is an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. In addition, we describe computational approaches to be used in drug repurposing and highlight examples of in silico studies of drug development efforts against SARS-CoV-2.", "qid": 29, "docid": "q6bpic9m", "rank": 75, "score": 0.7636704444885254}, {"content": "Title: The SARS-CoV-2 main protease as drug target Content: The unprecedented pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is threatening global health. The virus emerged in late 2019 and can cause a severe disease associated with significant mortality. Several vaccine development and drug discovery campaigns are underway. The SARS-CoV-2 main protease is considered a promising drug target, as it is dissimilar to human proteases. Sequence and structure of the main protease are closely related to those from other betacoronaviruses, facilitating drug discovery attempts based on previous lead compounds. Covalently binding peptidomimetics and small molecules are investigated. Various compounds show antiviral activity in infected human cells.", "qid": 29, "docid": "f8aolprb", "rank": 76, "score": 0.7636462450027466}, {"content": "Title: Reconstructing SARS-CoV-2 response signaling and regulatory networks Content: Several molecular datasets have been recently compiled to characterize the activity of SARS-CoV-2 within human cells. Here we extend computational methods to integrate several different types of sequence, functional and interaction data to reconstruct networks and pathways activated by the virus in host cells. We identify the key proteins in these networks and further intersect them with genes differentially expressed at conditions that are known to impact viral activity. Several of the top ranked genes do not directly interact with virus proteins though some were shown to impact other coronaviruses highlighting the importance of large scale data integration for understanding virus and host activity.", "qid": 29, "docid": "m8yyntls", "rank": 77, "score": 0.7636274099349976}, {"content": "Title: Docking study of Chloroquine and Hydroxychloroquine interaction with SARS-CoV-2 spike glycoprotein-An in silico insight into the comparative efficacy of repurposing antiviral drugs. Content: Recent outbreak of novel Coronavirus disease (Covid-19) pandemic around the world is associated with severe acute respiratory syndrome. The death toll associated with the pandemic is increasing day by day. SARS-CoV-2 is an enveloped virus and there are ample evidences that its Spike protein (S-protein) is mainly associated with pathogenesis as it is surface-exposed and mediates entry into host cells by binding to angiotensin-converting enzyme-2 (ACE-2) receptor. Therefore, it is the main target of neutralizing antibodies upon infection and there is always a quest to inhibit the S-protein which in turn may help in controlling diseases caused by SARS-CoV-2 in humans. The role of Chloroquine and Hydroxychloroquine as potential treatments for Covid-19 is still under debate globally because of some side effects associated with it. This study involves the In silico interactions of Chloroquine and Hydroxychloroquine with the S-protein of SARS-CoV-2. With the help of various computational methods, we have re-explored the potential role of both of these antiviral drugs for the treatment of Covid-19 patients by comparing the efficacy of both of the drugs to bind to S-protein at its host receptor region. In our research Hydroxychloroquine exhibited potential inhibitory effectsof S-protein with binding energy -7.28 kcal/mol than Chloroquine (-6.30 kcal/mol) at SARS-CoV-2 receptor recognition of susceptible cells. The outcomes of this research strongly appeal for in vivo trials of Hydroxychloroquine for the patients infected with Covid-19. Furthermore, the recommended doses of Hydroxychloroquine may reduce the chances of catching Covid-19 to the healthcare workers and staff who are in contact with or delivering direct care to coronavirus patients as long as they have not been diagnosed with Covid-19. We further hypothesize that the comparative S-protein-drug docking interactions may help to understand the comparative efficacy of other candidate repurposing drugs until discovery of a proper vaccine.", "qid": 29, "docid": "gwm36n75", "rank": 78, "score": 0.7636175155639648}, {"content": "Title: Alignment of virus-host protein-protein interaction networks by integer linear programming: SARS-CoV-2 Content: Beside socio-economic issues, coronavirus pandemic COVID-19, the infectious disease caused by the newly discovered coronavirus SARS-CoV-2, has caused a deep impact in the scientific community, that has considerably increased its effort to discover the infection strategies of the new virus. Among the extensive and crucial research that has been carried out in the last few months, the analysis of the virus-host relationship plays an important role in drug discovery. Virus-host protein-protein interactions are the active agents in virus replication, and the analysis of virus-host protein-protein interaction networks is fundamental to the study of the virus-host relationship. We have adapted and implemented a recent integer linear programming model for protein-protein interaction network alignment to virus-host networks, and obtained a consensus alignment of the SARS-CoV-1 and SARS-CoV-2 virus-host protein-protein interaction networks. Despite the lack of shared human proteins in these virus-host networks and the low number of preserved virus-host interactions, the consensus alignment revealed aligned human proteins that share a function related to viral infection, as well as human proteins of high functional similarity that interact with SARS-CoV-1 and SARS-CoV-2 proteins, whose alignment would preserve these virus-host interactions.", "qid": 29, "docid": "iynga1d9", "rank": 79, "score": 0.7632917165756226}, {"content": "Title: In silico Molecular Docking Analysis Targeting SARS-CoV-2 Spike Protein and Selected Herbal Constituents Content: In modern drug discovery, molecular docking analysis is routinely used to understand and predict the interaction between a drug molecule and a target protein from a microbe Drugs identified in this way may inhibit the entry and replication of pathogens in host cells The SARS-CoV-2 associated coronavirus disease, COVID-19, has become the most contagious and deadly pandemic disease in the world today In abeyance of any specific vaccine or therapeutic against SARS-CoV-2, the burgeoning situation urges a need for effective drugs to treat the virus-infected patients Herbal medicines have been used as natural remedies for treating various infectious diseases since ancient times The spike (S) protein of SARS-CoV-2 is important for the attachment and pathogenesis of the virus Therefore, this study focused on the search of useful ligands for S protein among active constituents present in common herbs that could serve as efficient remedies for COVID-19 We analysed the binding efficiency of twelve compounds present in common herbs with the S protein of SARS-CoV-2 through molecular docking analysis and also results are validated with two different docking tools The binding efficiency of ligands was scored based on their predicted pharmacological interactions coupled with binding energy estimates In docking analysis, compound \"I\" (Epigallocatechin gallate (EGCG)) was found to have the highest binding affinity with the viral S protein, followed by compounds, \"F\" (Curcumin),\"D\" (Apigenin) and \"E\" (Chrysophanol) The present study corroborates that compound \"I\" (EGCG) mostly present in the integrants of green tea, shows the highest potentiality for acting as an inhibitor of SARS-CoV-2 Further, characterization of the amino acid residues comprising the viral binding site and the nature of the hydrogen bonding involved in the ligand-receptor interaction revealed significant findings with herbal compound \"I\" (EGCG) binding to the S protein at eight amino acid residues The binding sites are situated near to the amino acids which are required for virus pathogenicity The findings of the present study need in vivo experiments to prove the utility of \"I\", \"F\",\"D\" and \"E\" compounds and their further use in making herb-based anti-SARS-CoV-2 product in near future This analysis may help to create a new ethno-drug formulation for preventing or curing the COVID-19", "qid": 29, "docid": "1sxhza50", "rank": 80, "score": 0.7632414102554321}, {"content": "Title: SARS-CoV-2 and SARS-CoV Spike-RBD Structure and Receptor Binding Comparison and Potential Implications on Neutralizing Antibody and Vaccine Development Content: SARS-CoV-2 and SARS-CoV share a common human receptor ACE2. Protein-protein interaction structure modeling indicates that spike-RBD of the two viruses also has similar overall binding conformation and binding free energy to ACE2. In vitro assays using recombinant ACE2 proteins and ACE2 expressing cells confirmed the two coronaviruses\u2019 similar binding affinities to ACE2. The above studies provide experimental supporting evidences and possible explanation for the high transmissibility observed in the SARS-CoV-2 outbreak. Potent ACE2-blocking SARS-CoV neutralizing antibodies showed limited cross-binding and neutralizing activities to SARS-CoV-2. ACE2-non-blocking SARS-CoV RBD antibodies, though with weaker neutralizing activities against SARS-CoV, showed positive cross-neutralizing activities to SARS-CoV-2 with an unknown mechanism. These findings suggest a trade-off between the efficacy and spectrum for therapeutic antibodies to different coronaviruses, and hence highlight the possibilities and challenges in developing broadly protecting antibodies and vaccines against SARS-CoV-2 and its future mutants.", "qid": 29, "docid": "nhq0oq8y", "rank": 81, "score": 0.7631324529647827}, {"content": "Title: The COVID-19 Gene and Drug Set Library Content: The coronavirus (CoV) severe acute respiratory syndrome (SARS)-CoV-2 (COVID-19) pandemic has received rapid response by the research community to offer suggestions for repurposing of approved drugs as well as to improve our understanding of the COVID-19 viral life cycle molecular mechanisms. In a short period, tens of thousands of research preprints and other publications have emerged including those that report lists of experimentally validated drugs and compounds as potential COVID-19 therapies. In addition, gene sets from interacting COVID-19 virus-host proteins and differentially expressed genes when comparing infected to uninfected cells are being published at a fast rate. To organize this rapidly accumulating knowledge, we developed the COVID-19 Gene and Drug Set Library (https://amp.pharm.mssm.edu/covid19/), a collection of gene and drug sets related to COVID-19 research from multiple sources. The COVID-19 Gene and Drug Set Library is delivered as a web-based interface that enables users to view, download, analyze, visualize, and contribute gene and drug sets related to COVID-19 research. To evaluate the content of the library, we performed several analyses including comparing the results from 6 in-vitro drug screens for COVID-19 repurposing candidates. Surprisingly, we observe little overlap across these initial screens. The most common and unique hit across these screen is mefloquine, a malaria drug that should receive more attention as a potential therapeutic for COVID-19. Overall, the library of gene and drug sets can be used to identify community consensus, make researchers and clinicians aware of the development of new potential therapies, as well as allow the research community to work together towards a cure for COVID-19.", "qid": 29, "docid": "ps7nl8ns", "rank": 82, "score": 0.7630549669265747}, {"content": "Title: Repurposing low\u2013molecular-weight drugs against the main protease of severe acute respiratory syndrome coronavirus 2 Content: The coronavirus disease (COVID-19) pandemic caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected the global healthcare system. Drug repurposing is a feasible method for emergency treatment. As low\u2013molecular-weight drugs have high potential to completely match interactions with essential SARS-CoV-2 targets, we propose a strategy to identify such drugs using the fragment-based approach. Herein, using ligand- and protein-observed fragment screening approaches, we identified niacin and hit 1 binding to the catalytic pocket of the main protease of the SARS-CoV-2 (Mpro), thereby modestly inhibiting the enzymatic activity of Mpro. Chemical shift perturbations induced by niacin and hit 1 indicate a partial overlap of their binding sites, i.e., the catalytic pocket of Mpro may accommodate derivatives with large molecular sizes. Therefore, we searched for drugs containing niacin or hit 1 pharmacophores and identified carmofur, bendamustine, triclabendazole, and emedastine; these drugs are highly capable of inhibiting protease activity. Our study demonstrates that the fragment-based approach is a feasible strategy for identifying low\u2013molecular-weight drugs against the SARS-CoV-2 and other potential targets lacking specific drugs.", "qid": 29, "docid": "dpble2jd", "rank": 83, "score": 0.7625349760055542}, {"content": "Title: Eltrombopag is a potential target for drug intervention in SARS-CoV-2 spike protein Content: The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a current global threat for which there is an urgent need to search for an effective therapy. The transmembrane spike (S) glycoprotein of SARS-CoV-2 directly binds to the host angiotensin-converting enzyme 2 (ACE2) and mediates viral entrance, which is therefore considered as a promising drug target. Considering that new drug development is a time-consuming process, drug repositioning may facilitate rapid drug discovery dealing with sudden infectious diseases. Here, we compared the differences between the virtual structural proteins of SARS-CoV-2 and SARS-CoV, and selected a pocket mainly localizing in the fusion cores of S2 domain for drug screening. A virtual drug design algorithm screened the Food and Drug Administration-approved drug library of 1234 compounds, and 13 top scored compounds were obtained through manual screening. Through in vitro molecular interaction experiments, eltrombopag was further verified to possess a high binding affinity to S protein plus human ACE2 and could potentially affect the stability of the ACE2-S protein complex. Hence, it is worth further exploring eltrombopag as a potential drug for the treatment of SARS-CoV-2 infection.", "qid": 29, "docid": "ogiicyik", "rank": 84, "score": 0.7623184323310852}, {"content": "Title: COVID-19: Viral-host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection Content: Background Epidemiological, virological and pathogenetic characteristics of SARS-CoV-2 infection are under evaluation. A better understanding of the pathophysiology associated with COVID-19 is crucial to improve treatment modalities and to develop effective prevention strategies. Transcriptomic and proteomic data on the host response against SARS-CoV-2 still have anecdotic character; currently available data from other coronavirus infections are therefore a key source of information. Methods We investigated selected molecular aspects of three human coronavirus (HCoV) infections, namely SARS-CoV, MERS-CoV and HCoV-229E, through a network based-approach. A functional analysis of HCoV-host interactome was carried out in order to provide a theoretic host-pathogen interaction model for HCoV infections and in order to translate the results in prediction for SARS-CoV-2 pathogenesis. The 3D model of S-glycoprotein of SARS-CoV-2 was compared to the structure of the corresponding SARS-CoV, HCoV-229E and MERS-CoV S-glycoprotein. SARS-CoV, MERS-CoV, HCoV-229E and the host interactome were inferred through published protein-protein interactions (PPI) as well as gene co-expression, triggered by HCoV S-glycoprotein in host cells. Results Although the amino acid sequences of the S-glycoprotein were found to be different between the various HCoV, the structures showed high similarity, but the best 3D structural overlap shared by SARS-CoV and SARS-CoV-2, consistent with the shared ACE2 predicted receptor. The host interactome, linked to the S-glycoprotein of SARS-CoV and MERS-CoV, mainly highlighted innate immunity pathway components, such as Toll Like receptors, cytokines and chemokines. Conclusions In this paper, we developed a network-based model with the aim to define molecular aspects of pathogenic phenotypes in HCoV infections. The resulting pattern may facilitate the process of structure-guided pharmaceutical and diagnostic research with the prospect to identify potential new biological targets.", "qid": 29, "docid": "co81fi08", "rank": 85, "score": 0.7621557712554932}, {"content": "Title: Putative Inhibitors of SARS-CoV-2 Main Protease from A Library of Marine Natural Products: A Virtual Screening and Molecular Modeling Study Content: The current emergency due to the worldwide spread of the COVID-19 caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a great concern for global public health. Already in the past, the outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle Eastern respiratory syndrome (MERS) in 2012 demonstrates the potential of coronaviruses to cross-species borders and further underlines the importance of identifying new-targeted drugs. An ideal antiviral agent should target essential proteins involved in the lifecycle of SARS-CoV. Currently, some HIV protease inhibitors (i.e., Lopinavir) are proposed for the treatment of COVID-19, although their effectiveness has not yet been assessed. The main protease (M(pro)) provides a highly validated pharmacological target for the discovery and design of inhibitors. We identified potent M(pro) inhibitors employing computational techniques that entail the screening of a Marine Natural Product (MNP) library. MNP library was screened by a hyphenated pharmacophore model, and molecular docking approaches. Molecular dynamics and re-docking further confirmed the results obtained by structure-based techniques and allowed this study to highlight some crucial aspects. Seventeen potential SARS-CoV-2 M(pro) inhibitors have been identified among the natural substances of marine origin. As these compounds were extensively validated by a consensus approach and by molecular dynamics, the likelihood that at least one of these compounds could be bioactive is excellent.", "qid": 29, "docid": "578lsck9", "rank": 86, "score": 0.7619626522064209}, {"content": "Title: Binding site analysis of potential protease inhibitors of COVID-19 using AutoDock Content: Recent outbreak of COVID-19 caused by SARS-CoV-2 in December 2019 raised global health concerns. Re-purposing the available protease inhibitor drugs for immediate use in treatment in SARS-CoV-2 infections could improve the currently available clinical management. The current study, aims to predict theoretical structure for protease of COVID-19 and to explore further whether this protein can serve as a target for protease inhibitor drugs such as remdesivir, nelfinavir, lopinavir, ritonavir and &#945;-ketoamide. While the 3D structure of protease was predicted using SWISS MODEL server, molecular interaction studies between protein and ligands were performed using AutoDock software. The predicted protease model was reasonably good based on reports generated by different validation servers. The study further revealed that all the protease inhibitor drugs got docked with negative dock energy onto the target protein. Molecular interaction studies showed that protease structure had multiple active site residues for remdesivir, while for remaining ligands the structure had only one active site residue each. From the output of multiple sequence alignment, it is evident that ligand binding sites were conserved. The current in silico study thus, provides structural insights about the protease of COVID-19 and also its molecular interactions with some of the known protease inhibitors.", "qid": 29, "docid": "rr6wwtv2", "rank": 87, "score": 0.7611719369888306}, {"content": "Title: In Silico Discovery of Candidate Drugs against Covid-19 Content: Previous studies reported that Angiotensin converting enzyme 2 (ACE2) is the main cell receptor of SARS-CoV and SARS-CoV-2. It plays a key role in the access of the virus into the cell to produce the final infection. In the present study we investigated in silico the basic mechanism of ACE2 in the lung and provided evidences for new potentially effective drugs for Covid-19. Specifically, we used the gene expression profiles from public datasets including The Cancer Genome Atlas, Gene Expression Omnibus and Genotype-Tissue Expression, Gene Ontology and pathway enrichment analysis to investigate the main functions of ACE2-correlated genes. We constructed a protein-protein interaction network containing the genes co-expressed with ACE2. Finally, we focused on the genes in the network that are already associated with known drugs and evaluated their role for a potential treatment of Covid-19. Our results demonstrate that the genes correlated with ACE2 are mainly enriched in the sterol biosynthetic process, Aryldialkylphosphatase activity, adenosylhomocysteinase activity, trialkylsulfonium hydrolase activity, acetate-CoA and CoA ligase activity. We identified a network of 193 genes, 222 interactions and 36 potential drugs that could have a crucial role. Among possible interesting drugs for Covid-19 treatment, we found Nimesulide, Fluticasone Propionate, Thiabendazole, Photofrin, Didanosine and Flutamide.", "qid": 29, "docid": "i0mti49x", "rank": 88, "score": 0.7609795331954956}, {"content": "Title: Peptide-like and small-molecule inhibitors against Covid-19 Content: Coronavirus disease strain (SARS-CoV-2) was discovered in 2019, and it is spreading very fast around the world causing the disease Covid-19. Currently, more than 1.6 million individuals are infected, and several thousand are dead across the globe because of Covid-19. Here, we utilized the in-silico approaches to identify possible protease inhibitors against SARS-CoV-2. Potential compounds were screened from the CHEMBL database, ZINC database, FDA approved drugs and molecules under clinical trials. Our study is based on 6Y2F and 6W63 co-crystallized structures available in the protein data bank (PDB). Seven hundred compounds from ZINC/CHEMBL databases and fourteen hundred compounds from drug-bank were selected based on positive interactions with the reported binding site. All the selected compounds were subjected to standard-precision (SP) and extra-precision (XP) mode of docking. Generated docked poses were carefully visualized for known interactions within the binding site. Molecular mechanics-generalized born surface area (MM-GBSA) calculations were performed to screen the best compounds based on docking scores and binding energy values. Molecular dynamics (MD) simulations were carried out on four selected compounds from the CHEMBL database to validate the stability and interactions. MD simulations were also performed on the PDB structure 6YF2F to understand the differences between screened molecules and co-crystallized ligand. We screened 300 potential compounds from various databases, and 66 potential compounds from FDA approved drugs. Cobicistat, ritonavir, lopinavir, and darunavir are in the top screened molecules from FDA approved drugs. The screened drugs and molecules may be helpful in fighting with SARS-CoV-2 after further studies.", "qid": 29, "docid": "x4kirba0", "rank": 89, "score": 0.7609219551086426}, {"content": "Title: Data and Text Mining Help Identify Key Proteins Involved in the Molecular Mechanisms Shared by SARS-CoV-2 and HIV-1 Content: Viruses can be spread from one person to another; therefore, they may cause disorders in many people, sometimes leading to epidemics and even pandemics. New, previously unstudied viruses and some specific mutant or recombinant variants of known viruses constantly appear. An example is a variant of coronaviruses (CoV) causing severe acute respiratory syndrome (SARS), named SARS-CoV-2. Some antiviral drugs, such as remdesivir as well as antiretroviral drugs including darunavir, lopinavir, and ritonavir are suggested to be effective in treating disorders caused by SARS-CoV-2. There are data on the utilization of antiretroviral drugs against SARS-CoV-2. Since there are many studies aimed at the identification of the molecular mechanisms of human immunodeficiency virus type 1 (HIV-1) infection and the development of novel therapeutic approaches against HIV-1, we used HIV-1 for our case study to identify possible molecular pathways shared by SARS-CoV-2 and HIV-1. We applied a text and data mining workflow and identified a list of 46 targets, which can be essential for the development of infections caused by SARS-CoV-2 and HIV-1. We show that SARS-CoV-2 and HIV-1 share some molecular pathways involved in inflammation, immune response, cell cycle regulation.", "qid": 29, "docid": "28c4j1by", "rank": 90, "score": 0.7605481743812561}, {"content": "Title: Data and Text Mining Help Identify Key Proteins Involved in the Molecular Mechanisms Shared by SARS-CoV-2 and HIV-1. Content: Viruses can be spread from one person to another; therefore, they may cause disorders in many people, sometimes leading to epidemics and even pandemics. New, previously unstudied viruses and some specific mutant or recombinant variants of known viruses constantly appear. An example is a variant of coronaviruses (CoV) causing severe acute respiratory syndrome (SARS), named SARS-CoV-2. Some antiviral drugs, such as remdesivir as well as antiretroviral drugs including darunavir, lopinavir, and ritonavir are suggested to be effective in treating disorders caused by SARS-CoV-2. There are data on the utilization of antiretroviral drugs against SARS-CoV-2. Since there are many studies aimed at the identification of the molecular mechanisms of human immunodeficiency virus type 1 (HIV-1) infection and the development of novel therapeutic approaches against HIV-1, we used HIV-1 for our case study to identify possible molecular pathways shared by SARS-CoV-2 and HIV-1. We applied a text and data mining workflow and identified a list of 46 targets, which can be essential for the development of infections caused by SARS-CoV-2 and HIV-1. We show that SARS-CoV-2 and HIV-1 share some molecular pathways involved in inflammation, immune response, cell cycle regulation.", "qid": 29, "docid": "mfc4mrya", "rank": 91, "score": 0.7605481743812561}, {"content": "Title: COVID-19: viral-host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection Content: BACKGROUND: Epidemiological, virological and pathogenetic characteristics of SARS-CoV-2 infection are under evaluation. A better understanding of the pathophysiology associated with COVID-19 is crucial to improve treatment modalities and to develop effective prevention strategies. Transcriptomic and proteomic data on the host response against SARS-CoV-2 still have anecdotic character; currently available data from other coronavirus infections are therefore a key source of information. METHODS: We investigated selected molecular aspects of three human coronavirus (HCoV) infections, namely SARS-CoV, MERS-CoV and HCoV-229E, through a network based-approach. A functional analysis of HCoV-host interactome was carried out in order to provide a theoretic host-pathogen interaction model for HCoV infections and in order to translate the results in prediction for SARS-CoV-2 pathogenesis. The 3D model of S-glycoprotein of SARS-CoV-2 was compared to the structure of the corresponding SARS-CoV, HCoV-229E and MERS-CoV S-glycoprotein. SARS-CoV, MERS-CoV, HCoV-229E and the host interactome were inferred through published protein-protein interactions (PPI) as well as gene co-expression, triggered by HCoV S-glycoprotein in host cells. RESULTS: Although the amino acid sequences of the S-glycoprotein were found to be different between the various HCoV, the structures showed high similarity, but the best 3D structural overlap shared by SARS-CoV and SARS-CoV-2, consistent with the shared ACE2 predicted receptor. The host interactome, linked to the S-glycoprotein of SARS-CoV and MERS-CoV, mainly highlighted innate immunity pathway components, such as Toll Like receptors, cytokines and chemokines. CONCLUSIONS: In this paper, we developed a network-based model with the aim to define molecular aspects of pathogenic phenotypes in HCoV infections. The resulting pattern may facilitate the process of structure-guided pharmaceutical and diagnostic research with the prospect to identify potential new biological targets.", "qid": 29, "docid": "mbjgbj6o", "rank": 92, "score": 0.7604754567146301}, {"content": "Title: COVID-19: viral\u2013host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection Content: BACKGROUND: Epidemiological, virological and pathogenetic characteristics of SARS-CoV-2 infection are under evaluation. A better understanding of the pathophysiology associated with COVID-19 is crucial to improve treatment modalities and to develop effective prevention strategies. Transcriptomic and proteomic data on the host response against SARS-CoV-2 still have anecdotic character; currently available data from other coronavirus infections are therefore a key source of information. METHODS: We investigated selected molecular aspects of three human coronavirus (HCoV) infections, namely SARS-CoV, MERS-CoV and HCoV-229E, through a network based-approach. A functional analysis of HCoV\u2013host interactome was carried out in order to provide a theoretic host\u2013pathogen interaction model for HCoV infections and in order to translate the results in prediction for SARS-CoV-2 pathogenesis. The 3D model of S-glycoprotein of SARS-CoV-2 was compared to the structure of the corresponding SARS-CoV, HCoV-229E and MERS-CoV S-glycoprotein. SARS-CoV, MERS-CoV, HCoV-229E and the host interactome were inferred through published protein\u2013protein interactions (PPI) as well as gene co-expression, triggered by HCoV S-glycoprotein in host cells. RESULTS: Although the amino acid sequences of the S-glycoprotein were found to be different between the various HCoV, the structures showed high similarity, but the best 3D structural overlap shared by SARS-CoV and SARS-CoV-2, consistent with the shared ACE2 predicted receptor. The host interactome, linked to the S-glycoprotein of SARS-CoV and MERS-CoV, mainly highlighted innate immunity pathway components, such as Toll Like receptors, cytokines and chemokines. CONCLUSIONS: In this paper, we developed a network-based model with the aim to define molecular aspects of pathogenic phenotypes in HCoV infections. The resulting pattern may facilitate the process of structure-guided pharmaceutical and diagnostic research with the prospect to identify potential new biological targets.", "qid": 29, "docid": "tq48w43o", "rank": 93, "score": 0.76035076379776}, {"content": "Title: Comparative transcriptome analyses reveal genes associated with SARS-CoV-2 infection of human lung epithelial cells Content: Understanding the molecular mechanism of SARS-CoV-2 infection (the cause of COVID-19) is a scientific priority for 2020. Various research groups are working toward development of vaccines and drugs, and many have published genomic and transcriptomic data related to this viral infection. The power inherent in publicly available data can be demonstrated via comparative transcriptome analyses. In the current study, we collected high-throughput gene expression data related to human lung epithelial cells infected with SARS-CoV-2 or other respiratory viruses (SARS, H1N1, rhinovirus, avian influenza, and Dhori) and compared the effect of these viruses on the human transcriptome. The analyses identified fifteen genes specifically expressed in cells transfected with SARS-CoV-2; these included CSF2 (colony-stimulating factor 2) and S100A8 and S100A9 (calcium-binding proteins), all of which are involved in lung/respiratory disorders. The analyses showed that genes involved in the Type1 interferon signaling pathway and the apoptosis process are commonly altered by infection of SARS-CoV-2 and influenza viruses. Furthermore, results of protein-protein interaction analyses were consistent with a functional role of CSF2 in COVID-19 disease. In conclusion, our analysis has revealed cellular genes associated with SARS-CoV-2 infection of the human lung epithelium; these are potential therapeutic targets.", "qid": 29, "docid": "ll0y4gpk", "rank": 94, "score": 0.7603370547294617}, {"content": "Title: Attacking COVID-19 Progression using Multi-Drug Therapy for Synergetic Target Engagement Content: COVID-19 is a devastating respiratory and inflammatory illness caused by a new coronavirus that is rapidly spreading throughout the human population. Over the past 6 months, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, has already infected over 11.6 million (25% located in United States) and killed more than 540K people around the world. As we face one of the most challenging times in our recent history, there is an urgent need to identify drug candidates that can attack SARS-CoV-2 on multiple fronts. We have therefore initiated a computational dynamics drug pipeline using molecular modeling, structure simulation, docking and machine learning models to predict the inhibitory activity of several million compounds against two essential SARS-CoV-2 viral proteins and their host protein interactors; S/Ace2, Tmprss2, Cathepsins L and K, and Mpro to prevent binding, membrane fusion and replication of the virus, respectively. All together we generated an ensemble of structural conformations that increase high quality docking outcomes to screen over>6 million compounds including all FDA-approved drugs, drugs under clinical trial (>3000) and an additional>30 million selected chemotypes from fragment libraries. Our results yielded an initial set of 350 high value compounds from both new and FDA-approved compounds that can now be tested experimentally in appropriate biological model systems. We anticipate that our results will initiate screening campaigns and accelerate the discovery of COVID-19 treatments.", "qid": 29, "docid": "4qyrtzhu", "rank": 95, "score": 0.7601916193962097}, {"content": "Title: In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication Content: A novel coronavirus, named SARS-CoV-2, emerged in 2019 from Hubei region in China and rapidly spread worldwide. As no approved therapeutics exists to treat Covid-19, the disease associated to SARS-Cov-2, there is an urgent need to propose molecules that could quickly enter into clinics. Repurposing of approved drugs is a strategy that can bypass the time consuming stages of drug development. In this study, we screened the Prestwick Chemical Library\u00ae composed of 1,520 approved drugs in an infected cell-based assay. 90 compounds were identified. The robustness of the screen was assessed by the identification of drugs, such as Chloroquine derivatives and protease inhibitors, already in clinical trials. The hits were sorted according to their chemical composition and their known therapeutic effect, then EC50 and CC50 were determined for a subset of compounds. Several drugs, such as Azithromycine, Opipramol, Quinidine or Omeprazol present antiviral potency with 2<EC50<20\u00b5M. By providing new information on molecules inhibiting SARS-CoV-2 replication in vitro, this study could contribute to the short-term repurposing of drugs against Covid-19.", "qid": 29, "docid": "m7dwbheg", "rank": 96, "score": 0.75993812084198}, {"content": "Title: Master Regulator Analysis of the SARS-CoV-2/Human interactome Content: the recent epidemic outbreak of a novel human coronavirus called SARS-CoV-2 and causing the respiratory tract disease COVID-19 has reached worldwide resonance and a global effort is being undertaken to characterize the molecular features and evolutionary origins of this virus. In this paper, we set out to shed light on the SARS-CoV-2/host receptor recognition, a crucial factor for successful virus infection. Based on the current knowledge of the interactome between SARS-CoV-2 and host cell proteins, we performed Master Regulator Analysis to detect which parts of the human interactome are most affected by the infection. We detected, amongst others, affected apoptotic and mitochondrial mechanisms, and a downregulation of the ACE2 protein receptor, notions that can be used to develop specific therapies against this new virus.", "qid": 29, "docid": "aazntg4c", "rank": 97, "score": 0.7595721483230591}, {"content": "Title: Structural Similarity of SARS-CoV2 Mpro and HCV NS3/4A Proteases Suggests New Approaches for Identifying Existing Drugs Useful as COVID-19 Therapeutics. Content: During the current COVID-19 pandemic more than 160,000 people have died worldwide as of mid-April 2020, and the global economy has been crippled. Effective control of the SARS-CoV2 virus that causes the COVID-19 pandemic requires both vaccines and antivirals. Antivirals are particularly crucial to treat infected people during the period of time that an effective vaccine is being developed and deployed. Because the development of specific antiviral drugs can take a considerable length of time, an important approach is to identify existing drugs already approved for use in humans which could be repurposed as COVID-19 therapeutics. Here we focus on antivirals directed against the SARS-CoV2 Mpro protease, which is required for virus replication. A structural similarity search showed that the Hepatitis C virus (HCV) NS3/4A protease has a striking three-dimensional structural similarity to the SARS-CoV2 Mpro protease, particularly in the arrangement of key active site residues. We used virtual docking predictions to assess the hypothesis that existing drugs already approved for human use or clinical testing that are directed at the HCV NS3/4A protease might fit well into the active-site cleft of the SARS-CoV2 protease (Mpro). AutoDock docking scores for 12 HCV protease inhibitors and 9 HIV-1 protease inhibitors were determined and compared to the docking scores for an \u03b1-ketoamide inhibitor of Mpro, which has recently been shown to inhibit SARS-CoV2 virus replication in cell culture. We identified eight HCV protease inhibitors that bound to the Mpro active site with higher docking scores than the \u03b1-ketoamide inhibitor, suggesting that these protease inhibitors may effectively bind to the Mpro active site. These results provide the rationale for us to test the identified HCV protease inhibitors as inhibitors of the SARS-CoV2 protease, and as inhibitors of SARS-CoV2 virus replication. Subsequently these repurposed drugs could be evaluated as COVID-19 therapeutics.", "qid": 29, "docid": "vvf3ei6v", "rank": 98, "score": 0.7595094442367554}, {"content": "Title: Bacterial protein azurin and derived peptides as potential anti-SARS-CoV-2 agents: insights from molecular docking and molecular dynamics simulations Content: The current pandemic SARS-CoV-2 has wreaked havoc in the world, and neither drugs nor vaccine is available for the treatment of this disease. Thus, there is an immediate need for novel therapeutics that can combat this deadly infection. In this study, we report the therapeutic assessment of azurin and its peptides: p18 and p28 against the viral structural S-protein and non-structural 3CLpro and PLpro proteins. Among the analyzed complexes, azurin docked relatively well with the S2 domain of S-protein compared to the other viral proteins. The derived peptide p18 bound to the active site domain of the PLpro protein; however, in other complexes, lesser interactions were recorded. The second azurin derived peptide p28, fared the best among the docked proteins. p28 interacted with all the three viral proteins and the host ACE-2 receptor by forming several electrostatic and hydrogen bonds with the S-protein, 3CLpro, and PLpro. MD simulations indicated that p28 exhibited a strong affinity to S-protein and ACE-2 receptor, indicating a possibility of p28 as a protein-protein interaction inhibitor. Our data suggest that the p28 has potential as an anti-SARS-CoV-2 agent and can be further exploited to establish its validity in the treatment of current and future SARS-CoV crisis.Communicated by Ramaswamy H. Sarma.", "qid": 29, "docid": "812vjcr7", "rank": 99, "score": 0.7594648003578186}, {"content": "Title: Bacterial protein azurin and derived peptides as potential anti-SARS-CoV-2 agents: insights from molecular docking and molecular dynamics simulations. Content: The current pandemic SARS-CoV-2 has wreaked havoc in the world, and neither drugs nor vaccine is available for the treatment of this disease. Thus, there is an immediate need for novel therapeutics that can combat this deadly infection. In this study, we report the therapeutic assessment of azurin and its peptides: p18 and p28 against the viral structural S-protein and non-structural 3CLpro and PLpro proteins. Among the analyzed complexes, azurin docked relatively well with the S2 domain of S-protein compared to the other viral proteins. The derived peptide p18 bound to the active site domain of the PLpro protein; however, in other complexes, lesser interactions were recorded. The second azurin derived peptide p28, fared the best among the docked proteins. p28 interacted with all the three viral proteins and the host ACE-2 receptor by forming several electrostatic and hydrogen bonds with the S-protein, 3CLpro, and PLpro. MD simulations indicated that p28 exhibited a strong affinity to S-protein and ACE-2 receptor, indicating a possibility of p28 as a protein-protein interaction inhibitor. Our data suggest that the p28 has potential as an anti-SARS-CoV-2 agent and can be further exploited to establish its validity in the treatment of current and future SARS-CoV crisis.Communicated by Ramaswamy H. Sarma.", "qid": 29, "docid": "pb0wvujy", "rank": 100, "score": 0.7594648003578186}]}
{"query": "is remdesivir an effective treatment for COVID-19", "hits": [{"content": "Title: Montelukast drug activity and potential against SARS-CoV-2 Content: COVID-19 presents a major worldwide public health emergency. Many research efforts are ongoing to find effective antiviral treatments via novel drug design or drug repurposing (Duarte et al., 2020). One drug, remdesivir, has been shown to have activity against the SARS-CoV-2 RNA dependent RNA polymerase (RdRp), and has been used clinically in severe COVID-19 disease, but more accessible and readily available treatments are needed for all stages of infection. This article is protected by copyright. All rights reserved.", "qid": 30, "docid": "w3ido97l", "rank": 1, "score": 0.8717136383056641}, {"content": "Title: Montelukast drug activity and potential against SARS-CoV-2. Content: COVID-19 presents a major worldwide public health emergency. Many research efforts are ongoing to find effective antiviral treatments via novel drug design or drug repurposing (Duarte et al., 2020). One drug, remdesivir, has been shown to have activity against the SARS-CoV-2 RNA dependent RNA polymerase (RdRp), and has been used clinically in severe COVID-19 disease, but more accessible and readily available treatments are needed for all stages of infection. This article is protected by copyright. All rights reserved.", "qid": 30, "docid": "ntozf7ba", "rank": 2, "score": 0.8717136383056641}, {"content": "Title: Remdesivir use in patients with coronavirus COVID-19 disease: a systematic review and meta-analysis Content: Background Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, has led to significant global mortality and morbidity. Until now, no treatment has proven to be effective in COVID-19. To explore whether the use of remdesivir, initially an experimental broad-spectrum antiviral, is effective in the treatment of hospitalized patients with COVID-19, we conducted a systematic review and meta-analysis of randomized, placebo-controlled trials investigating its use. Methods A rapid search of the MEDLINE and EMBASE medical databases was conducted for randomized controlled trials. A systematic approach was used to screen, abstract, and critically appraise the studies. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method was applied to rate the certainty and quality of the evidence reported per study. Results Two RCTs studies were identified (n=1,299). A fixed-effects meta-analysis revealed reductions in mortality (RR=0.69, 0.49 to 0.99), time to clinical improvement (3.95 less days, from 3.86 days less to 4.05 less days ), serious adverse events (RR=0.77, 0.63 to 0.94) and all adverse events (RR=0.87, 0.79 to 0.96). Conclusion In this rapid systematic review, we present pooled evidence from the 2 included RCT studies that reveal that remdesivir has a modest yet significant reduction in mortality and significantly improves the time to recovery, as well as significantly reduced risk in adverse events and serious adverse events. It is more than likely that as an antiviral, remdesivir is not sufficient on its own and may be suitable in combination with other antivirals or treatments such as convalescent plasma. Research is ongoing to clarify and contextual these promising findings.", "qid": 30, "docid": "7xc47la7", "rank": 3, "score": 0.8646070957183838}, {"content": "Title: Remdesivir investigational trials in COVID-19: a critical reappraisal Content: Abstract During outbreak of emerging disease, the most important aim is to discover an effective drug to save life. Consequently, a lot of effort are generally made by the industry to promote clinical trials with new drugs. Here we review evidence of the 8 most recent reports including 3 randomized controlled trials on the clinical efficacy of remdesivir in treating COVID-19 patient. We conclude that it is far too premature to identify remdesivir as a curative or life-saving intervention.", "qid": 30, "docid": "pkklt77i", "rank": 4, "score": 0.8593853712081909}, {"content": "Title: Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Aditional Benefit Content: Remdesivir is one of the most promising drugs to treat COVID-19 based on the following facts: remdesivir has a broad-spectrum antiviral mechanism of action; it demonstrated in vitro activity against SARS-CoV-2 and in vivo efficacy in animal models against the similar coronavirus MERS-CoV; its safety profile has been tested in Ebola patients and in compassionate use in COVID-19 patients. Currently, remdesivir is being investigated in ten randomized controlled trials against COVID-19. The dose regimen of remdesivir is an IV loading dose of 200 mg on day 1 followed by daily IV maintenance doses of 100 mg for 5-9 days. Based on our data analysis, however, remdesivir with IV administration alone is unlikely to achieve excellent clinical efficacy. This analysis is based on the following observations: plasma exposures of remdesivir and its active metabolite are unlikely to be correlated with its clinical efficacy; remdesivir and its active metabolites are unlikely to be adequate in the lung to kill the SARS-CoV-2 virus. Even if remdesivir demonstrates benefits in the current randomized controlled trials, its efficacy may be limited. We suggest that a combination of an IV and pulmonary delivery dose regimen should be studied immediately to realize a potentially more effective antiviral therapy against COVID-19. Graphical abstract.", "qid": 30, "docid": "r0znh1bi", "rank": 5, "score": 0.8536777496337891}, {"content": "Title: Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Aditional Benefit Content: Remdesivir is one of the most promising drugs to treat COVID-19 based on the following facts: remdesivir has a broad-spectrum antiviral mechanism of action; it demonstrated in vitro activity against SARS-CoV-2 and in vivo efficacy in animal models against the similar coronavirus MERS-CoV; its safety profile has been tested in Ebola patients and in compassionate use in COVID-19 patients. Currently, remdesivir is being investigated in ten randomized controlled trials against COVID-19. The dose regimen of remdesivir is an IV loading dose of 200 mg on day 1 followed by daily IV maintenance doses of 100 mg for 5\u20139 days. Based on our data analysis, however, remdesivir with IV administration alone is unlikely to achieve excellent clinical efficacy. This analysis is based on the following observations: plasma exposures of remdesivir and its active metabolite are unlikely to be correlated with its clinical efficacy; remdesivir and its active metabolites are unlikely to be adequate in the lung to kill the SARS-CoV-2 virus. Even if remdesivir demonstrates benefits in the current randomized controlled trials, its efficacy may be limited. We suggest that a combination of an IV and pulmonary delivery dose regimen should be studied immediately to realize a potentially more effective antiviral therapy against COVID-19. [Figure: see text]", "qid": 30, "docid": "4178ui2c", "rank": 6, "score": 0.848105788230896}, {"content": "Title: Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2 Content: Background Effective therapeutics to treat COVID-19 are urgently needed. Remdesivir is a nucleotide prodrug with in vitro and in vivo efficacy against coronaviruses. Here, we tested the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection. Methods To evaluate the effect of remdesivir treatment on SARS-CoV-2 disease outcome, we used the recently established rhesus macaque model of SARS-CoV-2 infection that results in transient lower respiratory tract disease. Two groups of six rhesus macaques were infected with SARS-CoV-2 and treated with intravenous remdesivir or an equal volume of vehicle solution once daily. Clinical, virological and histological parameters were assessed regularly during the study and at necropsy to determine treatment efficacy. Results In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs. Virus titers in bronchoalveolar lavages were significantly reduced as early as 12hrs after the first treatment was administered. At necropsy on day 7 after inoculation, lung viral loads of remdesivir-treated animals were significantly lower and there was a clear reduction in damage to the lung tissue. Conclusions Therapeutic remdesivir treatment initiated early during infection has a clear clinical benefit in SARS-CoV-2-infected rhesus macaques. These data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to severe pneumonia.", "qid": 30, "docid": "p6uliadr", "rank": 7, "score": 0.8438386917114258}, {"content": "Title: Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2 Content: Effective therapeutics to treat COVID-19 are urgently needed. While many investigational, approved, and repurposed drugs have been suggested, preclinical data from animal models can guide the search for effective treatments by ruling out treatments without in vivo efficacy. Remdesivir (GS-5734) is a nucleotide analog prodrug with broad antiviral activity1,2, that is currently investigated in COVID-19 clinical trials and recently received Emergency Use Authorization from the US Food and Drug Administration3,4. In animal models, remdesivir treatment was effective against MERS-CoV and SARS-CoV infection.2,5,6 In vitro, remdesivir inhibited replication of SARS-CoV-2.7,8 Here, we investigated the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection9. In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs and reduced virus titers in bronchoalveolar lavages 12hrs after the first treatment administration. Virus shedding from the upper respiratory tract was not reduced by remdesivir treatment. At necropsy, lung viral loads of remdesivir-treated animals were lower and there was a reduction in damage to the lungs. Thus, therapeutic remdesivir treatment initiated early during infection had a clinical benefit in SARS-CoV-2-infected rhesus macaques. Although the rhesus macaque model does not represent the severe disease observed in a proportion of COVID-19 patients, our data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to pneumonia.", "qid": 30, "docid": "jxbch44o", "rank": 8, "score": 0.8434897661209106}, {"content": "Title: Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Content: Effective therapeutics to treat COVID-19 are urgently needed. While many investigational, approved, and repurposed drugs have been suggested, preclinical data from animal models can guide the search for effective treatments by ruling out treatments without in vivo efficacy. Remdesivir (GS-5734) is a nucleotide analog prodrug with broad antiviral activity1,2, that is currently investigated in COVID-19 clinical trials and recently received Emergency Use Authorization from the US Food and Drug Administration3,4. In animal models, remdesivir treatment was effective against MERS-CoV and SARS-CoV infection.2,5,6 In vitro, remdesivir inhibited replication of SARS-CoV-2.7,8 Here, we investigated the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection9. In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs and reduced virus titers in bronchoalveolar lavages 12hrs after the first treatment administration. Virus shedding from the upper respiratory tract was not reduced by remdesivir treatment. At necropsy, lung viral loads of remdesivir-treated animals were lower and there was a reduction in damage to the lungs. Thus, therapeutic remdesivir treatment initiated early during infection had a clinical benefit in SARS-CoV-2-infected rhesus macaques. Although the rhesus macaque model does not represent the severe disease observed in a proportion of COVID-19 patients, our data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to pneumonia.", "qid": 30, "docid": "1cph1uij", "rank": 9, "score": 0.8434897065162659}, {"content": "Title: Efficacy and Safety of Remdesivir for COVID-19 Treatment: An Analysis of Randomized, Double-Blind, Placebo-Controlled Trials Content: BACKGROUND Remdesivir, an inhibitor of viral RNA-dependent RNA polymerases, has been identified as a candidate for COVID-19 treatment. However, the therapeutic effect of remdesivir is controversial. METHODS We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, from inception to June 11, 2020 for randomized controlled trials on the clinical efficacy of remdesivir. The main outcomes were discharge rate, mortality, and adverse events. This study is registered at INPLASY (INPLASY202060046). RESULTS Data of 1075 subjects showed that remdesivir significantly increased the discharge rate of patients with COVID-19 compared with the placebo (50.4% vs. 45.29%; relative risk [RR] 1.19 [95% confidence interval [CI], 1.05-1.34], I2 = 0.0%, P = 0.754). It also significantly decreased mortality (8.18% vs. 12.70%; RR 0.64 [95% CI, 0.44-0.92], I2 = 45.7%, P = 0.175) compared to the placebo. Data of 1296 subjects showed that remdesivir significantly decreased the occurrence of serious adverse events (RR 0.77 [95% CI, 0.63-0.94], I2 = 0.0%, P = 0.716). CONCLUSION Remdesivir is efficacious and safe for the treatment of COVID-19. TRIAL REGISTRATION NUMBER This study is registered at the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY202060046).", "qid": 30, "docid": "qxsr3uii", "rank": 10, "score": 0.8430408239364624}, {"content": "Title: That Escalated Quickly: Remdesivir's Place in Therapy for COVID-19 Content: Remdesivir is a nucleoside antiviral recently studied in several randomized trials for treatment of COVID-19. The available observational and prospective data are conflicting, requiring clinicians to critically evaluate and reconcile results to determine patient populations that may optimally benefit from remdesivir therapy, especially while drug supply is scarce. In this review, we analyze pertinent clinical remdesivir data for patients with COVID-19 from January 1, 2020, through May 31, 2020.", "qid": 30, "docid": "ioqvxhar", "rank": 11, "score": 0.8421713709831238}, {"content": "Title: Antiviral treatment of COVID-19 Content: Currently, there is not any specific effective antiviral treatment for COVID-19. Although most of the COVID-19 patients have mild or moderate courses, up to 5%\u00ad10% can have severe, potentially life threatening course, there is an urgent need for effective drugs. Optimized supportive care remains the mainstay of therapy. There have been more than 300 clinical trials going on, various antiviral and immunomodulating agents are in various stages of evaluation for COVID-19 in those trials and some of them will be published in the next couple of months. Despite the urgent need to find an effective antiviral treatment for COVID-19 through randomized controlled studies, certain agents are being used all over the world based on either in-vitro or extrapolated evidence or observational studies. The most frequently used agents both in Turkey and all over the world including chloroquine, hydroxychloroquine, lopinavir/ritonavir, favipiravir and remdesivir will be reviewed here .Nitazoxanide and ivermectin were also included in this review as they have recently been reported to have an activity against SARS-CoV-2 in vitro and are licensed for the treatment of some other human infections.", "qid": 30, "docid": "4g878n13", "rank": 12, "score": 0.836056649684906}, {"content": "Title: Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. Content: Importance The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection. Observations No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19. Conclusions and Relevance The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.", "qid": 30, "docid": "8cvjsisw", "rank": 13, "score": 0.8357712030410767}, {"content": "Title: The journey of remdesivir: from Ebola to COVID-19 Content: Countries around the world are currently fighting the coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a betacoronavirus, belonging to the same genus as severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV. Currently, there are no proven antiviral therapies for COVID-19. Numerous clinical trials have been initiated to identify an effective treatment. One leading candidate is remdesivir (GS-5734), a broad-spectrum antiviral that was initially developed for the treatment of Ebola virus (EBOV). Although remdesivir performed well in preclinical studies, it did not meet efficacy endpoints in a randomized trial conducted during an Ebola outbreak. Remdesivir holds promise for treating COVID-19 based on in vitro activity against SARS-CoV-2, uncontrolled clinical reports, and limited data from randomized trials. Overall, current data are insufficient to judge the efficacy of remdesivir for COVID-19, and the results of additional randomized studies are eagerly anticipated. In this narrative review, we provide an overview of Ebola and coronavirus outbreaks. We then summarize preclinical and clinical studies of remdesivir for Ebola and COVID-19.", "qid": 30, "docid": "aivub6mi", "rank": 14, "score": 0.8354641199111938}, {"content": "Title: Antiviral treatment of COVID-19 Content: Currently, there is not any specific effective antiviral treatment for COVID-19. Although most of the COVID-19 patients have mild or moderate courses, up to 5%\u201310% can have severe, potentially life threatening course, there is an urgent need for effective drugs. Optimized supportive care remains the mainstay of therapy. There have been more than 300 clinical trials going on, various antiviral and immunomodulating agents are in various stages of evaluation for COVID-19 in those trials and some of them will be published in the next couple of months. Despite the urgent need to find an effective antiviral treatment for COVID-19 through randomized controlled studies, certain agents are being used all over the world based on either in-vitro or extrapolated evidence or observational studies. The most frequently used agents both in Turkey and all over the world including chloroquine, hydroxychloroquine, lopinavir/ritonavir, favipiravir and remdesivir will be reviewed here .Nitazoxanide and ivermectin were also included in this review as they have recently been reported to have an activity against SARS-CoV-2 in vitro and are licensed for the treatment of some other human infections.", "qid": 30, "docid": "qq6l6yrx", "rank": 15, "score": 0.8350497484207153}, {"content": "Title: Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review Content: Importance: The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection. Observations: No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19. Conclusions and Relevance: The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.", "qid": 30, "docid": "yth9hh5q", "rank": 16, "score": 0.8328083753585815}, {"content": "Title: Rapid review for the anti-coronavirus effect of remdesivir Content: The outbreak of SARS-CoV-2 rapidly spread across China and worldwide. Remdesivir had been proposed as a promising option for treating coronavirus disease 2019 (COVID-19). We provided a rapid review to critically assess the potential anti-coronavirus effect of remdesivir on COVID-19 and other coronaviruses based on the most up-to-date evidence. Even though remdesivir was proposed as a promising option for treating COVID-19 based on laboratory experiments and reports from compassionate use, its safety and effect in humans requires high-quality evidence from well-designed and adequately-powered clinical trials for further clarification.", "qid": 30, "docid": "a0drmmf7", "rank": 17, "score": 0.832019031047821}, {"content": "Title: Rapid review for the anti-coronavirus effect of remdesivir. Content: The outbreak of SARS-CoV-2 rapidly spread across China and worldwide. Remdesivir had been proposed as a promising option for treating coronavirus disease 2019 (COVID-19). We provided a rapid review to critically assess the potential anti-coronavirus effect of remdesivir on COVID-19 and other coronaviruses based on the most up-to-date evidence. Even though remdesivir was proposed as a promising option for treating COVID-19 based on laboratory experiments and reports from compassionate use, its safety and effect in humans requires high-quality evidence from well-designed and adequately-powered clinical trials for further clarification.", "qid": 30, "docid": "4el6qq3n", "rank": 18, "score": 0.832019031047821}, {"content": "Title: Remdesivir in COVID-19: A critical review of pharmacology, pre-clinical and clinical studies Content: BACKGROUND & AIMS: Remdesivir is a broad spectrum anti-viral drug that has shown to inhibit SARS-CoV-2, in vitro and in vivo. In absence of any effective treatment for SARS-CoV-2 infection (COVID-19), remdesivir has been tried for a compassionate use in severe COVID-19. Newer randomized controlled studies that have recently become available, showed a mixed result. We aimed to systematically search the literature to understand the pharmacology and clinical effects of remdesivir in patients with COVID-19. METHODS: We systematically searched the PubMed, ClinicalTrial.Org and MedRxiv database up till May 5, 2020 using specific key words such as \u201cRemdesivir\u201d or \u2018GS-5734\u2033 AND \u201cCOVID-19\u201d or \u201cSARS-CoV-2\u201d and retrieved all the article published in English language, that have reported the pharmacology and the clinical outcomes of remdesivir in patients with COVID-19. RESULTS: Initial compassionate use of remdesivir has shown a fairly good result, but difficult to quantify, in the absence of control arm. While the very first double-blind, placebo-controlled, randomized trial conducted in Wuhan, did not find any significant benefit compared to the control, the preliminary result of another similar multi-country trial has shown a significant faster time to recovery but without any difference in mortality. CONCLUSIONS: Remdesivir has shown a mixed result in patients with COVID-19 with an acceptable side effect. However, jury is still out while awaiting the results from the forthcoming trials.", "qid": 30, "docid": "gqqdx2r5", "rank": 19, "score": 0.8299264311790466}, {"content": "Title: Remdesivir in the treatment of coronavirus disease 2019 (COVID-19): a simplified summary Content: The pandemic of COVID-19 (Coronavirus Disease-2019) is an extremely contagious respiratory illness due to a novel coronavirus, SARS-CoV-2. Certain drugs have several protein targets and many illnesses share overlapping molecular paths. In such cases, reusing drugs for more than one objective and finding their novice uses can considerably decrease the time in finding new cures for unforeseen diseases. Remdesivir has been recently a strong candidate for the treatment of Covid-19. In this commentary, we have portrayed the structure of the coronavirus in a simple way as well as the site where remdesivir acts. We have also displayed the ongoing clinical trials, as well as a published study that was conducted on compassionate base. The covid-19 pandemic might wean down by the end of summer 2020, but the risk of seasonality exists. Therefore, future disposal of agents such as remdesivir might be crucial for ensuring an efficient treatment, decrease mortality and allow early discharge. Communicated by Ramaswamy H. Sarma", "qid": 30, "docid": "np6nfvf2", "rank": 20, "score": 0.8295413255691528}, {"content": "Title: Remdesivir in COVID-19: A critical review of pharmacology, pre-clinical and clinical studies Content: BACKGROUND & AIMS: Remdesivir is a broad spectrum anti-viral drug that has shown to inhibit SARS-CoV-2, in vitro and in vivo. In absence of any effective treatment for SARS-CoV-2 infection (COVID-19), remdesivir has been tried for a compassionate use in severe COVID-19. Newer randomized controlled studies that have recently become available, showed a mixed result. We aimed to systematically search the literature to understand the pharmacology and clinical effects of remdesivir in patients with COVID-19. METHODS: We systematically searched the PubMed, ClinicalTrial.Org and MedRxiv database up till May 5, 2020 using specific key words such as \"Remdesivir\" or 'GS-5734\u00e2\u0080\u00b3 AND \"COVID-19\" or \"SARS-CoV-2\" and retrieved all the article published in English language, that have reported the pharmacology and the clinical outcomes of remdesivir in patients with COVID-19. RESULTS: Initial compassionate use of remdesivir has shown a fairly good result, but difficult to quantify, in the absence of control arm. While the very first double-blind, placebo-controlled, randomized trial conducted in Wuhan, did not find any significant benefit compared to the control, the preliminary result of another similar multi-country trial has shown a significant faster time to recovery but without any difference in mortality. CONCLUSIONS: Remdesivir has shown a mixed result in patients with COVID-19 with an acceptable side effect. However, jury is still out while awaiting the results from the forthcoming trials.", "qid": 30, "docid": "1eiw7bxh", "rank": 21, "score": 0.8283265233039856}, {"content": "Title: Remdesivir for the Treatment of Covid-19 \u2014 Preliminary Report Content: BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). CONCLUSIONS: Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.)", "qid": 30, "docid": "uohbxoeb", "rank": 22, "score": 0.8274460434913635}, {"content": "Title: Pharmacologicaltreatment of COVID-19: lights and shadows Content: At the end of December 2019, a novel coronavirus, the severe acute respiratory syndrome coronavirus 2, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China and then the entire world, forcing the World Health Organization to make the assessment that the coronavirus disease (COVID-19) can be characterized as a pandemic, the first ever caused by a coronavirus. To date, clinical evidence and guidelines based on reliable data and randomized clinical trials for the treatment of COVID-19 are lacking. In the absence of definitive management protocols, many treatments for COVID-19 are currently being evaluated and tested worldwide. Some of these options were soon abandoned due to ineffectiveness, while others showed promising results. The basic treatments are mainly represented by antiviral drugs, even if the evidence is not satisfactory. Among the antivirals, the most promising appears to be remdesivir. Corticosteroids and tocilizumab seem to guarantee positive results in selected patients so far, although the timing of starting therapy and the most appropriate therapeutic schemes remain to be clarified. Efficacy of the other drugs is still uncertain, and they are currently used as a cocktail of treatments in the absence of definitive guidelines. What will represent the real solution to the enormous problem taking place worldwide is the identification of a safe and effective vaccine, for which enormous efforts and investments are underway.", "qid": 30, "docid": "o29773cz", "rank": 23, "score": 0.8256845474243164}, {"content": "Title: Efficacy and harms of remdesivir for the treatment of COVID-19: a systematic review and meta-analysis Content: Background: We evaluated the efficacy and safety of remdesivir for the treatment of COVID-19. Methods: Systematic review in five engines, pre-print webpages and RCT registries until May 22, 2020 for randomized controlled trials (RCTs) and observational studies evaluating remdesivir on confirmed, COVID-19 adults with pneumonia and/or respiratory insufficiency. Primary outcomes were all-cause mortality, clinical improvement or recovery, need for invasive ventilation, and serious adverse events (SAE). Secondary outcomes included length of hospital stay, progression of pneumonia, and adverse events (AE). Inverse variance random effects meta-analyses were performed. Results: Two placebo-controlled RCTs (n=1300) and two case series (n=88) were included. All studies used remdesivir 200mg IV the first day and 100mg IV for 9 more days, and followed up until 28 days. Wang et al. RCT was stopped early due to AEs; ACTT-1 was preliminary reported at 15-day follow up. Time to clinical improvement was not decreased in Wang et al. RCT, but median time to recovery was decreased by 4 days in ACTT-1. Remdesivir did not decrease all-cause mortality (RR 0.71, 95%CI 0.39 to 1.28) and need for invasive ventilation at 14 days (RR 0.57, 95%CI 0.23 to 1.42), but had fewer SAEs (RR 0.77, 95%CI 0.63 to 0.94). AEs were similar between remdesivir and placebo arms. Risk of bias ranged from some concerns to high risk in RCTs. Interpretation: There is paucity of adequately powered and fully reported RCTs evaluating effects of remdesivir in adult, hospitalized COVID-19 patients. Remdesivir should not be recommended for the treatment of severe COVID-19.", "qid": 30, "docid": "4vfk99f5", "rank": 24, "score": 0.824415922164917}, {"content": "Title: Remdesivir for the Treatment of Covid-19 - Preliminary Report Content: BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). CONCLUSIONS: Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACCT-1 ClinicalTrials.gov number, NCT04280705.).", "qid": 30, "docid": "tn2xfmry", "rank": 25, "score": 0.8239274024963379}, {"content": "Title: Case reports study of the first five patients COVID-19 treated with remdesivir in France Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as responsible for the COVID-19 outbreak worldwide. Data on treatment are scare and parallels are made between SARS-CoV-2 and other coronavirus. Remdesivir is a broad spectrum antiviral with efficient in vitro activity against SARS-CoV-2 and controversial evidence of clinical improvement in severe COVID-19 patients. We aimed to describe the clinical outcome and virological monitoring of the first five COVID-19 patients admitted in ICU for severe pneumonia related to SARS-CoV-2 and treated with remdesivir in the University hospital of Bichat, Paris, France. SARS-CoV-2 RT-qPCR in blood plasma, lower and upper respiratory tract were monitored. Among the five treated patients, two needed mechanical ventilation and one high flow cannula oxygen. A significant decrease in SARS-CoV-2 viral load from upper respiratory tract was observed in most cases but two died with active SARS-CoV-2 replication in the lower respiratory tract. Plasma samples were positive for SARS-CoV-2 in only one patient. Remdesivir was interrupted for side effects among four patients, including 2 ALT elevations (3 to 5 N) and 2 renal failures requiring renal replacement. This case series of five COVID-19 patients requiring ICU for a respiratory distress and treated with remdesivir, highlights the complexity of remdesivir use in such critically ill patients.", "qid": 30, "docid": "oc0m6r5c", "rank": 26, "score": 0.8206630945205688}, {"content": "Title: Case reports study of the first five patients COVID-19 treated with remdesivir in France Content: Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as responsible for the COVID-19 outbreak worldwide. Data on treatment are scare and parallels are made between SARS-CoV-2 and other coronavirus. Remdesivir is a broad spectrum antiviral with efficient in vitro activity against SARS-CoV-2 and controversial evidence of clinical improvement in severe COVID-19 patients. We aimed to describe the clinical outcome and virological monitoring of the first five COVID-19 patients admitted in ICU for severe pneumonia related to SARS-CoV-2 and treated with remdesivir in the University hospital of Bichat, Paris, France. SARS-CoV-2 RT-qPCR in blood plasma, lower and upper respiratory tract were monitored. Among the five treated patients, two needed mechanical ventilation and one high flow cannula oxygen. A significant decrease in SARS-CoV-2 viral load from upper respiratory tract was observed in most cases but two died with active SARS-CoV-2 replication in the lower respiratory tract. Plasma samples were positive for SARS-CoV-2 in only one patient. Remdesivir was interrupted for side effects among four patients, including 2 ALT elevations (3 to 5 N) and 2 renal failures requiring renal replacement. This case series of five COVID-19 patients requiring ICU for a respiratory distress and treated with remdesivir, highlights the complexity of remdesivir use in such critically ill patients.", "qid": 30, "docid": "m69ceq2t", "rank": 27, "score": 0.8204351663589478}, {"content": "Title: Antiviral therapy in management of COVID-19: a systematic review on current evidence. Content: Background The purpose of the current systematic review is to evaluate the efficacy of antiviral therapies in treatment of COVID-19. In addition, clinical trials on the efficacy of antiviral therapies in the management of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov) or Middle East Respiratory Syndrome coronavirus (MERS-CoV) have also been reviewed, in order to identify potential treatment options for COVID-19. Method An extensive search was performed in Medline, Embase, Scopus, Web of Science and CENTRAL databases until the end of March 15, 2020. Two independent researchers performed the screening, and finally the related studies were included. Results Only one clinical trial on the efficacy of antiviral therapy in management of COVID-19 was found. The results depicted that adding Lopinavir-Ritonavir to the standard treatment regimen of patients with severe COVID-19 has no benefits. Moreover, 21 case-series and case-report studies reported the prescription of antiviral agents in COVID-19, none of which can be used to determine the efficacy of antiviral therapies in confronting COVID-19. In addition, no clinical trials were found to be performed on the efficacy of antiviral agents in the management of SARS-CoV and MERS-CoV. Conclusion The current evidence impede researchers from proposing an appropriate antiviral therapy against COVID-19, making the current situation a serious concern for international organizations such as World Health Organization (WHO). In the time of the current pandemic and future epidemics, organizations such as WHO should pursue more proactive actions and plan well-designed clinical trials so that their results can be used in managing future epidemics.", "qid": 30, "docid": "bfchqn2g", "rank": 28, "score": 0.8203614354133606}, {"content": "Title: Antiviral therapy in management of COVID-19: a systematic review on current evidence Content: BACKGROUND: The purpose of the current systematic review is to evaluate the efficacy of antiviral therapies in treatment of COVID-19. In addition, clinical trials on the efficacy of antiviral therapies in the management of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov) or Middle East Respiratory Syndrome coronavirus (MERS-CoV) have also been reviewed, in order to identify potential treatment options for COVID-19. METHOD: An extensive search was performed in Medline, Embase, Scopus, Web of Science and CENTRAL databases until the end of March 15, 2020. Two independent researchers performed the screening, and finally the related studies were included. RESULTS: Only one clinical trial on the efficacy of antiviral therapy in management of COVID-19 was found. The results depicted that adding Lopinavir-Ritonavir to the standard treatment regimen of patients with severe COVID-19 has no benefits. Moreover, 21 case-series and case-report studies reported the prescription of antiviral agents in COVID-19, none of which can be used to determine the efficacy of antiviral therapies in confronting COVID-19. In addition, no clinical trials were found to be performed on the efficacy of antiviral agents in the management of SARS-CoV and MERS-CoV. CONCLUSION: The current evidence impede researchers from proposing an appropriate antiviral therapy against COVID-19, making the current situation a serious concern for international organizations such as World Health Organization (WHO). In the time of the current pandemic and future epidemics, organizations such as WHO should pursue more proactive actions and plan well-designed clinical trials so that their results can be used in managing future epidemics.", "qid": 30, "docid": "jlqee1b8", "rank": 29, "score": 0.8173664808273315}, {"content": "Title: A promising antiviral candidate drug for the COVID-19 pandemic: A mini-review of remdesivir Content: Remdesivir (GS-5734), a viral RNA-dependent RNA polymerase (RdRP) inhibitor that can be used to treat a variety of RNA virus infections, is expected to be an effective treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. On May 1, 2020, The U.S. Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) for remdesivir to treat COVID-19 patients. In light of the COVID-19 pandemic, this review presents comprehensive information on remdesivir, including information regarding the milestones, intellectual properties, anti-coronavirus mechanisms, preclinical research and clinical trials, and in particular, the chemical synthesis, pharmacology, toxicology, pharmacodynamics and pharmacokinetics of remdesivir. Furthermore, perspectives regarding the use of remdesivir for the treatment of COVID-19 are also discussed.", "qid": 30, "docid": "ygbfvjz8", "rank": 30, "score": 0.816947340965271}, {"content": "Title: A promising antiviral candidate drug for the COVID-19 pandemic: A mini-review of remdesivir. Content: Remdesivir (GS-5734), a viral RNA-dependent RNA polymerase (RdRP) inhibitor that can be used to treat a variety of RNA virus infections, is expected to be an effective treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. On May 1, 2020, The U.S. Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) for remdesivir to treat COVID-19 patients. In light of the COVID-19 pandemic, this review presents comprehensive information on remdesivir, including information regarding the milestones, intellectual properties, anti-coronavirus mechanisms, preclinical research and clinical trials, and in particular, the chemical synthesis, pharmacology, toxicology, pharmacodynamics and pharmacokinetics of remdesivir. Furthermore, perspectives regarding the use of remdesivir for the treatment of COVID-19 are also discussed.", "qid": 30, "docid": "bz1lz2ze", "rank": 31, "score": 0.8169472217559814}, {"content": "Title: Efficacy of remdesivir versus placebo for the treatment of COVID-19: A protocol for systematic review and meta-analysis of randomized controlled trials Content: Background: In spite of the global containment on prevention efforts, the spread of coronavirus disease 2019 (COVID-19) is continuing to rise, with 1.1 million confirmed cases and 60,124 deaths recorded worldwide since 04 April 2020. The outbreak has a significant threat to international health and economy. At present, there is no approved vaccine or treatment for the disease, while efforts are underway. Remdesivir, a nucleotide-analogue antiviral drug developed for Ebola, is determined to prevent and stop infections with COVID-19, while results are yet controversial. Here, we aim to conduct a systematic review and meta-analysis of randomized controlled trials to compare the effectiveness of remdesivir and placebo in patients with COVID-19. Method and analysis: We will search MEDLINE-PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and Google scholar databases without restriction in year of publication. We will include randomized controlled trials that assessed the effectiveness of remdesivir versus placebo for patients confirmed with COVID-19. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA 2015) guidelines for the design and reporting of the results. The primary endpoint will be time to clinical recovery. The secondary endpoints will be all cause mortality, discharged date, frequency of respiratory progression, and treatment-emergent adverse events. Two independent authors will perform study selection, data extraction, and methodology quality assessment. RevMan 5.3 software will be used for statistical analysis. Random/fixed effect model will be carried out to calculate mean differences for continuous outcomes and risk ratio for dichotomous outcomes between remdesivir and placebo. Ethics and dissemination: This study does not require ethical approval, because no participants data will be involved in this systematic review and meta-analysis. The findings of this study will be published in reputable and peer-reviewed journal. Registration: This review protocol is submitted in PROSPERO database for registration and we will include the registration number in the revised version of the manuscript. Keywords: 2019 novel coronavirus, 2019-nCoV, Coronavirus diseases 2019, COVID-19, SARS-cov-2, Remdesivir, Randomized Controlled Trials. Systematic review, Meta-analysis, protocol", "qid": 30, "docid": "aosmo568", "rank": 32, "score": 0.8152542114257812}, {"content": "Title: Coronavirus drug, water warning and virus-research funding. Content: One of the world\u2019s best hopes for treating COVID-19 \u2014 a compound called remdesivir \u2014 has been authorized as a therapy against the disease On 1 May, the US Food and Drug Administration (FDA) granted an \u2018emergency-use authorization\u2019 for clinicians to use the drug, which is administered intravenously, in hospitals for people with severe COVID-19", "qid": 30, "docid": "5kcl80sj", "rank": 33, "score": 0.8150530457496643}, {"content": "Title: Impacts of remdesivir on dynamics and efficacy stratified by the severity of COVID-19: a simulated two-arm controlled study Content: Background: The impact of remdesivir on length of stay of hospitalization, high-risk state, and death stratified by the severity of COVID-19 at enrollment is controversial. Methods: We applied a simulated two-arm controlled study design to the data on compassionate use of remdesivir as a secondary analysis. Dynamics of risk states and death from COVID-19 patients defined by the six-point disease severity recommended by the WHO R&D and the time to discharge from hospital were used to evaluate the efficacy of remdesivir treatment compared with standard care. Results: Stratified by the risk state at enrollment, low-risk patients exhibited the highest efficacy of remdesivir in reducing subsequent progression to high-risk state by 67% (relative risk (RR)=0.33,95% CI: 0.30-0.35) and further to death by 55% (RR=0.45, 95%CI: 0.39-0.50). For the medium-risk patients, less but still statistically significant efficacy results were noted in reducing progression to high-risk state by 52% (RR=0.48, 95% CI: 0.45-0.51) and further to death by 40% (RR=0.60, 95% CI:0.54-0.66). High-risk state patients treated with remdesivir led to a 25% statistically significant reduction in death (RR=0.75, 95% CI: 0.69-0.82). Regarding the outcome of discharge, remdesivir treatment was most effective for medium-risk patients at enrollment (RR: 1.41, 95% CI: 1.35-1.47) followed by high- (RR=1.34, 95% CI: 1.27-1.42) and low-risk patients (RR=1.28, 95% CI: 1.25-1.31). Conclusion: Our results with a simulated two-arm controlled study have provided a new insight into the precision treatment of remdesivir for COVID-19 patients based on risk-stratified efficacy.", "qid": 30, "docid": "4od9gu6y", "rank": 34, "score": 0.8136669993400574}, {"content": "Title: The use of convalescent plasma therapy and remdesivir in the successful management of a critically ill obstetric patient with novel coronavirus 2019 infection: A case report Content: Remdesivir is a novel therapeutic with known activity against SARS CoV-2 and related coronaviruses. Remdesivir, as well as convalescent plasma therapy, are currently under investigation as potential therapies for patients with Coronavirus Disease 19 (COVID-19). In this case report we summarize the use of convalescent plasma therapy and then remdesivir as a late addition in the treatment of a critically ill obstetric patient with COVID-19. The patient subsequently improved, was extubated 5 days after initiation of remdesivir, was transitioned to room air 24 h later, and discharged at the completion of remdesivir therapy.", "qid": 30, "docid": "fxi8ss2s", "rank": 35, "score": 0.81192547082901}, {"content": "Title: The use of convalescent plasma therapy and remdesivir in the successful management of a critically ill obstetric patient with novel coronavirus 2019 infection: A case report Content: Remdesivir is a novel therapeutic with known activity against SARS CoV-2 and related coronaviruses. Remdesivir, as well as convalescent plasma therapy, are currently under investigation as potential therapies for patients with Coronavirus Disease 19 (COVID-19). In this case report we summarize the use of convalescent plasma therapy and then remdesivir as a late addition in the treatment of a critically ill obstetric patient with COVID-19. The patient subsequently improved, was extubated 5\u00e2\u0080\u00afdays after initiation of remdesivir, was transitioned to room air 24\u00e2\u0080\u00afh later, and discharged at the completion of remdesivir therapy.", "qid": 30, "docid": "6wwmbgw7", "rank": 36, "score": 0.8115181922912598}, {"content": "Title: Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial Content: Summary Background No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. Methods We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged \u226518 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2\u201310 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir\u2013ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656. Findings Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1\u00b723 [95% CI 0\u00b787\u20131\u00b775]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1\u00b752 [0\u00b795\u20132\u00b743]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. Interpretation In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. Funding Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.", "qid": 30, "docid": "bzeqs5oh", "rank": 37, "score": 0.8114854097366333}, {"content": "Title: Antiviral therapy in management of COVID-19: a systematic review on current evidence Content: Background: The purpose of the current systematic review is to evaluate the efficacy of antiviral therapies in treatment of COVID-19 In addition, clinical trials on the efficacy of antiviral therapies in the management of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov) or Middle East Respiratory Syndrome coronavirus (MERS-CoV) have also been reviewed, in order to identify potential treatment options for COVID-19 Method: An extensive search was performed in Medline, Embase, Scopus, Web of Science and CENTRAL databases until the end of March 15, 2020 Two independent researchers performed the screening, and finally the related studies were included Results: Only one clinical trial on the efficacy of antiviral therapy in management of COVID-19 was found The results depicted that adding Lopinavir-Ritonavir to the standard treatment regimen of patients with severe COVID-19 has no benefits Moreover, 21 case-series and case-report studies reported the prescription of antiviral agents in COVID-19, none of which can be used to determine the efficacy of antiviral therapies in confronting COVID-19 In addition, no clinical trials were found to be performed on the efficacy of antiviral agents in the management of SARS-CoV and MERS-CoV Conclusion: The current evidence impede researchers from proposing an appropriate antiviral therapy against COVID-19, making the current situation a serious concern for international organizations such as World Health Organization (WHO) In the time of the current pandemic and future epidemics, organizations such as WHO should pursue more proactive actions and plan well-designed clinical trials so that their results can be used in managing future epidemics", "qid": 30, "docid": "be3udel6", "rank": 38, "score": 0.8101638555526733}, {"content": "Title: Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial Content: BACKGROUND: No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. METHODS: We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged &#8805;18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2-10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir-ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656. FINDINGS: Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1\u00b723 [95% CI 0\u00b787-1\u00b775]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1\u00b752 [0\u00b795-2\u00b743]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. INTERPRETATION: In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. FUNDING: Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.", "qid": 30, "docid": "c74zdtnn", "rank": 39, "score": 0.8090402483940125}, {"content": "Title: Antivirals for COVID-19. Content: Drugs targeting RNA respiratory viruses has resulted in few effective therapies, highlighting challenges for antivirals to treat COVID-19. Several antivirals are being investigated for symptomatic COVID-19 but no definitive data support their clinical use. Remdesivir, with good in vitro activity against SARS-CoV2, appeared to result in favorable outcomes for hospitalized patients in a compassionate use series with shortened time to recovery and a modest decrease in mortality. Currently, remdesivir is available in phase III clinical trials, the compassionate use program, and eventually through the emergency use authorization. A randomized controlled trial of lopinavir/ritonavir demonstrated no apparent clinical or virologic benefit and drug-drug interactions and side effects further limit its utility. Antivirals to treat influenza (oseltamivir) have limited activity against SARS-CoV-2, but favipiravir and umifenovir, influenza antivirals available internationally, have distinct viral targets and require further investigation. Antivirals with evidence of clinical activity must be studied as treatment and prophylaxis for those at high risk for severe COVID-19.", "qid": 30, "docid": "eaqxifxu", "rank": 40, "score": 0.8088424205780029}, {"content": "Title: Remdesivir in Treatment of COVID-19: A Systematic Benefit\u2013Risk Assessment Content: INTRODUCTION: There is a need to identify effective, safe treatments for COVID-19 (coronavirus disease) rapidly, given the current, ongoing pandemic. A systematic benefit\u2013risk assessment was designed and conducted to examine the benefit\u2013risk profile of remdesivir in COVID-19 patients compared with standard of care, placebo or other treatments. A key objective of this study was to provide a platform for a dynamic systematic benefit\u2013risk evaluation, which starts with inevitably limited information (to meet the urgent unmet public health need worldwide), then update the benefit\u2013risk evaluation as more data become available. METHODS: The Benefit\u2013Risk Action Team (BRAT) framework was used to assess the overall benefit\u2013risk of the use of remdesivir as a treatment for COVID-19 compared with standard of care, placebo or other treatments. We searched PubMed, Google Scholar and government agency websites to identify literature reporting clinical outcomes in patients taking remdesivir for COVID-19. A value tree was constructed and key benefits and risks were ranked by two clinicians in order of considered importance. RESULTS: Using the BRAT method, several key benefits and risks for use of remdesivir in COVID-19 compared with placebo have been identified. In one trial, the benefit of time to clinical improvement was not statistically significant (21 vs 23 days, HR 1.23, 95% CI 0.87\u20131.75), although the study was underpowered. In another trial, a shorter time to recovery in patients treated with remdesivir was observed (11 vs 15 days), with non-significant reduced mortality risk (8% vs 12%). Risk data were only available from one trial. This trial reported fewer serious adverse events in patients taking remdesivir (18%) compared with the placebo group (26%); however, more patients in the remdesivir group discontinued treatment as a result of an adverse event compared with those patients receiving placebo (12% vs 5%). CONCLUSIONS: Preliminary clinical trial results suggest that there may be a favourable benefit\u2013risk profile for remdesivir compared with placebo in severe COVID-19 infection and further data on benefits would strengthen this evaluation. There is limited safety data for remdesivir, which should be obtained in further studies. The current framework summarises the key anticipated benefits and risks for which further data are needed. Ongoing clinical trial data can be incorporated into the framework when available to provide an updated benefit\u2013risk assessment.", "qid": 30, "docid": "xrvynfr6", "rank": 41, "score": 0.8081024885177612}, {"content": "Title: Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses Content: Abstract Recent international epidemics of coronavirus-associated illnesses underscore the urgent medical and public health need for vaccine development and regulatory body approved therapies. In particular, the current coronavirus disease 2019 (COVID-19) pandemic has quickly intensified interest in developing treatment options to mitigate impact on human life. Remdesivir (GS-5734\u2122) is a broad-spectrum antiviral drug that is now being tested as a potential treatment for COVID-19 in international, multi-site clinical trials. Currently available evidence about the antiviral effects of remdesivir against coronaviruses is primarily based on in vitro and in vivo studies (including some on a chemically related compound, GS-441524\u2122), which have demonstrated largely favorable findings. As the pandemic progresses, information from human compassionate use cases will continue to accumulate before the clinical trials are concluded. It is imperative for public health practitioners and the One Health community to stay up to date on the most promising potential therapeutic options that are under investigation. Thus, the purpose of this review is to synthesize the knowledge to date about remdesivir as a therapeutic option for coronaviruses, with a special focus on information relevant to the One Health community.", "qid": 30, "docid": "95fc828i", "rank": 42, "score": 0.8075391054153442}, {"content": "Title: Efficacy of remdesivir in patients with COVID-19: a protocol for systematic review and meta-analysis of randomised controlled trials Content: BACKGROUND: Despite global containment measures to fight the coronavirus disease 2019 (COVID-19), the pandemic continued to rise, rapidly spread across the world, and resulting in 2.6 million confirmed cases and 185 061 deaths worldwide as of 23 April 2020. Yet, there are no approved vaccines or drugs to make the disease less deadly, while efforts are underway. Remdesivir, a nucleotide-analogue antiviral drug developed for Ebola, is determined to prevent and stop infections with COVID-19, while results are yet controversial. Here, we aim to conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) to evaluate the efficacy of remdesivir in patients with COVID-19. METHOD AND ANALYSIS: We will search MEDLINE-PubMed, Embase, Cochrane Library, ClinicalTrials.gov and Google scholar databases for articles published as of 30 June 2020 and we will complete the study on 30 August 2020. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 guidelines for the design and reporting of the results. We will include RCTs that assessed the efficacy of remdesivir versus placebo or standard of care. The primary endpoint will be time to clinical recovery. The secondary endpoints will be proportion of participants relieved from clinical symptoms defined at the time (in hours) from initiation of the study treatment, all-cause mortality, discharged date, frequency of respiratory progression and treatment-emergent adverse events. RevMan V.5.3 software will be used for statistical analysis. Random effects model will be carried out to calculate mean differences for continuous outcome data and risk ratio for dichotomous outcome data between remdesivir and placebo or standard of care. ETHICS AND DISSEMINATION: There are no ethical considerations associated with this study as we will use publicly available data from previously published studies. We plan to publish results in open-access peer-reviewed journals and present at international and national conferences. PROSPERO REGISTRATION NUMBER: CRD42020177953.", "qid": 30, "docid": "kcrmi3x8", "rank": 43, "score": 0.8071647882461548}, {"content": "Title: Probable Molecular Mechanism of Remdesivir for the Treatment of COVID-19: Need to Know More Content: Abstract COVID-19 is now pandemic throughout the world. Scientist, doctors are searching for effective therapy of this diseases. The remdesivir, an antiviral drug, is appeared as \u2018molecule of hope\u2019 for the treatment of this disease. USFDA approve this drug for the treatment of COVID-19. The molecular mechanism is unknown. In this paper, we tried to describe the probable molecular mechanism of remdesivir to inhibit the RNA synthesis of SARS-CoV-2. However, more detail mechanism is needed to understand mechanism of action of remdesivir.", "qid": 30, "docid": "2lwzhqer", "rank": 44, "score": 0.8067977428436279}, {"content": "Title: Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19 Content: [Image: see text] The global pandemic of SARS-CoV-2, the causative viral pathogen of COVID-19, has driven the biomedical community to action\u2014to uncover and develop antiviral interventions. One potential therapeutic approach currently being evaluated in numerous clinical trials is the agent remdesivir, which has endured a long and winding developmental path. Remdesivir is a nucleotide analogue prodrug that perturbs viral replication, originally evaluated in clinical trials to thwart the Ebola outbreak in 2014. Subsequent evaluation by numerous virology laboratories demonstrated the ability of remdesivir to inhibit coronavirus replication, including SARS-CoV-2. Here, we provide an overview of remdesivir\u2019s discovery, mechanism of action, and the current studies exploring its clinical effectiveness.", "qid": 30, "docid": "zdfx3zo3", "rank": 45, "score": 0.80634605884552}, {"content": "Title: Remdesivir in Treatment of COVID-19: A Systematic Benefit-Risk Assessment Content: INTRODUCTION: There is a need to identify effective, safe treatments for COVID-19 (coronavirus disease) rapidly, given the current, ongoing pandemic. A systematic benefit-risk assessment was designed and conducted to examine the benefit-risk profile of remdesivir in COVID-19 patients compared with standard of care, placebo or other treatments. A key objective of this study was to provide a platform for a dynamic systematic benefit-risk evaluation, which starts with inevitably limited information (to meet the urgent unmet public health need worldwide), then update the benefit-risk evaluation as more data become available. METHODS: The Benefit-Risk Action Team (BRAT) framework was used to assess the overall benefit-risk of the use of remdesivir as a treatment for COVID-19 compared with standard of care, placebo or other treatments. We searched PubMed, Google Scholar and government agency websites to identify literature reporting clinical outcomes in patients taking remdesivir for COVID-19. A value tree was constructed and key benefits and risks were ranked by two clinicians in order of considered importance. RESULTS: Using the BRAT method, several key benefits and risks for use of remdesivir in COVID-19 compared with placebo have been identified. In one trial, the benefit of time to clinical improvement was not statistically significant (21 vs 23 days, HR 1.23, 95% CI 0.87-1.75), although the study was underpowered. In another trial, a shorter time to recovery in patients treated with remdesivir was observed (11 vs 15 days), with non-significant reduced mortality risk (8% vs 12%). Risk data were only available from one trial. This trial reported fewer serious adverse events in patients taking remdesivir (18%) compared with the placebo group (26%); however, more patients in the remdesivir group discontinued treatment as a result of an adverse event compared with those patients receiving placebo (12% vs 5%). CONCLUSIONS: Preliminary clinical trial results suggest that there may be a favourable benefit-risk profile for remdesivir compared with placebo in severe COVID-19 infection and further data on benefits would strengthen this evaluation. There is limited safety data for remdesivir, which should be obtained in further studies. The current framework summarises the key anticipated benefits and risks for which further data are needed. Ongoing clinical trial data can be incorporated into the framework when available to provide an updated benefit-risk assessment.", "qid": 30, "docid": "gxogowwb", "rank": 46, "score": 0.8062229156494141}, {"content": "Title: Early experience with remdesivir in SARS-CoV-2 pneumonia Content: At present, there is no definitive antiviral treatment for coronavirus disease 2019 (COVID-19). We describe our early experience with remdesivir in four critically ill COVID-19 patients. Patients received a 200 mg loading dose, followed by 100 mg daily intravenously for up to 10 days. All patients had been previously treated with other antivirals before remdesivir initiation. One patient experienced a torsade de pointes requiring cardiac resuscitation and one died due to multiple organ failure. Three patients showed biochemical signs of liver injury. Lymphocyte count increased in all patients soon after remdesivir initiation. Nasal swab SARS-CoV-2 RNA became negative in three of four patients after 3 days of therapy. We observed an in vivo virological effect of remdesivir in four critically ill, COVID-19 patients, coupled with a significant burden of adverse events. Although limited by the low number of subjects studied, our preliminary experience may be relevant for clinicians treating COVID-19.", "qid": 30, "docid": "mp3qb33p", "rank": 47, "score": 0.8060899972915649}, {"content": "Title: Remdesivir Efficacy in Coronavirus Disease 2019 (COVID-19): A Systematic Review Content: Background: Researchers are working hard to find an effective treatment for the new coronavirus 2019. We performed a comprehensive systematic review to investigate the latest clinical evidence on the treatment efficacy and safety of Remdesivir in hospitalized patients with COVID-19. Methods: We performed a systematic search of the Pubmed, Embase, Web of Science, Google scholar, and MedRxiv for relevant observational and interventional studies. Measured outcomes were mortality rates, improvement rates, time to clinical improvement, all adverse event rates and severe adverse event rates. Results: 3 RCTs and 2 cohorts were included in our study. In 2 cohort studies, patients received Remdesivir for 10 days. 2 RCTs evaluated 10-day treatment of Remdesivir efficacy versus placebo group and the other RCT compared its 5-day regimen versus 10-day regimen. Visual inspection of the forest plots revealed that Remdesivir efficacy was not much different in reducing 28-day mortality versus 14-day mortality rates. Besides, 10-day treatment regimen overpowers 5-day treatment and placebo in decreasing time to clinical improvement. All adverse event rates did not have significant difference; however, severe adverse event rate was lower in 5-day Remdesivir group compared to 10-day and placebo groups. Conclusion: 5-day course of Remdesivir therapy in COVID-19 patients is probably efficacious and safe and patients without invasive mechanical ventilation benefit the most. Treatment can be extended to 10 days if satisfactory improvement is not seen by day 5. Most benefits from Remdesivir therapy take place in the first 14 days of the start of the treatment.", "qid": 30, "docid": "6tcwu832", "rank": 48, "score": 0.8055413365364075}, {"content": "Title: Possible therapeutic agents for COVID-19: a comprehensive review Content: INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged in China. There are no available vaccines or antiviral drugs for COVID-19 patients. Herein, we represented possible therapeutic agents that may stand as a potential therapy against COVID-19. AREAS COVERED: We searched PubMed, Google Scholar, and clinicaltrials.gov for relevant papers. We showed some agents with potentially favorable efficacy, acceptable safety as well as good pharmacokinetic profiles. Several therapies are under assessment to evaluate their efficacy and safety for COVID-19. However, some drugs were withdrawn due to their side effects after demonstrating some clinical efficacy. Indeed, the most effective therapies could be organ function support, convalescent plasma, anticoagulants, and immune as well as antiviral therapies, especially anti-influenza drugs due to the similarities between respiratory viruses regarding viral entry, uncoating, and replication. We encourage giving more attention to favipiravir, remdesivir, and measles vaccine. EXPERT OPINION: A combination, at least dual or even triple therapy, of the aforementioned efficacious and safe therapies is greatly recommended for COVID-19. Further, patients should have a routine assessment for their coagulation and bleeding profiles as well as their inflammatory and cytokine concentrations.", "qid": 30, "docid": "nau52q1s", "rank": 49, "score": 0.8046692609786987}, {"content": "Title: Possible therapeutic agents for COVID-19: a comprehensive review. Content: INTRODUCTION Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged in China. There are no available vaccines or antiviral drugs for COVID-19 patients. Herein, we represented possible therapeutic agents that may stand as a potential therapy against COVID-19. AREAS COVERED We searched PubMed, Google Scholar, and clinicaltrials.gov for relevant papers. We showed some agents with potentially favorable efficacy, acceptable safety as well as good pharmacokinetic profiles. Several therapies are under assessment to evaluate their efficacy and safety for COVID-19. However, some drugs were withdrawn due to their side effects after demonstrating some clinical efficacy. Indeed, the most effective therapies could be organ function support, convalescent plasma, anticoagulants, and immune as well as antiviral therapies, especially anti-influenza drugs due to the similarities between respiratory viruses regarding viral entry, uncoating, and replication. We encourage giving more attention to favipiravir, remdesivir, and measles vaccine. EXPERT OPINION A combination, at least dual or even triple therapy, of the aforementioned efficacious and safe therapies is greatly recommended for COVID-19. Further, patients should have a routine assessment for their coagulation and bleeding profiles as well as their inflammatory and cytokine concentrations.", "qid": 30, "docid": "zgtxfx28", "rank": 50, "score": 0.8032744526863098}, {"content": "Title: Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post_treatment hospitalisation status Content: SARS-CoV-2 is causing an increasing number of deaths worldwide because no effective treatment is currently available. Remdesivir has shown in vitro activity against coronaviruses and is a possible antiviral treatment for SARS-CoV-2 infection. This prospective (compassionate), open-label study of remdesivir, which was conducted at Luigi Sacco Hospital, Milan, Italy, between February 23 and March 20, 2020, involved patients with SARS-CoV-2 pneumonia aged \u226518 years undergoing mechanical ventilation or with an oxygen saturation level of \u226494% in air or a National Early Warning Score 2 of \u22654. The primary outcome was the change in clinical status based on a 7-category ordinal scale (1 = not hospitalised, resuming normal daily activities; 7 = deceased). The 35 patients enrolled from February 23 to March 20, 2020, included 18 in intensive care unit (ICU), and 17 in our infectious diseases ward (IDW). The 10-day course of remdesivir was completed by 22 patients (63%) and discontinued by 13, of whom eight (22.8%) discontinued because of adverse events. The median follow-up was 39 days (IQR 25-44). At day 28, 14 (82.3%) patients from IDW were discharged, two were still hospitalized and one died (5.9%), whereas in ICU 6 (33.3%) were discharged, 8 (44.4%) patients died, three (16.7%) were still mechanically ventilated and one (5.6%) was improved but still hospitalized. Hypertransaminasemia and acute kidney injury were the most frequent severe adverse events observed (42.8% and 22.8% of the cases, respectively). Our data suggest that remdesivir can benefit patients with SARS-CoV-2 pneumonia hospitalised outside ICU where clinical outcome was better and adverse events are less frequently observed. Ongoing randomised controlled trials will clarify its real efficacy and safety, who to treat, and when.", "qid": 30, "docid": "nzxbogga", "rank": 51, "score": 0.8026896715164185}, {"content": "Title: Available Evidence and Ongoing Clinical Trials of Remdesivir: Could It Be a Promising Therapeutic Option for COVID-19? Content: The novel coronavirus strain, severe acute respiratory syndrome coronavirus-2, the causative agent of COVID-19 emerged in Wuhan, China, in December 2019 and is skyrocketing throughout the globe and become a global public health emergency. Despite promising preventive measures being taken, there is no vaccine or drug therapy officially approved to prevent or treat the infection. Everybody is waiting the findings of ongoing clinical trials in various chemical and biological products. This review is specifically aimed to summarize the available evidence and ongoing clinical trials of remdesivir as a potential therapeutic option for COVID-19. Remdesivir is an investigational drug having broad spectrum antiviral activity with its target RNA dependent RNA polymerase. It has not yet been officially approved for Ebola and Coronaviruses. Several studies showed that remdesivir had promising in vitro and in vivo antiviral activities against SARS-CoV-1 and MERS-CoV strains. On the top of this, it exhibited a promising in vitro activity against SARS-CoV-2 strains though there are no published studies that substantiate its activity in vivo until the time of this review. There are few phase 3 randomized double-blind placebo controlled trials on the way to investigate the safety and efficacy of remdesivir. Of which, one completed double blind, placebo controlled trial showed that remdesivir showed faster time to clinical improvement in severe COVID-19 patients compared to placebo though not found statistically significant. In addition, two phase 3 randomized open label clinical trials coordinated by Gilead Sciences are being conducted. In addition, WHO Solidarity trial and INSERM DisCoVeRy trials (randomized open labels) were launched recently.", "qid": 30, "docid": "tasbdhs1", "rank": 52, "score": 0.8022670745849609}, {"content": "Title: Compassionate Use of Remdesivir for Patients with Severe Covid-19 Content: BACKGROUND: Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. METHODS: We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day. RESULTS: Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. CONCLUSIONS: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.)", "qid": 30, "docid": "oyr4klqk", "rank": 53, "score": 0.8021265864372253}, {"content": "Title: Remdesivir: Review of Pharmacology, Pre-clinical Data, and Emerging Clinical Experience for COVID-19 Content: The global pandemic of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created an urgent need for effective antivirals. Remdesivir (formerly GS-5734) is a nucleoside analogue pro-drug currently being evaluated in COVID-19 clinical trials. Its unique structural features allow high concentrations of the active triphosphate metabolite to be delivered intracellularly and it evades proofreading to successfully inhibit viral RNA synthesis. In pre-clinical models, remdesivir has demonstrated potent antiviral activity against diverse human and zoonotic \u00df-coronaviruses, including SARS-CoV-2. In this article, we critically review available data on remdesivir with an emphasis on biochemistry, pharmacology, pharmacokinetics, and in vitro activity against coronaviruses as well as clinical experience and current progress in COVID-19 clinical trials.", "qid": 30, "docid": "gk2p9w2d", "rank": 54, "score": 0.8015972375869751}, {"content": "Title: Compassionate Use of Remdesivir for Patients with Severe Covid-19 Content: BACKGROUND: Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. METHODS: We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day. RESULTS: Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. CONCLUSIONS: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.).", "qid": 30, "docid": "kxds6r7t", "rank": 55, "score": 0.8014587759971619}, {"content": "Title: Remdesivir in treatment of COVID-19: A systematic benefit-risk assessment Content: Background: There is a need to identify effective, safe treatments for COVID-19 (coronavirus disease) rapidly, given the current, ongoing pandemic. A systematic benefit-risk assessment was designed and conducted to strengthen the ongoing understanding of the benefit-risk balance for remdesivir in COVID-19 treatment by using a structured method which uses all available data. Methods: The Benefit-Risk Action Team (BRAT) framework was used to assess the overall benefit-risk of the use of remdesivir as a treatment for COVID-19 compared to standard of care, placebo or other treatments. We searched PubMed,Google Scholar and government agency websites to identify literature reporting clinical outcomes in patients taking remdesivir for COVID-19. A value tree was constructed and key benefits and risks were ranked by two clinicians in order of considered importance. Results: Several key benefits and risks for use of remdesivir in COVID-19 compared to placebo have been identified. In one trial, the benefit of time to clinical improvement was not statistically significant (21 vs 23 days, HR=1.23, 95% CI: 0.87, 1.75), although the study was underpowered. In another trial, a shorter time to recovery in patients treated with remdesivir was observed (11 vs 15 days), with non-significant reduced mortality risk (8% vs 12%). Risk data were only available from one trial. This trial reported fewer serious adverse events in patients taking remdesivir (18%) comparted to the placebo group (26%), however more patients in the remdesivir group discontinued treatment as a result of an adverse event compared to those patients receiving placebo (12% vs 5%). Conclusions: Preliminary clinical trial results suggest a favourable benefit-risk profile for remdesivir compared to placebo, however there is limited safety data available at the current time. The current framework summarises the key anticipated benefits and risks for which further data are needed. Ongoing clinical trial data can be incorporated into the framework when available to provide an updated benefit-risk assessment.", "qid": 30, "docid": "dieaqxmi", "rank": 56, "score": 0.8011918067932129}, {"content": "Title: The COVID-19 pandemic: is our medicine still evidence-based? Content: There is no randomized controlled trial that demonstrated the efficacy of antiviral therapy against COVID-19 yet. However, physicians are prescribing different drugs to a large part of COVID-19 population in the hope they will cure them. This does not reflect the evidence-based medicine approach. What we need is more evidence-based knowledge about what routine care practices we should to apply to ameliorate symptoms of patients and fight COVID-19 pathology.", "qid": 30, "docid": "x82yaoxc", "rank": 57, "score": 0.8011013269424438}, {"content": "Title: An Update on Current Therapeutic Drugs Treating COVID-19 Content: The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presented unprecedented challenges to the healthcare systems in almost every country around the world. Currently, there are no proven effective vaccines or therapeutic agents against the virus. Current clinical management includes infection prevention and control measures and supportive care including supplemental oxygen and mechanical ventilatory support. Evolving research and clinical data regarding the virologic SARS-CoV-2 suggest a potential list of repurposed drugs with appropriate pharmacological effects and therapeutic efficacies in treating COVID-19 patients. In this review, we will update and summarize the most common and plausible drugs for the treatment of COVID-19 patients. These drugs and therapeutic agents include antiviral agents (remdesivir, hydroxychloroquine, chloroquine, lopinavir, umifenovir, favipiravir, and oseltamivir), and supporting agents (Ascorbic acid, Azithromycin, Corticosteroids, Nitric oxide, IL-6 antagonists), among others. We hope that this review will provide useful and most updated therapeutic drugs to prevent, control, and treat COVID-19 patients until the approval of vaccines and specific drugs targeting SARS-CoV-2.", "qid": 30, "docid": "0jr31q5g", "rank": 58, "score": 0.8000813126564026}, {"content": "Title: Probable Molecular Mechanism of Remdesivir for the Treatment of COVID-19: Need to Know More Content: COVID-19 is now pandemic throughout the world. Scientist, doctors are searching for effective therapy of this diseases. The remdesivir, an antiviral drug, is appeared as 'molecule of hope' for the treatment of this disease. USFDA gave emergency approval to this drug for the treatment of COVID-19. The molecular mechanism is unknown. In this paper, we tried to describe the probable molecular mechanism of remdesivir to inhibit the RNA synthesis of SARS-CoV-2. However, more detail mechanism is needed to understand mechanism of action of remdesivir.", "qid": 30, "docid": "8n6eybze", "rank": 59, "score": 0.7999390363693237}, {"content": "Title: COVID-19 Treatment: Close to a Cure? - A Rapid Review of Pharmacotherapies for the Novel Coronavirus Content: Currently, there is no approved therapy for COVID-19. The World Health Organization therefore endorse supportive care only. However, frontline clinicians and researchers have been experimenting with several virus-based and host-based therapeutics since the outbreak in China. China's National Health Commission has issued the first COVID-19 Treatment Guideline with therapy suggestions (7th edition attached) which inspired following clinical studies worldwide. Major therapeutics are evaluated in this review. Key evidence from in vitro researches, animal models and clinical researches in emerging coronaviruses are examined. Antiviral therapies remdesivir, lopinavir/ritonavir and umifenovir, if considered, could be initiated before the peak of viral replication for optimal outcomes. Ribavirin may be beneficial as an add-on therapy and is ineffective as a monotherapy. Corticosteroids use should be limited to indicating comorbidities. IVIG is not recommended due to lack of data in COVID-19. Xuebijing may benefit patients with complications of bacterial pneumonia or sepsis. The efficacy of interferon is unclear due to conflicting outcomes in coronavirus studies. Chloroquine and hydroxychloroquine have shown in vitro inhibition of SARS-CoV-2, and the studies on clinical efficacy and whether the benefits outweigh the risk of dysrhythmias remain inconclusive. For patients who developed cytokine release syndrome, interleukin-6 inhibitors may be beneficial.", "qid": 30, "docid": "ptoyu3in", "rank": 60, "score": 0.7998474836349487}, {"content": "Title: COVID-19 Treatment: Close to a Cure? \u2013 A Rapid Review of Pharmacotherapies for the Novel Coronavirus Content: Currently, there is no approved therapy for COVID-19. The World Health Organization therefore endorse supportive care only. However, frontline clinicians and researchers have been experimenting with several virus-based and host-based therapeutics since the outbreak in China. China's National Health Commission has issued the first COVID-19 Treatment Guideline with therapy suggestions (7(th) edition attached) which inspired following clinical studies worldwide. Major therapeutics are evaluated in this review. Key evidence from in vitro researches, animal models and clinical researches in emerging coronaviruses are examined. Antiviral therapies remdesivir, lopinavir/ritonavir and umifenovir, if considered, could be initiated before the peak of viral replication for optimal outcomes. Ribavirin may be beneficial as an add-on therapy and is ineffective as a monotherapy. Corticosteroids use should be limited to indicating comorbidities. IVIG is not recommended due to lack of data in COVID-19. Xuebijing may benefit patients with complications of bacterial pneumonia or sepsis. The efficacy of interferon is unclear due to conflicting outcomes in coronavirus studies. Chloroquine and hydroxychloroquine have shown in vitro inhibition of SARS-CoV-2, and the studies on clinical efficacy and whether the benefits outweigh the risk of dysrhythmias remain inconclusive. For patients who developed cytokine release syndrome, interleukin-6 inhibitors may be beneficial.", "qid": 30, "docid": "369kax2m", "rank": 61, "score": 0.799784779548645}, {"content": "Title: Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post-treatment hospitalisation status Content: SARS-CoV-2 is causing an increasing number of deaths worldwide because no effective treatment is currently available. Remdesivir has shown in vitro activity against coronaviruses and is a possible antiviral treatment for SARS-CoV-2 infection. This prospective (compassionate), open-label study of remdesivir, which was conducted at Luigi Sacco Hospital, Milan, Italy, between February 23 and March 20, 2020, involved patients with SARS-CoV-2 pneumonia aged &#8805;18 years undergoing mechanical ventilation or with an oxygen saturation level of &#8804;94 % in air or a National Early Warning Score 2 of &#8805;4. The primary outcome was the change in clinical status based on a 7-category ordinal scale (1 = not hospitalised, resuming normal daily activities; 7 = deceased). The 35 patients enrolled from February 23 to March 20, 2020, included 18 in intensive care unit (ICU), and 17 in our infectious diseases ward (IDW). The 10-day course of remdesivir was completed by 22 patients (63 %) and discontinued by 13, of whom eight (22.8 %) discontinued because of adverse events. The median follow-up was 39 days (IQR 25-44). At day 28, 14 (82.3 %) patients from IDW were discharged, two were still hospitalized and one died (5.9 %), whereas in ICU 6 (33.3 %) were discharged, 8 (44.4 %) patients died, three (16.7 %) were still mechanically ventilated and one (5.6 %) was improved but still hospitalized. Hypertransaminasemia and acute kidney injury were the most frequent severe adverse events observed (42.8 % and 22.8 % of the cases, respectively). Our data suggest that remdesivir can benefit patients with SARS-CoV-2 pneumonia hospitalised outside ICU where clinical outcome was better and adverse events are less frequently observed. Ongoing randomised controlled trials will clarify its real efficacy and safety, who to treat, and when.", "qid": 30, "docid": "pdc3bv33", "rank": 62, "score": 0.7994011044502258}, {"content": "Title: Remdesivir: Review of pharmacology, pre\u2010clinical data and emerging clinical experience for COVID\u201019 Content: The global pandemic of novel coronavirus disease 2019 (COVID\u201019) caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) has created an urgent need for effective antivirals. Remdesivir (formerly GS\u20105734) is a nucleoside analogue pro\u2010drug currently being evaluated in COVID\u201019 clinical trials. Its unique structural features allow high concentrations of the active triphosphate metabolite to be delivered intracellularly and it evades proofreading to successfully inhibit viral RNA synthesis. In pre\u2010clinical models, remdesivir has demonstrated potent antiviral activity against diverse human and zoonotic \u03b2\u2010coronaviruses, including SARS\u2010CoV\u20102. In this article we critically review available data on remdesivir with an emphasis on biochemistry, pharmacology, pharmacokinetics and in vitro activity against coronaviruses as well as clinical experience and current progress in COVID\u201019 clinical trials.", "qid": 30, "docid": "uo8k6qic", "rank": 63, "score": 0.7986317873001099}, {"content": "Title: Medical Management of COVID-19: Evidence and Experience Content: Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and this infectious disease is termed COVID-19 in short. On a global scale, as of June 1, 2020, the World Health Organization (WHO) published statistics of 6,057,853 infected patients and 371,166 deaths worldwide. Despite reported observational data about the experimental use of certain drugs, there is no conclusively proven curative therapy for COVID-19 as of now; however, remdesivir received emergency use authorization (EUA) by the Food and Drug Administration (FDA) recently for use in patients hospitalized with COVID-19. There are several ongoing clinical trials related to the pharmacological choices of therapy for COVID-19 patients; however, drug trials related to observational studies so far have yielded mixed results and therefore have created a sense of confusion among healthcare professionals (HCPs). In this review article, we seek to collate and provide a summary of treatment strategies for COVID-19 patients with a variable degree of illness and discuss pharmacologic and other therapies intended to be used either as experimental medicine/therapy or as part of supportive care in complicated cases of COVID-19.", "qid": 30, "docid": "svnz1ghh", "rank": 64, "score": 0.798628568649292}, {"content": "Title: Treatment options for COVID-19: the reality and challenges Content: Abstract An outbreak related to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019. An extremely high potential for dissemination resulted in the global coronavirus disease 2019 (COVID-19) pandemic in 2020. Despite the worsening trends of COVID-19, no drugs are validated to have significant efficacy in clinical treatment of COVID-19 patients in large-scale studies. Remdesivir is considered the most promising antiviral agent; it works by inhibiting the activity of RNA-dependent RNA polymerase (RdRp). A large-scale study investigating the clinical efficacy of remdesivir (200 mg on day 1, followed by 100 mg once daily) is on-going. The other excellent anti-influenza RdRp inhibitor favipiravir is also being clinically evaluated for its efficacy in COVID-19 patients. The protease inhibitor lopinavir/ritonavir (LPV/RTV) alone is not shown to provide better antiviral efficacy than standard care. However, the regimen of LPV/RTV plus ribavirin was shown to be effective against SARS-CoV in vitro. Another promising alternative is hydroxychloroquine (200 mg thrice daily) plus azithromycin (500 mg on day 1, followed by 250 mg once daily on day 2-5), which showed excellent clinical efficacy on Chinese COVID-19 patients and anti-SARS-CoV-2 potency in vitro. The roles of teicoplanin (which inhibits the viral genome exposure in cytoplasm) and monoclonal and polyclonal antibodies in the treatment of SARS-CoV-2 are under investigation. Avoiding the prescription of non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors, or angiotensin II type I receptor blockers is advised for COVID-19 patients.", "qid": 30, "docid": "j8n06hzx", "rank": 65, "score": 0.7979377508163452}, {"content": "Title: Old and re-purposed drugs for the treatment of COVID-19 Content: INTRODUCTION: The coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed since December 2019. It has caused a global pandemic with more than three hundred thousand case fatalities. However, apart from supportive care by respirators, no standard medical therapy is validated. AREAS COVERED: This paper presents old drugs with potential in vitro efficacy against SARS-CoV-2. The in vitro database, adverse effects, and potential toxicities of these drugs are reviewed regarding their feasibility of clinical prescription for the treatment of patients with COVID-19. To obtain convincing recommendations, we referred to opinions from the US National Institute of Health regarding drugs repurposed for COVID-19 therapy. EXPERT OPINION: Although strong evidence of well-designed randomized controlled studies regarding COVID-19 therapy is presently lacking, remdesivir, teicoplanin, hydroxychloroquine (not in combination with azithromycin), and ivermectin might be effective antiviral drugs and are deemed promising candidates for controlling SARS-CoV-2. In addition, tocilizumab might be considered as the supplementary treatment for COVID-19 patients with cytokine release syndrome. In future, clinical trials regarding a combination of potentially effective drugs against SARS-CoV-2 need to be conducted to establish the optimal regimen for the treatment of patients with moderate-to-severe COVID-19.", "qid": 30, "docid": "hn12194u", "rank": 66, "score": 0.7979340553283691}, {"content": "Title: Old and re-purposed drugs for the treatment of COVID-19. Content: Introduction: The coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed since December 2019. It has caused a global pandemic with more than three hundred thousand case fatalities. However, apart from supportive care by respirators, no standard medical therapy is validated.Areas covered: This paper presents old drugs with potential in vitro efficacy against SARS-CoV-2. The in vitro database, adverse effects, and potential toxicities of these drugs are reviewed regarding their feasibility of clinical prescription for the treatment of patients with COVID-19. To obtain convincing recommendations, we referred to opinions from the US National Institute of Health regarding drugs repurposed for COVID-19 therapy.Expert opinion: Although strong evidence of well-designed randomized controlled studies regarding COVID-19 therapy is presently lacking, remdesivir, teicoplanin, hydroxychloroquine (not in combination with azithromycin), and ivermectin might be effective antiviral drugs and are deemed promising candidates for controlling SARS-CoV-2. In addition, tocilizumab might be considered as the supplementary treatment for COVID-19 patients with cytokine release syndrome. In future, clinical trials regarding a combination of potentially effective drugs against SARS-CoV-2 need to be conducted to establish the optimal regimen for the treatment of patients with moderate-to-severe COVID-19.", "qid": 30, "docid": "mbv8vb2r", "rank": 67, "score": 0.7979340553283691}, {"content": "Title: Potential specific therapies in COVID-19 Content: COVID-19 has grown into a global pandemic that has strained healthcare throughout the world. There is a sense of urgency in finding a cure for this deadly virus. In this study, we reviewed the empiric options used in common practice for COVID-19, based on the literature available online, with an emphasis on human experiences with these treatments on severe acute respiratory syndrome-associated coronavirus (SARS-COV-1) and other viruses. Convalescent blood products are the most promising potential treatment for use in COVID-19. The use of chloroquine or hydroxychloroquine (HCQ), remdesivir, and tocilizumab are some of the other promising potential therapies; however, they are yet to be tested in randomized clinical trials (RCTs). The use of lopinavir-ritonavir did not prove beneficial in a large RCT. The use of corticosteroids should be avoided in COVID-19 pneumonia unless used for other indications, based on the suggestion of harm in patients with SARS-COV-1 and Middle Eastern Respiratory Syndrome (MERS) infection. The reviews of this paper are available via the supplemental material section.", "qid": 30, "docid": "agdec3vz", "rank": 68, "score": 0.7972862720489502}, {"content": "Title: Potential pharmacological agents for COVID-19 Content: A novel coronavirus disease 2019 (COVID-19) infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) first emerged in December 2019 in Wuhan, China, has become a global pandemic. Currently, the management of COVID-19 infection is mainly supportive. Several clinical trials worldwide are evaluating several drugs approved for other indications, as well as multiple investigational agents for the treatment and prevention of COVID-19. Here, we give a brief overview of pharmacological agents and other therapies which are under investigation as treatment options or adjunctive agents for patients infected with COVID-19 and for chemoprophylaxis for the prevention of COVID-19 infection. At the time of writing this commentary, there is no peer-reviewed published evidence from randomized clinical trials of any pharmacological agents improving outcomes in COVID-19 patients. However, it was reported that remdesivir an investigational antiviral agent hastens clinical recovery, but a study is yet to be published in peer-reviewed medical journal.", "qid": 30, "docid": "yoo3ic2c", "rank": 69, "score": 0.7966315746307373}, {"content": "Title: Potential pharmacological agents for COVID-19. Content: A novel coronavirus disease 2019 (COVID-19) infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) first emerged in December 2019 in Wuhan, China, has become a global pandemic. Currently, the management of COVID-19 infection is mainly supportive. Several clinical trials worldwide are evaluating several drugs approved for other indications, as well as multiple investigational agents for the treatment and prevention of COVID-19. Here, we give a brief overview of pharmacological agents and other therapies which are under investigation as treatment options or adjunctive agents for patients infected with COVID-19 and for chemoprophylaxis for the prevention of COVID-19 infection. At the time of writing this commentary, there is no peer-reviewed published evidence from randomized clinical trials of any pharmacological agents improving outcomes in COVID-19 patients. However, it was reported that remdesivir an investigational antiviral agent hastens clinical recovery, but a study is yet to be published in peer-reviewed medical journal.", "qid": 30, "docid": "6cm1vp7h", "rank": 70, "score": 0.7966315746307373}, {"content": "Title: COVID-19 treatment: Combining anti-inflammatory and antiviral therapeutics using a network-based approach Content: To date, there are no effective antiviral medications for COVID-19. Drug repurposing, a strategy that uses existing drugs, offers potential prevention and treatment options for COVID-19. We discuss one treatment strategy that combines anti-inflammatory (melatonin) and antiviral (toremifene) agents for patients infected with SARS-CoV-2 from network medicine-based findings. We also describe the pathobiology and immunologic characteristics of COVID-19 and highlight the rationale of combination drug treatment to rescue the pulmonary and cardiovascular conditions resulting from COVID-19. A preliminary analysis reveals a high potential for the synergistic effects of melatonin and toremifene to reduce viral infection and replication, and the aberrant host inflammatory responses, offering strong biologic plausibility as an effective therapy for COVID-19.", "qid": 30, "docid": "jkniia2l", "rank": 71, "score": 0.7965211272239685}, {"content": "Title: COVID-19 treatment: Combining anti-inflammatory and antiviral therapeutics using a network-based approach. Content: To date, there are no effective antiviral medications for COVID-19. Drug repurposing, a strategy that uses existing drugs, offers potential prevention and treatment options for COVID-19. We discuss one treatment strategy that combines anti-inflammatory (melatonin) and antiviral (toremifene) agents for patients infected with SARS-CoV-2 from network medicine-based findings. We also describe the pathobiology and immunologic characteristics of COVID-19 and highlight the rationale of combination drug treatment to rescue the pulmonary and cardiovascular conditions resulting from COVID-19. A preliminary analysis reveals a high potential for the synergistic effects of melatonin and toremifene to reduce viral infection and replication, and the aberrant host inflammatory responses, offering strong biologic plausibility as an effective therapy for COVID-19.", "qid": 30, "docid": "8bp1kjhj", "rank": 72, "score": 0.7965211272239685}, {"content": "Title: The immunology of COVID-19: is immune modulation an option for treatment? Content: In December, 2019, an outbreak of COVID-19 emerged in Wuhan, China and quickly spread globally. As of May 7, 2020, there were 3 672 238 confirmed infections and 254 045 deaths attributed to COVID-19. Evidence has shown that there are asymptomatic carriers of COVID-19 who can transmit the disease to others. The virus incubation time shows a wide range (0\u201324 days) and the virus displays a high infectivity. It is therefore urgent to develop an effective therapy to treat patients with COVID-19 and to control the spread of the causative agent, severe respiratory syndrome coronavirus 2. Repurposing of approved drugs is widely adopted to fight newly emerged diseases such as COVID-19, as these drugs have known pharmacokinetic and safety profiles. As pathological examination has confirmed the involvement of immune hyperactivation and acute respiratory distress syndrome in fatal cases of COVID-19, several disease-modifying anti-rheumatic drugs (DMARDS), such as hydroxychloroquine and tocilizumab, have been proposed as potential therapies for the treatment of COVID-19. In this Review, we discuss the immunological aspects of COVID-19 and the potential implication of DMARDs in treating this disease.", "qid": 30, "docid": "mbv45kei", "rank": 73, "score": 0.7962057590484619}, {"content": "Title: Natural History of COVID-19 and Current Knowledge on Treatment Therapeutic Options Content: Despite intense research there is currently no effective vaccine available against the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in the later 2019 and responsible for the COVID-19 pandemic. This infectious and communicable disease has become one of the major public health challenges in the world. The clinical management of COVID-19 has been limited to infection prevention and control measures associated with supportive care such as supplemental oxygen and mechanical ventilation. Meanwhile efforts to find an effective treatment to inhibit virus replication, mitigate the symptoms, increase survival and decrease mortality rate are ongoing. Several classes of drugs, many of them already in use for other diseases, are being evaluated based on the body of clinical knowledge obtained from infected patients regarding to the natural history and evolution of the infection. Herein we will provide an updated overview of the natural history and current knowledge on drugs and therapeutic agents being tested for the prevention and treatment of COVID-19. These include different classes of drugs such as antiviral agents (chloroquine, ivermectin, nitazoxanide, hydroxychloroquine, lopinavir, remdesivir, tocilizumab), supporting agents (Vitamin C, Vitamin D, azithromycin, corticosteroids) and promising investigational vaccines. Considering the controversies and excessive number of compounds being tested and reported in the literature we hope that this review can provide useful and updated consolidated information on potential drugs used to prevent, control and treat COVID-19 patients worldwide.", "qid": 30, "docid": "rirzes0m", "rank": 74, "score": 0.7959417104721069}, {"content": "Title: Current pharmacological treatments for COVID-19: What's next? Content: Since December 2019 SARS-Cov-2 was found responsible for the disease COVID-19, which has spread worldwide. No specific therapies/vaccines are yet available for the treatment of COVID-19. Drug repositioning may offer a strategy and a number of drugs have been repurposed, including lopinavir/ritonavir, remdesivir, favipiravir and tocilizumab. This paper describes the main pharmacological properties of such drugs administered to patients with COVID-19, focusing on their antiviral, immune-modulatory and/or anti-inflammatory actions. Where available, data from clinical trials involving patients with COVID-19 are reported. Preliminary clinical trials seem to support their benefit. However, such drugs in COVID-19 patients have peculiar safety profiles. Thus, adequate clinical trials are necessary for these compounds. Nevertheless, while waiting for effective preventive measures i.e. vaccines, many clinical trials on drugs belonging to different therapeutic classes are currently underway. Their results will help us in defining the best way to treat COVID-19 and reducing its symptoms and complications.", "qid": 30, "docid": "q2debvsi", "rank": 75, "score": 0.7959073781967163}, {"content": "Title: Pharmacological and non-pharmacological efforts at prevention, mitigation, and treatment for COVID-19 Content: A global outbreak of the SARS-CoV-2 virus has infected millions of people over a short period of time. The communicability and increased mortality from the SARS-CoV-2 infection mandated the WHO to declare COVID-19 a worldwide pandemic. The virus outbreak has spread when there are no approved vaccines, treatments, or prophylactic therapies available. Researchers from all over the world have prioritized development of vaccines and antivirals. Several vaccine projects have seen successes in preclinical, phase I, and phase II clinical trials using recombinant DNA, mRNA, live attenuated virus, S-protein subunits, virus like particles, and viral vectors. Initial findings from antivirals such as remdesivir, favipiravir, danoprevir or lopinavir with ritonavir are presented. Immunomodulatory molecules such as sarilumab, tocilizumab, janus kinase inhibitors, and hyperimmune convalescent plasma have mixed outcomes from initial clinical findings; however, pending randomized controlled trials will assist national health institutions to make treatment recommendations for COVID-19. Where compassionate use of remdesivir has shown some benefits, therapies such as hydroxychloroquine have proven harmful due to their toxicities. This review discusses pharmacological interventions at play and evidence-based successes and limitations of non-pharmacological therapies such as social distancing, personal protective equipment, and ventilator support associated with the prevention and treatment of COVID-19.", "qid": 30, "docid": "np8jr9qk", "rank": 76, "score": 0.7952179312705994}, {"content": "Title: Pharmacological and non-pharmacological efforts at prevention, mitigation, and treatment for COVID-19. Content: A global outbreak of the SARS-CoV-2 virus has infected millions of people over a short period of time. The communicability and increased mortality from the SARS-CoV-2 infection mandated the WHO to declare COVID-19 a worldwide pandemic. The virus outbreak has spread when there are no approved vaccines, treatments, or prophylactic therapies available. Researchers from all over the world have prioritized development of vaccines and antivirals. Several vaccine projects have seen successes in preclinical, phase I, and phase II clinical trials using recombinant DNA, mRNA, live attenuated virus, S-protein subunits, virus like particles, and viral vectors. Initial findings from antivirals such as remdesivir, favipiravir, danoprevir or lopinavir with ritonavir are presented. Immunomodulatory molecules such as sarilumab, tocilizumab, janus kinase inhibitors, and hyperimmune convalescent plasma have mixed outcomes from initial clinical findings; however, pending randomized controlled trials will assist national health institutions to make treatment recommendations for COVID-19. Where compassionate use of remdesivir has shown some benefits, therapies such as hydroxychloroquine have proven harmful due to their toxicities. This review discusses pharmacological interventions at play and evidence-based successes and limitations of non-pharmacological therapies such as social distancing, personal protective equipment, and ventilator support associated with the prevention and treatment of COVID-19.", "qid": 30, "docid": "gxhztof5", "rank": 77, "score": 0.795217752456665}, {"content": "Title: Use of Remdesivir in the Management of COVID-19: A Systematic Review on Current Evidences. Content: The rapid progression of corona virus disease in 2019 (COVID-19) pandemic has become an unprecedented global concern. This systemic review aimed at evaluating the available evidence on efficacy, safety to identify any promising role for compassionate use of remdesivir in patient suffered for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) as re-purposeful use. We searched PubMed, EMBASE, Cochrane Library for randomized controlled trials (RCTs), prospective case series studies and case reports that evaluated use of remdesivir in COVID-19. The outcomes were mortality, recovery rate, length of hospital stay and clinical outcome. Though the drug remdesivir (RDV) is not approved by the FDA, still the \"Emergency Use Authorization\" (EUA) for compassionate use in severe cases is endorsed. After vigorous searching, screening and sorting of completed and published scientific evidences in electronic database, there were only 2 randomized control trial (RCT), 2 uncontrolled trials found until April 2020. We also included 3 published case reports to analyze the validity use of RDV because of the scarcity of evidence based reports. Remdesivir was thought to be one of the promising options for treating the patients of COVID-19 based on few laboratory experiments and reports from some compassionate use and case reports. The safety and efficacy of this drug in COVID-19 cases require high-quality evidence from well-designed and adequately-powered clinical trials with proper sample size for precise decision.", "qid": 30, "docid": "x89iy0m2", "rank": 78, "score": 0.7945274114608765}, {"content": "Title: Potential effectiveness and safety of antiviral agents in children with coronavirus disease 2019: a rapid review and meta-analysis. Content: Background The COVID-19 outbreak presents a new, life-threatening disease. Our aim was to assess the potential effectiveness and safety of antiviral agents for COVID-19 in children. Methods Electronic databases (MEDLINE, Embase, Web of Science, the Cochrane library, CBM, CNKI, and Wanfang Data) from their inception to March 31, 2020 were searched for randomized controlled trials (RCTs), clinical controlled trials and cohort studies of interventions with antiviral agents for children (less than 18 years of age) with COVID-19. Results A total of 23 studies with 6,008 patients were included. There was no direct evidence and all of evidence were indirect. The risks of bias in all studies were moderate to high in general. The effectiveness and safety of antiviral agents for children with COVID-19 is uncertain: For adults with COVID-19, lopinavir/ritonavir had no effect on mortality [risk ratio (RR) =0.77; 95% confidence interval (CI), 0.45 to 1.30]. Arbidol and hydroxychloroquine (HCQ) had no benefit on probability of negative PCR test (RR =1.27; 95% CI, 0.93 to 1.73; RR =0.93; 95% CI, 0.73 to 1.18) respectively. For adults with SARS, interferon was associated with reduced corticosteroid dose [weighted mean difference (WMD) = -0.14 g; 95% CI, -0.21 to -0.07] but had no effect on mortality (RR =0.72; 95% CI, 0.28 to 1.88); ribavirin did not reduce mortality (RR =0.68; 95% CI, 0.43 to 1.06) and was associated with high risk of severe adverse reactions; and oseltamivir had no effect on mortality (RR =0.87; 95% CI, 0.55 to 1.38). Ribavirin combined with interferon was also not effective in adults with MERS and associated with adverse reactions. Conclusions There is no evidence showing the effectiveness of antiviral agents for children with COVID-19, and the clinical efficacy of existing antiviral agents is still uncertain. We do not suggest clinical routine use of antivirals for COVID-19 in children, with the exception of clinical trials.", "qid": 30, "docid": "pp7w0ikh", "rank": 79, "score": 0.7924731969833374}, {"content": "Title: Current pharmacological treatments for SARS-COV-2: A narrative review Content: The novel coronavirus, later identified as SARS-CoV-2, originating from Wuhan in China in November 2019, quickly spread around the world becoming a pandemic. Despite the knowledge of previous coronaviruses, such as those responsible for the SARS and MERS-CoV epidemic, there is no drug or prophylaxis treatment to this day. The rapid succession of scientific findings on SARS-CoV-2 provides a significant number of potential drug targets. Nevertheless, at the same time, the high quantity of clinical data, generated by a large number of rapidly infected people, require accurate tests regarding effective medical treatments. Several in vitro and in vivo studies were rapidly initiated after the outbreak of the pandemic COVID-19. Initial clinical studies revealed the promising potential of remdesivir that demonstrated a powerful and specific in vitro antiviral activity for COVID-19. Promising effects appear to be attributable to hydroxychloroquine. Remdesivir and hydroxychloroquine are being tested in ongoing randomized trials. In contrast, oseltamivir was not effective and corticosteroids are not currently recommended. However, few data from ongoing clinical trials are identifying low molecular weight heparins, innate immune system stimulating agents, and inflammatory modulating agents as potential effective agents. The authors assume that the current pandemic will determine the need for a systematic approach based on big data analysis for identifying effective drugs to defeat SARS-Cov-2. This work is aimed to be a general reference point and to provide an overview as comprehensive as possible regarding the main clinical trials in progress at the moment.", "qid": 30, "docid": "303b23dd", "rank": 80, "score": 0.7915915250778198}, {"content": "Title: Current evidence for directed and supportive investigational therapies against COVID-19 Content: Coronavirus disease 2019 (COVID-19) is a global health crisis. There is currently a great need for effective and safe therapies directed at the disease, but no drugs are presently registered for use in COVID-19. Several directed therapies have been proposed, and most are still in clinical trials. Currently available published, peer-reviewed results mostly involve small sample sizes with study limitations restricting the interpretation of the findings. Many trials currently published also do not have a control group, limiting the interpretation of the effect of the intervention. Investigational directed therapies as well as investigational supportive therapies against COVID-19 are reviewed here. Chloroquine and hydroxychloroquine show promise as directed therapies, but current trial results are conflicting. Lopinavir/ritonavir also shows potential, but was started late in the disease course in most trials. No randomised controlled evidence is currently available for remdesivir and favipiravir. Corticosteroid use is not recommended for directed therapy against COVID-19, and the role of tocilizumab is currently unclear, based on limited evidence. Early initiation of investigational directed therapies may provide benefit in selected patients. The results from larger randomised controlled trials will clarify the place of these therapies in COVID-19 treatment.", "qid": 30, "docid": "f33eb1nf", "rank": 81, "score": 0.7914856672286987}, {"content": "Title: Potential Effectiveness and Safety of Antiviral Agents in Children with Coronavirus Disease 2019: A Rapid Review and Meta-Analysis Content: Background: The COVID-19 outbreak presents a new, life-threatening disease. Our aim was to assess the potential effectiveness and safety of antiviral agents for COVID-19 in children. Methods: Electronic databases from their inception to March, 31 2020 were searched for randomized controlled trials, clinical controlled trials and cohort studies of interventions with antiviral agents for children (less than 18 years of age) with COVID-19. Results: A total of 23 studies of indirect evidence with 6008 patients were included. The risks of bias in all studies were moderate to high in general. The effectiveness and safety of antiviral agents for children with COVID-19 is uncertain: For adults with COVID-19, lopinavir/ritonavir had no effect on mortality (risk ratio [RR]= 0.77, 95% confidence interval [CI] 0.45 to 1.30) and probability of negative PCR test (RR=0.98, 95 CI% 0.82 to 1.18). Arbidol had no benefit on probability of negative PCR test (RR=1.27, 95% CI 0.93 to 1.73). Hydroxychloroquine was not associated with increasing the probability of negative PCR result (RR=0.93, 95% CI 0.73 to 1.18). For adults with SARS, interferon was associated with reduced corticosteroid dose (weighted mean difference [WMD]=-0.14 g, 95% CI -0.21 to -0.07) but had no effect on mortality (RR=0.72, 95% CI 0.28 to 1.88); ribavirin did not reduce mortality (RR=0.68, 95% CI % 0.43 to 1.06) and was associated with high risk of severe adverse reactions; and oseltamivir had no effect on mortality (RR=0.87, 95% CI 0.55 to 1.38). Ribavirin combined with interferon was also not effective in adults with MERS and associated with adverse reactions. Conclusions: There is no evidence showing the effectiveness of antiviral agents for children with COVID-19, and the clinical efficacy of existing antiviral agents is still uncertain. We do not suggest clinical routine use of antivirals for COVID-19 in children, with the exception of clinical trials. Keywords: Antiviral agents; children; COVID-19; meta-analysis; rapid review.", "qid": 30, "docid": "xuo2jrfq", "rank": 82, "score": 0.791012167930603}, {"content": "Title: Systematic and Statistical Review of COVID19 Treatment Trials Content: Objective: The following systematic review and meta-analysis compiles the current data regarding human controlled COVID-19 treatment trials. Methods: An electronic search of the literature compiled studies pertaining to human controlled treatment trials with COVID-19. Medications assessed included lopinavir/ritonavir, arbidol, hydroxychloroquine, favipiravir, and heparin. Statistical analyzes were performed for common viral clearance endpoints whenever possible. Results: Lopinavir/ritonavir showed no significant effect on viral clearance for COVID-19 cases (OR 0.95 [95% CI 0.50-1.83]). Hydroxychloroquine also showed no significant effect on COVID-19 viral clearance rates (OR 2.16 [95% CI 0.80-5.84]). Arbidol showed no seven-day (OR 1.63 [95% CI 0.76-3.50]) or 14-day viral (OR 5.37 [95% CI 0.35-83.30]) clearance difference compared to lopinavir/ritonavir. Review of literature showed no significant clinical improvement with lopinavir/ritonavir, arbidol, hydroxychloroquine, or remdesivir. Favipiravir showed quicker symptom improvement compared to lopinavir/ritonavir and arbidol. Heparin showed improvement with severe COVID-19 cases. Conclusion: Current medications do not show significant effect on COVID-19 viral clearance rates. Favipiravir shows favorable results compared to other tested medications. Heparin shows benefit for severe cases of COVID-19.", "qid": 30, "docid": "suo3syr1", "rank": 83, "score": 0.789527177810669}, {"content": "Title: Rethinking antiviral effects for COVID-19 in clinical studies: early initiation is key to successful treatment Content: Development of an effective antiviral drug for COVID-19 is a global health priority. Although several candidate drugs have been identified through in vitro and in vivo models, consistent and compelling evidence for effective drugs from clinical studies is limited. The lack of evidence could be in part due to heterogeneity of virus dynamics among patients and late initiation of treatment. We first quantified the heterogeneity of viral dynamics which could be a confounder in compassionate use programs. Second, we demonstrated that an antiviral drug is unlikely to be effective if initiated after a short period following symptom onset. For accurate evaluation of the efficacy of an antiviral drug for COVID-19, antiviral treatment should be initiated before or soon after symptom onset in randomized clinical trials.", "qid": 30, "docid": "6xph6ya7", "rank": 84, "score": 0.7881873846054077}, {"content": "Title: Systematic and Statistical Review of Coronavirus Disease 19 Treatment Trials Content: The following systematic review and meta-analysis compile the current data regarding human controlled COVID-19 treatment trials. An electronic search of the literature compiled studies pertaining to human controlled treatment trials with COVID-19. Medications assessed included lopinavir/ritonavir, arbidol, hydroxychloroquine, tocilizumab, favipiravir, heparin, and dexamethasone. Statistical analyses were performed for common viral clearance endpoints whenever possible. Lopinavir/ritonavir showed no significant effect on viral clearance for COVID-19 cases (OR 0.95 [95% CI 0.50\u20131.83]). Hydroxychloroquine also showed no significant effect on COVID-19 viral clearance rates (OR 2.16 [95% CI 0.80\u20135.84]). Arbidol showed no 7-day (OR 1.63 [95% CI 0.76\u20133.50]) or 14-day viral (OR 5.37 [95% CI 0.35\u201383.30]) clearance difference compared to lopinavir/ritonavir. Review of literature showed no significant clinical improvement with lopinavir/ritonavir, arbidol, hydroxychloroquine, or remdesivir. Tocilizumab showed mixed results regarding survival. Favipiravir showed quicker symptom improvement compared to lopinavir/ritonavir and arbidol. Heparin and dexamethasone showed improvement with severe COVID-19 cases requiring supplemental oxygenation. Current medications do not show significant effect on COVID-19 viral clearance rates. Tocilizumab showed mixed results regarding survival. Favipiravir shows favorable results compared to other tested medications. Heparin and dexamethasone show benefit especially for severe COVID-19 cases.", "qid": 30, "docid": "07tdrd4w", "rank": 85, "score": 0.7876363396644592}, {"content": "Title: Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. Content: BACKGROUND Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19). METHODS We conducted a randomized, open-label, phase 3 trial involving hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of 94% or less while they were breathing ambient air, and radiologic evidence of pneumonia. Patients were randomly assigned in a 1:1 ratio to receive intravenous remdesivir for either 5 days or 10 days. All patients received 200 mg of remdesivir on day 1 and 100 mg once daily on subsequent days. The primary end point was clinical status on day 14, assessed on a 7-point ordinal scale. RESULTS In total, 397 patients underwent randomization and began treatment (200 patients for 5 days and 197 for 10 days). The median duration of treatment was 5 days (interquartile range, 5 to 5) in the 5-day group and 9 days (interquartile range, 5 to 10) in the 10-day group. At baseline, patients randomly assigned to the 10-day group had significantly worse clinical status than those assigned to the 5-day group (P = 0.02). By day 14, a clinical improvement of 2 points or more on the ordinal scale occurred in 64% of patients in the 5-day group and in 54% in the 10-day group. After adjustment for baseline clinical status, patients in the 10-day group had a distribution in clinical status at day 14 that was similar to that among patients in the 5-day group (P = 0.14). The most common adverse events were nausea (9% of patients), worsening respiratory failure (8%), elevated alanine aminotransferase level (7%), and constipation (7%). CONCLUSIONS In patients with severe Covid-19 not requiring mechanical ventilation, our trial did not show a significant difference between a 5-day course and a 10-day course of remdesivir. With no placebo control, however, the magnitude of benefit cannot be determined. (Funded by Gilead Sciences; GS-US-540-5773 ClinicalTrials.gov number, NCT04292899.).", "qid": 30, "docid": "zbi0llig", "rank": 86, "score": 0.7872632145881653}, {"content": "Title: Large trial yields strongest evidence yet that antiviral drug can help COVID-19 patients Content: A candidate treatment for COVID-19 has shown convincing\u2014albeit modest\u2014benefit for the first time in a large, carefully controlled clinical trial in hospitalized patients The infected people who received remdesivir, an experimental drug made by Gilead Sciences that cripples an enzyme several viruses use to copy their RNA, recovered in an average of 11 days versus 15 in patients who received a placebo \u201cAlthough a 31% improvement doesn\u2019t seem like a knockout, 100% [success], it is a very important proof of concept,\u201d said Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases (NIAID), during an Oval Office meeting in which President Donald Trump was asked by media about a statement Gilead had released on the results The patients treated with remdesivir also had a lower mortality rate\u20148% versus 11 6% in the group given the placebo\u2014but this positive trend did not reach statistical significance, Fauci noted (The full results from the trial have not been made public in a preprint or peer-reviewed paper )", "qid": 30, "docid": "bjgy98r8", "rank": 87, "score": 0.7866621017456055}, {"content": "Title: Should lCU COVID-19 patients empirically receive therapeutic doses of anticoagulant? Content: In spite of many ongoing attempts to repurpose existing antivirals, no drugs have emerged yet with the desirable activity against SARS-CoV-2. Hydroxychloroquine, lopinavir/ritonavir, remdesivir, umifenovir, favipiravir, ribavirin and beta-interferon-1 gave rise to variable but still inconsistent proof of clinical efficacy in the treatment of COVID-19. Pathogenetic studies have shown significant differences between commonly defined viral pneumonia and COVID-19 pulmonary disease. In severe forms, immune/inflammatory alterations reminiscent of disease forms like Macrophage Activation Syndrome (MAS) have been described, and therapeutic options other than anti-infective have been proposed and implemented, such as anti-inflammatory and anticoagulative agents. The thrombotic phenomena described in the pulmonary vascular bed of patients with severe COVID-19 suggest the administration of low-molecular weight heparin (LMWH) as standard measure in hospitalized patients with COVID-19.", "qid": 30, "docid": "9hdo3jpb", "rank": 88, "score": 0.7865567803382874}, {"content": "Title: Current pharmacological treatments for COVID\u201019: What's next? Content: Since December 2019 SARS\u2010Cov\u20102 was found responsible for the disease COVID\u201019, which has spread worldwide. No specific therapies/vaccines are yet available for the treatment of COVID\u201019. Drug repositioning may offer a strategy and a number of drugs have been repurposed, including lopinavir/ritonavir, remdesivir, favipiravir and tocilizumab. This paper describes the main pharmacological properties of such drugs administered to patients with COVID\u201019, focusing on their antiviral, immune\u2010modulatory and/or anti\u2010inflammatory actions. Where available, data from clinical trials involving patients with COVID\u201019 are reported. Preliminary clinical trials seem to support their benefit. However, such drugs in COVID\u201019 patients have peculiar safety profiles. Thus, adequate clinical trials are necessary for these compounds. Nevertheless, while waiting for effective preventive measures i.e. vaccines, many clinical trials on drugs belonging to different therapeutic classes are currently underway. Their results will help us in defining the best way to treat COVID\u201019 and reducing its symptoms and complications.", "qid": 30, "docid": "gsoxaso9", "rank": 89, "score": 0.7862286567687988}, {"content": "Title: Treatment Considerations for COVID-19: A Critical Review of the Evidence (or Lack Thereof) Content: Abstract The novel severe acute respiratory syndrome coronavirus 2 is causing a worldwide pandemic that may lead to a highly morbid and potentially fatal coronavirus disease-19 (COVID-19). There is currently no drug that has been proven as an effective therapy for COVID-19. Several candidate drugs are being considered and evaluated for treatment. This includes clinically-available drugs, such as chloroquine, hydroxychloroquine, and lopinavir/ritonavir, which are being repurposed for the treatment of COVID-19. Novel experimental therapies, such as remdesivir and favipiravir, are also actively being investigated for antiviral efficacy. Clinically-available and investigational immunomodulators, such as the IL-6 inhibitors tocilizumab and sarilumab and the anti-GMCSF lenzilumab, are being tested for their anticipated effect in counteracting the pro-inflammatory cytokine environment that characterizes severe and critical COVID-19. This review article examines the evidence behind the potential use of these leading drug candidates for the treatment of COVID-19. The authors conclude, based on this review, that there is still no high-quality evidence to support any of these proposed drug therapies. The authors, therefore, encourage the enrollment of eligible patients to multiple ongoing clinical trials that assess the efficacy and safety of these candidate therapies. Until the results of controlled trials are available, none of the suggested therapeutics is clinically proven as an effective therapy for COVID-19.", "qid": 30, "docid": "iymmf4k6", "rank": 90, "score": 0.7860163450241089}, {"content": "Title: Repurposing Therapeutics for Potential Treatment of SARS-CoV-2: A Review Content: The need for proven disease-specific treatments for the novel pandemic coronavirus SARS-CoV-2 necessitates a worldwide search for therapeutic options. Since the SARS-CoV-2 virus shares extensive homology with SARS-CoV and MERS-CoV, effective therapies for SARS-CoV and MERS-CoV may also have therapeutic potential for the current COVID-19 outbreak. To identify therapeutics that might be repositioned for treatment of the SARS-CoV-2 disease COVID-19, we strategically reviewed the literature to identify existing therapeutics with evidence of efficacy for the treatment of the three coronaviruses that cause severe respiratory illness (SARS-CoV, MERS-CoV, and SARS-CoV-2). Mechanistic and in vitro analyses suggest multiple promising therapeutic options with potential for repurposing to treat patients with COVID-19. Therapeutics with particularly high potential efficacy for repurposing include camostat mesylate, remdesivir, favipiravir, tocilizumab, baricitinib, convalescent plasma, and humanized monoclonal antibodies. Camostat mesylate has shown therapeutic potential, likely by preventing viral entry into epithelial cells. In early research, the targeted antivirals remdesivir and favipiravir appear to benefit patients by decreasing viral replication; clinical trials suggest that remdesivir speeds recovery from COVID-19. Tocilizumab and baricitinib appear to improve mortality by preventing a severe cytokine storm. Convalescent plasma and humanized monoclonal antibodies offer passive immunity and decreased recovery time. This review highlights potential therapeutic options that may be repurposed to treat COVID-19 and suggests opportunities for further research.", "qid": 30, "docid": "fy8tyj9a", "rank": 91, "score": 0.7856634855270386}, {"content": "Title: Repurposing Therapeutics for Potential Treatment of SARS-CoV-2: A Review. Content: The need for proven disease-specific treatments for the novel pandemic coronavirus SARS-CoV-2 necessitates a worldwide search for therapeutic options. Since the SARS-CoV-2 virus shares extensive homology with SARS-CoV and MERS-CoV, effective therapies for SARS-CoV and MERS-CoV may also have therapeutic potential for the current COVID-19 outbreak. To identify therapeutics that might be repositioned for treatment of the SARS-CoV-2 disease COVID-19, we strategically reviewed the literature to identify existing therapeutics with evidence of efficacy for the treatment of the three coronaviruses that cause severe respiratory illness (SARS-CoV, MERS-CoV, and SARS-CoV-2). Mechanistic and in vitro analyses suggest multiple promising therapeutic options with potential for repurposing to treat patients with COVID-19. Therapeutics with particularly high potential efficacy for repurposing include camostat mesylate, remdesivir, favipiravir, tocilizumab, baricitinib, convalescent plasma, and humanized monoclonal antibodies. Camostat mesylate has shown therapeutic potential, likely by preventing viral entry into epithelial cells. In early research, the targeted antivirals remdesivir and favipiravir appear to benefit patients by decreasing viral replication; clinical trials suggest that remdesivir speeds recovery from COVID-19. Tocilizumab and baricitinib appear to improve mortality by preventing a severe cytokine storm. Convalescent plasma and humanized monoclonal antibodies offer passive immunity and decreased recovery time. This review highlights potential therapeutic options that may be repurposed to treat COVID-19 and suggests opportunities for further research.", "qid": 30, "docid": "inibtytf", "rank": 92, "score": 0.7856634855270386}, {"content": "Title: Can mesenchymal stem cell therapy be the interim management of COVID-19? Content: COVID-19 pandemic has accounted for ~ 4.3 million confirmed cases and ~ 292,000 deaths (till 12th May, 2020) across the globe since its outbreak. Several anti-viral drugs such as RNA dependent RNA polymerase inhibitors (remdesivir, favipiravir, ribavirin), protease inhibitors (lopinavir, ritonavir) and drugs targeting endocytic pathway (hydroxychloroquine) are being evaluated for COVID-19 but standard therapeutics yet not available. Severe health deterioration in critically ill patients is characterized by pulmonary edema, severe respiratory distress, cytokine storm and septic shock. To combat cytokine storm, immune-therapy targeting IL-1, IL-2, IL-6 and TNF\u03b1 are being evaluated and one of the promising immune-modulator is the mesenchymal stem cells (MSCs) that can surmount the severity of COVID-19 infections. Recent studies have shown that MSC-therapy significantly dampens the cytokine storm in critically ill COVID-19 patients. This communication endows with the insight of stem cell therapy and summarizes the recent studies on COVID-19 patients.", "qid": 30, "docid": "dhuekl5b", "rank": 93, "score": 0.7856563329696655}, {"content": "Title: [Farmakoter\u00e1pi\u00e1s lehetos\u00e9gek SARS-CoV-2-fertoz\u00e9s/COVID\u00ad19-betegs\u00e9g eset\u00e9n]/ Pharmacological options in treating SASR-CoV-2 infection/COVID-19 Content: There is currently no proven effective therapy for COVID-19. Here we discuss the drugs most investigated for the treatment of the disease. All the listed therapies are experimental at this stage. However, due to the severe healthcare effects of the pandemic and the potentially fatal outcome of COVID-19 patients treated in the intensive care units, their off-label use should none-the-less be considered. Orv Hetil. 2020; 161(17): 685\u00ad688.", "qid": 30, "docid": "ql3fvmrs", "rank": 94, "score": 0.7855789661407471}, {"content": "Title: Remdesivir inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice. Content: Summary Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the novel viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV) potently inhibits SARS-CoV-2 replication in human lung cells and primary human airway epithelial cultures (EC50 = 0.01 \u03bcM). Weaker activity is observed in Vero E6 cells (EC50 = 1.65 \u03bcM) due to their low capacity to metabolize RDV. To rapidly evaluate in vivo efficacy, we engineered a chimeric SARS-CoV encoding the viral target of RDV, the RNA-dependent RNA polymerase, of SARS-CoV-2. In mice infected with chimeric virus, therapeutic RDV administration diminishes lung viral load and improves pulmonary function compared to vehicle treated animals. These data demonstrate that RDV is potently active against SARS-CoV-2 in vitro and in vivo, supporting its further clinical testing for treatment of COVID-19.", "qid": 30, "docid": "9sjdb7f3", "rank": 95, "score": 0.7854975461959839}, {"content": "Title: Remdesivir for 5 or 10 Days in Patients with Severe Covid-19 Content: BACKGROUND: Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19). METHODS: We conducted a randomized, open-label, phase 3 trial involving hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of 94% or less while they were breathing ambient air, and radiologic evidence of pneumonia. Patients were randomly assigned in a 1:1 ratio to receive intravenous remdesivir for either 5 days or 10 days. All patients received 200 mg of remdesivir on day 1 and 100 mg once daily on subsequent days. The primary end point was clinical status on day 14, assessed on a 7-point ordinal scale. RESULTS: In total, 397 patients underwent randomization and began treatment (200 patients for 5 days and 197 for 10 days). The median duration of treatment was 5 days (interquartile range, 5 to 5) in the 5-day group and 9 days (interquartile range, 5 to 10) in the 10-day group. At baseline, patients randomly assigned to the 10-day group had significantly worse clinical status than those assigned to the 5-day group (P = 0.02). By day 14, a clinical improvement of 2 points or more on the ordinal scale occurred in 64% of patients in the 5-day group and in 54% in the 10-day group. After adjustment for baseline clinical status, patients in the 10-day group had a distribution in clinical status at day 14 that was similar to that among patients in the 5-day group (P = 0.14). The most common adverse events were nausea (9% of patients), worsening respiratory failure (8%), elevated alanine aminotransferase level (7%), and constipation (7%). CONCLUSIONS: In patients with severe Covid-19 not requiring mechanical ventilation, our trial did not show a significant difference between a 5-day course and a 10-day course of remdesivir. With no placebo control, however, the magnitude of benefit cannot be determined. (Funded by Gilead Sciences; GS-US-540-5773 ClinicalTrials.gov number, NCT04292899.).", "qid": 30, "docid": "pibcxe1x", "rank": 96, "score": 0.7854313850402832}, {"content": "Title: COVID-19: An Update about the Discovery Clinical Trial Content: Finding efficacious and safe treatments for COVID-19 emerges as a crucial need in order to control the spread of the pandemic. Whereas plasma therapy attracts much interest, the European project Discovery focuses on the potentialities of small molecules like remdesivir, the combination of lopinavir/ritonavir, hydroxychloroquine, and chloroquine. Results recently published on the clinical evaluation of those drugs are compiled in this brief report, although complete data are still impatiently awaited.", "qid": 30, "docid": "sqrbj5r4", "rank": 97, "score": 0.7850309610366821}, {"content": "Title: Treatment options for COVID-19: The reality and challenges Content: An outbreak related to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019. An extremely high potential for dissemination resulted in the global coronavirus disease 2019 (COVID-19) pandemic in 2020. Despite the worsening trends of COVID-19, no drugs are validated to have significant efficacy in clinical treatment of COVID-19 patients in large-scale studies. Remdesivir is considered the most promising antiviral agent; it works by inhibiting the activity of RNA-dependent RNA polymerase (RdRp). A large-scale study investigating the clinical efficacy of remdesivir (200 mg on day 1, followed by 100 mg once daily) is on-going. The other excellent anti-influenza RdRp inhibitor favipiravir is also being clinically evaluated for its efficacy in COVID-19 patients. The protease inhibitor lopinavir/ritonavir (LPV/RTV) alone is not shown to provide better antiviral efficacy than standard care. However, the regimen of LPV/RTV plus ribavirin was shown to be effective against SARS-CoV in vitro. Another promising alternative is hydroxychloroquine (200 mg thrice daily) plus azithromycin (500 mg on day 1, followed by 250 mg once daily on day 2-5), which showed excellent clinical efficacy on Chinese COVID-19 patients and anti-SARS-CoV-2 potency in vitro. The roles of teicoplanin (which inhibits the viral genome exposure in cytoplasm) and monoclonal and polyclonal antibodies in the treatment of SARS-CoV-2 are under investigation. Avoiding the prescription of non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors, or angiotensin II type I receptor blockers is advised for COVID-19 patients.", "qid": 30, "docid": "qsd49pvm", "rank": 98, "score": 0.7843307256698608}, {"content": "Title: What do we know about remdesivir drug interactions? Content: The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS\u2010Co\u2010V\u20102) has resulted in a critical need to rapidly develop new pharmacologic interventions and disseminate information. This has led to confusing and conflicting information on drug efficacy. Remdesivir has emerged as a promising treatment for SARS\u2010Co\u2010V\u20102 infection yet published clinical pharmacology and drug interaction studies are limited. Additional studies of the disposition of remdesivir, its active metabolite (GS\u2010441524), and its triphosphate metabolite (GS\u2010443902) are needed.", "qid": 30, "docid": "5ijdl5sl", "rank": 99, "score": 0.783867597579956}, {"content": "Title: COVID-19: The Potential Role of Copper and N-acetylcysteine (NAC) in a Combination of Candidate Antiviral Treatments Against SARS-CoV-2. Content: BACKGROUND On March 11, 2020, the World Health Organization (WHO) declared the outbreak of coronavirus disease (COVID-19) a pandemic. Since then, thousands of people have suffered and died, making the need for a treatment of severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) more crucial than ever. MATERIALS AND METHODS The authors carried out a search in PubMed, ClinicalTrials.gov and New England Journal of Medicine (NEJM) for COVID-19 to provide information on the most promising treatments against SARS-CoV-2. RESULTS Possible COVID-19 agents with promising efficacy and favorable safety profile were identified. The results support the combination of copper, N-acetylcysteine (NAC), colchicine and nitric oxide (NO) with candidate antiviral agents, remdesivir or EIDD-2801, as a treatment for patients positive for SARS-CoV-2. CONCLUSION The authors propose to study the effects of the combination of copper, NAC, colchicine, NO and currently used experimental antiviral agents, remdesivir or EIDD-2801, as a potential treatment scheme for SARS-COV-2.", "qid": 30, "docid": "va9ihthm", "rank": 100, "score": 0.7829297184944153}]}
{"query": "How does the coronavirus differ from seasonal flu?", "hits": [{"content": "Title: Coronavirus, as a source of pandemic pathogens Content: The coronavirus and the influenza virus have similarities and differences. In order to comprehensively compare them, their genome sequencing data were examined by principal component analysis. Variations in coronavirus were smaller than those in a subclass of the influenza virus. In addition, differences among coronaviruses in a variety of hosts were small. These characteristics may have facilitated the infection of different hosts. Although many of the coronaviruses were more conservative, those repeatedly found among humans showed annual changes. If SARS-CoV-2 changes its genome like the Influenza H type, it will repeatedly spread every few years. In addition, the coronavirus family has many other candidates for subsequent pandemics. One Sentence Summary The genome data of coronavirus were compared to influenza virus, to investigate its spreading mechanism and future status. Coronavirus would repeatedly spread every few years. In addition, the coronavirus family has many other candidates for subsequent pandemics.", "qid": 31, "docid": "431ksdno", "rank": 1, "score": 0.7808679342269897}, {"content": "Title: The Seasonal End of Human Coronavirus Hospital Admissions with Implications for SARS-CoV-2 Content: The seasonality of influenza viruses and endemic human coronaviruses was tracked over an 8-year period to assess key epidemiologic reduction points in disease incidence for an urban area in the northeast United States. Patients admitted to a pediatric hospital with worsening respiratory symptoms were tested using a multiplex PCR assay from nasopharyngeal swabs. The additive seasonal effects of outdoor temperatures and indoor relative humidity (RH) were evaluated. The 8-year average peak activity of human coronaviruses occurred in the first week of January, when droplet and contact transmission was enabled by the low indoor RH of 20-30%. Previous studies have shown that an increase in RH to 50% has been associated with markedly reduced viability and transmission of influenza virus and animal coronaviruses. As disease incidence was reduced by 50% in early March, to 75% in early April, to greater than 99% at the end of April, a relationship was observed from colder temperatures in January with a low indoor RH to a gradual increase in outdoor temperatures in April with an indoor RH of 45-50%. As a lipid-bound, enveloped virus with similar size characteristics to endemic human coronaviruses, SARS-CoV-2 should be subject to the same dynamics of reduced viability and transmission with increased humidity. In addition to the major role of social distancing, the transition from lower to higher indoor RH with increasing outdoor temperatures could have an additive effect on the decrease in SARS-CoV-2 cases in May. Over the 8-year period of this study, human coronavirus activity was either zero or >99% reduction in the months of June through September, and the implication would be that SARS-Cov-2 may follow a similar pattern.", "qid": 31, "docid": "3xw4qjoy", "rank": 2, "score": 0.7729802131652832}, {"content": "Title: Coronavirus HKU1 and other coronavirus infections in Hong Kong. Content: We have recently described the discovery of a novel coronavirus, coronavirus HKU1 (CoV-HKU1), associated with community-acquired pneumonia. However, the clinical spectrum of disease and the epidemiology of CoV-HKU1 infections in relation to infections with other respiratory viruses are unknown. In this 12-month prospective study, 4,181 nasopharyngeal aspirates from patients with acute respiratory tract infections were subjected to reverse transcription-PCRs specific for CoV-HKU1 and human coronaviruses NL63 (HCoV-NL63), OC43 (HCoV-OC43), and 229E (HCoV-229E). Coronaviruses were detected in 87 (2.1%) patients, with 13 (0.3%) positive for CoV-HKU1, 17 (0.4%) positive for HCoV-NL63, 53 (1.3%) positive for HCoV-OC43, and 4 (0.1%) positive for HCoV-229E. Of the 13 patients with CoV-HKU1 infections, 11 were children and 8 had underlying diseases. Similar to the case for other coronaviruses, upper respiratory infection was the most common presentation of CoV-HKU1 infections, although pneumonia, acute bronchiolitis, and asthmatic exacerbation also occurred. Despite a shorter duration of fever (mean, 1.7 days) and no difference in maximum temperature in children with CoV-HKU1 infections compared to patients with most other respiratory virus infections, a high incidence of febrile seizures (50%) was noted, which was significantly higher than those for HCoV-OC43 (14%), adenovirus (9%), human parainfluenza virus 1 (0%), and respiratory syncytial virus (8%) infections. CoV-HKU1 and HCoV-OC43 infections peaked in winter, although cases of the former also occurred in spring to early summer. This is in contrast to HCoV-NL63 infections, which mainly occurred in early summer and autumn but were absent in winter. Two genotypes of CoV-HKU1 cocirculated during the study period. Continuous studies over a longer period are warranted to ascertain the seasonal variation and relative importance of the different coronaviruses. Similar studies in other countries are required to better determine the epidemiology and genetic diversity of CoV-HKU1.", "qid": 31, "docid": "ccrupdwj", "rank": 3, "score": 0.7700799703598022}, {"content": "Title: Epidemiology and Clinical Symptoms Related to Seasonal Coronavirus Identified in Patients with Acute Respiratory Infections Consulting in Primary Care over Six Influenza Seasons (2014-2020) in France Content: There is currently debate about human coronavirus (HCoV) seasonality and pathogenicity, as epidemiological data are scarce. Here, we provide epidemiological and clinical features of HCoV patients with acute respiratory infection (ARI) examined in primary care general practice. We also describe HCoV seasonality over six influenza surveillance seasons (week 40 to 15 of each season) from the period 2014/2015 to 2019/2020 in Corsica (France). A sample of patients of all ages presenting for consultation for influenza-like illness (ILI) or ARI was included by physicians of the French Sentinelles Network during this period. Nasopharyngeal samples were tested for the presence of 21 respiratory pathogens by real-time RT-PCR. Among the 1389 ILI/ARI patients, 105 were positive for at least one HCoV (7.5%). On an annual basis, HCoVs circulated from week 48 (November) to weeks 14-15 (May) and peaked in week 6 (February). Overall, among the HCoV-positive patients detected in this study, HCoV-OC43 was the most commonly detected virus, followed by HCoV-NL63, HCoV-HKU1, and HCoV-229E. The HCoV detection rates varied significantly with age (p = 0.00005), with the age group 0-14 years accounting for 28.6% (n = 30) of HCoV-positive patients. Fever and malaise were less frequent in HCoV patients than in influenza patients, while sore throat, dyspnoea, rhinorrhoea, and conjunctivitis were more associated with HCoV positivity. In conclusion, this study demonstrates that HCoV subtypes appear in ARI/ILI patients seen in general practice, with characteristic outbreak patterns primarily in winter. This study also identified symptoms associated with HCoVs in patients with ARI/ILI. Further studies with representative samples should be conducted to provide additional insights into the epidemiology and clinical features of HCoVs.", "qid": 31, "docid": "5qhguue3", "rank": 4, "score": 0.7641785144805908}, {"content": "Title: Epidemiology and Clinical Symptoms Related to Seasonal Coronavirus Identified in Patients with Acute Respiratory Infections Consulting in Primary Care over Six Influenza Seasons (2014-2020) in France. Content: There is currently debate about human coronavirus (HCoV) seasonality and pathogenicity, as epidemiological data are scarce. Here, we provide epidemiological and clinical features of HCoV patients with acute respiratory infection (ARI) examined in primary care general practice. We also describe HCoV seasonality over six influenza surveillance seasons (week 40 to 15 of each season) from the period 2014/2015 to 2019/2020 in Corsica (France). A sample of patients of all ages presenting for consultation for influenza-like illness (ILI) or ARI was included by physicians of the French Sentinelles Network during this period. Nasopharyngeal samples were tested for the presence of 21 respiratory pathogens by real-time RT-PCR. Among the 1389 ILI/ARI patients, 105 were positive for at least one HCoV (7.5%). On an annual basis, HCoVs circulated from week 48 (November) to weeks 14-15 (May) and peaked in week 6 (February). Overall, among the HCoV-positive patients detected in this study, HCoV-OC43 was the most commonly detected virus, followed by HCoV-NL63, HCoV-HKU1, and HCoV-229E. The HCoV detection rates varied significantly with age (p = 0.00005), with the age group 0-14 years accounting for 28.6% (n = 30) of HCoV-positive patients. Fever and malaise were less frequent in HCoV patients than in influenza patients, while sore throat, dyspnoea, rhinorrhoea, and conjunctivitis were more associated with HCoV positivity. In conclusion, this study demonstrates that HCoV subtypes appear in ARI/ILI patients seen in general practice, with characteristic outbreak patterns primarily in winter. This study also identified symptoms associated with HCoVs in patients with ARI/ILI. Further studies with representative samples should be conducted to provide additional insights into the epidemiology and clinical features of HCoVs.", "qid": 31, "docid": "1n5ej08f", "rank": 5, "score": 0.7641785144805908}, {"content": "Title: Seasonality of Coronavirus 229E, HKU1, NL63 and OC43 from 2014-2020 Content: Abstract The possibility of seasonality of Covid-19 is being discussed; here we show clinical microbiology laboratory data illustrating seasonality of coronaviruses 229E, HKU1, NL63 and OC43. The data shown are specific to the four studied coronaviruses, and may or may not generalize to Covid-19.", "qid": 31, "docid": "clxza5zy", "rank": 6, "score": 0.7582352161407471}, {"content": "Title: Epidemiology of seasonal coronaviruses: Establishing the context for COVID-19 emergence Content: Public health preparedness for coronavirus disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal coronaviruses (sCoVs) and other cocirculating viruses in the West of Scotland, UK. We analyzed routine diagnostic data for >70,000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43 and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.", "qid": 31, "docid": "6tzx945b", "rank": 7, "score": 0.7560734748840332}, {"content": "Title: Epidemiology and clinical presentations of the four human coronaviruses 229E, HKU1, NL63, and OC43 detected over 3 years using a novel multiplex real-time PCR method. Content: Four human coronaviruses (HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43) are associated with a range of respiratory outcomes, including bronchiolitis and pneumonia. Their epidemiologies and clinical characteristics are poorly described and are often reliant on case reports. To address these problems, we conducted a large-scale comprehensive screening for all four coronaviruses by analysis of 11,661 diagnostic respiratory samples collected in Edinburgh, United Kingdom, over 3 years between July 2006 and June 2009 using a novel four-way multiplex real-time reverse transcription-PCR (RT-PCR) assay. Coronaviruses were detected in 0.3 to 0.85% of samples in all age groups. Generally, coronaviruses displayed marked winter seasonality between the months of December and April and were not detected in summer months, which is comparable to the pattern seen with influenza viruses. HCoV-229E was the exception; detection was confined to the winter of 2008 and was sporadic in the following year. There were additional longer-term differences in detection frequencies between seasons, with HCoV-OC43 predominant in the first and third seasons and HCoV-HKU1 dominating in the second (see Results for definitions of seasons). A total of 11 to 41% of coronaviruses detected were in samples testing positive for other respiratory viruses, although clinical presentations of coronavirus monoinfections were comparable to those of viruses which have an established role in respiratory disease, such as respiratory syncytial virus, influenza virus, and parainfluenza viruses. The novel multiplex assay for real-time pan-coronavirus detection enhances respiratory virus diagnosis, overcomes potential diagnostic problems arising through seasonal variation in coronavirus frequency, and provides novel insights into the epidemiology and clinical implications of coronaviruses.", "qid": 31, "docid": "g5shtcs5", "rank": 8, "score": 0.7554788589477539}, {"content": "Title: Species\u2010specific clinical characteristics of human coronavirus infection among otherwise healthy adolescents and adults Content: Human coronavirus (HCoV) is a known cause of influenza\u2010like illness (ILI). In a multisite, observational, longitudinal study of ILI among otherwise healthy adolescents and adults, 12% of subjects were PCR\u2010positive for HCoV. The distribution of species was as follows: HCoV\u2010OC43 (34%), HCoV\u2010229E (28%), HCoV\u2010NL63 (22%), and HCoV\u2010HKU1 (16%). We did not observe species\u2010specific differences in the clinical characteristics of HCoV infection, with the exception of HCoV\u2010HKU1, for which the severity of gastrointestinal symptoms trended higher on the fourth day of illness.", "qid": 31, "docid": "6sq1d5jt", "rank": 9, "score": 0.753148078918457}, {"content": "Title: Comparison of the clinical characteristics and outcomes of hospitalized adult COVID-19 and influenza patients: a prospective observational study Content: Objective We compared the clinical characteristics, findings and outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19) or influenza to detect relevant differences. Methods From December 2019 to April 2020, we recruited all eligible hospitalized adults with respiratory infection to a prospective observational study at the HUS Jorvi Hospital, Finland. Influenza and SARS-CoV-2 infections were confirmed by RT-PCR. Follow-up lasted for at least 30 days from admission. Results We included 61 patients, of whom 28 were COVID-19 and 33 influenza patients with median ages of 53 and 56 years. Majority of both COVID-19 and influenza patients were men (61% vs 67%) and had at least one comorbidity (68% vs 85%). Pulmonary diseases and current smoking were less common among COVID-19 than influenza patients (5 [18%] vs 15 [45%], P=0.03 and 1 [4%] vs 10 [30%], P=0.008). In chest x-ray at admission, ground-glass opacities and consolidations were more frequent among COVID-19 than influenza patients (19 [68%] and 7 [21%], P < 0.001). Severe disease and intensive care unit (ICU) admission occurred more often among COVID-19 than influenza patients (26 [93%] vs 19 [58%], P=0.003 and 8 [29%] vs 2 [6%], P=0.034). COVID-19 patients were hospitalized longer than influenza patients (6 days [IQR 4-21] vs 3 [2-4], P<0.001). Conclusion Bilateral ground-glass opacities and consolidations in chest X-ray may help to differentiate COVID-19 from influenza. Hospitalized COVID-19 patients had more severe disease, required longer hospitalization and were admitted to ICU more often than influenza patients, which has important implications for public health policies.", "qid": 31, "docid": "ru2hv6pz", "rank": 10, "score": 0.7528928518295288}, {"content": "Title: Symptomatology during seasonal coronavirus infections in children is associated with viral and bacterial co-detection Content: Lower respiratory tract symptoms during seasonal coronavirus infections in children are associated with RSV co-detection and increased levels of Haemophilus and Fusobacterium species.", "qid": 31, "docid": "9objjgsj", "rank": 11, "score": 0.7525005340576172}, {"content": "Title: Seasonality of infectious diseases and severe acute respiratory syndrome\u2013what we don't know can hurt us Content: Summary The novel severe acute respiratory syndrome (SARS) coronavirus caused severe disease and heavy economic losses before apparently coming under complete control. Our understanding of the forces driving seasonal disappearance and recurrence of infectious diseases remains fragmentary, thus limiting any predictions about whether, or when, SARS will recur. It is true that most established respiratory pathogens of human beings recur in wintertime, but a new appreciation for the high burden of disease in tropical areas reinforces questions about explanations resting solely on cold air or low humidity. Seasonal variation in host physiology may also contribute. Newly emergent zoonotic diseases such as ebola or pandemic strains of influenza have recurred in unpredictable patterns. Most established coronaviruses exhibit winter seasonality, with a unique ability to establish persistent infections in a minority of infected animals. Because SARS coronavirus RNA can be detected in the stool of some individuals for at least 9 weeks, recurrence of SARS from persistently shedding human or animal reservoirs is biologically plausible.", "qid": 31, "docid": "ax87r0bj", "rank": 12, "score": 0.7506253719329834}, {"content": "Title: A Case Series of Patients Coinfected With Influenza and COVID-19 Content: Coronavirus disease 2019, also called COVID-19, is a global pandemic resulting in significant morbidity and mortality worldwide. In the United States, influenza infection occurs mainly during winter and several factors influence the burden of the disease, including circulating virus characteristics, vaccine effectiveness that season, and the duration of the season. We present a case series of 3 patients with coinfection of COVID-19 and influenza, with 2 of them treated successfully and discharged home. We reviewed the literature of patients coinfected with both viruses and discussed the characteristics, as well as treatment options.", "qid": 31, "docid": "u6grnk7p", "rank": 13, "score": 0.7493255138397217}, {"content": "Title: On the global trends and spread of the COVID-19 outbreak: preliminary assessment of the potential relation between location-specific temperature and UV index Content: The novel coronavirus, since its first outbreak in December, has, up till now, affected approximately 114,542 people across 115 countries. Many international agencies are devoting efforts to enhance the understanding of the evolving COVID-19 outbreak on an international level, its influences, and preparedness. At present, COVID-19 appears to affect individuals through person-to-person means, like other commonly found cold or influenza viruses. It is widely known and acknowledged that viruses causing influenza peak during cold temperatures and gradually subside in the warmer temperature, owing to their seasonality. Thus, COVID-19, due to its regular flu-like symptoms, is also expected to show similar seasonality and subside as the global temperatures rise in the northern hemisphere with the onset of spring. Despite these speculations, however, the systematic analysis in the global perspective of the relation between COVID-19 spread and meteorological parameters is unavailable. Here, by analyzing the region- and city-specific affected global data and corresponding meteorological parameters, we show that there is an optimum range of temperature and UV index strongly affecting the spread and survival of the virus, whereas precipitation, relative humidity, cloud cover, etc. have no effect on the virus. Unavailability of pharmaceutical interventions would require greater preparedness and alert for the effective control of COVID-19. Under these conditions, the information provided here could be very helpful for the global community struggling to fight this global crisis. It is, however, important to note that the information presented here clearly lacks any physiological evidences, which may merit further investigation. Thus, any attempt for management, implementation, and evaluation strategies responding to the crisis arising due to the COVID-19 outbreak must not consider the evaluation presented here as the foremost factor.", "qid": 31, "docid": "4ry9b68l", "rank": 14, "score": 0.7472639083862305}, {"content": "Title: Epidemiology of seasonal coronaviruses: Establishing the context for COVID-19 emergence Content: Public health preparedness for coronavirus disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal human coronaviruses (sCoVs) and other cocirculating viruses in the West of Scotland, UK. We analyzed routine diagnostic data for >70,000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43 and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.", "qid": 31, "docid": "snp8o9fw", "rank": 15, "score": 0.7464141845703125}, {"content": "Title: Clinico-epidemiological characteristics of acute respiratory infections by coronavirus OC43, NL63 and 229E Content: Abstract Background and objectives Acute respiratory infection is a very common condition in the general population. The majority of these infections are due to viruses. This study attempted to determine the clinical and epidemiological characteristics of adult patients with respiratory infection by the coronavirus OC43, NL63 and 229E. Patients and methods Between January 2013 and February 2014, we prospectively studied all patients with suspected clinical respiratory infection by taking throat swabs and performing a reverse transcription polymerase chain reaction in search of coronavirus. Results In 48 cases (7.0% of the 686 enrolled patients; 12.6% of the 381 in whom a virus was detected) the presence of a coronavirus demonstrated. In 24 cases, the virus was OC43 (50%); in 14 cases, the virus was NL63 (29%); and in 10 cases, the virus was 229E (21%). The mean age was 54.5 years, with a slight predominance of men. The most common clinical presentations were nonspecific influenza symptoms (43.7%), pneumonia (29.2%) and chronic obstructive pulmonary disease exacerbation (8.3%). Fifty-two percent of the patients required hospitalization, and 2 patients required intensive care. There were no deaths. Conclusion Acute respiratory infections caused by coronavirus mainly affect middle-aged male smokers, who are often affected by previous diseases. The most common clinical picture has been nonspecific influenza symptoms.", "qid": 31, "docid": "m0w8804y", "rank": 16, "score": 0.7461686134338379}, {"content": "Title: The clinical characteristics of pneumonia patients coinfected with 2019 novel coronavirus and influenza virus in Wuhan, China Content: The outbreak of 2019 novel coronavirus (COVID-19) infection emerged in Wuhan, China, in December 2019. Since then the novel coronavirus pneumonia disease has been spreading quickly and many countries and territories have been affected, with major outbreaks in China, South Korea, Italy, and Iran. Influenza virus has been known as a common pathogen in winter and it can cause pneumonia. It was found clinically that very few patients were diagnosed with both COVID-19 and influenza virus. A total of 5 of the 115 patients confirmed with COVID-19 were also diagnosed with influenza virus infection, with three cases being influenza A and two cases being influenza B. In this study, we describe the clinical characteristics of those patients who got infected with COVID-19 as well as influenza virus. Common symptoms at onset of illness included fever (five [100%] patients), cough (five [100%] patients), shortness of breath (five [100%] patients), nasal tampon (three [60%] patients), pharyngalgia (three [60%] patients), myalgia (two [40%] patients), fatigue (two [40%] patients), headache (two [40%] patients), and expectoration (two [40%] patients). The laboratory results showed that compared to the normal values, the patients' lymphocytes were reduced (four [80%] patients), and liver functions alanine aminotransferase and aspartate aminotransferase (two [40%] patients and two [40%] patients) and C-reactive protein (four [80%] patients) were increased when admitted to hospital. They stayed in the hospital for 14, 30, 17, 12, and 19 days (28.4 \u00b1 7.02), respectively. The main complications for the patients were acute respiratory distress syndrome (one [20%] patients), acute liver injury (three [60%] patients), and diarrhea (two [40%] patients). All patients were given antiviral therapy (including oseltamivir), oxygen inhalation, and antibiotics. Three patients were treated with glucocorticoids including two treated with oral glucocorticoids. One of the five patients had transient hemostatic medication for hemoptysis. Fortunately, all patients did not need intensive care unit and were discharged from the hospital without death. In conclusion, those patients with both COVID-19 and influenza virus infection did not appear to show a more severe condition because based on the laboratory findings, imaging studies, and patient prognosis, they showed similar clinical characteristics as those patients with COVID-19 infection only. However, it is worth noting that the symptoms of nasal tampon and pharyngalgia may be more prone to appear for those coinfection patients.", "qid": 31, "docid": "tdptzh5n", "rank": 17, "score": 0.7460314035415649}, {"content": "Title: Coronavirus Occurrence and Transmission Over 8 Years in the HIVE Cohort of Households in Michigan Content: BACKGROUND: As part of the Household Influenza Vaccine Evaluation (HIVE) study, acute respiratory infections (ARI) have been identified in children and adults from 2010 to 2018. METHODS: Annually, 890 to 1441 individuals were followed and contacted weekly to report ARIs. Specimens collected during illness were tested for human coronaviruses (HCoV) types OC43, 229E, HKU1, and NL63. RESULTS: In total, 993 HCoV infections were identified during the 8 years, with OC43 most commonly seen and 229E the least. HCoVs were detected in a limited time period, between December and April/May and peaked in January/February. Highest infection frequency was in children <5 years (18 per 100 person-years), with little variation in older age groups (range, 7 to 11 per 100 person-years). Overall, 9% of adult cases and 20% of cases in children were associated with medical consultation. Of the 993 infections, 260 were acquired from an infected household contact. The serial interval between index and household-acquired cases ranged from 3.2 to 3.6 days and the secondary infection risk ranged from 7.2% to 12.6% by type. CONCLUSIONS: Coronaviruses are sharply seasonal. They appear, based on serial interval and secondary infection risk, to have similar transmission potential to influenza A(H3N2) in the same population.", "qid": 31, "docid": "gfztjt6p", "rank": 18, "score": 0.7459721565246582}, {"content": "Title: Coronavirus occurrence and transmission over 8 years in the HIVE cohort of households in Michigan Content: BACKGROUND: As part of the Household Influenza Vaccine Evaluation (HIVE) study, acute respiratory infections (ARI) have been identified in children and adults over 8 years. METHODS: Annually, 890 to 1441 individuals were followed and contacted weekly to report ARIs. Specimens collected during illness were tested for human coronaviruses (HCoV) types OC43, 229E, HKU1, and NL63. RESULTS: In total, 993 HCoV infections were identified over 8 years, with OC43 most commonly seen and 229E the least. HCoVs were detected in a limited time period, between December and April/May, and peaked in January/February. Highest infection frequency was in children <5 years (18 per 100 person-years), with little variation in older age groups (range: 7 to 11 per 100 person-years). Overall, 9% of adult cases and 20% of cases in children were associated with medical consultation. Of the 993 infections, 260 were acquired from an infected household contact. The serial interval between index and household-acquired cases ranged from 3.2 to 3.6 days and the secondary infection risk ranged from 7.2% to 12.6% by type. CONCLUSIONS: Coronaviruses are sharply seasonal. They appear, based on serial interval and secondary infection risk, to have similar transmission potential to influenza A(H3N2) in the same population.", "qid": 31, "docid": "u5q5ghrc", "rank": 19, "score": 0.7456420660018921}, {"content": "Title: Human Coronavirus and Acute Respiratory Illness in Older Adults with Chronic Obstructive Pulmonary Disease Content: BackgroundThe clinical features and incidence of human coronavirus (HCoV) infections in chronically ill older adults need better definition MethodsHCoV infection was determined on the basis of a 4-fold increase in serum antibody and the detection of HCoV by reverse-transcription polymerase chain reaction. Laboratory-documented influenza (LDI) was detected by serologic assay and culture. HCoV illnesses were compared with other acute respiratory illnesses identified by active surveillance, during the 1998\u201399 winter respiratory-virus season, of 2215 patients with chronic obstructive pulmonary disease who were \u2a7e50 years old and who received influenza vaccines ResultsHCoV-229E and HCoV-OC43 were associated with 90 (14%) of 665 illnesses (HCoV-229E in 22, HCoV-OC43 in 67, and both in 1), LDI with 107 (16%) of 678 illnesses. In multivariate logistic regression analysis, myalgia was less likely with HCoV infection than with LDI (OR, 0.27 [95% confidence limit, 0.13\u20130.58]). A majority of these HCoV and LDI illnesses exhibited each of 11 symptoms and signs of acute respiratory illness. Spirometric results worsened most often with LDI, and many acute respiratory illnesses, regardless of etiology, were associated with hospitalization. A total of 8 illnesses were associated with HCoV-NL63, 1 with HCoV-HKU1 ConclusionsThe frequencies of HCoV and LDI illnesses were similar. HCoV illness was less severe than LDI illness, was accompanied by multiple respiratory and systemic symptoms, and was associated with hospitalization", "qid": 31, "docid": "fhfxnr76", "rank": 20, "score": 0.7421947717666626}, {"content": "Title: Comparison of Hospitalized Patients with pneumonia caused by COVID-19 and influenza A in children under 5 years Content: BACKGROUND: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in Wuhan, considerable attention has been paid on its epidemiology and clinical characteristics in children patients. However, it is also crucial for clinicians to differentiate COVID-19 from other respiratory infectious diseases, such as influenza viruses. METHODS: This was a retrospective study. Two group of COVID-19 patients (n=57) and influenza A patients (n=59) were enrolled. We analyzed and compared their clinical manifestations, imaging characteristics and treatments. RESULTS: The proportions of cough (70.2%), fever (54.4%) and gastrointestinal symptoms (14.1%) in COVID-19 patients were lower than those of influenza A patients (98.3%, P<0.001; 84.7%, P<0.001; and 35.6%, P=0.007; respectively). In addition, COVID-19 patients showed significantly lower levels of leukocytes (7.87 vs. 9.89\u00d7109/L, P=0.027), neutrophils (2.43 vs. 5.16\u00d7109/L, P<0.001), C-reactive protein (CRP; 3.7 vs. 15.1mg/L, P=0.001) and procalcitonin (PCT; 0.09 vs. 0.68mm/h, P<0.001), while lymphocyte levels (4.58 vs. 3.56\u00d7109/L; P=0.006) were significantly higher compared with influenza A patients. In terms of CT imaging, ground-glass opacification in chest CT was more common in COVID-19 patients than in influenza A patients (42.1% vs. 15%, P=0.032). In contrast, consolidation was more common in influenza A patients (25%) than that in COVID-19 patients (5.2%, P=0.025). CONCLUSION: The clinical manifestations and laboratory tests of COVID-19 children are milder than those of influenza A children under 5 years. Additionally, imaging results more commonly presented as ground-glass opacities in COVID-19 patients.", "qid": 31, "docid": "qapadc6p", "rank": 21, "score": 0.741169810295105}, {"content": "Title: Increasing similarity in the dynamics of influenza in two adjacent subtropical Chinese cities following the relaxation of border restrictions. Content: The drivers of influenza seasonality remain heavily debated, especially in tropical/subtropical regions where influenza activity can peak in winter, during the rainy season, or remain constant throughout the year. We compared the epidemiological and evolutionary patterns of seasonal influenza epidemics in Hong Kong and Shenzhen, two adjacent cities in subtropical southern China. This comparison represents a unique natural experiment, as connectivity between these two cities has increased over the past decade. We found that, whilst summer influenza epidemics in Shenzhen used to peak 1-3 months later than those in Hong Kong, the difference decreased after 2005 (P<0.0001). Phylogenetic analysis revealed that influenza isolates from Shenzhen have become genetically closer to those circulating in Hong Kong over time (P = 0.045). Furthermore, although Shenzhen isolates used to be more distant from the global putative source of influenza viruses than isolates from Hong Kong (P<0.001), this difference has narrowed (P = 0.02). Overall, our study reveals that influenza activities show remarkably distinct epidemiological and evolutionary patterns in adjacent subtropical cities and suggests that human mobility patterns can play a major role in influenza dynamics in the subtropics.", "qid": 31, "docid": "rgrp73ca", "rank": 22, "score": 0.7398087382316589}, {"content": "Title: Direct Measurement of Rates of Asymptomatic Infection and Clinical Care-Seeking for Seasonal Coronavirus Content: The pandemic potential of the novel coronavirus (nCoV) that emerged in Wuhan, China, during December 2019 is strongly tied to the number and contagiousness of undocumented human infections. Here we present findings from a proactive longitudinal sampling study of acute viral respiratory infections that documents rates of asymptomatic infection and clinical care seeking for seasonal coronavirus. We find that the majority of infections are asymptomatic by most symptom definitions and that only 4% of individuals experiencing a seasonal coronavirus infection episode sought medical care for their symptoms. These numbers indicate that a very high percentage of seasonal coronavirus infections are undocumented and provide a reference for understanding the spread of the emergent nCoV.", "qid": 31, "docid": "90tccg03", "rank": 23, "score": 0.7395079135894775}, {"content": "Title: The clinical characteristics of pneumonia patients coinfected with 2019 novel coronavirus and influenza virus in Wuhan, China Content: The outbreak of 2019 novel coronavirus (COVID\u201019) infection emerged in Wuhan, China, in December 2019. Since then the novel coronavirus pneumonia disease has been spreading quickly and many countries and territories have been affected, with major outbreaks in China, South Korea, Italy, and Iran. Influenza virus has been known as a common pathogen in winter and it can cause pneumonia. It was found clinically that very few patients were diagnosed with both COVID\u201019 and influenza virus. A total of 5 of the 115 patients confirmed with COVID\u201019 were also diagnosed with influenza virus infection, with three cases being influenza A and two cases being influenza B. In this study, we describe the clinical characteristics of those patients who got infected with COVID\u201019 as well as influenza virus. Common symptoms at onset of illness included fever (five [100%] patients), cough (five [100%] patients), shortness of breath (five [100%] patients), nasal tampon (three [60%] patients), pharyngalgia (three [60%] patients), myalgia (two [40%] patients), fatigue (two [40%] patients), headache (two [40%] patients), and expectoration (two [40%] patients). The laboratory results showed that compared to the normal values, the patients' lymphocytes were reduced (four [80%] patients), and liver functions alanine aminotransferase and aspartate aminotransferase (two [40%] patients and two [40%] patients) and C\u2010reactive protein (four [80%] patients) were increased when admitted to hospital. They stayed in the hospital for 14, 30, 17, 12, and 19 days (28.4 \u00b1 7.02), respectively. The main complications for the patients were acute respiratory distress syndrome (one [20%] patients), acute liver injury (three [60%] patients), and diarrhea (two [40%] patients). All patients were given antiviral therapy (including oseltamivir), oxygen inhalation, and antibiotics. Three patients were treated with glucocorticoids including two treated with oral glucocorticoids. One of the five patients had transient hemostatic medication for hemoptysis. Fortunately, all patients did not need intensive care unit and were discharged from the hospital without death. In conclusion, those patients with both COVID\u201019 and influenza virus infection did not appear to show a more severe condition because based on the laboratory findings, imaging studies, and patient prognosis, they showed similar clinical characteristics as those patients with COVID\u201019 infection only. However, it is worth noting that the symptoms of nasal tampon and pharyngalgia may be more prone to appear for those coinfection patients.", "qid": 31, "docid": "7uoia564", "rank": 24, "score": 0.7385598421096802}, {"content": "Title: Epidemiology characteristics of human coronaviruses in patients with respiratory infection symptoms and phylogenetic analysis of HCoV-OC43 during 2010-2015 in Guangzhou Content: Human coronavirus (HCoV) is one of the most common causes of respiratory tract infection throughout the world. To investigate the epidemiological and genetic variation of HCoV in Guangzhou, south China, we collected totally 13048 throat and nasal swab specimens from adults and children with fever and acute upper respiratory infection symptoms in Gunazhou, south China between July 2010 and June 2015, and the epidemiological features of HCoV and its species were studied. Specimens were screened for HCoV by real-time RT-PCR, and 7 other common respiratory viruses were tested simultaneously by PCR or real-time PCR. HCoV was detected in 294 cases (2.25%) of the 13048 samples, with most of them inpatients (251 cases, 85.4% of HCoV positive cases) and young children not in nursery (53.06%, 156 out of 294 HCoV positive cases). Four HCoVs, as OC43, 229E, NL63 and HKU1 were detected prevalent during 2010\u20132015 in Guangzhou, and among the HCoV positive cases, 60.20% were OC43, 16.67% were 229E, 14.97% were NL63 and 7.82% were HKU1. The month distribution showed that totally HCoV was prevalent in winter, but differences existed in different species. The 5 year distribution of HCoV showed a peak-valley distribution trend, with the detection rate higher in 2011 and 2013 whereas lower in 2010, 2012 and 2014. The age distribution revealed that children (especially those <3 years old) and old people (>50 years) were both high risk groups to be infected by HCoV. Of the 294 HCoV positive patients, 34.69% (101 cases) were co-infected by other common respiratory viruses, and influenza virus was the most common co-infecting virus (30/101, 29.70%). Fifteen HCoV-OC43 positive samples of 2013\u20132014 were selected for S gene sequencing and phylogenetic analysis, and the results showed that the 15 strains could be divided into 2 clusters in the phylogenetic tree, 12 strains of which formed a separate cluster that was closer to genotype G found in Malaysia. It was revealed for the first time that genotype B and genotype G of HCoV-OC43 co-circulated and the newly defined genotype G was epidemic as a dominant genotype during 2013\u20132014 in Guanzhou, south China.", "qid": 31, "docid": "6u2qryih", "rank": 25, "score": 0.7385357618331909}, {"content": "Title: A comparative-descriptive analysis of clinical characteristics in 2019-coronavirus-infected children and adults Content: Acute respiratory disease caused by 2019 novel coronavirus (2019-nCoV) has rapidly spread throughout China. Children and adults show a different clinical course. The purpose of the current study is to comparatively analyze the clinical characteristics of 2019-nCoV infection in children and adults and to explore the possible causes for the discrepancies present. The medical records of 25 adults and 7 children confirmed cases of 2019-2019-nCoV acute respiratory diseases were reviewed retrospectively. All children were family clusters. The total adult patients were differentiated into the local residents of Wuhan, a history of travel to Wuhan and direct contact with people from Wuhan. The numbers were 14 (56%), 10 (40%), and 1 (4%), respectively. The median incubation period of children and adults was 5 days (ranged, 3-12 days) and 4 days (ranged, 2-12 days), respectively. Diarrhoea and/or vomiting (57.1%) were demic by World Health Organiza more common in children, whereas for adults it was myalgia or fatigue (52%). On admission, the percentage of children having pneumonia (5%, 71.4%) was roughly the same as adults (20%, 80%). A total of 20% of adults had leucopoenia, but leukocytosis was more frequently in children (28.6%, P=.014). A higher number of children had elevated creatine kinase isoenzyme (57.1% vs 4%, P=.004). Antiviral therapy was given to all adult patients but to none of the children. In summary, knowledge of these differences between children and adults will not only be helpful for the clinical diagnosis of 2019-nCoV disease, but also for a future discussion on age-specific coronavirus infection.", "qid": 31, "docid": "ltdfyzay", "rank": 26, "score": 0.7383890151977539}, {"content": "Title: A six-year descriptive epidemiological study of human coronavirus infections in hospitalized patients in Hong Kong Content: We conducted a six-year epidemiological study on human coronaviruses (HCoVs) circulating in Hong Kong, using 8275 nasopharyngeal samples from patients with acute respiratory tract infections. HCoVs were detected in 77 (0.93%) of the samples by a pan-HCoV RT-PCR assay. The most frequently detected HCoV species was HCoV-OC43 (0.58%), followed by HCoV-229E (0.15%), HCoV-HKU1 (0.13%) and HCoV-NL63 (0.07%). HCoVs were detected throughout the study period (September 2008\u2013August 2014), with the highest detection rate from September 2010 to August 2011 (22/1500, 1.47%). Different seasonal patterns of each HCoV species in Hong Kong were noted. HCoV-OC43 was predominant in the fall and winter, whereas HCoV-HKU1 showed peak activity in winter, with a few cases occurred in spring and summer. HCoV-229E mainly occurred in winter and spring, while HCoV-NL63 was predominant in summer and autumn. HCoVs most commonly infect the elderly and young children, with median age of 79.5 years (range, 22 days to 95 years). Intriguingly, the detection rate of HCoV-OC43 in the age group of > 80 years (26/2380, 1.09%) was significantly higher than that in the age group of 0\u201310 years (12/2529, 0.47%) (P < 0.05). These data provides new insight into the epidemiology of coronaviruses. [Image: see text]", "qid": 31, "docid": "0mzoti1m", "rank": 27, "score": 0.7382714748382568}, {"content": "Title: Epidemiology of Seasonal Coronaviruses: Establishing the Context for the Emergence of Coronavirus Disease 2019 Content: Public health preparedness for coronavirus (CoV) disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal CoVs (sCoVs) and other cocirculating viruses in the West of Scotland, United Kingdom. We analyzed routine diagnostic data for >70 000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43, and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently, and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.", "qid": 31, "docid": "tdy818j9", "rank": 28, "score": 0.7376688122749329}, {"content": "Title: Overview: The history and pediatric perspectives of severe acute respiratory syndromes: Novel or just like SARS Content: Many respiratory viral infections such as influenza and measles result in severe acute respiratory symptoms and epidemics. In the spring of 2003, an epidemic of coronavirus pneumonia spread from Guangzhou to Hong Kong and subsequently to the rest of the world. The WHO coined the acronym SARS (severe acute respiratory syndrome) and subsequently the causative virus as SARS\u2010CoV. In the summer of 2012, epidemic of pneumonia occurred again in Saudi Arabia which was subsequently found to be caused by another novel coronavirus. WHO coined the term MERS (Middle East respiratory syndrome) to denote the Middle East origin of the novel virus (MERS\u2010CoV). In the winter of 2019, another outbreak of pneumonia occurred in Wuhan, China which rapidly spread globally. Yet another novel coronavirus was identified as the culprit and has been named SARS\u2010CoV\u20102 due to its similarities with SARS\u2010CoV, and the disease as coronavirus disease\u20102019. This overview aims to compare and contrast the similarities and differences of these three major episodes of coronavirus outbreak, and conclude that they are essentially the same viral respiratory syndromes caused by similar strains of coronavirus with different names. Coronaviruses have caused major epidemics and outbreaks worldwide in the last two decades. From an epidemiological perspective, they are remarkably similar in the mode of spread by droplets. Special focus is placed on the pediatric aspects, which carry less morbidity and mortality in all three entities.", "qid": 31, "docid": "4oz6r7op", "rank": 29, "score": 0.737384557723999}, {"content": "Title: Human coronaviruses and other respiratory infections in young adults on a university campus: Prevalence, symptoms, and shedding Content: BACKGROUND: The prevalence, symptom course, and shedding in persons infected with the 4 most common human coronaviruses (HCoV)\u2010229E, HKU1, NL63, and OC43 are poorly described. OBJECTIVES: We estimate their prevalence and associated symptoms among college students identified via a social network study design. PATIENTS/METHODS: We collected 1\u20103 samples (n = 250 specimens) from 176 participants between October 2012 and January 17, 2013: participants with acute respiratory infection (ARI; cough and body aches or chills or fever/feverishness) and their social contacts. Virus was detected using RT\u2010PCR. RESULTS: 30.4% (76/250) of specimens tested positive for any virus tested, and 4.8% (12/250) were positive for 2 or more viruses. Human coronaviruses (HCoVs [22.0%; 55/250]), rhinovirus (7.6%; 19/250), and influenza A (6.4%; 16/250) were most prevalent. Symptoms changed significantly over time among ARI participants with HCoV: the prevalence of cough and chills decreased over 6 days (P = .04, and P = .01, respectively), while runny nose increased over the same period (P = .02). HCoV\u2010NL63 was the most frequent virus detected 6 days following symptom onset (8.9%), followed by rhinovirus (6.7%). CONCLUSIONS: During a 3\u2010month period covering a single season, HCoVs were common, even among social contacts without respiratory symptoms; specific symptoms may change over the course of HCoV\u2010associated illness and were similar to symptoms from influenza and rhinovirus.", "qid": 31, "docid": "t33cp9li", "rank": 30, "score": 0.7362442016601562}, {"content": "Title: Clinical disease in children associated with newly described coronavirus subtypes. Content: OBJECTIVES Coronaviruses cause upper respiratory illness and occasionally lower tract disease in susceptible populations. In this study we examined the prevalence of 4 human coronaviruses, including subtypes OC43, 229E, and the recently described NL63 and HKU1 in a pediatric population presenting to a children's hospital. PATIENTS AND METHODS Specimens collected over a 1-year period from pediatric patients presenting with acute respiratory illness were analyzed for the presence of 4 coronavirus subtypes using consensus and subtype-specific real-time reverse-transcription polymerase chain reaction assays. The demographic and clinical characteristics associated with coronavirus infection were examined retrospectively. RESULTS Coronaviruses were detected in 66 of 1043 children. Eight, 11, 19, and 28 specimens were positive for subtypes 229E, NL63, OC43, and HKU1, respectively. Coronaviruses were detected throughout the study period; all 4 of the subtypes were present simultaneously in December. The acute clinical features were similar across subtypes. Of 32 children infected with a coronavirus as the sole respiratory pathogen, 13 had lower respiratory tract disease. Children whose only detectable respiratory virus was a coronavirus were more likely to have underlying chronic disease than were children coinfected with another respiratory virus. CONCLUSIONS Although 4 subtypes of coronavirus were detected, the recently discovered coronavirus subtypes NL63 and HKU1 accounted for the majority of coronaviruses detected in our cohort of mostly hospitalized children with respiratory symptoms. New subtypes likely represent a substantial portion of previously unexplained respiratory illnesses.", "qid": 31, "docid": "z1qh8286", "rank": 31, "score": 0.7360376119613647}, {"content": "Title: Seasonality of Respiratory Viral Infections Content: The seasonal cycle of respiratory viral diseases has been widely recognized for thousands of years, as annual epidemics of the common cold and influenza disease hit the human population like clockwork in the winter season in temperate regions. Moreover, epidemics caused by viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and the newly emerging SARS-CoV-2 occur during the winter months. The mechanisms underlying the seasonal nature of respiratory viral infections have been examined and debated for many years. The two major contributing factors are the changes in environmental parameters and human behavior. Studies have revealed the effect of temperature and humidity on respiratory virus stability and transmission rates. More recent research highlights the importance of the environmental factors, especially temperature and humidity, in modulating host intrinsic, innate, and adaptive immune responses to viral infections in the respiratory tract. Here we review evidence of how outdoor and indoor climates are linked to the seasonality of viral respiratory infections. We further discuss determinants of host response in the seasonality of respiratory viruses by highlighting recent studies in the field. Expected final online publication date for the Annual Review of Virology, Volume 7 is September 29, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.", "qid": 31, "docid": "5dfg0f5d", "rank": 32, "score": 0.7360012531280518}, {"content": "Title: Seasonality of Respiratory Viral Infections. Content: The seasonal cycle of respiratory viral diseases has been widely recognized for thousands of years, as annual epidemics of the common cold and influenza disease hit the human population like clockwork in the winter season in temperate regions. Moreover, epidemics caused by viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and the newly emerging SARS-CoV-2 occur during the winter months. The mechanisms underlying the seasonal nature of respiratory viral infections have been examined and debated for many years. The two major contributing factors are the changes in environmental parameters and human behavior. Studies have revealed the effect of temperature and humidity on respiratory virus stability and transmission rates. More recent research highlights the importance of the environmental factors, especially temperature and humidity, in modulating host intrinsic, innate, and adaptive immune responses to viral infections in the respiratory tract. Here we review evidence of how outdoor and indoor climates are linked to the seasonality of viral respiratory infections. We further discuss determinants of host response in the seasonality of respiratory viruses by highlighting recent studies in the field. Expected final online publication date for the Annual Review of Virology, Volume 7 is September 29, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.", "qid": 31, "docid": "1npav6m4", "rank": 33, "score": 0.7360012531280518}, {"content": "Title: Epidemiology and clinical characteristics of human coronaviruses OC43, 229E, NL63, and HKU1: a study of hospitalized children with acute respiratory tract infection in Guangzhou, China Content: Human coronaviruses (HCoV) OC43, 229E, NL63, and HKU1 are common respiratory viruses which cause various respiratory diseases, including pneumonia. There is a paucity of evidence on the epidemiology and clinical manifestations of these four HCoV strains worldwide. We collected 11,399 throat swabs from hospitalized children with acute respiratory tract infection from July 2009 to June 2016 in Guangzhou, China. These were tested for four strains of HCoV infection using real-time polymerase chain reaction (PCR). HCoV-positive patients were then tested for 11 other respiratory pathogens. 4.3% (489/11399) of patients were positive for HCoV, of which 3.0% were positive for OC43 (346/11399), 0.6% for 229E (65/11399), 0.5% for NL63 (60/11399), and 0.3% for HKU1 (38/11399). Patients aged 7\u201312 months had the highest prevalence of HCoV and OC43 when compared with other age groups (p < 0.001). The peak seasons of infection varied depending on the HCoV strain. Patients infected with a single strain of HCoV infection were less likely to present fever (\u2265 38 \u00b0C) (p = 0.014) and more likely to present pulmonary rales (p = 0.043) than those co-infected with more than one HCoV strain or other respiratory pathogens. There were also significant differences in the prevalence of certain symptoms, including coughing (p = 0.032), pneumonia (p = 0.026), and abnormal pulmonary rales (p = 0.002) according to the strain of HCoV detected. This retrospective study of the prevalence of four HCoV strains and clinical signs among a large population of pediatric patients in a subtropical region of China provides further insight into the epidemiology and clinical features of HCoV.", "qid": 31, "docid": "9erqp86r", "rank": 34, "score": 0.7358314990997314}, {"content": "Title: Clinical Impact of Human Coronaviruses 229E and OC43 Infection in Diverse Adult Populations Content: Background. The incidence and clinical impact of coronavirus (CoV) infection in elderly persons and those with underlying cardiopulmonary disease over a long duration is not well described. We determined the incidence and clinical impact of 229E and OC43 CoV in this population during 4 consecutive winters, and compared illnesses to influenza A, respiratory syncytial virus, and human metapneumovirus. Methods. CoV 229E and OC43 were detected by reverse transcription polymerase chain reaction and serology in 4 adult populations under surveillance for acute respiratory illness during the winters of 1999\u20132003. Cohorts included healthy young adults, healthy elderly adults, high-risk adults with underlying cardiopulmonary disease, and a hospitalized group. Results. Three hundred ninety-eight CoV infections were identified, with annual infection rates ranging from 2.8% to 26% in prospective cohorts, and prevalence ranging from 3.3% to 11.1% in the hospitalized cohort. The incidence of infections with each strain was similar, although asymptomatic infection and viral coinfection was significantly more common with 229E than OC43 infection. Although the incidence and clinical manifestations were similar for each strain, OC43-infected subjects tended to seek more medical care, as OC43 was twice as common as 229E among the hospitalized cohort. Conclusions. CoV infections in the elderly are frequent, likely causing substantial medical disease burden.", "qid": 31, "docid": "pvoe8enz", "rank": 35, "score": 0.7355514168739319}, {"content": "Title: Human coronavirus in young children hospitalized for acute respiratory illness and asymptomatic controls. Content: BACKGROUND Human coronaviruses (HCoVs) have been detected in children with upper and lower respiratory symptoms, but little is known about their relationship with severe respiratory illness. OBJECTIVE To compare the prevalence of HCoV species among children hospitalized for acute respiratory illness and/or fever (ARI/fever) with that among asymptomatic controls and to assess the severity of outcomes among hospitalized children with HCoV infection compared with other respiratory viruses. METHODS From December 2003 to April 2004 and October 2004 to April 2005, we conducted prospective, population-based surveillance of children <5 years of age hospitalized for ARI/fever in 3 US counties. Asymptomatic outpatient controls were enrolled concurrently. Nasal/throat swabs were tested for HCoV species HKU1, NL63, 229E, and OC43 by real-time reverse-transcription polymerase chain reaction. Specimens from hospitalized children were also tested for other common respiratory viruses. Demographic and medical data were collected by parent/guardian interview and medical chart review. RESULTS Overall, HCoV was detected in 113 (7.6%) of 1481 hospitalized children (83 [5.7%] after excluding 30 cases coinfected with other viruses) and 53 (7.1%) of 742 controls. The prevalence of HCoV or individual species was not significantly higher among hospitalized children than controls. Hospitalized children testing positive for HCoV alone tended to be less ill than those infected with other viruses, whereas those coinfected with HCoV and other viruses were clinically similar to those infected with other viruses alone. CONCLUSIONS In this study of children hospitalized for ARI/fever, HCoV infection was not associated with hospitalization or with increased severity of illness.", "qid": 31, "docid": "vbye4nrj", "rank": 36, "score": 0.7353946566581726}, {"content": "Title: Comparison of Hospitalized Patients with pneumonia caused by COVID-19 and influenza A in children under 5 years Content: Abstract Background Since the outbreak of Coronavirus Disease 2019 (COVID-19) in Wuhan, considerable attention has been paid on its epidemiology and clinical characteristics in children patients. However, it is also crucial for clinicians to differentiate COVID-19 from other respiratory infectious diseases, such as influenza viruses. Methods This was a retrospective study. Two group of COVID-19 patients (n=57) and influenza A patients (n=59) were enrolled. We analyzed and compared their clinical manifestations, imaging characteristics and treatments. Results The proportions of cough (70.2%), fever (54.4%) and gastrointestinal symptoms (14.1%) in COVID-19 patients were lower than those of influenza A patients (98.3%, P<0.001; 84.7%, P<0.001; and 35.6%, P=0.007; respectively). In addition, COVID-19 patients showed significantly lower levels of leukocytes (7.87 vs. 9.89\u00d7109/L, P=0.027), neutrophils (2.43 vs. 5.16\u00d7109/L, P<0.001), C-reactive protein (CRP; 3.7 vs. 15.1mg/L, P=0.001) and procalcitonin (PCT; 0.09 vs. 0.68mm/h, P<0.001), while lymphocyte levels (4.58 vs. 3.56\u00d7109/L; P=0.006) were significantly higher compared with influenza A patients. In terms of CT imaging, ground-glass opacification in chest CT was more common in COVID-19 patients than in influenza A patients (42.1% vs. 15%, P=0.032). In contrast, consolidation was more common in influenza A patients (25%) than that in COVID-19 patients (5.2%, P=0.025). Conclusion The clinical manifestations and laboratory tests of COVID-19 children are milder than those of influenza A children under 5 years. Additionally, imaging results more commonly presented as ground-glass opacities in COVID-19 patients.", "qid": 31, "docid": "1cfwj5uq", "rank": 37, "score": 0.7352655529975891}, {"content": "Title: A comparative-descriptive analysis of clinical characteristics in 2019-Coronavirus-infected children and adults. Content: Acute respiratory disease (ARD) caused by 2019 novel coronavirus (2019-nCoV) has rapidly spread throughout China. Children and adults show a different clinical course. The purpose of the current study is to comparatively analyze the clinical characteristics of 2019-nCoV infection in children and adults and to explore the possible causes for the discrepancies present. The medical records of 25 adults and 7 children confirmed cases of 2019-nCoV ARD were reviewed retrospectively. All children were family clusters. The total adult patients were differentiated into: the local residents of Wuhan, a history of travel to Wuhan and direct contact with people from Wuhan. The numbers were 14 (56%), 10 (40%) & 1 (4%), respectively. The median incubation period of children and adults was 5 days (range 3-12 days) and 4 days (range 2-12 days), respectively. Diarrhoea and/or vomiting (57.1%) were more common in children, whereas for adults it was myalgia or fatigue (52%). On admission, the percentage of children having pneumonia (5, 71.4%) was roughly the same as adults (20, 80%). 20% of adults had leucopoenia, but leukocytosis was more frequently in children (28.6%, P=0.014). A higher number of children had elevated creatine kinase isoenzyme (57.1% vs. 4%, P=0.004). Antiviral therapy was given to all adult patients but to none of the children. In summary, knowledge of these differences between children and adults will not only be helpful for the clinical diagnosis of 2019 novel coronavirus disease (COVID-19), but also for a future discussion on age-specific coronavirus infection. This article is protected by copyright. All rights reserved.", "qid": 31, "docid": "4oocm6o1", "rank": 38, "score": 0.7343525886535645}, {"content": "Title: A persistently infecting coronavirus in hibernating Myotis lucifugus, the North American little brown bat Content: Bats are important reservoir hosts for emerging viruses, including coronaviruses that cause diseases in people. Although there have been several studies on the pathogenesis of coronaviruses in humans and surrogate animals, there is little information on the interactions of these viruses with their natural bat hosts. We detected a coronavirus in the intestines of 53/174 hibernating little brown bats (Myotis lucifugus), as well as in the lungs of some of these individuals. Interestingly, the presence of the virus was not accompanied by overt inflammation. Viral RNA amplified from little brown bats in this study appeared to be from two distinct clades. The sequences in clade 1 were very similar to the archived sequence derived from little brown bats and the sequences from clade 2 were more closely related to the archived sequence from big brown bats. This suggests that two closely related coronaviruses may circulate in little brown bats. Sequence variation among coronavirus detected from individual bats suggested that infection occurred prior to hibernation, and that the virus persisted for up to 4 months of hibernation in the laboratory. Based on the sequence of its genome, the coronavirus was placed in the Alphacoronavirus genus, along with some human coronaviruses, bat viruses and the porcine epidemic diarrhoea virus. The detection and identification of an apparently persistent coronavirus in a local bat species creates opportunities to understand the dynamics of coronavirus circulation in bat populations.", "qid": 31, "docid": "5iw42yjq", "rank": 39, "score": 0.7336070537567139}, {"content": "Title: Human Coronavirus Infections in Israel: Epidemiology, Clinical Symptoms and Summer Seasonality of HCoV-HKU1 Content: Human coronaviruses (HCoVs) cause mild to severe respiratory diseases. Six types of HCoVs have been discovered, the most recent one termed the Middle East respiratory syndrome coronavirus (MERS-CoV). The aim of this study is to monitor the circulation of HCoV types in the population during 2015\u20132016 in Israel. HCoVs were detected by real-time PCR analysis in 1910 respiratory samples, collected from influenza-like illness (ILI) patients during the winter sentinel influenza survey across Israel. Moreover, 195 HCoV-positive samples from hospitalized patients were detected during one year at Soroka University Medical Center. While no MERS-CoV infections were detected, 10.36% of patients in the survey were infected with HCoV-OC43 (43.43%), HCoV-NL63 (44.95%), and HCoV-229E (11.62%) viruses. The HCoVs were shown to co-circulate with respiratory syncytial virus (RSV) and to appear prior to influenza virus infections. HCoV clinical symptoms were more severe than those of RSV infections but milder than influenza symptoms. Hospitalized patients had similar HCoV types percentages. However, while it was absent from the public winter survey, 22.6% of the patients were HCoV-HKU1 positives, mainly during the spring-summer period.", "qid": 31, "docid": "yg8qo13v", "rank": 40, "score": 0.7335629463195801}, {"content": "Title: Coronavirus Immunoreactivity in Individuals With a Recent Onset of Psychotic Symptoms Content: Prenatal influenza exposure increases the risk for schizophrenia and brings to question how other respiratory viruses may contribute to neuropsychiatric disease etiopathology. Human coronaviruses cause respiratory infections that range in seriousness from common colds to severe acute respiratory syndrome. Like influenza, coronaviruses can be neurotropic. To test for associations between coronaviruses and serious mental disorders, we utilized a recently developed assay and measured immunoglobulin G (IgG) response against 4 human coronavirus strains (229E, HKU1, NL63, and OC43) in 106 patients with a recent onset of psychotic symptoms and 196 nonpsychiatric controls. We expressed results quantitatively as antibody levels and qualitatively as seroprevalence relative to a defined seropositivity cutoff value. Patient IgG levels were higher than controls for HKU1, NL63, and OC43, with HKU1 and NL63 both showing highly significant patient-to-control differences (HKU1, P \u2264 .002; NL63, P \u2264 .00001). All 4 coronaviruses were more seroprevalent in patients vs controls, with greatest intergroup differences observed for HKU1 (93% vs 77%, P \u2264 .0001). HKU1 and NL63 associations with the patient group were further supported by multivariate analyses that controlled for age, gender, race, socioeconomic status, and smoking status (HKU1, odds ratio [OR] = 1.32, 95% confidence interval [CI] = 1.03\u20131.67, P \u2264 .027; NL63, OR = 2.42, 95% CI = 1.25\u20134.66, P \u2264 .008). Among patients, NL63 was associated with schizophrenia-spectrum (OR = 3.10, 95% CI = 1.27\u20137.58, P \u2264 .013) but not mood disorders. HKU1 and NL63 coronavirus exposures may represent comorbid risk factors in neuropsychiatric disease. Future studies should explore links between the timing of coronavirus infections and subsequent development of schizophrenia and other disorders with psychotic symptoms.", "qid": 31, "docid": "q41elfwt", "rank": 41, "score": 0.7334597110748291}, {"content": "Title: COVID-19 in 2 Persons with Mild Upper Respiratory Tract Symptoms on a Cruise Ship, Japan Content: We describe 2 cases of coronavirus disease in patients with mild upper respiratory symptoms. Both patients worked on a cruise ship quarantined off the coast of Japan. One patient had persistent, low-grade upper respiratory tract symptoms without fever. The other patient had rapid symptom cessation but persistent viral RNA detection.", "qid": 31, "docid": "9xqw6rmo", "rank": 42, "score": 0.7328949570655823}, {"content": "Title: Overview: The history and pediatric perspectives of severe acute respiratory syndromes: Novel or just like SARS Content: Many respiratory viral infections such as influenza and measles result in severe acute respiratory symptoms and epidemics. In the spring of 2003, an epidemic of coronavirus pneumonia spread from Guangzhou to Hong Kong and subsequently to the rest of the world. The WHO coined the acronym SARS (severe acute respiratory syndrome) and subsequently the causative virus as SARS-CoV. In the summer of 2012, epidemic of pneumonia occurred again in Saudi Arabia which was subsequently found to be caused by another novel coronavirus. WHO coined the term MERS (Middle East respiratory syndrome) to denote the Middle East origin of the novel virus (MERS-CoV). In the winter of 2019, another outbreak of pneumonia occurred in Wuhan, China which rapidly spread globally. Yet another novel coronavirus was identified as the culprit and has been named SARS-CoV-2 due to its similarities with SARS-CoV, and the disease as coronavirus disease-2019. This overview aims to compare and contrast the similarities and differences of these three major episodes of coronavirus outbreak, and conclude that they are essentially the same viral respiratory syndromes caused by similar strains of coronavirus with different names. Coronaviruses have caused major epidemics and outbreaks worldwide in the last two decades. From an epidemiological perspective, they are remarkably similar in the mode of spread by droplets. Special focus is placed on the pediatric aspects, which carry less morbidity and mortality in all three entities.", "qid": 31, "docid": "49ybh6fj", "rank": 43, "score": 0.7327273488044739}, {"content": "Title: Genetic variability of human coronavirus OC43\u2010, 229E\u2010, and NL63\u2010like strains and their association with lower respiratory tract infections of hospitalized infants and immunocompromised patients Content: In the winter\u2013spring seasons 2003\u20132004 and 2004\u20132005, 47 (5.7%) patients with acute respiratory infection associated with human coronavirus (hCoV) 229E\u2010, NL63\u2010, and OC43\u2010like strains were identified among 823 (597 immunocompetent and 226 immunocompromised) patients admitted to hospital with acute respiratory syndromes. Viral infections were diagnosed by either immunological (monoclonal antibodies) or molecular (RT\u2010PCR) methods. Each of two sets of primer pairs developed for detection of all CoVs (panCoV) failed to detect 15 of the 53 (28.3%) hCoV strains identified. On the other hand, all hCoV strains could be detected by using type\u2010specific primers targeting genes 1ab and N. The HuH\u20107 cell line was found to be susceptible to isolation and identification of OC43\u2010 and 229E\u2010like strains. Overall, hCoV infection was caused by OC43\u2010like, 229E\u2010like, and NL63\u2010like strains in 25 (53.2%), 10 (21.3%), and 9 (19.1%) patients, respectively. In addition, three patients (6.4%) were infected by untypeable hCoV strains. NL63\u2010like strains were not found to circulate in 2003\u20132004, and 229E\u2010like strains did not circulate in 2004\u20132005, while OC43\u2010like strains were detected in both seasons. The monthly distribution reached a peak during January through March. Lower predominated over upper respiratory tract infections in each age group. In addition, hCoV infections interested only immunocompetent infants and young children during the first year of life, while all adults were immunocompromised patients. Coinfections of hCoVs and other respiratory viruses (mostly interesting the first year of life) were observed in 14 of the 47 (29.8%) patients and were associated with severe respiratory syndromes more frequently than hCoV single infections (P = 0.002). In conclusion, the use of multiple primer sets targeting different genes is recommended for diagnosis of all types of hCoV infection. In addition, the detection of still untypeable hCoV strains suggests that the number of hCoVs involved in human pathology might further increase. Finally, hCoVs should be screened routinely for in both infants and immunocompromised patients with acute respiratory infection. J. Med. Virol. 78:938\u2013949, 2006. \u00a9 2006 Wiley\u2010Liss, Inc.", "qid": 31, "docid": "cmjnb0al", "rank": 44, "score": 0.73265141248703}, {"content": "Title: [Seroepidemiological study of coronavirus infection in children and adults in St. Petersburg]. Content: As the result of prolonged (17 years) observations of patients with acute respiratory infections hospitalized in basic departments of clinics of the Research Institute of Influenza, coronavirus infection was found to be the cause of respiratory diseases, on the average, in 12% of cases (in some years in 6.8% to 28.6% of cases). The analysis of extensive morbidity rates among different age groups of the population showed that children were affected by coronavirus infection 5-7 times more often than adults. Three year cycles of this infection were established. The periods of coronaviruses activation were accompanied by their detection in patient material by electron-microscopy, a sharp increase of immune response of patients as well as in the number of nosocomial infections and the proportion of the monoinfection of the coronavirus nature. Coronaviruses played the leading role among other viruses in the etiology of hospital respiratory infections. Mucosal antibodies to coronaviruses in the secretions of the nasal cavity proved to be more important than serum antibodies not only in protection from infection, but also in the pattern of clinical manifestations of the disease.", "qid": 31, "docid": "9yg2ikfm", "rank": 45, "score": 0.7319827675819397}, {"content": "Title: Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza Content: Importance: It is uncertain whether coronavirus disease 2019 (COVID-19) is associated with a higher risk of ischemic stroke than would be expected from a viral respiratory infection. Objective: To compare the rate of ischemic stroke between patients with COVID-19 and patients with influenza, a respiratory viral illness previously associated with stroke. Design, Setting, and Participants: This retrospective cohort study was conducted at 2 academic hospitals in New York City, New York, and included adult patients with emergency department visits or hospitalizations with COVID-19 from March 4, 2020, through May 2, 2020. The comparison cohort included adults with emergency department visits or hospitalizations with influenza A/B from January 1, 2016, through May 31, 2018 (spanning moderate and severe influenza seasons). Exposures: COVID-19 infection confirmed by evidence of severe acute respiratory syndrome coronavirus 2 in the nasopharynx by polymerase chain reaction and laboratory-confirmed influenza A/B. Main Outcomes and Measures: A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, mechanisms, and outcomes. We used logistic regression to compare the proportion of patients with COVID-19 with ischemic stroke vs the proportion among patients with influenza. Results: Among 1916 patients with emergency department visits or hospitalizations with COVID-19, 31 (1.6%; 95% CI, 1.1%-2.3%) had an acute ischemic stroke. The median age of patients with stroke was 69 years (interquartile range, 66-78 years); 18 (58%) were men. Stroke was the reason for hospital presentation in 8 cases (26%). In comparison, 3 of 1486 patients with influenza (0.2%; 95% CI, 0.0%-0.6%) had an acute ischemic stroke. After adjustment for age, sex, and race, the likelihood of stroke was higher with COVID-19 infection than with influenza infection (odds ratio, 7.6; 95% CI, 2.3-25.2). The association persisted across sensitivity analyses adjusting for vascular risk factors, viral symptomatology, and intensive care unit admission. Conclusions and Relevance: In this retrospective cohort study from 2 New York City academic hospitals, approximately 1.6% of adults with COVID-19 who visited the emergency department or were hospitalized experienced ischemic stroke, a higher rate of stroke compared with a cohort of patients with influenza. Additional studies are needed to confirm these findings and to investigate possible thrombotic mechanisms associated with COVID-19.", "qid": 31, "docid": "um8e05j7", "rank": 46, "score": 0.7319231033325195}, {"content": "Title: Seasonal influenza activity in Hong Kong and its association with meteorological variations. Content: Influenza seasons appear consistently in the temperate regions, but are more variable in tropical/subtropical regions. The determinant for such variation remains poorly understood. This study documented the activity of influenza over a 10-year period in Hong Kong; examining its association with changes in temperature and relative humidity. The two types of influenza exhibited different correlations with meteorological variations. Influenza A showed two seasonal peaks occurring respectively in winter/spring and summer months in most years. Influenza B showed a clear winter/spring peak, but its activity during summer months was more variable. Cold and humid conditions were associated with a higher activity of both influenza A and B. In contrast, hot and humid conditions were associated with a higher activity of influenza A, but were associated with only a moderate, less consistent increase in the activity of influenza B. A trend of increase in the magnitude of summer peaks of influenza A, but not influenza B, was observed. A hypothetical 2 degrees C rise in temperature would decrease the proportion of favorable days for influenza A in December-April from 78% to 57%, but an increase from 58% to 71% in May-November; with a similar effect (from 83% to 62%) for influenza B during December-April, but a modest change (from 17% to 18%) during May-November. The presence of two seasonal peaks of influenza annually emphasizes the need to evaluate the duration of protective immunity offered by vaccination. Further study on the effects of climate change and global warming on the activity of influenza is warranted.", "qid": 31, "docid": "sy53tfr6", "rank": 47, "score": 0.7318310737609863}, {"content": "Title: Does COVID-19 infection impact on the trend of seasonal influenza infection? 11 countries and regions, from 2014 to 2020 Content: OBJECTIVES: Infection due to the 2019 novel coronavirus disease (COVID-19) is dramatically widespread around the world. The COVID-19 pandemic could increase public concern to prevent infectious disease. The present study aimed to assess the relationship between the COVID-19 epidemic and the potential decrease in seasonal influenza cases. METHODS: This study was performed to show trends in seasonal influenza cases from the 2014-2015 season to the 2019-2020 season in 11 countries and regions, and evaluate whether the trends in the 2019-2020 season were different before and after the COVID-19 pandemic compared to previous seasons using a quasi-experimental difference-in-difference design. RESULTS: In East Asia, the number of seasonal influenza cases in the 2019-20 season was lower after the COVID-19 transmission compared to previous years. However, this was not the case in American countries or in European countries. CONCLUSION: The COVID-19 epidemic might have altered health behaviors, resulting in an unexpected reduction of seasonal influenza cases.", "qid": 31, "docid": "l11puhp4", "rank": 48, "score": 0.7315253019332886}, {"content": "Title: Influenza vaccination in the COVID-19 era Content: Influenza spreads globally annually with significant paediatric and adult attack rates and considerable morbidity, mortality and the exacerbation of extant chronic disease. In the northern and southern hemispheres, outbreaks occur mainly in the respective winter seasons. Influenza vaccination is available but only partially effective. In the absence of a vaccine, in winter, novel coronavirus COVID-19 will also circulate in parallel with seasonal influenza. Thus far it appears that with the current strains of these two viruses, the clinical outcome of co-infection is not significantly worse than infection with COVID-19 alone. However, several strains of influenza circulate, including strains still to come. Similarly, COVID-19 has several strains, with probably more to come. This paper discusses these issues and estimates ideal minimum influenza vaccination coverage based on an estimated influenza Basic Reproduction Number (R0) of 0.9-2.1 so as to obtain herd immunity or approach it. There is a strong argument for attempting near universal population coverage with the annual influenza vaccine leading up to next winter.", "qid": 31, "docid": "fm0dwft0", "rank": 49, "score": 0.7313369512557983}, {"content": "Title: Children in Coronaviruses\u2019 Wonderland: What Clinicians Need to Know Content: Human coronaviruses (HCoVs) commonly cause mild upper-respiratory tract illnesses but can lead to more severe and diffusive diseases. A variety of signs and symptoms may be present, and infections can range in severity from the common cold and sore throat to more serious laryngeal or tracheal infections, bronchitis, and pneumonia. Among the seven coronaviruses that affect humans (SARS)-CoV, the Middle East respiratory syndrome (MERS)-CoV, and the most recent coronavirus disease 2019 (COVID-19) represent potential life-threatening diseases worldwide. In adults, they may cause severe pneumonia that evolves in respiratory distress syndrome and multiorgan failure with a high mortality rate. Children appear to be less susceptible to develop severe clinical disease and present usually with mild and aspecific symptoms similar to other respiratory infections typical of childhood. However, some children, such as infants, adolescents, or those with underlying diseases may be more at-risk categories and require greater caution from clinicians. Available data on pediatric coronavirus infections are rare and scattered in the literature. The purpose of this review is to provide to clinicians a complete and updated panel useful to recognize and characterize the broad spectrum of clinical manifestations of coronavirus infections in the pediatric age.", "qid": 31, "docid": "3plpi6i9", "rank": 50, "score": 0.7310295701026917}, {"content": "Title: Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza. Content: Importance It is uncertain whether coronavirus disease 2019 (COVID-19) is associated with a higher risk of ischemic stroke than would be expected from a viral respiratory infection. Objective To compare the rate of ischemic stroke between patients with COVID-19 and patients with influenza, a respiratory viral illness previously associated with stroke. Design, Setting, and Participants This retrospective cohort study was conducted at 2 academic hospitals in New York City, New York, and included adult patients with emergency department visits or hospitalizations with COVID-19 from March 4, 2020, through May 2, 2020. The comparison cohort included adults with emergency department visits or hospitalizations with influenza A/B from January 1, 2016, through May 31, 2018 (spanning moderate and severe influenza seasons). Exposures COVID-19 infection confirmed by evidence of severe acute respiratory syndrome coronavirus 2 in the nasopharynx by polymerase chain reaction and laboratory-confirmed influenza A/B. Main Outcomes and Measures A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, mechanisms, and outcomes. We used logistic regression to compare the proportion of patients with COVID-19 with ischemic stroke vs the proportion among patients with influenza. Results Among 1916 patients with emergency department visits or hospitalizations with COVID-19, 31 (1.6%; 95% CI, 1.1%-2.3%) had an acute ischemic stroke. The median age of patients with stroke was 69 years (interquartile range, 66-78 years); 18 (58%) were men. Stroke was the reason for hospital presentation in 8 cases (26%). In comparison, 3 of 1486 patients with influenza (0.2%; 95% CI, 0.0%-0.6%) had an acute ischemic stroke. After adjustment for age, sex, and race, the likelihood of stroke was higher with COVID-19 infection than with influenza infection (odds ratio, 7.6; 95% CI, 2.3-25.2). The association persisted across sensitivity analyses adjusting for vascular risk factors, viral symptomatology, and intensive care unit admission. Conclusions and Relevance In this retrospective cohort study from 2 New York City academic hospitals, approximately 1.6% of adults with COVID-19 who visited the emergency department or were hospitalized experienced ischemic stroke, a higher rate of stroke compared with a cohort of patients with influenza. Additional studies are needed to confirm these findings and to investigate possible thrombotic mechanisms associated with COVID-19.", "qid": 31, "docid": "r0t22zpm", "rank": 51, "score": 0.730268120765686}, {"content": "Title: Comparative Analysis of Early-Stage Clinical Features Between COVID-19 and Influenza A H1N1 Virus Pneumonia Content: Introduction: Influenza virus pneumonia and COVID-19 are two different types of respiratory viral pneumonia but with very similar clinical manifestations. The aim of the present study was to help clinicians gain a better understanding about differences between Influenza virus pneumonia and COVID-19 by comparative analysis of the early-stage clinical features. Methods: Clinical data of patients with confirmed diagnosis of COVID-19 and influenza A pneumonia identified in our hospital were collected and analyzed retrospectively to identify the clinical features that could differentiate between the two types of viral pneumonia. Results: The two types of viral pneumonia mainly affected adults, especially people over 50 years, with no gender difference between them. Fever, cough, sputum and muscle soreness were the most common symptoms of COVID-19. Some patients with COVID-19 may also exhibit digestive tract symptoms. Elevation of C-reactive protein (CRP) was a more common phenomenon in patients with COVID-19 than that in patients with influenza A H1N1 virus pneumonia. In addition, eosinophil count was decreased and the monocyte percentage was increased in COVID-19 patients. The grid-form shadow was a typical presentation of COVID-19 on the lung CT image, and the disease usually progressed quickly within a week. Conclusion: Influenza pneumonia and COVID-19 are two different types of respiratory viral pneumonia with very similar clinical manifestations. The percentage of monocytes is increased and the eosinophil count is decreased in COVID-19. Glass-ground density exudation shadow located peripherally is the typical sign of COVID-19 on the lung CT image, and the shadow often with grid-form sign. These features may not be typically observed in patients with influenza pneumonia. Chest CT scan combined with nucleic acid detection is an effective and accurate method for diagnosing COVID-19. Blood routine test has a limited diagnostic value in differentiating the two forms of pneumonia.", "qid": 31, "docid": "5dontosm", "rank": 52, "score": 0.7299014329910278}, {"content": "Title: Incubation period as part of the case definition of severe respiratory illness caused by a novel coronavirus. Content: Non-specific symptoms of acute respiratory viral infections make it difficult for many countries without ongoing transmission of a novel coronavirus to rule out other possibilities including influenza before isolating imported febrile individuals with a possible exposure history. The incubation period helps differential diagnosis, and up to two days is suggestive of influenza. It is worth including the incubation period in the case definition of novel coronavirus infection.", "qid": 31, "docid": "xfiqlck4", "rank": 53, "score": 0.729588508605957}, {"content": "Title: Molecular epidemiology and characterization of human coronavirus in Thailand, 2012\u20132013 Content: BACKGROUND: Coronavirus causes respiratory infections in humans. To determine the prevalence of human coronavirus (HCoV) infection among patients with influenza-like illness, 5833 clinical samples from nasopharyngeal swabs and aspirates collected between January 2012 and December 2013 were examined. RESULTS: HCoV was found in 46 (0.79 %) samples. There were 19 (0.32 %) HCoV-HKU1, 19 (0.32 %) HCoV-NL63, 5 (0.09 %) HCoV-229E, and 3 (0.05 %) HCoV-OC43. None of the sample tested positive for MERS-CoV. The majority (54 %) of the HCoV-positive patients were between the ages of 0 and 5 years. HCoV was detected throughout the 2-year period and generally peaked from May to October, which coincided with the rainy season. Phylogenetic trees based on the alignment of the spike (S) gene sequences suggest an emergence of a new clade for HCoV-229E. CONCLUSIONS: The data in this study provide an insight into the prevalence of the recent circulating HCoVs in the region.", "qid": 31, "docid": "x6736prq", "rank": 54, "score": 0.7294811606407166}, {"content": "Title: Coronavirus and Other Respiratory Illnesses Comparing Older with Young Adults Content: Abstract Background Study of human coronavirus and other virus-associated respiratory illnesses is needed to describe their clinical effects on chronically ill, older adults. Methods A prospective study during 2009 to 2013 clinically assessed acute respiratory illnesses soon after onset and 3 to 4 weeks later in patients aged \u226560 years with chronic lung and heart diseases (group 1, 100 subjects) and healthy adults aged 18 to 40 years (group 2, 101 subjects). Respiratory secretions were tested for nucleic acids of a panel of respiratory viruses. An increase in antibody titer was assessed for 4 coronavirus strains. Results Virus-associated illnesses (29 [39.1%] of 74 illnesses in group 1 and 59 [48.7%] of 121 illnesses in group 2) occurred in all calendar quarters, most commonly in the first and fourth quarters. Coronaviruses (group 1: 14 [18.9%] illnesses; group 2: 26 [21.5%] illnesses) and enteroviruses/rhinoviruses (group 1: 14 [18.9%] illnesses; group 2: 37 [30.6%] illnesses) were most common. Virus co-infections occurred in 10 illnesses. Illnesses with 9 to 11 symptoms were more common in group 1 (17 [23.0%]) than in group 2 (15 [12.4%]) (P < .05). Compared with group 2, more group 1 subjects reported dyspnea, more severe disease of longer duration, and treatment for acute illness with prednisone and antibiotics. Coronavirus-associated illnesses (percent of illnesses, group 1 vs group 2) were characterized by myalgias (21% vs 68%, P < .01), chills (50% vs 52%), dyspnea (71% vs 24%, P < .01), headache (64% vs 72%), malaise (64% vs 84%), cough (86% vs 68%), sputum production (86% vs 60%), sore throat (64% vs 80%), and nasal congestion (93% vs 96%). Conclusions Respiratory illnesses were commonly associated with coronaviruses and enteroviruses/rhinoviruses affecting chronically ill, older patients more than healthy, young adults.", "qid": 31, "docid": "bsf8s4mh", "rank": 55, "score": 0.7293270826339722}, {"content": "Title: Characteristics of respiratory virus infection during the outbreak of 2019 novel coronavirus in Beijing Content: BACKGROUND: Coronavirus disease 2019 (COVID-19) is spreading. Here, we summarized the composition of pathogens in fever clinic patients and analyzed the characteristics of different respiratory viral infections. METHODS: Retrospectively collected patients with definite etiological results using nasal and pharyngeal swabs in a fever clinic. RESULTS: Overall, 1860 patients were screened, and 136 patients were enrolled. 72 (52.94%) of them were diagnosed as influenza (Flu) A virus infection. 32 (23.53%) of them were diagnosed as Flu B virus infection. 18 (13.24%) and 14 (10.29%) of them were diagnosed as COVID-19 and respiratory syncytial virus (RSV) infections, respectively. The COVID-19 group had a higher rate of contact with the epidemic area within 14 days and of clustering onset than other groups. Fever was the most common symptom in these patients. The ratio of fever to the highest temperature was higher in Flu A virus infection patients than in COVID-19 patients. COVID-19 patients had a lower white blood cell count and neutrophil count than Flu A virus and RSV infection groups, but higher lymphocyte count than Flu A and B virus infection groups. The COVID-19 group (83.33%) had a higher rate of pneumonia in chest CT scans than Flu A and B virus infection groups. CONCLUSIONS: Influenza viruses accounted for a large proportion of respiratory virus infection even during the epidemic of COVID-19 in Beijing. No single symptom or laboratory finding was suggestive of a specific respiratory virus; however, epidemic history was significant for the screening of COVID-19.", "qid": 31, "docid": "eu79h4ee", "rank": 56, "score": 0.729057788848877}, {"content": "Title: A new threat from an old enemy: Re\u00ademergence of coronavirus (Review) Content: The new outbreak of coronavirus from December 2019 has brought attention to an old viral enemy and has raised concerns as to the ability of current protection measures and the healthcare system to handle such a threat. It has been known since the 1960s that coronaviruses can cause respiratory infections in humans; however, their epidemic potential was understood only during the past two decades. In the present review, we address current knowledge on coronaviruses from a short history to epidemiology, pathogenesis, clinical manifestation of the disease, as well as treatment and prevention strategies. Although a great amount of research and efforts have been made worldwide to prevent further outbreaks of coronavirus\u00adassociated disease, the spread and lethality of the 2019 outbreak (COVID\u00ad19) is proving to be higher than previous epidemics on account of international travel density and immune naivety of the population. Only strong, joint and coordinated efforts of worldwide healthcare systems, researchers, and pharmaceutical companies and receptive national leaders will succeed in suppressing an outbreak of this scale.", "qid": 31, "docid": "fw0d8807", "rank": 57, "score": 0.7290256023406982}, {"content": "Title: Influenza vaccination in the COVID-19 era Content: Abstract Influenza spreads globally annually with significant paediatric and adult attack rates and considerable morbidity, mortality and the exacerbation of extant chronic disease. In the northern and southern hemispheres, outbreaks occur mainly in the respective winter seasons. Influenza vaccination is available but only partially effective. In the absence of a vaccine, in winter, novel coronavirus COVID-19 will also circulate in parallel with seasonal influenza. Thus far it appears that with the current strains of these two viruses, the clinical outcome of co-infection is not significantly worse than infection with COVID-19 alone. However, several strains of influenza circulate, including strains still to come. Similarly, COVID-19 has several strains, with probably more to come. This paper discusses these issues and estimates ideal minimum influenza vaccination coverage based on an estimated influenza Basic Reproduction Number (R0) of 0.9\u20132.1 so as to obtain herd immunity or approach it. There is a strong argument for attempting near universal population coverage with the annual influenza vaccine leading up to next winter.", "qid": 31, "docid": "8ikiyqkp", "rank": 58, "score": 0.7290036678314209}, {"content": "Title: Human Coronaviruses 229E and NL63: Close Yet Still So Far Content: HCoV-NL63 and HCoV-229E are two of the four human coronaviruses that circulate worldwide. These two viruses are unique in their relationship towards each other. Phylogenetically, the viruses are more closely related to each other than to any other human coronavirus, yet they only share 65% sequence identity. Moreover, the viruses use different receptors to enter their target cell. HCoV-NL63 is associated with croup in children, whereas all signs suggest that the virus probably causes the common cold in healthy adults. HCoV-229E is a proven common cold virus in healthy adults, so it is probable that both viruses induce comparable symptoms in adults, even though their mode of infection differs. Here, we present an overview of the current knowledge on both human coronaviruses, focusing on similarities and differences.", "qid": 31, "docid": "3zq8l5z0", "rank": 59, "score": 0.7285547852516174}, {"content": "Title: Coronavirus Disease of 2019: a Mimicker of Dengue Infection? Content: At the beginning of 2020, the national health system and medical communities are faced with unprecedented public health challenges. A novel strain of coronavirus, later identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally, marking another pandemic of coronaviruses. This viral disease is responsible for devastating pneumonia, named coronavirus disease of 2019 (COVID-19), and projected to persist until the end of the year. In tropical countries, however, concerns arise regarding the similarities of COVID-19 with other infectious diseases due to the same chief complaint, which is fever. One of the infectious disease of a primary concern is dengue infection, which its peak season is approaching. Others report that there are cases of serological cross-reaction of COVID-19 and dengue infection. In this comprehensive review, we underscore the importance of knowing similar clinical presentations of both diseases and emphasize why excluding COVID-19 in the differentials in the setting of a pandemic is imprudent.", "qid": 31, "docid": "yajhp7bb", "rank": 60, "score": 0.7284905910491943}, {"content": "Title: Clinical features of COVID-19 and influenza: A comparative study on Nord Franche-Comte cluster Content: Clinical descriptions about influenza-like illnesses (ILI) in COVID-19 seem non-specific. We aimed to compare the clinical features of COVID-19 and influenza. We retrospectively investigated the clinical features and outcomes of confirmed cases of COVID-19 and influenza in Nord Franche-Comt\u00e9 Hospital between February 26(th) and March 14(th) 2020. We used SARS-CoV-2 RT-PCR and influenza virus A/B RT-PCR in respiratory samples to confirm the diagnosis. We included 124 patients. The mean age was 59(\u00b119[19-98]) years with 69% female. 70 patients with COVID-19 and 54 patients with influenza A/B. Regarding age, sex and comorbidities, no differences were found between the two groups except a lower Charlson index in COVID-19 group (2[\u00b12.5] vs 3[\u00b12.4],p=0.003). Anosmia (53% vs 17%,p<0.001), dysgeusia (49% vs 20%,p=0.001), diarrhea (40% vs 20%,p=0.021), frontal headache (26% vs 9%,p=0.021) and bilateral cracklings sounds (24% vs 9%,p=0.034) were statistically more frequent in COVID-19. Sputum production (52% vs 29%,p=0.010), dyspnea (59% vs 34%,p=0.007), sore throat (44% vs 20%,p=0.006), conjunctival hyperhemia (30% vs 4%,p<0.001), tearing (24% vs 6%,p=0.004), vomiting (22% vs 3%,p=0.001) and rhonchi sounds (17% vs 1%,p=0.002) were more frequent with influenza infection. We described several clinical differences which can help the clinicians during the co-circulation of influenza and SARS-CoV-2.", "qid": 31, "docid": "2pmpspuj", "rank": 61, "score": 0.7284795641899109}, {"content": "Title: A new threat from an old enemy: Re-emergence of coronavirus (Review) Content: The new outbreak of coronavirus from December 2019 has brought attention to an old viral enemy and has raised concerns as to the ability of current protection measures and the healthcare system to handle such a threat. It has been known since the 1960s that coronaviruses can cause respiratory infections in humans; however, their epidemic potential was understood only during the past two decades. In the present review, we address current knowledge on coronaviruses from a short history to epidemiology, pathogenesis, clinical manifestation of the disease, as well as treatment and prevention strategies. Although a great amount of research and efforts have been made worldwide to prevent further outbreaks of coronavirus-associated disease, the spread and lethality of the 2019 outbreak (COVID-19) is proving to be higher than previous epidemics on account of international travel density and immune naivety of the population. Only strong, joint and coordinated efforts of worldwide healthcare systems, researchers, and pharmaceutical companies and receptive national leaders will succeed in suppressing an outbreak of this scale.", "qid": 31, "docid": "9jb3w0zu", "rank": 62, "score": 0.7282525300979614}, {"content": "Title: Clinical features of COVID-19 and influenza: a comparative study on Nord Franche-Comte cluster Content: Clinical descriptions about influenza-like illnesses (ILI) in COVID-19 seem non-specific. We aimed to compare the clinical features of COVID-19 and influenza. We retrospectively investigated the clinical features and outcomes of confirmed cases of COVID-19 and influenza in Nord Franche-Comt\u00e9 Hospital between February 26th and March 14th 2020. We used SARS-CoV-2 RT-PCR and influenza virus A/B RT-PCR in respiratory samples to confirm the diagnosis. We included 124 patients. The mean age was 59 (\u00b119 [19-98]) years with 69% female. 70 patients with COVID-19 and 54 patients with influenza A/B. Regarding age, sex and comorbidities, no differences were found between the two groups except a lower Charlson index in COVID-19 group (2 [\u00b12.5] vs 3 [\u00b12.4],p = 0.003). Anosmia (53% vs 17%,p < 0.001), dysgeusia (49% vs 20%,p = 0.001), diarrhea (40% vs 20%,p = 0.021), frontal headache (26% vs 9%,p = 0.021) and bilateral cracklings sounds (24% vs 9%,p = 0.034) were statistically more frequent in COVID-19. Sputum production (52% vs 29%,p = 0.010), dyspnea (59% vs 34%,p = 0.007), sore throat (44% vs 20%,p = 0.006), conjunctival hyperhemia (30% vs 4%,p < 0.001), tearing (24% vs 6%,p = 0.004), vomiting (22% vs 3%,p = 0.001) and rhonchi sounds (17% vs 1%,p = 0.002) were more frequent with influenza infection. We described several clinical differences which can help the clinicians during the co-circulation of influenza and SARS-CoV-2.", "qid": 31, "docid": "q684l6kh", "rank": 63, "score": 0.7282488942146301}, {"content": "Title: Co-infection with Influenza A and COVID-19 Content: COVID-19, also called severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2), originated in Wuhan, China. It has caused significant morbidity and mortality worldwide and has been declared a global pandemic by the WHO. Influenza occurs mainly during the winter, with the burden of disease determined by several factors, including the effectiveness of the vaccine that season, the characteristics of the circulating viruses, and how long the season lasts. We describe the case of a 66-year-old woman who was diagnosed with influenza A and COVID-19 co-infection. LEARNING POINTS: COVID-19 can co-occur with other viral infections. Some of these co-infections have active treatments, while supportive treatment is the mainstay of treatment for others.", "qid": 31, "docid": "9i024s08", "rank": 64, "score": 0.7279208898544312}, {"content": "Title: Analysis clinical features of COVID-19 infection in secondary epidemic area and report potential biomarkers in evaluation Content: Objective: Based on the clinical characteristics of infected patients with novel coronavirus in secondary epidemic areas,we aimed to identify potential biomarkers for the evaluation of novel coronavirus-infected patients,guide the diagnosis and treatment of this disease in secondary epidemic areas and provide a reference for the clinical prevention and control of this epidemic situation. Methods: The clinical data of 33 patients with respiratory symptoms caused by the novel coronavirus in Wenzhou city from January 15 to February 12,2020,were thoroughly reviewed. At the onset of the disease,we found that the primary symptoms were fever,cough,fatigue,chest tightness,chest pain and specific blood test results. According to the patients'histories,the patients were divided into two groups: those who spent time in the main epidemic area and those who did not spend time in the main epidemic area. The differences in the clinical manifestations between these two groups were analyzed. Results: The main clinical symptoms of patients infected with novel coronavirus in the secondary epidemic area were respiratory tract ailments and systemic symptoms. After grouping patients based on the presence or absence of residency in or travel history to the main epidemic area, there was no significant difference between the baseline data of these two groups, and there were no significant differences in symptoms and signs between the two groups (P>0.05). Some patients had abnormally increased serum amyloid protein A (SAA). There were statistically significant differences in the leukocyte count/C-reactive protein,monocyte ratio/C-reactive protein,neutrophil count/C-reactive protein,monocyte count/C-reactive protein and hemoglobin/C-reactive protein values between the two groups (P < 0.05). Conclusion: Respiratory tract ailments and systemic symptoms were the primary symptoms of novel coronavirus infection in the secondary epidemic area; these symptoms are not typical. The abnormal increase in serum amyloid protein (SAA) may be used as an auxiliary index for diagnosis and treatment. CRP changes before other blood parameters and thus may be an effective evaluation index for patients with COVID-19 infection.", "qid": 31, "docid": "1frc4zya", "rank": 65, "score": 0.7277626395225525}, {"content": "Title: Epidemiology of human coronavirus NL63 infection among hospitalized patients with pneumonia in Taiwan Content: Abstract Background/Purpose Human coronavirus (HCoV) NL63 is recognized in association with upper or lower respiratory tract illnesses in children. This study surveyed the prevalence of HCoV-NL63 and influenza viruses in patients with influenza-like illness in Taiwan during 2010\u20132011. Methods Throat samples from 107 hospitalized patients with pneumonia and 175 outpatients with influenza-like illness were examined using real-time polymerase chain reaction assays with virus-specific primers, and then virus-positive specimens were confirmed by sequencing the polymerase chain reaction products. Results HCoV-NL63 infection was identified in 8.4% (9/107) of hospitalized patients with pneumonia, but not found in outpatients with influenza-like illness. Age distribution of HCoV-NL63 infection in hospitalized patients with pneumonia indicated that the group aged 16\u201325 years (20%) had the highest positive rate compared with the other groups, and exhibited a similar age-specific pattern to influenza A/H1N1 infection, but not influenza A/H3N2 and B infections in hospitalized patients. Seasonal prevalence of HCoV-NL63 infection was late winter, overlapping the highest peak of the influenza A/H1N1 epidemic during December 2010 to March 2011 in Taiwan. Co-infection of HCoV-NL63 and influenza A/H1N1 was detected in three hospitalized patients. Clinical manifestation analysis indicated that the main symptoms for HCoV-NL63 infection included fever (88.9%), cough (77.8%), and pneumonia (100%). Co-infection caused significantly higher rates of breathing difficulties, cough, and sore throat than those of single infection with HCoV-NL63 and influenza A/H1N1. Phylogenetic analysis indicated a low level of heterogeneity between Taiwan and global HCoV-NL63 strains. Conclusion Understanding epidemiology of HCoV-NL63 in Taiwan provides an insight for worldwide surveillance of HCoV-NL63 infection.", "qid": 31, "docid": "m2hylhd3", "rank": 66, "score": 0.7275381088256836}, {"content": "Title: Collateral Benefit of COVID-19 Control Measures on Influenza Activity, Taiwan Content: Taiwan has strictly followed infection control measures to prevent spread of coronavirus disease. Meanwhile, nationwide surveillance data revealed drastic decreases in influenza diagnoses in outpatient departments, positivity rates of clinical specimens, and confirmed severe cases during the first 12 weeks of 2020 compared with the same period of 2019.", "qid": 31, "docid": "3fnxxprl", "rank": 67, "score": 0.7274506092071533}, {"content": "Title: Collateral Benefit of COVID-19 Control Measures on Influenza Activity, Taiwan. Content: Taiwan has strictly followed infection control measures to prevent spread of coronavirus disease. Meanwhile, nationwide surveillance data revealed drastic decreases in influenza diagnoses in outpatient departments, positivity rates of clinical specimens, and confirmed severe cases during the first 12 weeks of 2020 compared with the same period of 2019.", "qid": 31, "docid": "4614dnx5", "rank": 68, "score": 0.7274506092071533}, {"content": "Title: Diversity of Coronavirus Spikes: Relationship to Pathogen Entry and Dissemination Content: Coronaviruses are widespread in the environment, infecting humans, domesticated and wild mammals, and birds. Infections cause a variety of diseases including bronchitis, gastroenteritis, hepatitis, and encephalitis, with symptoms ranging from being nearly undetectable to rapidly fatal. A combination of interacting variables determine the pattern and severity of coronavirus-induced disease, including the infecting virus strain, its transmission strategy, and the age and immune status of the infected host. Coronavirus pathogenesis is best understood by discerning how each of these variables dictates clinical outcomes. This chapter focuses on variabilities amongst the spike (S) proteins of infecting virus strains. Diversity of coronavirus surface proteins likely contributes to epidemic disease, an important and timely topic given the recent emergence of the human SARS coronavirus.", "qid": 31, "docid": "ork8mgkz", "rank": 69, "score": 0.7273972034454346}, {"content": "Title: Coronavirus Infection in Acute Lower Respiratory Tract Disease of Infants Content: A serologic surveillance of lower respiratory tract disease in 417 hospitalized children under 18 months of age revealed infection with coronaviruses (strains OC43 and/or 229E) in 34 (8.2%). During the same interval, one of 13 control infants was infected. There were two distinct periods lasting six and 14 weeks, respectively, during which the incidence rose to as high as 18.9% of patients with lower respiratory tract disease. The incidence of coronavirus infection in patients with pneumonia and bronchiolitis was higher than the incidences of adenoviruses, influenza, parainfluenza viruses types 1 and 2, and rhinoviruses, and lower only than the incidences of parainfluenza virus type 3 and respiratory syncytial virus. Coronaviruses serologically similar or identical to strain 229E were recovered from frozen nasal washes obtained during the acute phase of pneumonia in two children.", "qid": 31, "docid": "va27t39c", "rank": 70, "score": 0.7272132635116577}, {"content": "Title: Analysis of Covid-19 and non-Covid-19 viruses, including influenza viruses, to determine the influence of intensive preventive measures in Japan Content: BACKGROUND: Severe acute respiratory coronavirus 2 (SARS-CoV-2) has spread and caused death worldwide. Preventive measures and infection control are underway, and some areas show signs of convergence. Other viruses in addition to SARS-CoV-2 cause cold-like symptoms and spread in the winter. However, the extent to which SARS-CoV-2, influenza viruses and other causative viruses have prevailed since implementing preventive measures is unclear. OBJECTIVES: We aim to investigate the incidence of causative viruses and pathogens in patients. STUDY DESIGN: We collected 191 nasopharyngeal swabs from patients with cold-like symptoms in Japan. All samples were subjected to multiplex PCR with the FilmArray Respiratory Panel and reverse transcription PCR (RT-PCR) to detect SARS-CoV-2. RESULTS: FilmArray Respiratory Panel analysis detected at least one virus in 32 of 191 patients with cold-like symptoms (21%). Of these, we frequently identified human rhinoviruses/enteroviruses (5.8%, n=11), human metapneumovirus (3.7%, n=7), coronavirus 229E (2.1%, n=4) and coronavirus OC43 (1.6%, n=3); while no influenza viruses were detected. RT-PCR analysis detected SARS-CoV-2 (4.2%, n=8) in patients who were not infected with the aforementioned respiratory viruses. CONCLUSIONS: Co-infection with SARS-CoV-2 and other viruses was not observed. Causative viruses remain prevalent after implementing preventive measures. SARS-CoV-2 differs from influenza viruses in its infectivity.", "qid": 31, "docid": "8hr8wyrr", "rank": 71, "score": 0.7266724109649658}, {"content": "Title: Epidemiological and clinical features of human coronavirus infections among different subsets of patients Content: BACKGROUND: Epidemiological and clinical data of human coronaviruses (HCoVs) infections are restricted to span 1\u20133 years at most. We conducted a comprehensive 9\u2010year study on HCoVs by analyzing 1137 respiratory samples from four subsets of patients (asymptomatic, general community, with comorbidities, and hospitalized) in S\u00e3o Paulo, Brazil. METHODS: A pan\u2010coronavirus RT\u2010PCR screening assay was performed, followed by species\u2010specific real\u2010time RT\u2010PCR monoplex assays. RESULTS: Human coronaviruses were detected in 88 of 1137 (7.7%) of the samples. The most frequently detected HCoV species were NL63 (50.0%) and OC43 (27.3%). Patients with comorbidities presented the highest risk of acquiring coronavirus infection (odds ratio = 4.17; 95% confidence interval = 1.9\u20139.3), and children with heart diseases revealed a significant HCoV infection presence. Dyspnea was more associated with HCoV\u2010229E infections (66.6%), and cyanosis was reported only in HCoV\u2010OC43 infections. There were interseasonal differences in the detection frequencies, with HCoV\u2010229E being predominant in the year 2004 (61.5%) and HCoV\u2010NL63 (70.8%) in 2008. CONCLUSIONS: Our data provide a novel insight into the epidemiology and clinical knowledge of HCoVs among different subsets of patients, revealing that these viruses may cause more than mild respiratory tract disease.", "qid": 31, "docid": "fwf5j4ex", "rank": 72, "score": 0.7264461517333984}, {"content": "Title: Risk stratification of hospitalized COVID-19 patients through comparative studies of laboratory results with influenza Content: Background The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 overlaps with the flu season. Methods We compared clinical and laboratory results from 719 influenza and 973 COVID-19 patients from January to April 2020. We compiled laboratory results from the first 14 days of the hospitalized patients using parameters that are most significantly different between COVID-19 and influenza and hierarchically clustered COVID-19 patients based on these data. The clinical outcomes were compared among different clusters. Results Temporal analyses of laboratory results revealed that compared to influenza, patients with COVID-19 exhibited a continued increase in the white blood cell count, rapid decline of hemoglobin, more rapid increase in blood urea nitrogen (BUN) and D-dimer, and higher level of alanine transaminase, C-reactive protein, ferritin, and fibrinogen. Using these results, we sub-classified the COVID-19 patients into 5 clusters through a hierarchical clustering analysis. We then reviewed the medical record of these patients and risk stratified them based on the clinical outcomes. The cluster with the highest risk showed 27.8% fatality, 94% ICU admission, 94% intubation, and 28% discharge rates compared to 0%, 38%, 22%, and 88% in the lowest risk cluster, respectively. Patients in the highest risk cluster had leukocytosis including neutrophilia and monocytosis, severe anemia, higher BUN, creatinine, D-dimer, alkaline phosphatase, bilirubin, and troponin. Conclusions There are significant differences in the clinical and laboratory courses between COVID-19 and influenza. Risk stratification in hospitalized COVID-19 patients using laboratory data could be useful to predict clinical outcomes and pathophysiology of these patients.", "qid": 31, "docid": "p38x1q8s", "rank": 73, "score": 0.7264438271522522}, {"content": "Title: Modelling the Extremes of Seasonal Viruses and Hospital Congestion: The Example of Flu in a Swiss Hospital Content: Viruses causing flu or milder coronavirus colds are often referred to as\"seasonal viruses\"as they tend to subside in warmer months. In other words, meteorological conditions tend to impact the activity of viruses, and this information can be exploited for the operational management of hospitals. In this study, we use three years of daily data from one of the biggest hospitals in Switzerland and focus on modelling the extremes of hospital visits from patients showing flu-like symptoms and the number of positive cases of flu. We propose employing a discrete Generalized Pareto distribution for the number of positive and negative cases, and a Generalized Pareto distribution for the odds of positive cases. Our modelling framework allows for the parameters of these distributions to be linked to covariate effects, and for outlying observations to be dealt with via a robust estimation approach. Because meteorological conditions may vary over time, we use meteorological and not calendar variations to explain hospital charge extremes, and our empirical findings highlight their significance. We propose a measure of hospital congestion and a related tool to estimate the resulting CaRe (Charge-at-Risk-estimation) under different meteorological conditions. The relevant numerical computations can be easily carried out using the freely available GJRM R package. The introduced approach could be applied to several types of seasonal disease data such as those derived from the new virus SARS-CoV-2 and its COVID-19 disease which is at the moment wreaking havoc worldwide. The empirical effectiveness of the proposed method is assessed through a simulation study.", "qid": 31, "docid": "ziujiigl", "rank": 74, "score": 0.726089596748352}, {"content": "Title: Using the diagnostic model based on routine laboratory tests to distinguish patients infected with SARS-CoV-2 from those infected with influenza virus Content: Abstract Background The differential diagnosis between novel coronavirus pneumonia patients (NCPP) and influenza patients (IP) remains a challenge in clinical practice. Methods Between January 2018 and March 2020, 1027 NCPP and 1140 IP were recruited from Tongji hospital. Blood routine examination, biochemical indicators, and coagulation function analysis were performed in all participants simultaneously. Results There was no sex predominance in NCPP. The NCPP were frequently encountered in the sixth and seventh decades of life. The mean age of NCPP (56\u00b116 years) was higher than IP (47\u00b117 years), but without statistical difference. Although most results of routine laboratory tests between NCPP and IP had no significant difference, some laboratory tests showed an obvious change in NCPP. We observed that NCPP had significantly decreased white blood cells, alkaline phosphatase, and d-dimer, compared with IP. However, the results of lactate dehydrogenase, erythrocyte sedimentation rate and fibrinogen were significantly increased in NCPP compared with those in IP. The diagnostic model based on combination of eighteen routine laboratory indicators showed an area under the curve of 0.796 (95% CI, 0.777 to 0.814), with a sensitivity of 46.93% and a specificity of 90.09% when using a cutoff value of 0.598. Conclusions Some routine laboratory results had statistical difference between NCPP and IP. A diagnostic model based on combination of routine laboratory results provides an adjunct approach in the differential diagnosis between NCPP and IP.", "qid": 31, "docid": "acgfwjwi", "rank": 75, "score": 0.7260481119155884}, {"content": "Title: Using a diagnostic model based on routine laboratory tests to distinguish patients infected with SARS-CoV-2 from those infected with influenza virus Content: BACKGROUND: The differential diagnosis between novel coronavirus pneumonia patients (NCPP) and influenza patients (IP) remains a challenge in clinical practice. METHODS: Between January 2018 and March 2020, 1,027 NCPP and 1,140 IP were recruited from Tongji hospital. Routine blood examination, biochemical indicators and coagulation function analysis were simultaneously performed in all participants. RESULTS: There was no sex predominance in NCPP. The NCPP were frequently encountered in the sixth and seventh decades of life. The mean age of NCPP (56\u00b116 years) was higher than IP (47\u00b117 years), but without statistical difference. Although most results of routine laboratory tests between NCPP and IP had no significant differences, some laboratory tests showed an obvious change in NCPP. It was observed that NCPP had significantly decreased white blood cells, alkaline phosphatase and d-dimer compared with IP. However, the results of lactate dehydrogenase, erythrocyte sedimentation rate and fibrinogen were significantly increased in NCPP compared with IP. The diagnostic model based on a combination of 18 routine laboratory indicators showed an area under the curve of 0.796 (95% CI, 0.777-0.814), with a sensitivity of 46.93% and specificity of 90.09% when using a cut-off value of 0.598. CONCLUSIONS: Some routine laboratory results had statistical difference between NCPP and IP. A diagnostic model based on a combination of routine laboratory results provided an adjunct approach in the differential diagnosis between NCPP and IP.", "qid": 31, "docid": "yzr5jq1a", "rank": 76, "score": 0.7254928350448608}, {"content": "Title: Pan-human coronavirus and human bocavirus SYBR Green and TaqMan PCR assays; use in studying influenza A viruses co-infection and risk of hospitalization Content: PURPOSE: Influenza A viruses, human coronaviruses (hCoV) and human bocavirus (hBoV) are emerging respiratory viruses. This study investigated the association between influenza A viruses co-infection with hBoV and hCoV and severity and the sensitivity of a real-time polymerase chain reaction (RT-PCR) assay for identification of 15 coronaviruses. METHODOLOGY: Published sequences for the 15 human coronaviruses were used to design a consensus PCR targeting the replicase open reading frame 1b. A previously published PCR targeting the NS1 Gene of all known human bocavirus strains was also utilized. A series of 217 samples from patients aged 37.7 (SD \u00b1 30.4)] with seasonal influenza A viruses (SeasFluA) identified between 06/2011 and 06/2012 in NW England were tested for hCoV and hBoV using RT-PCR. Association between co-infection and disease outcome was assessed using logistic regression. RESULTS: The limit of detection of hCoV RT-PCR assay was 2 copies/\u00b5l of human coronavirus RNA template, a sensitivity comparable to a previously published SYBR green assay for human coronaviruses. A total of 12 hCoV and 17 hBoV were identified in the 217 influenza A positive samples. A higher proportion (61.5 %; 8/13) of SeasFluA/hBoV co-infections were identified in patients that were admitted either to a general ward or the intensive care unit compared to 44.3 % (66/149) of single SeasFlu A virus infections (OR 2.5 95 % CI 0.67\u20139.34, p = 0.17). In a stratified analysis, there was a trend towards higher association between FluA, hCoV and hBoV with increasing age (especially in patients aged 24\u201345 years and >65 year old). CONCLUSION: Our hCoV RT-PCR protocol appeared to be of adequate analytical sensitivity for diagnosis. More and larger studies are needed to confirm the role of hCoV, hBoV in causing severe disease when they co-infect with influenza A viruses.", "qid": 31, "docid": "ph15z424", "rank": 77, "score": 0.7250701189041138}, {"content": "Title: Comparison of Hospitalized Patients With ARDS Caused by COVID-19 and H1N1 Content: BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19) in China in December 2019, considerable attention has been focused on its elucidation. However, it is also important for clinicians and epidemiologists to differentiate COVID-19 from other respiratory infectious diseases such as influenza viruses. RESEARCH QUESTION: The aim of this study was to explore the different clinical presentations between COVID-19 and influenza A (H1N1) pneumonia in patients with ARDS. STUDY DESIGN AND METHODS: This analysis was a retrospective case-control study. Two independent cohorts of patients with ARDS infected with either COVID-19 (n = 73) or H1N1 (n = 75) were compared. Their clinical manifestations, imaging characteristics, treatments, and prognosis were analyzed and compared. RESULTS: The median age of patients with COVID-19 was higher than that of patients with H1N1, and there was a higher proportion of male subjects among the H1N1 cohort (P < .05). Patients with COVID-19 exhibited higher proportions of nonproductive coughs, fatigue, and GI symptoms than those of patients with H1N1 (P < .05). Patients with H1N1 had higher Sequential Organ Failure Assessment (SOFA) scores than patients with COVID-19 (P < .05). The Pao2/Fio2 of 198.5 mm Hg in the COVID-19 cohort was significantly higher than the Pao2/Fio2 of 107.0 mm Hg in the H1N1 cohort (P < .001). Ground-glass opacities was more common in patients with COVID-19 than in patients with H1N1 (P < .001). There was a greater variety of antiviral therapies administered to COVID-19 patients than to H1N1 patients. The in-hospital mortality of patients with COVID-19 was 28.8%, whereas that of patients with H1N1 was 34.7% (P = .483). SOFA score-adjusted mortality of H1N1 patients was significantly higher than that of COVID-19 patients, with a rate ratio of 2.009 (95% CI, 1.563-2.583; P < .001). INTERPRETATION: There were many differences in clinical presentations between patients with ARDS infected with either COVID-19 or H1N1. Compared with H1N1 patients, patients with COVID-19-induced ARDS had lower severity of illness scores at presentation and lower SOFA score-adjusted mortality.", "qid": 31, "docid": "pblqcb8d", "rank": 78, "score": 0.7250320911407471}, {"content": "Title: Human Coronavirus (HCoV) Infection Among Adults in Cleveland, Ohio: An Increasingly Recognized Respiratory Pathogen Content: BACKGROUND: Human Coronaviruses (CoV) have been long recognized as a common cause of respiratory tract disease including severe respiratory tract illness, yet there are few recent studies characterizing disease among adults in the United States. Here, we describe CoV infections and clinical characteristics among adults (>18 years) presenting with respiratory illness in Cleveland, Ohio. METHODS: Between February 1, 2016 and April 30, 2017, 2949 nasopharyngeal swab specimens were analyzed by NxTAG Respiratory Pathogen Panel in adults presenting with respiratory illness at MetroHealth Medical Center. Clinical data were collected on adults whose samples screened positive for CoV-HKU1, CoV-OC43, CoV-229E or CoV-NL63. RESULTS: Coronaviruses were detected in 192 (6.5%) adults including 105 (3.5%) OC43, 67 (2.3%) 229E, 13 (0.4%) HKU1 and 7 (0.2%) NL63. The majority of adults with coronavirus infection were females (66.2%) with a median age of 53 years. Common comorbidities included smoking (40.0%), asthma (38.0%), COPD (35.4%), and inhaled corticosteroid use (28.6%). Eighty-five (46.4%) required admission to the hospital. Common presenting symptoms included shortness of breath (42.7%) and cough (31.0%) whereas fever was uncommon (12.5%). Gastrointestinal symptoms were more common in HKU1 and NL63 infected adults. Seventy-three percent of coronavirus disease occurred between the months of January and March. Despite the recognition of coronavirus infection, 70 (36.5%) received antibiotics for their disease. CONCLUSION: This study provides needed insight into clinical characteristics and severity associated with coronavirus infection in adults. Coronavirus infection should be considered in differential diagnosis of respiratory tract illness in adults including those that require hospitalization, have a history of smoking and have pulmonary comorbidities. DISCLOSURES: All authors: No reported disclosures.", "qid": 31, "docid": "2pyauukk", "rank": 79, "score": 0.723822832107544}, {"content": "Title: Analysis of human coronavirus 229E spike and nucleoprotein genes demonstrates genetic drift between chronologically distinct strains. Content: Historically, coronaviruses have been recognized as a cause of minor respiratory infections in humans. However, the recent identification of three novel human coronaviruses, one causing severe acute respiratory syndrome (SARS), has prompted further examination of these viruses. Previous studies of geographically and chronologically distinct Human coronavirus 229E (HCoV-229E) isolates have found only limited variation within S gene nucleotide sequences. In contrast, analysis of the S genes of contemporary Human coronavirus OC43 variants identified in Belgium revealed two distinct viruses circulating during 2003 and 2004. Here, the S and N gene sequences of 25 HCoV-229E variants identified in Victoria, Australia, between 1979 and 2004 in patients with symptomatic infections were determined. Phylogenetic analysis showed clustering of the isolates into four groups, with evidence of increasing divergence with time. Evidence of positive selection in the S gene was also established.", "qid": 31, "docid": "i1x9bx9g", "rank": 80, "score": 0.7236229181289673}, {"content": "Title: Relative disease burdens of COVID-19 and seasonal influenza in New York City, February 1 - April 18, 2020. Content: Comparisons between the mortality burdens of COVID-19 and seasonal influenza often fail to account for the fact that the United States Centers for Disease Control and Prevention (CDC) reports annual influenza mortality estimates which are calculated based upon a series of assumptions about the underreporting of flu deaths. COVID-19 deaths, in contrast, are being reported as raw counts. In this report, we compare COVID-19 death counts to seasonal influenza death counts in New York City during the interval from February 1 - April 18, 2020. Using this approach, COVID-19 appears to have caused 21.4 times the number of deaths as seasonal influenza during the same period. We also assessed excess mortality in order to verify this finding. New York City has had approximately 13,032 excess all-cause mortality deaths during this time period. We assume that most of these deaths are COVID-19 related. We therefore calculated the ratio of excess deaths (i.e. assumed COVID-19 deaths) to seasonal influenza deaths during the same time interval and found a similar ratio of 21.1 COVID-19 to seasonal influenza deaths. Our findings are consistent with conditions on the ground today. Comparing COVID-19 deaths with CDC estimates of yearly influenza-related deaths would suggest that, this year, seasonal influenza has killed approximately the same number of Americans as COVID-19 has. This does not comport with the realities of the pandemic we see today.", "qid": 31, "docid": "wtqwghon", "rank": 81, "score": 0.7236170768737793}, {"content": "Title: Infections by human coronavirus-NL in hospitalized children. Content: BACKGROUND A new human coronavirus (HCoV), HCoV-NL, was recently reported for Dutch patients with acute respiratory tract infections (ARTI). Little information is available on the incidence, clinical manifestations and epidemiologic features of HCoV-NL infections. METHODS We performed a prospective study of symptomatic (case subjects with ARTI) and asymptomatic (control subjects undergoing elective surgery) children, <or=3 years of age, hospitalized in Canada during 2 winter seasons (2001-2003), to look at the prevalence of respiratory viruses. Reverse transcription-PCR assays were used to retrospectively detect HCoV-NL and to correlate its presence with clinical symptoms. RESULTS HCoV-NL was detected in nasopharyngeal aspirates from 3.0% of young children (12 of 396 children) hospitalized for treatment of ARTI (case subjects), compared with 1.7% of asymptomatic control subjects (3 of 177 children) (P = 0.6). Nine (75.0%) of the symptomatic children had mixed viral infections. The mean age and mean duration of hospitalization of case subjects were 10.1 months and 4.9 days, respectively. Final diagnoses consisted of bronchiolitis or bronchitis (9 of 12 cases), pneumonitis (1 of 12 cases) and upper respiratory tract infections (2 of 12 cases), although 2 of 3 subjects with single HCoV-NL infections had upper respiratory tract infections only. Sequence analysis of the 1a and spike genes revealed that multiple HCoV-NL strains circulated in the same geographical area in each of the 2 winter seasons. Variability was more pronounced for the spike gene, with 2 clusters of strains. CONCLUSIONS HCoV-NL was not a major respiratory pathogen in Canada during our study, as shown by its low detection rate in hospitalized children with ARTI, coupled with the high frequency of additional pathogens and its occasional detection in healthy children.", "qid": 31, "docid": "qmcw42pw", "rank": 82, "score": 0.7234408855438232}, {"content": "Title: Epidemiology and Clinical Features of Human Coronaviruses in the Pediatric Population Content: BACKGROUND: The epidemiology and clinical features of human coronaviruses (HCoVs) in children are not fully characterized. METHODS: A retrospective study of children with HCoV detected by reverse-transcriptase polymerase chain reaction (RT-PCR) was performed for a community cohort and a children\u2019s hospital in the same community from January 2013 to December 2014. The RT-PCR assay detected HCoV 229E, HKU1, NL63, and OC43 in nasal swabs from symptomatic children \u226418 years. Factors associated with increased severity of illness in hospitalized children were assessed by multivariable logistic regression. RESULTS: Human coronavirus was detected in 261 children, 49 and 212 from the community and hospital, respectively. The distribution of HCoV types and seasonal trends were similar in the community and hospital. Community cases were older than hospitalized cases (median age, 4.4 versus 1.7 years, respectively; P < .01), and a minority of community cases (26.5%) sought medical attention. Among the hospitalized children with HCoV detected, 39 (18.4%) received respiratory support and 24 (11.3%) were admitted to the pediatric intensive care unit (PICU). Age <2 years (odds ratio [OR] = 5.0; 95% confidence interval [CI], 1.9\u201313.1) and cardiovascular (OR = 3.9; 95% CI, 1.6\u20139.5), genetic/congenital (OR = 2.8; 95% CI, 1.1\u20137.0), and respiratory chronic complex conditions ([CCCs] OR = 4.5; 95% CI, 1.7\u201312.0) were associated with receiving respiratory support. Genetic/congenital (OR = 2.8; 95% CI, 1.1\u20137.4) CCCs were associated with PICU admission. Severity of illness was similar among hospitalized children with different HCoV types. CONCLUSIONS: Children in the community with HCoV detected generally had mild illness as demonstrated by few medically attended cases. In hospitalized children, young age and CCCs, but not HCoV type, were associated with increased severity of illness.", "qid": 31, "docid": "xz2hnym0", "rank": 83, "score": 0.7231950759887695}, {"content": "Title: A Comparison of Clinical and Chest CT Findings in Patients With Influenza A (H1N1) Virus Infection and Coronavirus Disease (COVID-19) Content: OBJECTIVE. The purpose of this study was to compare clinical and chest CT findings in patients with influenza A (H1N1) pneumonia and coronavirus disease (COVID-19) pneumonia. MATERIALS AND METHODS. Thirty patients with diagnosed influenza A (H1N1) virus infection (group A) and 30 patients with diagnosed COVID-19 (group B) were retrospectively enrolled in the present study. The clinical characteristics and chest CT findings of the two groups were compared. RESULTS. Fever, cough, expectoration, and dyspnea were the main symptoms in both groups with viral pneumonia, with cough and expectoration more frequently found in group A. Lymphopenia, an elevated C-reactive protein level, and an increased erythrocyte sedimentation rate were common laboratory test findings in the two groups. The median time from symptom onset to CT in group A and group B was 6 and 15 days, respectively, and the median total CT score of the pulmonary lobes involved was 6 and 13, respectively. Linear opacification, crazy-paving sign, vascular enlargement, were more common in group B. In contrast, bronchiectasis and pleural effusion were more common in group A. Other common CT features, including peripheral or peribronchovascular distribution, ground-glass opacities (GGOs), consolidation, subpleural line, air bronchogram, and bronchial distortion, did not show statistical significance. CONCLUSION. On CT, the significant differences between influenza A (H1N1) pneumonia and COVID-19 pneumonia were findings of linear opacification, crazy-paving sign, vascular enlargement, pleural thickening, and pleural effusion, which were more common in patients with COVID-19 pneumonia, and bronchiectasis and pleural effusion, which were more common in patients with influenza A (H1N1) pneumonia. Other imaging findings, including peripheral or peribronchovascular distribution, ground-glass opacities (GGO), consolidation, subpleural line, air bronchogram, and bronchial distortion, were not significantly different between the two patient groups.", "qid": 31, "docid": "y7c0ynin", "rank": 84, "score": 0.7231529951095581}, {"content": "Title: A Comparison of Clinical and Chest CT Findings in Patients With Influenza A (H1N1) Virus Infection and Coronavirus Disease (COVID-19). Content: OBJECTIVE. The purpose of this study was to compare clinical and chest CT findings in patients with influenza A (H1N1) pneumonia and coronavirus disease (COVID-19) pneumonia. MATERIALS AND METHODS. Thirty patients with diagnosed influenza A (H1N1) virus infection (group A) and 30 patients with diagnosed COVID-19 (group B) were retrospectively enrolled in the present study. The clinical characteristics and chest CT findings of the two groups were compared. RESULTS. Fever, cough, expectoration, and dyspnea were the main symptoms in both groups with viral pneumonia, with cough and expectoration more frequently found in group A. Lymphopenia, an elevated C-reactive protein level, and an increased erythrocyte sedimentation rate were common laboratory test findings in the two groups. The median time from symptom onset to CT in group A and group B was 6 and 15 days, respectively, and the median total CT score of the pulmonary lobes involved was 6 and 13, respectively. Linear opacification, crazy-paving sign, vascular enlargement, were more common in group B. In contrast, bronchiectasis and pleural effusion were more common in group A. Other common CT features, including peripheral or peribronchovascular distribution, ground-glass opacities (GGOs), consolidation, subpleural line, air bronchogram, and bronchial distortion, did not show statistical significance. CONCLUSION. On CT, the significant differences between influenza A (H1N1) pneumonia and COVID-19 pneumonia were findings of linear opacification, crazy-paving sign, vascular enlargement, pleural thickening, and pleural effusion, which were more common in patients with COVID-19 pneumonia, and bronchiectasis and pleural effusion, which were more common in patients with influenza A (H1N1) pneumonia. Other imaging findings, including peripheral or peribronchovascular distribution, ground-glass opacities (GGO), consolidation, subpleural line, air bronchogram, and bronchial distortion, were not significantly different between the two patient groups.", "qid": 31, "docid": "1qjmktdl", "rank": 85, "score": 0.7231529355049133}, {"content": "Title: [Be alert to superposed effect of seasonal influenza while fighting against novel coronavirus pneumonia] Content: The novel coronavirus pneumonia (NCP) continues to spread throughout the country, and the prevention and control of the epidemic has entered a critical period. However, southern cities with severe outbreaks are about to enter the seasonal influenza season. We should strengthen the epidemiological investigation, optimize the laboratory testing strategy, take effective measures, strengthen the prevention and control of influenza epidemic, and minimize the interference to the new coronavirus epidemic.", "qid": 31, "docid": "euecd8bd", "rank": 86, "score": 0.7230639457702637}, {"content": "Title: [Be alert to superposed effect of seasonal influenza while fighting against novel coronavirus pneumonia]. Content: The novel coronavirus pneumonia (NCP) continues to spread throughout the country, and the prevention and control of the epidemic has entered a critical period. However, southern cities with severe outbreaks are about to enter the seasonal influenza season. We should strengthen the epidemiological investigation, optimize the laboratory testing strategy, take effective measures, strengthen the prevention and control of influenza epidemic, and minimize the interference to the new coronavirus epidemic.", "qid": 31, "docid": "4d979wj4", "rank": 87, "score": 0.7230639457702637}, {"content": "Title: Mortality of the COVID-19 outbreak in Sweden in relation to previous severe disease outbreaks Content: Influenza viruses have caused disease outbreaks in human societies for a long time. Influenza often has rapid onset and relatively short duration, both in the individual and in the population. The case fatality rate varies for different strains of the virus, as do the effects on total mortality. Outbreaks related to coronavirus infections have recently become a global concern but much less is known about the dynamics of these outbreaks and their effects on mortality. In this work, disease outbreaks in Sweden, in the time period of 1860-2020, are characterized and compared to the currently ongoing COVID-19 outbreak. The focus is on outbreaks with a sharp increase in all-cause mortality. Outbreak onset is defined as the time point when deaths counts starts to increase consistently for a period of 10 days. The duration of the outbreak is defined as the time period in which mortality rates are elevated. Excess mortality is estimated by standard methods. In total there were 15 outbreaks detected in the time period, the first 14 were likely caused by influenza virus infections, the last by SARS-CoV-2. The mortality dynamics of the SARS-CoV-2 outbreak is shown to be similar to outbreaks due to influenza virus, and in terms of the number of excess deaths, might become the worst outbreak since the 'Spanish flu' of 1918-1919.", "qid": 31, "docid": "djtte922", "rank": 88, "score": 0.7229366302490234}, {"content": "Title: Modeling the impact of mass influenza vaccination and public health interventions on COVID-19 epidemics with limited detection capability Content: The emerging coronavirus SARS-CoV-2 has caused a COVID-19 pandemic. SARS-CoV-2 causes a generally mild, but sometimes severe and even life-threatening infection, known as COVID-19. Currently, there exist no effective vaccines or drugs and, as such, global public authorities have so far relied upon non pharmaceutical interventions (NPIs). Since COVID-19 symptoms are aspecific and may resemble a common cold, if it should come back with a seasonal pattern and coincide with the influenza season, this would be particularly challenging, overwhelming and straining the healthcare systems, particularly in resource-limited contexts, and would increase the likelihood of nosocomial transmission. In the present study, we devised a mathematical model focusing on the treatment of people complaining of influenza-like-illness (ILI) symptoms, potentially at risk of contracting COVID-19 or other emerging/re-emerging respiratory infectious agents during their admission at the health-care setting, who will occupy the detection kits causing a severe shortage of testing resources. The model is used to assess the effect of mass influenza vaccination on the spread of COVID-19 and the other respiratory pathogens in the case of a coincidence of the outbreak with the influenza season. Here, we show that increasing influenza vaccine uptake or enhancing the public health interventions would facilitate the management of respiratory outbreaks coinciding with the peak flu season, especially, compensate the shortage of the detection resources. However, how to increase influenza vaccination coverage rate remains challenging. Public health decision- and policy-makers should adopt evidence-informed strategies to improve influenza vaccine uptake.", "qid": 31, "docid": "9m10jl7r", "rank": 89, "score": 0.72288978099823}, {"content": "Title: 2448. Clinical Presentation and Outcomes of Long-Term Care Residents with Coronavirus Respiratory Infection: A Retrospective Cohort Study Content: BACKGROUND: Human coronaviruses (CoVs) are a major cause of respiratory infection and institutional outbreaks, yet the epidemiology and clinical outcomes of these viruses is poorly described among the elderly residing in long-term care facilities (LTCFs). METHODS: We performed a retrospective cohort study of LTCF residents with positive nasopharyngeal or mid-turbinate swabs for CoVs (OC43, 229E, NL63 and HKU1) between January 2013 and December 2018. Demographic and clinical data were obtained from resident charts including clinical presentation, treatment, outcome, and transmission to other residents. Variables were compared using univariate analysis. RESULTS: 3268 residents met inclusion criteria (median age 93 years, 90% male) comprising 7.5% (246/3268) of all positive respiratory virus specimens detected during the study period. 97(39%) of cases were associated with a respiratory outbreak while 149(61%) were sporadic cases that did not result in transmission. OC43 (52%) was the most commonly identified CoV and was more commonly associated with outbreak cases (76% vs. 37%; P < 0.001). In total, 87% of all cases had two or more of runny nose/congestion, cough, sore throat/hoarse voice or fever. The most common symptoms among residents were cough (85%), runny nose/congestion (79%), and sore throat/hoarse voice (59%) and only 17% of residents had a measured temperature of \u2265 37.8C. Only 6% of residents received antibiotic treatment for suspected secondary bacterial pneumonia. The 30-day mortality rate was 3.7% with 67% of deaths attributable to the CoV infection. There was no statistically significant difference in symptoms, treatment or outcomes associated with outbreaks or seasonality. CONCLUSION: CoVs make up an important proportion of respiratory viral infections among LTCF residents and may result in frequent outbreaks. Most residents remain afebrile and have self-limited illness while only a small minority develop secondary bacterial pneumonia and death. Given these findings the benefits of control measures should be weighed against the impact on resident quality of life. DISCLOSURES: All authors: No reported disclosures.", "qid": 31, "docid": "oeivtuvd", "rank": 90, "score": 0.7224324345588684}, {"content": "Title: Chest Computed Tomography Findings in COVID-19 and Influenza: A Narrative Review Content: OBJECTIVE: The COVID-19 pandemic and annual influenza epidemic are responsible for thousands of deaths globally. With a similarity in clinical as well as laboratory findings, there is a need to differentiate these two conditions on chest CT scan. This paper attempts to use existing literature to draw out differences in chest CT findings in COVID-19 and influenza. METHODS: A search was conducted using PubMed. 17 original studies on chest CT findings in COVID-19 and influenza were identified for full-text review and data analysis. Findings. COVID-19 and influenza share similar chest CT findings. The differences found show that COVID-19 ground-glass opacities are usually peripherally located with the lower lobes being commonly involved, while influenza has a central, peripheral, or random distribution usually affecting the five lobes. Vascular engorgement, pleural thickening, and subpleural lines were reported in COVID-19 patients. In contrast, pneumomediastinum and pneumothorax were reported only in studies on influenza. Conclusion and Relevance. COVID-19 and influenza have overlapping chest CT features with few differences which can assist in telling apart the two pathologies. Additional studies are needed to further define the differences and degree between COVID-19 and influenza.", "qid": 31, "docid": "27dmsmbu", "rank": 91, "score": 0.7220137119293213}, {"content": "Title: Clinical presentation and virological assessment of hospitalized cases of coronavirus disease 2019 in a travel-associated transmission cluster Content: Background: In coronavirus disease 2019 (COVID-19), current case definitions presume mainly lower respiratory tract infection. However, cases seen outside the epicenter of the epidemic may differ in their overall clinical appearance due to more sensitive case finding. Methods: We studied viral load courses by RT-PCR in oro- and nasopharyngeal swabs, sputum, stool, blood, and urine in nine hospitalized cases. Infectious virus was detected by cell culture. Active replication was demonstrated by analysis of viral subgenomic replicative intermediates. Serology including neutralization testing was done to characterize immune response. Results: Seven cases had upper respiratory tract disease. Lower respiratory tract symptoms seen in two cases were limited. Clinical sensitivity of RT-PCR on swabs taken on days 1-5 of symptoms was 100%, with no differences comparing swab and sputum samples taken simultaneously. Average viral load was 6.76x10E5 copies per swab during the first 5 days. Live virus isolates were obtained from swabs during the first week of illness. Proof of active viral replication in upper respiratory tract tissues was obtained by detection of subgenomic viral RNA. Shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after about one week. Conclusions: The present study shows that COVID-19 can often present as a common cold-like illness. SARS-CoV-2 can actively replicate in the upper respiratory tract, and is shed for a prolonged time after symptoms end, including in stool. These findings suggest adjustments of current case definitions and re-evaluation of the prospects of outbreak containment.", "qid": 31, "docid": "gunn55f9", "rank": 92, "score": 0.7219624519348145}, {"content": "Title: Reproduction of East-African bats may guide risk mitigation for coronavirus spillover Content: BACKGROUND: Bats provide important ecosystem services; however, current evidence supports that they host several zoonotic viruses, including species of the Coronaviridae family. If bats in close interaction with humans host and shed coronaviruses with zoonotic potential, such as the Severe Acute Respiratory Syndrome virus, spillover may occur. Therefore, strategies aiming to mitigate potential spillover and disease emergence, while supporting the conservation of bats and their important ecological roles are needed. Past research suggests that coronavirus shedding in bats varies seasonally following their reproductive cycle; however, shedding dynamics have been assessed in only a few species, which does not allow for generalization of findings across bat taxa and geographic regions. METHODS: To assess the generalizability of coronavirus shedding seasonality, we sampled hundreds of bats belonging to several species with different life history traits across East Africa at different times of the year. We assessed, via Bayesian modeling, the hypothesis that chiropterans, across species and spatial domains, experience seasonal trends in coronavirus shedding as a function of the reproductive cycle. RESULTS: We found that, beyond spatial, taxonomic, and life history differences, coronavirus shedding is more expected when pups are becoming independent from the dam and that juvenile bats are prone to shed these viruses. CONCLUSIONS: These findings could guide policy aimed at the prevention of spillover in limited-resource settings, where longitudinal surveillance is not feasible, by identifying high-risk periods for coronavirus shedding. In these periods, contact with bats should be avoided (for example, by impeding or forbidding people access to caves). Our proposed strategy provides an alternative to culling \u2013 an ethically questionable practice that may result in higher pathogen levels \u2013 and supports the conservation of bats and the delivery of their key ecosystem services.", "qid": 31, "docid": "6znmkvy9", "rank": 93, "score": 0.7219055891036987}, {"content": "Title: Characteristics of respiratory virus infection during the outbreak of 2019 novel coronavirus in Beijing Content: Abstract Background Coronavirus disease 2019 (COVID-19) is spreading. Here, we summarized the composition of pathogens in fever clinic patients and analyzed characteristics of different respiratory virus infection. Methods Retrospectively collected patients with definite etiological results using nasal and pharyngeal swabs in fever clinic. Results Totally, 1860 patients were screened and 136 patients were enrolled. 72 (52.94%) of them were diagnosed as influenza (Flu) A virus infection. 32 (23.53%) of them were diagnosed as Flu B virus infection. 18 (13.24%) and 14 (10.29%) of them were diagnosed as COVID-19 and respiratory syncytial virus (RSV) infection respectively. COVID-19 group had a higher rate of contact with epidemic area within 14 days and clustering onset than other groups. Fever was the most common symptom in these patients. The ratio of fever and the highest temperature were higher in Flu A virus infection patients than in COVID-19 patients. COVID-19 patients had lower white blood cell count and neutrophil count than Flu A virus and RSV infection group, but higher lymphocyte count than Flu A and B virus infection groups. COVID-19 group (83.33%) had higher rate of pneumonia in chest CT scan than Flu A and B virus infection groups. Conclusions Influenza viruses accounted for a large proportion of respiratory virus infection even during the epidemic of COVID-19 in Beijing. No single symptom or laboratory finding was suggestive of specific respiratory virus, however, epidemic history was important for screening of COVID-19.", "qid": 31, "docid": "pqvlh3eg", "rank": 94, "score": 0.7218844294548035}, {"content": "Title: Evidence of human coronavirus HKU1 and human bocavirus in Australian children Content: Abstract Undiagnosed cases of respiratory tract disease suspected of an infectious aetiology peak during the winter months. Since studies applying molecular diagnostic assays usually report reductions in the number of undiagnosed cases of infectious disease compared to traditional techniques, we applied PCR assays to investigate the role of two recently described viruses, namely human coronavirus (HCoV) HKU1 and human bocavirus (HBoV), in a hospital-based paediatric population. Both viruses were found among Australia children with upper or lower respiratory tract disease during the autumn and winter of 2004, contributing to 21.1% of all microbial diagnoses, with individual incidences of 3.1% (HCoV-HKU1) and 5.6% (HBoV) among 324 specimens. HBoV was found to coincide with another virus in more than half of all instances and displayed a single genetic lineage, whilst HCoV-HKU1 was more likely to occur in the absence of another microbe and strains could be divided into two genetic lineages which we propose be termed HCoV-HKU1 type A and type B. Children under the age of 2 years were most at risk of infection by these viruses which contribute significantly to the microbial burden among patients with respiratory tract disease during the colder months.", "qid": 31, "docid": "092cd8ap", "rank": 95, "score": 0.7207311391830444}, {"content": "Title: Being a front-line dentist during the Covid-19 pandemic: a literature review Content: Coronavirus is an enveloped virus with positive-sense single-stranded RNA. Coronavirus infection in humans mainly affects the upper respiratory tract and to a lesser extent the gastrointestinal tract. Clinical symptoms of coronavirus infections can range from relatively mild (similar to the common cold) to severe (bronchitis, pneumonia, and renal involvement). The disease caused by the 2019 novel coronavirus (2019-nCoV) was called Covid-19 by the World Health Organization in February 2020. Face-to-face communication and consistent exposure to body fluids such as blood and saliva predispose dental care workers at serious risk for 2019-nCoV infection. As demonstrated by the recent coronavirus outbreak, information is not enough. During dental practice, blood and saliva can be scattered. Accordingly, dental practice can be a potential risk for dental staff, and there is a high risk of cross-infection. This article addresses all information collected to date on the virus, in accordance with the guidelines of international health care institutions, and provides a comprehensive protocol for managing possible exposure to patients or those suspected of having coronavirus.", "qid": 31, "docid": "gyvvcnuf", "rank": 96, "score": 0.7206960916519165}, {"content": "Title: Modeling the impact of mass influenza vaccination and public health interventions on COVID-19 epidemics with limited detection capability Content: The emerging coronavirus SARS-CoV-2 has caused a COVID-19 pandemic. SARS-CoV-2 causes a generally mild, but sometimes severe and even life-threatening infection, known as COVID-19. Currently, there exist no effective vaccines or drugs and, as such, global public authorities have so far relied upon non pharmaceutical interventions (NPIs). Since COVID-19 symptoms are aspecific and may resemble a common cold, if it should come back with a seasonal pattern and coincide with the influenza season, this would be particularly challenging, overwhelming and straining the healthcare systems, particularly in resource-limited contexts, and would increase the likelihood of nosocomial transmission. In the present study, we devised a mathematical model focusing on the treatment of people complaining of influenza-like-illness (ILI) symptoms, potentially at risk of contracting COVID-19 or other emerging/re-emerging respiratory infectious agents during their admission at the health-care setting, who will occupy the detection kits causing a severe shortage of testing resources. The model is used to assess the effect of mass influenza vaccination on the spread of COVID-19 and other respiratory pathogens in the case of a coincidence of the outbreak with the influenza season. Here, we show that increasing influenza vaccine uptake or enhancing the public health interventions would facilitate the management of respiratory outbreaks coinciding with the peak flu season, especially, compensate the shortage of the detection resources. However, how to increase influenza vaccination coverage rate remains challenging. Public health decision- and policy-makers should adopt evidence-informed strategies to improve influenza vaccine uptake.", "qid": 31, "docid": "epzu032t", "rank": 97, "score": 0.720482587814331}, {"content": "Title: Human Coronavirus in the 2014 Winter Season as a Cause of Lower Respiratory Tract Infection Content: PURPOSE: During the late autumn to winter season (October to December) in the Republic of Korea, respiratory syncytial virus (RSV) is the most common pathogen causing lower respiratory tract infections (LRTIs). Interestingly, in 2014, human coronavirus (HCoV) caused not only upper respiratory infections but also LRTIs more commonly than in other years. Therefore, we sought to determine the epidemiology, clinical characteristics, outcomes, and severity of illnesses associated with HCoV infections at a single center in Korea. MATERIALS AND METHODS: We retrospectively identified patients with positive HCoV respiratory specimens between October 2014 and December 2014 who were admitted to Severance Children\u2019s Hospital at Yonsei University Medical Center for LRTI. Charts of the patients with HCoV infection were reviewed and compared with RSV infection. RESULTS: During the study period, HCoV was the third most common respiratory virus and accounted for 13.7% of infections. Coinfection was detected in 43.8% of children with HCoV. Interestingly, one patient had both HCoV-OC43 and HCoV-NL63. Mild pneumonia was most common (60.4%) with HCoV, and when combined with RSV, resulted in bronchiolitis. Two patients required care in the intensive care unit. However, compared with that of RSV infection, the disease course HCoV was short. CONCLUSION: Infections caused by HCoVs are common, and can cause LRTIs. During an epidemic season, clinicians should be given special consideration thereto. When combined with other medical conditions, such as neurologic or cardiologic diseases, intensive care unit (ICU) care may be necessary.", "qid": 31, "docid": "k7g7ybyp", "rank": 98, "score": 0.720349133014679}, {"content": "Title: Human (non\u2010severe acute respiratory syndrome) coronavirus infections in hospitalised children in France Content: Aim: This study has two objectives: to study the clinical symptoms associated with the detection of the four human coronaviruses (HCoVs), 229E, OC43, NL63 and HKU1 types, in the respiratory specimens sampled from hospitalised children in France between September 2004 and May 2005; and to develop a multiplex reverse transcription polymerase chain reaction (RT\u2010PCR) assay allowing for the simultaneous detection of the four HCoVs. Methods: 1002 respiratory specimens were tested for HCoVs. The clinical and epidemiological data were compared on the basis of the type HCoV infection. Results: A hundred coronaviruses, 33 NL63, 2229E, 27 OC43 and 38 HKU1, were detected in 97 (9.8%) of 1002 samples negative in routine tests. The clinical and epidemiological characteristics of the study children were compared in three groups, 24 OC43\u2010, 27 NL63\u2010 and 34 HKU1\u2010infected children. HCoVs were identified mainly in children with upper and lower respiratory tract infections (50.5% vs. 29.4%). The significant difference in clinical presentation between the three coronavirus groups was the very low association between lower respiratory tract illness and HKU1 detection. Conclusions: HCoV detection in hospitalised children without any other respiratory virus detection was associated with upper and a significant rate of lower respiratory tract illness. The four types of HCoVs were detected, and new types NL63 and HKU1 represented a substantial portion of detection. The multiplex RT\u2010PCR enabled a sensitive one\u2010time detection and the characterisation of all of the known HCoV types with the exception severe acute respiratory syndrome\u2010coronavirus.", "qid": 31, "docid": "aaf5isj7", "rank": 99, "score": 0.7202389240264893}, {"content": "Title: Characteristic CT findings distinguishing 2019 novel coronavirus disease (COVID-19) from influenza pneumonia Content: OBJECTIVES: To investigate the different CT characteristics which may distinguish influenza from 2019 coronavirus disease (COVID-19). METHODS: A total of 13 confirmed patients with COVID-19 were enrolled from January 16, 2020, to February 25, 2020. Furthermore, 92 CT scans of confirmed patients with influenza pneumonia, including 76 with influenza A and 16 with influenza B, scanned between January 1, 2019, to February 25, 2020, were retrospectively reviewed. Pulmonary lesion distributions, number, attenuation, lobe predomination, margin, contour, ground-glass opacity involvement pattern, bronchial wall thickening, air bronchogram, tree-in-bud sign, interlobular septal thickening, intralobular septal thickening, and pleural effusion were evaluated in COVID-19 and influenza pneumonia cohorts. RESULTS: Peripheral and non-specific distributions in COVID-19 showed a markedly higher frequency compared with the influenza group (p < 0.05). Most lesions in COVID-19 showed balanced lobe localization, while in influenza pneumonia they were predominantly located in the inferior lobe (p < 0.05). COVID-19 presented a clear lesion margin and a shrinking contour compared with influenza pneumonia (p < 0.05). COVID-19 had a patchy or combination of GGO and consolidation opacities, while a cluster-like pattern and bronchial wall thickening were more frequently seen in influenza pneumonia (p < 0.05). The lesion number and attenuation, air bronchogram, tree-in-bud sign, interlobular septal thickening, and intralobular septal thickening were not significantly different between the two groups (all p > 0.05). CONCLUSIONS: Though viral pneumonias generally show similar imaging features, there are some characteristic CT findings which may help differentiating COVID-19 from influenza pneumonia. KEY POINTS: \u00e2\u0080\u00a2 CT can play an early warning role in the diagnosis of COVID-19 in the case of no epidemic exposure. \u00e2\u0080\u00a2 CT could be used for the differential diagnosis of influenza and COVID-19 with satisfactory accuracy. \u00e2\u0080\u00a2 COVID-19 had a patchy or combination of GGO and consolidation opacities with peripheral distribution and balanced lobe predomination.", "qid": 31, "docid": "6m8xicjc", "rank": 100, "score": 0.7201404571533203}]}
{"query": "Does SARS-CoV-2 have any subtypes, and if so what are they?", "hits": [{"content": "Title: The global population of SARS-CoV-2 is composed of six major subtypes Content: The World Health Organization characterized the COVID-19 as a pandemic in March 2020, the second pandemic of the 21st century. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-stranded RNA betacoronavirus of the family Coronaviridae. Expanding virus populations, as that of SARS-CoV-2, accumulate a number of narrowly shared polymorphisms imposing a confounding effect on traditional clustering methods. In this context, approaches that reduce the complexity of the sequence space occupied by the SARS-CoV-2 population are necessary for a robust clustering. Here, we proposed the subdivision of the global SARS-CoV-2 population into sixteen well-defined subtypes by focusing on the widely shared polymorphisms in nonstructural (nsp3, nsp4, nsp6, nsp12, nsp13 and nsp14) cistrons, structural (spike and nucleocapsid) and accessory (ORF8) genes. Six virus subtypes were predominant in the population, but all sixteen showed amino acid replacements which might have phenotypic implications. We hypothesize that the virus subtypes detected in this study are records of the early stages of the SARS-CoV-2 diversification that were randomly sampled to compose the virus populations around the world, a typical founder effect. The genetic structure determined for the SARS-CoV-2 population provides substantial guidelines for maximizing the effectiveness of trials for testing the candidate vaccines or drugs.", "qid": 32, "docid": "h0q93in1", "rank": 1, "score": 0.8025411367416382}, {"content": "Title: Genetic Grouping of SARS-CoV-2 Coronavirus Sequences using Informative Subtype Markers for Pandemic Spread Visualization Content: We propose an efficient framework for genetic subtyping of SARS-CoV-2, the novel coronavirus that causes the COVID-19 pandemic. Efficient viral subtyping enables visualization and modeling of the geographic distribution and temporal dynamics of disease spread. Subtyping thereby advances the development of effective containment strategies and, potentially, therapeutic and vaccine strategies. However, identifying viral subtypes in real-time is challenging: SARS-CoV-2 is a novel virus, and the pandemic is rapidly expanding. Viral subtypes may be difficult to detect due to rapid evolution; founder effects are more significant than selection pressure; and the clustering threshold for subtyping is not standardized. We propose to identify mutational signatures of available SARS-CoV-2 sequences using a population-based approach: an entropy measure followed by frequency analysis. These signatures, Informative Subtype Markers (ISMs), define a compact set of nucleotide sites that characterize the most variable (and thus most informative) positions in the viral genomes sequenced from different individuals. Through ISM compression, we find that certain distant nucleotide variants covary, including non-coding and ORF1ab sites covarying with the D614G spike protein mutation which has become increasingly prevalent as the pandemic has spread. ISMs are also useful for downstream analyses, such as spatiotemporal visualization of viral dynamics. By analyzing sequence data available in the GISAID database, we validate the utility of ISM-based subtyping by comparing spatiotemporal analyses using ISMs to epidemiological studies of viral transmission in Asia, Europe, and the United States. In addition, we show the relationship of ISMs to phylogenetic reconstructions of SARS-CoV-2 evolution, and therefore, ISMs can play an important complementary role to phylogenetic tree-based analysis, such as is done in the Nextstrain [1] project. The developed pipeline dynamically generates ISMs for newly added SARS-CoV-2 sequences and updates the visualization of pandemic spatiotemporal dynamics, and is available on Github at https://github.com/EESI/ISM and via an interactive website at https://covid19-ism.coe.drexel.edu/. Author Summary The novel coronavirus responsible for COVID-19, SARS-CoV-2, expanded to reportedly 8.7 million confirmed cases worldwide by June 21, 2020. The global SARS-CoV-2 pandemic highlights the importance of tracking viral transmission dynamics in real-time. Through June 2020, researchers have obtained genetic sequences of SARS-CoV-2 from over 47,000 samples from infected individuals worldwide. Since the virus readily mutates, each sequence of an infected individual contains useful information linked to the individual\u2019s exposure location and sample date. But, there are over 30,000 bases in the full SARS-CoV-2 genome\u2014so tracking genetic variants on a whole-sequence basis becomes unwieldy. We describe a method to instead efficiently identify and label genetic variants, or \u201csubtypes\u201d of SARS-CoV-2. Applying this method results in a compact, 11 base-long compressed label, called an Informative Subtype Marker or \u201cISM\u201d. We define viral subtypes for each ISM, and show how regional distribution of subtypes track the progress of the pandemic. Major findings include (1) covarying nucleotides with the spike protein which has spread rapidly and (2) tracking emergence of a local subtype across the United States connected to Asia and distinct from the outbreak in New York, which is found to be connected to Europe.", "qid": 32, "docid": "9siu7wgs", "rank": 2, "score": 0.7999016046524048}, {"content": "Title: Understanding the possible origin and genotyping of first Bangladeshi SARS-CoV-2 strain Content: The novel coronavirus, SARS-CoV-2, causes the unfathomable pandemic in the history of humankind. Bangladesh is also a victim of this critical situation. To investigate the genomic features of the pathogen, the first complete genome of the virus has very recently been published. Therefore, the long awaiting questions regarding the possible origin and typing of the strain(s) can now be answered. Here, we endeavor to mainly discuss the published reports or online-accessed data (results) regarding those issues and presented a comprehensive picture of the typing of the virus alongside the probable origin of the sub-clade containing Bangladeshi strain. Our observation suggested that this strain might have originated from the United Kingdom (UK) or other European countries epidemiologically linked to the UK. According to different genotyping classification schemes, this strain belongs to A2a clade under G major clade, is of B and/or L type, and is a SARS-CoV-2a sub-strain. In the forwarding days, randomized genome data will certainly voluminate in Bangladesh, however because of globalization and immigrant movements, we urgently need a mass regional sequencing approach targeting the partial or complete genome that can link the epidemiological data and may help in further clinical interventions. This article is protected by copyright. All rights reserved.", "qid": 32, "docid": "3dm9duoz", "rank": 3, "score": 0.7843763828277588}, {"content": "Title: A Novel Synonymous Mutation of SARS-CoV-2: Is This Possible to Affect Their Antigenicity and Immunogenicity? Content: The S glycoprotein of coronaviruses is important for viral entry and pathogenesis with most variable sequences. Therefore, we analyzed the S gene sequences of SARS-CoV-2 to better understand the antigenicity and immunogenicity of this virus in this study. In phylogenetic analysis, two subtypes (SARS-CoV-2a and -b) were confirmed within SARS-CoV-2 strains. These two subtypes were divided by a novel synonymous mutation of D614G. This may play a crucial role in the evolution of SARS-CoV-2 to evade the host immune system. The region containing this mutation point was confirmed as a B-cell epitope located in the S1 domain, and SARS-CoV-2b strains exhibited severe reduced antigenic indexes compared to SARS-CoV-2a in this area. This may allow these two subtypes to have different antigenicity. If the two subtypes have different serological characteristics, a vaccine for both subtypes will be more effective to prevent COVID-19. Thus, further study is urgently required to confirm the antigenicity of these two subtypes.", "qid": 32, "docid": "1sbnewog", "rank": 4, "score": 0.7832870483398438}, {"content": "Title: Genomic variations of SARS-CoV-2 suggest multiple outbreak sources of transmission Content: We examined 169 genomes of SARS-CoV-2 and found that they can be classified into two major genotypes, Type I and Type II. Type I can be further divided into Type IA and IB. Our phylogenetic analysis showed that the Type IA resembles the ancestral SARS-CoV-2 most. Type II was likely evolved from Type I and predominant in the infections. Our results suggest that Type II SARS-CoV-2 was the source of the outbreak in the Wuhan Huanan market and it was likely originated from a super-spreader. The outbreak caused by the Type I virus should have occurred somewhere else, because the patients had no direct link to the market. Furthermore, by analyzing three genomic sites that distinguish Type I and Type II strains, we found that synonymous changes at two of the three sites confer higher protein translational efficiencies in Type II strains than in Type I strains, which might explain why Type II strains are predominant, implying that Type II is more contagious (transmissible) than Type I. These findings could be valuable for the current epidemic prevention and control.", "qid": 32, "docid": "a12708qd", "rank": 5, "score": 0.7825037240982056}, {"content": "Title: Understanding the possible origin and genotyping of first Bangladeshi SARS\u2010CoV\u20102 strain Content: The novel coronavirus, SARS\u2010CoV\u20102, causes the unfathomable pandemic in the history of humankind. Bangladesh is also a victim of this critical situation. To investigate the genomic features of the pathogen, the first complete genome of the virus has very recently been published. Therefore, the long awaiting questions regarding the possible origin and typing of the strain(s) can now be answered. Here, we endeavor to mainly discuss the published reports or online\u2010accessed data (results) regarding those issues and presented a comprehensive picture of the typing of the virus alongside the probable origin of the sub\u2010clade containing Bangladeshi strain. Our observation suggested that this strain might have originated from the United Kingdom (UK) or other European countries epidemiologically linked to the UK. According to different genotyping classification schemes, this strain belongs to A2a clade under G major clade, is of B and/or L type, and is a SARS\u2010CoV\u20102a sub\u2010strain. In the forwarding days, randomized genome data will certainly voluminate in Bangladesh, however because of globalization and immigrant movements, we urgently need a mass regional sequencing approach targeting the partial or complete genome that can link the epidemiological data and may help in further clinical interventions. This article is protected by copyright. All rights reserved.", "qid": 32, "docid": "68g8noys", "rank": 6, "score": 0.7806721329689026}, {"content": "Title: Comparative genomics provides an operational classification system and reveals early emergence and biased spatio-temporal distribution of SARS-CoV-2 Content: Effective systems for the analysis of molecular data are of fundamental importance for real-time monitoring of the spread of infectious diseases and the study of pathogen evolution. While the Nextstrain and GISAID portals offer widely used systems for the classification of SARS-CoV-2 genomes, both present relevant limitations. Here we propose a highly reproducible method for the systematic classification of SARS-CoV-2 viral types. To demonstrate the validity of our approach, we conduct an extensive comparative genomic analysis of more than 20,000 SARS-CoV-2 genomes. Our classification system delineates 12 clusters and 4 super-clusters in SARS-CoV-2, with a highly biased spatio-temporal distribution worldwide, and provides important observations concerning the evolutionary processes associated with the emergence of novel viral types. Based on the estimates of SARS-CoV-2 evolutionary rate and genetic distances of genomes of the early pandemic phase, we infer that SARS-CoV-2 could have been circulating in humans since August-November 2019. The observed pattern of genomic variability is remarkably similar between all clusters and super-clusters, being UTRs and the s2m element, a highly conserved secondary structure element, the most variable genomic regions. While several polymorphic sites that are specific to one or more clusters were predicted to be under positive or negative selection, overall, our analyses also suggest that the emergence of novel genome types is unlikely to be driven by widespread convergent evolution and independent fixation of advantageous substitutions. While, in the absence of rigorous experimental validation, several questions concerning the evolutionary processes and the phenotypic characteristics (increased/decreased virulence) remain open, we believe that the approach outlined in this study can be of relevance for the tracking and functional characterization of different types of SARS-CoV-2 genomes.", "qid": 32, "docid": "yoe84ta7", "rank": 7, "score": 0.77557373046875}, {"content": "Title: Controlling the SARS-CoV-2 outbreak, insights from large scale whole genome sequences generated across the world Content: Background SARS-CoV-2 most likely evolved from a bat beta-coronavirus and started infecting humans in December 2019. Since then it has rapidly infected people around the world, with more than 4.5 million confirmed cases by the middle of May 2020. Early genome sequencing of the virus has enabled the development of molecular diagnostics and the commencement of therapy and vaccine development. The analysis of the early sequences showed relatively few evolutionary selection pressures. However, with the rapid worldwide expansion into diverse human populations, significant genetic variations are becoming increasingly likely. The current limitations on social movement between countries also offers the opportunity for these viral variants to become distinct strains with potential implications for diagnostics, therapies and vaccines. Methods We used the current sequencing archives (NCBI and GISAID) to investigate 15,487 whole genomes, looking for evidence of strain diversification and selective pressure. Results We used 6,294 SNPs to build a phylogenetic tree of SARS-CoV-2 diversity and noted strong evidence for the existence of two major clades and six sub-clades, unevenly distributed across the world. We also noted that convergent evolution has potentially occurred across several locations in the genome, showing selection pressures, including on the spike glycoprotein where we noted a potentially critical mutation that could affect its binding to the ACE2 receptor. We also report on mutations that could prevent current molecular diagnostics from detecting some of the sub-clades. Conclusion The worldwide whole genome sequencing effort is revealing the challenge of developing SARS-CoV-2 containment tools suitable for everyone and the need for data to be continually evaluated to ensure accuracy in outbreak estimations.", "qid": 32, "docid": "tutit2bc", "rank": 8, "score": 0.7720597386360168}, {"content": "Title: Unsupervised cluster analysis of SARS-CoV-2 genomes reflects its geographic progression and identifies distinct genetic subgroups of SARS-CoV-2 virus Content: Over 10,000 viral genome sequences of the SARS-CoV-2 virus have been made readily available during the ongoing coronavirus pandemic since the initial genome sequence of the virus was released on the open access Virological website (http://virological.org/) early on January 11. We utilize the published data on the single stranded RNAs of 11, 132 SARS-CoV-2 patients in the GISAID (Elbe and Buckland-Merrett, 2017; Shu and McCauley, 2017) database, which contains fully or partially sequenced SARS-CoV-2 samples from laboratories around the world. Among many important research questions which are currently being investigated, one aspect pertains to the genetic characterization/classification of the virus. We analyze data on the nucleotide sequencing of the virus and geographic information of a subset of 7, 640 SARS-CoV-2 patients without missing entries that are available in the GISAID database. Instead of modelling the mutation rate, applying phylogenetic tree approaches, etc., we here utilize a model-free clustering approach that compares the viruses at a genome-wide level. We apply principal component analysis to a similarity matrix that compares all pairs of these SARS-CoV-2 nucleotide sequences at all loci simultaneously, using the Jaccard index (Jaccard, 1901; Tan et al., 2005; Prokopenko et al., 2016; Schlauch et al., 2017). Our analysis results of the SARS-CoV-2 genome data illustrates the geographic and chronological progression of the virus, starting from the first cases that were observed in China to the current wave of cases in Europe and North America. We also observe that, based on their sequence data, the SARS-CoV-2 viruses cluster in distinct genetic subgroups. It is the subject of ongoing research to examine whether the genetic subgroup could be related to diseases outcome and its potential implications for vaccine development.", "qid": 32, "docid": "xnamt7q4", "rank": 9, "score": 0.7695078253746033}, {"content": "Title: The impact of super-spreaders in COVID-19: mapping genome variation worldwide Content: The human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the major pandemic of the 21st century. We analyzed >4,700 SARS-CoV-2 genomes and associated meta-data retrieved from public repositories. SARS-CoV-2 sequences have a high sequence identity (>99.9%), which drops to >96% when compared to bat coronavirus. We built a mutation-annotated reference SARS-CoV-2 phylogeny with two main macro-haplogroups, A and B, both of Asian origin, and >160 sub-branches representing virus strains of variable geographical origins worldwide, revealing a uniform mutation occurrence along branches that could complicate the design of future vaccines. The root of SARS-CoV-2 genomes locates at the Chinese haplogroup B1, with a TMRCA dating to 12 November 2019 - thus matching epidemiological records. Sub-haplogroup A2a originates in China and represents the major non-Asian outbreak. Multiple founder effect episodes, most likely associated with super-spreader hosts, explain COVID-19 pandemic to a large extent.", "qid": 32, "docid": "qw05apnf", "rank": 10, "score": 0.7630773782730103}, {"content": "Title: The phylogeny of SARS coronavirus Content: Different tree-building methods consistently place the SARS corona-virus (SARS-CoV) as a basal Group 2 coronavirus rather than as an ungrouped species as concluded by others. Detailed comparisons of the SARS-CoV genomic sequence with those of six other coronaviruses failed to find evidence of recombination or genomic rearrangement using computational methods designed for that purpose.", "qid": 32, "docid": "wr7vrild", "rank": 11, "score": 0.7597136497497559}, {"content": "Title: Analysis of RNA sequences of 3636 SARS-CoV-2 collected from 55 countries reveals selective sweep of one virus type. Content: Background & objectives SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) is evolving with the progression of the pandemic. This study was aimed to investigate the diversity and evolution of the coronavirus SARS-CoV-2 with progression of the pandemic over time and to identify similarities and differences of viral diversity and evolution across geographical regions (countries). Methods Publicly available data on type definitions based on whole-genome sequences of the SARS-CoV-2 sampled during December and March 2020 from 3636 infected patients spread over 55 countries were collected. Phylodynamic analyses were performed and the temporal and spatial evolution of the virus was examined. Results It was found that (i) temporal variation in frequencies of types of the coronavirus was significant; ancestral viruses of type O were replaced by evolved viruses belonging to type A2a; (ii) spatial variation was not significant; with the spread of SARS-CoV-2, the dominant virus was the A2a type virus in every geographical region; (iii) within a geographical region, there was significant micro-level variation in the frequencies of the different viral types, and (iv) the evolved coronavirus of type A2a swept rapidly across all continents. Interpretation & conclusions SARS-CoV-2 belonging to the A2a type possesses a non-synomymous variant (D614G) that possibly eases the entry of the virus into the lung cells of the host. This may be the reason why the A2a type has an advantage to infect and survive and as a result has rapidly swept all geographical regions. Therefore, large-scale sequencing of coronavirus genomes and, as required, of host genomes should be undertaken in India to identify regional and ethnic variation in viral composition and its interaction with host genomes. Further, careful collection of clinical and immunological data of the host can provide deep learning in relation to infection and transmission of the types of coronavirus genomes.", "qid": 32, "docid": "b61alj5x", "rank": 12, "score": 0.7583101987838745}, {"content": "Title: Analysis of RNA sequences of 3636 SARS-CoV-2 collected from 55 countries reveals selective sweep of one virus type Content: Background & objectives: SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) is evolving with the progression of the pandemic. This study was aimed to investigate the diversity and evolution of the coronavirus SARS-CoV-2 with progression of the pandemic over time and to identify similarities and differences of viral diversity and evolution across geographical regions (countries). Methods: Publicly available data on type definitions based on whole-genome sequences of the SARS-CoV-2 sampled during December and March 2020 from 3636 infected patients spread over 55 countries were collected. Phylodynamic analyses were performed and the temporal and spatial evolution of the virus was examined. Results: It was found that (i) temporal variation in frequencies of types of the coronavirus was significant; ancestral viruses of type O were replaced by evolved viruses belonging to type A2a; (ii) spatial variation was not significant; with the spread of SARS-CoV-2, the dominant virus was the A2a type virus in every geographical region; (iii) within a geographical region, there was significant micro-level variation in the frequencies of the different viral types, and (iv) the evolved coronavirus of type A2a swept rapidly across all continents. Interpretation & conclusions: SARS-CoV-2 belonging to the A2a type possesses a non-synomymous variant (D614G) that possibly eases the entry of the virus into the lung cells of the host. This may be the reason why the A2a type has an advantage to infect and survive and as a result has rapidly swept all geographical regions. Therefore, large-scale sequencing of coronavirus genomes and, as required, of host genomes should be undertaken in India to identify regional and ethnic variation in viral composition and its interaction with host genomes. Further, careful collection of clinical and immunological data of the host can provide deep learning in relation to infection and transmission of the types of coronavirus genomes.", "qid": 32, "docid": "04bi0d50", "rank": 13, "score": 0.7581750154495239}, {"content": "Title: Early Phylogenetic Diversification of SARS-CoV-2: Determination of Variants and the Effect on Epidemiology, Immunology, and Diagnostics. Content: The phylogenetic clustering of 95 SARS-CoV-2 sequences from the first 3 months of the pandemic reveals insights into the early evolution of the virus and gives first indications of how the variants are globally distributed. Variants might become a challenge in terms of diagnostics, immunology, and effectiveness of drugs. All available whole genome sequence data from the NCBI database (March 16, 2020) were phylogenetically analyzed, and gene prediction as well as analysis of selected variants were performed. Antigenic regions and the secondary protein structure were predicted for selected variants. While some clusters are presenting the same variant with 100% identical bases, other SARS-CoV-2 lineages show a beginning diversification and phylogenetic clustering due to base substitutions and deletions in the genomes. First molecular epidemiological investigations are possible with the results by adding metadata as travelling history to the presented data. The advantage of variants in source tracing can be a challenge in terms of virulence, immune response, and immunological memory. Variants of viruses often show differences in virulence or antigenicity. This must also be considered in decisions like herd immunity. Diagnostic methods might not work if the variations or deletions are in target regions for the detection of the pathogen. One base substitution was detected in a primer binding site.", "qid": 32, "docid": "3sxlvoxf", "rank": 14, "score": 0.757088303565979}, {"content": "Title: Comparative genomics suggests limited variability and similar evolutionary patterns between major clades of SARS-CoV-2 Content: Phylogenomic analysis of SARS-CoV-2 as available from publicly available repositories suggests the presence of 3 prevalent groups of viral episomes (super-clades), which are mostly associated with outbreaks in distinct geographic locations (China, USA and Europe). While levels of genomic variability between SARS-CoV-2 isolates are limited, to our knowledge, it is not clear whether the observed patterns of variability in viral super-clades reflect ongoing adaptation of SARS-CoV-2, or merely genetic drift and founder effects. Here, we analyze more than 1100 complete, high quality SARS-CoV-2 genome sequences, and provide evidence for the absence of distinct evolutionary patterns/signatures in the genomes of the currently known major clades of SARS-CoV-2. Our analyses suggest that the presence of distinct viral episomes at different geographic locations are consistent with founder effects, coupled with the rapid spread of this novel virus. We observe that while cross species adaptation of the virus is associated with hypervariability of specific protein coding regions (including the RDB domain of the spike protein), the more variable genomic regions between extant SARS-CoV-2 episomes correspond with the 3\u2019 and 5\u2019 UTRs, suggesting that at present viral protein coding genes should not be subjected to different adaptive evolutionary pressures in different viral strains. Although this study can not be conclusive, we believe that the evidence presented here is strongly consistent with the notion that the biased geographic distribution of SARS-CoV-2 isolates should not be associated with adaptive evolution of this novel pathogen.", "qid": 32, "docid": "uubndgio", "rank": 15, "score": 0.7569327354431152}, {"content": "Title: Dissemination and co-circulation of SARS-CoV2 subclades exhibiting enhanced transmission associated with increased mortality in Western Europe and the United States Content: Mechanisms underlying the acute respiratory distress syndrome (ARDS)-like clinical manifestations leading to deaths in patients who develop COVID-19 remain uncharacterized. While multiple factors could influence these clinical outcomes, we explored if differences in transmissibility and pathogenicity of SARS-CoV2 variants could contribute to these terminal clinical consequences of COVID-19. We analyzed 34,412 SARS-CoV2 sequences deposited in the Global Initiative for Sharing All Influenza Data (GISAID) SARS-CoV2 sequence database to determine if regional differences in circulating strain variants correlated with increased mortality in Europe, the United States, and California. We found two subclades descending from the Wuhan HU-1 strain that rapidly became dominant in Western Europe and the United States. These variants contained nonsynonymous nucleotide mutations in the Orf1ab segment encoding RNA-dependent RNA polymerase (C14408T), the spike protein gene (A23403G), and Orf1a (G25563T), which resulted in non-conservative amino acid substitutions P323L, D614G, and Q57H, respectively. In Western Europe, the A23403G-C14408T subclade dominated, while in the US, the A23403G-C14408T-G25563T mutant became the dominant strain in New York and parts of California. The high cumulative frequencies of both subclades showed inconsistent but significant association with high cumulative CFRs in some of the regions. When the frequencies of the subclades were analyzed by their 7-day moving averages across each epidemic, we found co-circulation of both subclades to temporally correlate with peak mortality periods. We postulate that in areas with high numbers of these co-circulating subclades, a person may get serially infected. The second infection may trigger a hyperinflammatory response similar to the antibody-dependent enhancement (ADE) response, which could explain the ARDS-like manifestations observed in people with co-morbidity, who may not mount sufficient levels of neutralizing antibodies against the first infection. Further studies are necessary but the implication of such a mechanism will need to be considered for all current COVID-19 vaccine designs.", "qid": 32, "docid": "02bwyi1w", "rank": 16, "score": 0.7553614974021912}, {"content": "Title: Understanding evolution of SARS\u2010CoV\u20102: a perspective from analysis of genetic diversity of RdRp gene Content: BACKGROUND & OBJECTIVES: COVID\u201019 emerged as the first example of \u201cDisease X\u201d, a hypothetical disease of humans caused by an unknown infectious agent that was named as novel coronavirus and subsequently designated as SARS\u2010CoV\u20102. The origin of the outbreak at the animal market in Wuhan, China implies it as a case of zoonotic spillover. The study was designed to understand evolution of Betacoronaviruses and in particular diversification of SARS\u2010CoV\u20102 using RdRp gene, a stable genetic marker. METHODS: Phylogenetic and population stratification analyses were carried out using Maximum likelihood and Bayesian methods, respectively. RESULTS: Molecular phylogeny using RdRp, showed that SARS\u2010CoV\u20102 isolates cluster together. Bat\u2010CoV isolate RaTG13 and Pangolin\u2010CoVs are observed to branch off prior to SARS\u2010CoV\u20102 cluster. While SARS\u2010CoV form a single cluster, Bat\u2010CoVs form multiple clusters. Population\u2010based analyses revealed that both SARS\u2010CoV\u20102 and SARS\u2010CoV form separate clusters with no admixture. Bat\u2010CoVs were found to have single and mixed ancestry and clustered as four sub\u2010populations. CONCLUSIONS: Population\u2010based analyses of Betacoronaviruses using RdRp, revealed that SARS\u2010CoV\u20102 is a homogeneous population. SARS\u2010CoV\u20102 appears to have evolved from Bat\u2010CoV isolate RaTG13, which diversified from a common ancestor from which Pangolin\u2010CoVs have also evolved. The admixed Bat\u2010CoV sub\u2010populations indicate that bats serve as reservoirs harboring virus ensembles that are responsible for zoonotic spillovers such as SARS\u2010CoV and SARS\u2010CoV\u20102. The extent of admixed isolates of Bat\u2010CoVs observed in population diversification studies underline the need for periodic surveillance of bats and other animal reservoirs for potential spillovers as a measure towards preparedness for emergence of zoonosis. This article is protected by copyright. All rights reserved.", "qid": 32, "docid": "rwsfw1ei", "rank": 17, "score": 0.7546797394752502}, {"content": "Title: No evidence for distinct types in the evolution of SARS-CoV-2 Content: A recent study by Tang et al. (2020) claimed that two major types of SARS-CoV-2 had evolved in the ongoing COVID-19 pandemic and that one of these types was more \u201caggressive\u201d than the other. Given the repercussions of these claims and the intense media coverage of these types of articles, we have examined in detail the data presented by Tang et al, and show that the major conclusions of that paper cannot be substantiated. Using examples from other viral outbreaks we discuss the difficulty in demonstrating the existence or nature of a functional effect of a viral mutation, and we advise against overinterpretation of genomic data during the pandemic.", "qid": 32, "docid": "m61qihyq", "rank": 18, "score": 0.754601001739502}, {"content": "Title: Decoding SARS-CoV-2 Transmission and Evolution and Ramifications for COVID-19 Diagnosis, Vaccine, and Medicine Content: Tremendous effort has been given to the development of diagnostic tests, preventive vaccines, and therapeutic medicines for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much of this development has been based on the reference genome collected on January 5, 2020. Based on the genotyping of 15\u00e2\u0080\u00af140 genome samples collected up to June 1, 2020, we report that SARS-CoV-2 has undergone 8309 single mutations which can be clustered into six subtypes. We introduce mutation ratio and mutation h-index to characterize the protein conservativeness and unveil that SARS-CoV-2 envelope protein, main protease, and endoribonuclease protein are relatively conservative, while SARS-CoV-2 nucleocapsid protein, spike protein, and papain-like protease are relatively nonconservative. In particular, we have identified mutations on 40% of nucleotides in the nucleocapsid gene in the population level, signaling potential impacts on the ongoing development of COVID-19 diagnosis, vaccines, and antibody and small-molecular drugs.", "qid": 32, "docid": "lzrxdi6a", "rank": 19, "score": 0.7522034049034119}, {"content": "Title: Ten challenging questions about SARS-CoV-2 and COVID-19. Content: INTRODUCTION Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently introduced as a global public health problem by the World Health Organization (WHO). The virus outbreak has been documented around the world. Updating data in different aspects of the virus could force us to revise our idea about the main questions concerning coronavirus disease-19 (COVID-19). AREAS COVERED Although our knowledge about the SARS-CoV-2 and COVID-19 is largely based on the very limited data, the information is growing rapidly. The renewed answers to the specific research questions concerning updating data not only reveal gaps for future research but also re-categorized our information. Here, we attempt to briefly discuss ten important questions about SARS-CoV-2 and COVID-19. EXPERT OPINION Since our knowledge about different aspects of SARS-CoV-2 appears to be in its infancy and is rapidly changing, the provision of the right data is more difficult in this regard. However, we try to rely on results from more extensive research to answer the main questions about this new virus. Therefore, further studies, particularly in the context of the virus pathogenesis, diagnosis, treatment, and vaccine development, are warranted.", "qid": 32, "docid": "l7riy8ox", "rank": 20, "score": 0.7520354986190796}, {"content": "Title: Mutation landscape of SARS-CoV-2 reveals three mutually exclusive clusters of leading and trailing single nucleotide substitutions Content: The COVID-19 pandemic has spread across the globe at an alarming rate in the last four months. However, unlike any of the previous global outbreaks the availability of hundreds of SARS-CoV-2 sequences provides us with a unique opportunity to understand viral evolution in real time. We analysed 480 full-length (>29000 nt) sequences from the 1575 SARS-CoV-2 sequences available and identified 37 single-nucleotide substitutions occurring in >1% of the genomes. Majority of the substitutions were C to T or G to A. We identify C/Gs with an upstream TTT trinucleotide motif as hotspots for mutations in the SARS-CoV-2 genome. Interestingly, two of the 37 substitutions occur within highly conserved secondary structures in the 5\u2019 and 3\u2019 untranslated regions that are critical for the virus life cycle. Furthermore, clustering analysis revealed unique geographical distribution of SARS-CoV-2 variants defined by their mutation profile. Of note, we observed several co-occurring mutations that almost never occur individually. We define 3 mutually exclusive lineages (A1, B1 and C1) of SARS-CoV-2 which account for about three quarters of the genomes analysed. We identify lineage-defining leading mutations in the SARS-CoV-2 genome which precede the occurrence of sub-lineage defining trailing mutations. The identification of mutually exclusive lineage-defining mutations with geographically restricted patterns of distribution has potential implications for diagnosis, pathogenesis and vaccine design. Our work provides novel insights on the temporal evolution of SARS-CoV-2.", "qid": 32, "docid": "miujzgtd", "rank": 21, "score": 0.751456081867218}, {"content": "Title: Decoding SARS-CoV-2 transmission, evolution and ramification on COVID-19 diagnosis, vaccine, and medicine Content: Tremendous effort has been given to the development of diagnostic tests, preventive vaccines, and therapeutic medicines for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much of this development has been based on the reference genome collected on January 5, 2020. Based on the genotyping of 6156 genome samples collected up to April 24, 2020, we report that SARS-CoV-2 has had 4459 alarmingly mutations which can be clustered into five subtypes. We introduce mutation ratio and mutation $h$-index to characterize the protein conservativeness and unveil that SARS-CoV-2 envelope protein, main protease, and endoribonuclease protein are relatively conservative, while SARS-CoV-2 nucleocapsid protein, spike protein, and papain-like protease are relatively non-conservative. In particular, the nucleocapsid protein has more than half its genes changed in the past few months, signaling devastating impacts on the ongoing development of COVID-19 diagnosis, vaccines, and drugs.", "qid": 32, "docid": "u6ewlh16", "rank": 22, "score": 0.7511513233184814}, {"content": "Title: Polymorphism and selection pressure of SARS-CoV-2 vaccine and diagnostic antigens: implications for immune evasion and serologic diagnostic performance Content: The ongoing SARS-CoV-2 pandemic has triggered multiple efforts for serological tests and vaccine development. Most of these tests and vaccines are based on the Spike glycoprotein (S) or the Nucleocapsid (N) viral protein. Conservation of these antigens among viral strains is critical to ensure optimum diagnostic test performance and broad protective efficacy, respectively. We assessed N and S antigen diversity from 17,853 SARS-CoV-2 genome sequences and evaluated selection pressure. Up to 6-7 incipient phylogenetic clades were identified for both antigens, confirming early variants of the S antigen and identifying new ones. Significant diversifying selection was detected at multiple sites for both antigens. Some sequence variants have already spread in multiple regions, in spite of their low frequency. In conclusion, the N and S antigens of SARS-CoV-2 are well conserved antigens, but new clades are emerging and may need to be included in future diagnostic and vaccine formulations.", "qid": 32, "docid": "grnibz2t", "rank": 23, "score": 0.7506629228591919}, {"content": "Title: SARS-CoV-2: virus mutations in specific European populations Content: Abstract The SARS-CoV-2 virus is being intensively studied, particularly, its evolution in the increasingly available sequences between countries/continents with classical phylogenetic tree representation. More recently, certain protein mutations are correlated with specific functional impacts. Our clinical data from patients suggest different clinical symptoms between European countries. Among others, SARS-CoV-2 mutations could explain these disparities. Our analyses point out an association of diverse mutations, including co-evolving ones, in a few SARS-CoV-2 proteins, with specific countries. We therefore suggest combining clinical information from patients and the determination of the associated SARS-CoV-2 genome to better understand the specific symptoms.", "qid": 32, "docid": "y5th0mrf", "rank": 24, "score": 0.750328540802002}, {"content": "Title: Quantification of Intra-Host Genomic Diversity of SARS-CoV-2 Allows a High-Resolution Characterization of Viral Evolution and Reveals Functionally Convergent Variants Content: A global cross-discipline effort is ongoing to characterize the evolution of SARS-CoV-2 virus and generate reliable epidemiological models of its diffusion. To this end, phylogenomic approaches leverage accumulating genomic mutations as barcodes to track the evolutionary history of the virus and can benefit from the surge of sequences deposited in public databases. Yet, such methods typically rely on consensus sequences representing the dominant virus lineage, whereas a complex sublineage architecture is often observed within single hosts. Furthermore, most approaches do not account for variants accumulation processes and might produce inaccurate results in condition of limited sampling, as witnessed in most countries affected by the epidemics. We introduce VERSO (Viral Evolution ReconStructiOn), a new comprehensive framework for the characterization of viral evolution and transmission from sequencing data of viral genomes. our approach accounts for accumulation of clonal mutations and uncertainty in the data, by taking advantage of the achievements of research in cancer evolution, to deliver robust phylogenomic lineage models, and exploits intra-host variant frequency profiles to characterize the sublineage similarity among samples, which may derive from uncovered infection events. The application of our approach to RNA-sequencing data of 162 SARS-CoV-2 samples generates a high-resolution model of evolution and spread, which improves recent findings on viral types and highlights the existence of patterns of co-occurrence of minor variants, revealing likely infection paths among hosts harboring the same viral lineage. The in-depth analysis of the mutational landscape of SARS-CoV-2 confirms a statistically significant increase of genomic diversity in time and identifies a number of variants that are transiting from minor to clonal state in the population. We also show that standard phylogenetic methods can produce unreliable results when handling datasets with noise and sampling limitations, as proven by the further application of VERSO to 12419 consensus sequences included in GISAID database. Notably, VERSO allows to pinpoint minor variants that might be positively or negatively selected across distinct lineages, thus driving the design of treatments and vaccines. In particular, minor variant g.29039A>U, detected in multiple viral lineages and validated on independent samples, shows that SARS-CoV-2 can lose its main Nucleocapsid immunogenic epitopes, raising concerns about the effectiveness of vaccines targeting the C-terminus of this protein. Finally, we here release the likely SARS-CoV-2 ancestral genome, obtained by resolving ambiguous SNPs that distinguish two widely-used reference genomes from human samples, by employing the Pangolin-CoV and the Bat-CoV-RaTG13 genomes. Our results show that the joint application of our framework and data-driven epidemiological models might allow to deliver a high-resolution platform for pathogen surveillance and analysis.", "qid": 32, "docid": "ea78sjcs", "rank": 25, "score": 0.7502797842025757}, {"content": "Title: Decoding SARS-CoV-2 Transmission and Evolution and Ramifications for COVID-19 Diagnosis, Vaccine, and Medicine Content: [Image: see text] Tremendous effort has been given to the development of diagnostic tests, preventive vaccines, and therapeutic medicines for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much of this development has been based on the reference genome collected on January 5, 2020. Based on the genotyping of 15 140 genome samples collected up to June 1, 2020, we report that SARS-CoV-2 has undergone 8309 single mutations which can be clustered into six subtypes. We introduce mutation ratio and mutation h-index to characterize the protein conservativeness and unveil that SARS-CoV-2 envelope protein, main protease, and endoribonuclease protein are relatively conservative, while SARS-CoV-2 nucleocapsid protein, spike protein, and papain-like protease are relatively nonconservative. In particular, we have identified mutations on 40% of nucleotides in the nucleocapsid gene in the population level, signaling potential impacts on the ongoing development of COVID-19 diagnosis, vaccines, and antibody and small-molecular drugs.", "qid": 32, "docid": "13tc3loo", "rank": 26, "score": 0.750038743019104}, {"content": "Title: Hidden genomic diversity of SARS-CoV-2: implications for qRT-PCR diagnostics and transmission Content: The COVID-19 pandemic has sparked an urgent need to uncover the underlying biology of this devastating disease. Though RNA viruses mutate more rapidly than DNA viruses, there are a relatively small number of single nucleotide polymorphisms (SNPs) that differentiate the main SARS-CoV-2 clades that have spread throughout the world. In this study, we investigated over 7,000 SARS-CoV-2 datasets to unveil both intrahost and interhost diversity. Our intrahost and interhost diversity analyses yielded three major observations. First, the mutational profile of SARS-CoV-2 highlights iSNV and SNP similarity, albeit with high variability in C>T changes. Second, iSNV and SNP patterns in SARS-CoV-2 are more similar to MERS-CoV than SARS-CoV-1. Third, a significant fraction of small indels fuel the genetic diversity of SARS-CoV-2. Altogether, our findings provide insight into SARS-CoV-2 genomic diversity, inform the design of detection tests, and highlight the potential of iSNVs for tracking the transmission of SARS-CoV-2.", "qid": 32, "docid": "2nijfrn5", "rank": 27, "score": 0.7491112947463989}, {"content": "Title: Ten challenging questions about SARS-CoV-2 and COVID-19 Content: INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently introduced as a global public health problem by the World Health Organization (WHO). The virus outbreak has been documented around the world. Updating data in different aspects of the virus could force us to revise our idea about the main questions concerning coronavirus disease-19 (COVID-19). AREAS COVERED: Although our knowledge about the SARS-CoV-2 and COVID-19 is largely based on the very limited data, the information is growing rapidly. The renewed answers to the specific research questions concerning updating data not only reveal gaps for future research but also re-categorized our information. Here, we attempt to briefly discuss 10 important questions about SARS-CoV-2 and COVID-19. EXPERT OPINION: Since our knowledge about different aspects of SARS-CoV-2 appears to be in its infancy and is rapidly changing, the provision of the right data is more difficult in this regard. However, we try to rely on results from more extensive research to answer the main questions about this new virus. Therefore, further studies, particularly in the context of the virus pathogenesis, diagnosis, treatment, and vaccine development, are warranted.", "qid": 32, "docid": "tst7ss76", "rank": 28, "score": 0.7490148544311523}, {"content": "Title: From SARS and MERS CoVs to SARS\u2010CoV\u20102: Moving toward more biased codon usage in viral structural and nonstructural genes Content: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) is an emerging disease with fatal outcomes. In this study, a fundamental knowledge gap question is to be resolved by evaluating the differences in biological and pathogenic aspects of SARS\u2010CoV\u20102 and the changes in SARS\u2010CoV\u20102 in comparison with the two prior major COV epidemics, SARS and Middle East respiratory syndrome (MERS) coronaviruses. METHODS: The genome composition, nucleotide analysis, codon usage indices, relative synonymous codons usage, and effective number of codons (ENc) were analyzed in the four structural genes; Spike (S), Envelope (E), membrane (M), and Nucleocapsid (N) genes, and two of the most important nonstructural genes comprising RNA\u2010dependent RNA polymerase and main protease (Mpro) of SARS\u2010CoV\u20102, Beta\u2010CoV from pangolins, bat SARS, MERS, and SARS CoVs. RESULTS: SARS\u2010CoV\u20102 prefers pyrimidine rich codons to purines. Most high\u2010frequency codons were ending with A or T, while the low frequency and rare codons were ending with G or C. SARS\u2010CoV\u20102 structural proteins showed 5 to 20 lower ENc values, compared with SARS, bat SARS, and MERS CoVs. This implies higher codon bias and higher gene expression efficiency of SARS\u2010CoV\u20102 structural proteins. SARS\u2010CoV\u20102 encoded the highest number of over\u2010biased and negatively biased codons. Pangolin Beta\u2010CoV showed little differences with SARS\u2010CoV\u20102 ENc values, compared with SARS, bat SARS, and MERS CoV. CONCLUSION: Extreme bias and lower ENc values of SARS\u2010CoV\u20102, especially in Spike, Envelope, and Mpro genes, are suggestive for higher gene expression efficiency, compared with SARS, bat SARS, and MERS CoVs.", "qid": 32, "docid": "4jky78sl", "rank": 29, "score": 0.7487908601760864}, {"content": "Title: From SARS and MERS CoVs to SARS-CoV-2: Moving toward more biased codon usage in viral structural and nonstructural genes Content: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging disease with fatal outcomes. In this study, a fundamental knowledge gap question is to be resolved by evaluating the differences in biological and pathogenic aspects of SARS-CoV-2 and the changes in SARS-CoV-2 in comparison with the two prior major COV epidemics, SARS and Middle East respiratory syndrome (MERS) coronaviruses. METHODS: The genome composition, nucleotide analysis, codon usage indices, relative synonymous codons usage, and effective number of codons (ENc) were analyzed in the four structural genes; Spike (S), Envelope (E), membrane (M), and Nucleocapsid (N) genes, and two of the most important nonstructural genes comprising RNA-dependent RNA polymerase and main protease (Mpro) of SARS-CoV-2, Beta-CoV from pangolins, bat SARS, MERS, and SARS CoVs. RESULTS: SARS-CoV-2 prefers pyrimidine rich codons to purines. Most high-frequency codons were ending with A or T, while the low frequency and rare codons were ending with G or C. SARS-CoV-2 structural proteins showed 5 to 20 lower ENc values, compared with SARS, bat SARS, and MERS CoVs. This implies higher codon bias and higher gene expression efficiency of SARS-CoV-2 structural proteins. SARS-CoV-2 encoded the highest number of over-biased and negatively biased codons. Pangolin Beta-CoV showed little differences with SARS-CoV-2 ENc values, compared with SARS, bat SARS, and MERS CoV. CONCLUSION: Extreme bias and lower ENc values of SARS-CoV-2, especially in Spike, Envelope, and Mpro genes, are suggestive for higher gene expression efficiency, compared with SARS, bat SARS, and MERS CoVs.", "qid": 32, "docid": "oxxrnw1r", "rank": 30, "score": 0.7483366131782532}, {"content": "Title: Genetic analysis of SARS-CoV-2 strains collected from North Africa: viral origins and mutational spectrum Content: In Morocco two waves of SARS-CoV-2 infections have been recorded. The first one occurred from March 02, 2020 with infections mostly imported from Europe and the second one dominated by local infections. At the time of writing, the genetic diversity of Moroccan isolates of SARS-CoV-2 has not yet been reported. The present study aimed to analyze first the genomic variation of the twenty-eight Moroccan strains of SARS-CoV-2 isolated from March 03, 2020 to May 15, 2020, to compare their distributions with twelve other viral genomes from North Africa as well as to identify their possible sources. Our finding revealed 61 mutations in the Moroccan genomes of SARS-CoV-2 compared to the reference sequence Wuhan-Hu-1/2019, of them 23 (37.7%) were present in two or more genomes. Focusing on non-synonymous mutations, 29 (47.54%) were distributed in five genes (ORF1ab, spike, membrane, nucleocapsid and ORF3a) with variable frequencies. The non-structural protein coding regions nsp3-Multi domain and nsp12-RdRp of the ORF1ab gene harbored more mutations, with six for each. The comparison of genetic variants of fourty North African strains revealed that two non-synonymous mutations D614G (in spike) and Q57H (in ORF3a) were common in four countries (Morocco, Tunisia, Algeria and Egypt), with a prevalence of 92.5% (n = 37) and 42.5% (n = 17), respectively, of the total genomes. Phylogenetic analysis showed that the Moroccan and Tunisian SARS-CoV-2 strains were closely related to those from different origins (Asia, Europe, North and South America) and distributed in different distinct subclades. This could indicate different sources of infection with no specific strain dominating yet in in these countries. These results have the potential to lead to new comprehensive investigations combining genomic data, epidemiological information and the clinical characteristics of patients with SARS-CoV-2.", "qid": 32, "docid": "8871aifz", "rank": 31, "score": 0.7480078935623169}, {"content": "Title: On the origin and continuing evolution of SARS-CoV-2 Content: The SARS-CoV-2 epidemic started in late December 2019 in Wuhan, China, and has since impacted a large portion of China and raised major global concern. Herein, we investigated the extent of molecular divergence between SARS-CoV-2 and other related coronaviruses. Although we found only 4% variability in genomic nucleotides between SARS-CoV-2 and a bat SARS-related coronavirus (SARSr-CoV; RaTG13), the difference at neutral sites was 17%, suggesting the divergence between the two viruses is much larger than previously estimated. Our results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by mutations and natural selection besides recombination. Population genetic analyses of 103 SARS-CoV-2 genomes indicated that these viruses evolved into two major types (designated L and S), that are well defined by two different SNPs that show nearly complete linkage across the viral strains sequenced to date. Although the L type (\u223c70%) is more prevalent than the S type (\u223c30%), the S type was found to be the ancestral version. Whereas the L type was more prevalent in the early stages of the outbreak in Wuhan, the frequency of the L type decreased after early January 2020. Human intervention may have placed more severe selective pressure on the L type, which might be more aggressive and spread more quickly. On the other hand, the S type, which is evolutionarily older and less aggressive, might have increased in relative frequency due to relatively weaker selective pressure. These findings strongly support an urgent need for further immediate, comprehensive studies that combine genomic data, epidemiological data, and chart records of the clinical symptoms of patients with coronavirus disease 2019 (COVID-19).", "qid": 32, "docid": "j99cgsjt", "rank": 32, "score": 0.747096836566925}, {"content": "Title: CoV2ID: Detection and Therapeutics Oligo Database for SARS-CoV-2 Content: The ability to detect the SARS-CoV-2 in a widespread epidemic is crucial for screening of carriers and for the success of quarantine efforts. Methods based on real-time reverse transcription polymerase chain reaction (RT-qPCR) and sequencing are being used for virus detection and characterization. However, RNA viruses are known for their high genetic diversity which poses a challenge for the design of efficient nucleic acid-based assays. The first SARS-CoV-2 genomic sequences already showed novel mutations, which may affect the efficiency of available screening tests leading to false-negative diagnosis or inefficient therapeutics. Here we describe the CoV2ID (http://covid.portugene.com/), a free database built to facilitate the evaluation of molecular methods for detection of SARS-CoV-2 and treatment of COVID-19. The database evaluates the available oligonucleotide sequences (PCR primers, RT-qPCR probes, etc.) considering the genetic diversity of the virus. Updated sequences alignments are used to constantly verify the theoretical efficiency of available testing methods. Detailed information on available detection protocols are also available to help laboratories implementing SARS-CoV-2 testing.", "qid": 32, "docid": "mg2dziuw", "rank": 33, "score": 0.7469720840454102}, {"content": "Title: Monophyletic Relationship between Severe Acute Respiratory Syndrome Coronavirus and Group 2 Coronaviruses Content: Although primary genomic analysis has revealed that severe acute respiratory syndrome coronavirus (SARS CoV) is a new type of coronavirus, the different protein trees published in previous reports have provided no conclusive evidence indicating the phylogenetic position of SARS CoV. To clarify the phylogenetic relationship between SARS CoV and other coronaviruses, we compiled a large data set composed of 7 concatenated protein sequences and performed comprehensive analyses, using the maximum-likelihood, Bayesian-inference, and maximum-parsimony methods. All resulting phylogenetic trees displayed an identical topology and supported the hypothesis that the relationship between SARS CoV and group 2 CoVs is monophyletic. Relationships among all major groups were well resolved and were supported by all statistical analyses.", "qid": 32, "docid": "005b2j4b", "rank": 34, "score": 0.7469704747200012}, {"content": "Title: Mega-phylogeny sheds light on SARS-CoV-2 spatial phylogenetic structure Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent RNA virus that spread around the planet in about 4 months. The consequences of this rapid spread on the virus evolution are under investigation. In this work, we analyzed ca. 9,000 SARS-CoV-2 genomes from Africa, America, Asia, Europe, and Oceania. We show that the virus is a complex of slightly different genetic variants that are unevenly distributed on Earth. Furthermore, we demonstrate that SARS-CoV-2 phylogeny is spatially structured. We hypothesize this could be the result of founder effects occurring as a consequence of, and local evolution occurring after, long-distance dispersal. In light of our results, we discuss how dispersal may constitute an opportunity for the virus to fix otherwise rare, and/or develop new, mutations. Based on previous studies, the possibility that this could significantly affect the virus phenotype is not remote. Relevance A cluster of pneumonia cases of unknown etiology was reported in December 2019 in Wuhan, Hubei province, China. Since then, hundreds of thousands of people have died all around the planet. Quickly after the pandemic onset, metagenomic studies showed the causative agent, now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belonged to the Betacoronavirus genus, responsible for spillover events in 2002 and 2012 (severe acute respiratory syndrome and Middle East respiratory syndrome, respectively). The zoonotic origins of these viruses (possibly bats, camelids, pangolins and/or palm civets) have received much attention. However, other evolutionary aspects, such as spatial variation, have received comparatively little attention. This study shows that SARS-CoV-2 variants, which we call virotypes, are heterogeneously distributed on Earth and demonstrates that the virus phylogeny is geographically structured. We explain how this may be due to founder effects combined with high mutation rates.", "qid": 32, "docid": "3k5lmawz", "rank": 35, "score": 0.7463018894195557}, {"content": "Title: The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus Content: SARS-CoV-1 and SARS-CoV-2 are not phylogenetically closely related; however, both use the ACE2 receptor in humans for cell entry. This is not a universal sarbecovirus trait; for example, many known sarbecoviruses related to SARS-CoV-1 have two deletions in the receptor binding domain of the spike protein that render them incapable of using human ACE2. Here, we report three novel sarbecoviruses from Rwanda and Uganda which are phylogenetically intermediate to SARS-CoV-1 and SARS-CoV-2 and demonstrate via in vitro studies that they are also unable to utilize human ACE2. Furthermore, we show that the observed pattern of ACE2 usage among sarbecoviruses is most likely due to recombination. We show that the lineage that includes SARS-CoV-2 is most likely the ancestral ACE2-using lineage, and that recombination with at least one virus from this group conferred ACE2 usage to the progenitor of SARS-CoV-1 at some time in the past. We argue that alternative scenarios such as convergent evolution are much less parsimonious; we show that biogeography and patterns of host tropism support the plausibility of a recombination scenario; and we propose a competitive release hypothesis to explain how this recombination event could have occurred and why it is evolutionarily advantageous. The findings provide important insights into the natural history of ACE2 usage for both SARS-CoV-1 and SARS-CoV-2, and a greater understanding of the evolutionary mechanisms that shape zoonotic potential of coronaviruses. This study also underscores the need for increased surveillance for sarbecoviruses in southwestern China, where most ACE2-using viruses have been found to date, as well as other regions including Africa, where these viruses have only recently been discovered.", "qid": 32, "docid": "k0osv3ay", "rank": 36, "score": 0.7459499835968018}, {"content": "Title: The genomic variation landscape of globally-circulating clades of SARS-CoV-2 defines a genetic barcoding scheme Content: We describe fifteen major mutation events from 2,058 high-quality SARS-CoV-2 genomes deposited up to March 31st, 2020. These events define five major clades (G, I, S, D and V) of globally-circulating viral populations, representing 85.7% of all sequenced cases, which we can identify using a 10 nucleotide genetic classifier or barcode. We applied this barcode to 4,000 additional genomes deposited between March 31st and April 15th and classified successfully 95.6% of the clades demonstrating the utility of this approach. An analysis of amino acid variation in SARS-CoV-2 ORFs provided evidence of substitution events in the viral proteins involved in both host-entry and genome replication. The systematic monitoring of dynamic changes in the SARS-CoV-2 genomes of circulating virus populations over time can guide therapeutic and prophylactic strategies to manage and contain the virus and, also, with available efficacious antivirals and vaccines, aid in the monitoring of circulating genetic diversity as we proceed towards elimination of the agent. The barcode will add the necessary genetic resolution to facilitate tracking and monitoring of infection clusters to distinguish imported and indigenous cases and thereby aid public health measures seeking to interrupt transmission chains without the requirement for real-time complete genomes sequencing.", "qid": 32, "docid": "drqhuhk4", "rank": 37, "score": 0.7456487417221069}, {"content": "Title: Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility Content: Direct massively parallel sequencing of SARS-CoV-2 genome was undertaken from nasopharyngeal and oropharyngeal swab samples of infected individuals in Eastern India. Seven of the isolates belonged to the A2a clade, while one belonged to the B4 clade. Specific mutations, characteristic of the A2a clade, were also detected, which included the P323L in RNA-dependent RNA polymerase and D614G in the Spike glycoprotein. Further, our data revealed emergence of novel subclones harbouring nonsynonymous mutations, viz. G1124V in Spike (S) protein, R203K, and G204R in the nucleocapsid (N) protein. The N protein mutations reside in the SR-rich region involved in viral capsid formation and the S protein mutation is in the S(2) domain, which is involved in triggering viral fusion with the host cell membrane. Interesting correlation was observed between these mutations and travel or contact history of COVID-19 positive cases. Consequent alterations of miRNA binding and structure were also predicted for these mutations. More importantly, the possible implications of mutation D614G (in S(D) domain) and G1124V (in S(2) subunit) on the structural stability of S protein have also been discussed. Results report for the first time a bird\u2019s eye view on the accumulation of mutations in SARS-CoV-2 genome in Eastern India. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12038-020-00046-1) contains supplementary material, which is available to authorized users.", "qid": 32, "docid": "6dsx7pey", "rank": 38, "score": 0.7456143498420715}, {"content": "Title: Limited SARS-CoV-2 diversity within hosts and following passage in cell culture Content: Since the first reports of pneumonia associated with a novel coronavirus (COVID-19) emerged in Wuhan, Hubei province, China, there have been considerable efforts to sequence the causative virus, SARS-CoV-2 (also referred to as hCoV-19) and to make viral genomic information available quickly on shared repositories. As of 30 March 2020, 7,680 consensus sequences have been shared on GISAID, the principal repository for SARS-CoV-2 genetic information. These sequences are primarily consensus sequences from clinical and passaged samples, but few reports have looked at diversity of virus populations within individual hosts or cultures. Understanding such diversity is essential to understanding viral evolutionary dynamics. Here, we characterize within-host viral diversity from a primary isolate and passaged samples, all originally deriving from an individual returning from Wuhan, China, who was diagnosed with COVID-19 and subsequently sampled in Wisconsin, United States. We use a metagenomic approach with Oxford Nanopore Technologies (ONT) GridION in combination with Illumina MiSeq to capture minor within-host frequency variants \u22651%. In a clinical swab obtained from the day of hospital presentation, we identify 15 single nucleotide variants (SNVs) \u22651% frequency, primarily located in the largest gene \u2013 ORF1a. While viral diversity is low overall, the dominant genetic signatures are likely secondary to population size changes, with some evidence for mild purifying selection throughout the genome. We see little to no evidence for positive selection or ongoing adaptation of SARS-CoV-2 within cell culture or in the primary isolate evaluated in this study. Author Summary Within-host variants are critical for addressing molecular evolution questions, identifying selective pressures imposed by vaccine-induced immunity and antiviral therapeutics, and characterizing interhost dynamics, including the stringency and character of transmission bottlenecks. Here, we sequenced SARS-CoV-2 viruses isolated from a human host and from cell culture on three distinct Vero cell lines using Illumina and ONT technologies. We show that SARS-CoV-2 consensus sequences can remain stable through at least two serial passages on Vero 76 cells, suggesting SARS-CoV-2 can be propagated in cell culture in preparation for in-vitro and in-vivo studies without dramatic alterations of its genotype. However, we emphasize the need to deep-sequence viral stocks prior to use in experiments to characterize sub-consensus diversity that may alter outcomes.", "qid": 32, "docid": "izu5x2d4", "rank": 39, "score": 0.745593786239624}, {"content": "Title: A dynamic nomenclature proposal for SARS-CoV-2 to assist genomic epidemiology Content: The ongoing pandemic spread of a novel human coronavirus, SARS-COV-2, associated with severe pneumonia disease (COVID-19), has resulted in the generation of thousands of virus genome sequences. The rate of genome generation is unprecedented, yet there is currently no coherent nor accepted scheme for naming the expanding phylogenetic diversity of SARS-CoV-2. We present a rational and dynamic virus nomenclature that uses a phylogenetic framework to identify those lineages that contribute most to active spread. Our system is made tractable by constraining the number and depth of hierarchical lineage labels and by flagging and declassifying virus lineages that become unobserved and hence are likely inactive. By focusing on active virus lineages and those spreading to new locations this nomenclature will assist in tracking and understanding the patterns and determinants of the global spread of SARS-CoV-2.", "qid": 32, "docid": "l7ymcyw7", "rank": 40, "score": 0.7448663711547852}, {"content": "Title: Global genetic diversity patterns and transmissions of SARS-CoV-2 Content: Background: Since it was firstly discovered in China, the SARS-CoV-2 epidemic has caused a substantial health emergency and economic stress in the world. However, the global genetic diversity and transmissions are still unclear. Methods: 3050 SARS-CoV-2 genome sequences were retrieved from GIASID database. After aligned by MAFFT, the mutation patterns were identified by phylogenetic tree analysis. Results: We detected 17 high frequency (>6%) mutations in the 3050 sequences. Based on these mutations, we classed the SARS-CoV-2 into four main groups and 10 subgroups. We found that group A was mainly presented in Asia, group B was primarily detected in North America, group C was prevailingly appeared in Asia and Oceania and group D was principally emerged in Europe and Africa. Additionally, the distribution of these groups was different in age, but was similar in gender. Group A, group B1 and group C2 were declined over time, inversely, group B2, group C3 and group D were rising. At last, we found two apparent expansion stages (late Jan-2020 and late Feb-2020 to early Mar-2020, respectively). Notably, most of groups are quickly expanding, especially group D. Conclusions: We classed the SARS-CoV-2 into four main groups and 10 subgroups based on different mutation patterns at first time. The distribution of the 10 subgroups was different in geography, time and age, but not in gender. Most of groups are rapidly expanding, especially group D. Therefore, we should attach importance to these genetic diversity patterns of SARS-CoV-2 and take more targeted measures to constrain its spread.", "qid": 32, "docid": "r3t4bd78", "rank": 41, "score": 0.7448164224624634}, {"content": "Title: Transcriptional Difference between SARS-COV-2 and other Human Coronaviruses Revealed by Sub-genomic RNA Profiling Content: SARS-COV-2 and all other coronaviruses express its 3 prime genes by forming sub-genomic RNA. As the genome of these virus exist in RNA form, only by profiling the relative abundance of these sgRNAs, can the viral transcriptome be revealed. Utilizing publically available meta-transcriptomic data generated from patient samples, we were able to infer the viral transcriptome in vivo, which is distinct from the in vitro one derived from cell culture. Inter-sample diversity was also observed and a sample specific transcript was identified. By doing the same analysis to MERS and SARS data, we were able to compare the three in terms of transcription. Among the differences, SARS-COV-2 has significantly elevated expression of the Spike gene, which may contribute to its high transmissibility. Highlights The in vivo transcriptome of SARS-CoV-2 revealed by sgRNA profiling, for 25 patient samples around the globe. The Spike protein expression is an order of magnitude higher in SARS-CoV-2 than MERS-CoV or SARS-CoV, possibly contributing to the virus\u2019 elevated transmissibility. The in vivo SARS-CoV-2 transcriptomes, as inferred from human patient data was distinct from the in vitro one derived from cell line culture, all the accessory genes were up-regulated in vivo, suggesting intricate expression regulation mechanism for the small viral genome.", "qid": 32, "docid": "6tytbgpq", "rank": 42, "score": 0.744715690612793}, {"content": "Title: Genome Analysis of SARS-CoV-2 Isolate from Bangladesh Content: Recently the first genome sequence for a Severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 isolate from Bangladesh became available. The sequencing was carried out by the Child Health Research Foundation and provided the first insight into the genetic details of the viral strain responsible for the SARS-CoV-2 infections in Bangladesh. Here we carried out a comparative study were we explored the phylogenetic relationship between the Bangladeshi isolate with other isolates from different parts of the world. Afterwards we identified single nucleotide variants in the Bangladeshi isolate, using the Wuhan virus reference sequence. We found a total of 9 variants in the Bangladeshi isolate using 2 separate tools. Barring 2, the rest of these variants were also observed in other isolates from different countries. Most of the variants occurred in the ORF1ab gen. Another noteworthy finding was a sequence of three consecutive variants in the N protein gene that were observed in other isolates as well. Lastly the phylogenetic analysis revealed a close relationship between the Bangladeshi isolate and those from Taiwan, Kazakhstan, Greece, California, Spain, Israel, and Sri Lanka.", "qid": 32, "docid": "gygi11gk", "rank": 43, "score": 0.7446455359458923}, {"content": "Title: Evidence of Increasing Diversification of Emerging SARS-CoV-2 Strains Content: BACKGROUND: On January 30th, 2020, an outbreak of atypical pneumonia caused by a novel Betacoronavirus (\u00dfCoV), named SARS-CoV-2, was declared a public health emergency of international concern by the World Health Organization. For this reason, a detailed evolutionary analysis of SARS-CoV-2 strains currently circulating in different geographic regions of the world was performed. METHODS: A compositional analysis as well as a Bayesian coalescent analysis of complete genome sequences of SARS-CoV-2 strains recently isolated in Europe, North America, South America and Asia was performed. RESULTS: The results of these studies revealed a diversification of SARS-CoV-2 strains in three different genetic clades. Co-circulation of different clades in different countries, as well as different genetic lineages within different clades were observed. The time of the most recent common ancestor (tMRCA) was established to be around November 1, 2019. A mean rate of evolution of 6.57 x 10-4 substitutions per site per year was found. A significant migration rate per genetic lineage per year from Europe to South America was also observed. CONCLUSION: The results of these studies revealed an increasing diversification of SARS-CoV-2 strains. High evolutionary rates and fast population growth characterizes the population dynamics of SARS-CoV-2 strains. This article is protected by copyright. All rights reserved.", "qid": 32, "docid": "1h1hwbos", "rank": 44, "score": 0.7445613741874695}, {"content": "Title: Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility. Content: Direct massively parallel sequencing of SARS-CoV-2 genome was undertaken from nasopharyngeal and oropharyngeal swab samples of infected individuals in Eastern India. Seven of the isolates belonged to the A2a clade, while one belonged to the B4 clade. Specific mutations, characteristic of the A2a clade, were also detected, which included the P323L in RNA-dependent RNA polymerase and D614G in the Spike glycoprotein. Further, our data revealed emergence of novel subclones harbouring nonsynonymous mutations, viz. G1124V in Spike (S) protein, R203K, and G204R in the nucleocapsid (N) protein. The N protein mutations reside in the SR-rich region involved in viral capsid formation and the S protein mutation is in the S2 domain, which is involved in triggering viral fusion with the host cell membrane. Interesting correlation was observed between these mutations and travel or contact history of COVID-19 positive cases. Consequent alterations of miRNA binding and structure were also predicted for these mutations. More importantly, the possible implications of mutation D614G (in SD domain) and G1124V (in S2 subunit) on the structural stability of S protein have also been discussed. Results report for the first time a bird's eye view on the accumulation of mutations in SARS-CoV-2 genome in Eastern India.", "qid": 32, "docid": "02cfyuf4", "rank": 45, "score": 0.744120180606842}, {"content": "Title: A snapshot of SARS-CoV-2 genome availability up to 30th March, 2020 and its implications Content: The SARS-CoV-2 pandemic has been growing exponentially, affecting nearly 900 thousand people and causing enormous distress to economies and societies worldwide. A plethora of analyses based on viral sequences has already been published, in scientific journals as well as through non-peer reviewed channels, to investigate SARS-CoV-2 genetic heterogeneity and spatiotemporal dissemination. We examined full genome sequences currently available to assess the presence of sufficient information for reliable phylogenetic and phylogeographic studies in countries with the highest toll of confirmed cases. Although number of-available full-genomes is growing daily, and the full dataset contains sufficient phylogenetic information that would allow reliable inference of phylogenetic relationships, country-specific SARS-CoV-2 datasets still present severe limitations. Studies assessing within country spread or transmission clusters should be considered preliminary at best, or hypothesis generating. Hence the need for continuing concerted efforts to increase number and quality of the sequences required for robust tracing of the epidemic. Significance Statement Although genome sequences of SARS-CoV-2 are growing daily and contain sufficient phylogenetic information, country-specific data still present severe limitations and should be interpreted with caution.", "qid": 32, "docid": "8vl0okiv", "rank": 46, "score": 0.7440155744552612}, {"content": "Title: Emerging phylogenetic structure of the SARS-CoV-2 pandemic Content: Since spilling over into humans, SARS-CoV-2 has rapidly spread across the globe, accumulating significant genetic diversity. The structure of this genetic diversity, and whether it reveals epidemiological insights, are fundamental questions for understanding the evolutionary trajectory of this virus. Here we use a recently developed phylodynamic approach to uncover phylogenetic structures underlying the SARS-CoV-2 pandemic. We find support for three SARS-CoV-2 lineages co-circulating, each with significantly different demographic dynamics concordant with known epidemiological factors. For example, Lineage C emerged in Europe with a high growth rate in late February, just prior to the exponential increase in cases in several European countries. Mutations that characterize Lineage C in particular are non-synonymous and occur in functionally important gene regions responsible for viral replication and cell entry. Even though Lineages A and B had distinct demographic patterns, they were much more difficult to distinguish. Continuous application of phylogenetic approaches to track the evolutionary epidemiology of SARS-CoV-2 lineages will be increasingly important to validate the efficacy of control efforts and monitor significant evolutionary events in the future.", "qid": 32, "docid": "3b5jk6o3", "rank": 47, "score": 0.7436031103134155}, {"content": "Title: Regaining perspective on SARS-CoV-2 molecular tracing and its implications Content: During the past three months, a new coronavirus (SARS-CoV-2) epidemic has been growing exponentially, affecting over 100 thousand people worldwide, and causing enormous distress to economies and societies of affected countries. A plethora of analyses based on viral sequences has already been published, in scientific journals as well as through non-peer reviewed channels, to investigate SARS-CoV-2 genetic heterogeneity and spatiotemporal dissemination. We examined all full genome sequences currently available to assess the presence of sufficient information for reliable phylogenetic and phylogeographic studies. Our analysis clearly shows severe limitations in the present data, in light of which any finding should be considered, at the very best, preliminary and hypothesis-generating. Hence the need for avoiding stigmatization based on partial information, and for continuing concerted efforts to increase number and quality of the sequences required for robust tracing of the epidemic.", "qid": 32, "docid": "szg12wfa", "rank": 48, "score": 0.7428693771362305}, {"content": "Title: Temporal evolution and adaptation of SARS-COV 2 codon usage Content: The outbreak of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has caused an unprecedented pandemic. Since the first sequenced whole-genome of SARS-CoV-2 on January 2020, the identification of its genetic variants has become crucial in tracking and evaluating their spread across the globe. In this study, we compared 15,259 SARS-CoV-2 genomes isolated from 60 countries since the outbreak of this novel coronavirus with the first sequenced genome in Wuhan to quantify the evolutionary divergence of SARS-CoV-2. Thus, we compared the codon usage patterns, every two weeks, of 13 of SARS-CoV-2 genes encoding for the membrane protein (M), envelope (E), spike surface glycoprotein (S), nucleoprotein (N), non-structural 3C-like proteinase (3CLpro), ssRNA-binding protein (RBP), 2\u2019-O-ribose methyltransferase (OMT), endoRNase (RNase), helicase, RNA-dependent RNA polymerase (RdRp), Nsp7, Nsp8, and exonuclease ExoN. As a general rule, we find that SARS-CoV-2 genome tends to diverge over time by accumulating mutations on its genome and, specifically, on the coding sequences for proteins N and S. Interestingly, different patterns of codon usage were observed among these genes. Genes S, Nsp7, NSp8, tend to use a norrower set of synonymous codons that are better optimized to the human host. Conversely, genes E and M consistently use a broader set of synonymous codons, which does not vary with respect to the reference genome. We identified key SARS-CoV-2 genes (S, N, ExoN, RNase, RdRp, Nsp7 and Nsp8) suggested to be causally implicated in the virus adaptation to the human host.", "qid": 32, "docid": "xh41koro", "rank": 49, "score": 0.7428388595581055}, {"content": "Title: The novel Coronavirus enigma: Phylogeny and mutation analyses of SARS-CoV-2 viruses circulating in India during early 2020 Content: Background This is a comprehensive analysis of 46 Indian SARS-CoV-2 genome sequences available from the NCBI and GISAID repository during early 2020. Evolutionary dynamics, gene-specific phylogeny and emergence of the novel co-evolving mutations in nine structural and non-structural genes among circulating SARS-CoV-2 strains in ten states of India have been assessed. Materials and methods 46 SARS-CoV-2 nucleotide sequences submitted from India were downloaded from the GISAID (39/46) or from NCBI (7/46) database. Phylogenetic study and analyses of mutation were based on the nine structural and non-structural genes of SARS-CoV-2 strains. Secondary structure of RdRP/NSP12 protein was predicted with respect to the novel A97V mutation. Results Phylogenetic analyses revealed the evolution of \u201cgenome-type clusters\u201d and adaptive selection of \u201cL\u201d type SARS-CoV-2 strains with genetic closeness to the bat SARS-like coronaviruses than pangolin or MERS-CoVs. With regards to the novel co-evolving mutations, 2 groups are seen to circulate in India at present: the \u201cmajor group\u201d (52.2%) and the \u201cminor group\u201d (30.4%), harboring four and five co-existing mutations, respectively. The \u201cmajor group\u201d mutations fall in the A2a clade. All the minor group mutations, except 11083G>T (L37F, NSP6) were unique to the Indian isolates. Conclusion The study highlights rapidly evolving SARS-CoV-2 virus and co-circulation of multiple clades and sub-clades, driving this pandemic worldwide. This comprehensive study is a potential resource for monitoring the novel mutations in the viral genome, changes in viral pathogenesis, for designing vaccines and other therapeutics.", "qid": 32, "docid": "915srotp", "rank": 50, "score": 0.742605984210968}, {"content": "Title: Genetic Diversity and Genomic Epidemiology of SARS-COV-2 in Morocco Content: COVID-A9 is an infection disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), declared as a pandemic due to its rapid expansion worldwide. In this study we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 using 22 virus genome sequences reported by three different laboratories in Morocco till the date 07/06/2020 as well as (40366) virus genomes from all around the world. The SARS-CoV-2 genomes from Moroccan patients revealed 62 mutations of which 30 were missense mutations. The mutations Spike_D614G and NSP12_P323L were present in all the 22 analyzed sequences, followed by N_G204R and N_R203K which occurred in 9 among the 22 sequences. The mutations NSP10_R134S, NSP15_D335N, NSP16_I169L, NSP3_L431H, NSP3_P1292L and Spike_V6F occurred one time in our sequences with no record in other sequence worldwide. These mutations should be investigated to figure out their potential effects on all around the world virulence. Phylogenetic analyses revealed that Moroccan SARS-CoV-2 genomes included 9 viruses pertaining to clade 20A, 9 to clade 20B and 2 to clade 20C. This finding suggest that the epidemic spread in Morocco did not show a predominant SARS-CoV-2 route. For multiple and unrelated introductions of SARS-CoV-2 into Morocco via different routes have occurred, giving rise to the diversity of virus genomes in the country. Furthermore, very likely, the SARS-CoV-2 virus circulated in cryptic way in Morocco starting from the fifteen January before the discovering of the first case the second of March.", "qid": 32, "docid": "zb1pzdd0", "rank": 51, "score": 0.7422841191291809}, {"content": "Title: Evidence of Increasing Diversification of Emerging SARS\u2010CoV\u20102 Strains Content: BACKGROUND: On January 30th, 2020, an outbreak of atypical pneumonia caused by a novel Betacoronavirus (\u03b2CoV), named SARS\u2010CoV\u20102, was declared a public health emergency of international concern by the World Health Organization. For this reason, a detailed evolutionary analysis of SARS\u2010CoV\u20102 strains currently circulating in different geographic regions of the world was performed. METHODS: A compositional analysis as well as a Bayesian coalescent analysis of complete genome sequences of SARS\u2010CoV\u20102 strains recently isolated in Europe, North America, South America and Asia was performed. RESULTS: The results of these studies revealed a diversification of SARS\u2010CoV\u20102 strains in three different genetic clades. Co\u2010circulation of different clades in different countries, as well as different genetic lineages within different clades were observed. The time of the most recent common ancestor (tMRCA) was established to be around November 1, 2019. A mean rate of evolution of 6.57 x 10(\u20104) substitutions per site per year was found. A significant migration rate per genetic lineage per year from Europe to South America was also observed. CONCLUSION: The results of these studies revealed an increasing diversification of SARS\u2010CoV\u20102 strains. High evolutionary rates and fast population growth characterizes the population dynamics of SARS\u2010CoV\u20102 strains. This article is protected by copyright. All rights reserved.", "qid": 32, "docid": "ew2kjq5s", "rank": 52, "score": 0.7422256469726562}, {"content": "Title: Chasing the origin of SARS-CoV-2 in Canada\u2019s COVID-19 cases: A genomics study Content: The emergence and global spread of SARS-CoV-2 has had profound social and economic consequences and has shed light on the importance of continued and additional investment in global health and infectious disease surveillance. Identifying changes in viral genomes provides key insights into viral diversity, how viruses spread within populations, and viral strategies for evasion of host immune systems. Here we report twenty-five SARS-CoV-2 genome sequences collected from some of the first COVID-19 cases in eastern Ontario, Canada (March 18-30, 2020). The reported genomes belong to the S-clade (n=2) and G-clade (n=23) of SARS-CoV-2 and contain 45 polymorphic sites including one shared missense and three unique synonymous variants in the gene encoding the spike protein. A phylogenetic analysis enabled the tracing of viral origin and potential transmission into and within Canada. There may be as many as sixteen unique infection events represented in these samples, including at least three that were likely introduced from Europe and seven from the USA. In addition, four separate genomes are each shared by multiple patients, suggesting a common origin or community spread even during this early stage of infection. These results demonstrate how molecular epidemiology and evolutionary phylogenetics can help local health units track origins and vectors of spread for emerging diseases like SARS-CoV-2. Earlier detection and screening in this way could improve the effectiveness of regional public health interventions to prevent future pandemics.", "qid": 32, "docid": "8gtnbm1c", "rank": 53, "score": 0.7421678304672241}, {"content": "Title: Genome-Wide Identification and Characterization of Point Mutations in the SARS-CoV-2 Genome Content: OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has been rapidly spreading worldwide. Although the causal relationship among mutations and the features of SARS-CoV-2 such as rapid transmission, pathogenicity, and tropism, remains unclear, our results of genomic mutations in SARS-CoV-2 may help to interpret the interaction between genomic characterization in SARS-CoV-2 and infectivity with the host. METHODS: A total of 4,254 genomic sequences of SARS-CoV-2 were collected from the Global Initiative on Sharing all Influenza Data (GISAID). Multiple sequence alignment for phylogenetic analysis and comparative genomic approach for mutation analysis were conducted using Molecular Evolutionary Genetics Analysis (MEGA), and an in-house program based on Perl language, respectively. RESULTS: Phylogenetic analysis of SARS-CoV-2 strains indicated that there were 3 major clades including S, V, and G, and 2 subclades (G.1 and G.2). There were 767 types of synonymous and 1,352 types of non-synonymous mutation. ORF1a, ORF1b, S, and N genes were detected at high frequency, whereas ORF7b and E genes exhibited low frequency. In the receptor-binding domain (RBD) of the S gene, 11 non-synonymous mutations were observed in the region adjacent to the angiotensin converting enzyme 2 (ACE2) binding site. CONCLUSION: It has been reported that the rapid infectivity and transmission of SARS-CoV-2 associated with host receptor affinity are derived from several mutations in its genes. Without these genetic mutations to enhance evolutionary adaptation, species recognition, host receptor affinity, and pathogenicity, it would not survive. It is expected that our results could provide an important clue in understanding the genomic characteristics of SARS-CoV-2.", "qid": 32, "docid": "shn7vx3d", "rank": 54, "score": 0.7421626448631287}, {"content": "Title: Understanding evolution of SARS-CoV-2: A perspective from analysis of genetic diversity of RdRp gene Content: Coronavirus disease 2019 emerged as the first example of \"Disease X\", a hypothetical disease of humans caused by an unknown infectious agent that was named as novel coronavirus and subsequently designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The origin of the outbreak at the animal market in Wuhan, China implies it as a case of zoonotic spillover. The study was designed to understand evolution of Betacoronaviruses and in particular diversification of SARS-CoV-2 using RNA dependent RNA polymerase (RdRp) gene, a stable genetic marker. Phylogenetic and population stratification analyses were carried out using maximum likelihood and Bayesian methods, respectively. Molecular phylogeny using RdRp showed that SARS-CoV-2 isolates cluster together. Bat-CoV isolate RaTG13 and Pangolin-CoVs are observed to branch off prior to SARS-CoV-2 cluster. While SARS-CoV form a single cluster, Bat-CoVs form multiple clusters. Population-based analyses revealed that both SARS-CoV-2 and SARS-CoV form separate clusters with no admixture. Bat-CoVs were found to have single and mixed ancestry and clustered as four sub-populations. Population-based analyses of Betacoronaviruses using RdRp revealed that SARS-CoV-2 is a homogeneous population. SARS-CoV-2 appears to have evolved from Bat-CoV isolate RaTG13, which diversified from a common ancestor from which Pangolin-CoVs have also evolved. The admixed Bat-CoV sub-populations indicate that bats serve as reservoirs harboring virus ensembles that are responsible for zoonotic spillovers such as SARS-CoV and SARS-CoV-2. The extent of admixed isolates of Bat-CoVs observed in population diversification studies underline the need for periodic surveillance of bats and other animal reservoirs for potential spillovers as a measure towards preparedness for emergence of zoonosis.", "qid": 32, "docid": "s9gje0pz", "rank": 55, "score": 0.7419344186782837}, {"content": "Title: Isolation, Sequence, Infectivity, and Replication Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2. Content: Since its emergence in Wuhan, China, in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected \u22486 million persons worldwide. As SARS-CoV-2 spreads across the planet, we explored the range of human cells that can be infected by this virus. We isolated SARS-CoV-2 from 2 infected patients in Toronto, Canada; determined the genomic sequences; and identified single-nucleotide changes in representative populations of our virus stocks. We also tested a wide range of human immune cells for productive infection with SARS-CoV-2. We confirm that human primary peripheral blood mononuclear cells are not permissive for SARS-CoV-2. As SARS-CoV-2 continues to spread globally, it is essential to monitor single-nucleotide polymorphisms in the virus and to continue to isolate circulating viruses to determine viral genotype and phenotype by using in vitro and in vivo infection models.", "qid": 32, "docid": "a9h25l7j", "rank": 56, "score": 0.7416422367095947}, {"content": "Title: Relative rates of non-pneumonic SARS coronavirus infection and SARS coronavirus pneumonia Content: Summary Background Although the genome of severe acute respiratory syndrome coronavirus (SARS-CoV) has been sequenced and a possible animal reservoir identified, seroprevalence studies and mass screening for detection of subclinical and non-pneumonic infections are still lacking. Methods We cloned and purified the nucleocapsid protein and spike polypeptide of SARS-CoV and examined their immunogenicity with serum from patients with SARS-CoV pneumonia. An ELISA based on recombinant nucleocapsid protein for IgG detection was tested with serum from 149 healthy blood donors who donated 3 years previously and with serum positive for antibodies against SARS-CoV (by indirect immunofluorescence assay) from 106 patients with SARS-CoV pneumonia. The seroprevalence of SARS-CoV was studied with the ELISA in healthy blood donors who donated during the SARS outbreak in Hong Kong, non-pneumonic hospital inpatients, and symptom-free health-care workers. All positive samples were confirmed by two separate western-blot assays (with recombinant nucleocapsid protein and recombinant spike polypeptide). Findings Western-blot analysis showed that the nucleocapsid protein and spike polypeptide of SARS-CoV are highly immunogenic. The specificity of the IgG antibody test (ELISA with positive samples confirmed by the two western-blot assays) was 100%, and the sensitivity was 94\u00b73%. Three of 400 healthy blood donors who donated during the SARS outbreak and one of 131 non-pneumonic paediatric inpatients were positive for IgG antibodies, confirmed by the two western-blot assays (total, 0\u00b748% of our study population). Interpretation Our findings support the existence of subclinical or non-pneumonic SARS-CoV infections. Such infections are more common than SARS-CoV pneumonia in our locality.", "qid": 32, "docid": "ctx39vhi", "rank": 57, "score": 0.740500807762146}, {"content": "Title: Ancestral origin, antigenic resemblance and epidemiological insights of novel coronavirus (SARS-CoV-2): Global burden and Bangladesh perspective Content: SARS-CoV-2, a new coronavirus strain responsible for COVID-19 has emerged in Wuhan City, China and still continuing its worldwide pandemic nature. Considering the severity of the disease, a number of studies are underway, and full genomic sequences have already been released in the last few weeks to enable the understanding of the evolutionary origin and molecular characteristics of this virus. Bioinformatics analysis, satellite derived imaging data and epidemiological attributes were employed to investigate origin, immunogenic resemblance and global threat of newly pandemic SARS-CoV-2 including Bangladesh perspective. Based on currently available genomic information, a phylogeny study was employed focusing four types of representative viral proteins (spike, membrane, envelope and nucleoprotein) of SARS-CoV-2, HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63, HKU1, MERS-CoV, HKU4, HKU5 and BufCoV-HKU26. The findings clearly demonstrated that SARS-CoV-2 exhibited evolutionary convergent relation with previously reported SARS-CoV. It was also found that SARS-CoV-2 proteins were highly similar and identical to SARS-CoV proteins, though proteins from other coronaviruses showed lower level of similarity and identical patterns. The cross-checked conservancy analysis of SARS-CoV-2 antigenic epitopes showed significant conservancy with antigenic epitopes derived from SARS-CoV. The study also prioritized the temperature comparison through satellite imaging alongside compiling and analyzing the epidemiological outbreak information on the 2019 novel coronavirus based on several open datasets on COVID-19 (SARS-CoV-2) and discussed possible threats to Bangladesh.", "qid": 32, "docid": "a4jn6gpk", "rank": 58, "score": 0.7399996519088745}, {"content": "Title: Extended ORF8 Gene Region Is Valuable in the Epidemiological Investigation of Severe Acute Respiratory Syndrome-Similar Coronavirus Content: Severe acute respiratory syndrome coronavirus (SARS-CoV) was discovered as a novel pathogen in the 2002-2003 SARS epidemic. The emergence and disappearance of this pathogen have brought questions regarding its source and evolution. Within the genome sequences of 281 SARS-CoVs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and SARS-related CoVs (SARSr-CoVs), a ~430 bp genomic region (from 27 701 bp to 28 131 bp in AY390556.1) with regular variations was investigated. This ~430 bp region overlaps with the ORF8 gene and is prone to deletions and nucleotide substitutions. Its complexity suggested the need for a new genotyping method for coronaviruses related to SARS-similar coronaviruses (SARS-CoV, SARSr-CoV, and SARS-CoV-2). Bat SARSr-CoV presented 3 genotypes, of which type 0 is only seen in bat SARSr-CoV, type I is present in SARS in the early phase, and type II is found in all SARS-CoV-2. This genotyping also shows potential usage in distinguishing the SARS-similar coronaviruses from different hosts and geographic areas. This genomic region has important implications for predicting the epidemic trend and studying the evolution of coronavirus.", "qid": 32, "docid": "sl560i2a", "rank": 59, "score": 0.7397586107254028}, {"content": "Title: Full-genome sequences of the first two SARS-CoV-2 viruses from India Content: BACKGROUND & OBJECTIVES: Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has globally affected 195 countries. In India, suspected cases were screened for SARS-CoV-2 as per the advisory of the Ministry of Health and Family Welfare. The objective of this study was to characterize SARS-CoV-2 sequences from three identified positive cases as on February 29, 2020. METHODS: Throat swab/nasal swab specimens for a total of 881 suspected cases were screened by E gene and confirmed by RdRp (1), RdRp (2) and N gene real-time reverse transcription-polymerase chain reactions and next-generation sequencing. Phylogenetic analysis, molecular characterization and prediction of B- and T-cell epitopes for Indian SARS-CoV-2 sequences were undertaken. RESULTS: Three cases with a travel history from Wuhan, China, were confirmed positive for SARS-CoV-2. Almost complete (29,851 nucleotides) genomes of case 1, case 3 and a fragmented genome for case 2 were obtained. The sequences of Indian SARS-CoV-2 though not identical showed high (~99.98%) identity with Wuhan seafood market pneumonia virus (accession number: NC 045512). Phylogenetic analysis showed that the Indian sequences belonged to different clusters. Predicted linear B-cell epitopes were found to be concentrated in the S1 domain of spike protein, and a conformational epitope was identified in the receptor-binding domain. The predicted T-cell epitopes showed broad human leucocyte antigen allele coverage of A and B supertypes predominant in the Indian population. INTERPRETATION & CONCLUSIONS: The two SARS-CoV-2 sequences obtained from India represent two different introductions into the country. The genetic heterogeneity is as noted globally. The identified B- and T-cell epitopes may be considered suitable for future experiments towards the design of vaccines and diagnostics. Continuous monitoring and analysis of the sequences of new cases from India and the other affected countries would be vital to understand the genetic evolution and rates of substitution of the SARS-CoV-2.", "qid": 32, "docid": "vhb280gz", "rank": 60, "score": 0.7397109866142273}, {"content": "Title: Full-genome sequences of the first two SARS-CoV-2 viruses from India Content: Background & objectives: Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has globally affected 195 countries. In India, suspected cases were screened for SARS-CoV-2 as per the advisory of the Ministry of Health and Family Welfare. The objective of this study was to characterize SARS-CoV-2 sequences from three identified positive cases as on February 29, 2020. Methods: Throat swab/nasal swab specimens for a total of 881 suspected cases were screened by E gene and confirmed by RdRp (1), RdRp (2) and N gene real-time reverse transcription-polymerase chain reactions and next-generation sequencing. Phylogenetic analysis, molecular characterization and prediction of B- and T-cell epitopes for Indian SARS-CoV-2 sequences were undertaken. Results: Three cases with a travel history from Wuhan, China, were confirmed positive for SARS-CoV-2. Almost complete (29,851 nucleotides) genomes of case 1, case 3 and a fragmented genome for case 2 were obtained. The sequences of Indian SARS-CoV-2 though not identical showed high (~99.98%) identity with Wuhan seafood market pneumonia virus (accession number: NC 045512). Phylogenetic analysis showed that the Indian sequences belonged to different clusters. Predicted linear B-cell epitopes were found to be concentrated in the S1 domain of spike protein, and a conformational epitope was identified in the receptor-binding domain. The predicted T-cell epitopes showed broad human leucocyte antigen allele coverage of A and B supertypes predominant in the Indian population. Interpretation & conclusions: The two SARS-CoV-2 sequences obtained from India represent two different introductions into the country. The genetic heterogeneity is as noted globally. The identified B- and T-cell epitopes may be considered suitable for future experiments towards the design of vaccines and diagnostics. Continuous monitoring and analysis of the sequences of new cases from India and the other affected countries would be vital to understand the genetic evolution and rates of substitution of the SARS-CoV-2.", "qid": 32, "docid": "35wfw3zn", "rank": 61, "score": 0.7397109866142273}, {"content": "Title: Amino acid variation analysis of surface spike glycoprotein at 614 in SARS-CoV-2 strains Content: Abstract As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to disperse globally with worrisome speed, identifying amino acid variations in the virus could help to understand the characteristics of it. Here, we studied 489 SARS-CoV-2 genomes obtained from 32 countries from the Nextstrain database and performed phylogenetic tree analysis by clade, country, and genotype of the surface spike glycoprotein (S protein) at site 614. We found that virus strains from mainland China were mostly distributed in Clade B and Clade undefined in the phylogenetic tree, with very few found in Clade A. In contrast, Clades A2 (one case) and A2a (112 cases) predominantly contained strains from European regions. Moreover, Clades A2 and A2a differed significantly from those of mainland China in age of infected population (P = 0.0071, mean age 40.24 to 46.66), although such differences did not exist between the US and mainland China. Further analysis demonstrated that the variation of the S protein at site 614 (QHD43416.1: p.614D>G) was a characteristic of stains in Clades A2 and A2a. Importantly, this variation was predicted to have neutral or benign effects on the function of the S protein. In addition, global quality estimates and 3D protein structures tended to be different between the two S proteins. In summary, we identified different genomic epidemiology among SARS-CoV-2 strains in different clades, especially in an amino acid variation of the S protein at 614, revealing potential viral genome divergence in SARS-CoV-2 strains.", "qid": 32, "docid": "gquo184w", "rank": 62, "score": 0.7396672368049622}, {"content": "Title: Coding potential and sequence conservation of SARS-CoV-2 and related animal viruses Content: In December 2019, a novel human-infecting coronavirus (SARS-CoV-2) was recognized in China. In a few months, SARS-CoV-2 has caused thousands of disease cases and deaths in several countries. Phylogenetic analyses indicated that SARS-CoV-2 clusters with SARS-CoV in the Sarbecovirus subgenus and viruses related to SARS-CoV-2 were identified from bats and pangolins. Coronaviruses have long and complex genomes with high plasticity in terms of gene content. To date, the coding potential of SARS-CoV-2 remains partially unknown. We thus used available sequences of bat and pangolin viruses to determine the selective events that shaped the genome structure of SARS-CoV-2 and to assess its coding potential. By searching for signals of significantly reduced variability at synonymous sites (dS), we identified six genomic regions, one of these corresponding to the programmed -1 ribosomal frameshift. The most prominent signal of dS reduction was observed within the E gene. A genome-wide analysis of conserved RNA structures indicated that this region harbors a putative functional RNA element that is shared with the SARS-CoV lineage. Additional signals of reduced dS indicated the presence of internal ORFs. Whereas the presence ORF9a (internal to N) was previously proposed by homology with a well characterized protein of SARS-CoV, ORF3h (for hypothetical, within ORF3a) was not previously described. The predicted product of ORF3h has 90% identity with the corresponding predicted product of SARS-CoV and displays features suggestive of a viroporin. Finally, analysis of the putative ORF10 revealed high dN/dS (3.82) in SARS-CoV-2 and related coronaviruses. In the SARS-CoV lineage, the ORF is predicted to encode a truncated protein and is neutrally evolving. These data suggest that ORF10 encodes a functional protein in SARS-CoV-2 and that positive selection is driving its evolution. Experimental analyses will be necessary to validate and characterize the coding and non-coding functional elements we identified.", "qid": 32, "docid": "dbem6cfo", "rank": 63, "score": 0.7395539283752441}, {"content": "Title: Extended ORF8 Gene Region Is Valuable in the Epidemiological Investigation of Severe Acute Respiratory Syndrome\u2013Similar Coronavirus Content: Severe acute respiratory syndrome coronavirus (SARS-CoV) was discovered as a novel pathogen in the 2002\u20132003 SARS epidemic. The emergence and disappearance of this pathogen have brought questions regarding its source and evolution. Within the genome sequences of 281 SARS-CoVs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and SARS-related CoVs (SARSr-CoVs), a ~430 bp genomic region (from 27 701 bp to 28 131 bp in AY390556.1) with regular variations was investigated. This ~430 bp region overlaps with the ORF8 gene and is prone to deletions and nucleotide substitutions. Its complexity suggested the need for a new genotyping method for coronaviruses related to SARS-similar coronaviruses (SARS-CoV, SARSr-CoV, and SARS-CoV-2). Bat SARSr-CoV presented 3 genotypes, of which type 0 is only seen in bat SARSr-CoV, type I is present in SARS in the early phase, and type II is found in all SARS-CoV-2. This genotyping also shows potential usage in distinguishing the SARS-similar coronaviruses from different hosts and geographic areas. This genomic region has important implications for predicting the epidemic trend and studying the evolution of coronavirus.", "qid": 32, "docid": "lttavvly", "rank": 64, "score": 0.739493727684021}, {"content": "Title: SARS-CoV-2 is well adapted for humans. What does this mean for re-emergence? Content: In a side-by-side comparison of evolutionary dynamics between the 2019/2020 SARS-CoV-2 and the 2003 SARS-CoV, we were surprised to find that SARS-CoV-2 resembles SARS-CoV in the late phase of the 2003 epidemic after SARS-CoV had developed several advantageous adaptations for human transmission. Our observations suggest that by the time SARS-CoV-2 was first detected in late 2019, it was already pre-adapted to human transmission to an extent similar to late epidemic SARS-CoV. However, no precursors or branches of evolution stemming from a less human-adapted SARS-CoV-2-like virus have been detected. The sudden appearance of a highly infectious SARS-CoV-2 presents a major cause for concern that should motivate stronger international efforts to identify the source and prevent near future re-emergence. Any existing pools of SARS-CoV-2 progenitors would be particularly dangerous if similarly well adapted for human transmission. To look for clues regarding intermediate hosts, we analyze recent key findings relating to how SARS-CoV-2 could have evolved and adapted for human transmission, and examine the environmental samples from the Wuhan Huanan seafood market. Importantly, the market samples are genetically identical to human SARS-CoV-2 isolates and were therefore most likely from human sources. We conclude by describing and advocating for measured and effective approaches implemented in the 2002-2004 SARS outbreaks to identify lingering population(s) of progenitor virus.", "qid": 32, "docid": "sphwclzs", "rank": 65, "score": 0.7392683029174805}, {"content": "Title: The origin and underlying driving forces of the SARS-CoV-2 outbreak Content: The spread of SARS-CoV-2 since December 2019 has become a pandemic and impacted many aspects of human society. Here, we analyzed genetic variation of SARS-CoV-2 and its related coronavirus and found the evidence of intergenomic recombination. After correction for mutational bias, analysis of 137 SARS-CoV-2 genomes as of 2/23/2020 revealed the excess of low frequency mutations on both synonymous and nonsynonymous sites which is consistent with recent origin of the virus. In contrast to adaptive evolution previously reported for SARS-CoV in its brief epidemic in 2003, our analysis of SARS-CoV-2 genomes shows signs of relaxation of selection. The sequence similarity of the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression. Therefore, SARS-CoV-2 might have cryptically circulated within humans for years before being recently noticed. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and reveal critical steps required for effective spreading. Two mutations, 84S in orf8 protein and 251V in orf3 protein, occurred coincidentally with human intervention. The 84S first appeared on 1/5/2020 and reached a plateau around 1/23/2020, the lockdown of Wuhan. 251V emerged on 1/21/2020 and rapidly increased its frequency. Thus, the roles of these mutations on infectivity need to be elucidated. Genetic diversity of SARS-CoV-2 collected from China was two time higher than those derived from the rest of the world. In addition, in network analysis, haplotypes collected from Wuhan city were at interior and have more mutational connections, both of which are consistent with the observation that the outbreak of cov-19 was originated from China. SUMMARY In contrast to adaptive evolution previously reported for SARS-CoV in its brief epidemic, our analysis of SARS-CoV-2 genomes shows signs of relaxation of selection. The sequence similarity of the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression. Therefore, SARS-CoV-2 might have cryptically circulated within humans for years before being recently noticed. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and reveal critical steps required for effective spreading. Two mutations, 84S in orf8 protein and 251V in orf3 protein, occurred coincidentally with human intervention. The 84S first appeared on 1/5/2020 and reached a plateau around 1/23/2020, the lockdown of Wuhan. 251V emerged on 1/21/2020 and rapidly increased its frequency. Thus, the roles of these mutations on infectivity need to be elucidated.", "qid": 32, "docid": "bawgldfi", "rank": 66, "score": 0.7391930222511292}, {"content": "Title: Isolation, Sequence, Infectivity, and Replication Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2 Content: Since its emergence in Wuhan, China, in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected &#8776;6 million persons worldwide. As SARS-CoV-2 spreads across the planet, we explored the range of human cells that can be infected by this virus. We isolated SARS-CoV-2 from 2 infected patients in Toronto, Canada; determined the genomic sequences; and identified single-nucleotide changes in representative populations of our virus stocks. We also tested a wide range of human immune cells for productive infection with SARS-CoV-2. We confirm that human primary peripheral blood mononuclear cells are not permissive for SARS-CoV-2. As SARS-CoV-2 continues to spread globally, it is essential to monitor single-nucleotide polymorphisms in the virus and to continue to isolate circulating viruses to determine viral genotype and phenotype by using in vitro and in vivo infection models.", "qid": 32, "docid": "hrgb0e03", "rank": 67, "score": 0.7390791177749634}, {"content": "Title: Response to \"Comments on \"Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross-species transmission from snake to human\" and \"Codon bias analysis alone is uninformative for identifying host(s) of new virus\" Content: We have recently reported for the first time that SARS-CoV-2 maybe a bat-originated coronavirus with a recombination occurred within the spike (S) protein gene based on phylogenetic and simplot analyses1 . These two conclusions are supported by findings recently reported by others and are well accepted in the field of SARS-CoV-2 research2-4 . This article is protected by copyright. All rights reserved.", "qid": 32, "docid": "3x2psny9", "rank": 68, "score": 0.7390038967132568}, {"content": "Title: Multi-Omics and Integrated Network Approach to Unveil Evolutionary Patterns, Mutational Hotspots, Functional Crosstalk and Regulatory Interactions in SARS-CoV-2 Content: SARS-CoV-2 responsible for the pandemic of the Severe Acute Respiratory Syndrome resulting in infections and death of millions worldwide with maximum cases and mortality in USA. The current study focuses on understanding the population specific variations attributing its high rate of infections in specific geographical regions which may help in developing appropriate treatment strategies for COVID-19 pandemic. Rigorous phylogenetic network analysis of 245 complete SARS-CoV-2 genomes inferred five central clades named a (ancestral), b, c, d and e (subtype e1 & e2) showing both divergent and linear evolution types. The clade d & e2 were found exclusively comprising of USA strains with highest known mutations. Clades were distinguished by ten co-mutational combinations in proteins; Nsp3, ORF8, Nsp13, S, Nsp12, Nsp2 and Nsp6 generated by Amino Acid Variations (AAV). Our analysis revealed that only 67.46 % of SNP mutations were carried by amino acid at phenotypic level. T1103P mutation in Nsp3 was predicted to increase the protein stability in 238 strains except six strains which were marked as ancestral type; whereas com (P5731L & Y5768C) in Nsp13 were found in 64 genomes of USA highlighting its 100% co-occurrence. Docking study highlighted mutation (D7611G) caused reduction in binding of Spike proteins with ACE2, but it also showed better interaction with TMPRSS2 receptor which may contribute to its high transmissibility in USA strains. In addition, we found host proteins, MYO5A, MYO5B & MYO5C had maximum interaction with viral hub proteins (Nucleocapsid, Spike & Membrane). Thus, blocking the internalization pathway by inhibiting MYO-5 proteins which could be an effective target for COVID-19 treatment. The functional annotations of the Host-Pathogen Interaction (HPI) network were found to be highly associated with hypoxia and thrombotic conditions confirming the vulnerability and severity of infection in the patients. We also considered the presence of CpG islands in Nsp1 and N proteins which may confers the ability of SARS-CoV-2 to enter and trigger methyltransferase activity inside host cell.", "qid": 32, "docid": "m2px0pyj", "rank": 69, "score": 0.7389001846313477}, {"content": "Title: Whole genome and phylogenetic analysis of two SARS-CoV-2 strains isolated in Italy in January and February 2020: additional clues on multiple introductions and further circulation in Europe Content: Whole genome sequences of SARS-CoV-2 obtained from two patients, a Chinese tourist visiting Rome and an Italian, were compared with sequences from Europe and elsewhere. In a phylogenetic tree, the Italian patient\u2019s sequence clustered with sequences from Germany while the tourist\u2019s sequence clustered with other European sequences. Some additional European sequences in the tree segregated outside the two clusters containing the patients\u2019 sequences. This suggests multiple SARS-CoV-2 introductions in Europe or virus evolution during circulation.", "qid": 32, "docid": "48ul34xo", "rank": 70, "score": 0.7388519644737244}, {"content": "Title: Emerging coronaviruses: first SARS, second MERS and third SARS-CoV-2: epidemiological updates of COVID-19 Content: Since December 2019, the emergence of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection has been reported unexpectedly in Wuhan, China, with staggering infection speed across China and around the world To date, seven known strains of HCoVs belonging to four genera (i e , alpha?, beta?, gamma, and delta-CoV) have been recognized;the latest one has been identified as the SARS-CoV-2 Although the common transmission routes of SARS-CoV-2 is the respiratory tract, it seems that other routes such as the gastrointestinal tract may be effective for the entry of the virus in the body Although there are no biological markers to predict the susceptibility of humans to COVID-19, several risk factors have been identified to predict the susceptibility of patients to COVID-19 Initial data revealed that males, pregnant women, elderly, and underlying conditions predispose patients to higher morbidity or mortality and also might be at risk for a severe infection of COVID-19 There is a greater need to better understand the mechanisms and risk factors of transmission routes To date, despite the whole world effort to review various aspects of SARS-CoV-2, including epidemiology, clinical manifestations, diagnosis, and treatment options, there are still gaps in the knowledge of this disease and many issues remain unclear Therefore, there is an urgent need for update data on SARS-CoV-2 Here, this study provide the current epidemiological status (transmission routes and risk of transmission, possible origins and source, mortality and morbidity risk, and geographical distribution) of the SARS-CoV-2 in the world in 2020", "qid": 32, "docid": "o908k448", "rank": 71, "score": 0.7386994957923889}, {"content": "Title: Genomic characterization of a novel SARS-CoV-2 Content: A new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated with human to human transmission and extreme human sickness has been as of late announced from the city of Wuhan in China. Our objectives were to mutation analysis between recently reported genomes at various times and locations and to characterize the genomic structure of SARS-CoV-2 using bioinformatics programs. Information on the variation of viruses is of considerable medical and biological impacts on the prevention, diagnosis, and therapy of infectious diseases. To understand the genomic structure and variations of the SARS-CoV-2. The study analyzed 95 SARS-CoV-2 complete genome sequences available in GenBank, National MicrobiologyData Center (NMDC) and NGDC Genome Warehouse from December-2019 until 05 of April-2020. The genomic signature analysis demonstrates that a strong association between the time of sample collection, location of sample and accumulation of genetic diversity. We found 116 mutations, the three most common mutations were 8782C>T in ORF1ab gene, 28144T>C in ORF8 gene and 29095C>T in the N gene. The mutations might affect the severity and spread of the SARS-CoV-2. The finding heavily supports an intense requirement for additional prompt, inclusive investigations that combine genomic detail, epidemiological information and graph records of the clinical features of patients with COVID-19.", "qid": 32, "docid": "mp3196kj", "rank": 72, "score": 0.7384891510009766}, {"content": "Title: Emerging coronaviruses: first SARS, second MERS and third SARS-CoV-2: epidemiological updates of COVID-19. Content: Since December 2019, the emergence of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection has been reported unexpectedly in Wuhan, China, with staggering infection speed across China and around the world. To date, seven known strains of HCoVs belonging to four genera (i.e., \u03b1?, \u03b2?, \u03b3, and \u03b4-CoV) have been recognized; the latest one has been identified as the SARS-CoV-2. Although the common transmission routes of SARS-CoV-2 is the respiratory tract, it seems that other routes such as the gastrointestinal tract may be effective for the entry of the virus in the body. Although there are no biological markers to predict the susceptibility of humans to COVID-19, several risk factors have been identified to predict the susceptibility of patients to COVID-19. Initial data revealed that males, pregnant women, elderly, and underlying conditions predispose patients to higher morbidity or mortality and also might be at risk for a severe infection of COVID-19. There is a greater need to better understand the mechanisms and risk factors of transmission routes. To date, despite the whole world effort to review various aspects of SARS-CoV-2, including epidemiology, clinical manifestations, diagnosis, and treatment options, there are still gaps in the knowledge of this disease and many issues remain unclear. Therefore, there is an urgent need for update data on SARS-CoV-2. Here, this study provide the current epidemiological status (transmission routes and risk of transmission, possible origins and source, mortality and morbidity risk, and geographical distribution) of the SARS-CoV-2 in the world in 2020.", "qid": 32, "docid": "kkknzw2i", "rank": 73, "score": 0.7384865880012512}, {"content": "Title: Identification of unique mutations in SARS-CoV-2 strains isolated from India suggests its attenuated pathotype Content: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first reported in Wuhan, China in November 2019 has developed into a pandemic since March 2020, causing substantial human casualties and economic losses. Studies on SARS-CoV-2 are being carried out at an unprecedented rate to tackle this threat. Genomics studies, in particular, are indispensable to elucidate the dynamic nature of the RNA genome of SARS-CoV-2. RNA viruses are marked by their unique ability to undergo high rates of mutation in their genome, much more frequently than their hosts, which diversifies their strengths qualifying them to elude host immune response and amplify drug resistance. In this study, we sequenced and analyzed the genomic information of the SARS-CoV-2 isolates from two infected Indian patients and explored the possible implications of point mutations in its biology. In addition to multiple point mutations, we found a remarkable similarity between relatively common mutations of 36-nucleotide deletion in ORF8 of SARS-CoV-2. Our results corroborate with the earlier reported 29-nucleotide deletion in SARS, which was frequent during the early stage of human-to-human transmission. The results will be useful to understand the biology of SARS-CoV-2 and itsattenuation for vaccine development.", "qid": 32, "docid": "fujejfwb", "rank": 74, "score": 0.7380256056785583}, {"content": "Title: Evolution and Variation of the SARS-CoV Genome Content: Knowledge of the evolution of pathogens is of great medical and biological significance to the prevention, diagnosis, and therapy of infectious diseases. In order to understand the origin and evolution of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus), we collected complete genome sequences of all viruses available in GenBank, and made comparative analyses with the SARS-CoV. Genomic signature analysis demonstrates that the coronaviruses all take the TGTT as their richest tetranucleotide except the SARS-CoV. A detailed analysis of the forty-two complete SARS-CoV genome sequences revealed the existence of two distinct genotypes, and showed that these isolates could be classified into four groups. Our manual analysis of the BLASTN results demonstrates that the HE (hemagglutinin-esterase) gene exists in the SARS-CoV, and many mutations made it unfamiliar to us.", "qid": 32, "docid": "8oz6bgz4", "rank": 75, "score": 0.7380154132843018}, {"content": "Title: Whole genome and phylogenetic analysis of two SARS-CoV-2 strains isolated in Italy in January and February 2020: additional clues on multiple introductions and further circulation in Europe Content: Whole genome sequences of SARS-CoV-2 obtained from two patients, a Chinese tourist visiting Rome and an Italian, were compared with sequences from Europe and elsewhere. In a phylogenetic tree, the Italian patient's sequence clustered with sequences from Germany while the tourist's sequence clustered with other European sequences. Some additional European sequences in the tree segregated outside the two clusters containing the patients' sequences. This suggests multiple SARS-CoV-2 introductions in Europe or virus evolution during circulation.", "qid": 32, "docid": "o6rr66kc", "rank": 76, "score": 0.7379887700080872}, {"content": "Title: SARS-CoV Genome Polymorphism: A Bioinformatics Study Content: A dataset of 103 SARS-CoV isolates (101 human patients and 2 palm civets) was investigated on different aspects of genome polymorphism and isolate classification. The number and the distribution of single nucleotide variations (SNVs) and insertions and deletions, with respect to a \u201cprofile\u201d, were determined and discussed (\"profile\" being a sequence containing the most represented letter per position). Distribution of substitution categories per codon positions, as well as synonymous and non-synonymous substitutions in coding regions of annotated isolates, was determined, along with amino acid (a.a.) property changes. Similar analysis was performed for the spike (S) protein in all the isolates (55 of them being predicted for the first time). The ratio Ka/Ks confirmed that the S gene was subjected to the Darwinian selection during virus transmission from animals to humans. Isolates from the dataset were classified according to genome polymorphism and genotypes. Genome polymorphism yields to two groups, one with a small number of SNVs and another with a large number of SNVs, with up to four subgroups with respect to insertions and deletions. We identified three basic nine-locus genotypes: TTTT/TTCGG, CGCC/TTCAT, and TGCC/TTCGT, with four subgenotypes. Both classifications proposed are in accordance with the new insights into possible epidemiological spread, both in space and time.", "qid": 32, "docid": "9ot6khmh", "rank": 77, "score": 0.7379123568534851}, {"content": "Title: Coding potential and sequence conservation of SARS-CoV-2 and related animal viruses Content: Abstract In December 2019, a novel human-infecting coronavirus (SARS-CoV-2) was recognized in China. In a few months, SARS-CoV-2 has caused thousands of disease cases and deaths in several countries. Phylogenetic analyses indicated that SARS-CoV-2 clusters with SARS-CoV in the Sarbecovirus subgenus and viruses related to SARS-CoV-2 were identified from bats and pangolins. Coronaviruses have long and complex genomes with high plasticity in terms of gene content. To date, the coding potential of SARS-CoV-2 remains partially unknown. We thus used available sequences of bat and pangolin viruses to determine the selective events that shaped the genome structure of SARS-CoV-2 and to assess its coding potential. By searching for signals of significantly reduced variability at synonymous sites (dS), we identified six genomic regions, one of these corresponding to the programmed \u22121 ribosomal frameshift. The most prominent signal of dS reduction was observed within the E gene. A genome-wide analysis of conserved RNA structures indicated that this region harbors a putative functional RNA element that is shared with the SARS-CoV lineage. Additional signals of reduced dS indicated the presence of internal ORFs. Whereas the presence ORF9a (internal to N) was previously proposed by homology with a well characterized protein of SARS-CoV, ORF3h (for hypothetical, within ORF3a) was not previously described. The predicted product of ORF3h has 90% identity with the corresponding predicted product of SARS-CoV and displays features suggestive of a viroporin. Finally, analysis of the putative ORF10 revealed high dN/dS (3.82) in SARS-CoV-2 and related coronaviruses. In the SARS-CoV lineage, the ORF is predicted to encode a truncated protein and is neutrally evolving. These data suggest that ORF10 encodes a functional protein in SARS-CoV-2 and that positive selection is driving its evolution. Experimental analyses will be necessary to validate and characterize the coding and non-coding functional elements we identified.", "qid": 32, "docid": "zaxjj9q7", "rank": 78, "score": 0.7378197908401489}, {"content": "Title: Distinct genetic spectrums and evolution patterns of SARS-CoV-2 Content: Four signature groups of single-nucleotide variants (SNVs) were identified using two-way clustering method in about twenty thousand high quality and high coverage SARS-CoV-2 complete genome sequences. Some frequently occurred SNVs predominate but are mutually exclusively presented in patients from different countries and areas. These major SNV signatures exhibited distinguished evolution patterns overtime. Although it was rare, our data indicated possible cross-infections with multiple groups of SNVs existed simultaneously in some patients, suggesting infections from different SARS-CoV-2 clades or potential re-combination of SARS-CoV-2 sequences. Interestingly nucleotide substitutions among SARS-CoV-2 genomes tend to occur at the sites where one bat RaTG13 coronavirus sequences differ from Wuhan-Hu-1 genome, indicating the tolerance of mutations on those sites or suggesting that major viral strains might exist between Wuhan-Hu-1 and RaTG13 coronavirus.", "qid": 32, "docid": "xly61tfw", "rank": 79, "score": 0.7377281785011292}, {"content": "Title: Molecular and serological assays for SARS-CoV-2: insights from genome and clinical characteristics Content: BACKGROUND: The ongoing outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a challenge for worldwide public health. A reliable laboratory assay is essential both to confirm suspected patients and to exclude patients infected with other respiratory viruses, thereby facilitating the control of global outbreak scenarios. CONTENT: In this review, we focus on the genomic, transmission and clinical characteristics of SARS-CoV-2, and comprehensively summarize the principles and related details of assays for SARS-CoV-2. We also explore the quality assurance measures for these assays. SUMMARY: SARS-CoV-2 has some unique gene sequences and specific transmission and clinical features that can inform the conduct of molecular and serological assays in many aspects, including the design of primers, the selection of specimens and testing strategies at different disease stages. Appropriate quality assurance measures for molecular and serological assays are needed to maintain testing proficiency. Because serological assays have the potential to identify later stages of the infection and to confirm highly suspected cases with negative molecular assay results, a combination of these two assays is needed to achieve a reliable capacity to detect SARS-CoV-2.", "qid": 32, "docid": "b3v4n84f", "rank": 80, "score": 0.7376725077629089}, {"content": "Title: Broad and differential animal ACE2 receptor usage by SARS-CoV-2 Content: The COVID-19 pandemic has caused an unprecedented global public health and economy crisis. The origin and emergence of its causal agent, SARS-CoV-2, in the human population remains mysterious, although bat and pangolin were proposed to be the natural reservoirs. Strikingly, comparing to the SARS-CoV-2-like CoVs identified in bats and pangolins, SARS-CoV-2 harbors a polybasic furin cleavage site in its spike (S) glycoprotein. SARS-CoV-2 uses human ACE2 as its receptor to infect cells. Receptor recognition by the S protein is the major determinant of host range, tissue tropism, and pathogenesis of coronaviruses. In an effort to search for the potential intermediate or amplifying animal hosts of SARS-CoV-2, we examined receptor activity of ACE2 from 14 mammal species and found that ACE2 from multiple species can support the infectious entry of lentiviral particles pseudotyped with the wild-type or furin cleavage site deficient S protein of SARS-CoV-2. ACE2 of human/rhesus monkey and rat/mouse exhibited the highest and lowest receptor activity, respectively. Among the remaining species, ACE2 from rabbit and pangolin strongly bound to the S1 subunit of SARS-CoV-2 S protein and efficiently supported the pseudotyped virus infection. These findings have important implications for understanding potential natural reservoirs, zoonotic transmission, human-to-animal transmission, and use of animal models.", "qid": 32, "docid": "f03san07", "rank": 81, "score": 0.7375420331954956}, {"content": "Title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach Content: The newly identified SARS-CoV-2 has now been reported from around 183 countries with more than a million confirmed human cases including more than 68000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins have gotten substantial attention recently. Spike glycoprotein is widely considered as a possible target to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment tools. In this study, 483 unique variations have been identified among the genomes including 25 non-synonymous mutations and one deletion in the spike protein of SARS-CoV-2. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction with receptor molecules. In addition, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on our findings, potential inhibitors can be designed and tested targeting these proposed sites of variation.", "qid": 32, "docid": "vf32wxkx", "rank": 82, "score": 0.7373124361038208}, {"content": "Title: The novel coronavirus SARS-CoV-2: From a zoonotic infection to coronavirus disease 2019 Content: The novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2 is an international public health emergency. Until now, the intermediate host and mechanisms of the interspecies jump of this virus are unknown. Phylogenetic analysis of all available bat CoV complete genomes was performed to analyze the relationships between bat CoV and SARS-CoV-2. To suggest a possible intermediate host, another phylogenetic reconstruction of CoV genomes obtained from animals that were hypothetically commercialized in the Chinese markets was also carried out. Moreover, mutation analysis was executed to suggest genomic regions that may have permitted the adaptation of SARS-CoV-2 to the human host. The phylogenetic analysis demonstrated that SARS-CoV-2 formed a cluster with the bat CoV isolate RaTG13. Possible CoV interspecies jumps among bat isolates were also observed. The phylogenetic tree reconstructed from CoV strains belonging to different animals demonstrated that SARS-CoV-2, bat RaTG13, and pangolin CoV genomes formed a monophyletic cluster, demonstrating that pangolins may be suggested as SARS-CoV-2 intermediate hosts. Three AA substitutions localized in the S1 portion of the S gene were observed, some of which have been correlated to structural modifications of the S protein which may facilitate SARS-CoV-2 tropism to human cells. Our analysis shows the tight relationship between SARS-CoV-2 and bat SARS-like strains. It also hypothesizes that pangolins might have been possible intermediate hosts of the infection. Some of the observed AA substitutions in the S-binding protein may serve as possible adaptation mutations in humans but more studies are needed to elucidate their function.", "qid": 32, "docid": "5qn5h7p5", "rank": 83, "score": 0.7371619343757629}, {"content": "Title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach Content: The newly identified SARS-CoV-2 has now been reported from around 185 countries with more than a million confirmed human cases including more than 120,000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins need to be explored to understand the biology of the virus. Spike glycoprotein is one of the major targets to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment. In this study, 483 unique variations have been identified among the genomes of SARS-CoV-2 including 25 nonsynonymous mutations and one deletion in the spike (S) protein. Among the 26 variations detected in S, 12 variations were located at the N-terminal domain (NTD) and 6 variations at the receptor-binding domain (RBD) which might alter the interaction of S protein with the host receptor angiotensin-converting enzyme 2 (ACE2). Besides, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on results reported herein, potential inhibitors against S protein can be designed by considering these variations and their impact on protein structure.", "qid": 32, "docid": "c5fygzvz", "rank": 84, "score": 0.7368128299713135}, {"content": "Title: Investigating the genomic landscape of novel coronavirus (2019-nCoV) to identify non-synonymous mutations for use in diagnosis and drug design Content: This study presents a comprehensive phylogenetic analysis of SARS-CoV2 isolates to understand discrete mutations that are occurring between patient samples. The analysis unravel various amino acid mutations in the viral proteins which may provide an explanation for varying treatment efficacies of different inhibitory drugs and a future direction towards a combinatorial treatment therapies based on the kind of mutation in the viral genome.", "qid": 32, "docid": "ttte21up", "rank": 85, "score": 0.736458957195282}, {"content": "Title: Global Spread of SARS-CoV-2 Subtype with Spike Protein Mutation D614G is Shaped by Human Genomic Variations that Regulate Expression of TMPRSS2 and MX1 Genes Content: COVID-19 pandemic is a major human tragedy. Worldwide, SARS-CoV-2 has already infected over 3 million and has killed about 230,000 people. SARS-CoV-2 originated in China and, within three months, has evolved to an additional 10 subtypes. One particular subtype with a non-silent (Aspartate to Glycine) mutation at 614th position of the Spike protein (D614G) rapidly outcompeted other pre-existing subtypes, including the ancestral. We assessed that D614G mutation generates an additional serine protease (Elastase) cleavage site near the S1-S2 junction of the Spike protein. We also identified that a single nucleotide deletion (delC) at a known variant site (rs35074065) in a cis-eQTL of TMPRSS2, is extremely rare in East Asians but is common in Europeans and North Americans. The delC allele facilitates entry of the 614G subtype into host cells, thus accelerating the spread of 614G subtype in Europe and North America where the delC allele is common. The delC allele at the cis-eQTL locus rs35074065 of TMPRSS2 leads to overexpression of both TMPRSS2 and a nearby gene MX1. The cis-eQTL site, rs35074065 overlaps with a transcription factor binding site of an activator (IRF1) and a repressor (IRF2). IRF1 activator can bind to variant delC allele, but IRF2 repressor fails to bind. Thus, in an individual carrying the delC allele, there is only activation, but no repression. On viral entry, IRF1 mediated upregulation of MX1 leads to neutrophil infiltration and processing of 614G mutated Spike protein by neutrophil Elastase. The simultaneous processing of 614G spike protein by TMPRSS2 and Elastase serine proteases facilitates the entry of the 614G subtype into host cells. Thus, SARS-CoV-2, particularly the 614G subtype, has spread more easily and with higher frequency to Europe and North America where the delC allele regulating expression of TMPRSS2 and MX1 host proteins is common, but not to East Asia where this allele is rare.", "qid": 32, "docid": "bbhf4qus", "rank": 86, "score": 0.7364562749862671}, {"content": "Title: Phylogenetic network analysis of SARS-CoV-2 genomes Content: In a phylogenetic network analysis of 160 complete human severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) genomes, we find three central variants distinguished by amino acid changes, which we have named A, B, and C, with A being the ancestral type according to the bat outgroup coronavirus. The A and C types are found in significant proportions outside East Asia, that is, in Europeans and Americans. In contrast, the B type is the most common type in East Asia, and its ancestral genome appears not to have spread outside East Asia without first mutating into derived B types, pointing to founder effects or immunological or environmental resistance against this type outside Asia. The network faithfully traces routes of infections for documented coronavirus disease 2019 (COVID-19) cases, indicating that phylogenetic networks can likewise be successfully used to help trace undocumented COVID-19 infection sources, which can then be quarantined to prevent recurrent spread of the disease worldwide.", "qid": 32, "docid": "d5qzzvy3", "rank": 87, "score": 0.7363560199737549}, {"content": "Title: Mutations strengthened SARS-CoV-2 infectivity Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is a major concern in coronavirus disease 2019 (COVID-19) prevention and economic reopening. However, rigorous determination of SARS-COV-2 infectivity is essentially impossible owing to its continuous evolution with over 13752 single nucleotide polymorphisms (SNP) variants in six different subtypes. We develop an advanced machine learning algorithm based on the algebraic topology to quantitatively evaluate the binding affinity changes of SARS-CoV-2 spike glycoprotein (S protein) and host angiotensin-converting enzyme 2 (ACE2) receptor following the mutations. Based on mutation-induced binding affinity changes, we reveal that five out of six SARS-CoV-2 subtypes have become either moderately or slightly more infectious, while one subtype has weakened its infectivity. We find that SARS-CoV-2 is slightly more infectious than SARS-CoV according to computed S protein-ACE2 binding affinity changes. Based on a systematic evaluation of all possible 3686 future mutations on the S protein receptor-binding domain (RBD), we show that most likely future mutations will make SARS-CoV-2 more infectious. Combining sequence alignment, probability analysis, and binding affinity calculation, we predict that a few residues on the receptor-binding motif (RBM), i.e., 452, 489, 500, 501, and 505, have very high chances to mutate into significantly more infectious COVID-19 strains.", "qid": 32, "docid": "8s8gezpz", "rank": 88, "score": 0.7363065481185913}, {"content": "Title: Characterizations of SARS-CoV-2 mutational profile, spike protein stability and viral transmission Content: The recent pandemic of SARS-CoV-2 infection has affected more than 3.0 million people worldwide with more than 200 thousand reported deaths. The SARS-CoV-2 genome has a capability of gaining rapid mutations as the virus spreads. Whole genome sequencing data offers a wide range of opportunities to study the mutation dynamics. The advantage of increasing amount of whole genome sequence data of SARS-CoV-2 intrigued us to explore the mutation profile across the genome, to check the genome diversity and to investigate the implications of those mutations in protein stability and viral transmission. Four proteins, surface glycoprotein, nucleocapsid, ORF1ab and ORF8 showed frequent mutations, while envelop, membrane, ORF6 and ORF7a proteins showed conservation in terms of amino acid substitutions. Some of the mutations across different proteins showed co-occurrence, suggesting their functional cooperation in stability, transmission and adaptability. Combined analysis with the frequently mutated residues identified 20 viral variants, among which 12 specific combinations comprised more than 97% of the isolates considered for the analysis. Analysis of protein structure stability of surface glycoprotein mutants indicated viability of specific variants and are more prone to be temporally and spatially distributed across the globe. Similar empirical analysis of other proteins indicated existence of important functional implications of several variants. Analysis of co-occurred mutants indicated their structural and/or functional interaction among different SARS-COV-2 proteins. Identification of frequently mutated variants among COVID-19 patients might be useful for better clinical management, contact tracing and containment of the disease.", "qid": 32, "docid": "86byq11c", "rank": 89, "score": 0.7361740469932556}, {"content": "Title: Supporting pandemic response using genomics and bioinformatics: A case study on the emergent SARS-CoV-2 outbreak Content: Pre-clinical responses to fast-moving infectious disease outbreaks heavily depend on choosing the best isolates for animal models that inform diagnostics, vaccines and treatments. Current approaches are driven by practical considerations (e.g. first available virus isolate) rather than a detailed analysis of the characteristics of the virus strain chosen, which can lead to animal models that are not representative of the circulating or emerging clusters. Here, we suggest a combination of epidemiological, experimental and bioinformatic considerations when choosing virus strains for animal model generation. We discuss the currently chosen SARS-CoV-2 strains for international coronavirus disease (COVID-19) models in the context of their phylogeny as well as in a novel alignment-free bioinformatic approach. Unlike phylogenetic trees, which focus on individual shared mutations, this new approach assesses genome-wide co-developing functionalities and hence offers a more fluid view of the 'cloud of variances' that RNA viruses are prone to accumulate. This joint approach concludes that while the current animal models cover the existing viral strains adequately, there is substantial evolutionary activity that is likely not considered by the current models. Based on insights from the non-discrete alignment-free approach and experimental observations, we suggest isolates for future animal models.", "qid": 32, "docid": "md8en2qy", "rank": 90, "score": 0.7360222339630127}, {"content": "Title: Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins. Content: The outbreak of COVID-19 poses unprecedent challenges to global health1. The new coronavirus, SARS-CoV-2, shares high sequence identity to SARS-CoV and a bat coronavirus RaTG132. While bats may be the reservoir host for various coronaviruses3,4, whether SARS-CoV-2 has other hosts remains ambiguous. In this study, one coronavirus isolated from a Malayan pangolin showed 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S genes, respectively. In particular, the receptor-binding domain within the S protein of the Pangolin-CoV is virtually identical to that of SARS-CoV-2, with one noncritical amino acid difference. Results of comparative genomic analysis suggest that SARS-CoV-2 might have originated from the recombination of a Pangolin-CoV-like virus with a Bat-CoV-RaTG13-like virus. The Pangolin-CoV was detected in 17 of 25 Malayan pangolins analyzed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against Pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus that is highly related to SARS-CoV-2 in pangolins suggests that they have the potential to act as the intermediate host of SARS-CoV-2. The newly identified coronavirus in the most-trafficked mammal could represent a future threat to public health if wildlife trade is not effectively controlled.", "qid": 32, "docid": "xcsl2evz", "rank": 91, "score": 0.7360140085220337}, {"content": "Title: Emergence of multiple variants of SARS-CoV-2 with signature structural changes Content: This study explores the divergence pattern of SARS-CoV-2 using whole genome sequences of the isolates from various COVID-19 affected countries. The phylogenomic analysis indicates the presence of at least four distinct groups of the SARS-CoV-2 genomes. The emergent groups have been found to be associated with signature structural changes in specific proteins. Also, this study reveals the differential levels of divergence patterns for the protein coding regions. Moreover, we have predicted the impact of structural changes on a couple of important viral proteins via structural modelling techniques. This study further advocates for more viral genetic studies with associated clinical outcomes and hosts\u2019 response for better understanding of SARS-CoV-2 pathogenesis enabling better mitigation of this pandemic situation.", "qid": 32, "docid": "bu1bc2bi", "rank": 92, "score": 0.7358511686325073}, {"content": "Title: Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity Content: Monitoring the mutation dynamics of SARS-CoV-2 is critical for the development of effective approaches to contain the pathogen. By analyzing 106 SARS-CoV-2 and 39 SARS genome sequences, we provided direct genetic evidence that SARS-CoV-2 has a much lower mutation rate than SARS. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. The discrepant phylogenies for the spike protein and its receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARS-CoV-2. Despite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a mutation that leads to weaker receptor binding capability, which concerns a SARS-CoV-2 sample collected on 27th January 2020 from India. This represents the first report of a significant SARS-CoV-2 mutant, and raises the alarm that the ongoing vaccine development may become futile in future epidemic if more mutations were identified. Highlights Based on the currently available genome sequence data, we proved that SARS-COV-2 genome has a much lower mutation rate and genetic diversity than SARS during the 2002-2003 outbreak. The spike (S) protein encoding gene of SARS-COV-2 is found relatively more conserved than other protein-encoding genes, which is a good indication for the ongoing antiviral drug and vaccine development. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. We confirmed a previously reported rearrangement in the S protein arrangement of SARS-COV-2, and propose that this rearrangement should have occurred between human SARS-CoV and a bat SARS-CoV, at a time point much earlier before SARS-COV-2 transmission to human. We provided first evidence that a mutated SARS-COV-2 with reduced human ACE2 receptor binding affinity have emerged in India based on a sample collected on 27th January 2020.", "qid": 32, "docid": "t8q99tlq", "rank": 93, "score": 0.7358094453811646}, {"content": "Title: Virus strain from a mild COVID-19 patient in Hangzhou represents a new trend in SARS-CoV-2 evolution potentially related to Furin cleavage site. Content: The mutations in the SARS-CoV-2 virus genome during the spread of COVID-19 have been unclear. In 788 COVID-19 patients from Zhejiang province, we observed decreased rate of severe/critical cases, increased liver/kidney damage, and prolonged period of nuclear acid positivity, compared with patients in Wuhan, China. To investigate the underlying mechanisms, we isolated one strain of SARS-CoV-2 (ZJ01) from a mild COVID-19 patient. Thirty-five specific gene mutations were identified by gene alignment. Further phylogenetic analysis and relative synonymous codon usage heat map results suggested that ZJ01 may be a potential evolutionary branch of SARS-CoV-2. We classified 54 virus strains collected globally based on the base (C or T) at positions 8824 and 28247. ZJ01 has T at both sites and is currently the only known TT type. The prediction of the Furin cleavage site (FCS) and sequence alignment of the virus family indicated that the FCS may be an important site of coronavirus evolution. ZJ01 mutations identified near the FCS (F1-2) caused changes in the structure and electrostatic distribution of the S surface protein, further affecting the binding capacity of Furin. Single-cell sequencing and ACE2-Furin co-expression results confirmed that the Furin expression was higher in the whole body, especially in glands, liver, kidneys, and colon. Thus, FCS may help SARS-CoV-2 infect these organs. The evolutionary pattern of SARS-CoV-2 towards FCS formation may result in its clinical symptom becoming closer to HKU-1 and OC43 (the source of FCS sequence-PRRA) caused mild flu-like symptoms, further showing potential in differentiating into mild COVID-19 subtypes.", "qid": 32, "docid": "0s7oq0uv", "rank": 94, "score": 0.7356511950492859}, {"content": "Title: Early Spread of SARS-Cov-2 in the Icelandic Population Content: BACKGROUND Limited data exist on how SARS-CoV-2 enters and spreads in the general population. METHODS We used two strategies for SARS-CoV-2 testing: targeted testing of high-risk individuals (n=4,551) and a population screening (n=5,502). We sequenced SARS-CoV-2 from 340 individuals. RESULTS On March 22 2020, 528 had tested positive for SARS-CoV-2 in the targeted testing (11.6%) and 50 in the population screening (0.9%); approximately 0.2% of the Icelandic population. Large fractions of positives had travelled outside Iceland (38.4% and 34.0%). Fewer under 10 years old were positive than those older: 2.8% vs. 12.3% for targeted testing (P=1.6e-9) and 0.0% vs. 1.0% for population screening (P=0.031). Fewer females were positive in the targeted testing than males (9.5% vs. 14.6%, P=6.8e-9). SARS-CoV-2 came from eight clades, seven A clades and one B clade. The clade composition differed between the testing groups and changed with time. In the early targeted testing, 65.0% of clades were A2a1 and A2a2 derived from Italian and Austrian skiing areas, but in the later targeted testing went down to 30.6% and were overtaken by A1a and A2a, the most common clades in the population screening. CONCLUSION SARS-CoV-2 has spread widely in Iceland outside of the high-risk groups. Several strains cause these infections and their relative contribution changed rapidly. Children and females are less vulnerable than adults and males. To contain the pandemic we must increase the scope of the testing.", "qid": 32, "docid": "bbmcenpy", "rank": 95, "score": 0.7355461120605469}, {"content": "Title: Virus strain from a mild COVID-19 patient in Hangzhou represents a new trend in SARS-CoV-2 evolution potentially related to Furin cleavage site Content: The mutations in the SARS-CoV-2 virus genome during COVID-19 dissemination are unclear. In 788 COVID-19 patients from Zhejiang province, we observed decreased rate of severe/critical cases compared with patients in Wuhan. For mechanisms exploration, we isolated one strain of SARS-CoV-2 (ZJ01) from a mild COVID-19 patient. Thirty-five specific gene mutations were identified. Phylogenetic and relative synonymous codon usage analysis suggested that ZJ01 may be a potential evolutionary branch of SARS-CoV-2. We classified 54 global virus strains based on the base (C or T) at positions 8824 and 28247 while ZJ01 has T at both sites. The prediction of the Furin cleavage site (FCS) and sequence alignment indicated that the FCS may be an important site of coronavirus evolution. ZJ01 mutations identified near the FCS (F1-2) caused changes in the structure and electrostatic distribution of the S surface protein, further affecting the binding capacity of Furin. Single-cell sequencing and ACE2-Furin co-expression results confirmed that the Furin expression was especially higher in glands, liver, kidneys, and colon. The evolutionary pattern of SARS-CoV-2 towards FCS formation may result in its clinical symptom becoming closer to HKU-1 and OC43 caused mild flu-like symptoms, further showing its potential in differentiating into mild COVID-19 subtypes.", "qid": 32, "docid": "iljmhdd1", "rank": 96, "score": 0.7354444265365601}, {"content": "Title: Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction Content: The emergence of SARS-CoV-2 has led to the current global coronavirus pandemic and more than one million infections since December 2019. The exact origin of SARS-CoV-2 remains elusive, but the presence of a distinct motif in the S1/S2 junction region suggests the possible acquisition of cleavage site(s) in the spike protein that promoted cross-species transmission. Through plaque purification of Vero-E6 cultured SARS-CoV-2, we found a series of variants which contain 15-30-bp deletions (Del-mut) or point mutations respectively at the S1/S2 junction. Examination of the original clinical specimen from which the isolate was derived, and 26 additional SARS-CoV-2 positive clinical specimens, failed to detect these variants. Infection of hamsters shows that one of the variants (Del-mut-1) which carries deletion of 10 amino acids (30bp) does not cause the body weight loss or more severe pathological changes in the lungs that is associated with wild type virus infection. We suggest that the unique cleavage motif promoting SARS-CoV-2 infection in humans may be under strong selective pressure, given that replication in permissive Vero-E6 cells leads to the loss of this adaptive function. It would be important to screen the prevalence of these variants in asymptomatic infected cases. The potential of the Del-mut variants as an attenuated vaccine or laboratory tool should be evaluated.", "qid": 32, "docid": "mgsaoz3j", "rank": 97, "score": 0.7353839874267578}, {"content": "Title: SARS-CoV-2 genomic and subgenomic RNAs in diagnostic samples are not an indicator of active replication Content: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in China in late December 2019 and has spread worldwide. Coronaviruses are enveloped, positive sense, single-stranded RNA viruses and employ a complicated pattern of virus genome length RNA replication as well as transcription of genome length and leader containing subgenomic RNAs. Although not fully understood, both replication and transcription are thought to take place in so-called double-membrane vesicles in the cytoplasm of infected cells. We here describe detection of SARS-CoV-2 subgenomic RNAs in diagnostic samples up to 17 days after initial detection of infection, and provide a likely explanation not only for extended PCR positivity of such samples, but also for discrepancies in results of different PCR methods described by others. Overall, we present evidence that subgenomic RNAs may not be an indicator of active coronavirus replication/infection, but that these RNAs, similar to the virus genome RNA, may be rather stable, and thus detectable for an extended period, most likely due to their close association with cellular membranes.", "qid": 32, "docid": "1qnwi5s7", "rank": 98, "score": 0.7351003885269165}, {"content": "Title: COVID-19: From bench to bed side Content: BACKGROUND AND AIMS: The last two decades have experienced the outbreaks of three different coronaviruses in the different parts of the world namely; Severe acute respiratory syndrome cornonavirus-1 (SARS-CoV-1), Middle East respiratory syndrome (MERS-CoV) and Severe acute respiratory syndrome cornonavirus-2 (SARS-CoV-2). We aimed to delineate the differences in viral dynamics and clinical features between them and tried to focus on every basic details of SARS-COV-2 (COVID-19) that every health care provider must know. METHODS: We systematically searched the PubMed database up till April 2, 2020 and retrieved all the articles published on SARS-CoV-2, SARS-CoV-1, MERS-CoV that dealt with viral dynamics. RESULTS: Ample data is available to suggest the differences in etiology, transmission cycle, diagnosis, genetics, hosts, reproductive rates, clinical features, laboratory diagnosis and radiological features between SARS-CoV-1, MERS-CoV and SARS-CoV-2. CONCLUSION: Although SARS-CoV-2 (COVID-19) is more infectious than SARS-CoV-1 and MERS-CoV, most infections are generally mild and self-limiting. However, case-fatality rates are very high in patients with COVID-19 with comorbidities, compared to SARS-CoV-1 and MERS-CoV.", "qid": 32, "docid": "o409ie16", "rank": 99, "score": 0.7350142002105713}, {"content": "Title: Rapid whole genome sequence typing reveals multiple waves of SARS-CoV-2 spread Content: As the pandemic SARS-CoV-2 virus has spread globally its genome has diversified to an extent that distinct clones can now be recognized, tracked, and traced. Identifying clonal groups allows for assessment of geographic spread, transmission events, and identification of new or emerging strains that may be more virulent or more transmissible. Here we present a rapid, whole genome, allele-based method (GNUVID) for assigning sequence types to sequenced isolates of SARS-CoV-2 sequences. This sequence typing scheme can be updated with new genomic information extremely rapidly, making our technique continually adaptable as databases grow. We show that our method is consistent with phylogeny and recovers waves of expansion and replacement of sequence types/clonal complexes in different geographical locations. GNUVID is available as a command line application (https://github.com/ahmedmagds/GNUVID).", "qid": 32, "docid": "ee5xw1r8", "rank": 100, "score": 0.7349721789360046}]}
{"query": "What vaccine candidates are being tested for Covid-19?", "hits": [{"content": "Title: Vaccines for COVID-19: The current state of play Content: There is a strong consensus globally that a COVID-19 vaccine is likely the most effective approach to sustainably controlling the COVID-19 pandemic. An unprecedented research effort and global coordination has resulted in a rapid development of vaccine candidates and initiation of trials. Here, we review vaccine types, and progress with 10 vaccine candidates against SARS-CoV-2 - the virus that causes COVID-19 - currently undergoing early phase human trials. We also consider the many challenges of developing and deploying a new vaccine on a global scale, and recommend caution with respect to our expectations of the timeline that may be ahead.", "qid": 33, "docid": "o8bkorjn", "rank": 1, "score": 0.8065743446350098}, {"content": "Title: Vaccines for COVID-19: the current state of play Content: There is a strong consensus globally that a COVID-19 vaccine is likely the most effective approach to sustainably controlling the COVID-19 pandemic. An unprecedented research effort and global coordination has resulted in a rapid development of vaccine candidates and initiation of trials. Here, we review vaccine types, and progress with 10 vaccine candidates against SARS-CoV-2 \u2013 the virus that causes COVID-19 - currently undergoing early phase human trials. We also consider the many challenges of developing and deploying a new vaccine on a global scale, and recommend caution with respect to our expectations of the timeline that may be ahead.", "qid": 33, "docid": "ievuxa6k", "rank": 2, "score": 0.8055766820907593}, {"content": "Title: COVID-19: A Review of Emerging Preventative Vaccines and Treatment Strategies Content: COVID-19, which was first detected in the Hubei province of China, has become a global phenomenon. The effects and devastation on both health and economy have been global. At present, there is a substantial amount of research being done to discover suitable treatment modalities. Efforts have been made on the development of potential efficacious vaccines. The development of a vaccine can be complex, expensive as well as time-consuming. Currently, various ongoing clinical trials are in progress that are investigating either pharmacologic therapies or vaccines against this virus. We, in this brief review have tried to address the process and current development efforts of vaccine in progress.", "qid": 33, "docid": "4ytphmji", "rank": 3, "score": 0.7699957489967346}, {"content": "Title: The potential danger of suboptimal antibody responses in COVID-19 Content: There is a desperate need for effective therapies and vaccines for SARS-CoV-2 to mitigate the growing economic crisis that has ensued from societal lockdown. Vaccines are being developed at an unprecedented speed and are already in clinical trials, without preclinical testing for safety and efficacy. Yet, safety evaluation of candidate vaccines must not be overlooked.", "qid": 33, "docid": "xee6npr3", "rank": 4, "score": 0.7646490335464478}, {"content": "Title: How Close are We to a COVID-19 Vaccine? Content: This review provides an overview regarding the main aspects of candidate COVID-19 vaccines and pathophysiology of disease The types of biotechnological candidate vaccines to be developed against COVID-19, their degree of protection and the pathophysiological mechanism of the disease were analyzed in this review article The literature data on which cruxes for the development of biotechnological candidate vaccines to be wended are based was researched Data that could give reference to various biotechnological candidate vaccines were reviewed For this purpose, up-to-date literature data was utilized The ways to succeed in the development of a vaccine requiring a technological infrastructure are to synthesize the data obtained from long term trials and to put them into practice subsequently The vaccines to be developed by means of recombinant DNA technology will be a source of inspiration to people for further studies After a rapid process of vaccine development, the use of COVID-19 vaccine can be mainstreamed among people to prevent the disease As a result of these practices, the evaluation of which vaccine will be more safe, reliable and effective will be performed after phase studies", "qid": 33, "docid": "asw56fla", "rank": 5, "score": 0.7641226053237915}, {"content": "Title: COVID-19 vaccines move toward clinic Content: Drug developers are moving their experimental vaccines for COVID-19 into clinical trials at a frenetic pace Trials for five such vaccines have begun in China Two are being tested in the US, with a third slated to start this month And trials of two more are due to begin in the UK and Australia in the coming weeks \u201cEverything from basic science to clinical science is progressing at a pace faster than ever before\u2014and very appropriately, given the grave nature of the current global crisis,\u201d says Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center The World Health Organization says at least 70 COVID-19 vaccines are in development, while scientists at the Coalition for Epidemic Preparedness Innovations (CEPI) have counted 115 Moderna was the first to begin clinical testing of a COVID-19 vaccine, just 66 days after downloading the genome of SARS-CoV-2,", "qid": 33, "docid": "y2bylnte", "rank": 6, "score": 0.7634356617927551}, {"content": "Title: Fighting COVID-19: A quick review of diagnoses, therapies, and vaccines Content: The coronavirus disease 2019 (COVID-19) pandemic caused by a novel coronavirus, SARS-CoV-2, has infected more than 4.9 million individuals and resulted in over 300,000 deaths globally. The rapid spread of the virus and the precipitously increasing numbers of cases necessitate the urgent development of accurate diagnostic methods, effective treatments, and vaccines. Here, we review the progress of developing diagnostic methods, therapies, and vaccines for SARS-CoV-2 with a focus on current clinical trials and their challenges. For diagnosis, nucleic acid amplification tests remain the mainstay diagnostics for laboratory confirmation of SARS-CoV-2 infection, while serological antibody tests are used to aid contact tracing, epidemiological, and vaccine evaluation studies. Viral isolation is not recommended for routine diagnostic procedures due to safety concerns. Currently, no single effective drug or specific vaccine is available against SARS-CoV-2. Some candidate drugs targeting different levels and stages of human responses against COVID-19 such as cell membrane fusion, RNA-dependent RNA polymerase, viral protease inhibitor, interleukin 6 blocker, and convalescent plasma may improve the clinical outcomes of critical COVID-19 patients. Other supportive care measures for critical patients are still necessary. Advances in genetic sequencing and other technological developments have sped up the establishment of a variety of vaccine platforms. Accordingly, numerous vaccines are under development. Vaccine candidates against SARS-CoV-2 are mainly based upon the viral spike protein due to its vital role in viral infectivity, and most of these candidates have recently moved into clinical trials. Before the efficacy of such vaccines in humans is demonstrated, strong international coordination and collaboration among studies, pharmaceutical companies, regulators, and governments are needed to limit further damage due the emerging SARS-CoV-2 virus.", "qid": 33, "docid": "2vevp0fg", "rank": 7, "score": 0.7620052099227905}, {"content": "Title: Fighting COVID-19: a quick review of diagnoses, therapies, and vaccines Content: The COVID-19 pandemic caused by a novel coronavirus, SARS-CoV-2, has infected more than 4.9 million individuals and resulted in over 300,000 deaths globally. The rapid spread of the virus and the precipitously increasing numbers of cases necessitate the urgent development of accurate diagnostic methods, effective treatments, and vaccines. Here, we review the progress of developing diagnostic methods, therapies, and vaccines for SARS-CoV-2 with a focus on current clinical trials and their challenges. For diagnosis, nucleic acid amplification tests remain the mainstay diagnostics for laboratory confirmation of SARS-CoV-2 infection, while serological antibody tests are used to aid contact tracing, epidemiological, and vaccine evaluation studies. Viral isolation is not recommended for routine diagnostic procedures due to safety concerns. Currently, no single effective drug or specific vaccine is available against SARS-CoV-2. Some candidate drugs targeting different levels and stages of human responses against COVID-19 such as cell membrane fusion, RNA-dependent RNA polymerase, viral protease inhibitor, interleukin 6 blocker, and convalescent plasma may improve the clinical outcomes of critical COVID-19 patients. Other supportive care measures for critical patients are still necessary. Advances in genetic sequencing and other technological developments have sped up the establishment of a variety of vaccine platforms. Accordingly, numerous vaccines are under development. Vaccine candidates against SARS-CoV-2 are mainly based upon the viral spike protein due to its vital role in viral infectivity, and most of these candidates have recently moved into clinical trials. Before the efficacy of such vaccines in humans is demonstrated, strong international coordination and collaboration among studies, pharmaceutical companies, regulators, and governments are needed to limit further damage due the emerging SARS-CoV-2 virus.", "qid": 33, "docid": "0g7a9s5z", "rank": 8, "score": 0.7601022720336914}, {"content": "Title: Covid-19 treatment: The race against time Content: The new outbreak of the novel coronavirus infection emerged in Wuhan-China in late 2019, by the end of Mar 2020, it has spread in more than 178 countries and territories. There is no vaccine or antiviral treatment for COVID-19. Currently, there are several drugs and vaccines being tested for their potential activity against the disease. In this review, we briefly discuss some of the investigational drugs and vaccines being tested against COVID-19 as well as their potential drawbacks.", "qid": 33, "docid": "natp8lbj", "rank": 9, "score": 0.7561857104301453}, {"content": "Title: Will the coronavirus help mRNA and DNA vaccines prove their worth? Content: Biotech companies, pharma firms, universities, and government agencies are all rushing to start clinical trials of newly created gene-based vaccines for COVID-19 Developer;Technology;Phase I clinical trial Moderna and National Institutes of Health;mRNA vaccine;Began in March 2020 CanSino Biologics;Adenoviral vector vaccine;Began in March 2020 BioNTech, Shanghai Fosun Pharmaceutical, and Pfizer;mRNA vaccine;April 2020 Inovio Pharmaceuticals and Wistar Institute;DNA vaccine;April 2020 University of Oxford;Adenoviral vector vaccine;April 2020 CureVac;mRNA vaccine;By early summer Imperial College London;mRNA vaccine;Early summer Arcturus Therapeutics and Duke-NUS Medical School;mRNA vaccine;Second half of 2020 Johnson & Johnson and Biomedical Advanced Research and Development Authority;Adenoviral vector vaccine;By September Altimmune;Adenoviral vector vaccine;Q3 2020 Translate Bio and Sanofi Pasteur;mRNA vaccine;By end of 2020 eTheRNA Immunotherapies;mRNA vaccine;2021 Karolinska Institute;DNA vaccine;2021 University of Pennsylvania and Duke Human Vaccine Institute;mRNA vaccine;Unknown", "qid": 33, "docid": "30dhqh0g", "rank": 10, "score": 0.7556564807891846}, {"content": "Title: SARS-CoV-2 SPIKE PROTEIN: an optimal immunological target for vaccines Content: COVID-19 has rapidly spread all over the world, progressing into a pandemic. This situation has urgently impelled many companies and public research institutes to concentrate their efforts on research for effective therapeutics. Here, we outline the strategies and targets currently adopted in developing a vaccine against SARS-CoV-2. Based on previous evidence and experience with SARS and MERS, the primary focus has been the Spike protein, considered as the ideal target for COVID-19 immunotherapies.", "qid": 33, "docid": "13z63d4y", "rank": 11, "score": 0.7555928230285645}, {"content": "Title: The vaccine journey for COVID-19: a comprehensive systematic review of current clinical trials in humans Content: INTRODUCTION: Since December 2019, there has been an outbreak of a novel beta-coronavirus (SARS-CoV-2) in Wuhan, China. On March the 11th the World Health Organization (WHO) declared COVID-19 as a pandemic, with over 118,000 cases in more than 110 countries around the world. In response to the global coronavirus disease 2019 (COVID-19) emergency, clinical trial research assessing the efficacy and safety of experimental vaccines to prevent COVID-19 are emerging at an unprecedented rate. The aim of this systematic review is to summarize the preliminary experiences and ongoing clinical trials of the major candidates and challenges of the vaccine strategies in humans. EVIDENCE ACQUISITION: After a priori protocol registration with PROSPERO (181483), a systematic research of the published literature was conducted on 24 April 2020 using Medline (via PubMed), Embase (via Ovid), and WHO databases. Moreover, to explore the more recent literature we also searched the preprint server medRxiv. Finally, we scrutinized the Cochrane COVID-19 study register and the COVID-19 section of ClinicalTrials.gov database for identifying relevant ongoing clinical trials. Thereafter we selected the articles according to the PRISMA guidelines. Animal or in-vitro experimental studies were excluded. Moreover editorials, commentaries, abstracts, reviews, book chapters, and articles not in English were not included. EVIDENCE SYNTHESIS: Our search identified 1359 published papers, 478 pre-print articles and 367 ongoing clinical trials. Finally, only ten ongoing clinical trials met the inclusion criteria. Specifically, seven developed vaccines for the S protein of SARS-CoV-2 and three clinical trials assessed the protective role of BCG vaccine against COVID-19. The first group included phase I/II trials with different types of molecules (DNA or mRNA vaccine, bacterial plasmid or viral vectors), the latter were phase III/IV trials designed on the basis of a heterologous lymphocyte activation by the BCG vaccine. CONCLUSIONS: This new disease is pushing the scientific community to develop swiftly a safe and effective vaccine. Notwithstanding the limitations of our analysis, given by the absence of available results, we try to provide a comprehensive view of the ongoing clinical trials in humans. Our analysis reveals a worldwide effort of both scientists and enterprises to achieve one of the most challenging goals of our century.", "qid": 33, "docid": "xt8tld2i", "rank": 12, "score": 0.7553418874740601}, {"content": "Title: Intention to participate in a COVID-19 vaccine clinical trial and to get vaccinated against COVID-19 in France during the pandemic Content: Background: The world is facing the COVID-19 pandemic. Development of vaccine is challenging. Aim: To determine the proportion of people who intend to get vaccinated against COVID-19 in France or to participate in a vaccine clinical trial. Methods: We conducted an anonymous on-line survey from the 26th of March to the 20th of April 2020. Primary endpoints were the intention to get vaccinated against COVID-19 if a vaccine was available or participate in a vaccine clinical trial. Results: Three thousand two hundred and fifty nine individuals answered the survey; women accounted for 67.4 % of the responders, 670 (20.6 %) were under 30 years of age, 1,502 (46.1 %) between 30-49 years, 803 (24.6 %) between 50-64 years, 271 (8.3%) between 65-80 years, 13 (0.4%) over 80 years of age. According to their statements, 2.512 participants (77.6%, 95 % CI 76.2-79 %) will certainly or probably agree to get vaccinated against COVID-19. Older age, male gender, fear about COVID-19, being healthcare workers and individual perceived risk were associated with COVID-19 vaccine acceptance Vaccine hesitancy was associated with a decrease in COVID-19 vaccine acceptance. One thousand and five hundred and fifty responders (47.6 % 95 % CI 45.9-49.3 %) will certainly or probably agree to participate in a COVID-19 vaccine clinical trial. Conclusions and Relevance: Nearly 75 % and 48 % of the survey responders were likely to accept vaccination or participation in a clinical trial against COVID-19. Vaccine hesitancy will be the major barrier to COVID-19 vaccine uptake.", "qid": 33, "docid": "sribl7kt", "rank": 13, "score": 0.7518640756607056}, {"content": "Title: COVID-19 vaccines: Knowing the unknown Content: Vaccine development against SARS-CoV-2 has drawn attention around the globe due to the exploding pandemic. Although COVID-19 is caused by a new coronavirus, SARS-CoV-2, previous research on other coronavirus vaccines, such as FIPV, SARS, and MERS, has provided valuable information for the rapid development of COVID-19 vaccine. However, important knowledge gaps remain - some are specific to SARS-CoV-2, others are fundamental to immunology and vaccinology. Here, we discuss areas that need to be addressed for COVID-19 vaccine development, and what can be learned from examples of vaccine development in the past. Since the beginning of the outbreak, the research progress on COVID-19 has been remarkable. We are therefore optimistic about the rapid development of COVID-19 vaccine.", "qid": 33, "docid": "hotn7qha", "rank": 14, "score": 0.7452391386032104}, {"content": "Title: Public Willingness to Get Vaccinated Against COVID-19: How AI-Developed Vaccines Can Affect Acceptance Content: Vaccines for COVID-19 are currently under clinical trials. These vaccines are crucial for eradicating the novel coronavirus. Despite the potential, there exist conspiracies related to vaccines online, which can lead to vaccination hesitancy and, thus, a longer-standing pandemic. We used a between-subjects study design (N=572 adults in the US and UK) to understand the public willingness towards vaccination against the novel coronavirus under various circumstances. Our survey findings suggest that people are more reluctant to vaccinate their children compared to themselves. Explicitly stating the high effectiveness of the vaccine against COVID-19 led to an increase in vaccine acceptance. Interestingly, our results do not indicate any meaningful variance due to the use of artificial intelligence (AI) in developing vaccines, if these systems are described to be in use alongside human researchers. We discuss the public's expectation of local governments in assuring the safety and effectiveness of a future COVID-19 vaccine.", "qid": 33, "docid": "uhb8k967", "rank": 15, "score": 0.7422823905944824}, {"content": "Title: Why Challenge Trials of SARS-CoV-2 Vaccines Could Be Ethical Despite Risk of Severe Adverse Events Content: Human challenge trials to test the efficacy of vaccine candidates against SARS-CoV-2, the novel coronavirus behind Covid-19, could save considerable time and many lives. But they may initially seem unethical because they expose healthy volunteers to a live virus that is killing many people and for which no cure exists. This article argues that this is not the correct test of their ethics. The correct test is comparative. And in the special circumstances of the Covid-19 pandemic, human challenge trials meet the correct test better than standard efficacy testing would.", "qid": 33, "docid": "bd7f9mgj", "rank": 16, "score": 0.7416397333145142}, {"content": "Title: Global efforts on vaccines for COVID-19: Since, sooner or later, we all will catch the coronavirus Content: COVID-19 is an emerging infectious disease that has turned into a pandemic. It spreads through droplet transmission of the new coronavirus SARS-CoV-2. It is an RNA virus displaying a spike protein as the major surface protein with significant sequence similarity to SARS-CoV which causes severe acute respiratory syndrome. The receptor binding domain of the spike protein interacts with the human angiotensin converting enzyme 2 and is considered as the antigenic determinant for stimulating an immune response. While multiple candidate vaccines are currently under different stages of development, there are no known therapeutic interventions at the moment. This review describes the key genetic features that are being considered for generating vaccine candidates by employing innovative technologies. It also highlights the global efforts being undertaken to deliver vaccines for COVID-19 through unprecedented international cooperation and future challenges post development.", "qid": 33, "docid": "z5q82rmp", "rank": 17, "score": 0.7408876419067383}, {"content": "Title: Global efforts on vaccines for COVID-19: Since, sooner or later, we all will catch the coronavirus. Content: COVID-19 is an emerging infectious disease that has turned into a pandemic. It spreads through droplet transmission of the new coronavirus SARS-CoV-2. It is an RNA virus displaying a spike protein as the major surface protein with significant sequence similarity to SARS-CoV which causes severe acute respiratory syndrome. The receptor binding domain of the spike protein interacts with the human angiotensin converting enzyme 2 and is considered as the antigenic determinant for stimulating an immune response. While multiple candidate vaccines are currently under different stages of development, there are no known therapeutic interventions at the moment. This review describes the key genetic features that are being considered for generating vaccine candidates by employing innovative technologies. It also highlights the global efforts being undertaken to deliver vaccines for COVID-19 through unprecedented international cooperation and future challenges post development.", "qid": 33, "docid": "sdtiyrab", "rank": 18, "score": 0.7408876419067383}, {"content": "Title: The vaccine journey for COVID-19: a comprehensive systematic review of current clinical trials in humans. Content: INTRODUCTION Since December 2019, there has been an outbreak of a novel beta-coronavirus (SARS-CoV-2) in Wuhan, China. On March the 11th the World Health Organization (WHO) declared COVID-19 as a pandemic, with over 118,000 cases in more than 110 countries around the world. In response to the global coronavirus disease 2019 (COVID-19) emergency, clinical trial research assessing the efficacy and safety of experimental vaccines to prevent COVID-19 are emerging at an unprecedented rate. The aim of this systematic review is to summarize the preliminary experiences and ongoing clinical trials of the major candidates and challenges of the vaccine strategies in humans. EVIDENCE ACQUISITION After a priori protocol registration with PROSPERO (181483), a systematic research of the published literature was conducted on 24 April 2020 using Medline (via PubMed), Embase (via Ovid), and WHO databases. Moreover, to explore the more recent literature we also searched the preprint server medRxiv. Finally, we scrutinized the Cochrane COVID-19 study register and the COVID-19 section of ClinicalTrials.gov database for identifying relevant ongoing clinical trials. Thereafter we selected the articles according to the PRISMA guidelines. Animal or in-vitro experimental studies were excluded. Moreover editorials, commentaries, abstracts, reviews, book chapters, and articles not in English were not included. EVIDENCE SYNTHESIS Our search identified 1359 published papers, 478 pre-print articles and 367 ongoing clinical trials. Finally, only ten ongoing clinical trials met the inclusion criteria. Specifically, seven developed vaccines for the S protein of SARS-CoV-2 and three clinical trials assessed the protective role of BCG vaccine against COVID-19. The first group included phase I/II trials with different types of molecules (DNA or mRNA vaccine, bacterial plasmid or viral vectors), the latter were phase III/IV trials designed on the basis of a heterologous lymphocyte activation by the BCG vaccine. CONCLUSIONS This new disease is pushing the scientific community to develop swiftly a safe and effective vaccine. Notwithstanding the limitations of our analysis, given by the absence of available results, we try to provide a comprehensive view of the ongoing clinical trials in humans. Our analysis reveals a worldwide effort of both scientists and enterprises to achieve one of the most challenging goals of our century.", "qid": 33, "docid": "1yrcbm7e", "rank": 19, "score": 0.7400414943695068}, {"content": "Title: SARS-CoV-2 (COVID-19) Vaccine Development and Production: An Ethical Way Forward Content: The world awaits a SARS-CoV-2 virus (i.e., COVID-19 disease) vaccine to keep the populace healthy, fully reopen their economies, and return their social and healthcare systems to \"normal.\" Vaccine safety and efficacy requires meticulous testing and oversight; this paper describes how despite grandiose public statements, the current vaccine development, testing, and production methods may prove to be ethically dubious, medically dangerous, and socially volatile. The basic moral concern is the potential danger to the health of human test subjects and, eventually, many vaccine recipients. This is further complicated by economic and political pressures to reduce government oversight on rushed vaccine testing and production, nationalistic distribution goals, and failure to plan for the widespread immunization needed to produce global herd immunity. As this paper asserts, the public must be better informed to assess promises about the novel vaccines being produced and to tolerate delays and uncertainty.", "qid": 33, "docid": "jwa2gkb9", "rank": 20, "score": 0.740020751953125}, {"content": "Title: Progress and Prospects on Vaccine Development against SARS-CoV-2 Content: In December 2019, the outbreak of pneumonia caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a serious pandemic in China and other countries worldwide. So far, more than 460,000 confirmed cases were diagnosed in nearly 190 countries, causing globally over 20,000 deaths. Currently, the epidemic is still spreading and there is no effective means to prevent the infection. Vaccines are proved to be the most effective and economical means to prevent and control infectious diseases. Several countries, companies, and institutions announced their programs and progress on vaccine development against the virus. While most of the vaccines are under design and preparation, there are some that have entered efficacy evaluation in animals and initial clinical trials. This review mainly focused on the progress and our prospects on field of vaccine development against SARS-CoV-2.", "qid": 33, "docid": "gl0wiyt2", "rank": 21, "score": 0.7393681406974792}, {"content": "Title: COVID-19 Vaccine: Vaccinate the Young to Protect the Old? Content: When we have a vaccine against COVID-19, who should be vaccinated first? The question is relevant because, initially, vaccine availability will likely be limited. After healthcare and some other essential workers, it might seem the most obvious candidates are the elderly and other groups that are more vulnerable to the virus. However, we argue that this is not necessarily the case. Protecting the most vulnerable might require prioritizing vaccinating children in order to maximize the benefits of indirect immunity for the elderly and the other vulnerable groups. Whether this will be the best strategy from a public health perspective will depend on characteristics of the vaccine and of the virus, which are currently unknown. Here, we assess this possibility from an ethical point of view, by drawing comparisons and analogies with the case of the flu vaccination and with other examples of health policies and practices. We conclude that there are strong ethical reasons to vaccinate the young to protect the old, provided that the risks imposed on children are reasonable, even if that implies using children as a means to protect the elderly and the vulnerable.", "qid": 33, "docid": "zuh71yz3", "rank": 22, "score": 0.7385638356208801}, {"content": "Title: SARS-CoV-2 (COVID-19) Vaccine Development and Production: An Ethical Way Forward Content: The world awaits a SARS-CoV-2 virus (i.e., COVID-19 disease) vaccine to keep the populace healthy, fully reopen their economies, and return their social and healthcare systems to \u201cnormal.\u201d Vaccine safety and efficacy requires meticulous testing and oversight; this paper describes how despite grandiose public statements, the current vaccine development, testing, and production methods may prove to be ethically dubious, medically dangerous, and socially volatile. The basic moral concern is the potential danger to the health of human test subjects and, eventually, many vaccine recipients. This is further complicated by economic and political pressures to reduce government oversight on rushed vaccine testing and production, nationalistic distribution goals, and failure to plan for the widespread immunization needed to produce global herd immunity. As this paper asserts, the public must be better informed to assess promises about the novel vaccines being produced and to tolerate delays and uncertainty.", "qid": 33, "docid": "vqim4t6x", "rank": 23, "score": 0.7383319735527039}, {"content": "Title: Natural History of COVID-19 and Current Knowledge on Treatment Therapeutic Options Content: Despite intense research there is currently no effective vaccine available against the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in the later 2019 and responsible for the COVID-19 pandemic. This infectious and communicable disease has become one of the major public health challenges in the world. The clinical management of COVID-19 has been limited to infection prevention and control measures associated with supportive care such as supplemental oxygen and mechanical ventilation. Meanwhile efforts to find an effective treatment to inhibit virus replication, mitigate the symptoms, increase survival and decrease mortality rate are ongoing. Several classes of drugs, many of them already in use for other diseases, are being evaluated based on the body of clinical knowledge obtained from infected patients regarding to the natural history and evolution of the infection. Herein we will provide an updated overview of the natural history and current knowledge on drugs and therapeutic agents being tested for the prevention and treatment of COVID-19. These include different classes of drugs such as antiviral agents (chloroquine, ivermectin, nitazoxanide, hydroxychloroquine, lopinavir, remdesivir, tocilizumab), supporting agents (Vitamin C, Vitamin D, azithromycin, corticosteroids) and promising investigational vaccines. Considering the controversies and excessive number of compounds being tested and reported in the literature we hope that this review can provide useful and updated consolidated information on potential drugs used to prevent, control and treat COVID-19 patients worldwide.", "qid": 33, "docid": "rirzes0m", "rank": 24, "score": 0.7377135753631592}, {"content": "Title: Comprehensive overview of COVID-19 clinical trials. Content: Here, we present an overview of the clinical trials that are currently being conducted or have concluded to date on COVID-19 globally. A comprehensive search was conducted to present 16 trial registries from around the world. Collectively, there are 1,528 trials reported for COVID-19 to date. Out of them, 50 studies included paediatric age group from day 0 to less than or equal to 18 years of age. A few 18 studies involve only females and 20 only males. There are 2 trials currently underway in Bangladesh, 4 in Pakistan and 13 in India. Overall, 940 trials are related to medicines and/or interventions. They include standard of care for any viral illness, antivirals, anti-inflammatory and immune altering medications. Two out of 10 vaccine trials are novel vaccines. It is knowledgeable and resourceful to reach out to the concerned sponsor if a physician thinks his patient can benefit from the trials in the region.", "qid": 33, "docid": "fti60hts", "rank": 25, "score": 0.7365595102310181}, {"content": "Title: Comprehensive overview of COVID-19 clinical trials Content: Here, we present an overview of the clinical trials that are currently being conducted or have concluded to date on COVID-19 globally. A comprehensive search was conducted to present 16 trial registries from around the world. Collectively, there are 1,528 trials reported for COVID-19 to date. Out of them, 50 studies included paediatric age group from day 0 to less than or equal to 18 years of age. A few 18 studies involve only females and 20 only males. There are 2 trials currently underway in Bangladesh, 4 in Pakistan and 13 in India. Overall, 940 trials are related to medicines and/or interventions. They include standard of care for any viral illness, antivirals, anti-inflammatory and immune altering medications. Two out of 10 vaccine trials are novel vaccines. It is knowledgeable and resourceful to reach out to the concerned sponsor if a physician thinks his patient can benefit from the trials in the region.", "qid": 33, "docid": "7nm7s0l5", "rank": 26, "score": 0.7365594506263733}, {"content": "Title: Validation and performance of a quantitative IgG assay for the screening of SARS-CoV-2 antibodies Content: The current COVID-19 epidemic imposed an unpreceded challenge to the scientific community in terms of treatment, epidemiology, diagnosis, social interaction, fiscal policies and many other areas. The development of accurate and reliable diagnostic tools (high specificity and sensitivity) is crucial in the current period, the near future and in the long term. These assays should provide guidance to identify immune presumptive protected persons, potential plasma, and/or B cell donors and vaccine development among others. Also, such assays will be contributory in supporting prospective and retrospective studies to identify the prevalence and incidence of COVID-19 and to characterize the dynamics of the immune response. As of today, only thirteen serological assays have received the Emergency Use Authorization (EUA) by the U.S. Federal Drug Administration (FDA). In this work we describe the development and validation of a quantitative IgG enzyme-linked immunoassay (ELISA) using the recombinant SARS-CoV-2 Spike Protein S1 domain, containing the receptor-binding domain (RBD), showing 98% sensitivity and 98.9% specificity. The assay showed to be useful to test for SARS-CoV-2 IgG antibodies in plasma samples from COVID-19-recovered subjects as potential donors for plasmapheresis. This assay is currently under review by the Federal Drug Administration for an Emergency Use Authorization request (Submission Number EUA201115).", "qid": 33, "docid": "sxfrjs58", "rank": 27, "score": 0.735458493232727}, {"content": "Title: Vaccines and Drug Therapeutics to Lock Down Novel Coronavirus Disease 2019 (COVID-19): A Systematic Review of Clinical Trials Content: The ongoing novel coronavirus disease 2019 (COVID-19) pandemic has been responsible for millions of infections and hundreds of thousands of deaths. To date, there is no approved targeted treatment, and many investigational therapeutic agents and vaccine candidates are being considered for the treatment of COVID-19. To extract and summarize information on potential vaccines and therapeutic agents against COVID-19 at different stages of clinical trials from January to March 2020, we reviewed major clinical trial databases such as ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP), and other primary registries between January and March 15, 2020. Interventional studies at different phases under the COVID-19 pipeline were included. A total of 249 clinical trials were identified between January to March 15, 2020. After filtering observational studies (194 studies), a total of 56 interventional trials were considered. The majority of clinical trials have been conducted on chloroquine (n=10) and traditional Chinese medications (TCMs; n=10), followed by antivirals (n=8), anti-inflammatory/immunosuppressants (n=9), cellular therapies (n=4), combinations of different antivirals therapies (n=3), antibacterial (n=1), and other therapies (n=5). Five vaccines are under phase I, and there are a couple of phase III trials on the Bacillus Calmette-Gu\u00e9rin (BCG) vaccine under investigation among healthcare workers. Many novel compounds and vaccines against COVID-19 are currently under investigation. Some candidates have been tested for other viral infections and are listed for clinical trials against the COVID-19 pipeline. Currently, there are no effective specific antivirals or drug combinations available for the treatment of COVID-19.", "qid": 33, "docid": "p36zubnf", "rank": 28, "score": 0.7352535128593445}, {"content": "Title: Progress and Challenges in the Development of COVID-19 Vaccines and Current Understanding of SARS-CoV-2- Specific Immune Responses Content: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading globally, and the WHO has declared this outbreak a pandemic. Vaccines are an effective way to prevent the rapid spread of COVID-19. Furthermore, the immune response against SARS-CoV-2 infection needs to be understood for the development of an efficient and safe vaccine. Here, we review the current understanding of vaccine targets and the status of vaccine development for COVID-19. We also describe host immune responses to highly pathogenic human coronaviruses in terms of innate and adaptive immunities.", "qid": 33, "docid": "pc7efh1v", "rank": 29, "score": 0.7332155704498291}, {"content": "Title: Progress and Challenges in the Development of COVID-19 Vaccines and Current Understanding of SARS-CoV-2- Specific Immune Responses. Content: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading globally, and the WHO has declared this outbreak a pandemic. Vaccines are an effective way to prevent the rapid spread of COVID-19. Furthermore, the immune response against SARS-CoV-2 infection needs to be understood for the development of an efficient and safe vaccine. Here, we review the current understanding of vaccine targets and the status of vaccine development for COVID-19. We also describe host immune responses to highly pathogenic human coronaviruses in terms of innate and adaptive immunities.", "qid": 33, "docid": "m7yii8el", "rank": 30, "score": 0.7332155704498291}, {"content": "Title: Emerging manufacturers engagements in the COVID -19 vaccine research, development and supply Content: The World Health Organization declared the COVID-19 disease as a pandemic requiring a rapid response. Through online search, direct communication with network members and an internal survey, engagements of developing countries' vaccine manufacturers' network members in the research and development of COVID-19 vaccines and their capacities in the manufacturing, fill-finish and distribution of vaccines were assessed. Currently, 19 network members engaged in research and development of COVID-19 vaccines, using six principal technology platforms. In addition, an internal survey showed that the number of vaccines supplied collectively by 37 members, in 2018-19, was about 3.5 billion doses annually. Almost a third of network members having vaccines prequalified by the World Health Organization comply with international regulations and mechanisms to distribute vaccines across borders. The use of existing manufacturing, fill-finish and distribution capabilities can support an efficient roll-out of vaccines against COVID-19, while maintaining supply security of existing vaccines for on-going immunization programmes.", "qid": 33, "docid": "jtel5mvt", "rank": 31, "score": 0.7329436540603638}, {"content": "Title: Emerging Manufacturers engagements in the COVID -19 vaccine research, development and supply Content: The World Health Organization declared the COVID-19 disease as a pandemic requiring a rapid response. Through online search, direct communication with network members and an internal survey, engagements of developing countries\u2019 vaccine manufacturers\u2019 network members in the research and development of COVID-19 vaccines and their capacities in the manufacturing, fill-finish and distribution of vaccines were assessed. Currently, 19 network members engaged in research and development of COVID-19 vaccines, using six principal technology platforms. In addition, an internal survey showed that the number of vaccines supplied collectively by 37 members, in 2018-19, was about 3.5 billion doses annually. Almost a third of network members having vaccines prequalified by the World Health Organization comply with international regulations and mechanisms to distribute vaccines across borders. The use of existing manufacturing, fill-finish and distribution capabilities can support an efficient roll-out of vaccines against COVID-19, while maintaining supply security of existing vaccines for on-going immunization programmes.", "qid": 33, "docid": "rtphlwjr", "rank": 32, "score": 0.732937216758728}, {"content": "Title: Low-Cost and High-Throughput Testing of COVID-19 Viruses and Antibodies via Compressed Sensing: System Concepts and Computational Experiments Content: Coronavirus disease 2019 (COVID-19) is an ongoing pandemic infectious disease outbreak that has significantly harmed and threatened the health and lives of millions or even billions of people. COVID-19 has also negatively impacted the social and economic activities of many countries significantly. With no approved vaccine available at this moment, extensive testing of COVID-19 viruses in people are essential for disease diagnosis, virus spread confinement, contact tracing, and determining right conditions for people to return to normal economic activities. Identifying people who have antibodies for COVID-19 can also help select persons who are suitable for undertaking certain essential activities or returning to workforce. However, the throughputs of current testing technologies for COVID-19 viruses and antibodies are often quite limited, which are not sufficient for dealing with COVID-19 viruses' anticipated fast oscillating waves of spread affecting a significant portion of the earth's population. In this paper, we propose to use compressed sensing (group testing can be seen as a special case of compressed sensing when it is applied to COVID-19 detection) to achieve high-throughput rapid testing of COVID-19 viruses and antibodies, which can potentially provide tens or even more folds of speedup compared with current testing technologies. The proposed compressed sensing system for high-throughput testing can utilize expander graph based compressed sensing matrices developed by us \\cite{Weiyuexpander2007}.", "qid": 33, "docid": "5t38x587", "rank": 33, "score": 0.7324026823043823}, {"content": "Title: COVID\u201019 vaccines: knowing the unknown Content: Vaccine development against SARS\u2010CoV\u20102 has drawn attention around the globe due to the exploding pandemic. Although COVID\u201019 is caused by a new coronavirus, SARS\u2010CoV\u20102, previous research on other coronavirus vaccines, such as FIPV, SARS and MERS, has provided valuable information for the rapid development of COVID\u201019 vaccine. However, important knowledge gaps remain \u2013 some are specific to SARS\u2010CoV\u20102, others are fundamental to immunology and vaccinology. Here we discuss areas that need to be addressed for COVID\u201019 vaccine development, and what can be learned from examples of vaccine development in the past. Since the beginning of the outbreak, the research progress on COVID\u201019 has been remarkable. We are therefore optimistic about the rapid development of COVID\u201019 vaccine. This article is protected by copyright. All rights reserved", "qid": 33, "docid": "tdvb0fhv", "rank": 34, "score": 0.7312705516815186}, {"content": "Title: The SARS-CoV-2 Vaccine Pipeline: an Overview Content: Purpose of Review: The goal of this review is to provide a timely overview on efforts to develop a vaccine for the 2019 novel coronavirus SARS-CoV-2, the causative agent of coronavirus disease (COVID-19). Recent Findings: Previous research efforts to develop a severe acute respiratory syndrome coronavirus (SARS-CoV) vaccine in the years following the 2003 pandemic have opened the door for investigators to design vaccine concepts and approaches for the COVID-19 epidemic in China. Both SARS-CoV and SARS-CoV-2 exhibit a high degree of genetic similarity and bind to the same host cell ACE2 receptor. Based on previous experience with SARS-CoV vaccines, it is expected that all COVID-19 vaccines will require careful safety evaluations for immunopotentiation that could lead to increased infectivity or eosinophilic infiltration. Besides this, a COVID-19 vaccine target product profile must address vaccinating at-risk human populations including frontline healthcare workers, individuals over the age of 60, and those with underlying and debilitating chronic conditions. Among the vaccine technologies under evaluation are whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines. Summary: Each current vaccine strategy has distinct advantages and disadvantages. Therefore, it is paramount that multiple strategies be advanced quickly and then evaluated for safety and efficacy. Ultimately, the safety studies to minimize undesired immunopotentiation will become the most significant bottleneck in terms of time.", "qid": 33, "docid": "7jsponjx", "rank": 35, "score": 0.7311906814575195}, {"content": "Title: The SARS-CoV-2 Vaccine Pipeline: an Overview Content: PURPOSE OF REVIEW: The goal of this review is to provide a timely overview on efforts to develop a vaccine for the 2019 novel coronavirus SARS-CoV-2, the causative agent of coronavirus disease (COVID-19). RECENT FINDINGS: Previous research efforts to develop a severe acute respiratory syndrome coronavirus (SARS-CoV) vaccine in the years following the 2003 pandemic have opened the door for investigators to design vaccine concepts and approaches for the COVID-19 epidemic in China. Both SARS-CoV and SARS-CoV-2 exhibit a high degree of genetic similarity and bind to the same host cell ACE2 receptor. Based on previous experience with SARS-CoV vaccines, it is expected that all COVID-19 vaccines will require careful safety evaluations for immunopotentiation that could lead to increased infectivity or eosinophilic infiltration. Besides this, a COVID-19 vaccine target product profile must address vaccinating at-risk human populations including frontline healthcare workers, individuals over the age of 60, and those with underlying and debilitating chronic conditions. Among the vaccine technologies under evaluation are whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines. SUMMARY: Each current vaccine strategy has distinct advantages and disadvantages. Therefore, it is paramount that multiple strategies be advanced quickly and then evaluated for safety and efficacy. Ultimately, the safety studies to minimize undesired immunopotentiation will become the most significant bottleneck in terms of time.", "qid": 33, "docid": "rl2qxd03", "rank": 36, "score": 0.73119056224823}, {"content": "Title: A Review of Potential Antiviral Drugs and Vaccines to Treat COVID-19 Content: Coronavirus disease 19 (COVID-19) is a challenge to the whole humanity COVID-19 was first reported in China and rigorous researches are going on for developing vaccine for the pandemic This review was prepared by following PRISMA guidelines and used the resources from the Web of Science and PubMed This research focuses on the niches of symptoms and vaccines for COVID-19 The research for vaccine involves research for new vaccine and drug repurposing Out of various drug repurposing options, Remdesivir, and Favipiravir, Chloroquine and Lopinavir/Ritonavir were found to be the popular ones for treating COVID-19 patients across the world Even though there are concerns regarding asymptotic patients, the most dominant symptoms of COVID-19 are fever and cough, followed by Dyspnoea and muscle ache This review concludes that the COVID-19 related research should focus on developing immunity vaccines, and repurposing of drugs Research on the problems of quarantine life, patient monitoring, and usage of information technology in facing COVID-19 will improve the quality of patient handling during the pandemic The research on the effectiveness of various models of lockdown and regulation of social life during lockdown periods, improving the safety of health care workers in the workplace will definitely help the governments in their fight against COVID-19", "qid": 33, "docid": "shm1y5r1", "rank": 37, "score": 0.7310804724693298}, {"content": "Title: Animal Model Prescreening: Pre-exposure to SARS-CoV-2 impacts responses in the NHP model Content: COVID-19 presents herculean challenges to research and scientific communities for producing diagnostic and treatment solutions. Any return to normalcy requires rapid development of countermeasures, with animal models serving as a critical tool in testing vaccines and therapeutics. Animal disease status and potential COVID-19 exposure prior to study execution may severely bias efficacy testing. We developed a toolbox of immunological and molecular tests to monitor countermeasure impact on disease outcome and evaluate pre-challenge COVID-19 status. Assay application showed critical necessity for animal pre-screening. Specifically, real-time PCR results documented pre-exposure of an African Green Monkey prior to SARS-CoV-2 challenge with sequence confirmation as a community-acquired exposure. Longitudinal monitoring of nasopharyngeal swabs and serum showed pre-exposure impacted both viral disease course and resulting immunological response. This study demonstrates utility in a comprehensive pre-screening strategy for animal models, which captured the first documented case of community-acquired, non-human primate infection. One Sentence Summary Pre-exposure to SARS-CoV-2 affects biomarker responses in animal models, highlighting a need for robust pre-screening protocols prior to medical countermeasure studies.", "qid": 33, "docid": "rbt84zet", "rank": 38, "score": 0.7298799753189087}, {"content": "Title: On setting expectations for a SARS-CoV-2 Vaccine Content: The global coronavirus pandemic is unlike any other since 1918. A century of dramatic medical advances has produced a public expectation that the medical field will rapidly provide solutions to restore normalcy. In under 6 months, since SARS-CoV-2 was identified, the massive international effort to develop a SARS-CoV-2 vaccine has generated more than 140 vaccines in different stages of development with 9 already recruiting into clinical trials posted on clinicaltrials.gov. The long-term strategy to handle COVID-19 will almost certainly rely on vaccines. But, what type of protection can we realistically expect to achieve from vaccines and when?", "qid": 33, "docid": "7lk8h93q", "rank": 39, "score": 0.728922426700592}, {"content": "Title: COVID-19 vaccine development and the way forward Content: The whole globe is reeling under the COVID-19 pandemic now. With the scale and severity of infection, number of deaths and lack of any definite therapeutic armamentarium, the vaccine development has been accelerated at a never-before pace. A wide variety of vaccine technologies and platforms are being attempted. Out of the over 108 efforts, 100 are in preclinical and eight in Phase 1 or 2 trial stage. While the availability of newer technologies has facilitated development, there are several challenges on the way including limited understanding of the pathophysiology, targeting humoral or mucosal immunity, lack of suitable animal model, poor success of human severe acute respiratory syndrome/Middle East Respiratory Syndrome vaccines, limited efficacy of influenza vaccines, and immune exaggeration with animal coronavirus vaccines. With the current scenario with political, funding, research, and regulatory supports, if everything sails through smoothly, the successful vaccine is expected in 12-18 months. Modestly efficacious vaccine may be also a good achievement.", "qid": 33, "docid": "8boyzwxf", "rank": 40, "score": 0.7282086610794067}, {"content": "Title: COVID-19 vaccine development and the way forward. Content: The whole globe is reeling under the COVID-19 pandemic now. With the scale and severity of infection, number of deaths and lack of any definite therapeutic armamentarium, the vaccine development has been accelerated at a never-before pace. A wide variety of vaccine technologies and platforms are being attempted. Out of the over 108 efforts, 100 are in preclinical and eight in Phase 1 or 2 trial stage. While the availability of newer technologies has facilitated development, there are several challenges on the way including limited understanding of the pathophysiology, targeting humoral or mucosal immunity, lack of suitable animal model, poor success of human severe acute respiratory syndrome/Middle East Respiratory Syndrome vaccines, limited efficacy of influenza vaccines, and immune exaggeration with animal coronavirus vaccines. With the current scenario with political, funding, research, and regulatory supports, if everything sails through smoothly, the successful vaccine is expected in 12-18 months. Modestly efficacious vaccine may be also a good achievement.", "qid": 33, "docid": "d51wognj", "rank": 41, "score": 0.7282086610794067}, {"content": "Title: Why Challenge Trials of SARS\u2010CoV\u20102 Vaccines Could Be Ethical Despite Risk of Severe Adverse Events Content: Human challenge trials to test the efficacy of vaccine candidates against SARS\u2010CoV\u20102, the novel coronavirus behind Covid\u201019, could save considerable time and many lives. But they may initially seem unethical because they expose healthy volunteers to a live virus that is killing many people and for which no cure exists. This article argues that this is not the correct test of their ethics. The correct test is comparative. And in the special circumstances of the Covid\u201019 pandemic, human challenge trials meet the correct test better than standard efficacy testing would.", "qid": 33, "docid": "3059lhea", "rank": 42, "score": 0.7277858257293701}, {"content": "Title: Vaccines against Coronaviruses: The State of the Art Content: The emerging epidemic caused by the new coronavirus SARS-CoV-2 represents the most important socio-health threat of the 21st century. The high contagiousness of the virus, the strong impact on the health system of the various countries and the absence to date of treatments able to improve the prognosis of the disease make the introduction of a vaccine indispensable, even though there are currently no approved human coronavirus vaccines. The aim of the study is to carry out a review of the medical literature concerning vaccine candidates for the main coronaviruses responsible for human epidemics, including recent advances in the development of a vaccine against COVID-19. This extensive review carried out on the vaccine candidates of the main epidemic coronaviruses of the past has shown that the studies in animal models suggest a high efficacy of potential vaccines in providing protection against viral challenges. Similar human studies have not yet been carried out, as the main trials are aimed at assessing mainly vaccine safety and immunogenicity. Whereas the severe acute respiratory syndrome (SARS-CoV) epidemic ended almost two decades ago and the Middle East respiratory syndrome (MERS-CoV) epidemic is now better controlled, as it is less contagious due to the high lethality of the virus, the current SARS-CoV-2 pandemic represents a problem that is certainly more compelling, which pushes us to accelerate the studies not only for the production of vaccines but also for innovative pharmacological treatments. SARS-CoV-2 vaccines might come too late to affect the first wave of this pandemic, but they might be useful if additional subsequent waves occur or in a post-pandemic perspective in which the virus continues to circulate as a seasonal virus.", "qid": 33, "docid": "x5zvwtj7", "rank": 43, "score": 0.7273827791213989}, {"content": "Title: Vaccines against Coronaviruses: The State of the Art. Content: The emerging epidemic caused by the new coronavirus SARS-CoV-2 represents the most important socio-health threat of the 21st century. The high contagiousness of the virus, the strong impact on the health system of the various countries and the absence to date of treatments able to improve the prognosis of the disease make the introduction of a vaccine indispensable, even though there are currently no approved human coronavirus vaccines. The aim of the study is to carry out a review of the medical literature concerning vaccine candidates for the main coronaviruses responsible for human epidemics, including recent advances in the development of a vaccine against COVID-19. This extensive review carried out on the vaccine candidates of the main epidemic coronaviruses of the past has shown that the studies in animal models suggest a high efficacy of potential vaccines in providing protection against viral challenges. Similar human studies have not yet been carried out, as the main trials are aimed at assessing mainly vaccine safety and immunogenicity. Whereas the severe acute respiratory syndrome (SARS-CoV) epidemic ended almost two decades ago and the Middle East respiratory syndrome (MERS-CoV) epidemic is now better controlled, as it is less contagious due to the high lethality of the virus, the current SARS-CoV-2 pandemic represents a problem that is certainly more compelling, which pushes us to accelerate the studies not only for the production of vaccines but also for innovative pharmacological treatments. SARS-CoV-2 vaccines might come too late to affect the first wave of this pandemic, but they might be useful if additional subsequent waves occur or in a post-pandemic perspective in which the virus continues to circulate as a seasonal virus.", "qid": 33, "docid": "zi1l5883", "rank": 44, "score": 0.7273827791213989}, {"content": "Title: Current Status of Treatment Options, Clinical Trials, and Vaccine Development for SARS-CoV-2 Infection Content: The severe acute respiratory syndrome virus (SARS-CoV-2), a novel coronavirus first discovered in Wuhan, China in December 2019 causes the Coronavirus Disease 19 (COVID-19), which presents with a wide range of clinical symptoms from mild or moderate to severe and critical illnesses With the continuing transmission of the virus worldwide and the rapidly evolving situation globally, the World Health Organization (WHO) declared the COVID-19 outbreak a pandemic in March Currently, there is no proven specific treatment for this potentially deadly disease beyond supportive care However, a massive effort has been put globally into the investigation of medications and other interventional measures to fight COVID-19 Convalescent plasma therapy from recovered patients has recently drawn considerable interest Several alternative medical treatments, although evidence of their efficacy still lacking, have also gained popularity, especially in countries with such traditions such as India and China Rapid repurposing of drugs for COVID-19 has revealed a few promising candidate antiviral agents, but further research, especially high quality randomized controlled trials, will be needed to prove their efficacy and safety in the clinical use to treat COVID-19 Vaccine development has been the imperative task in the battle against SARS-CoV-2 While clinical trials have been launched for several candidate vaccines, research on COVID-19 vaccines is still at an early stage So far, optimized supportive care remains the best practice against COVID-19", "qid": 33, "docid": "0j5bg59c", "rank": 45, "score": 0.7271885871887207}, {"content": "Title: Generation of antibodies against COVID-19 virus for development of diagnostic tools Content: The COVID-19 China coronavirus started in Dec 2019 was challenged by the lack of accurate serological diagnostic tool for this deadly disease to quickly identify and isolate the infected patients. The generation of COVID-19-specific antibodies is essential for such tasks. Here we report that polyclonal and monoclonal antibodies were generated by immunizing animals with synthetic peptides corresponding to different areas of Nucleoprotein (N) of COVID-19. The specificities of the COVID-19 antibodies were assessed by Western Blot analysis against NPs from COVID-19, MERS and SARS. Antibodies were used for immunohistochemistry staining of the tissue sections from COVID-19 infected patient, as a potential diagnostic tool. A Sandwich ELISA kit was quickly assembled for quantitation of the virus/NP of COVID-19 concentrations in the vaccine preparations. Development of POCT is also aggressively undergoing.", "qid": 33, "docid": "1s0exznp", "rank": 46, "score": 0.7263708114624023}, {"content": "Title: Operationalizing COVID-19 testing: Who, what, when, where, why, and how Content: The authors review the rationale behind and approaches to testing for COVID-19, the quality of currently available tests, the role of data analytics in strategizing testing, and using the electronic medical record and other programs designed to steward COVID-19 testing and follow-up of patients.", "qid": 33, "docid": "4zb3dfja", "rank": 47, "score": 0.7259478569030762}, {"content": "Title: Operationalizing COVID-19 testing: Who, what, when, where, why, and how. Content: The authors review the rationale behind and approaches to testing for COVID-19, the quality of currently available tests, the role of data analytics in strategizing testing, and using the electronic medical record and other programs designed to steward COVID-19 testing and follow-up of patients.", "qid": 33, "docid": "09acb1kl", "rank": 48, "score": 0.7259478569030762}, {"content": "Title: Defining Protective Epitopes for COVID\u201019 Vaccination Models Content: Recent papers in the Journal provide tangible avenues for COVID\u201019 vaccine production as immunoreactive epitopes are brought to the forefront in these and many other emerging studies.(1,2) The development of a consistent predictable animal model of COVID\u201019 infection is evidently also a welcome event for preliminary antiviral and vaccine assessments and surely brings us to another level of progression.(3) This article is protected by copyright. All rights reserved.", "qid": 33, "docid": "77mw0dws", "rank": 49, "score": 0.7244264483451843}, {"content": "Title: Another Set of Coronavirus Vaccine Candidates Content: I surveyed the coronavirus vaccine landscape in this post, and then detailed some of the larger efforts in the field here (several updates have been added to that one since its initial posting) Now it\u2019s time to look at several programs that aren\u2019t in either of those, but still have plenty of serious science behind them For an example of a relatively new technology that\u2019s now in use for human patients, there\u2019s the VSV (vesicular stomatitis virus) platform, which was used to produce the Ebola vaccine now manufactured by Merck Stat has an excellent long-form article from earlier this year about how this came about, and it\u2019s well worth a read, both for the history itself and as a look into the ups and downs of vaccine research in general The Yale team behind that one had developed a promising vaccine candidate for the SARS coronavirus during its epidemic, and they\u2019re using those lessons in their current work If you look at that second link above on vaccine candidates, you will note that there are several using adenovirus vectors \u2013 this is conceptually the same sort of thing, but using a livestock virus (VSV) instead of human or primate-associated adenoviruses I don\u2019t know if the Yale team has partnered with anyone yet, but I should also mention another connection of theirs, a spinoff company called CaroGen that has another engineered virus platform that is also being put to use against SARS-CoV-2 These projects are aiming at FDA approval for Phase I trials, but there\u2019s no word yet on what such an application might go in", "qid": 33, "docid": "zwf26o63", "rank": 50, "score": 0.7239404916763306}, {"content": "Title: An evaluation of COVID-19 serological assays informs future diagnostics and exposure assessment Content: The world is entering a new era of the COVID-19 pandemic in which there is an increasing call for reliable antibody testing. To support decision making on the deployment of serology for either population screening or diagnostics, we present a detailed comparison of serological COVID-19 assays. We show that among the selected assays there is a wide diversity in assay performance in different scenarios and when correlated to virus neutralizing antibodies. The Wantai ELISA detecting total immunoglobulins against the receptor binding domain of SARS CoV-2, has the best overall characteristics to detect functional antibodies in different stages and severity of disease, including the potential to set a cut-off indicating the presence of protective antibodies. The large variety of available serological assays requires proper assay validation before deciding on deployment of assays for specific applications.", "qid": 33, "docid": "cv2dg9tg", "rank": 51, "score": 0.7233797907829285}, {"content": "Title: Design of a peptide-based subunit vaccine against novel coronavirus SARS-CoV-2 Content: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. In the absence of any antiviral or immunomodulatory therapies, the disease is spreading at an alarming rate. A possibility of a resurgence of COVID-19 in places where lockdowns have already worked is also developing. Thus, for controlling COVID-19, vaccines may be a better option than drugs. An mRNA-based anti-COVID-19 candidate vaccine has entered a phase 1 clinical trial. However, its efficacy and potency have to be evaluated and validated. Since vaccines have high failure rates, as an alternative, we are presenting a new, designed multi-peptide subunit-based epitope vaccine against COVID-19. The recombinant vaccine construct comprises an adjuvant, cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes joined by linkers. The computational data suggest that the vaccine is non-toxic, non-allergenic, thermostable, with the capability to elicit a humoral and cell-mediated immune response. The stabilization of the vaccine construct is validated with molecular dynamics simulation studies. This unique vaccine is made up of 33 highly antigenic epitopes from three proteins that have a prominent role in host-receptor recognition, viral entry, and pathogenicity. We advocate this vaccine must be synthesized and tested urgently as a public health priority.", "qid": 33, "docid": "8lktpcda", "rank": 52, "score": 0.722951352596283}, {"content": "Title: Towards Precision Medicine: Inclusion of Sex and Gender Aspects in COVID-19 Clinical Studies-Acting Now before It Is Too Late-A Joint Call for Action Content: The COVID-19 global pandemic is accelerating investigations for effective vaccines and repurposable validated therapeutics [...].", "qid": 33, "docid": "bfg81ha7", "rank": 53, "score": 0.7226762771606445}, {"content": "Title: Towards Precision Medicine: Inclusion of Sex and Gender Aspects in COVID-19 Clinical Studies\u2014Acting Now before It Is Too Late\u2014A Joint Call for Action Content: The COVID-19 global pandemic is accelerating investigations for effective vaccines and repurposable validated therapeutics [...].", "qid": 33, "docid": "ivpa40zg", "rank": 54, "score": 0.7226762175559998}, {"content": "Title: Current global vaccine and drug efforts against COVID-19: Pros and cons of bypassing animal trials Content: COVID-19 has become one of the biggest health concern, along with huge economic burden. With no clear remedies to treat the disease, doctors are repurposing drugs like chloroquine and remdesivir to treat COVID-19 patients. In parallel, research institutes in collaboration with biotech companies have identified strategies to use viral proteins as vaccine candidates for COVID-19. Although this looks promising, they still need to pass the test of challenge studies in animal models. As various models for SARS-CoV-2 are under testing phase, biotech companies have bypassed animal studies and moved to Phase I clinical trials. In view of the present outbreak, this looks a justified approach, but the problem is that in the absence of animal studies, we can never predict the outcomes in humans. Since animal models are critical for vaccine development and SARS-CoV-2 has different transmission dynamics, in this review we compare different animal models of SARS-CoV-2 with humans for their pathogenic, immune response and transmission dynamics that make them ideal models for vaccine testing for COVID-19. Another issue of using animal model is the ethics of using animals for research; thus, we also discuss the pros and cons of using animals for vaccine development studies.", "qid": 33, "docid": "3sepefqa", "rank": 55, "score": 0.720883846282959}, {"content": "Title: Current global vaccine and drug efforts against COVID-19: Pros and cons of bypassing animal trials. Content: COVID-19 has become one of the biggest health concern, along with huge economic burden. With no clear remedies to treat the disease, doctors are repurposing drugs like chloroquine and remdesivir to treat COVID-19 patients. In parallel, research institutes in collaboration with biotech companies have identified strategies to use viral proteins as vaccine candidates for COVID-19. Although this looks promising, they still need to pass the test of challenge studies in animal models. As various models for SARS-CoV-2 are under testing phase, biotech companies have bypassed animal studies and moved to Phase I clinical trials. In view of the present outbreak, this looks a justified approach, but the problem is that in the absence of animal studies, we can never predict the outcomes in humans. Since animal models are critical for vaccine development and SARS-CoV-2 has different transmission dynamics, in this review we compare different animal models of SARS-CoV-2 with humans for their pathogenic, immune response and transmission dynamics that make them ideal models for vaccine testing for COVID-19. Another issue of using animal model is the ethics of using animals for research; thus, we also discuss the pros and cons of using animals for vaccine development studies.", "qid": 33, "docid": "oa8vzf02", "rank": 56, "score": 0.720883846282959}, {"content": "Title: SARS-CoV-2 assays to detect functional antibody responses that block ACE2 recognition in vaccinated animals and infected patients Content: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has caused a global pandemic of COVID-19 resulting in cases of mild to severe respiratory distress and significant mortality. The global outbreak of this novel coronavirus has now infected >8 million people worldwide with >2 million cases in the US (June 17th, 2020). There is an urgent need for vaccines and therapeutics to combat the spread of this coronavirus. Similarly, the development of diagnostic and research tools to determine infection and vaccine efficacy are critically needed. Molecular assays have been developed to determine viral genetic material present in patients. Serological assays have been developed to determine humoral responses to the spike protein or receptor binding domain (RBD). Detection of functional antibodies can be accomplished through neutralization of live SARS-CoV2 virus, but requires significant expertise, an infectible stable cell line, a specialized BioSafety Level 3 (BSL-3) facility. As large numbers of people return from quarantine, it is critical to have rapid diagnostics that can be widely adopted and employed to assess functional antibody levels in the returning workforce. This type of surrogate neutralization diagnostic can also be used to assess humoral immune responses induced in patients from the large number of vaccine and immunotherapy trials currently on-going. Here we describe a rapid serological diagnostic assay for determining antibody receptor blocking and demonstrate the broad utility of the assay by measuring the antibody functionality of sera from small animals and non-human primates immunized with an experimental SARS-CoV-2 vaccine and using sera from infected patients.", "qid": 33, "docid": "qpbgq5d8", "rank": 57, "score": 0.7208546996116638}, {"content": "Title: A Snapshot of the Global Race for Vaccines Targeting SARS-CoV-2 and the COVID-19 Pandemic Content: A novel coronavirus SARS-CoV-2 causing Coronavirus disease 2019 (COVID-19) has entered the human population and has spread rapidly around the world in the first half of 2020 causing a global pandemic. The virus uses its spike glycoprotein receptor-binding domain to interact with host cell angiotensin-converting enzyme 2 (ACE2) sites to initiate a cascade of events that culminate in severe acute respiratory syndrome in some individuals. In efforts to curtail viral spread, authorities initiated far-reaching lockdowns that have disrupted global economies. The scientific and medical communities are mounting serious efforts to limit this pandemic and subsequent waves of viral spread by developing preventative vaccines and repurposing existing drugs as potential therapies. In this review, we focus on the latest developments in COVID-19 vaccine development, including results of the first Phase I clinical trials and describe a number of the early candidates that are emerging in the field. We seek to provide a balanced coverage of the seven main platforms used in vaccine development that will lead to a desired target product profile for the \u201cideal\u201d vaccine. Using tales of past vaccine discovery efforts that have taken many years or that have failed, we temper over exuberant enthusiasm with cautious optimism that the global medical community will reach the elusive target to treat COVID-19 and end the pandemic.", "qid": 33, "docid": "ozdwkkqn", "rank": 58, "score": 0.7203090190887451}, {"content": "Title: BCG vaccination strategy implemented to reduce the impact of COVID-19: Hype or Hope? Content: Abstract The Bacillus Calmette-Guerin vaccine (BCG vaccine) designed to prevent tuberculosis in children has been shown to induce a adaptive immune response in the body to fight against bacteria as well as other parasites and viruses. This knowledge has been reciprocated to generate the idea that this vaccine can also offer protection against severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). Some recent pre-print articles have highlighted that countries with mass BCG immunizations seems to have a lower incidence of coronavirus disease 2019 (COVID-19) compared to those without BCG immunization. There are yet no experimental proof of any such association and the world health organisation (WHO) is currently testing the theory with clinical trials on selected cohorts. Epidemiologists and other scientific experts has expressed both their hope and concern simultaneously regarding the success theory of BCG vaccination to prevent COVID-19. Though its still not verified in any way whether the BCG vaccination can actually prevent COVID-19 or not but we believe a thorough analytical research in this regard is indeed worth a shot.", "qid": 33, "docid": "3n1y7hjw", "rank": 59, "score": 0.7202147245407104}, {"content": "Title: Laboratory Tests for COVID-19: A Review of Peer-Reviewed Publications and Implications for Clinical UIse. Content: Diagnostic tests for the coronavirus infection 2019 (COVID-19) are critical for prompt diagnosis, treatment and isolation to break the cycle of transmission. A positive real-time reverse-transcriptase polymerase chain reaction (RT-PCR), in conjunction with clinical and epidemiologic data, is the current standard for diagnosis, but several challenges still exist. Serological assays help to understand epidemiology better and to evaluate vaccine responses but they are unreliable for diagnosis in the acute phase of illness or assuming protective immunity. Serology is gaining attention, mainly because of convalescent plasma gaining importance as treatment for clinically worsening COVID-19 patients. We provide a narrative review of peer-reviewed research studies on RT-PCR, serology and antigen immune-assays for COVID-19, briefly describe their lab methods and discuss their limitations for clinical practice.", "qid": 33, "docid": "ey34e59f", "rank": 60, "score": 0.7199735641479492}, {"content": "Title: [At least 68 vaccine candidates under development]. Content: The development of vaccines against SARS-CoV-2 is progressing at an unparalleled speed. As of the 29th of March, there were at least 68 vaccine candidates comprising several different vaccine designs, including whole killed virus, subunit, attenuated, viral vector, DNA and mRNA vaccines. Whilst it usually takes 10-15 years to develop a vaccine, it has only taken just over 9 weeks from the publication of the viral genetic sequence for the first vaccine candidate to reach clinical testing. Development has been expediated by using existing technological platforms and by performing preclinical and clinical testing simultaneously.", "qid": 33, "docid": "l9l6z1o0", "rank": 61, "score": 0.7194938659667969}, {"content": "Title: Analysis of SARS-CoV-2 Antibodies in COVID-19 Convalescent Plasma using a Coronavirus Antigen Microarray Content: The current practice for diagnosis of COVID-19, based on SARS-CoV-2 PCR testing of pharyngeal or respiratory specimens in a symptomatic patient at high epidemiologic risk, likely underestimates the true prevalence of infection. Serologic methods can more accurately estimate the disease burden by detecting infections missed by the limited testing performed to date. Here, we describe the validation of a coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2, in addition to SARS-CoV, MERS-CoV, common human coronavirus strains, and other common respiratory viruses. A comparison of antibody profiles detected on the array from control sera collected prior to the SARS-CoV-2 pandemic versus convalescent blood specimens from virologically confirmed COVID-19 cases demonstrates complete discrimination of these two groups. This array can be used as a diagnostic tool, as an epidemiologic tool to more accurately estimate the disease burden of COVID-19, and as a research tool to correlate antibody responses with clinical outcomes.", "qid": 33, "docid": "ax9btc74", "rank": 62, "score": 0.7192593812942505}, {"content": "Title: The quest to find an effective vaccine for COVID-19 Content: Professor Alan Glasper, from the University of Southampton, delves into history and discusses the international quest to develop an effective vaccine to tackle COVID-19.", "qid": 33, "docid": "0b6lu043", "rank": 63, "score": 0.7188493013381958}, {"content": "Title: The quest to find an effective vaccine for COVID-19. Content: Professor Alan Glasper, from the University of Southampton, delves into history and discusses the international quest to develop an effective vaccine to tackle COVID-19.", "qid": 33, "docid": "p1h7jlr1", "rank": 64, "score": 0.7188493013381958}, {"content": "Title: Cardiovascular disease due to novel coronavirus and the search for investigational therapies Content: OBJECTIVE: The primary purpose of the study was to investigate and to summarize the registered trials that listed COVID-19 as the primary condition. METHODS: We performed a search on ClinicalTrials.gov using the independent search terms COVID-19, SARS, and SARS-CoV-2 and then downloaded the data file on March 23, 2020. All trials were downloaded to a csv file and searched for appropriateness. RESULTS: Of 124 registered trials, 56 (45.2%) were listed as recruiting. The majority (85 [68.5%]) were classified as interventional, 37 (29.8%) as observational, and one (0.8%) each as either expanded access: individual patients|treatment investigational new drug/protocol or expanded access: intermediate-size population|treatment investigational new drug/protocol. There were 67 (54.0%) trials that listed drug as the type of study. Immunologic and antiviral trials were the most common, representing approximately 30% and 21%, respectively. When immunologic and antiviral drugs were used alone or in combination, they represented 41.9% and 34.4%, respectively. Antimalarial agents are represented in 7.5% of trials. Approximately 14% of trials involved traditional Chinese medicine. The study agents used solely or in combination represented approximately 80% of therapeutic approaches to COVID-19. CONCLUSIONS: There was a large and quick response on ClinicalTrials.gov to the COVID-19 outbreak. Many of the registered trials are currently recruiting new patients, whereas some will begin in the near future. Specific potential experimental therapies, including dosing and monitoring, might be found by reviewing content. Within ClinicalTrials.gov, patients, family members, health care professionals, and researchers can search and find ongoing and future trials for COVID-19.", "qid": 33, "docid": "y6mpjjr2", "rank": 65, "score": 0.7179550528526306}, {"content": "Title: An integrated in silico immuno-genetic analytical platform provides insights into COVID-19 serological and vaccine targets Content: Background The COVID-19 pandemic is causing a major global health and socio-economic burden, instigating the mobilisation of resources into the development of control tools, such as diagnostics and vaccines. The poor performance of some diagnostic serological tools has emphasised the need for up to date immune-informatic analyses to inform the selection of viable targets for further study. This requires the integration and analysis of genetic and immunological data for SARS-CoV-2 and its homology with other human coronavirus species to understand cross-reactivity. Methods We have developed an online tool for SARS-CoV-2 research, which combines an extensive epitope mapping and prediction meta-analysis, with an updated variant database (55,944 non-synonymous mutations) based on 16,087 whole genome sequences, and an analysis of human coronavirus homology. To demonstrate its utility, we present an integrated analysis of the SARS-CoV-2 spike and nucleocapsid proteins, which are candidate vaccine and serological diagnostic targets. Results Our analysis reveals that the nucleocapsid protein in its native form appears to be a sub-optimal target for use in serological diagnostic platforms. Whilst, a further analysis suggests that orf3a proteins may be a suitable alternative target for diagnostic assays. Conclusions The tool can be accessed online (http://genomics.lshtm.ac.uk/immuno) and will serve as a useful tool for biological discovery in the fight against SARS-CoV-2. Further, it may be adapted to inform on biological targets in future outbreaks, including new human coronaviruses that spill over from animal hosts.", "qid": 33, "docid": "0kxo3a4q", "rank": 66, "score": 0.717902421951294}, {"content": "Title: Why We (Probably) Must Deliberately Infect Content: In the grip of a pandemic of proportions that have not been seen for generations, some have proposed conducting \u201chuman challenge\u201d vaccine trials in which healthy volunteers are deliberately infected with the SARS-CoV-2 virus that causes COVID-19. Such trials might substantially speed up the search for a safe and effective vaccine and save many thousands of lives. I argue that such trials are not only permissible, but given reasonable assumptions, they are morally required, subject to some important caveats.", "qid": 33, "docid": "lxi6bi6a", "rank": 67, "score": 0.7178565263748169}, {"content": "Title: Interest in COVID-19 vaccine trials participation among young adults in China: Willingness, reasons for hesitancy, and demographic and psychosocial determinants Content: Background: With the demand for rapid COVID-19 vaccine development and evaluation, this paper aimed to describe the prevalence and correlates of willingness to participate in COVID-19 vaccine trials among university students in China. Methods: A cross-sectional survey with 1,912 Chinese university students was conducted during March and April 2020. Bivariate and multivariate analyses were performed to identify variables associated with willingness to participate. Results: The majority of participants (64.01%) indicated willingness to participate in COVID-19 vaccine trials. Hesitancy over signing informed consent documents, concerns over time necessary for participating in a medical study, and perceived COVID-19 societal stigma were identified as deterrents, whereas lower socioeconomic status, female gender, perception of likely COVID-19 infection during the pandemic, and COVID-19 prosocial behaviors were facilitative factors. Further, public health mistrust and hesitancy over signing informed consent documents had a significant interactive effect on vaccine trial willingness. Conclusions: High standards of ethical and scientific practice are needed in COVID-19 vaccine research, including providing potential participants full and accurate information and ensuring participation free of coercion, socioeconomic inequality, and stigma. Attending to the needs of marginalized groups and addressing psychosocial factors including stigma and public health mistrust may also be important to COVID-19 vaccine development and future uptake.", "qid": 33, "docid": "i20r4hsi", "rank": 68, "score": 0.7176772952079773}, {"content": "Title: SARS-CoV-2 Antibody Testing \u2013 Questions to be asked Content: ABSTRACT SARS-CoV-2 infection and development of COVID-19 disease presents a major healthcare challenge of global dimensions. Laboratory diagnostics of infected patients, and the assessment of immunity against the SARS-CoV-2 virus presents a major cornerstone in handling the pandemic. Currently there is an increase in demand of antibody testing and a large number of tests are already marketed or in the late stage of development. However, the interpretation of test results depends on many variables and factors, including sensitivity, specificity, potential cross-reactivity and cross-protectivity; the diagnostic value of antibodies of different isotypes, the use of antibody testing in identification of acutely ill patients or in epidemiological settings. In this article the recently established COVID-19 Task Force of the German Society for Clinical Chemistry and Laboratory Medicine (DGKL) addresses these issues based on the currently available datasets in this rapidly moving field.", "qid": 33, "docid": "tveeq4fj", "rank": 69, "score": 0.7173926830291748}, {"content": "Title: Disease X ver1.0: COVID-19 Content: The SARS-Cov2 has presented the world with a novel pandemic challenge requiring a rapid response. This article provides a May 2020 snapshot from Professor Paul Young, who is part of a group working with urgency on Australia\u2019s leading COVID-19 candidate vaccine.", "qid": 33, "docid": "4lruc5or", "rank": 70, "score": 0.7172832489013672}, {"content": "Title: COVID-19: How has the scientific community risen to the challenge? Content: As the novel coronavirus SARS-CoV-2 spreads around the world, scientists have raced to develop vaccines and tests in order to curb the infection.", "qid": 33, "docid": "humoykni", "rank": 71, "score": 0.7169252634048462}, {"content": "Title: COVID-19: Learning from Lessons To Guide Treatment and Prevention Interventions Content: Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and first emerged in December 2019 in Wuhan, Hubei province, China. Since then, the virus has rapidly spread to many countries. While the outbreak in China appears to be in decline, the disease has spread across the world, with a daily increase in the number of confirmed cases and infection-related deaths. Here, we highlight (i) the lessons that have been learnt so far and how they will benefit reducing the impact of COVID-19 disease and (ii) an update on the status of drug treatment and vaccine development to prevent COVID-19 and potential future related pandemics. Although the mortality rate is clearly higher than for influenza, the rate does seem to vary from country to country, possibly reflecting differences in how rapidly local health authorities respond to isolate and effectively care for the affected population. Drugs are urgently needed for both prophylaxis and the treatment of severely ill patients; however, no proven effective therapies for SARS-CoV-2 currently exist. A number of drugs that have been approved for other diseases are being tested for the treatment of COVID-19 patients, but there is an absence of data from appropriately designed clinical trials showing that these drugs, either alone or in combination, will prove effective. There is also a global urgency to develop a vaccine against COVID-19, but development and appropriate testing will take at least a year before such a vaccine will be globally available. This review summarizes the lessons learnt so far from the COVID-19 pandemic, examines the evidence regarding the drugs that are being tested for the treatment of COVID19, and describes the progress made in efforts to develop an effective vaccine.", "qid": 33, "docid": "svo94kuo", "rank": 72, "score": 0.7168605327606201}, {"content": "Title: An insight into the epitope-based peptide vaccine design strategy and studies against COVID-19 Content: SARS-CoV-2 is a new member of the coronavirus family and caused the pandemic of coronavirus disease 2019 (COVID-19) in 2020. It is crucial to design and produce an effective vaccine for the prevention of rapid transmission and possible deaths wcaused by the disease. Although intensive work and research are being carried out all over the world to develop a vaccine, an effective and approved formulation that can prevent the infection and limit the outbreak has not been announced yet. Among all types of vaccines, epitope-based peptide vaccines outshine with their low-cost production, easy modification in the structure, and safety. In this review, vaccine studies against COVID-19 have been summarized and detailed information about the epitope-based peptide vaccines against COVID-19 has been provided. We have not only compared the peptide vaccine with other types of vaccines but also presented comprehensive literature information about development steps for an effective and protective formulation to give an insight into on-going peptide vaccine studies against SARS-CoV-2.", "qid": 33, "docid": "j6gn8exx", "rank": 73, "score": 0.7167733907699585}, {"content": "Title: Towards effective COVID-19 vaccines: Updates, perspectives and challenges (Review) Content: In the current context of the pandemic triggered by SARS-COV-2, the immunization of the population through vaccination is recognized as a public health priority. In the case of SARS-COV-2, the genetic sequencing was done quickly, in one month. Since then, worldwide research has focused on obtaining a vaccine. This has a major economic impact because new technological platforms and advanced genetic engineering procedures are required to obtain a COVID-19 vaccine. The most difficult scientific challenge for this future vaccine obtained in the laboratory is the proof of clinical safety and efficacy. The biggest challenge of manufacturing is the construction and validation of production platforms capable of making the vaccine on a large scale.", "qid": 33, "docid": "0o05oskr", "rank": 74, "score": 0.7165387868881226}, {"content": "Title: Review on the global epidemiological situation and the efficacy of chloroquine and hydroxychloroquine for the treatment of COVID-19 Content: Covid-19 disease is caused by SARS-CoV-2, a virus belonging to the coronavirus family. Covid-19 is so new that there is currently no specific vaccine or treatment. Clinical trials are currently underway. In vitro tests are also being conducted to assess the efficacy of chloroquine and hydroxychloroquine for the treatment of this epidemic, which is considered a pandemic by the WHO. We note that the content of this review is dated. The information it contains is subject to change and modification as the epidemic progresses.", "qid": 33, "docid": "wbkn7yjh", "rank": 75, "score": 0.7163020372390747}, {"content": "Title: COVID-19 vaccines: A race against time in the middle of death and devastation! Content: The COVID-19 has turned in to a global human tragedy and economic devastation. Governments have implemented lockdown measures, blocked international travel, and enforced other public containment measures to mitigate the virus morbidity and mortality. As of today, no drug has the power to fight the infection and bring normalcy to the utter chaos. This leaves us with only one choice namely an effective and safe vaccine that shall be manufactured as soon as possible and available to all countries and populations affected by the pandemic at an affordable price. There has been an unprecedented fast track path taken in Research & Development (R&D) by the World community for developing an effective and safe vaccine. Platform technology has been exploited to develop candidate vaccines in a matter of days to weeks and as of now, 108 such vaccines are available. Six of these vaccines have entered clinical trials. As clinical trials are \u2018rate-limiting\u2019 and \u2018time-consuming\u2019, many innovative methods are in practice for a fast track. These include parallel phase I-II trials and obtaining efficacy data from phase IIb trials. Human \u2018challenge experiments\u2019 to confirm efficacy in humans is under serious consideration. The availability of the COVID-19 vaccine has become a race against time in the middle of death and devastation. There is an atmosphere of tremendous hype around the COVID-19 vaccine and developers are using every moment to make claims, which remain unverified. However, concerns are raised about a rush to deploy a COVID-19 vaccine. Applying \u2018Quick fix\u2019 and \u2018short cuts\u2019 can lead to errors with disastrous consequences.", "qid": 33, "docid": "u3ek83tn", "rank": 76, "score": 0.7158269882202148}, {"content": "Title: Determinants of intent to uptake Coronavirus vaccination among respondents in Saudi Arabia: a web-based national survey Content: Background Vaccine hesitancy is a potential threat to global public health. Since, there is an unprecedented global effort to develop a vaccine against the COVID-19 disease much less is known about its acceptance in the community. Understanding key determinants that influence the preferences and demands of a future vaccine by the community may help to develop strategies for improving the global vaccination program. This study aimed to assess the prevalence of the acceptancy of COVID-19 vaccine and their determinants among people in Saudi Arabia. Methods A web-based cross-sectional study was designed using snowball sampling strategies under a highly restricted environment. A bilingual self-administered anonymous questionnaire was designed and send to 1000 study participants through social media platforms and email. Study participants were recruited across the country, including the four major cities (Riyadh, Dammam, Jeddah, and Abha) in Saudi Arabia. Associations between COVID-19 vaccine acceptance and sociodemographic profile of the respondents were explored using the chi-squared test. Key determinants in predicting vaccine acceptancy among respondents were modelled using logistic regression analysis. Results Of the 1000 survey invitees 992 responded to the survey. The majority of the study participants (29.53%) were in the age group (36 to 45 years) and 65.8% were female and 17.9% were Non-Saudi participants. Of the 992 respondents 642 said they are interested in taking the COVID-19 vaccine once it is available. Willingness to accept a future COVID-19 vaccine is relatively high among older age groups (79.2% among 45+ year old), married participants (69.3%), participants with education levels of a postgraduate degree or higher (68.8%), non-Saudi (69.1%), workings with government sector (68.9%). In multivariate model, respondents who were above 45 years (aOR: 2.15; 95% CI: 1.08-3.21), and married (aOR: 1.79; 95% CI: 1.28-2.50) were significantly associated with vaccine acceptance (p < .05). Besides, people having trust in the health system were most likely to accept vaccination (aOR: 3.05; 95% CI: 1.13-4.92).Participants having a higher perceived risk of acquiring infection were 2.13 times higher odds of reporting their intention to uptake the COVID-19 vaccine (aOR: 2.13; 95% CI: 1.35-3.85). Conclusion Addressing sociodemographic determinants relating to the COVID-19 vaccination may help to increase uptake of the global vaccination program to tackle future pandemics. Targeted health education measures are needed among the general population to increase the uptake of the COVID-19 vaccine.", "qid": 33, "docid": "vysb2kr7", "rank": 77, "score": 0.7158129215240479}, {"content": "Title: Mutations on COVID-19 diagnostic targets Content: Effective, sensitive, and reliable diagnostic reagents are of paramount importance for combating the ongoing coronavirus disease 2019 (COVID-19) pandemic at a time there is no preventive vaccine nor specific drug available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It would be an absolute tragedy if currently used diagnostic reagents are undermined in any manner. Based on the genotyping of 7818 SARS-CoV-2 genome samples collected up to May 1, 2020, we reveal that essentially all of the current COVID-19 diagnostic targets have had mutations. We further show that SARS-CoV-2 has the most devastating mutations on the targets of various nucleocapsid (N) gene primers and probes, which have been unfortunately used by countries around the world to diagnose COVID-19. Our findings explain what has seriously gone wrong with a specific diagnostic reagent made in China. To understand whether SARS-CoV-2 genes have mutated unevenly, we have computed the mutation ratio and mutation $h$-index of all SARS-CoV genes, indicating that the N gene is the most non-conservative gene in the SARS-CoV-2 genome. Our findings enable researchers to target the most conservative SARS-CoV-2 genes and proteins for the design and development of COVID-19 diagnostic reagents, preventive vaccines, and therapeutic medicines.", "qid": 33, "docid": "8l7hrany", "rank": 78, "score": 0.715660810470581}, {"content": "Title: Prospects of Replication-Deficient Adenovirus Based Vaccine Development against SARS-CoV-2. Content: The current appearance of the new SARS coronavirus 2 (SARS-CoV-2) and it quickly spreading across the world poses a global health emergency. The serious outbreak position is affecting people worldwide and requires rapid measures to be taken by healthcare systems and governments. Vaccinations represent the most effective strategy to prevent the epidemic of the virus and to further reduce morbidity and mortality with long-lasting effects. Nevertheless, currently there are no licensed vaccines for the novel coronaviruses. Researchers and clinicians from all over the world are advancing the development of a vaccine against novel human SARS-CoV-2 using various approaches. Herein, we aim to present and discuss the progress and prospects in the field of vaccine research towards SARS-CoV-2 using adenovirus (AdV) replication deficient-based strategies, with a comprehension that may support research and combat this recent world health emergency.", "qid": 33, "docid": "gw6po8qg", "rank": 79, "score": 0.715427577495575}, {"content": "Title: Prospects of Replication-Deficient Adenovirus Based Vaccine Development against SARS-CoV-2 Content: The current appearance of the new SARS coronavirus 2 (SARS-CoV-2) and it quickly spreading across the world poses a global health emergency. The serious outbreak position is affecting people worldwide and requires rapid measures to be taken by healthcare systems and governments. Vaccinations represent the most effective strategy to prevent the epidemic of the virus and to further reduce morbidity and mortality with long-lasting effects. Nevertheless, currently there are no licensed vaccines for the novel coronaviruses. Researchers and clinicians from all over the world are advancing the development of a vaccine against novel human SARS-CoV-2 using various approaches. Herein, we aim to present and discuss the progress and prospects in the field of vaccine research towards SARS-CoV-2 using adenovirus (AdV) replication deficient-based strategies, with a comprehension that may support research and combat this recent world health emergency.", "qid": 33, "docid": "cofi4cue", "rank": 80, "score": 0.7154275178909302}, {"content": "Title: Overcoming the bottleneck to widespread testing: a rapid review of nucleic acid testing approaches for COVID-19 detection Content: The current COVID-19 pandemic presents a serious public health crisis, and a better understanding of the scope and spread of the virus would be aided by more widespread testing. Nucleic-acid-based tests currently offer the most sensitive and early detection of COVID-19. However, the \"gold standard\" test pioneered by the U.S. Centers for Disease Control and Prevention takes several hours to complete and requires extensive human labor, materials such as RNA extraction kits that could become in short supply, and relatively scarce qPCR machines. It is clear that a huge effort needs to be made to scale up current COVID-19 testing by orders of magnitude. There is thus a pressing need to evaluate alternative protocols, reagents, and approaches to allow nucleic-acid testing to continue in the face of these potential shortages. There has been a tremendous explosion in the number of papers written within the first weeks of the pandemic evaluating potential advances, comparable reagents, and alternatives to the \"gold-standard\" CDC RT-PCR test. Here we present a collection of these recent advances in COVID-19 nucleic acid testing, including both peer-reviewed and preprint articles. Due to the rapid developments during this crisis, we have included as many publications as possible, but many of the cited sources have not yet been peer-reviewed, so we urge researchers to further validate results in their own laboratories. We hope that this review can urgently consolidate and disseminate information to aid researchers in designing and implementing optimized COVID-19 testing protocols to increase the availability, accuracy, and speed of widespread COVID-19 testing.", "qid": 33, "docid": "opdva99w", "rank": 81, "score": 0.7149556279182434}, {"content": "Title: New blood tests for antibodies could show true scale of coronavirus pandemic Content: How many COVID-19 cases have gone undetected? And are those who had mild cases of the disease\u2014perhaps so mild they dismissed it as a cold or allergies\u2014immune to new infections? If so, they could slow the spread of the burgeoning pandemic Labs and companies around the world have raced to develop antibody tests, and a few have been used in small studies and received commercial approval, including several from China But so far, large-scale data from such tests\u2014for example showing what fraction of people in the hard-hit city of Wuhan, China, might now be immune\u2014is still lacking or at least not public Scientists hope that will soon change as more tests become available", "qid": 33, "docid": "ecxji8x8", "rank": 82, "score": 0.714739203453064}, {"content": "Title: Repurposed prophylaxis strategies for COVID-19: a systematic review Content: Introduction Efficient therapeutic strategies are needed to counter the COVID-19 pandemic, caused by the SARS- CoV-2 virus. In a context where specific vaccines are not yet available, the containment of the pandemic would be facilitated with efficient prophylaxis. Methods We screened several clinical trials repositories and platforms in search of the prophylactic strategies that are investigated against COVID-19 in late April 2020. Results Up to April 27, 2020, we found 68 clinical trials targeting medical workers (n=43, 63%), patients relatives (n=16, 24%) or individuals at risk of severe COVID-19 (n=5, 7%). (Hydroxy)chloroquine was the most frequently evaluated treatment (n=46, 68%), before BCG vaccine (n=5, 7%). Sixty-one (90%) clinical trials were randomized with a median of planned inclusions of 600 (IQR 255-1515). Conclusion The investigated prophylaxis strategies cover both pre- and post-exposure prophylaxis and study numerous immune enhancers and antivirals, although most research efforts are focused on (hydroxy)chloroquine.", "qid": 33, "docid": "au82vv0u", "rank": 83, "score": 0.7144426107406616}, {"content": "Title: Design of a peptide-based subunit vaccine against novel coronavirus SARS-CoV-2 Content: Abstract Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. In the absence of any antiviral or immunomodulatory therapies, the disease is spreading at an alarming rate. A possibility of a resurgence of COVID-19 in places where lockdowns have already worked is also developing. Thus, for controlling COVID-19, vaccines may be a better option than drugs. An mRNA-based anti-COVID-19 candidate vaccine has entered a phase 1 clinical trial. However, its efficacy and potency have to be evaluated and validated. Since vaccines have high failure rates, as an alternative, we are presenting a new, designed multi-peptide subunit-based epitope vaccine against COVID-19. The recombinant vaccine construct comprises an adjuvant, cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes joined by linkers. The computational data suggest that the vaccine is non-toxic, non-allergenic, thermostable, with the capability to elicit a humoral and cell-mediated immune response. The stabilization of the vaccine construct is validated with molecular dynamics simulation studies. This unique vaccine is made up of 33 highly antigenic epitopes from three proteins that have a prominent role in host-receptor recognition, viral entry, and pathogenicity. We advocate this vaccine must be synthesized and tested urgently as a public health priority.", "qid": 33, "docid": "d2j9wpqk", "rank": 84, "score": 0.7144063115119934}, {"content": "Title: COVID-19 Serological Tests: How Well Do They Actually Perform? Content: In only a few months after initial discovery in Wuhan, China, SARS-CoV-2 and the associated coronavirus disease 2019 (COVID-19) have become a global pandemic causing significant mortality and morbidity and implementation of strict isolation measures In the absence of vaccines and effective therapeutics, reliable serological testing must be a key element of public health policy to control further spread of the disease and gradually remove quarantine measures Serological diagnostic tests are being increasingly used to provide a broader understanding of COVID-19 incidence and to assess immunity status in the population However, there are discrepancies between claimed and actual performance data for serological diagnostic tests on the market In this study, we conducted a review of independent studies evaluating the performance of SARS-CoV-2 serological tests We found significant variability in the accuracy of marketed tests and highlight several lab-based and point-of-care rapid serological tests with high levels of performance The findings of this review highlight the need for ongoing independent evaluations of commercialized COVID-19 diagnostic tests", "qid": 33, "docid": "upwn9o2m", "rank": 85, "score": 0.7143896818161011}, {"content": "Title: SARS-CoV-2 transcriptome analysis and molecular cataloguing of immunodominant epitopes for multi-epitope based vaccine design Content: SARS-CoV-2 is a single-stranded RNA virus that has caused more than 0.29 million deaths worldwide as of May 2020, and influence of COVID-19 pandemic is increasing continuously in the absence of approved vaccine and drug. Moreover, very limited information is available about SARS-CoV-2 expressed regions and immune responses. In this paper an effort has been made, to facilitate vaccine development by proposing multiple epitopes as potential vaccine candidates by utilising SARS-CoV-2 transcriptome data. Here, publicly available RNA-seq data of SARS-CoV-2 infection in NHBE and A549 human cell lines were used to construct SARS-CoV-2 transcriptome to understand disease pathogenesis and immune responses. In the first step, epitope prediction, MHC class I and II gene identification for epitopes, population coverage, antigenicity, immunogenicity, conservation and crossreactivity analysis with host antigens were performed by using SARS-CoV-2 transcriptome, and in the second step, structural compatibility of identified T-and B-cell epitopes were evaluated with MHC molecules and B-cell receptors through molecular docking studies. Quantification of MHC gene expression was also performed that indicated high variation in allele types and expression level of MHC genes with respect to cell lines. In A549 cell line, HLA-A*30:01:01:01 and HLA-B*44:03:01:01 were highly expressed, whereas 92 variants of HLA-A*24 genes such as HLA-A*24:02:01:01, HLA-A*24:286, HLA-A*24:479Q, HLA-A*24:02:134 and HLA-A*24:02:116 were highly expressed in NHBE cell lines. Prevalence of HLA-A*24 alleles was suggested as risk factors for H1N1 infection, and associated with type-1 diabetes. HLA-C*03:03, linked with male infertility factors was also highly expressed in SARS-CoV-2 infected NHBE cell lines. Finally, three potential T-cell and five B-cell epitopes were selected for molecular docking studies with twenty-two MHC molecules and two B-cell receptors respectively. The results of in silico analysis indicated that proposed epitopes have high potential to recognize immune response of SARS-CoV-2 infection. This study will facilitate in vitro and in vivo vaccine related research studies.", "qid": 33, "docid": "oiepgu0v", "rank": 86, "score": 0.7139074802398682}, {"content": "Title: Vaccines for SARS-CoV-2: Lessons from Other Coronavirus Strains Content: The emergence of the strain of coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and its impact on global health have made imperative the development of effective and safe vaccines for this lethal strain. SARS-CoV-2 now adds to the list of coronavirus diseases that have threatened global health, along with the SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) coronaviruses that emerged in 2002/2003 and 2012, respectively. As of April 2020, no vaccine is commercially available for these coronavirus strains. Nevertheless, the knowledge obtained from the vaccine development efforts for MERS and SARS can be of high value for COVID-19 (coronavirus disease 2019). Here, we review the past and ongoing vaccine development efforts for clinically relevant coronavirus strains with the intention that this information helps in the development of effective and safe vaccines for COVID-19. In addition, information from naturally exposed individuals and animal models to coronavirus strains is described for the same purpose of helping into the development of effective vaccines against COVID-19.", "qid": 33, "docid": "ri91u0f1", "rank": 87, "score": 0.7138949036598206}, {"content": "Title: Vaccines for SARS-CoV-2: Lessons from Other Coronavirus Strains. Content: The emergence of the strain of coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and its impact on global health have made imperative the development of effective and safe vaccines for this lethal strain. SARS-CoV-2 now adds to the list of coronavirus diseases that have threatened global health, along with the SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) coronaviruses that emerged in 2002/2003 and 2012, respectively. As of April 2020, no vaccine is commercially available for these coronavirus strains. Nevertheless, the knowledge obtained from the vaccine development efforts for MERS and SARS can be of high value for COVID-19 (coronavirus disease 2019). Here, we review the past and ongoing vaccine development efforts for clinically relevant coronavirus strains with the intention that this information helps in the development of effective and safe vaccines for COVID-19. In addition, information from naturally exposed individuals and animal models to coronavirus strains is described for the same purpose of helping into the development of effective vaccines against COVID-19.", "qid": 33, "docid": "qu7ddcw9", "rank": 88, "score": 0.7138949036598206}, {"content": "Title: A deep dive into testing and management of COVID-19 for Australian high performance and professional sport Content: The purpose of testing for any communicable disease is to support clinicians in the diagnosis and management of individual patients and to describe transmission dynamics. The novel coronavirus is formally named SARS-CoV-2 and the clinical disease state resulting from an infection is known as COVID-19. Control of the COVID-19 pandemic requires clinicians, epidemiologists, and public health officials to utilise the most comprehensive, accurate and timely information available to manage the rapidly evolving COVID-19 environment. High performance sport is a unique context that may look towards comprehensive testing as a means of risk mitigation. Characteristics of the common testing options are discussed including the circumstances where additional testing may be of benefit and considerations for the associated risks. Finally, a review of the available technology that could be considered for use by medical staff at the point of care (PoC) in a high-performance sporting context is included.", "qid": 33, "docid": "na06mkr6", "rank": 89, "score": 0.7138717174530029}, {"content": "Title: Laboratory Tests for COVID-19: A Review of Peer-Reviewed Publications and Implications for Clinical UIse Content: Diagnostic tests for the coronavirus infection 2019 (COVID-19) are critical for prompt diagnosis, treatment and isolation to break the cycle of transmission A positive real-time reverse-transcriptase polymerase chain reaction (RT-PCR), in conjunction with clinical and epidemiologic data, is the current standard for diagnosis, but several challenges still exist Serological assays help to understand epidemiology better and to evaluate vaccine responses but they are unreliable for diagnosis in the acute phase of illness or assuming protective immunity Serology is gaining attention, mainly because of convalescent plasma gaining importance as treatment for clinically worsening COVID-19 patients We provide a narrative review of peer-reviewed research studies on RT-PCR, serology and antigen immune-assays for COVID-19, briefly describe their lab methods and discuss their limitations for clinical practice", "qid": 33, "docid": "hgc4ymok", "rank": 90, "score": 0.7133595943450928}, {"content": "Title: An overview on COVID-19: reality and expectation Content: Recently, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), commonly known as coronavirus disease-2019 (COVID-19) has rapidly spread across China and around the world. By the declaration of WHO, COVID-19 outbreak considered as a public health problem of international concern. The aim of this study is to provide a comprehensive view on COVID-19 and the future expectations to control virus progression. Patients with liver disease, diabetes, high blood pressure, and obesity are more susceptible to the incidence of COVID-19 infection. So, there is a rapid need for disease diagnosis, vaccine development, and drug discovery to detect, prevent, and treat this sudden and lethal virus. Real-time polymerase chain reaction (RT-PCR) is considered as a rapid, accurate, and specific tool for disease diagnosis. Under this emergency situation that the world facing against COVID-19, there are about 15 potential vaccine candidates tested globally based on messenger RNA, DNA-based, nanoparticle, synthetic, and modified virus-like particle. Certain drugs that are clinically approved for other diseases were tested against COVID-19 as chloroquine, hydroxychloroquine, ivermectin, favipiravir, ribavirin, and remdesivir. Convalescent plasma transfusion and traditional herbal medicine were also taken into consideration. Due to the absence of effective treatment or vaccines against COVID-19 so far, the precautionary measures according to WHO\u2019s strategic objectives are the only way to confront this crisis. Governments should adopt national medical care programs to reduce the risk of exposure to any future viral outbreaks especially to patients with pre-existing medical conditions.", "qid": 33, "docid": "ino9srb6", "rank": 91, "score": 0.7131243944168091}, {"content": "Title: A deep dive into testing and management of COVID-19 for Australian high performance and professional sport Content: Abstract The purpose of testing for any communicable disease is to support clinicians in the diagnosis and management of individual patients and to describe transmission dynamics. The novel coronavirus is formally named SARS-CoV-2 and the clinical disease state resulting from an infection is known as COVID-19. Control of the COVID-19 pandemic requires clinicians, epidemiologists, and public health officials to utilise the most comprehensive, accurate and timely information available to manage the rapidly evolving COVID-19 environment. High performance sport is a unique context that may look towards comprehensive testing as a means of risk mitigation. Characteristics of the common testing options are discussed including the circumstances where additional testing may be of benefit and considerations for the associated risks. Finally, a review of the available technology that could be considered for use by medical staff at the point of care (PoC) in a high-performance sporting context is included.", "qid": 33, "docid": "ofrcauh9", "rank": 92, "score": 0.7129905223846436}, {"content": "Title: Triaging moderate COVID-19 and other viral pneumonias from routine blood tests Content: The COVID-19 is sweeping the world with deadly consequences. Its contagious nature and clinical similarity to other pneumonias make separating subjects contracted with COVID-19 and non-COVID-19 viral pneumonia a priority and a challenge. However, COVID-19 testing has been greatly limited by the availability and cost of existing methods, even in developed countries like the US. Intrigued by the wide availability of routine blood tests, we propose to leverage them for COVID-19 testing using the power of machine learning. Two proven-robust machine learning model families, random forests (RFs) and support vector machines (SVMs), are employed to tackle the challenge. Trained on blood data from 208 moderate COVID-19 subjects and 86 subjects with non-COVID-19 moderate viral pneumonia, the best result is obtained in an SVM-based classifier with an accuracy of 84%, a sensitivity of 88%, a specificity of 80%, and a precision of 92%. The results are found explainable from both machine learning and medical perspectives. A privacy-protected web portal is set up to help medical personnel in their practice and the trained models are released for developers to further build other applications. We hope our results can help the world fight this pandemic and welcome clinical verification of our approach on larger populations.", "qid": 33, "docid": "qikmhoo4", "rank": 93, "score": 0.7128298282623291}, {"content": "Title: The hunt for covid-19 drugs Content: Many drugs and vaccines are now being developed and tested", "qid": 33, "docid": "cdctlduc", "rank": 94, "score": 0.7124390602111816}, {"content": "Title: Exercising caution in correlating COVID-19 incidence and mortality rates with BCG vaccination policies due to variable rates of SARS CoV-2 testing Content: TThe Bacillus Calmette-Guerin (BCG) vaccine provides protection against tuberculosis (TB), and is proposed to provide protection to non-TB infectious diseases. The COVID-19 outbreak results from infection with the novel coronavirus SARS-CoV-2 (CoV-2) and was declared a pandemic on March 11th, 2020. We queried whether the BCG vaccine offers protection against CoV-2 infection. We observed that countries with a current universal BCG vaccination policy have a significantly lower COVID-19 incidence than countries which never had a universal BCG policy or had one in the past. However, population density, median age, TB incidence, urban population, and, most significantly, CoV-2 testing rate, were also connected with BCG policy and could potentially confound the analysis. By limiting the analysis to countries with high CoV-2 testing rates, defined as greater than 2,500 tests per million inhabitants, these parameters were no longer statistically associated with BCG policy. When analyzing only countries with high testing rates, there was no longer a significant association between the number of COVID-19 cases per million inhabitants and the BCG vaccination policy. Although preliminary, our analyses indicate that the BCG vaccination may not offer protection against CoV-2 infection. While reporting biases may confound our observations, our findings support exercising caution in determining potential correlation between BCG vaccination and COVID-19 incidence, in part due significantly lower rates of CoV-2 testing per million inhabitants in countries with current universal BCG vaccination policy.", "qid": 33, "docid": "hsmhtei5", "rank": 95, "score": 0.712209939956665}, {"content": "Title: Cancer therapy and treatments during COVID-19 era Content: The COVID-19 pandemic has put a serious strain on health treatments as well at the economies of many nations. Unfortunately, there is not currently available vaccine for SARS-Cov-2/COVID-19. Various types of patients have delayed treatment or even routine check-ups and we are adapting to a virtual world. In many cases, surgeries are delayed unless they are essential. This is also true with regards to cancer treatments and screening. Interestingly, some existing drugs and nutraceuticals have been screened for their effects on COVID-19. Certain FDA approved drugs, vitamin, natural products and trace minerals may be repurposed to treat or improve the prevention of COVID-19 infections and disease progression. This review article will summarize how the treatments of various cancer patients has changed during the COVID-19 era as well as discuss the promise of some existing drugs and other agents to be repurposed to treat this disease.", "qid": 33, "docid": "i90x2r7t", "rank": 96, "score": 0.7121542692184448}, {"content": "Title: Guidance for evaluating and testing patients for COVID\u201019 Content: This month's selection provides guidance to evaluate and test patients for COVID\u201019.", "qid": 33, "docid": "47h8etwj", "rank": 97, "score": 0.7121216654777527}, {"content": "Title: Overcoming the bottleneck to widespread testing: A rapid review of nucleic acid testing approaches for COVID-19 detection. Content: The current COVID-19 pandemic presents a serious public health crisis, and a better understanding of the scope and spread of the virus would be aided by more widespread testing. Nucleic-acid based tests currently offer the most sensitive and early detection of COVID-19. However, the \"gold standard\" test pioneered by the United States Center for Disease Control & Prevention, takes several hours to complete and requires extensive human labor, materials such as RNA extraction kits that could become in short supply and relatively scarce qPCR machines. It is clear that a huge effort needs to be made to scale up current COVID-19 testing by orders of magnitude. There is thus a pressing need to evaluate alternative protocols, reagents, and approaches to allow nucleic-acid testing to continue in the face of these potential shortages. There has been a tremendous explosion in the number of papers written within the first weeks of the pandemic evaluating potential advances, comparable reagents, and alternatives to the \"gold-standard\" CDC RT-PCR test. Here we present a collection of these recent advances in COVID-19 nucleic acid testing, including both peer-reviewed and preprint articles. Due to the rapid developments during this crisis, we have included as many publications as possible, but many of the cited sources have not yet been peer-reviewed, so we urge researchers to further validate results in their own labs. We hope that this review can urgently consolidate and disseminate information to aid researchers in designing and implementing optimized COVID-19 testing protocols to increase the availability, accuracy, and speed of widespread COVID-19 testing.", "qid": 33, "docid": "b3wp314u", "rank": 98, "score": 0.7120417952537537}, {"content": "Title: The role of testing in infectious disease control: A case of COVID-19 in Africa Content: The dramatic increase in COVID-19 suspected cases in Africa has placed enormous burden on public and private clinical facilities. Till date, the most commonly used method for the identification and confirmation of the virus is the laboratory-based reverse transcription-polymerase chain reaction (RT-PCR) testing. Unfortunately, testing capacities have been limited in many parts of Africa because of inadequate test kits which have restricted scaling up beyond the few public health laboratories at designated locations. We present in this mini-review Africa's preparedness and readiness toward testing, why testing is crucial, the need to immediately strengthen existing facilities and what it involves as combined approaches for managing the COVID-19 crisis. The review highlights the urgent need for speedy expansion and distribution of several laboratory testing platforms to public health facilities and fully accredited private clinical laboratories, including real-time PCR and serological assays.", "qid": 33, "docid": "go8lly5h", "rank": 99, "score": 0.7120237350463867}, {"content": "Title: Screening for COVID-19: Patient factors predicting positive PCR test Content: To inform the efficient allocation of testing resources, we evaluated the characteristics of those tested for COVID-19 to determine predictors of a positive test. Recent travel and exposure to a confirmed case were both highly predictive of positive testing. Symptom-based screening strategies alone may be inadequate to control the ongoing pandemic.", "qid": 33, "docid": "658560av", "rank": 100, "score": 0.7119828462600708}]}
{"query": "What are the longer-term complications of those who recover from COVID-19?", "hits": [{"content": "Title: Survivorship after COVID-19 ICU stay Content: Prior studies of patient survivorship after an intensive care unit (ICU) stay suggest that many critically ill patients with COVID-19 will face long-lasting physical, cognitive and/or mental health impairments. This anticipated survivorship experience highlights the importance of collaboration between the fields of critical care and rehabilitation to optimize post-COVID-19 recovery.", "qid": 34, "docid": "lcqxnrge", "rank": 1, "score": 0.7858264446258545}, {"content": "Title: [Rehabilitation is crucial for severe COVID-19 survivors]. Content: COVID-19 survivors can have serious complications from this viral infection, particularly respiratory and cardiovascular with severe asthenia and fatigue. Several studies have already demonstrated the benefit of early rehabilitation after the acute phase, especially in patients who have been in intensive care. The authors present a rehabilitation program including interdisciplinary care with simple and reproducible clinical criteria.", "qid": 34, "docid": "jud53dmv", "rank": 2, "score": 0.78162682056427}, {"content": "Title: La r\u00e9habilitation: indispensable pour les survivants d'un COVID-19 s\u00e9v\u00e8re./ [Rehabilitation is crucial for severe COVID-19 survivors] Content: COVID-19 survivors can have serious complications from this viral infection, particularly respiratory and cardiovascular with severe asthenia and fatigue. Several studies have already demonstrated the benefit of early rehabilitation after the acute phase, especially in patients who have been in intensive care. The authors present a rehabilitation program including interdisciplinary care with simple and reproducible clinical criteria.", "qid": 34, "docid": "6ztf2n5w", "rank": 3, "score": 0.7816267013549805}, {"content": "Title: Long term complications and rehabilitation of COVID-19 patients. Content: With the ongoing pandemic of COVID-19 having caught the world almost unaware millions of people across the globe are presently grappling to deal with its acute effects . Our previous experience with members of the same corona virus family (SARS and MERS) which have caused two major epidemics in the past albeit of much lower magnitude , has taught us that the harmful effect of such outbreaks are not limited to acute complications alone .Long term cardiopulmonary, glucometabolic and neuropsychiatric complications have been documented following these infections .In the given circumstance it is therefore imperative to keep in mind the possible complications that may occur after the acute phase of the disease subsides and to prepare the healthcare system for such challenges.", "qid": 34, "docid": "7s04ygm2", "rank": 4, "score": 0.7777735590934753}, {"content": "Title: Long term complications and rehabilitation of COVID-19 patients Content: With the ongoing pandemic of COVID-19 having caught the world almost unaware millions of people across the globe are presently grappling to deal with its acute effects . Our previous experience with members of the same corona virus family (SARS and MERS) which have caused two major epidemics in the past albeit of much lower magnitude , has taught us that the harmful effect of such outbreaks are not limited to acute complications alone .Long term cardiopulmonary, glucometabolic and neuropsychiatric complications have been documented following these infections .In the given circumstance it is therefore imperative to keep in mind the possible complications that may occur after the acute phase of the disease subsides and to prepare the healthcare system for such challenges.", "qid": 34, "docid": "yudrouue", "rank": 5, "score": 0.7777734994888306}, {"content": "Title: Considerations for Postacute Rehabilitation for Survivors of COVID-19 Content: Coronavirus disease (COVID-19), the infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported on December 31, 2019. Because it has only been studied for just over three months, our understanding of this disease is still incomplete, particularly regarding its sequelae and long-term outcomes. Moreover, very little has been written about the rehabilitation needs of patients with COVID-19 after discharge from acute care. The objective of this report is to answer the question \u201cWhat rehabilitation services do survivors of COVID-19 require?\u201d The question was asked within the context of a subacute hospital delivering geriatric inpatient and outpatient rehabilitation services. Three areas relevant to rehabilitation after COVID-19 were identified. First, details of how patients may present have been summarized, including comorbidities, complications from an intensive care unit stay with or without intubation, and the effects of the virus on multiple body systems, including those pertaining to cardiac, neurological, cognitive, and mental health. Second, I have suggested procedures regarding the design of inpatient rehabilitation units for COVID-19 survivors, staffing issues, and considerations for outpatient rehabilitation. Third, guidelines for rehabilitation (physiotherapy, occupational therapy, speech-language pathology) following COVID-19 have been proposed with respect to recovery of the respiratory system as well as recovery of mobility and function. A thorough assessment and an individualized, progressive treatment plan which focuses on function, disability, and return to participation in society will help each patient to maximize their function and quality of life. Careful consideration of the rehabilitation environment will ensure that all patients recover as completely as possible.", "qid": 34, "docid": "gfzobzrg", "rank": 6, "score": 0.7758114337921143}, {"content": "Title: Considerations for Postacute Rehabilitation for Survivors of COVID-19 Content: Coronavirus disease (COVID-19), the infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported on December 31, 2019. Because it has only been studied for just over three months, our understanding of this disease is still incomplete, particularly regarding its sequelae and long-term outcomes. Moreover, very little has been written about the rehabilitation needs of patients with COVID-19 after discharge from acute care. The objective of this report is to answer the question \"What rehabilitation services do survivors of COVID-19 require?\" The question was asked within the context of a subacute hospital delivering geriatric inpatient and outpatient rehabilitation services. Three areas relevant to rehabilitation after COVID-19 were identified. First, details of how patients may present have been summarized, including comorbidities, complications from an intensive care unit stay with or without intubation, and the effects of the virus on multiple body systems, including those pertaining to cardiac, neurological, cognitive, and mental health. Second, I have suggested procedures regarding the design of inpatient rehabilitation units for COVID-19 survivors, staffing issues, and considerations for outpatient rehabilitation. Third, guidelines for rehabilitation (physiotherapy, occupational therapy, speech-language pathology) following COVID-19 have been proposed with respect to recovery of the respiratory system as well as recovery of mobility and function. A thorough assessment and an individualized, progressive treatment plan which focuses on function, disability, and return to participation in society will help each patient to maximize their function and quality of life. Careful consideration of the rehabilitation environment will ensure that all patients recover as completely as possible.", "qid": 34, "docid": "7l17lern", "rank": 7, "score": 0.7755911350250244}, {"content": "Title: Clinical characteristics and durations of hospitalized patients with COVID-19 in Beijing: a retrospective cohort study Content: Background: COVID-19 is still becoming an increasing global threat to public health. More detailed and specific characteristics of COVID-19 are needed to better understand this disease. Additionally, durations of COVID-19, e.g., the average time from exposure to recovery, which is of great value in understanding this disease, has not been reported so far. Aims: To give the information on clinical characteristics and different durations of COVID-19 and to identify the potential risk factors for longer hospitalization duration. Methods: In this retrospective study, we enrolled 77 patients (mean age: 52 years; 44.2% males) with laboratory-confirmed COVID-19 admitted to Beijing YouAn Hospital during 21st Jan and 8th February 2020. Epidemiological, clinical and radiological data on admission were collected; complications and outcomes were followed up until 29th February 2020. The study endpoint was the discharge within two weeks. Cox proportional-hazards regression was performed to identify risk factors for longer hospitalization duration. Results: Of 77 patients, there are 34 (44.2%) males, 24 (31.2%) with comorbidities, 22 (28.6%) lymphopenia, 20 (26.0%) categorized as severe patients, and 28 (36.4%) occurred complications. By the end of follow-up, 64 (83.1%) patients were discharged home after being tested negative for SARS-CoV-2 infections, 8 remained in hospital and 5 died. 36 (46.8%) patients were discharged within 14 days and thus reached the study endpoint, including 34 (59.6%) of 57 non-severe patients and 2 (10%) of 20 severe patients. The overall cumulative probability of the endpoint was 48.3%. Hospital length of stay and duration of exposure to discharge for 64 discharged patients were 13 (10-16.5) and 23 (18-24.5) days, respectively. Multivariable stepwise Cox regression model showed bilateral pneumonia on CT scan, shorter time from the illness onset to admission, the severity of disease and lymphopenia were independently associated with longer hospitalized duration. Conclusions: COVID-19 has significantly shorter duration of disease and hospital length of stay than SARS. Bilateral pneumonia on CT scan, shorter period of illness onset to admission, lymphopenia, the severity of disease are the risk factors for longer hospitalization duration of COVID-19.", "qid": 34, "docid": "n0uwy77g", "rank": 8, "score": 0.766944408416748}, {"content": "Title: Long-term conditions and severe acute respiratory syndrome SARS-CoV-2 (COVID-19) Content: Observation of infection trends through the course of the ongoing COVID-19 pandemic has indicated that those with certain pre-existing chronic conditions, such as hypertension, chronic obstructive pulmonary disease and obesity, are particularly likely to develop severe infection and experience disastrous sequelae, including near-fatal pneumonia. This article aims to outline how SARS-CoV-2 affects people and to consider why individuals living with long-term conditions are at increased risk from infection caused by this virus. A summary of available clinical guidelines with recommendations is presented, to provide community nurses with the up-to-date information required for protecting individuals living with a number of long-term conditions. Additionally, special measures required are outlined, so that community nurses may reflect on how to best provide nursing care for individuals living with long-term conditions and understand protection measures for individuals at increased risk from severe COVID-19.", "qid": 34, "docid": "s6oi477q", "rank": 9, "score": 0.7656617760658264}, {"content": "Title: Long-term conditions and severe acute respiratory syndrome SARS-CoV-2 (COVID-19). Content: Observation of infection trends through the course of the ongoing COVID-19 pandemic has indicated that those with certain pre-existing chronic conditions, such as hypertension, chronic obstructive pulmonary disease and obesity, are particularly likely to develop severe infection and experience disastrous sequelae, including near-fatal pneumonia. This article aims to outline how SARS-CoV-2 affects people and to consider why individuals living with long-term conditions are at increased risk from infection caused by this virus. A summary of available clinical guidelines with recommendations is presented, to provide community nurses with the up-to-date information required for protecting individuals living with a number of long-term conditions. Additionally, special measures required are outlined, so that community nurses may reflect on how to best provide nursing care for individuals living with long-term conditions and understand protection measures for individuals at increased risk from severe COVID-19.", "qid": 34, "docid": "4n2xmx2w", "rank": 10, "score": 0.7656617760658264}, {"content": "Title: Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery Content: BACKGROUND: The long-term pulmonary function and related physiological characteristics of COVID-19 survivors have not been studied in depth, thus many aspects are not understood. METHODS: COVID-19 survivors were recruited for high resolution computed tomography (HRCT) of the thorax, lung function and serum levels of SARS-CoV-2 IgG antibody tests 3 months after discharge. The relationship between the clinical characteristics and the pulmonary function or CT scores were investigated. FINDINGS: Fifty-five recovered patients participated in this study. SARS-CoV-2 infection related symptoms were detected in 35 of them and different degrees of radiological abnormalities were detected in 39 patients. Urea nitrogen concentration at admission was associated with the presence of CT abnormalities (P = 0.046, OR 7.149, 95% CI 1.038 to 49.216). Lung function abnormalities were detected in 14 patients and the measurement of D-dimer levels at admission may be useful for prediction of impaired diffusion defect (P = 0.031, OR 1.066, 95% CI 1.006 to 1.129). Of all the subjects, 47 of 55 patients tested positive for SARS-CoV-2 IgG in serum, among which the generation of Immunoglobulin G (IgG) antibody in female patients was stronger than male patients in infection rehabilitation phase. INTERPRETATION: Radiological and physiological abnormalities were still found in a considerable proportion of COVID-19 survivors without critical cases 3 months after discharge. Higher level of D-dimer on admission could effectively predict impaired DLCO after 3 months discharge. It is necessary to follow up the COVID-19 patients to appropriately manage any persistent or emerging long-term sequelae. FUNDING: Key Scientific Research Projects of Henan Higher Education Institutions", "qid": 34, "docid": "9cnuxusj", "rank": 11, "score": 0.7654356956481934}, {"content": "Title: LONG-TERM CLINICAL OUTCOMES IN SURVIVORS OF CORONAVIRUS OUTBREAKS AFTER HOSPITALISATION OR ICU ADMISSION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF FOLLOW-UP STUDIES Content: Objective: To determine the long-term clinical problems in adult survivors of coronavirus (CoV) infection [Coronavirus disease 2019 (COVID-19), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS)] after hospitalisation or Intensive Care Unit (ICU) admission. Design: Systematic review and meta-analysis of the literature. Data sources: Ovid MEDLINE, EMBASE, CINAHL Plus and PsycINFO were searched using the strategy: (Coronavirus OR Coronavirus Infections OR COVID OR SARS virus OR Severe acute respiratory syndrome OR MERS OR Middle east respiratory syndrome) AND (Follow-up OR Follow-up studies OR Prevalence). Original studies reporting the clinical outcomes of adult survivors of coronavirus outbreaks two months after discharge or three months after admission were included. The quality of the studies was assessed using the Oxford Centre for Evidence-Based Medicine (OCEBM) 2009 Level of Evidence Tool. Meta-analysis was conducted to derive pooled estimates of prevalence and severity for different outcomes at time points up to 6 months follow-up and beyond 6 months follow-up. Results: The search yielded 1169 studies of which 28 were included in this review. There were 15 Level 1b, 8 Level 2b, 2 Level 3b and 3 Level 4 studies by OCEBM grading. Pooled analysis of studies revealed that complications commonly observed were impaired diffusing capacity for carbon monoxide (DLCO) [prevalence of 27.26%, 95% CI 14.87 to 44.57] and reduced exercise capacity [(6-minute walking distance (6MWD) mean 461m, 95% CI 449.66 to 472.71] at 6 months with limited improvement beyond 6 months. Coronavirus survivors had considerable prevalence of psychological disorders such as post-traumatic stress disorder (PTSD) [38.80%, CI 30.93 to 47.31], depression [33.20%, CI 19.80 to 50.02] and anxiety [30.04%, CI 10.44 to 61.26) beyond 6 months. These complications were accompanied by low Short Form 36 (SF-36) scores at 6 months and beyond indicating reduced quality of life which is present long-term. Conclusions: The long term clinical problems in survivors of CoV infections (SARS and MERS) after hospitalisation or Intensive Care Unit (ICU) admission include respiratory dysfunction, reduced exercise capacity, psychological problems such as PTSD, depression and anxiety, and reduced quality of life. Critical care, rehabilitation and mental health services should anticipate a high prevalence of these problems following COVID-19 and ensure their adequate and timely management with the aim of restoring premorbid quality of life.", "qid": 34, "docid": "bzc7luwj", "rank": 12, "score": 0.7625402808189392}, {"content": "Title: Follow-up studies in COVID-19 recovered patients - is it mandatory? Content: The novel Coronavirus disease 2019 (COVID-19) is an illness caused due to Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The World Health Organization (WHO) has declared this outbreak a global health emergency and as on April 24, 2020, it has spread to 213 countries, with 25,91,015 confirmed cases and 742,855 cases have been recovered from COVID-19. In this dreadful situation our team has already published an article in the Science of the Total Environment, which elaborates the various aspects of the SARS-CoV-2 infection. In this situation, it is imperative to understand the possible outcome of COVID-19 recovered patients and determine if they have any other detrimental illnesses by longitudinal analysis to safeguard their life in future. It is necessary to follow-up these recovered patients and performs comprehensive assessments for detection and appropriate management towards their psychological, physical, and social realm. This urges us to suggest that it is highly important to provide counselling, moral support as well as a few recommended guidelines to the recovered patients and society to restore to normalcy. Epidemiological, clinical and immunological studies from COVID-19 recovered patients are particularly important to understand the disease and to prepare better for potential outbreaks in the future. Longitudinal studies on a larger cohort would help us to understand the in-depth prognosis as well as the pathogenesis of COVID-19. Also, follow-up studies will help us provide more information for the development of vaccines and drugs for these kinds of pandemics in the future. Hence, we recommend more studies are required to unravel the possible mechanism of COVID-19 infection and the after-effects of it to understand the characteristics of the virus and to develop the necessary precautionary measures to prevent it.", "qid": 34, "docid": "uqhaxqqh", "rank": 13, "score": 0.7607384920120239}, {"content": "Title: Rehabilitation and respiratory management in the acute and early post-acute phase. \"Instant paper from the field\" on rehabilitation answers to the Covid-19 emergency Content: Covid-19 is a respiratory infectious disease that can cause respiratory, physical and psychological long-term dysfunctions in patients. First recommendations on respiratory management were published, but they were not based on the specific needs due to Covid-19. In this paper we share the early experiences from the clinical field in Northern Italy, where the epidemic started in February. This paper summarizes the second webinar on Covid-19 (230 live attendees, 11,600 viewers of the recorded version) organized by the Italian Society of Physical and Rehabilitation Medicine about rehabilitation and in particular respiratory management in the acute (Intensive Care Unit - ICU) and immediate post-acute phases. There is the need to prepare for the post-acute phase. ICU length of stay is relatively long, with immobilisation in prone position. Some specific problems are described, including severe muscle weakness and fatigue, joint stiffness, dysphagia, (neuro)psychological problems, impaired functioning concerning mobility, activities of daily life and work. A lot is yet unknown and patients can experience long-term consequences as we know from the literature on the post-intensive care syndrome, but Covid-19 has unique features to be investigated and understood. As one colleague stated during the Covinar: this is a marathon, not a sprint .", "qid": 34, "docid": "6bq3g51s", "rank": 14, "score": 0.7588791847229004}, {"content": "Title: Rehabilitation and respiratory management in the acute and early post-acute phase. \"Instant paper from the field\" on rehabilitation answers to the Covid-19 emergency. Content: Covid-19 is a respiratory infectious disease that can cause respiratory, physical and psychological long-term dysfunctions in patients. First recommendations on respiratory management were published, but they were not based on the specific needs due to Covid-19. In this paper we share the early experiences from the clinical field in Northern Italy, where the epidemic started in February. This paper summarizes the second webinar on Covid-19 (230 live attendees, 11,600 viewers of the recorded version) organized by the Italian Society of Physical and Rehabilitation Medicine about rehabilitation and in particular respiratory management in the acute (Intensive Care Unit - ICU) and immediate post-acute phases. There is the need to prepare for the post-acute phase. ICU length of stay is relatively long, with immobilisation in prone position. Some specific problems are described, including severe muscle weakness and fatigue, joint stiffness, dysphagia, (neuro)psychological problems, impaired functioning concerning mobility, activities of daily life and work. A lot is yet unknown and patients can experience long-term consequences as we know from the literature on the post-intensive care syndrome, but Covid-19 has unique features to be investigated and understood. As one colleague stated during the Covinar: this is a marathon, not a sprint\u2026.", "qid": 34, "docid": "2exi7j6u", "rank": 15, "score": 0.7586393356323242}, {"content": "Title: Follow-up studies in COVID-19 recovered patients - is it mandatory? Content: Abstract The novel Coronavirus disease 2019 (COVID-19) is an illness caused due to Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The World Health Organization (WHO) has declared this outbreak a global health emergency and as on April 24, 2020, it has spread to 213 countries, with 25,91,015 confirmed cases and 742,855 cases have been recovered from COVID-19. In this dreadful situation our team has already published an article in the Science of the Total Environment, which elaborates the various aspects of the SARS-CoV-2 infection. In this situation, it is imperative to understand the possible outcome of COVID-19 recovered patients and determine if they have any other detrimental illnesses by longitudinal analysis to safeguard their life in future. It is necessary to follow-up these recovered patients and performs comprehensive assessments for detection and appropriate management towards their psychological, physical, and social realm. This urges us to suggest that it is highly important to provide counselling, moral support as well as a few recommended guidelines to the recovered patients and society to restore to normalcy. Epidemiological, clinical and immunological studies from COVID-19 recovered patients are particularly important to understand the disease and to prepare better for potential outbreaks in the future. Longitudinal studies on a larger cohort would help us to understand the in-depth prognosis as well as the pathogenesis of COVID-19. Also, follow-up studies will help us provide more information for the development of vaccines and drugs for these kinds of pandemics in the future. Hence, we recommend more studies are required to unravel the possible mechanism of COVID-19 infection and the after-effects of it to understand the characteristics of the virus and to develop the necessary precautionary measures to prevent it.", "qid": 34, "docid": "8p9d1c9k", "rank": 16, "score": 0.7578245401382446}, {"content": "Title: Patient Follow-up after Discharge after COVID-19 Pneumonia: Considerations for Infectious Control Content: Coronavirus disease 2019 (COVID-19) represents a significant global medical issue, with a growing number of cumulative confirmed cases. However, a large number of COVID-19 patients have overcome the disease, meeting hospital discharge criteria, and are gradually returning to work and social life. Nonetheless, COVID-19 may cause further downstream issues in these patients, such as due to possible reactivation of the virus, long-term pulmonary defects, and post-traumatic stress disorder. In this study, we therefore queried relevant literature concerning SARS, MERS, and COVID-19 for reference to come to a consensus on follow-up strategies. We found that strategies such as implementation of PCR testing, imaging surveillance, and psychological assessments, starting at the time of discharge, were necessary for long-term follow-up. If close care is given to every aspect of coronavirus management, we expect that the pandemic outbreak will soon be overcome. This article is protected by copyright. All rights reserved.", "qid": 34, "docid": "x7rzvmcr", "rank": 17, "score": 0.7571746706962585}, {"content": "Title: Patient Follow\u2010up after Discharge after COVID\u201019 Pneumonia: Considerations for Infectious Control Content: Coronavirus disease 2019 (COVID\u201019) represents a significant global medical issue, with a growing number of cumulative confirmed cases. However, a large number of COVID\u201019 patients have overcome the disease, meeting hospital discharge criteria, and are gradually returning to work and social life. Nonetheless, COVID\u201019 may cause further downstream issues in these patients, such as due to possible reactivation of the virus, long\u2010term pulmonary defects, and post\u2010traumatic stress disorder. In this study, we therefore queried relevant literature concerning SARS, MERS, and COVID\u201019 for reference to come to a consensus on follow\u2010up strategies. We found that strategies such as implementation of PCR testing, imaging surveillance, and psychological assessments, starting at the time of discharge, were necessary for long\u2010term follow\u2010up. If close care is given to every aspect of coronavirus management, we expect that the pandemic outbreak will soon be overcome. This article is protected by copyright. All rights reserved.", "qid": 34, "docid": "3cr5x88g", "rank": 18, "score": 0.7564563155174255}, {"content": "Title: Rehabilitation management of patients with COVID-19. Lessons learned from the first experiences in China Content: Corona virus disease 2019 (COVID-19) is a new disease characterized by lung damage and involvement in multiple tissues and organs in the whole body. Some of the patients may have long-term impairment and dysfunctions, including pulmonary fibrosis, heart, liver, kidney, nerve and immune system. Rehabilitation has certain beneficial effect in the acute stage, and especially in the recovery stage, including improving respiratory function, exercise endurance, self-care in daily living activities, as well as psychological support, etc. Rehabilitation is not offside or absent. A reasonable rehabilitation program needs scientific research to avoid arbitrary conclusions.", "qid": 34, "docid": "i1i8ab07", "rank": 19, "score": 0.7524559497833252}, {"content": "Title: Effect and enlightenment of rehabilitation medicine in COVID-19 management. Content: Corona virus disease 2019 (COVID-19) is a new disease characterized by lung damage and involvement in multiple tissues and organs in the whole body. Some of the patients may have long-term impairment and dysfunctions, including pulmonary fibrosis, heart, liver, kidney, nerve and immune system. Rehabilitation has certain beneficial effect in the acute stage, and especially in the recovery stage, including improving respiratory function, exercise endurance, self-care in daily living activities, as well as psychological support, etc. Rehabilitation is not offside or absent. A reasonable rehabilitation program needs scientific research to avoid arbitrary conclusions.", "qid": 34, "docid": "0354z6wh", "rank": 20, "score": 0.7524559497833252}, {"content": "Title: Post-COVID-19 global health strategies: the need for an interdisciplinary approach Content: For survivors of severe COVID-19 disease, having defeated the virus is just the beginning of an uncharted recovery path. What follows after the acute phase of SARS-CoV-2 infection depends on the extension and severity of viral attacks in different cell types and organs. Despite the ridiculously large number of papers that have flooded scientific journals and preprint-hosting websites, a clear clinical picture of COVID-19 aftermath is vague at best. Without larger prospective observational studies that are only now being started, clinicians can retrieve information just from case reports and or small studies. This is the time to understand how COVID-19 goes forward and what consequences survivors may expect to experience. To this aim, a multidisciplinary post-acute care service involving several specialists has been established at the Fondazione Policlinico Universitario A. Gemelli IRCSS (Rome, Italy). Although COVID-19 is an infectious disease primarily affecting the lung, its multi-organ involvement requires an interdisciplinary approach encompassing virtually all branches of internal medicine and geriatrics. In particular, during the post-acute phase, the geriatrician may serve as the case manager of a multidisciplinary team. The aim of this article is to describe the importance of the interdisciplinary approach--coordinated by geriatrician--to cope the potential post-acute care needs of recovered COVID-19 patients.", "qid": 34, "docid": "rd6cqdsf", "rank": 21, "score": 0.7511641979217529}, {"content": "Title: COVID-19 Guide for the Rehabilitation Clinician: A Review of Non-Pulmonary Manifestations and Complications Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) \u2013 also known as COVID-19 \u2013 is primarily known for respiratory illness. While it is clear that patients with moderate to severe cases of COVID-19 will require pulmonary rehabilitation, physiatrists will need to consider effective management plans for COVID-19 survivors with extra-pulmonary involvement. This report will summarize key non-pulmonary considerations to guide rehabilitation clinicians who may be involved in the care of COVID-19 survivors with the best available early evidence.", "qid": 34, "docid": "7y9bdzpd", "rank": 22, "score": 0.7510468363761902}, {"content": "Title: COVID-19 Guide for the Rehabilitation Clinician: A Review of Non-Pulmonary Manifestations and Complications Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - also known as COVID-19 - is primarily known for respiratory illness. While it is clear that patients with moderate to severe cases of COVID-19 will require pulmonary rehabilitation, physiatrists will need to consider effective management plans for COVID-19 survivors with extra-pulmonary involvement. This report will summarize key non-pulmonary considerations to guide rehabilitation clinicians who may be involved in the care of COVID-19 survivors with the best available early evidence.", "qid": 34, "docid": "kde77s2g", "rank": 23, "score": 0.7509195804595947}, {"content": "Title: Characteristics of SARS-CoV-2 positive and complicated COVID-19 patient cohorts in Israel: A comparative analysis Content: Reliably identifying patients at increased risk for COVID-19 complications could guide clinical decisions, public health policies, and preparedness efforts. The most globally accepted definitions of at-risk patients rely, primarily, on epidemiological characterization of hospitalized COVID-19 patients. However, such characterization overlooks, and fails to correct for, the prevalence of existing conditions in the wider SARS-CoV-2 positive population. Here, we use the complete medical records of 4,353 Israeli SARS-CoV-2 positive individuals, of whom 173 experienced moderate or severe symptoms of COVID-19, to identify the conditions that increase the risk of disease complications, in various age and sex strata. Our analysis suggests that cardiovascular and kidney diseases, obesity, and hypertension are significant risk factors for COVID-19 complications, as previously reported. Interestingly, it also indicates that depression (e.g., odds ratio, OR, for males 65 years or older: 2.94, 95% confidence intervals [1.55, 5.58]; P-value = 0.014) as well cognitive and neurological disorder (e.g., OR for individuals [\u2265] 65 year old: 2.65 [1.69, 4.17]; P-value < 0.001) are significant risk factors; and that smoking and background of respiratory diseases do not significantly increase the risk of complications. Adjusting existing risk definitions following these observations may improve their accuracy and impact the global pandemic containment efforts.", "qid": 34, "docid": "iaykn3yi", "rank": 24, "score": 0.7501509189605713}, {"content": "Title: Autoimmune haemolytic anaemia associated with COVID\u201019 infection Content: Among patients with SARS-CoV-2 infection (also known as Covid-19), pneumonia, respiratory failure, and acute respiratory distress syndrome are frequently encountered complications (Zhou et al, 2020). Although the pathophysiology underlying severe Covid-19 remains poorly understood, accumulating evidence argue for hyperinflammatory syndrome causing fulminant and fatal cytokines release associated with disease severity and poor outcome (Mehta et al, 2020). However, the spectrum of complications is broader and include among others various auto-immune disorders such as autoimmune thrombocytopenia, Guillain-Barr\u00e9 and antiphospholipid syndrome (Zhang et al, 2020; Zulfiqar et al, 2020; Toscano et al, 2020). In this report we describe 7 patients from 6 French and Belgian Hospitals who developed a first episode of autoimmune hemolytic anemia (AIHA) during a Covid-19 infection.", "qid": 34, "docid": "wm5297kw", "rank": 25, "score": 0.7490983605384827}, {"content": "Title: How to Detect and Track Chronic Neurologic Sequelae of Covid-19? Use of Auditory Brainstem Responses and Neuroimaging for Long-term Patient Follow-up Content: This review intends to provide an overview of the current knowledge on neurologic sequelae of COVID-19 and their possible etiology, and, based on available data, proposes possible improvements in current medical care procedures. We conducted a thorough review of the scientific literature on neurologic manifestations of COVID-19, the neuroinvasive propensity of known coronaviruses (CoV) and their possible effects on brain structural and functional integrity. It appears that around one third of COVID-19 patients admitted to intensive care units (ICU) for respiratory difficulties exhibit neurologic symptoms. This may be due to progressive brain damage and dysfunction triggered by severe hypoxia and hypoxemia, heightened inflammation and SARS-CoV-2 dissemination into brain parenchyma, as suggested by current reports and analyses of previous CoV outbreaks. Viral invasion of the brain may particularly target and alter brainstem and thalamic functions and, consequently, result in sensorimotor dysfunctions and psychiatric disorders. Moreover, data collected from other structurally homologous CoV suggest that SARS-CoV-2 infection may lead to brain cell degeneration and demyelination similar to multiple sclerosis (MS). Hence, current evidence warrants further evaluation and long-term follow-up of possible neurologic sequelae in COVID-19 patients. It may be particularly relevant to evaluate brainstem integrity in recovered patients, as it is suspected that this cerebral area may particularly be dysfunctional following SARS-CoV-2 infection. Because CoV infection can potentially lead to chronic neuroinflammation and progressive demyelination, neuroimaging features and signs of MS may also be evaluated in the long term in recovered COVID-19 patients.", "qid": 34, "docid": "4ud6awrw", "rank": 26, "score": 0.7490184903144836}, {"content": "Title: HOW TO DETECT AND TRACK CHRONIC NEUROLOGIC SEQUELAE OF COVID-19? USE OF AUDITORY BRAINSTEM RESPONSES AND NEUROIMAGING FOR LONG-TERM PATIENT FOLLOW-UP. Content: This review intends to provide an overview of the current knowledge on neurologic sequelae of COVID-19 and their possible etiology, and, based on available data, proposes possible improvements in current medical care procedures. We conducted a thorough review of the scientific literature on neurologic manifestations of COVID-19, the neuroinvasive propensity of known coronaviruses (CoV) and their possible effects on brain structural and functional integrity. It appears that around one third of COVID-19 patients admitted to intensive care units (ICU) for respiratory difficulties exhibit neurologic symptoms. This may be due to progressive brain damage and dysfunction triggered by severe hypoxia and hypoxemia, heightened inflammation and SARS-CoV-2 dissemination into brain parenchyma, as suggested by current reports and analyses of previous CoV outbreaks. Viral invasion of the brain may particularly target and alter brainstem and thalamic functions and, consequently, result in sensorimotor dysfunctions and psychiatric disorders. Moreover, data collected from other structurally homologous CoV suggest that SARS-CoV-2 infection may lead to brain cell degeneration and demyelination similar to multiple sclerosis (MS). Hence, current evidence warrants further evaluation and long-term follow-up of possible neurologic sequelae in COVID-19 patients. It may be particularly relevant to evaluate brainstem integrity in recovered patients, as it is suspected that this cerebral area may particularly be dysfunctional following SARS-CoV-2 infection. Because CoV infection can potentially lead to chronic neuroinflammation and progressive demyelination, neuroimaging features and signs of MS may also be evaluated in the long term in recovered COVID-19 patients.", "qid": 34, "docid": "e1t3qcw7", "rank": 27, "score": 0.7490184307098389}, {"content": "Title: Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study Content: BACKGROUND: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. METHODS: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. FINDINGS: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74\u00b70%) had emergency surgery and 280 (24\u00b78%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26\u00b71%) patients. 30-day mortality was 23\u00b78% (268 of 1128). Pulmonary complications occurred in 577 (51\u00b72%) of 1128 patients; 30-day mortality in these patients was 38\u00b70% (219 of 577), accounting for 81\u00b77% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1\u00b775 [95% CI 1\u00b728-2\u00b740], p<0\u00b70001), age 70 years or older versus younger than 70 years (2\u00b730 [1\u00b765-3\u00b722], p<0\u00b70001), American Society of Anesthesiologists grades 3-5 versus grades 1-2 (2\u00b735 [1\u00b757-3\u00b753], p<0\u00b70001), malignant versus benign or obstetric diagnosis (1\u00b755 [1\u00b701-2\u00b739], p=0\u00b7046), emergency versus elective surgery (1\u00b767 [1\u00b706-2\u00b763], p=0\u00b7026), and major versus minor surgery (1\u00b752 [1\u00b701-2\u00b731], p=0\u00b7047). INTERPRETATION: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. FUNDING: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research.", "qid": 34, "docid": "7mcin9ib", "rank": 28, "score": 0.7487678527832031}, {"content": "Title: Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study Content: BACKGROUND: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. METHODS: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. FINDINGS: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74\u00b70%) had emergency surgery and 280 (24\u00b78%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26\u00b71%) patients. 30-day mortality was 23\u00b78% (268 of 1128). Pulmonary complications occurred in 577 (51\u00b72%) of 1128 patients; 30-day mortality in these patients was 38\u00b70% (219 of 577), accounting for 82\u00b76% (219 of 265) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1\u00b775 [95% CI 1\u00b728\u20132\u00b740], p<0\u00b70001), age 70 years or older versus younger than 70 years (2\u00b730 [1\u00b765\u20133\u00b722], p<0\u00b70001), American Society of Anesthesiologists grades 3\u20135 versus grades 1\u20132 (2\u00b735 [1\u00b757\u20133\u00b753], p<0\u00b70001), malignant versus benign or obstetric diagnosis (1\u00b755 [1\u00b701\u20132\u00b739], p=0\u00b7046), emergency versus elective surgery (1\u00b767 [1\u00b706\u20132\u00b763], p=0\u00b7026), and major versus minor surgery (1\u00b752 [1\u00b701\u20132\u00b731], p=0\u00b7047). INTERPRETATION: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. FUNDING: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research.", "qid": 34, "docid": "p8ckcvyj", "rank": 29, "score": 0.7486282587051392}, {"content": "Title: Post-COVID-19 global health strategies: the need for an interdisciplinary approach Content: For survivors of severe COVID-19 disease, having defeated the virus is just the beginning of an uncharted recovery path. What follows after the acute phase of SARS-CoV-2 infection depends on the extension and severity of viral attacks in different cell types and organs. Despite the ridiculously large number of papers that have flooded scientific journals and preprint-hosting websites, a clear clinical picture of COVID-19 aftermath is vague at best. Without larger prospective observational studies that are only now being started, clinicians can retrieve information just from case reports and or small studies. This is the time to understand how COVID-19 goes forward and what consequences survivors may expect to experience. To this aim, a multidisciplinary post-acute care service involving several specialists has been established at the Fondazione Policlinico Universitario A. Gemelli IRCSS (Rome, Italy). Although COVID-19 is an infectious disease primarily affecting the lung, its multi-organ involvement requires an interdisciplinary approach encompassing virtually all branches of internal medicine and geriatrics. In particular, during the post-acute phase, the geriatrician may serve as the case manager of a multidisciplinary team. The aim of this article is to describe the importance of the interdisciplinary approach\u2013\u2013coordinated by geriatrician\u2013\u2013to cope the potential post-acute care needs of recovered COVID-19 patients.", "qid": 34, "docid": "vjdwh19x", "rank": 30, "score": 0.748522162437439}, {"content": "Title: Successful recovery from severe COVID-19 pneumonia after kidney transplantation: The interplay between immunosuppression and novel therapy including tocilizumab Content: Although immunosuppressed patients may be more prone to SARS-CoV-2 infection with atypical presentation, long-term immunosuppression therapy may provide some sort of protection for severe clinical complications of COVID-19. The interaction between immunosuppression and new antiviral drugs in the treatment of transplanted patients contracting COVID-19 has not yet been fully investigated. Moreover, data regarding the optimal management of these patients are still very limited. We report a case of the successful recovery from severe COVID-19 of a kidney-transplanted patient treated with hydroxychloroquine, lopinavir/ritonavir, steroid, and tocilizumab.", "qid": 34, "docid": "z0jp7dt7", "rank": 31, "score": 0.7483177781105042}, {"content": "Title: Functional characteristics of patients with SARS-CoV-2 pneumonia at 30 days post infection Content: More than half of patients with Covid-19 pneumonia exhibit abnormal lung function 30 days after symptoms onset, without clear relationship with pneumonia extent on chest-CT. This pleads for systematic and long-term follow-up of patients with Covid.", "qid": 34, "docid": "xtwdnq83", "rank": 32, "score": 0.7481322288513184}, {"content": "Title: COVID-19 Cardiac Injury: Implications for Long-Term Surveillance and Outcomes in Survivors Content: Up to 20-30% of patients hospitalized with coronavirus disease (COVID-19) have evidence of myocardial involvement. Acute cardiac injury in patients hospitalized with COVID-19 is associated with higher morbidity and mortality. There are no data on how acute treatment for COVID-19 may affect convalescent phase or long-term cardiac recovery and function. Myocarditis from other viral pathogens can evolve into overt or subclinical myocardial dysfunction, and sudden death has been described in the convalescent phase of viral myocarditis. This raises concerns for patients recovering from COVID-19. Some patients will have subclinical and possibly overt cardiovascular abnormalities. Patients with ostensibly recovered cardiac function may still be at risk for cardiomyopathy and cardiac arrhythmias. Screening for residual cardiac involvement in the convalescent phase for patients recovered from COVID-19 associated cardiac injury is needed. The type of testing, and therapies for post COVID-19 myocardial dysfunction will need to be determined. Therefore, now is the time to plan for appropriate registries and clinical trials to properly assess these issues and prepare for long-term sequelae of \u201cpost-COVID-19 Cardiac Syndrome\u201d", "qid": 34, "docid": "3tna1y5o", "rank": 33, "score": 0.7478727102279663}, {"content": "Title: COVID-19 presenting with ophthalmoparesis from cranial nerve palsy Content: Neurological complications of COVID-19 are not well described. We report two patients who were diagnosed with COVID-19 after presenting with diplopia and ophthalmoparesis.", "qid": 34, "docid": "jkj9wcl1", "rank": 34, "score": 0.7470903992652893}, {"content": "Title: COVID-19 presenting with ophthalmoparesis from cranial nerve palsy. Content: Neurological complications of COVID-19 are not well described. We report two patients who were diagnosed with COVID-19 after presenting with diplopia and ophthalmoparesis.", "qid": 34, "docid": "bjh9tck8", "rank": 35, "score": 0.7470903992652893}, {"content": "Title: Building a COVID-19 Vulnerability Index Content: COVID-19 is an acute respiratory disease that has been classified as a pandemic by the World Health Organization. Information regarding this particular disease is limited, however, it is known to have high mortality rates, particularly among individuals with preexisting medical conditions. Creating models to identify individuals who are at the greatest risk for severe complications due to COVID-19 will be useful to help for outreach campaigns in mitigating the diseases worst effects. While information specific to COVID-19 is limited, a model using complications due to other upper respiratory infections can be used as a proxy to help identify those individuals who are at the greatest risk. We present the results for three models predicting such complications, with each model having varying levels of predictive effectiveness at the expense of ease of implementation.", "qid": 34, "docid": "37dadupn", "rank": 36, "score": 0.7470234632492065}, {"content": "Title: Risk Factors Associated With Long-Term Hospitalization in Patients With COVID-19: A Single-Centered, Retrospective Study Content: Background: The coronavirus disease 19 (COVID-19) pandemic has become a global threat. Few studies have explored the risk factors for the recovery time of patients with COVID-19. This study aimed to explore risk factors associated with long-term hospitalization in patients with COVID-19. Methods: In this retrospective study, patients with laboratory-confirmed COVID-19 hospitalized in a hospital in Wuhan by March 30, 2020, were included. Demographic, clinical, laboratory, and radiological data from COVID-19 patients on hospital admission were extracted and were compared between the two groups, defined as short- and long-term hospitalization, respectively according to the median hospitalization time. Univariable and multivariable logistic regression methods were performed to identify risk factors associated with long-term hospitalization in patients with COVID-19. Results: A total of 125 discharged patients with COVID-19 were reviewed, including 123 general patients and two severe patients. The median hospitalization time was 13.0 days (IQR 10.0\u201317.0). Among them, 66 patients were discharged <14 days (short-term group) and 59 patients were discharged \u226514 days (long-term group). Compared with the short-term group, patients in the long-term group had significantly higher levels of C-reactive protein (P = 0.000), troponin I (P = 0.002), myoglobin (P = 0.037), aspartate aminotransferase (P = 0.005), lactic dehydrogenase (P = 0.000), prothrombin time (P = 0.030), fibrinogen (P = 0.000), and D-dimer (P = 0.006), but had significantly lower levels of lymphocyte count (P = 0.001), platelet count (P = 0.017), albumin (P = 0.001), and calcium (P = 0.000). Additionally, the incidences of hypocalcemia (P = 0.001), hyponatremia (P = 0.021), hypochloremia (P = 0.019), and bilateral pneumonia (P = 0.000) in the long-term group were significantly higher than those in the short-term group. Multivariable regression showed that hypocalcemia (P = 0.007, OR 3.313, 95% CI 1.392\u20137.886), hypochloremia (P = 0.029, OR 2.663, 95% CI 1.104\u20136.621), and bilateral pneumonia (P = 0.009, OR 5.907, 95% CI 1.073\u201332.521) were independent risk factors associated with long-term hospitalization in patients with COVID-19. Furthermore, a ROC curve where the area under the ROC was 0.766 for retained variables is presented. Conclusions: Hypocalcemia, hypochloremia, and bilateral pneumonia on hospital admission were independent risk factors associated with long-term hospitalization in patients with COVID-19. To the best of our knowledge, this is the first study to highlight the importance of electrolyte imbalance in predicting the hospitalization time of patients with COVID-19.", "qid": 34, "docid": "xzpqxwr2", "rank": 37, "score": 0.7468922138214111}, {"content": "Title: The War on COVID-19 Pandemic: Role of Rehabilitation Professionals and Hospitals Content: The global outbreak of coronavirus disease (COVID-19) has created an unprecedented challenge to the society. Currently, the United States stands as the most affected country, and the entire healthcare system is affected, from emergency department, intensive care unit, post-acute care, outpatient, to home care. Considering the debility, neurological, pulmonary, neuromuscular and cognitive complications, rehabilitation professionals can play an important role in the recovery process for individuals with COVID-19. Clinicians across the nation\u2019s rehabilitation system have already begun working to initiate intensive care unit-based rehabilitation care and develop programs, settings and specialized care to meet the short- and long-term needs of these individuals. We describe the anticipated rehabilitation demands, and the strategies to meet the needs of this population. The complications from COVID-19 can be reduced by (1) delivering interdisciplinary rehabilitation that is initiated early and continued throughout the acute hospital stay, (2) providing patient/family education for self-care after discharge from inpatient rehabilitation at either acute or subacute settings, and (3) continuing rehabilitation care in the outpatient setting, and at home through ongoing therapy either in-person or via telehealth.", "qid": 34, "docid": "f09fxnk9", "rank": 38, "score": 0.7464214563369751}, {"content": "Title: Coronavirus Disease 2019 (COVID-19) in Cancer Patients Content: The Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the most talked-about clinical entity in early 2020. As an infection that spreads easily and has a significant mortality rate, it has caused global panic rarely seen before. Many of the measures taken by governments worldwide will have long-lasting impacts on the wellbeing of the population at large. It has been widely reported that the most vulnerable patients have been most negatively affected by SARS-CoV-2 (COVID-19). In this study, we have tried to search the currently available data on the outcomes of infected cancer patients. Most of the data points to the very challenging nature of treating such patients. Their overall outcomes seem to be worse than in the general population, and it may be difficult to differentiate which potential complications are a result of the primary oncologic disease versus the infection. Management presents its own set of challenges, including but not limited to, deciding whether postponing cancer treatment until the infection resolves is going to benefit the patient and how to organize all aspects of patient care when social contact is as limited as it is for patients newly diagnosed with COVID-19. We believe that as more data becomes available, it is going to be necessary to publish detailed guidelines on how to approach this unique clinical challenge.", "qid": 34, "docid": "ev1nx60h", "rank": 39, "score": 0.7451117634773254}, {"content": "Title: Clinical Characteristics and Outcomes of COVID-19 Patients With a History of Stroke in Wuhan, China Content: BACKGROUND AND PURPOSE: Information on stroke survivors infected with coronavirus disease 2019 (COVID-19) is limited. The aim of this study was to describe specific clinical characteristics and outcomes of patients with COVID-19 with a history of stroke. METHODS: All the confirmed cases of COVID-19 at Tongji Hospital from January 27 to March 5, 2020, were included in our cohort study. Clinical data were analyzed and compared between patients with and without a history of stroke. RESULTS: Of the included 1875 patients with COVID-19, 50 patients had a history of stroke. The COVID-19 patients with medical history of stroke were older with more comorbidities, had higher neutrophil count, and lower lymphocyte and platelet counts than those without history of stroke. The levels of D-dimers, cardiac troponin I, NT pro-brain natriuretic peptide, and interleukin-6 were also markedly higher in patients with history of stroke. Stroke survivors who underwent COVID-19 developed more acute respiratory distress syndrome and received more noninvasive mechanical ventilation. Data from propensity-matched analysis indicated a higher proportion of patients with COVD-19 with a history of stroke were admitted to the intensive care unit requiring mechanical ventilation and were more likely to be held in the unit or die, compared with non-stroke history COVID-19 patients. CONCLUSIONS: Patients with COVID-19 with a history of stroke had more severe clinical symptoms and poorer outcomes compared with those without a history of stroke.", "qid": 34, "docid": "6tvhegbx", "rank": 40, "score": 0.743120551109314}, {"content": "Title: The cognitive consequences of the COVID-19 epidemic: collateral damage? Content: Recovery from coronavirus disease 2019 (COVID-19) will be principally defined in terms of remission from respiratory symptoms, however both clinical and animal studies have shown that coronaviruses may spread to the nervous system. A systematic search on previous viral epidemics revealed that while there has been relatively little research in this area, clinical studies have commonly reported neurological disorders and cognitive difficulties. Little is known with regard to their incidence, duration or underlying neural basis. The hippocampus appears to be particularly vulnerable to coronavirus infections, thus increasing the probability of post-infection memory impairment, and acceleration of neurodegenerative disorders such as Alzheimer\u2019s disease. Future knowledge of the impact of COVID-19, from epidemiological studies and clinical practice, will be needed to develop future screening and treatment programmes to minimize the long-term cognitive consequences of COVID-19.", "qid": 34, "docid": "cb7k2zbe", "rank": 41, "score": 0.7429908514022827}, {"content": "Title: Consideration of prevention and management of long-term consequences of post-acute respiratory distress syndrome in patients with COVID-19 Content: This manuscript provides support for physical therapists to focus on the long-term, as well as the short-term, consequences of acute respiratory distress syndrome (ARDS) associated with COVID-19. Since late November 2019, COVID-19 has become a global health pandemic and threat. Although most people have no or mild symptoms, COVID-19 spreads aggressively and can lead to ARDS rapidly in a proportion of individuals. The evidence supports that gas exchange and countering the negative effects of bed rest and immobility are priorities in severely affected patients admitted to the intensive care unit (ICU). However, in recent years, research has focused on poor long-term functional outcomes in patients with ARDS, often associated with ICU-acquired weakness, deconditioning, and myopathies and neuropathies. In addition to physical therapists providing respiratory support in the ICU, the literature unequivocally supports the view that early intervention for ICU management of patients with ARDS secondary to COVID-19 needs to focus on reducing contributors to impaired long-term function, with direct attention paid to preventing or managing ICU-acquired weakness, deconditioning, and myopathies and neuropathies, in conjunction with respiratory care.", "qid": 34, "docid": "ygosfou2", "rank": 42, "score": 0.7427046895027161}, {"content": "Title: Consideration of prevention and management of long-term consequences of post-acute respiratory distress syndrome in patients with COVID-19. Content: This manuscript provides support for physical therapists to focus on the long-term, as well as the short-term, consequences of acute respiratory distress syndrome (ARDS) associated with COVID-19. Since late November 2019, COVID-19 has become a global health pandemic and threat. Although most people have no or mild symptoms, COVID-19 spreads aggressively and can lead to ARDS rapidly in a proportion of individuals. The evidence supports that gas exchange and countering the negative effects of bed rest and immobility are priorities in severely affected patients admitted to the intensive care unit (ICU). However, in recent years, research has focused on poor long-term functional outcomes in patients with ARDS, often associated with ICU-acquired weakness, deconditioning, and myopathies and neuropathies. In addition to physical therapists providing respiratory support in the ICU, the literature unequivocally supports the view that early intervention for ICU management of patients with ARDS secondary to COVID-19 needs to focus on reducing contributors to impaired long-term function, with direct attention paid to preventing or managing ICU-acquired weakness, deconditioning, and myopathies and neuropathies, in conjunction with respiratory care.", "qid": 34, "docid": "3xfhjddg", "rank": 43, "score": 0.7427046895027161}, {"content": "Title: What if the worst consequences of COVID-19 concerned non-COVID patients? Content: We highlight in this short article the side-effects of COVID-19 pandemic on the management of non-COVID patients, with potential detrimental and irreversible complications. We thus propose adjusted strategies to deal with both COVID and non-COVID patients.", "qid": 34, "docid": "bi7hy7pk", "rank": 44, "score": 0.7423142790794373}, {"content": "Title: Addressing male sexual and reproductive health in the wake of COVID-19 outbreak Content: PURPOSE: The COVID-19 pandemic, caused by the SARS-CoV-2, represents an unprecedented challenge for healthcare. COVID-19 features a state of hyperinflammation resulting in a \u201ccytokine storm\u201d, which leads to severe complications, such as the development of micro-thrombosis and disseminated intravascular coagulation (DIC). Despite isolation measures, the number of affected patients is growing daily: as of June 12th, over 7.5 million cases have been confirmed worldwide, with more than 420,000 global deaths. Over 3.5 million patients have recovered from COVID-19; although this number is increasing by the day, great attention should be directed towards the possible long-term outcomes of the disease. Despite being a trivial matter for patients in intensive care units (ICUs), erectile dysfunction (ED) is a likely consequence of COVID-19 for survivors, and considering the high transmissibility of the infection and the higher contagion rates among elderly men, a worrying phenomenon for a large part of affected patients. METHODS: A literature research on the possible mechanisms involved in the development of ED in COVID-19 survivors was performed. RESULTS: Endothelial dysfunction, subclinical hypogonadism, psychological distress and impaired pulmonary hemodynamics all contribute to the potential onset of ED. Additionally, COVID-19 might exacerbate cardiovascular conditions; therefore, further increasing the risk of ED. Testicular function in COVID-19 patients requires careful investigation for the unclear association with testosterone deficiency and the possible consequences for reproductive health. Treatment with phosphodiesterase-5 (PDE5) inhibitors might be beneficial for both COVID-19 and ED. CONCLUSION: COVID-19 survivors might develop sexual and reproductive health issues. Andrological assessment and tailored treatments should be considered in the follow-up.", "qid": 34, "docid": "qjfe2t9v", "rank": 45, "score": 0.7413471341133118}, {"content": "Title: Chronic Living in a Communicable World Content: By April 2020, COVID-19 lockdowns had restricted the movements of over half the world's population. As health authorities advise people living with chronic conditions to self-isolate because they are at particular risk of serious complications and death, the epidemiological split between communicable and noncommunicable disease is tenuous. We argue that much more is at stake for people living with (multiple) medical conditions than being \"at risk\" of infection of coronavirus. We emphasize the need to attend to the long-term effects of COVID-19, but also the importance of the continued care of people living with other lifelong medical conditions.", "qid": 34, "docid": "gmcj27xz", "rank": 46, "score": 0.7412889003753662}, {"content": "Title: Chronic Living in a Communicable World. Content: By April 2020, COVID-19 lockdowns had restricted the movements of over half the world's population. As health authorities advise people living with chronic conditions to self-isolate because they are at particular risk of serious complications and death, the epidemiological split between communicable and noncommunicable disease is tenuous. We argue that much more is at stake for people living with (multiple) medical conditions than being \"at risk\" of infection of coronavirus. We emphasize the need to attend to the long-term effects of COVID-19, but also the importance of the continued care of people living with other lifelong medical conditions.", "qid": 34, "docid": "xui949ap", "rank": 47, "score": 0.7412889003753662}, {"content": "Title: COVID-19 Cardiac Injury: Implications for Long-Term Surveillance and Outcomes in Survivors Content: Up to 20-30% of patients hospitalized with coronavirus disease (COVID-19) have evidence of myocardial involvement. Acute cardiac injury in patients hospitalized with COVID-19 is associated with higher morbidity and mortality. There are no data on how acute treatment for COVID-19 may affect convalescent phase or long-term cardiac recovery and function. Myocarditis from other viral pathogens can evolve into overt or subclinical myocardial dysfunction, and sudden death has been described in the convalescent phase of viral myocarditis. This raises concerns for patients recovering from COVID-19. Some patients will have subclinical and possibly overt cardiovascular abnormalities. Patients with ostensibly recovered cardiac function may still be at risk for cardiomyopathy and cardiac arrhythmias. Screening for residual cardiac involvement in the convalescent phase for patients recovered from COVID-19 associated cardiac injury is needed. The type of testing, and therapies for post COVID-19 myocardial dysfunction will need to be determined. Therefore, now is the time to plan for appropriate registries and clinical trials to properly assess these issues and prepare for long-term sequelae of \"post-COVID-19 Cardiac Syndrome\".", "qid": 34, "docid": "bsqpkjcj", "rank": 48, "score": 0.7411993741989136}, {"content": "Title: Return to sports after COVID-19: a position paper from the Dutch Sports Cardiology Section of the Netherlands Society of Cardiology Content: The coronavirus disease 2019 (COVID-19) pandemic has led to preventive measures worldwide. With the decline of infection rates, less stringent restrictions for sports and exercise are being implemented. COVID-19 is associated with significant cardiovascular complications; however there are limited data on cardiovascular complications and long-term outcomes in both competitive (elite) athletes and highly active individuals. Based on different categories of disease severity (asymptomatic, regional/systemic symptoms, hospitalisation, myocardial damage, and/or myocarditis), in this point-of-view article we offer the (sports) cardiologist or sports physician in the Netherlands a practical guide to pre-participation screening, and diagnostic and management strategies in all athletes >16 years of age after COVID-19 infection.", "qid": 34, "docid": "ele6eq56", "rank": 49, "score": 0.740872859954834}, {"content": "Title: Does SARS-CoV-2 infection cause chronic neurological complications? Content: The current pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has created an unparalleled health crisis. Besides the acute respiratory infection, CoVs are neuroinvasive causing additional inflammation and neurodegeneration. This is likely also true of SARS-CoV-2 given reports of neurological manifestations in coronavirus disease 2019 (COVID-19) positive patients. Older adults > 65 years of age constitute a high-risk group prone to severe infection and death. Despite the higher mortality rate, a majority of cases are expected to recover and survive from this viral outbreak. But, the long-term consequences of SARS-CoV-2 neuroinfection are unknown. We discuss these potential chronic changes to the central nervous system (CNS) in relation to accelerated brain aging and age-related neurodegenerative disorders.", "qid": 34, "docid": "u0h8ayde", "rank": 50, "score": 0.7407439947128296}, {"content": "Title: Long-term clinical outcomes in survivors of severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus outbreaks after hospitalisation or ICU admission: A systematic review and meta-analysis Content: OBJECTIVE: To determine long-term clinical outcomes in survivors of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus infections after hospitalization or intensive care unit admission. DATA SOURCES: Ovid MEDLINE, EMBASE, CINAHL Plus, and PsycINFO were searched. STUDY SELECTION: Original studies reporting clinical outcomes of adult SARS and MERS survivors 3 months after admission or 2 months after discharge were included. DATA EXTRACTION: Studies were graded using the Oxford Centre for Evidence-Based Medicine 2009 Level of Evidence Tool. Meta-analysis was used to derive pooled estimates for prevalence/severity of outcomes up to 6 months after hospital discharge, and beyond 6 months after discharge. DATA SYNTHESIS: Of 1,169 identified studies, 28 were included in the analysis. Pooled analysis revealed that common complications up to 6 months after discharge were: impaired diffusing capacity for carbon monoxide (prevalence 27%, 95% confidence interval (CI) 15\u00ad45%); and reduced exercise capacity (mean 6-min walking distance 461 m, CI 450\u00ad473 m). The prevalences of post-traumatic stress disorder (39%, 95% CI 31\u00ad47%), depression (33%, 95% CI 20\u00ad50%) and anxiety (30%, 95% CI 10\u00ad61) beyond 6 months after discharge were considerable. Low scores on Short-Form 36 were identified beyond 6 months after discharge. CONCLUSION: Lung function abnormalities, psychological impairment and reduced exercise capacity were common in SARS and MERS survivors. Clinicians should anticipate and investigate similar long-term outcomes in COVID-19 survivors.", "qid": 34, "docid": "0sd7rv5v", "rank": 51, "score": 0.7401611804962158}, {"content": "Title: COVID-19 in post-transplantation patients- report of two cases. Content: Coronavirus Disease 2019 (COVID-19) has become a pandemic since March 2020. We describe here, two cases of COVID-19 infection in a post-transplant setting. First one is a 59-year old renal transplant recipient; the second is a 51-year old allogeneic bone marrow transplant recipient. Both patients were on immunosuppressant therapy and had stable graft function before COVID-19 infection. After the diagnosis of COVID-19, immunosuppressive agents were discontinued and methylprednisolone with prophylactic antibiotics were initiated, however, the lung injury progressed. The T cells were extremely low in both patients after infection. Both patients died despite the maximal mechanical ventilatory support. Therefore, the prognosis of COVID-19 pneumonia following transplantation is not optimistic and remains guarded. Lower T cell count may be a surrogate for poor outcome.", "qid": 34, "docid": "x97yw3ip", "rank": 52, "score": 0.7395964860916138}, {"content": "Title: Successful recovery from severe COVID\u201019 pneumonia after kidney transplantation: The interplay between immunosuppression and novel therapy including tocilizumab Content: Although immunosuppressed patients may be more prone to SARS\u2010CoV\u20102 infection with atypical presentation, long\u2010term immunosuppression therapy may provide some sort of protection for severe clinical complications of COVID\u201019. The interaction between immunosuppression and new antiviral drugs in the treatment of transplanted patients contracting COVID\u201019 has not yet been fully investigated. Moreover, data regarding the optimal management of these patients are still very limited. We report a case of the successful recovery from severe COVID\u201019 of a kidney\u2010transplanted patient treated with hydroxychloroquine, lopinavir/ritonavir, steroid, and tocilizumab.", "qid": 34, "docid": "fdpc6ym2", "rank": 53, "score": 0.7395830154418945}, {"content": "Title: Successful treatment of severe COVID-19 pneumonia in a liver transplant recipient Content: Coronavirus disease 2019 (COVID-19) pandemic spreads rapidly and may be an increasing challenge for transplant community. Clinical data on COVID-19 infection in transplant population is very limited. Herein we presented the clinical course and outcome of a 50-year-old male post liver transplantation who contracted COVID-19, with subsequent infection of his wife. The process of illness was representative. A therapeutic regime with temporary immunosuppression withdrawal and systemic low-dose corticosteroid as principle was involved in the management of the patient which made him recover from severe COVID-19 pneumonia.", "qid": 34, "docid": "0kthumgi", "rank": 54, "score": 0.7393203973770142}, {"content": "Title: Successful Treatment of Severe COVID-19 Pneumonia in a Liver Transplant Recipient. Content: Coronavirus disease 2019 (COVID-19) pandemic spreads rapidly and may be an increasing challenge for transplant community. Clinical data on COVID-19 infection in transplant population is very limited. Herein we presented the clinical course and outcome of a 50-year-old male post liver transplantation who contracted COVID-19, with subsequent infection of his wife. The process of illness was representative. A therapeutic regime with temporary immunosuppression withdrawal and systemic low-dose corticosteroid as principle was involved in the management of the patient which made him recover from severe COVID-19 pneumonia.", "qid": 34, "docid": "uiw9auzx", "rank": 55, "score": 0.7393203973770142}, {"content": "Title: Coagulopathy and Plausible Benefits of Anticoagulation Among COVID-19 Patients Content: The exceptional outbreak of COVID-19 pandemic has let the scientific community to work closely and quickly learnt things in a very short period of time. This has let us recognise that thromboembolic complications are responsible morbidity and mortality among the COVID-19 infected patients. Available data have suggested a possible multifactorial basis of this complications, and while efforts are being made to treat this infection, preventive measure with the use of systemic anticoagulation were quickly adopted to deal with this complication. Despite obvious benefits as appeared with the use of systemic anticoagulation, most of the emerged data were retrospective, and hence raise questions on the possible interplay of the confounders as well as long term benefits and safety of systemic anticoagulation.", "qid": 34, "docid": "diwqblnl", "rank": 56, "score": 0.7390937805175781}, {"content": "Title: The British Thoracic Society survey of rehabilitation to support recovery of the Post Covid -19 population. Content: Objectives Those discharged from hospital after treatment for Covid-19 are likely to have significant and ongoing symptoms, functional impairment and psychological disturbances. There is an immediate need to develop a safe and efficient discharge process and recovery programme. Pulmonary rehabilitation is well placed to deliver a rehabilitation programme for this group but will most likely need to be adapted for the post Covid-19 population. The purpose of this survey was to rapidly identify the components of a post-Covid-19 rehabilitation assessment and elements of a successful rehabilitation programme that would be required to deliver a comprehensive service for those post Covid-19 to inform service delivery. Design A survey comprising a series of closed questions and a free text comments box allowing for a qualitative analysis. Setting Online survey. Participants British Thoracic Society members and multi-professional clinicians, across specialities were invited to take part. Results 1031 participants responded from a broad range of specialities over 6 days. There was overwhelming support for early post discharge from hospital phase of the recovery programme to advise patients about the management of fatigue (95% agreed/ strongly agreed), breathlessness (94%), and mood disturbances (including symptoms of anxiety and depression) 92%. At the 6-8-week time point an assessment was considered important, focusing on the assessment of a broad range of possible symptoms and the need to potentially return to work. Recommendations for the intervention described a holistic programme focusing on symptom management, return of function and return to employment. The free text comments added depth to the survey and the need not to reinvent the wheel rather adapt well established (pulmonary rehabilitation) services to accommodate the needs of the post Covid-19 population. Conclusion The responses indicate the huge interest and the urgent need establish a programme to support and mitigate the long term impact of Covid-19.", "qid": 34, "docid": "s24y9vrw", "rank": 57, "score": 0.7390340566635132}, {"content": "Title: Pulmonary Rehabilitation for Patients with Coronavirus Disease 2019 (COVID-19) Content: As a highly infectious respiratory tract disease, coronavirus disease 2019 (COVID-19) can cause respiratory, physical, and psychological dysfunction in patients. Therefore, pulmonary rehabilitation is crucial for both admitted and discharged patients of COVID-19. In this study, based on the newly released pulmonary rehabilitation guidelines for patients with COVID-19, as well as evidence from the pulmonary rehabilitation of patients with severe acute respiratory syndrome, we investigated pulmonary rehabilitation for patients with COVID-19 having complications, such as chronic pulmonary disease, and established an intelligent respiratory rehabilitation model for these patients.", "qid": 34, "docid": "w4vvaio7", "rank": 58, "score": 0.7386241555213928}, {"content": "Title: A Case of COVID-19 Infection With Delayed Thromboembolic Complication on Warfarin Content: Novel coronavirus disease 2019 (COVID-19) pandemic has posed an unprecedented threat to humanity with more than eight million infections and 450,000 deaths reported worldwide so far. The spectrum of the disease varies from mild asymptomatic infection to severe disease with rapid progression to acute respiratory distress syndrome and multiorgan failure. It is associated with a prothrombotic state and hence there is a risk of thromboembolic complications in critically ill patients, even after recovery. However, the duration of prothrombotic risk after recovery is yet to be determined. We present the case of a 78-year-old man with a history of atrial fibrillation on warfarin who had been recently discharged to a nursing home after recovering from COVID-19 pneumonia and presented to the emergency department a month later with worsening shortness of breath and cough. He was found to have worsening respiratory failure with multiple segmental pulmonary emboli, despite being on warfarin, and supratherapeutic international normalized ratio (INR). He required mechanical ventilation and was started on steroids and therapeutic enoxaparin anticoagulation. This case highlights the risk of delayed thromboembolic complications in patients with COVID-19 infection and the need to identify the subgroup of patients with a higher risk of thromboembolism, such as discharges to nursing homes and those in need of oxygen requirement; and those with underlying comorbid conditions that may require anticoagulation for a longer duration. The role of heparin is being increasingly investigated in patients with COVID-19 infection; however, the role of other anticoagulants such as warfarin is yet to be defined.", "qid": 34, "docid": "rhoo2k3r", "rank": 59, "score": 0.7381218671798706}, {"content": "Title: Long-term clinical outcomes in survivors of severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus outbreaks after hospitalisation or ICU admission: A systematic review and meta-analysis. Content: OBJECTIVE To determine long-term clinical outcomes in survivors of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus infections after hospitalization or intensive care unit admission. DATA SOURCES Ovid MEDLINE, EMBASE, CINAHL Plus, and PsycINFO were searched. STUDY SELECTION Original studies reporting clinical outcomes of adult SARS and MERS survivors 3 months after admission or 2 months after discharge were included. DATA EXTRACTION Studies were graded using the Oxford Centre for Evidence-Based Medicine 2009 Level of Evidence Tool. Meta-analysis was used to derive pooled estimates for prevalence/severity of outcomes up to 6 months, and beyond. DATA SYNTHESIS Of 1,169 identified studies, 28 were included in the analysis. Pooled analysis revealed that common complications up to 6 months were: impaired diffusing capacity for carbon monoxide (prevalence 27%, 95% confidence interval (CI) 15-45%); and reduced exercise capacity ((mean 6-min walking distance 461 m, CI 450-473 m). The prevalences of post-traumatic stress disorder (39%, 95% CI 31-47%), depression (33%, 95% CI 20-50%) and anxiety (30%, 95% CI 10-61) beyond 6 months were considerable. Low scores on Short-Form 36 were identified at 6 months and beyond. CONCLUSION Lung function abnormalities, psychological impairment and reduced exercise capacity were common in SARS and MERS survivors. Clinicians should anticipate and investigate similar long-term outcomes in COVID-19 survivors.", "qid": 34, "docid": "bpiiddi7", "rank": 60, "score": 0.7378854155540466}, {"content": "Title: Virologic and clinical characteristics for prognosis of severe COVID-19: a retrospective observational study in Wuhan, China Content: Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has progressed to a pandemic associated with substantial morbidity and mortality. The WHO and the United States Center for Disease Control and Prevention (CDC) have issued interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19), but there is limited data on the virologic and clinical characteristics for prognosis of severe COVID-19. Methods: A total of 50 patients with severe COVID-19 were divided into good and poor recovery groups. The dynamic viral shedding and serological characteristics of SARS-CoV-2 were explored. The risk factors associated with poor recovery and lung lesion resolutions were identified. In addition, the potential relationships among the viral shedding, the pro-inflammatory response, and lung lesion evolutions were characterized. Results: A total of 58% of the patients had poor recovery and were more likely to have a prolonged interval of viral shedding. The longest viral shedding was 57 days after symptom onset. Older age, hyperlipemia, hypoproteinemia, corticosteroid therapy, consolidation on chest computed-tomography (CT), and prolonged SARS-CoV-2 IgM positive were all associated with poor recovery. Additionally, the odds of impaired lung lesion resolutions were higher in patients with hypoproteinemia, hyperlipemia, and elevated levels of IL-4 and ferritin. Finally, viral shedding and proinflammatory responses were closely correlated with lung lesion evolutions on chest CT. Conclusions Patients with severe COVID-19 have prolonged SARS-CoV-2 infection and delayed intermittent viral shedding. Older age, hyperlipemia, hypoproteinemia, corticosteroid usage, and prolonged SARS-CoV-2 IgM positive might be utilized as predicative factors for the patients with poor recovery.", "qid": 34, "docid": "4989atst", "rank": 61, "score": 0.7374303340911865}, {"content": "Title: Characteristics, comorbidities, 30-day outcome and in-hospital mortality of patients hospitalised with COVID-19 in a Swiss area - a retrospective cohort study. Content: BACKGROUND Since its first description in December 2019, coronavirus disease 19 (COVID-19) has spread worldwide. There is limited information about presenting characteristics and outcomes of Swiss patients requiring hospitalisation. Furthermore, outcomes 30 days after onset of symptoms and after hospital discharge have not been described. AIMS To describe the clinical characteristics, outcomes 30 days after onset of symptoms and in-hospital mortality of a cohort of patients hospitalised for COVID-19 in a Swiss area. METHODS In this retrospective cohort study, we included all inpatients hospitalised with microbiologically confirmed COVID-19 between 1 March and 12 April 2020 in the public hospital network of a Swiss area (Fribourg). Demographic data, comorbidities and outcomes were recorded. Rate of potential hospital-acquired infection, outcomes 30 days after onset of symptoms and in-hospital mortality are reported. RESULTS One hundred ninety-six patients were included in the study. In our population, 119 (61%) were male and the median age was 70 years. Forty-nine patients (25%) were admitted to the intensive care unit (ICU). The rate of potential hospital-acquired infection was 7%. Overall, 30 days after onset of symptoms 117 patients (60%) had returned home, 23 patients (12%) were in a rehabilitation facility, 18 patients (9%) in a medical ward, 6 patients (3%) in ICU and 32 (16%) patients had died. Among patients who returned home within 30 days, 73 patients (63%) reported persistent symptoms. The overall in-hospital mortality was 17%. CONCLUSION We report the first cohort of Swiss patients hospitalised with COVID-19. Thirty days after onset of the symptoms, 60% had returned home. Among them, 63% still presented symptoms. Studies with longer follow-up are needed to document long-term outcomes in patients hospitalised with COVID-19.", "qid": 34, "docid": "cpp2l8n5", "rank": 62, "score": 0.7371168732643127}, {"content": "Title: Detection of lung hypoperfusion in Covid-19 patients during recovery by digital imaging quantification Content: Purpose. A large number of patients affected by the SARS-Cov-2 virus worldwide undergo recovery of symptoms in about one month. Among these patients, the healing process is still under observation, with some patients in need of careful clinical monitoring. While the radiological findings have been shown to regress almost completely, little knowledge is available at the moment about other complications in the lung and in other organs. We then investigated the lung perfusion conditions in patients affected by COVID- 19 during recovery. Method. We retrospectively studied 20 patients, from 14 to 60 days after resolution of the COVID-19 symptoms, using chest CT. In a subgroup of 5 patients contrasted CT was used. Beside normal radiological evaluation of lung tissue, perfusion conditions were evaluated by digital image processing in the lung volume automatically segmented. Results. Pulmonary lung evaluation showed that COVID-19 pneumonia almost completely regressed, with mild focal areas affected by fibrous stripes. In patients that reported dyspnea, lung CT showed complete resolution of interstitial changes. Quantification of lung perfusion condition by contrasted CT, showed that dyspnea in 3 patients was associated with areas of hypoperfusion, while in 2 patients not reporting dyspnea perfusion conditions were comparable to normal controls. Conclusions. Although we obtained preliminary data, this is the first report on quantitative evaluation of hypoperfused lung tissue detected in recovering COVID-19 patients. These results suggest the need to further investigate these patients and to redefine the role of CT evaluation for diagnostic purposes as well as for evaluation of potential treatments.", "qid": 34, "docid": "sjv78l0y", "rank": 63, "score": 0.7368512153625488}, {"content": "Title: The Stanford Hall consensus statement for post-COVID-19 rehabilitation Content: The highly infectious and pathogenic novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2, has emerged causing a global pandemic. Although COVID-19 predominantly affects the respiratory system, evidence indicates a multisystem disease which is frequently severe and often results in death. Long-term sequelae of COVID-19 are unknown, but evidence from previous CoV outbreaks demonstrates impaired pulmonary and physical function, reduced quality of life and emotional distress. Many COVID-19 survivors who require critical care may develop psychological, physical and cognitive impairments. There is a clear need for guidance on the rehabilitation of COVID-19 survivors. This consensus statement was developed by an expert panel in the fields of rehabilitation, sport and exercise medicine (SEM), rheumatology, psychiatry, general practice, psychology and specialist pain, working at the Defence Medical Rehabilitation Centre, Stanford Hall, UK. Seven teams appraised evidence for the following domains relating to COVID-19 rehabilitation requirements: pulmonary, cardiac, SEM, psychological, musculoskeletal, neurorehabilitation and general medical. A chair combined recommendations generated within teams. A writing committee prepared the consensus statement in accordance with the appraisal of guidelines research and evaluation criteria, grading all recommendations with levels of evidence. Authors scored their level of agreement with each recommendation on a scale of 0-10. Substantial agreement (range 7.5-10) was reached for 36 recommendations following a chaired agreement meeting that was attended by all authors. This consensus statement provides an overarching framework assimilating evidence and likely requirements of multidisciplinary rehabilitation post COVID-19 illness, for a target population of active individuals, including military personnel and athletes.", "qid": 34, "docid": "qrpr0nz3", "rank": 64, "score": 0.7365090250968933}, {"content": "Title: The Stanford Hall consensus statement for post-COVID-19 rehabilitation. Content: The highly infectious and pathogenic novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2, has emerged causing a global pandemic. Although COVID-19 predominantly affects the respiratory system, evidence indicates a multisystem disease which is frequently severe and often results in death. Long-term sequelae of COVID-19 are unknown, but evidence from previous CoV outbreaks demonstrates impaired pulmonary and physical function, reduced quality of life and emotional distress. Many COVID-19 survivors who require critical care may develop psychological, physical and cognitive impairments. There is a clear need for guidance on the rehabilitation of COVID-19 survivors. This consensus statement was developed by an expert panel in the fields of rehabilitation, sport and exercise medicine (SEM), rheumatology, psychiatry, general practice, psychology and specialist pain, working at the Defence Medical Rehabilitation Centre, Stanford Hall, UK. Seven teams appraised evidence for the following domains relating to COVID-19 rehabilitation requirements: pulmonary, cardiac, SEM, psychological, musculoskeletal, neurorehabilitation and general medical. A chair combined recommendations generated within teams. A writing committee prepared the consensus statement in accordance with the appraisal of guidelines research and evaluation criteria, grading all recommendations with levels of evidence. Authors scored their level of agreement with each recommendation on a scale of 0-10. Substantial agreement (range 7.5-10) was reached for 36 recommendations following a chaired agreement meeting that was attended by all authors. This consensus statement provides an overarching framework assimilating evidence and likely requirements of multidisciplinary rehabilitation post COVID-19 illness, for a target population of active individuals, including military personnel and athletes.", "qid": 34, "docid": "hpf1epqg", "rank": 65, "score": 0.736508846282959}, {"content": "Title: Immediate and long-term consequences of COVID-19 infections for the development of neurological disease Content: Increasing evidence suggests that infection with Sars-CoV-2 causes neurological deficits in a substantial proportion of affected patients. While these symptoms arise acutely during the course of infection, less is known about the possible long-term consequences for the brain. Severely affected COVID-19 cases experience high levels of proinflammatory cytokines and acute respiratory dysfunction and often require assisted ventilation. All these factors have been suggested to cause cognitive decline. Pathogenetically, this may result from direct negative effects of the immune reaction, acceleration or aggravation of pre-existing cognitive deficits, or de novo induction of a neurodegenerative disease. This article summarizes the current understanding of neurological symptoms of COVID-19 and hypothesizes that affected patients may be at higher risk of developing cognitive decline after overcoming the primary COVID-19 infection. A structured prospective evaluation should analyze the likelihood, time course, and severity of cognitive impairment following the COVID-19 pandemic.", "qid": 34, "docid": "ds12pmp1", "rank": 66, "score": 0.7363526225090027}, {"content": "Title: COVID-19 and the elderly: insights into pathogenesis and clinical decision-making Content: The elderly may represent a specific cluster of high-risk patients for developing COVID-19 with rapidly progressive clinical deterioration. Indeed, in older individuals, immunosenescence and comorbid disorders are more likely to promote viral-induced cytokine storm resulting in life-threatening respiratory failure and multisystemic involvement. Early diagnosis and individualized therapeutic management should be developed for elderly subjects based on personal medical history and polypharmacotherapy. Our review examines the pathogenesis and clinical implications of ageing in COVID-19 patients; finally, we discuss the evidence and controversies in the management in the long-stay residential care homes and aspects of end-of-life care for elderly patients with COVID-19.", "qid": 34, "docid": "mnmn75vd", "rank": 67, "score": 0.736268162727356}, {"content": "Title: Clinical Characteristics on 25 Discharged Patients with COVID-19 Virus Returning Content: Here we report the clinical features of 25 discharged patients with COVID-19 recovery. Our analysis indicated that there was a significant inverse correlation existed between serum D-Dimer level and the duration of antiviral treatment, while lymphocyte concentration significantly positively correlated with the duration of virus reversal.", "qid": 34, "docid": "jarnavwl", "rank": 68, "score": 0.7355725169181824}, {"content": "Title: COVID-19 and immune checkpoint inhibitors: initial considerations Content: COVID-19 infections are characterized by inflammation of the lungs and other organs that ranges from mild and asymptomatic to fulminant and fatal. Patients who are immunocompromised and those with cardiopulmonary comorbidities appear to be particularly afflicted by this illness. During pandemic conditions, many aspects of cancer care have been impacted. One important clinical question is how to manage patients who need anticancer therapy, including immune checkpoint inhibitors (ICIs) during these conditions. Herein, we consider diagnostic and therapeutic implications of using ICI during this unprecedented period of COVID-19 infections. In particular, we consider the impact of ICI on COVID-19 severity, decisions surrounding continuing or interrupting therapy, diagnostic measures in patients with symptoms or manifestations potentially consistent with either COVID-19 or ICI toxicity, and resumption of therapy in infected patients. While more robust data are needed to guide clinicians on management of patients with cancer who may be affected by COVID-19, we hope this commentary provides useful insights for the clinical community.", "qid": 34, "docid": "kd7qi21t", "rank": 69, "score": 0.7350790500640869}, {"content": "Title: Establishment of a COVID-19 Recovery Unit in a Veteran Affairs (VA) Post-Acute Facility Content: Coronavirus disease 19 (COVID-19) is now an epidemic of global proportion with major adverse impacts on older adults, persons with chronic diseases, and especially residents of long-term care facilities. This health catastrophe has challenged healthcare facilities' capacity to deliver care to not only COVID-19 patients but all patients who need hospital care. We report on a novel approach of utilizing long-term care beds at a Department of Veterans Affairs healthcare facility for managing recovering COVID-19 patients.", "qid": 34, "docid": "3thnu3kk", "rank": 70, "score": 0.735059380531311}, {"content": "Title: A Multicentre Study of 2019 Novel Coronavirus Disease Outcomes of Cancer Patients in Wuhan, China Content: Background: At present, there is a global pandemic of coronavirus disease 2019 (COVID-19) pneumonia. Two previous case series from China have suggested that cancer patients are at a higher risk of COVID-19 pneumonia, but the reports were limited by small numbers and few clinical information. Objective: To study clinical characteristics and outcomes of cancer patients infected with COVID-19. Design: Retrospective study. Setting: Four designated COVID-16 hospitals in Wuhan, Hubei province, China. Participants: Medical records of 67 cancer patients admitted to hospitals between Jan 5, 2020 to Feb 18, 2020 were included. Measurements: Demographic, clinical, laboratory, radiological and treatment data were collected. Survival data of the cohort was cut-off on Mar 10, 2020. Results: Of the 67 patients (median age: 66 years), the median age of patients who had severe illness was older than that of patients who had mild symptoms (P<0.001). Forty-three (64.2%) patients had other concurrent chronic diseases, and the proportion of severe patients had co-morbidities was higher than patients with mild disease (P=0.004). Twenty-three (34.3%) patients were still at the anticancer treatment phase, but no tumour progression and recurrence was observed for all the patients during the treatment of COVID-19 pneumonia. About 70% of these patients had fever (n=53, 79.1%) and/or cough (n=50, 74.6%). Lymphocytopenia was the main laboratory finding accompanying increased C-reactive protein and procalcitonin in cancer patients, especially in severe cases. By Mar 10, 2020, 18 (26.9%) patients died from COVID-19, and 39 (58.2%) patients have been discharged. The median age of survivors was younger than that of deaths (P=0.014). Lung cancer (n=15, 22.4%) with COVID-19 was the most common cancer type and accounted for the highest proportion COVID-19 resulted deaths (33.3%, 5/15). We observed a tendency that patients at the follow-up phase had a better prognosis than that at anticancer treatment phase (P=0.095). Limitation: This is a retrospective study with only 67 cases from four hospitals. And some specific clinical information was insufficient. Conclusion: This study showed COVID-19 patients with cancer seem to have a higher proportion of severe cases and poorer prognosis. The tendency of poor prognosis was more obvious in patients at anticancer treatment phase. We should pay more intensive attentions to cancer patients infected with COVID-19.", "qid": 34, "docid": "8rxjju0t", "rank": 71, "score": 0.7349836826324463}, {"content": "Title: Spontaneous Pneumothorax Following COVID-19 Pneumonia Content: Patient presents with dyspnea after recovering from COVID-19 pneumonia and is found to have pneumothorax. This represents an under-reported sequelae of COVID-19.", "qid": 34, "docid": "4wlrv75c", "rank": 72, "score": 0.7349262237548828}, {"content": "Title: The potential long-term impact of the COVID-19 outbreak on patients with non-communicable diseases in Europe: consequences for healthy ageing Content: The early stages of the COVID-19 pandemic have focused on containing SARS-CoV-2 infection and identifying treatment strategies. While controlling this communicable disease is of utmost importance, the long-term effect on individuals with non-communicable diseases (NCD) is significant. Although certain NCDs appear to increase the severity of COVID-19 and mortality risk, SARS-CoV-2 infection in survivors with NCDs may also affect the progression of their pre-existing clinical conditions. Infection containment measures will have substantial short- and long-term consequences; social distancing and quarantine restrictions will reduce physical activity and increase other unhealthy lifestyles, thus increasing NCD risk factors and worsening clinical symptoms. Vitamin D levels might decrease and there might be a rise in mental health disorders. Many countries have made changes to routine management of NCD patients, e.g., cancelling non-urgent outpatient visits, which will have important implications for NCD management, diagnosis of new-onset NCDs, medication adherence, and NCD progression. We may have opportunities to learn from this unprecedented crisis on how to leverage healthcare technologies and improve procedures to optimize healthcare service provision. This article discusses how the COVID-19 outbreak and related infection control measures could hit the most frail individuals, worsening the condition of NCD patients, while further jeopardizing the sustainability of the healthcare systems. We suggest ways to define an integrated strategy that could involve both public institutional entities and the private sector to safeguard frail individuals and mitigate the impact of the outbreak.", "qid": 34, "docid": "bcd0y9c1", "rank": 73, "score": 0.7343211770057678}, {"content": "Title: COVID-19 pandemic. What should PRM specialists do? A clinician's perspective Content: BACKGROUND: COVID-19 pandemic is rapidly spreading all over the world, creating the risk for an healthcare collapse. While acute care and intensive care units are the main pillars of the early response to the disease, rehabilitative medicine should play an important part in allowing COVID-19 survivors to reduce disability and optimize the function of acute hospital setting. AIM: To share the experience and the international perspective of different rehabilitation centers, treating COVID-19 survivors. DESIGN: Not applicable. POPULATION: COVID-19 survivors. METHODS: A group of Physical Medicine & Rehabilitation specialists from eleven different countries in Europe and North America have shared their clinical experience in dealing with COVID-19 survivors and how they have managed the re-organization of rehabilitation services. RESULTS: In our experience the most important sequelae of severe and critical forms of COVID-19 are: 1) respiratory; 2) cognitive, central and peipheral nervous system; 3) deconditioning; 4) critical illness related myopathy and neuropathy; 5) dysphagia; 6) joint stiffness and pain; 7) psychiatric. CONCLUSIONS: We analyze all these consequences and propose some practical treatment options, based on current evidence and clinical experience, as well as several suggestions for management of rehabilitation services and patients with suspected or confirmed infection by SARS-CoV-2. CLINICAL REHABILITATION IMPACT: COVID-19 survivors have some specific rehabilitation needs. Experience from other centers may help colleagues in organizing their services and providing better care to their patients.", "qid": 34, "docid": "99b09xpi", "rank": 74, "score": 0.7338232398033142}, {"content": "Title: Clinical Features of COVID-19 in a Young Man with Massive Cerebral Hemorrhage\u2014Case Report Content: COVID-19 is currently a pandemic in the world, can invade multiple systems, and has a high morbidity and mortality. So far, no cases of acute cerebrovascular disease have been reported. This article reports the clinical features of a COVID-19 patient whose first symptom was cerebral hemorrhage. More importantly, after the craniotomy, the patient had high fever and it was difficult to retreat. After cerebrospinal fluid testing, it was determined that an intracranial infection had occurred. After anti-infection and plasma infusion of the recovered person, the patient\u2019s symptoms gradually improved. This case suggests that COVID-19 may infringe on cerebral blood vessels and cause cerebral hemorrhage. Transfusion of plasma from rehabilitation patients is effective for critically ill patients.", "qid": 34, "docid": "cso6l6ze", "rank": 75, "score": 0.7337599992752075}, {"content": "Title: The Impact of the COVID-19 Pandemic on Cancer Patients Content: In December 2019, a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused an outbreak of coronavirus disease 2019 (COVID-19). Severe complications have been reported to occur in 33% of patients with COVID-19 and include acute respiratory distress syndrome, acute renal failure, acute respiratory injury, septic shock, and severe pneumonia. Currently, there is no specific treatment or approved vaccine against COVID-19 and many clinical trials are currently investigating potential medications to treat COVID-19. The immunosuppressed status of some cancer patients (whether caused by the disease itself or the treatment) increases their risk of infection compared with the general population. This short review aims to focus on the impact of COVID-19 on a cancer patient and discuss management options and recommendation in addition to highlighting the currently available clinical guidelines and resources.", "qid": 34, "docid": "dtg18ob5", "rank": 76, "score": 0.7337026596069336}, {"content": "Title: Epidemiology of CoVID-19 and predictors of recovery in the Republic of Korea Content: Background: The recent CoVID-19 pandemic has emerged as a threat to global health. Though current evidence on the epidemiology of the disease is emerging, very little is known about the predictors of recovery. We describe the epidemiology of confirmed CoVID-19 patients in Republic of Korea and identify predictors of recovery. Materials and methods: Using publicly available data for confirmed CoVID-19 cases from the Korea Centers for Disease Control and Prevention from January 20, 2020 to April 30, 2020, we undertook descriptive analyses of cases stratified by sex, age group, place of exposure, date of confirmation and province. Correlation was tested among all predictors (sex, age group, place of exposure and province) with the Pearsons correlation coefficient. Associations between recovery from CoVID-19 and predictors were estimated using a multivariable logistic regression model. Results: Majority of the confirmed cases were females (56 percent), from 20-29 age group (24.3 percent), and primarily from three provinces Gyeongsangbuk (36.9 percent), Gyeonggi (20.5 percent) and Seoul (17.1 percent). Case fatality ratio was 2.1 percent and 41.6 percent cases recovered. Older patients, patients from certain provinces such as Daegu, Gyeonggi, Gyeongsangbuk, Jeju, Jeollabuk and Jeollanam, and those contracting the disease from healthcare settings had lower recovery. Conclusions: Our study adds to the very limited evidence base on potential predictors of recovery among confirmed CoVID-19 cases. We call additional research to explore the predictors of recovery and support development of policies to protect the vulnerable patient groups.", "qid": 34, "docid": "nmpppztq", "rank": 77, "score": 0.733253002166748}, {"content": "Title: \u201cClinical Characteristics, Outcomes and Prognosticators in Adult Patients Hospitalized with COVID-19\u201d Content: BACKGROUND: COVID-19 is a novel disease caused by SARS-CoV-2. METHODS: We conducted a retrospective evaluation of patients admitted with COVID-19 to one site in March 2020. Patients were stratified into three groups: survivors who did not receive mechanical ventilation (MV), survivors who received MV and those who received MV and died during hospitalization. RESULTS: There were 140 hospitalizations; 22 deaths (mortality rate 15.7%), 83 (59%) survived and did not receive MV, 35 (25%) received MV and survived; 18 (12.9%) received MV and died. Thee mean age of each group was 57.8, 55.8 and 72.7 years respectively (p=.0001). Of those who received MV and died, 61% were male (p=.01). More than half the patients (n=90, 64%) were African American. First measured d-dimer >575.5 ng/mL, procalcitonin > 0.24 ng/mL, LDH > 445.6 units/L and BNP > 104.75 pg/mL had odds ratios of 10.5, 5, 4.5 and 2.9 respectively for MV (p < .05 for all). Peak BNP > 167.5 pg/mL had an odds ratio of 6.7 for inpatient mortality when mechanically ventilated (p= .02). CONCLUSIONS: Age and gender may impact outcomes in COVID-19. D-dimer, procalcitonin, LDH and BNP may serve as early indicators of disease trajectory.", "qid": 34, "docid": "rluya5ui", "rank": 78, "score": 0.7330770492553711}, {"content": "Title: \"Clinical Characteristics, Outcomes and Prognosticators in Adult Patients Hospitalized with COVID-19\" Content: BACKGROUND: COVID-19 is a novel disease caused by SARS-CoV-2. METHODS: We conducted a retrospective evaluation of patients admitted with COVID-19 to one site in March 2020. Patients were stratified into three groups: survivors who did not receive mechanical ventilation (MV), survivors who received MV and those who received MV and died during hospitalization. RESULTS: There were 140 hospitalizations; 22 deaths (mortality rate 15.7%), 83 (59%) survived and did not receive MV, 35 (25%) received MV and survived; 18 (12.9%) received MV and died. Thee mean age of each group was 57.8, 55.8 and 72.7 years respectively (p=.0001). Of those who received MV and died, 61% were male (p=.01). More than half the patients (n=90, 64%) were African American. First measured d-dimer >575.5 ng/mL, procalcitonin > 0.24 ng/mL, LDH > 445.6 units/L and BNP > 104.75 pg/mL had odds ratios of 10.5, 5, 4.5 and 2.9 respectively for MV (p < .05 for all). Peak BNP > 167.5 pg/mL had an odds ratio of 6.7 for inpatient mortality when mechanically ventilated (p= .02). CONCLUSIONS: Age and gender may impact outcomes in COVID-19. D-dimer, procalcitonin, LDH and BNP may serve as early indicators of disease trajectory.", "qid": 34, "docid": "ylzuh3t3", "rank": 79, "score": 0.7330770492553711}, {"content": "Title: An unresponsive COVID-19 patient Content: Neurological manifestations and complications are increasingly reported in coronavirus disease-19 (COVID-19) patients. Although pulmonary manifestations are more common, patients with severe disease may present with neurological symptoms such as in our case. We describe a case report of a 50-year-old male without previous known comorbidity who was found unresponsive due to COVID-19-related neurological complications. During this pandemic, an emergency radiologist should be well acquainted with various neurological manifestations of COVID-19. In this article, we will discuss the pathogenesis, imaging findings, and differentials of this disease.", "qid": 34, "docid": "c0m8jjmk", "rank": 80, "score": 0.732952356338501}, {"content": "Title: An unresponsive COVID-19 patient. Content: Neurological manifestations and complications are increasingly reported in coronavirus disease-19 (COVID-19) patients. Although pulmonary manifestations are more common, patients with severe disease may present with neurological symptoms such as in our case. We describe a case report of a 50-year-old male without previous known comorbidity who was found unresponsive due to COVID-19-related neurological complications. During this pandemic, an emergency radiologist should be well acquainted with various neurological manifestations of COVID-19. In this article, we will discuss the pathogenesis, imaging findings, and differentials of this disease.", "qid": 34, "docid": "3dq2mf6l", "rank": 81, "score": 0.732952356338501}, {"content": "Title: Coronavirus Disease-2019 (COVID-19) and Cardiovascular Complications Content: The coronavirus disease-2019 (COVID-19) has become a global pandemic. It has spread to more than 100 countries, and more than 1 million cases have been confirmed. Although coronavirus causes severe respiratory infections in humans, accumulating data have demonstrated cardiac complications and poor outcome in patients with COVID-19. A large percent of patients have underlying cardiovascular disease, and they are at a high risk of developing cardiac complications. The basics of the virus, the clinical manifestations, and the possible mechanisms of cardiac complications in patients with COVID-19 are reviewed. Before an effective vaccine or medicine is available, supportive therapy and identifying patients who are at high risk of cardiac complications are important.", "qid": 34, "docid": "wkp58iov", "rank": 82, "score": 0.7328768968582153}, {"content": "Title: Possible effects of coronavurus infection (COVID-19) on the cardiovascular system/ \u0412\u041b\u0418\u042f\u041d\u0418\u0415 \u041a\u041e\u0420\u041e\u041d\u0410\u0412\u0418\u0420\u0423\u0421\u041d\u041e\u0419 \u0418\u041d\u0424\u0415\u041a\u0426\u0418\u0418 (COVID-19) \u041d\u0410 \u0421\u0415\u0420\u0414\u0415\u0427\u041d\u041e-\u0421\u041e\u0421\u0423\u0414\u0418\u0421\u0422\u0423\u042e \u0421\u0418\u0421\u0422\u0415\u041c\u0423 Content: Acute viral respiratory infections can increase the risk of progression of a pre-existing condition, including a cardiovascular pathology. Life-threatening complications of Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitate research into the cardiovascular effects of COVID-19 crucial for developing adequate treatment strategy for infected patients, especially those of advanced age. This article reviews the literature on the clinical and functional characteristics of patients with COVID-19, including those with poor outcomes. The article looks at the pathophysiological processes occurring in the cardiovascular system in the setting of SARS-CoV-2 infection, risk factors and death predictors. It also discusses continuation of therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in patients with COVID-19.", "qid": 34, "docid": "8dfkddal", "rank": 83, "score": 0.7324473857879639}, {"content": "Title: A Collaborative Multidisciplinary Approach to the Management of Coronavirus Disease 2019 in the Hospital Setting Content: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which presents an unprecedented challenge to medical providers worldwide. Although most SARS-CoV-2-infected individuals manifest with a self-limited mild disease that resolves with supportive care in the outpatient setting, patients with moderate to severe COVID-19 will require a multidisciplinary collaborative management approach for optimal care in the hospital setting. Laboratory and radiologic studies provide critical information on disease severity, management options, and overall prognosis. Medical management is mostly supportive with antipyretics, hydration, oxygen supplementation, and other measures as dictated by clinical need. Among its medical complications is a characteristic proinflammatory cytokine storm often associated with end-organ dysfunction, including respiratory failure, liver and renal insufficiency, cardiac injury, and coagulopathy. Specific recommendations for the management of these medical complications are discussed. Despite the issuance of emergency use authorization for remdesivir, there are still no proven effective antiviral and immunomodulatory therapies, and their use in COVID-19 management should be guided by clinical trial protocols or treatment registries. The medical care of patients with COVID-19 extends beyond their hospitalization. Postdischarge follow-up and monitoring should be performed, preferably using telemedicine, until the patients have fully recovered from their illness and are released from home quarantine protocols.", "qid": 34, "docid": "8t7pos8x", "rank": 84, "score": 0.7322810292243958}, {"content": "Title: The enduring grip of covid-19 Content: Contrary to medical expectation, many people with covid-19 are still experiencing symptoms weeks or even months later. Linda Geddes investigates what's going on", "qid": 34, "docid": "f95i3al5", "rank": 85, "score": 0.7313628792762756}, {"content": "Title: A one-year hospital-based prospective CVOID-19 open-cohort in the Eastern Mediterranean region: The Khorshid COVID Cohort (KCC) study Content: The COVID-19 is rapidly scattering worldwide, and the number of cases in the Eastern Mediterranean Region is rising, there is a need for immediate targeted actions. We designed a longitudinal study in a hot outbreak zone to analyze the serial findings between infected patients for detecting temporal changes from February 2020. In a hospital-based open-cohort study, patients are followed from admission until one year from their discharge (the 1st, 4th, 12th weeks, and the first year). The measurements included demographic, socio-economics, symptoms, health service diagnosis and treatment, contact history, and psychological variables. The signs improvement, death, length of stay in hospital were considered as primary, and impaired pulmonary function and psychotic disorders were considered as main secondary outcomes. Notably, In the last two follow-ups, each patient attends the hospital to complete the Patient Health Questionnaire-9 (PHQ-9) and the Depression Anxiety Stress Scales (DASS-21). Moreover, clinical symptoms and respiratory functions are being determined in such follow-ups. Among the first 600 COVID-19 cases, a total of 490 patients with complete information (39% female; the average age of 57 {+/-} 15 years) were analyzed. Seven percent of these patients died. The three main leading causes of admission were: fever (77%), dry cough (73%), and fatigue (69%). The most prevalent comorbidities between COVID-19 patients were hypertension (35%), diabetes (28%), and ischemic heart disease (14%). The percentage of primary composite endpoints (PCEP), defined as death, the use of mechanical ventilation, or admission to an intensive care unit was 18%. The following comorbidities were significantly different in the positive and negative PCEP groups: acute kidney disease (p=0.008) and diabetes (p=0.026). For signs and symptoms, fatigue (p=0.020) and sore throat (p=0.001) were significantly different. This long-term prospective Cohort may support healthcare professionals in the management of resources following this pandemic.", "qid": 34, "docid": "v6acv7zg", "rank": 86, "score": 0.7310338020324707}, {"content": "Title: O Cora\u00e7\u00e3o e a COVID-19: O que o Cardiologista Precisa Saber./ O Cora\u00e7\u00e3o e a COVID-19: O que o Cardiologista Precisa Saber./ The Heart and COVID-19: What Cardiologists Need to Know Content: In face of the pandemic of the novel coronavirus disease 2019 (COVID-19), the management of patients with cardiovascular risk factors and/or disease is challenging. The cardiovascular complications evidenced in patients with COVID-19 derive from several mechanisms, ranging from direct viral injury to complications secondary to the inflammatory and thrombotic responses to the infection. The proper care of patients with COVID-19 requires special attention to the cardiovascular system aimed at better outcomes.", "qid": 34, "docid": "tp2tm0vn", "rank": 87, "score": 0.7302807569503784}, {"content": "Title: The Heart and COVID-19: What Cardiologists Need to Know. Content: In face of the pandemic of the novel coronavirus disease 2019 (COVID-19), the management of patients with cardiovascular risk factors and/or disease is challenging. The cardiovascular complications evidenced in patients with COVID-19 derive from several mechanisms, ranging from direct viral injury to complications secondary to the inflammatory and thrombotic responses to the infection. The proper care of patients with COVID-19 requires special attention to the cardiovascular system aimed at better outcomes.", "qid": 34, "docid": "7icw3be3", "rank": 88, "score": 0.7302807569503784}, {"content": "Title: COVID-19 pandemic. What should PRM specialists do? A clinician's perspective. Content: BACKGROUND COVID-19 pandemic is rapidly spreading all over the world, creating the risk for an healthcare collapse. While acute care and intensive care units are the main pillars of the early response to the disease, rehabilitative medicine should play an important part in allowing COVID-19 survivors to reduce disability and optimize the function of acute hospital setting. AIM To share the experience and the international perspective of different rehabilitation centers, treating COVID-19 survivors. DESIGN Not applicable. POPULATION COVID-19 survivors. METHODS A group of Physical Medicine & Rehabilitation specialists from eleven different countries in Europe and North America have shared their clinical experience in dealing with COVID-19 survivors and how they have managed the re-organization of rehabilitation services. RESULTS In our experience the most important sequelae of severe and critical forms of COVID-19 are: 1) respiratory; 2) cognitive, central and peipheral nervous system; 3) deconditioning; 4) critical illness related myopathy and neuropathy; 5) dysphagia; 6) joint stiffness and pain; 7) psychiatric. CONCLUSIONS We analyze all these consequences and propose some practical treatment options, based on current evidence and clinical experience, as well as several suggestions for management of rehabilitation services and patients with suspected or confirmed infection by SARS-CoV-2. CLINICAL REHABILITATION IMPACT COVID-19 survivors have some specific rehabilitation needs. Experience from other centers may help colleagues in organizing their services and providing better care to their patients.", "qid": 34, "docid": "b80qpzko", "rank": 89, "score": 0.7302566766738892}, {"content": "Title: Large pulmonary cavity in COVID-19 cured patient case report. Content: Coronavirus Disease 2019 (COVID-19) is a pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak began in Wuhan, China, and spread rapidly, with many cases confirmed in multiple countries. Usually, after viral pneumonia were clinical cured, the pulmonary lesions of majority patients will gradually be absorbed to complete dissipation, very few severe patients may retain pulmonary interstitial inflammation and fibrosis (1-3). In this case, we described one unique COVID-19 patient, the symptoms were: dry cough, fatigue, poor appetite and subjective fever, moreover, the patient was a non-smoker, had no pulmonary bullous, no history of tuberculosis, and also no hypertension or diabetes. The patient received antiviral therapy, antibacterial therapy, recombinant human interferon-\u03b12a, vitamin C and oxygen inhalation. After two weeks of treatment and observation, the patient was clinical cured and discharged. However, two days later, the patient had a sudden chest stuffiness, CT images indicted: his lung didn't heal like others, but developed a large pulmonary cavity in the lower lobe of right lung. In hospital, the patient showed no symptoms of infection for another 14 days, and the pulmonary cavity remain unchanged. This case suggested: it is important to follow convalescent COVID-19 patients, especially their lung CT images, to make sure a fully recovery.", "qid": 34, "docid": "3as5g5rx", "rank": 90, "score": 0.7301690578460693}, {"content": "Title: Olfactory and Gustatory Outcomes in COVID-19: A Prospective Evaluation in Nonhospitalized Subjects Content: OBJECTIVE: To prospectively assess the rate and timing of recovery of olfactory (OD) and gustatory (GD) dysfunction in patients affected by COVID-19. STUDY DESIGN: Cohort study. SETTING: Population-based evaluation in a COVID-19 high-prevalence region. SUBJECTS AND METHODS: We analyzed the clinical course of OD and GD in a cohort of home-quarantined SARS-CoV-2-positive patients from Northern Italy. Physicians administered a survey-based questionnaire at recruitment (T0). During follow-up, patients responded to online dedicated surveys modulated according to symptoms at T0. RESULTS: A total of 151 patients completed the follow-up survey. OD and/or GD were observed in 83% and 89% of subjects, respectively. Resolution rates of OD and GD at 30 days from onset were 87% and 82%, respectively. Risk factors for late resolution were grade of dysfunction at onset (total vs partial), gender, and presence of nasal congestion. Three (2%) patients previously reporting complete resolution of symptoms complained of subsequent recurrence of OD and/or GD after a mean of 19 days from resolution of the previous episode. CONCLUSION: COVID-19-related OD and GD had high rate of resolution in the first month from onset of symptoms. However, in 10% to 15% of patients, these symptoms showed only partial improvement after this period.", "qid": 34, "docid": "1g5dcvgq", "rank": 91, "score": 0.7299652695655823}, {"content": "Title: Olfactory and Gustatory Outcomes in COVID-19: A Prospective Evaluation in Nonhospitalized Subjects Content: OBJECTIVE: To prospectively assess the rate and timing of recovery of olfactory (OD) and gustatory (GD) dysfunction in patients affected by COVID-19. STUDY DESIGN: Cohort study. SETTING: Population-based evaluation in a COVID-19 high-prevalence region. SUBJECTS AND METHODS: We analyzed the clinical course of OD and GD in a cohort of home-quarantined SARS-CoV-2\u2013positive patients from Northern Italy. Physicians administered a survey-based questionnaire at recruitment (T0). During follow-up, patients responded to online dedicated surveys modulated according to symptoms at T0. RESULTS: A total of 151 patients completed the follow-up survey. OD and/or GD were observed in 83% and 89% of subjects, respectively. Resolution rates of OD and GD at 30 days from onset were 87% and 82%, respectively. Risk factors for late resolution were grade of dysfunction at onset (total vs partial), gender, and presence of nasal congestion. Three (2%) patients previously reporting complete resolution of symptoms complained of subsequent recurrence of OD and/or GD after a mean of 19 days from resolution of the previous episode. CONCLUSION: COVID-19\u2013related OD and GD had high rate of resolution in the first month from onset of symptoms. However, in 10% to 15% of patients, these symptoms showed only partial improvement after this period.", "qid": 34, "docid": "y4abjk1v", "rank": 92, "score": 0.7296777963638306}, {"content": "Title: Eye care in the intensive care unit during the COVID-19 pandemic Content: Ocular complications in critical care patients are common. There has been a surge in intensive care admissions following the COVID-19 outbreak. The management of COVID-19 exposes patients to a number of specific risk factors for developing ocular complications, which include non-invasive ventilation, mechanical ventilation and prone positioning. Consequently, it is likely that there will be an increase in the number of ocular complications secondary to the management of COVID-19 patients in the intensive care unit setting, and these complications could lead to permanent visual loss and blindness. Increased awareness of eye care in the intensive care unit setting is therefore vital to help prevent visual loss and maintain quality of life for patients recovering from COVID-19.", "qid": 34, "docid": "yf82a3tn", "rank": 93, "score": 0.7293308973312378}, {"content": "Title: Eye care in the intensive care unit during the COVID-19 pandemic. Content: Ocular complications in critical care patients are common. There has been a surge in intensive care admissions following the COVID-19 outbreak. The management of COVID-19 exposes patients to a number of specific risk factors for developing ocular complications, which include non-invasive ventilation, mechanical ventilation and prone positioning. Consequently, it is likely that there will be an increase in the number of ocular complications secondary to the management of COVID-19 patients in the intensive care unit setting, and these complications could lead to permanent visual loss and blindness. Increased awareness of eye care in the intensive care unit setting is therefore vital to help prevent visual loss and maintain quality of life for patients recovering from COVID-19.", "qid": 34, "docid": "10nl5z6u", "rank": 94, "score": 0.7293308973312378}, {"content": "Title: Renal Involvement and Early Prognosis in Patients with COVID-19 Pneumonia Content: BACKGROUND: Some patients with COVID-19 pneumonia also present with kidney injury, and autopsy findings of patients who died from the illness sometimes show renal damage. However, little is known about the clinical characteristics of kidney-related complications, including hematuria, proteinuria, and AKI. METHODS: In this retrospective, single-center study in China, we analyzed data from electronic medical records of 333 hospitalized patients with COVID-19 pneumonia, including information about clinical, laboratory, radiologic, and other characteristics, as well as information about renal outcomes. RESULTS: We found that 251 of the 333 patients (75.4%) had abnormal urine dipstick tests or AKI. Of 198 patients with renal involvement for the median duration of 12 days, 118 (59.6%) experienced remission of pneumonia during this period, and 111 of 162 (68.5%) patients experienced remission of proteinuria. Among 35 patients who developed AKI (with AKI identified by criteria expanded somewhat beyond the 2012 Kidney Disease: Improving Global Outcomes definition), 16 (45.7%) experienced complete recovery of kidney function. We suspect that most AKI cases were intrinsic AKI. Patients with renal involvement had higher overall mortality compared with those without renal involvement (28 of 251 [11.2%] versus one of 82 [1.2%], respectively). Stepwise multivariate binary logistic regression analyses showed that severity of pneumonia was the risk factor most commonly associated with lower odds of proteinuric or hematuric remission and recovery from AKI. CONCLUSIONS: Renal abnormalities occurred in the majority of patients with COVID-19 pneumonia. Although proteinuria, hematuria, and AKI often resolved in such patients within 3 weeks after the onset of symptoms, renal complications in COVID-19 were associated with higher mortality.", "qid": 34, "docid": "2977zk38", "rank": 95, "score": 0.7293112277984619}, {"content": "Title: Demographic and Clinical Characteristics of the Severe Covid-19 Infections: First Report from Mashhad University of Medical Sciences, Iran Content: Purpose. To report a comparison between fatalities and recovery of the severe Covid-19 infected patients based on demographic and clinical characteristics. Methods. Between 5 March and 12 May 2020, of 4,000 patients, 1,278 were laboratory confirmed to be Covid-19 infection in Mashhad, Iran. Finally, 334 deceased and 733 recovered cases were assessed in terms of demography, exposure history, health outcomes and clinical symptoms. Results. Mean (SD) age for confirmed patients, for deceased cases and for recovered cases. Mean (SD) age for all confirmed-patients was 56.9 (18.74), for the fatalities 67.26 (15.77) and for those recovered 52.82 (17.91) years. The rise of the mortality rate in relation to seniority was statistically significant. Despite a high frequency of Covid-19 infections accrued in the age groups of 30-39 and 40-49 years, most of these cases (88.2 and 85.8%, respectively) recovered. The median (IQR) duration of hospitalization was 9.0 (9) days. The most prevalent co-morbidities were cardiovascular disorders (21%) and diabetes (16.3%). Fever (63.8%), cough (68.1%), and dyspnoea (72.7%) were the most frequent clinical symptoms. 5.2% of infected-cases were healthcare workers that two (3%) of them died. Most patients (48%) received both antiviral and antibiotic therapy. The mortality rate of Kaletra combination prescribed for severe cases was 46.7%. Conclusions. The characteristics of Covid-19 varied from died to survived infected patients. There were a higher number of fatalities in younger patients than in international studies. Diabetes and cardiovascular disorders were most prevalent co-morbidities. The study could not address the case-fatality rate of Covid-19 infection that remains for future studies.", "qid": 34, "docid": "460sr6iw", "rank": 96, "score": 0.7290937900543213}, {"content": "Title: Cancer and COVID-19: Unmasking their ties Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) and its clinical manifestation, the coronavirus disease 2019 (COVID19) have rapidly spread across the globe, leading to the declaration of a pandemic. While most present mild symptoms, it appears as though nearly 20% of confirmed patients develop significant complications. These include acute respiratory distress syndrome, septic shock and multi-organ failure, with a 3-6% mortality. A plethora of treatments has been or is being assessed, but to date, none has been proven effective. Management is mainly symptomatic, with organ support for the critically ill. Several reports, mainly case series, from across the world have concluded that patients with malignancy appear more susceptible to severe infection and mortality from COVID-19. This could be attributed to immunosuppression, co-existing medical conditions and underlying pulmonary compromise which is often the case in lung malignancy. Patients with haematological cancer and those who are receiving active chemotherapy treatment may be at greatest risk due to increased immunosuppression. This pandemic tested the resilience of worldwide health-care systems in an unprecedented manner. It has forced oncologists to rethink the entire diagnostic and therapeutic process, based on the local prevalence and impact of COVID-19. In this review we will discuss the impact of COVID-19 on patients affected by cancer, their diagnosis and management, as well as the pathophysiology of COVID-19 induced acute respiratory distress symptoms and currently investigated treatment approaches.", "qid": 34, "docid": "1j1490n4", "rank": 97, "score": 0.728940486907959}, {"content": "Title: Cancer and COVID-19: Unmasking their ties. Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) and its clinical manifestation, the coronavirus disease 2019 (COVID19) have rapidly spread across the globe, leading to the declaration of a pandemic. While most present mild symptoms, it appears as though nearly 20% of confirmed patients develop significant complications. These include acute respiratory distress syndrome, septic shock and multi-organ failure, with a 3-6% mortality. A plethora of treatments has been or is being assessed, but to date, none has been proven effective. Management is mainly symptomatic, with organ support for the critically ill. Several reports, mainly case series, from across the world have concluded that patients with malignancy appear more susceptible to severe infection and mortality from COVID-19. This could be attributed to immunosuppression, co-existing medical conditions and underlying pulmonary compromise which is often the case in lung malignancy. Patients with haematological cancer and those who are receiving active chemotherapy treatment may be at greatest risk due to increased immunosuppression. This pandemic tested the resilience of worldwide health-care systems in an unprecedented manner. It has forced oncologists to rethink the entire diagnostic and therapeutic process, based on the local prevalence and impact of COVID-19. In this review we will discuss the impact of COVID-19 on patients affected by cancer, their diagnosis and management, as well as the pathophysiology of COVID-19 induced acute respiratory distress symptoms and currently investigated treatment approaches.", "qid": 34, "docid": "cjbfe2y5", "rank": 98, "score": 0.728940486907959}, {"content": "Title: Clinical Characteristics and Outcomes of 74 Patients With Severe or Critical COVID-19 Content: BACKGROUND: The outbreak of the coronavirus disease (COVID-19) has led to a major concern and caused a pandemic globally. The goal of this study was to clarify the clinical characteristics of recovery and death in patients with severe or critical COVID-19. MATERIALS AND METHODS: In this retrospective single-center study, clinical data were collected from 74 severe or critical COVID-19 patients in Wuhan Fourth Hospital between Jan. 25th and Feb. 26th, 2020. All patients were divided into a recovery group or a death group according to clinical outcomes, and the differences between the groups were compared. RESULTS: Of the 74 patients enrolled in the study, 48 (64.9%) were severe cases and 26 (35.1%) were critical cases. Sixty (81.1%) patients were recovered and 14 (18.9%) died. Compared with recovery patients, patients in the death group were older, and had higher incidences of hypertension, coronary disease and dyspnea at admission. Laboratory tests for lactate dehydrogenase, creatine kinase, myoglobin, brain natriuretic peptide and D-dimer indicated higher levels in the death group. The PaO2:FiO2 ratio and minimum SpO2 were lower in the death group, and a higher proportion of these patients received noninvasive mechanical ventilation, invasive mechanical ventilation and extracorporeal membrane oxygenation treatment. CONCLUSIONS: Elderly patients with comorbidities are at higher risk of severe COVID-19 or death. Patients with a low blood gas index and poor coagulation function at admission had a high mortality rate. For such patients, comprehensive treatment should be performed as soon as possible to improve the prognosis and reduce mortality.", "qid": 34, "docid": "55r9zw55", "rank": 99, "score": 0.7287105321884155}, {"content": "Title: COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options Content: The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.", "qid": 34, "docid": "ubhntliy", "rank": 100, "score": 0.7284734845161438}]}
{"query": "What new public datasets are available related to COVID-19?", "hits": [{"content": "Title: COVID-19: A Survey on Public Medical Imaging Data Resources Content: This regularly updated survey provides an overview of public resources that offer medical images and metadata of COVID-19 cases. The purpose of this survey is to simplify the access to open COVID-19 image data resources for all scientists currently working on the coronavirus crisis.", "qid": 35, "docid": "z0bkpmpk", "rank": 1, "score": 0.8226957321166992}, {"content": "Title: CORD-19: The COVID-19 Open Research Dataset Content: The COVID-19 Open Research Dataset (CORD-19) is a growing resource of scientific papers on COVID-19 and related historical coronavirus research. CORD-19 is designed to facilitate the development of text mining and information retrieval systems over its rich collection of metadata and structured full text papers. Since its release, CORD-19 has been downloaded over 200K times and has served as the basis of many COVID-19 text mining and discovery systems. In this article, we describe the mechanics of dataset construction, highlighting challenges and key design decisions, provide an overview of how CORD-19 has been used, and describe several shared tasks built around the dataset. We hope this resource will continue to bring together the computing community, biomedical experts, and policy makers in the search for effective treatments and management policies for COVID-19.", "qid": 35, "docid": "4n6v5kfv", "rank": 2, "score": 0.8163717985153198}, {"content": "Title: CORD-19: The Covid-19 Open Research Dataset. Content: The Covid-19 Open Research Dataset (CORD-19) is a growing resource of scientific papers on Covid-19 and related historical coronavirus research. CORD-19 is designed to facilitate the development of text mining and information retrieval systems over its rich collection of metadata and structured full text papers. Since its release, CORD-19 has been downloaded over 75K times and has served as the basis of many Covid-19 text mining and discovery systems. In this article, we describe the mechanics of dataset construction, highlighting challenges and key design decisions, provide an overview of how CORD-19 has been used, and preview tools and upcoming shared tasks built around the dataset. We hope this resource will continue to bring together the computing community, biomedical experts, and policy makers in the search for effective treatments and management policies for Covid-19.", "qid": 35, "docid": "pt8nh7wx", "rank": 3, "score": 0.8135902881622314}, {"content": "Title: Lest We Forget: A Dataset of Coronavirus-Related News Headlines in Swiss Media Content: We release our COVID-19 news dataset, containing more than 10,000 links to news articles related to the Coronavirus pandemic published in the Swiss media since early January 2020. This collection can prove beneficial in mining and analysis of the reaction of the Swiss media and the COVID-19 pandemic and extracting insightful information for further research. We hope this dataset helps researchers and the public deliver results that will help analyse the pandemic and potentially lead to a better understanding of the events.", "qid": 35, "docid": "fu373osb", "rank": 4, "score": 0.8104346990585327}, {"content": "Title: Comparing and Integrating US COVID-19 Daily Data from Multiple Sources: A County-Level Dataset with Local Characteristics Content: Over the past several months, the outbreak of COVID-19 has been expanding over the world. A reliable and accurate dataset of the cases is vital for scientists to conduct related research and for policy-makers to make better decisions. We collect the COVID-19 daily reported data from four open sources: the New York Times, the COVID-19 Data Repository by Johns Hopkins University, the COVID Tracking Project at the Atlantic, and the USAFacts, and compare the similarities and differences among them. In addition, we examine the following problems which occur frequently: (1) the order dependencies violation, (2) the delay-reported issue on weekends and/or holidays, and (3) abnormal data point or data period. We also integrate the COVID-19 reported cases with the county-level auxiliary information of the local features from official sources, such as health infrastructure, demographic, socioeconomic, and environment information, which are important for understanding the spread of the virus.", "qid": 35, "docid": "yfuq8na6", "rank": 5, "score": 0.8078134059906006}, {"content": "Title: A large-scale COVID-19 Twitter chatter dataset for open scientific research -- an international collaboration Content: As the COVID-19 pandemic continues its march around the world, an unprecedented amount of open data is being generated for genetics and epidemiological research. The unparalleled rate at which many research groups around the world are releasing data and publications on the ongoing pandemic is allowing other scientists to learn from local experiences and data generated in the front lines of the COVID-19 pandemic. However, there is a need to integrate additional data sources that map and measure the role of social dynamics of such a unique world-wide event into biomedical, biological, and epidemiological analyses. For this purpose, we present a large-scale curated dataset of over 152 million tweets, growing daily, related to COVID-19 chatter generated from January 1st to April 4th at the time of writing. This open dataset will allow researchers to conduct a number of research projects relating to the emotional and mental responses to social distancing measures, the identification of sources of misinformation, and the stratified measurement of sentiment towards the pandemic in near real time.", "qid": 35, "docid": "21fhsooy", "rank": 6, "score": 0.8076810836791992}, {"content": "Title: A large-scale COVID-19 Twitter chatter dataset for open scientific research -- an international collaboration. Content: As the COVID-19 pandemic continues its march around the world, an unprecedented amount of open data is being generated for genetics and epidemiological research. The unparalleled rate at which many research groups around the world are releasing data and publications on the ongoing pandemic is allowing other scientists to learn from local experiences and data generated in the front lines of the COVID-19 pandemic. However, there is a need to integrate additional data sources that map and measure the role of social dynamics of such a unique world-wide event into biomedical, biological, and epidemiological analyses. For this purpose, we present a large-scale curated dataset of over 152 million tweets, growing daily, related to COVID-19 chatter generated from January 1st to April 4th at the time of writing. This open dataset will allow researchers to conduct a number of research projects relating to the emotional and mental responses to social distancing measures, the identification of sources of misinformation, and the stratified measurement of sentiment towards the pandemic in near real time.", "qid": 35, "docid": "1lisdjpm", "rank": 7, "score": 0.8076810836791992}, {"content": "Title: COVID-19: Open-data resources for monitoring, modeling, and forecasting the epidemic Content: We provide an insight into the open-data resources pertinent to the study of the spread of the Covid-19 pandemic and its control. We identify the variables required to analyze fundamental aspects like seasonal behavior, regional mortality rates, and effectiveness of government measures. Open-data resources, along with data-driven methodologies, provide many opportunities to improve the response of the different administrations to the virus. We describe the present limitations and difficulties encountered in most of the open-data resources. To facilitate the access to the main open-data portals and resources, we identify the most relevant institutions, on a global scale, providing Covid-19 information and/or auxiliary variables (demographics, mobility, etc.). We also describe several open resources to access Covid-19 datasets at a country-wide level (i.e., China, Italy, Spain, France, Germany, US, etc.). To facilitate the rapid response to the study of the seasonal behavior of Covid-19, we enumerate the main open resources in terms of weather and climate variables. We also assess the reusability of some representative open-data sources.", "qid": 35, "docid": "iukudcbo", "rank": 8, "score": 0.8063052296638489}, {"content": "Title: Open access institutional and news media tweet dataset for COVID-19 social science research Content: As COVID-19 quickly became one of the most concerned global crisis, the demand for data in academic research is also increasing. Currently, there are several open access Twitter datasets, but none of them is dedicated to the institutional and news media Twitter data collection, to fill this blank, we retrieved data from 69 institutional/news media Twitter accounts, 17 of them were related to government and international organizations, 52 of them were news media across North America, Europe and Asia. We believe our open access data can provide researchers more availability to conduct social science research.", "qid": 35, "docid": "5o12mbut", "rank": 9, "score": 0.7972769737243652}, {"content": "Title: Dataset for country profile and mobility analysis in the assessment of COVID-19 pandemic Content: Understanding the COVID-19 pandemic is a multidisciplinary effort that requires a significant number of variables. This dataset comprises (i) sociodemographic characteristics, compiled from 35 datasets obtained at UN Data; (ii) mobility metrics that can assist the analysis of social distancing, from Google Community Mobility Reports and; (iii) daily counts of cases and deaths by COVID-19, from the European Centre for Disease Prevention and Control and the Johns Hopkins University Center for Systems Science and Engineering. This unified dataset ranges from February 15, 2020 to April 26, 2020, a total of 72 days, and is provided as a collection of time series for 131 countries with 192 variables. The pipeline to preprocess and generate the dataset, along with the dataset itself, are versioned with the Data Version Control tool (DVC) and are thus easily reproducible.", "qid": 35, "docid": "2llnlr8a", "rank": 10, "score": 0.7969105243682861}, {"content": "Title: A review of mathematical modeling, artificial intelligence and datasets used in the study, prediction and management of COVID-19 Content: In the past few months, several works were published in regards to the dynamics and early detection of COVID-19 via mathematical modeling and Artificial intelligence (AI). The aim of this work is to provide the research community with comprehensive overview of the methods used in these studies as well as a compendium of available open source datasets in regards to COVID-19. In all, 61 journal articles, reports, fact sheets, and websites dealing with COVID-19 were studied and reviewed. It was found that most mathematical modeling done were based on the Susceptible-Exposed-Infected-Removed (SEIR) and Susceptible-infected-recovered (SIR) models while most of the AI implementations were Convolutional Neural Network (CNN) on X-ray and CT images. In terms of available datasets, they include aggregated case reports, medical images, management strategies, healthcare workforce, demography, and mobility during the outbreak. Both Mathematical modeling and AI have both shown to be reliable tools in the fight against this pandemic. Several datasets concerning the COVID-19 have also been collected and shared open source. However, much work is needed to be done in the diversification of the datasets. Other AI and modeling applications in healthcare should be explored in regards to this COVID-19.", "qid": 35, "docid": "3wfnnrvo", "rank": 11, "score": 0.7932612895965576}, {"content": "Title: MosMedData: Chest CT Scans with COVID-19 Related Findings Content: This dataset contains anonymised human lung computed tomography (CT) scans with COVID-19 related findings, as well as without such findings. A small subset of studies has been annotated with binary pixel masks depicting regions of interests (ground-glass opacifications and consolidations). CT scans were obtained between 1st of March, 2020 and 25th of April, 2020, and provided by municipal hospitals in Moscow, Russia. Permanent link: https://mosmed.ai/datasets/covid19_1110. This dataset is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND 3.0) License.", "qid": 35, "docid": "doazmz7c", "rank": 12, "score": 0.7927294969558716}, {"content": "Title: Open Data Resources for Fighting COVID-19 Content: We provide an insight into the open data resources pertinent to the study of the spread of Covid-19 pandemic and its control. We identify the variables required to analyze fundamental aspects like seasonal behaviour, regional mortality rates, and effectiveness of government measures. Open data resources, along with data-driven methodologies, provide many opportunities to improve the response of the different administrations to the virus. We describe the present limitations and difficulties encountered in most of the open-data resources. To facilitate the access to the main open-data portals and resources, we identify the most relevant institutions, at a world scale, providing Covid-19 information and/or auxiliary variables (demographics, mobility, etc.). We also describe several open resources to access Covid-19 data-sets at a country-wide level (i.e. China, Italy, Spain, France, Germany, U.S., etc.). In an attempt to facilitate the rapid response to the study of the seasonal behaviour of Covid-19, we enumerate the main open resources in terms of weather and climate variables. CONCO-Team: The authors of this paper belong to the CONtrol COvid-19 Team, which is composed of different researches from universities of Spain, Italy, France, Germany, United Kingdom and Argentina. The main goal of CONCO-Team is to develop data-driven methods for the better understanding and control of the pandemic.", "qid": 35, "docid": "lysvg3vw", "rank": 13, "score": 0.7914415597915649}, {"content": "Title: Mega-COV: A Billion-Scale Dataset of 65 Languages For COVID-19 Content: We describe Mega-COV, a billion-scale dataset from Twitter for studying COVID-19. The dataset is diverse (covers 234 countries), longitudinal (goes as back as 2007), multilingual (comes in 65 languages), and has a significant number of location-tagged tweets (~32M tweets). We release tweet IDs from the dataset, hoping it will be useful for studying various phenomena related to the ongoing pandemic and accelerating viable solutions to associated problems.", "qid": 35, "docid": "lk13v7j6", "rank": 14, "score": 0.7902084589004517}, {"content": "Title: MosMedData: Chest CT Scans With COVID-19 Related Findings Dataset Content: This dataset contains anonymised human lung computed tomography (CT) scans with COVID-19 related findings, as well as without such findings. A small subset of studies has been annotated with binary pixel masks depicting regions of interests (ground-glass opacifications and consolidations). CT scans were obtained between 1st of March, 2020 and 25th of April, 2020, and provided by municipal hospitals in Moscow, Russia. Permanent link: https://mosmed.ai/datasets/covid19_1110. This dataset is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND 3.0) License. Key words: artificial intelligence, COVID-19, machine learning, dataset, CT, chest, imaging", "qid": 35, "docid": "0b8250y7", "rank": 15, "score": 0.78934645652771}, {"content": "Title: Rapidly Bootstrapping a Question Answering Dataset for COVID-19 Content: We present CovidQA, the beginnings of a question answering dataset specifically designed for COVID-19, built by hand from knowledge gathered from Kaggle's COVID-19 Open Research Dataset Challenge. To our knowledge, this is the first publicly available resource of its type, and intended as a stopgap measure for guiding research until more substantial evaluation resources become available. While this dataset, comprising 124 question-article pairs as of the present version 0.1 release, does not have sufficient examples for supervised machine learning, we believe that it can be helpful for evaluating the zero-shot or transfer capabilities of existing models on topics specifically related to COVID-19. This paper describes our methodology for constructing the dataset and presents the effectiveness of a number of baselines, including term-based techniques and various transformer-based models. The dataset is available at http://covidqa.ai/", "qid": 35, "docid": "vaeyoxv7", "rank": 16, "score": 0.7862317562103271}, {"content": "Title: Coronaviruses and people with intellectual disability: an exploratory data analysis Content: BACKGROUND: Corona virus disease 2019 (COVID-19) has been announced as a new coronavirus disease by the World Health Organization. At the time of writing this article (April 2020), the world is drastically influenced by the COVID-19. Recently, the COVID-19 Open Research Dataset (CORD-19) was published. For researchers on ID such as ourselves, it is of key interest to learn whether this open research dataset may be used to investigate the virus and its consequences for people with an ID. METHODS: From CORD-19, we identified full-text articles containing terms related to the ID care and applied a text mining technique, specifically the term frequency-inverse document frequency analysis in combination with K-means clustering. RESULTS: Two hundred fifty-nine articles contained one or more of our specified terms related to ID. We were able to cluster these articles related to ID into five clusters on different topics, namely: mental health, viral diseases, diagnoses and treatments, maternal care and paediatrics, and genetics. CONCLUSION: The CORD-19 open research dataset consists of valuable information about not only COVID-19 disease but also ID and the relationship between them. We suggest researchers investigate literature-based discovery approaches on the CORD-19 and develop a new dataset that addresses the intersection of these two fields for further research.", "qid": 35, "docid": "sg8epmf0", "rank": 17, "score": 0.7849434614181519}, {"content": "Title: COVID-CT-Dataset: A CT Scan Dataset about COVID-19 Content: During the outbreak time of COVID-19, computed tomography (CT) is a useful manner for diagnosing COVID-19 patients. Due to privacy issues, publicly available COVID-19 CT datasets are highly difficult to obtain, which hinders the research and development of AI-powered diagnosis methods of COVID-19 based on CTs. To address this issue, we build an open-sourced dataset -- COVID-CT, which contains 349 COVID-19 CT images from 216 patients and 463 non-COVID-19 CTs. The utility of this dataset is confirmed by a senior radiologist who has been diagnosing and treating COVID-19 patients since the outbreak of this pandemic. We also perform experimental studies which further demonstrate that this dataset is useful for developing AI-based diagnosis models of COVID-19. Using this dataset, we develop diagnosis methods based on multi-task learning and self-supervised learning, that achieve an F1 of 0.90, an AUC of 0.98, and an accuracy of 0.89. According to the senior radiologist, models with such performance are good enough for clinical usage. The data and code are available at https://github.com/UCSD-AI4H/COVID-CT", "qid": 35, "docid": "55nifoqu", "rank": 18, "score": 0.784794270992279}, {"content": "Title: Weibo-COV: A Large-Scale COVID-19 Social Media Dataset from Weibo Content: With the rapid development of COVID-19, people are asked to maintain\"social distance\"and\"stay at home\". In this scenario, more and more social interactions move online, especially on social media like Twitter and Weibo. People post tweets to share information, express opinions and seek help during the pandemic, and these tweets on social media are valuable for studies against COVID19, such as early warning and outbreaks detection. Therefore, in this paper, we release a novel large-scale COVID-19 social media dataset from Weibo called Weibo-COV, covering more than 40 million tweets from 1 December 2019 to 30 April 2020. Moreover, the field information of the dataset is very rich, including basic tweets information, interactive information, location information and retweet network. We hope this dataset can promote studies of COVID-19 from multiple perspectives and enable better and faster researches to suppress the spread of this disease.", "qid": 35, "docid": "1bjt64o7", "rank": 19, "score": 0.784365177154541}, {"content": "Title: Coronaviruses and people with intellectual disability: an exploratory data analysis Content: BACKGROUND: Corona virus disease 2019 (COVID\u201019) has been announced as a new coronavirus disease by the World Health Organization. At the time of writing this article (April 2020), the world is drastically influenced by the COVID\u201019. Recently, the COVID\u201019 Open Research Dataset (CORD\u201019) was published. For researchers on ID such as ourselves, it is of key interest to learn whether this open research dataset may be used to investigate the virus and its consequences for people with an ID. METHODS: From CORD\u201019, we identified full\u2010text articles containing terms related to the ID care and applied a text mining technique, specifically the term frequency\u2013inverse document frequency analysis in combination with K\u2010means clustering. RESULTS: Two hundred fifty\u2010nine articles contained one or more of our specified terms related to ID. We were able to cluster these articles related to ID into five clusters on different topics, namely: mental health, viral diseases, diagnoses and treatments, maternal care and paediatrics, and genetics. CONCLUSION: The CORD\u201019 open research dataset consists of valuable information about not only COVID\u201019 disease but also ID and the relationship between them. We suggest researchers investigate literature\u2010based discovery approaches on the CORD\u201019 and develop a new dataset that addresses the intersection of these two fields for further research.", "qid": 35, "docid": "pksis5da", "rank": 20, "score": 0.783711314201355}, {"content": "Title: NAIST COVID: Multilingual COVID-19 Twitter and Weibo Dataset Content: Since the outbreak of coronavirus disease 2019 (COVID-19) in the late 2019, it has affected over 200 countries and billions of people worldwide. This has affected the social life of people owing to enforcements, such as\"social distancing\"and\"stay at home.\"This has resulted in an increasing interaction through social media. Given that social media can bring us valuable information about COVID-19 at a global scale, it is important to share the data and encourage social media studies against COVID-19 or other infectious diseases. Therefore, we have released a multilingual dataset of social media posts related to COVID-19, consisting of microblogs in English and Japanese from Twitter and those in Chinese from Weibo. The data cover microblogs from January 20, 2020, to March 24, 2020. This paper also provides a quantitative as well as qualitative analysis of these datasets by creating daily word clouds as an example of text-mining analysis. The dataset is now available on Github. This dataset can be analyzed in a multitude of ways and is expected to help in efficient communication of precautions related to COVID-19.", "qid": 35, "docid": "o8b1rtux", "rank": 21, "score": 0.7824534177780151}, {"content": "Title: Spatial-Temporal Dataset of COVID-19 Outbreak in China Content: We present Coronavirus disease 2019 (COVID-19) statistics in China dataset: daily statistics of the COVID-19 outbreak in China at the city/county level. For each city/country, we include the six most important numbers for epidemic research: daily new infections, accumulated infections, daily new recoveries, accumulated recoveries, daily new deaths, and accumulated deaths. We cross validate the dataset and the estimate error rate is about 0.04%. We then give several examples to show how to trace the spreading in particular cities or provinces, and also contrast the development of COVID-19 in all cities in China at the early, middle and late stages. We hope this dataset can help researchers around the world better understand the spreading dynamics of COVID-19 at a regional level, to inform intervention and mitigation strategies for policymakers.", "qid": 35, "docid": "0is1vyhy", "rank": 22, "score": 0.7786166667938232}, {"content": "Title: COVID-19-CT-CXR: a freely accessible and weakly labeled chest X-ray and CT image collection on COVID-19 from biomedical literature Content: The latest threat to global health is the COVID-19 outbreak. Although there exist large datasets of chest X-rays (CXR) and computed tomography (CT) scans, few COVID-19 image collections are currently available due to patient privacy. At the same time, there is a rapid growth of COVID-19-relevant articles in the biomedical literature. Here, we present COVID-19-CT-CXR, a public database of COVID-19 CXR and CT images, which are automatically extracted from COVID-19-relevant articles from the PubMed Central Open Access (PMC-OA) Subset. We extracted figures, associated captions, and relevant figure descriptions in the article and separated compound figures into subfigures. We also designed a deep-learning model to distinguish them from other figure types and to classify them accordingly. The final database includes 1,327 CT and 263 CXR images (as of May 9, 2020) with their relevant text. To demonstrate the utility of COVID-19-CT-CXR, we conducted four case studies. (1) We show that COVID-19-CT-CXR, when used as additional training data, is able to contribute to improved DL performance for the classification of COVID-19 and non-COVID-19 CT. (2) We collected CT images of influenza and trained a DL baseline to distinguish a diagnosis of COVID-19, influenza, or normal or other types of diseases on CT. (3) We trained an unsupervised one-class classifier from non-COVID-19 CXR and performed anomaly detection to detect COVID-19 CXR. (4) From text-mined captions and figure descriptions, we compared clinical symptoms and clinical findings of COVID-19 vs. those of influenza to demonstrate the disease differences in the scientific publications. We believe that our work is complementary to existing resources and hope that it will contribute to medical image analysis of the COVID-19 pandemic. The dataset, code, and DL models are publicly available at https://github.com/ncbi-nlp/COVID-19-CT-CXR.", "qid": 35, "docid": "ijceqi3y", "rank": 23, "score": 0.778003990650177}, {"content": "Title: COVID-19-CT-CXR: a freely accessible and weakly labeled chest X-ray and CT image collection on COVID-19 from biomedical literature. Content: The latest threat to global health is the COVID-19 outbreak. Although there exist large datasets of chest X-rays (CXR) and computed tomography (CT) scans, few COVID-19 image collections are currently available due to patient privacy. At the same time, there is a rapid growth of COVID-19-relevant articles in the biomedical literature. Here, we present COVID-19-CT-CXR, a public database of COVID-19 CXR and CT images, which are automatically extracted from COVID-19-relevant articles from the PubMed Central Open Access (PMC-OA) Subset. We extracted figures, associated captions, and relevant figure descriptions in the article and separated compound figures into subfigures. We also designed a deep-learning model to distinguish them from other figure types and to classify them accordingly. The final database includes 1,327 CT and 263 CXR images (as of May 9, 2020) with their relevant text. To demonstrate the utility of COVID-19-CT-CXR, we conducted four case studies. (1) We show that COVID-19-CT-CXR, when used as additional training data, is able to contribute to improved DL performance for the classification of COVID-19 and non-COVID-19 CT. (2) We collected CT images of influenza and trained a DL baseline to distinguish a diagnosis of COVID-19, influenza, or normal or other types of diseases on CT. (3) We trained an unsupervised one-class classifier from non-COVID-19 CXR and performed anomaly detection to detect COVID-19 CXR. (4) From text-mined captions and figure descriptions, we compared clinical symptoms and clinical findings of COVID-19 vs. those of influenza to demonstrate the disease differences in the scientific publications. We believe that our work is complementary to existing resources and hope that it will contribute to medical image analysis of the COVID-19 pandemic. The dataset, code, and DL models are publicly available at https://github.com/ncbi-nlp/COVID-19-CT-CXR.", "qid": 35, "docid": "uqfygev4", "rank": 24, "score": 0.778003990650177}, {"content": "Title: COVID-19 Image Data Collection: Prospective Predictions Are the Future Content: Across the world's coronavirus disease 2019 (COVID-19) hot spots, the need to streamline patient diagnosis and management has become more pressing than ever. As one of the main imaging tools, chest X-rays (CXRs) are common, fast, non-invasive, relatively cheap, and potentially bedside to monitor the progression of the disease. This paper describes the first public COVID-19 image data collection as well as a preliminary exploration of possible use cases for the data. This dataset currently contains hundreds of frontal view X-rays and is the largest public resource for COVID-19 image and prognostic data, making it a necessary resource to develop and evaluate tools to aid in the treatment of COVID-19. It was manually aggregated from publication figures as well as various web based repositories into a machine learning (ML) friendly format with accompanying dataloader code. We collected frontal and lateral view imagery and metadata such as the time since first symptoms, intensive care unit (ICU) status, survival status, intubation status, or hospital location. We present multiple possible use cases for the data such as predicting the need for the ICU, predicting patient survival, and understanding a patient's trajectory during treatment. Data can be accessed here: https://github.com/ieee8023/covid-chestxray-dataset", "qid": 35, "docid": "n0y7icl5", "rank": 25, "score": 0.7760437726974487}, {"content": "Title: COVID-19 Government Response Event Dataset (CoronaNet v.1.0) Content: Governments worldwide have implemented countless policies in response to the COVID-19 pandemic. We present an initial public release of a large hand-coded dataset of over 13,000 such policy announcements across more than 195 countries. The dataset is updated daily, with a 5-day lag for validity checking. We document policies across numerous dimensions, including the type of policy, national versus subnational enforcement, the specific human group and geographical region targeted by the policy, and the time frame within which each policy is implemented. We further analyse the dataset using a Bayesian measurement model, which shows the quick acceleration of the adoption of costly policies across countries beginning in mid-March 2020 through 24 May 2020. We believe that these data will be instrumental for helping policymakers and researchers assess, among other objectives, how effective different policies are in addressing the spread and health outcomes of COVID-19.", "qid": 35, "docid": "x7v4iwts", "rank": 26, "score": 0.7750924825668335}, {"content": "Title: COVID-19 Government Response Event Dataset (CoronaNet v.1.0). Content: Governments worldwide have implemented countless policies in response to the COVID-19 pandemic. We present an initial public release of a large hand-coded dataset of over 13,000 such policy announcements across more than 195 countries. The dataset is updated daily, with a 5-day lag for validity checking. We document policies across numerous dimensions, including the type of policy, national versus subnational enforcement, the specific human group and geographical region targeted by the policy, and the time frame within which each policy is implemented. We further analyse the dataset using a Bayesian measurement model, which shows the quick acceleration of the adoption of costly policies across countries beginning in mid-March 2020 through 24 May 2020. We believe that these data will be instrumental for helping policymakers and researchers assess, among other objectives, how effective different policies are in addressing the spread and health outcomes of COVID-19.", "qid": 35, "docid": "4dgvuaxr", "rank": 27, "score": 0.7750924825668335}, {"content": "Title: Visualising COVID-19 Research Content: The world has seen in 2020 an unprecedented global outbreak of SARS-CoV-2, a new strain of coronavirus, causing the COVID-19 pandemic, and radically changing our lives and work conditions. Many scientists are working tirelessly to find a treatment and a possible vaccine. Furthermore, governments, scientific institutions and companies are acting quickly to make resources available, including funds and the opening of large-volume data repositories, to accelerate innovation and discovery aimed at solving this pandemic. In this paper, we develop a novel automated theme-based visualisation method, combining advanced data modelling of large corpora, information mapping and trend analysis, to provide a top-down and bottom-up browsing and search interface for quick discovery of topics and research resources. We apply this method on two recently released publications datasets (Dimensions' COVID-19 dataset and the Allen Institute for AI's CORD-19). The results reveal intriguing information including increased efforts in topics such as social distancing; cross-domain initiatives (e.g. mental health and education); evolving research in medical topics; and the unfolding trajectory of the virus in different territories through publications. The results also demonstrate the need to quickly and automatically enable search and browsing of large corpora. We believe our methodology will improve future large volume visualisation and discovery systems but also hope our visualisation interfaces will currently aid scientists, researchers, and the general public to tackle the numerous issues in the fight against the COVID-19 pandemic.", "qid": 35, "docid": "hn37wkhf", "rank": 28, "score": 0.7748743295669556}, {"content": "Title: CovidNet: To Bring Data Transparency in the Era of COVID-19 Content: Timely, creditable, and fine-granular case information is vital for local communities and individual citizens to make rational and data-driven responses to the COVID-19 pandemic. This paper presents CovidNet, a COVID-19 tracking project associated with a large scale epidemic dataset, which was initiated by 1Point3Acres. To the best of our knowledge, the project is the only platform providing real-time global case information of more than 4,124 sub-divisions from over 27 countries worldwide with multi-language supports. The platform also offers interactive visualization tools to analyze the full historical case curves in each region. Initially launched as a voluntary project to bridge the data transparency gap in North America in January 2020, this project by far has become one of the major independent sources worldwide and has been consumed by many other tracking platforms. The accuracy and freshness of the dataset is a result of the painstaking efforts from our voluntary teamwork, crowd-sourcing channels, and automated data pipelines. As of May 18, 2020, the project website has been visited more than 200 million times and the CovidNet dataset has empowered over 522 institutions and organizations worldwide in policy-making and academic researches. All datasets are openly accessible for non-commercial purposes at https://coronavirus.1point3acres.com via a formal request through our APIs.", "qid": 35, "docid": "zxvim4t8", "rank": 29, "score": 0.7748686075210571}, {"content": "Title: COVID-19 Datasets: A Survey and Future Challenges Content: In December 2019, a novel virus named as COVID-19 emerged in the city of Wuhan, China. In early 2020, the COVID-19 virus spread in all continents of the world except Antarctica causing widespread infections and deaths due to its contagious characteristics and no medically proven treatment. The COVID-19 pandemic has been termed as most consequential global crisis after the World Wars. The first line of defense against the COVID-19 spread are the non-pharmaceutical measures like social distancing and personal hygiene. On the other hand, the medical service providers are the first responders for infected persons with severe symptoms of COVID-19. The great pandemic affecting billions of lives economically and socially has motivated the scientific community to come up with solutions based on computer-aided digital technologies for diagnosis, prevention, and estimation of COVID-19. Some of these efforts focus on statistical and Artificial Intelligence-based analysis of the available data concerning COVID-19. All of these scientific efforts necessitate that the data brought to service for the analysis should be open-source to promote the extension, validation, and collaboration of the work in the fight against the global pandemic. Our survey is motivated by the open-source efforts that can be mainly categorized as: (a) COVID-19 diagnosis from CT scans and X-ray images, (b) COVID-19 case reporting, transmission estimation, and prognosis from epidemiological, demographic, and mobility data, (c) COVID-19 emotional and sentiment analysis from social media, and (d) knowledge-based discovery and semantic analysis from the collection of scholarly articles covering COVID-19. We review and critically analyze works in these directions that are accompanied by open-source data and code. We hope that the article will provide the scientific community with an initiative to start open-source extensible and transparent research in the collective fight against COVID-19.", "qid": 35, "docid": "f9eqbaj5", "rank": 30, "score": 0.7718986868858337}, {"content": "Title: Online Information Search During COVID-19 Content: Public information search data from sources such as Google Trends affords researchers a perspective on what society does not know, or what society wants to find out prompted by, or in response to, developments in societal communication and news media events. In times of crisis, online public information search thus offers a window into the most urgent concerns of, and demands by society. By extension, such data offers a window into upcoming, and currently pressing demands on businesses, policymakers and researchers. This research note aims to illustrate some of these themes with a visual-based overview of the current COVID-19 / Coronavirus crisis.", "qid": 35, "docid": "as74qa0l", "rank": 31, "score": 0.770165205001831}, {"content": "Title: A New Resource for Genomics and Precision Health Information and Publications on the Investigation and Control of COVID-19 and other Coronaviruses Content: Summary We developed a new online database that contains the most updated published scientific literature, online news and reports, CDC and National Institutes of Health (NIH) resources. The tool captures emerging discoveries and applications of genomics, molecular, and other precision medicine and precision public health tools in the investigation and control of coronavirus diseases, including COVID-19, MERS-CoV, and SARS. Availability Coronavirus Disease Portal (CDP) can be freely accessed via https://phgkb.cdc.gov/PHGKB/coVInfoStartPage.action. Contact wyu@cdc.gov", "qid": 35, "docid": "1s0hhx71", "rank": 32, "score": 0.7696641683578491}, {"content": "Title: Using Reports of Own and Others' Symptoms and Diagnosis on Social Media to Predict COVID-19 Case Counts: Observational Infoveillance Study in Mainland China. Content: BACKGROUND COVID-19 has affected more than 200 countries and territories worldwide. It poses an extraordinary challenge for public health systems, because screening and surveillance capacity-especially during the beginning of the outbreak-is often severely limited, fueling the outbreak as many patients unknowingly infect others. OBJECTIVE We present an effort to collect and analyze COVID-19 related posts on the popular Twitter-like social media site in China, Weibo. To our knowledge, this infoveillance study employs the largest, most comprehensive and fine-grained social media data to date to predict COVID-19 case counts in mainland China. METHODS We built a Weibo user pool of 250 million, approximately half of the entire monthly active Weibo user population. Using a comprehensive list of 167 keywords, we retrieved and analyzed around 15 million COVID-19 related posts from our user pool, from November 1, 2019 to March 31, 2020. We developed a machine learning classifier to identify \"sick posts,\" which are reports of one's own and other people's symptoms and diagnosis related to COVID-19. Using officially reported case counts as the outcome, we then estimated the Granger causality of sick posts and other COVID-19 posts on daily case counts. For a subset of geotagged posts (3.10% of all retrieved posts), we also ran separate predictive models for Hubei province, the epicenter of the initial outbreak, and the rest of mainland China. RESULTS We found that reports of symptoms and diagnosis of COVID-19 significantly predicted daily case counts, up to 14 days ahead of official statistics, whereas other COVID-19 posts did not have similar predictive power. For the subset of geotagged posts, we found that the predictive pattern held true for both Hubei province and the rest of mainland China, regardless of unequal distribution of healthcare resources and outbreak timeline. CONCLUSIONS Public social media data can be usefully harnessed to predict infection cases and inform timely responses. Researchers and disease control agencies should pay close attention to the social media infosphere regarding COVID-19. On top of monitoring overall search and posting activities, leveraging machine learning approaches and theoretical understandings of information sharing behaviors is a promising approach to identifying true disease signals and improving the effectiveness of infoveillance. CLINICALTRIAL", "qid": 35, "docid": "kmijkfb5", "rank": 33, "score": 0.768824577331543}, {"content": "Title: A County-level Dataset for Informing the United States' Response to COVID-19 Content: As the coronavirus disease 2019 (COVID-19) becomes a global pandemic, policy makers must enact interventions to stop its spread. Data driven approaches might supply information to support the implementation of mitigation and suppression strategies. To facilitate research in this direction, we present a machine-readable dataset that aggregates relevant data from governmental, journalistic, and academic sources on the county level. In addition to county-level time-series data from the JHU CSSE COVID-19 Dashboard, our dataset contains more than 300 variables that summarize population estimates, demographics, ethnicity, housing, education, employment and in come, climate, transit scores, and healthcare system-related metrics. Furthermore, we present aggregated out-of-home activity information for various points of interest for each county, including grocery stores and hospitals, summarizing data from SafeGraph. By collecting these data, as well as providing tools to read them, we hope to aid researchers investigating how the disease spreads and which communities are best able to accommodate stay-at-home mitigation efforts. Our dataset and associated code are available at https://github.com/JieYingWu/COVID-19_US_County-level_Summaries.", "qid": 35, "docid": "rndc2v2b", "rank": 34, "score": 0.7688032388687134}, {"content": "Title: Using Reports of Own and Others' Symptoms and Diagnosis on Social Media to Predict COVID-19 Case Counts: Observational Infoveillance Study in Mainland China Content: Can public social media data be harnessed to predict COVID-19 case counts? We analyzed approximately 15 million COVID-19 related posts on Weibo, a popular Twitter-like social media platform in China, from November 1, 2019 to March 31, 2020. We developed a machine learning classifier to identify\"sick posts,\"which are reports of one's own and other people's symptoms and diagnosis related to COVID-19. We then modeled the predictive power of sick posts and other COVID-19 posts on daily case counts. We found that reports of symptoms and diagnosis of COVID-19 significantly predicted daily case counts, up to 14 days ahead of official statistics. But other COVID-19 posts did not have similar predictive power. For a subset of geotagged posts (3.10% of all retrieved posts), we found that the predictive pattern held true for both Hubei province and the rest of mainland China, regardless of unequal distribution of healthcare resources and outbreak timeline. Researchers and disease control agencies should pay close attention to the social media infosphere regarding COVID-19. On top of monitoring overall search and posting activities, it is crucial to sift through the contents and efficiently identify true signals from noise.", "qid": 35, "docid": "72fyre4z", "rank": 35, "score": 0.7683035135269165}, {"content": "Title: International Electronic Health Record-Derived COVID-19 Clinical Course Profiles: The 4CE Consortium Content: We leveraged the largely untapped resource of electronic health record data to address critical clinical and epidemiological questions about Coronavirus Disease 2019 (COVID-19). To do this, we formed an international consortium (4CE) of 96 hospitals across 5 countries (www.covidclinical.net). Contributors utilized the Informatics for Integrating Biology and the Bedside (i2b2) or Observational Medical Outcomes Partnership (OMOP) platforms to map to a common data model. The group focused on comorbidities and temporal changes in key laboratory test values. Harmonized data were analyzed locally and converted to a shared aggregate form for rapid analysis and visualization of regional differences and global commonalities. Data covered 27,584 COVID-19 cases with 187,802 laboratory tests. Case counts and laboratory trajectories were concordant with existing literature. Laboratory tests at the time of diagnosis showed hospital-level differences equivalent to country-level variation across the consortium partners. Despite the limitations of decentralized data generation, we established a framework to capture the trajectory of COVID-19 disease in patients and their response to interventions.", "qid": 35, "docid": "4y5279c5", "rank": 36, "score": 0.767751932144165}, {"content": "Title: What country, university or research institute, performed the best on COVID-19? Bibliometric analysis of scientific literature Content: In this article, we conduct data mining to discover the countries, universities and companies, produced or collaborated the most research on Covid-19 since the pandemic started. We present some interesting findings, but despite analysing all available records on COVID-19 from the Web of Science Core Collection, we failed to reach any significant conclusions on how the world responded to the COVID-19 pandemic. Therefore, we increased our analysis to include all available data records on pandemics and epidemics from 1900 to 2020. We discover some interesting results on countries, universities and companies, that produced collaborated most the most in research on pandemic and epidemics. Then we compared the results with the analysing on COVID-19 data records. This has created some interesting findings that are explained and graphically visualised in the article.", "qid": 35, "docid": "5mnmh84s", "rank": 37, "score": 0.7674961090087891}, {"content": "Title: Preserva\u00e7\u00e3o da privacidade no enfrentamento da COVID-19: dados pessoais e a pandemia global./ Preserva\u00e7\u00e3o da privacidade no enfrentamento da COVID-19: dados pessoais e a pandemia global./ Personal data usage and privacy considerations in the COVID-19 global pandemic Content: Data has become increasingly important and valuable for both scientists and health authorities searching for answers to the COVID-19 crisis. Due to difficulties in diagnosing this infection in populations around the world, initiatives supported by digital technologies are being developed by governments and private companies to enable the tracking of the public's symptoms, contacts and movements. Considering the current scenario, initiatives designed to support infection surveillance and monitoring are essential and necessary. Nonetheless, ethical, legal and technical questions abound regarding the amount and types of personal data being collected, processed, shared and used in the name of public health, as well as the concomitant or posterior use of this data. These challenges demonstrate the need for new models of responsible and transparent data and technology governance in efforts to control SARS-COV2, as well as in future public health emergencies.", "qid": 35, "docid": "d0f7qux9", "rank": 38, "score": 0.7668208479881287}, {"content": "Title: Personal data usage and privacy considerations in the COVID-19 global pandemic. Content: Data has become increasingly important and valuable for both scientists and health authorities searching for answers to the COVID-19 crisis. Due to difficulties in diagnosing this infection in populations around the world, initiatives supported by digital technologies are being developed by governments and private companies to enable the tracking of the public's symptoms, contacts and movements. Considering the current scenario, initiatives designed to support infection surveillance and monitoring are essential and necessary. Nonetheless, ethical, legal and technical questions abound regarding the amount and types of personal data being collected, processed, shared and used in the name of public health, as well as the concomitant or posterior use of this data. These challenges demonstrate the need for new models of responsible and transparent data and technology governance in efforts to control SARS-COV2, as well as in future public health emergencies.", "qid": 35, "docid": "03nh2f1g", "rank": 39, "score": 0.7668208479881287}, {"content": "Title: BIP4COVID19: Releasing impact measures for articles relevant to COVID-19 Content: Since the beginning of the 2019-20 coronavirus pandemic, a large number of relevant articles has been published or become available in preprint servers. These articles, along with earlier related literature, compose a valuable knowledge base affecting contemporary research studies, or even government actions to limit the spread of the disease and treatment decisions taken by physicians. However, the number of such articles is increasing at an intense rate making the exploration of the relevant literature and the identification of useful knowledge in it challenging. In this work, we describe BIP4COVID19, an open dataset compiled to facilitate the coronavirus-related literature exploration, by providing various indicators of scientific impact for the relevant articles. Finally, we provide a publicly accessible Web interface on top of our data, allowing the exploration of the publications based on the computed indicators.", "qid": 35, "docid": "6xkm2j0f", "rank": 40, "score": 0.7666928172111511}, {"content": "Title: A citizen science initiative for open data and visualization of COVID-19 outbreak in Kerala, India Content: India, the second most populated country in the world, reported its first COVID-19 case in the state of Kerala with a travel history from Wuhan. Subsequently, a surge of cases was observed in the state mainly through the individuals who traveled from Europe and the Middle East to Kerala, thus initiating an outbreak. Since public awareness through dissemination of reliable information plays a significant role in controlling the spread of the disease, the Department of Health Services, Government of Kerala initially released daily updates through daily textual bulletins. However, this unstructured data requires refinement and enrichment for upstream applications, such as visualization, and/or analysis. Here we reported a citizen science initiative that leveraged publicly available and crowd-verified data on COVID-19 outbreak in Kerala from the government bulletins, supplemented with the information from media outlets to generate reusable datasets. This data was further used to provide real-time analysis, and daily updates of COVID-19 cases in Kerala, through a user-friendly bilingual dashboard (https://covid19kerala.info/) for non-specialists. We ensured longevity and reusability of the dataset by depositing it in a public repository, aligning with open source principles for future analytical efforts. Finally, to show the scope of the sourced data, we also provided a snapshot of outbreak trends and demographic characteristics of the individuals affected with COVID-19 in Kerala during the first 99 days of the outbreak.", "qid": 35, "docid": "nbzbmrsd", "rank": 41, "score": 0.765999436378479}, {"content": "Title: No more business as usual: agile and effective responses to emerging pathogen threats require open data and open analytics Content: The current state of much of the Wuhan pneumonia virus (COVID-19) research shows a regrettable lack of data sharing and considerable analytical obfuscation. This impedes global research cooperation, which is essential for tackling public health emergencies, and requires unimpeded access to data, analysis tools, and computational infrastructure. Here we show that community efforts in developing open analytical software tools over the past ten years, combined with national investments into scientific computational infrastructure, can overcome these deficiencies and provide an accessible platform for tackling global health emergencies in an open and transparent manner. Specifically, we use all COVID-19 genomic data available in the public domain so far to (1) underscore the importance of access to raw data and to (2) demonstrate that existing community efforts in curation and deployment of biomedical software can reliably support rapid, reproducible research during global health crises. All our analyses are fully documented at https://github.com/galaxyproject/SARS-CoV-2.", "qid": 35, "docid": "v0yzur5h", "rank": 42, "score": 0.7657062411308289}, {"content": "Title: A Semantically Enriched Dataset based on Biomedical NER for the COVID19 Open Research Dataset Challenge Content: Research into COVID-19 is a big challenge and highly relevant at the moment. New tools are required to assist medical experts in their research with relevant and valuable information. The COVID-19 Open Research Dataset Challenge (CORD-19) is a\"call to action\"for computer scientists to develop these innovative tools. Many of these applications are empowered by entity information, i. e. knowing which entities are used within a sentence. For this paper, we have developed a pipeline upon the latest Named Entity Recognition tools for Chemicals, Diseases, Genes and Species. We apply our pipeline to the COVID-19 research challenge and share the resulting entity mentions with the community.", "qid": 35, "docid": "8lu58q4k", "rank": 43, "score": 0.7655256986618042}, {"content": "Title: CovidNLP: A Web Application for Distilling Systemic Implications of COVID-19 Pandemic with Natural Language Processing Content: The flood of conflicting COVID-19 research has revealed that COVID-19 continues to be an enigma. Although more than 14,000 research articles on COVID-19 have been published with the disease taking a pandemic proportion, clinicians and researchers are struggling to distill knowledge for furthering clinical management and research. In this study, we address this gap for a targeted user group, i.e. clinicians, researchers, and policymakers by applying natural language processing to develop a CovidNLP dashboard in order to speed up knowledge discovery. The WHO has created a repository of about more than 5000 peer-reviewed and curated research articles on varied aspects including epidemiology, clinical features, diagnosis, treatment, social factors, and economics. We summarised all the articles in the WHO Database through an extractive summarizer followed by an exploration of the feature space using word embeddings which were then used to visualize the summarized associations of COVID-19 as found in the text. Clinicians, researchers, and policymakers will not only discover the direct effects of COVID-19 but also the systematic implications such as the anticipated rise in TB and cancer mortality due to the non-availability of drugs during the export lockdown as highlighted by our models. These demonstrate the utility of mining massive literature with natural language processing for rapid distillation and knowledge updates. This can help the users understand, synthesize, and take pre-emptive action with the available peer-reviewed evidence on COVID-19. Our models will be continuously updated with new literature and we have made our resource CovidNLP publicly available in a user-friendly fashion at http://covidnlp.tavlab.iiitd.edu.in/.", "qid": 35, "docid": "g53it2al", "rank": 44, "score": 0.7649378776550293}, {"content": "Title: Large Arabic Twitter Dataset on COVID-19 Content: The 2019 coronavirus disease (COVID-19), emerged late December 2019 in China, is now rapidly spreading across the globe. At the time of writing this paper, the number of global confirmed cases has passed two millions and half with over 180,000 fatalities. Many countries have enforced strict social distancing policies to contain the spread of the virus. This have changed the daily life of tens of millions of people, and urged people to turn their discussions online, e.g., via online social media sites like Twitter. In this work, we describe the first Arabic tweets dataset on COVID-19 that we have been collecting since January 1st, 2020. The dataset would help researchers and policy makers in studying different societal issues related to the pandemic. Many other tasks related to behavioral change, information sharing, misinformation and rumors spreading can also be analyzed.", "qid": 35, "docid": "33m59ajn", "rank": 45, "score": 0.7639814019203186}, {"content": "Title: Epidemiological data from the COVID-19 outbreak, real-time case information Content: Cases of a novel coronavirus were first reported in Wuhan, Hubei province, China, in December 2019 and have since spread across the world. Epidemiological studies have indicated human-to-human transmission in China and elsewhere. To aid the analysis and tracking of the COVID-19 epidemic we collected and curated individual-level data from national, provincial, and municipal health reports, as well as additional information from online reports. All data are geo-coded and, where available, include symptoms, key dates (date of onset, admission, and confirmation), and travel history. The generation of detailed, real-time, and robust data for emerging disease outbreaks is important and can help to generate robust evidence that will support and inform public health decision making.", "qid": 35, "docid": "irt0wmt2", "rank": 46, "score": 0.7637642621994019}, {"content": "Title: COVID-19 Image Data Collection Content: This paper describes the initial COVID-19 open image data collection. It was created by assembling medical images from websites and publications and currently contains 123 frontal view X-rays.", "qid": 35, "docid": "53aq480d", "rank": 47, "score": 0.7636616826057434}, {"content": "Title: BIMCV COVID-19+: a large annotated dataset of RX and CT images from COVID-19 patients Content: This paper describes BIMCV COVID-19+, a large dataset from the Valencian Region Medical ImageBank (BIMCV) containing chest X-ray images CXR (CR, DX) and computed tomography (CT) imaging of COVID-19+ patients along with their radiological findings and locations, pathologies, radiological reports (in Spanish), DICOM metadata, Polymerase chain reaction (PCR), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) diagnostic antibody tests. The findings have been mapped onto standard Unified Medical Language System (UMLS) terminology and cover a wide spectrum of thoracic entities, unlike the considerably more reduced number of entities annotated in previous datasets. Images are stored in high resolution and entities are localized with anatomical labels and stored in a Medical Imaging Data Structure (MIDS) format. In addition, 10 images were annotated by a team of radiologists to include semantic segmentation of radiological findings. This first iteration of the database includes 1,380 CX, 885 DX and 163 CT studies from 1,311 COVID-19+ patients. This is, to the best of our knowledge, the largest COVID-19+ dataset of images available in an open format. The dataset can be downloaded from http://bimcv.cipf.es/bimcv-projects/bimcv-covid19.", "qid": 35, "docid": "j9mgdpmd", "rank": 48, "score": 0.7632497549057007}, {"content": "Title: Internet Search Patterns Reveal Clinical Course of Disease Progression for COVID-19 and Predict Pandemic Spread in 32 Countries Content: Effective public health response to COVID-19 relies on accurate and timely surveillance of local pandemic spread, as well as rapid characterization of the clinical course of disease in affected individuals. De novo diagnostic testing methods developed for emergent pandemics are subject to significant development delays and capacity limitations. There is a critical need for complementary surveillance approaches that can function at population-scale to inform public health decisions in real-time. Internet search patterns provide a number of important advantages relative to laboratory testing. We conducted a detailed global study of Internet search patterns related to COVID-19 symptoms in multiple languages across 32 countries on six continents. We found that Internet search patterns reveal a robust temporal pattern of disease progression for COVID-19: Initial symptoms of fever, dry cough, sore throat and chills are followed by shortness of breath an average of 5.22 days [95% CI 3.30-7.14] after symptom onset, matching the precise clinical course reported in the medical literature. Furthermore, we found that increases in COVID-19-symptom-related searches predict increases in reported COVID-19 cases and deaths 18.53 days [95% CI 15.98-21.08] and 22.16 days [95% CI 20.33-23.99] in advance, respectively. This is the first study to show that Internet search patterns can be used to reveal the detailed clinical course of a disease. These data can be used to track and predict the local spread of COVID-19 before widespread laboratory testing becomes available in each country, helping to guide the current public health response.", "qid": 35, "docid": "53s19r16", "rank": 49, "score": 0.7622387409210205}, {"content": "Title: CovidCounties - an interactive, real-time tracker of the COVID-19 pandemic at the level of US counties Content: Management of the COVID-19 pandemic has proven to be a significant challenge to policy makers. This is in large part due to uneven reporting and the absence of open-access visualization tools to present local trends and infer healthcare needs. Here we report the development of CovidCounties.org, an interactive web application that depicts daily disease trends at the level of US counties using time series plots and maps. This application is accompanied by a manually curated dataset that catalogs all major public policy actions made at the state-level, as well as technical validation of the primary data. Finally, the underlying code for the site is also provided as open source, enabling others to validate and learn from this work.", "qid": 35, "docid": "07v9qign", "rank": 50, "score": 0.7621787786483765}, {"content": "Title: Extending A Chronological and Geographical Analysis of Personal Reports of COVID-19 on Twitter to England, UK Content: The rapidly evolving COVID-19 pandemic presents challenges for actively monitoring its transmission. In this study, we extend a social media mining approach used in the US to automatically identify personal reports of COVID-19 on Twitter in England, UK. The findings indicate that natural language processing and machine learning framework could help provide an early indication of the chronological and geographical distribution of COVID-19 in England.", "qid": 35, "docid": "p531jjpm", "rank": 51, "score": 0.7621217966079712}, {"content": "Title: Pandemic Pulse: Unraveling and Modeling Social Signals during the COVID-19 Pandemic Content: We present and begin to explore a collection of social data that represents part of the COVID-19 pandemic's effects on the United States. This data is collected from a range of sources and includes longitudinal trends of news topics, social distancing behaviors, community mobility changes, web searches, and more. This multimodal effort enables new opportunities for analyzing the impacts such a pandemic has on the pulse of society. Our preliminary results show that the number of COVID-19-related news articles published immediately after the World Health Organization declared the pandemic on March 11, and that since that time have steadily decreased---regardless of changes in the number of cases or public policies. Additionally, we found that politically moderate and scientifically-grounded sources have, relative to baselines measured before the beginning of the pandemic, published a lower proportion of COVID-19 news than more politically extreme sources. We suggest that further analysis of these multimodal signals could produce meaningful social insights and present an interactive dashboard to aid further exploration.", "qid": 35, "docid": "71qh6yjr", "rank": 52, "score": 0.7602746486663818}, {"content": "Title: Tracking Social Media Discourse About the COVID-19 Pandemic: Development of a Public Coronavirus Twitter Data Set Content: BACKGROUND: At the time of this writing, the coronavirus disease (COVID-19) pandemic outbreak has already put tremendous strain on many countries' citizens, resources, and economies around the world. Social distancing measures, travel bans, self-quarantines, and business closures are changing the very fabric of societies worldwide. With people forced out of public spaces, much of the conversation about these phenomena now occurs online on social media platforms like Twitter. OBJECTIVE: In this paper, we describe a multilingual COVID-19 Twitter data set that we are making available to the research community via our COVID-19-TweetIDs GitHub repository. METHODS: We started this ongoing data collection on January 28, 2020, leveraging Twitter's streaming application programming interface (API) and Tweepy to follow certain keywords and accounts that were trending at the time data collection began. We used Twitter's search API to query for past tweets, resulting in the earliest tweets in our collection dating back to January 21, 2020. RESULTS: Since the inception of our collection, we have actively maintained and updated our GitHub repository on a weekly basis. We have published over 123 million tweets, with over 60% of the tweets in English. This paper also presents basic statistics that show that Twitter activity responds and reacts to COVID-19-related events. CONCLUSIONS: It is our hope that our contribution will enable the study of online conversation dynamics in the context of a planetary-scale epidemic outbreak of unprecedented proportions and implications. This data set could also help track COVID-19-related misinformation and unverified rumors or enable the understanding of fear and panic-and undoubtedly more.", "qid": 35, "docid": "vy46mpz0", "rank": 53, "score": 0.7597914934158325}, {"content": "Title: A real-time policy dashboard can aid global transparency in the response to coronavirus disease 2019 Content: There has been great provision of open data across the coronavirus disease 2019 (COVID-19) pandemic response, with, for example, dashboards presenting real-time descriptions of new daily cases and risk factors. Transparency has been an important discussion point and there have been concerns and criticisms of governments for not publishing the evidence base that is informing their decision-making. A 'policy dashboard' could act as a hub to show the localised reasoning behind COVID-19 policy decisions and allow the global health community to provide further support to governments and international stakeholders.", "qid": 35, "docid": "z2hobz7x", "rank": 54, "score": 0.7592534422874451}, {"content": "Title: A real-time policy dashboard can aid global transparency in the response to coronavirus disease 2019. Content: There has been great provision of open data across the coronavirus disease 2019 (COVID-19) pandemic response, with, for example, dashboards presenting real-time descriptions of new daily cases and risk factors. Transparency has been an important discussion point and there have been concerns and criticisms of governments for not publishing the evidence base that is informing their decision-making. A 'policy dashboard' could act as a hub to show the localised reasoning behind COVID-19 policy decisions and allow the global health community to provide further support to governments and international stakeholders.", "qid": 35, "docid": "n9ux7gqm", "rank": 55, "score": 0.7592534422874451}, {"content": "Title: Tracking Social Media Discourse About the COVID-19 Pandemic: Development of a Public Coronavirus Twitter Data Set Content: BACKGROUND: At the time of this writing, the coronavirus disease (COVID-19) pandemic outbreak has already put tremendous strain on many countries' citizens, resources, and economies around the world. Social distancing measures, travel bans, self-quarantines, and business closures are changing the very fabric of societies worldwide. With people forced out of public spaces, much of the conversation about these phenomena now occurs online on social media platforms like Twitter. OBJECTIVE: In this paper, we describe a multilingual COVID-19 Twitter data set that we are making available to the research community via our COVID-19-TweetIDs GitHub repository. METHODS: We started this ongoing data collection on January 28, 2020, leveraging Twitter\u2019s streaming application programming interface (API) and Tweepy to follow certain keywords and accounts that were trending at the time data collection began. We used Twitter\u2019s search API to query for past tweets, resulting in the earliest tweets in our collection dating back to January 21, 2020. RESULTS: Since the inception of our collection, we have actively maintained and updated our GitHub repository on a weekly basis. We have published over 123 million tweets, with over 60% of the tweets in English. This paper also presents basic statistics that show that Twitter activity responds and reacts to COVID-19-related events. CONCLUSIONS: It is our hope that our contribution will enable the study of online conversation dynamics in the context of a planetary-scale epidemic outbreak of unprecedented proportions and implications. This data set could also help track COVID-19-related misinformation and unverified rumors or enable the understanding of fear and panic\u2014and undoubtedly more.", "qid": 35, "docid": "gva2x8bu", "rank": 56, "score": 0.7592381238937378}, {"content": "Title: A Joint Dataset of Official COVID-19 Reports and the Governance, Trade and Competitiveness Indicators of World Bank Group Platforms Content: The presented cross-sectional dataset can be employed to analyze the governmental, trade, and competitiveness relationships of official COVID-19 reports. It contains 18 COVID-19 variables generated based on the official reports of 138 countries [1,2], as well as an additional 2203 governance, trade, and competitiveness indicators from the World Bank Group GovData360[3] and TCdata360[4] platforms. From these platforms, only annual indicators from 2015 and later were collected, and their missing values were replaced with previous annual values, in descending order by year, until 2015. During preprocessing, indicators (columns) were filtered out when the ratio of missing values exceeded 50%. Then, the same filtration was applied for the ratio of missing values above 25% in the case of countries (rows). Finally, duplicated variables were removed from the dataset. As a result of these steps, the missing value rate of the employed indicators was reduced to 4.25% on average. In addition to the database, the Kendall rank correlation matrix is provided to facilitate subsequent analysis. The dataset and the correlation matrix can be updated and customized with an R Notebook file, which is also available publicly in Mendeley Data [5].", "qid": 35, "docid": "6vmgqamd", "rank": 57, "score": 0.7588853240013123}, {"content": "Title: Automatic Text Summarization of COVID-19 Medical Research Articles using BERT and GPT-2 Content: With the COVID-19 pandemic, there is a growing urgency for medical community to keep up with the accelerating growth in the new coronavirus-related literature. As a result, the COVID-19 Open Research Dataset Challenge has released a corpus of scholarly articles and is calling for machine learning approaches to help bridging the gap between the researchers and the rapidly growing publications. Here, we take advantage of the recent advances in pre-trained NLP models, BERT and OpenAI GPT-2, to solve this challenge by performing text summarization on this dataset. We evaluate the results using ROUGE scores and visual inspection. Our model provides abstractive and comprehensive information based on keywords extracted from the original articles. Our work can help the the medical community, by providing succinct summaries of articles for which the abstract are not already available.", "qid": 35, "docid": "6oiaf2cc", "rank": 58, "score": 0.7583163976669312}, {"content": "Title: Machine Learning Maps Research Needs in COVID-19 Literature Content: Summary Manually assessing the scope of the thousands of publications on the COVID-19 (coronavirus disease 2019) pandemic is an overwhelming task. Shortcuts through metadata analysis (e.g., keywords) assume that studies are properly tagged. However, machine learning approaches can rapidly survey the actual text of coronavirus abstracts to identify research overlap between COVID-19 and other coronavirus diseases, research hotspots, and areas warranting exploration. We propose a fast, scalable, and reusable framework to parse novel disease literature. When applied to the COVID-19 Open Research Dataset (CORD-19), dimensionality reduction suggested that COVID-19 studies to date are primarily clinical-, modeling- or field-based, in contrast to the vast quantity of laboratory-driven research for other (non-COVID-19) coronavirus diseases. Topic modeling also indicated that COVID-19 publications have thus far focused primarily on public health, outbreak reporting, clinical care, and testing for coronaviruses, as opposed to the more limited number focused on basic microbiology, including pathogenesis and transmission.", "qid": 35, "docid": "3j4atdda", "rank": 59, "score": 0.757989764213562}, {"content": "Title: Mapping the South African health landscape in response to COVID-19 Content: When the COVID-19 disease pandemic infiltrated the world, there was an immediate need for accurate information. As with any outbreak, the outbreak follows a clear trajectory, and subsequently, the supporting information for that outbreak needs to address the needs associated with that stage of the outbreak. At first, there was a need to inform the public of the information related to the initial situation related to the\"who\"of the COVID-19 disease. However, as time continued, the\"where\",\"when\"and\"how to\"related questions started to emerge in relation to the public healthcare system themselves. Questions surrounding the health facilities including COVID-19 hospital bed capacity, locations of designated COVID-19 facilities, and general information related to these facilities were not easily accessible to the general public. Furthermore, the available information was found to be outdated, fragmented across several platforms, and still had gaps in the data related to these facilities. To rectify this problem, a group of volunteers working on the covid19za project stepped in to assist. Each member leading a part of the project chose to focus on one of four problems related to the challenges associated with the Hospital information including: data quality, data completeness, data source validation and data visualisation capacity. As the project developed, so did the sophistication of the data, visualisation and core function of the project. The future prospects of this project relate to a Progressive Web Application that will avail this information for the public as well as healthcare workers through comprehensive mapping and data quality.", "qid": 35, "docid": "paoehsob", "rank": 60, "score": 0.7577391862869263}, {"content": "Title: A globally available COVID-19 - Template for clinical imaging studies Content: Background The pandemic spread of COVID-19 has caused worldwide implications on societies and economies. Chest computed tomography (CT) has been found to support both, current diagnostic and disease monitoring. A joint approach to collect, analyze and share clinical and imaging information about COVID-19 in the highest quality possible is urgently needed. Methods An evidence-based reporting template was developed for assessing COVID-19 pneumonia using an FDA-approved medical software. The annotation of qualitative and quantitative findings including radiomics features is performed directly on primary imaging data. For data collection, secondary information from the patient history and clinical data such as symptoms and comorbidities are queried. Results License-royalty free, cloud-based web platform and on-premise deployments are offered. Hospitals can upload, assess, report and if pseudonymized share their COVID-19 cases. The aggregation of radiomics in correlation with rt-PCR, patient history, clinical and radiological findings, systematically documented in a single database, will lead to optimized diagnosis, risk stratification and response evaluation. A customizable analytics dashboard allows the explorative real-time data analysis of imaging features and clinical information. Conclusions The COVID-19-Template is based on a systematic, computer-assisted and context-guided approach to collect, analyze and share data. Epidemiological and clinical studies for therapies and vaccine candidates can be implemented in compliance with high data quality, integrity and traceability.", "qid": 35, "docid": "5s30ihv3", "rank": 61, "score": 0.7575904130935669}, {"content": "Title: Using Reports of Symptoms and Diagnoses on Social Media to Predict COVID-19 Case Counts in Mainland China: Observational Infoveillance Study Content: BACKGROUND: Coronavirus disease (COVID-19) has affected more than 200 countries and territories worldwide. This disease poses an extraordinary challenge for public health systems because screening and surveillance capacity is often severely limited, especially during the beginning of the outbreak; this can fuel the outbreak, as many patients can unknowingly infect other people. OBJECTIVE: The aim of this study was to collect and analyze posts related to COVID-19 on Weibo, a popular Twitter-like social media site in China. To our knowledge, this infoveillance study employs the largest, most comprehensive, and most fine-grained social media data to date to predict COVID-19 case counts in mainland China. METHODS: We built a Weibo user pool of 250 million people, approximately half the entire monthly active Weibo user population. Using a comprehensive list of 167 keywords, we retrieved and analyzed around 15 million COVID-19-related posts from our user pool from November 1, 2019 to March 31, 2020. We developed a machine learning classifier to identify \"sick posts,\" in which users report their own or other people's symptoms and diagnoses related to COVID-19. Using officially reported case counts as the outcome, we then estimated the Granger causality of sick posts and other COVID-19 posts on daily case counts. For a subset of geotagged posts (3.10% of all retrieved posts), we also ran separate predictive models for Hubei province, the epicenter of the initial outbreak, and the rest of mainland China. RESULTS: We found that reports of symptoms and diagnosis of COVID-19 significantly predicted daily case counts up to 14 days ahead of official statistics, whereas other COVID-19 posts did not have similar predictive power. For the subset of geotagged posts, we found that the predictive pattern held true for both Hubei province and the rest of mainland China regardless of the unequal distribution of health care resources and the outbreak timeline. CONCLUSIONS: Public social media data can be usefully harnessed to predict infection cases and inform timely responses. Researchers and disease control agencies should pay close attention to the social media infosphere regarding COVID-19. In addition to monitoring overall search and posting activities, leveraging machine learning approaches and theoretical understanding of information sharing behaviors is a promising approach to identify true disease signals and improve the effectiveness of infoveillance.", "qid": 35, "docid": "moscbmhi", "rank": 62, "score": 0.7574422359466553}, {"content": "Title: Mapping the Landscape of Artificial Intelligence Applications against COVID-19 Content: COVID-19, the disease caused by the SARS-CoV-2 virus, has been declared a pandemic by the World Health Organization, with over 2.5 million confirmed cases as of April 23, 2020. In this review, we present an overview of recent studies using Machine Learning and, more broadly, Artificial Intelligence, to tackle many aspects of the COVID-19 crisis at different scales including molecular, clinical, and societal applications. We also review datasets, tools, and resources needed to facilitate AI research. Finally, we discuss strategic considerations related to the operational implementation of projects, multidisciplinary partnerships, and open science. We highlight the need for international cooperation to maximize the potential of AI in this and future pandemics.", "qid": 35, "docid": "lr88hhyh", "rank": 63, "score": 0.7564411163330078}, {"content": "Title: Global Preparedness Against COVID-19: We Must Leverage the Power of Digital Health Content: The coronavirus disease (COVID-19) pandemic has revealed many areas of public health preparedness that are lacking, especially in lower- and middle-income countries. Digital interventions provide many opportunities for strengthening health systems and could be vital resources in the current public health emergency. We provide several use cases for infection control, home-based diagnosis and screening, empowerment through information, public health surveillance and epidemiology, and leveraging crowd-sourced data. A thoughtful, concerted effort-leveraging existing experience and robust enterprise-grade technologies-can have a substantive impact on the immediate and distal consequences of COVID-19.", "qid": 35, "docid": "obvl9nto", "rank": 64, "score": 0.7559890151023865}, {"content": "Title: Mining Twitter Data on COVID-19 for Sentiment analysis and frequent patterns Discovery Content: A study with a societal objective was carried out on people exchanging on social networks and more particularly on Twitter to observe their feelings on the COVID-19. A dataset of more than 600,000 tweets with hashtags like COVID and coronavirus posted between February 27, 2020 and March 25, 2020 was built. An exploratory treatment of the number of tweets posted by country, by language and other parameters revealed an overview of the apprehension of the pandemic around the world. A sentiment analysis was elaborated on the basis of the tweets posted in English because these constitute the great majority. On the other hand, the FP-Growth algorithm was adapted to the tweets in order to discover the most frequent patterns and its derived association rules, in order to highlight the tweeters insights relatively to COVID-19.", "qid": 35, "docid": "iah8zka4", "rank": 65, "score": 0.7554212212562561}, {"content": "Title: COVID-19 research in Wikipedia Content: Wikipedia is one of the main sources of free knowledge on the Web. During the first few months of the pandemic, over 5,200 new Wikipedia pages on COVID-19 have been created and have accumulated over 400M pageviews by mid June 2020.1 At the same time, an unprecedented amount of scientific articles on COVID-19 and the ongoing pandemic have been published online. Wikipedia\u2019s contents are based on reliable sources, primarily scientific literature. Given its public function, it is crucial for Wikipedia to rely on representative and reliable scientific results, especially so in a time of crisis. We assess the coverage of COVID-19-related research in Wikipedia via citations to a corpus of over 160,000 articles. We find that Wikipedia editors are integrating new research at a fast pace, and have cited close to 2% of the COVID-19 literature under consideration. While doing so, they are able to provide a representative coverage of COVID-19-related research. We show that all the main topics discussed in this literature are proportionally represented from Wikipedia, after accounting for article-level effects. We further use regression analyses to model citations from Wikipedia and show that Wikipedia editors on average rely on literature which is highly cited, widely shared on social media, and has been peer-reviewed.", "qid": 35, "docid": "fpl5lksl", "rank": 66, "score": 0.7550613880157471}, {"content": "Title: A structured open dataset of government interventions in response to COVID-19 Content: In response to the COVID-19 pandemic, governments have implemented a wide range of nonpharmaceutical interventions (NPIs). Monitoring and documenting government strategies during the COVID-19 crisis is crucial to understand the progression of the epidemic. Following a content analysis strategy of existing public information sources, we developed a specific hierarchical coding scheme for NPIs. We generated a comprehensive structured dataset of government interventions and their respective timelines of implementation. To improve transparency and motivate collaborative validation process, information sources are shared via an open library. We also provide codes that enable users to visualise the dataset. Standardization and structure of the dataset facilitate inter-country comparison and the assessment of the impacts of different NPI categories on the epidemic parameters, population health indicators, the economy, and human rights, among others. This dataset provides an in-depth insight of the government strategies and can be a valuable tool for developing relevant preparedness plans for pandemic. We intend to further develop and update this dataset on a weekly basis until the end of December 2020.", "qid": 35, "docid": "byr1qy54", "rank": 67, "score": 0.7550147771835327}, {"content": "Title: Use of Available Data To Inform The COVID-19 Outbreak in South Africa: A Case Study Content: The coronavirus disease (COVID-19), caused by the SARS-CoV-2 virus, was declared a pandemic by the World Health Organization (WHO) in February 2020. Currently, there are no vaccines or treatments that have been approved after clinical trials. Social distancing measures, including travel bans, school closure, and quarantine applied to countries or regions are being used to limit the spread of the disease and the demand on the healthcare infrastructure. The seclusion of groups and individuals has led to limited access to accurate information. To update the public, especially in South Africa, announcements are made by the minister of health daily. These announcements narrate the confirmed COVID-19 cases and include the age, gender, and travel history of people who have tested positive for the disease. Additionally, the South African National Institute for Communicable Diseases updates a daily infographic summarising the number of tests performed, confirmed cases, mortality rate, and the regions affected. However, the age of the patient and other nuanced data regarding the transmission is only shared in the daily announcements and not on the updated infographic. To disseminate this information, the Data Science for Social Impact research group at the University of Pretoria, South Africa, has worked on curating and applying publicly available data in a way that is computer-readable so that information can be shared to the public - using both a data repository and a dashboard. Through collaborative practices, a variety of challenges related to publicly available data in South Africa came to the fore. These include shortcomings in the accessibility, integrity, and data management practices between governmental departments and the South African public. In this paper, solutions to these problems will be shared by using a publicly available data repository and dashboard as a case study.", "qid": 35, "docid": "op4z052p", "rank": 68, "score": 0.7548607587814331}, {"content": "Title: Global Preparedness Against COVID-19: We Must Leverage the Power of Digital Health Content: The coronavirus disease (COVID-19) pandemic has revealed many areas of public health preparedness that are lacking, especially in lower- and middle-income countries. Digital interventions provide many opportunities for strengthening health systems and could be vital resources in the current public health emergency. We provide several use cases for infection control, home-based diagnosis and screening, empowerment through information, public health surveillance and epidemiology, and leveraging crowd-sourced data. A thoughtful, concerted effort\u2014leveraging existing experience and robust enterprise-grade technologies\u2014can have a substantive impact on the immediate and distal consequences of COVID-19.", "qid": 35, "docid": "ssy2bbrn", "rank": 69, "score": 0.7548360824584961}, {"content": "Title: Survey data of COVID-19-related Knowledge, Attitude, and Practices among Indonesian Undergraduate Students Content: The dataset presented in this paper is an examination of COVID-19-related knowledge, attitude, and practice among Indonesian undergraduate students. The data were collected during first month of college or university closure due to COVID-19 through a survey distributed via an online questionnaire, assessing sociodemographic information (6 items), knowledge (18 items), attitude (6 item), and practice (12 items), from 27(th) April and 2(nd) May, 2020, gathering a total of 6,249 responses. A combination of purposive and snowball techniques helped to select the respondents via Whatsapp from more than ten universities in Indonesia. The survey data were analyzed using descriptive and inferential statistics. The data will assist in preventing and curbing the spread of COVID-19 in the university and can assist with planning for educational interventions for students\u2019 awareness.", "qid": 35, "docid": "ecbs7a5f", "rank": 70, "score": 0.7546699047088623}, {"content": "Title: Public Opinions towards COVID-19 in California and New York on Twitter Content: Background: With the pandemic of COVID-19 and the release of related policies, discussions about the COVID-19 are widespread online. Social media becomes a reliable source for understanding public opinions toward this virus outbreak. Objective: This study aims to explore public opinions toward COVID-19 on social media by comparing the differences in sentiment changes and discussed topics between California and New York in the United States. Methods: A dataset with COVID-19-related Twitter posts was collected from March 5, 2020 to April 2, 2020 using Twitter streaming API. After removing any posts unrelated to COVID-19, as well as posts that contain promotion and commercial information, two individual datasets were created based on the geolocation tags with tweets, one containing tweets from California state and the other from New York state. Sentiment analysis was conducted to obtain the sentiment score for each COVID-19 tweet. Topic modeling was applied to identify top topics related to COVID-19. Results: While the number of COVID-19 cases increased more rapidly in New York than in California in March 2020, the number of tweets posted has a similar trend over time in both states. COVID-19 tweets from California had more negative sentiment scores than New York. There were some fluctuations in sentiment scores in both states over time, which might correlate with the policy changes and the severity of COVID-19 pandemic. The topic modeling results showed that the popular topics in both California and New York states are similar, with \"protective measures\" as the most prevalent topic associated with COVID-19 in both states. Conclusions: Twitter users from California had more negative sentiment scores towards COVID-19 than Twitter users from New York. The prevalent topics about COVID-19 discussed in both states were similar with some slight differences.", "qid": 35, "docid": "onipxf2z", "rank": 71, "score": 0.7544040679931641}, {"content": "Title: Tracing open data in emergencies: the case of the COVID-19 pandemic Content: BACKGROUND: The COVID-19 pandemic constitutes an ongoing, burning Public Health Emergency of International Concern (PHEIC). In 2015, the World Health Organization (WHO) adopted an open-data policy recommendation in such situations. OBJECTIVES: The present cross-sectional meta-research study aimed to assess the availability of open data and metrics and of articles pertaining to the COVID-19 outbreak in five high-impact journals. METHODS: All articles regarding the SARS-CoV-2, published in five high impact journals (Ann Intern Med, BMJ, JAMA, NEJM and Lancet) until March 14, 2020 were retrieved. Meta-data (namely the type of article, number of authors, number of patients, citations, errata, news and social media mentions) were extracted for each article in each journal in a systematic way. Google Scholar and Scopus were used for citations and author metrics respectively, and Altmetrics and PlumX were used for news and social media mentions retrieval. The degree of adherence to the PHEIC open data call was also evaluated. RESULTS: A total of 140 articles were published until March 14, 2020, mostly opinion papers. Sixteen errata followed these publications. The number of authors in each article ranged from 1 to 63, whereas the number of patients with a laboratory-confirmed SARS-CoV-2 infection reached 2,645. The impact of these publications reached a total of 4,210 cumulative crude citations and 342,790 news and social media mentions. Only one publication (0.7%) provided complete open data, while 32 (22.9%) included patient data. CONCLUSIONS: Even though a large number of manuscripts was produced since the pandemic, availability of open data remains restricted.", "qid": 35, "docid": "vhx430l3", "rank": 72, "score": 0.7540082931518555}, {"content": "Title: What Are People Asking About COVID-19? A Question Classification Dataset Content: We present COVID-Q, a set of 1,690 questions about COVID-19 from 13 sources, which we annotate into 15 question categories and 207 question classes. The most common questions in our dataset asked about transmission, prevention, and societal effects of COVID, and we found that many questions that appeared in multiple sources were not answered by any FAQ websites of reputable organizations such as the CDC and FDA. We post our dataset publicly at https://github.com/JerryWei03/COVID-Q . For classifying questions into 15 categories, a BERT baseline scored 58.1% accuracy when trained on 20 examples per class, and for classifying questions into 89 question classes, the baseline achieved 54.6% accuracy. We hope COVID-Q can be helpful either for direct use in developing applied systems or as a domain-specific resource for model evaluation.", "qid": 35, "docid": "bm99zrxz", "rank": 73, "score": 0.7539407014846802}, {"content": "Title: A Study of Knowledge Sharing related to Covid-19 Pandemic in Stack Overflow Content: The Covid-19 outbreak, beyond its tragic effects, has changed to an unprecedented extent almost every aspect of human activity throughout the world. At the same time, the pandemic has stimulated enormous amount of research by scientists across various disciplines, seeking to study the phenomenon itself, its epidemiological characteristics and ways to confront its consequences. Information Technology, and particularly Data Science, drive innovation in all related to Covid-19 biomedical fields. Acknowledging that software developers routinely resort to open question and answer communities like Stack Overflow to seek advice on solving technical issues, we have performed an empirical study to investigate the extent, evolution and characteristics of Covid-19 related posts. In particular, through the study of 464 Stack Overflow questions posted mainly in February and March 2020 and leveraging the power of text mining, we attempt to shed light into the interest of developers in Covid-19 related topics and the most popular technological problems for which the users seek information. The findings reveal that indeed this global crisis sparked off an intense and increasing activity in Stack Overflow with most post topics reflecting a strong interest on the analysis of Covid-19 data, primarily using Python technologies.", "qid": 35, "docid": "zqbw7uc9", "rank": 74, "score": 0.7539008259773254}, {"content": "Title: A Cross-Domain Approach to Analyzing the Short-Run Impact of COVID-19 on the U.S. Electricity Sector Content: The novel coronavirus disease (COVID-19) has rapidly spread around the globe in 2020, with the U.S. becoming the epicenter of COVID-19 cases since late March. As the U.S. begins to gradually resume economic activity, it is imperative for policymakers and power system operators to take a scientific approach to understanding and predicting the impact on the electricity sector. Here, we release a first-of-its-kind cross-domain open-access data hub, integrating data from across all existing U.S. wholesale electricity markets with COVID-19 case, weather, cellular location, and satellite imaging data. Leveraging cross-domain insights from public health and mobility data, we uncover a significant reduction in electricity consumption across that is strongly correlated with the rise in the number of COVID-19 cases, degree of social distancing, and level of commercial activity.", "qid": 35, "docid": "kirbycpf", "rank": 75, "score": 0.7538613080978394}, {"content": "Title: COVID-19Base: A knowledgebase to explore biomedical entities related to COVID-19 Content: We are presenting COVID-19Base, a knowledgebase highlighting the biomedical entities related to COVID-19 disease based on literature mining. To develop COVID-19Base, we mine the information from publicly available scientific literature and related public resources. We considered seven topic-specific dictionaries, including human genes, human miRNAs, human lncRNAs, diseases, Protein Databank, drugs, and drug side effects, are integrated to mine all scientific evidence related to COVID-19. We have employed an automated literature mining and labeling system through a novel approach to measure the effectiveness of drugs against diseases based on natural language processing, sentiment analysis, and deep learning. To the best of our knowledge, this is the first knowledgebase dedicated to COVID-19, which integrates such large variety of related biomedical entities through literature mining. Proper investigation of the mined biomedical entities along with the identified interactions among those, reported in COVID-19Base, would help the research community to discover possible ways for the therapeutic treatment of COVID-19.", "qid": 35, "docid": "hnutdxh5", "rank": 76, "score": 0.753851056098938}, {"content": "Title: Where we are in fighting against COVID-19 Content: On March 11, 2020, the World Health Organization announced the novel coronavirus disease (COVID-19) as a pandemic. Despite an increasing number of international attempts using maps to present and communicate COVID-19-related information in different organizations, most map products have only used the presentation function of maps. Against this backdrop, we offer an automatically daily-updated, color-blind-friendly, Tableau-based interactive dashboard to demonstrate where and how different countries are fighting against COVID-19. The dashboard allows users to specify countries they want to compare and aggregate relevant data on a daily, weekly, or monthly basis.", "qid": 35, "docid": "cs3dpp20", "rank": 77, "score": 0.7538440227508545}, {"content": "Title: Quantifying Policy Responses to a Global Emergency: Insights from the COVID-19 Pandemic Content: Public policy must confront emergencies that evolve in real time and in uncertain directions, yet little is known about the nature of policy response. Here we take the coronavirus pandemic as a global and extraordinarily consequential case, and study the global policy response by analyzing a novel dataset recording policy documents published by government agencies, think tanks, and intergovernmental organizations (IGOs) across 114 countries (37,725 policy documents from Jan 2nd through May 26th 2020). Our analyses reveal four primary findings. (1) Global policy attention to COVID-19 follows a remarkably similar trajectory as the total confirmed cases of COVID-19, yet with evolving policy focus from public health to broader social issues. (2) The COVID-19 policy frontier disproportionately draws on the latest, peer-reviewed, and high-impact scientific insights. Moreover, policy documents that cite science appear especially impactful within the policy domain. (3) The global policy frontier is primarily interconnected through IGOs, such as the WHO, which produce policy documents that are central to the COVID19 policy network and draw especially strongly on scientific literature. Removing IGOs' contributions fundamentally alters the global policy landscape, with the policy citation network among government agencies increasingly fragmented into many isolated clusters. (4) Countries exhibit highly heterogeneous policy attention to COVID-19. Most strikingly, a country's early policy attention to COVID-19 shows a surprising degree of predictability for the country's subsequent deaths. Overall, these results uncover fundamental patterns of policy interactions and, given the consequential nature of emergent threats and the paucity of quantitative approaches to understand them, open up novel dimensions for assessing and effectively coordinating global and local responses to COVID-19 and beyond.", "qid": 35, "docid": "zu2mns82", "rank": 78, "score": 0.7534537315368652}, {"content": "Title: Data-driven Analytical Models of COVID-2019 for Epidemic Prediction, Clinical Diagnosis, Policy Effectiveness and Contact Tracing: A Survey Content: The widely spread CoronaVirus Disease (COVID)-19 is one of the worst infectious disease outbreaks in history and has become an emergency of primary international concern. As the pandemic evolves, academic communities have been actively involved in various capacities, including accurate epidemic estimation, fast clinical diagnosis, policy effectiveness evaluation and development of contract tracing technologies. There are more than 23,000 academic papers on the COVID-19 outbreak, and this number is doubling every 20 days while the pandemic is still on-going [1]. The literature, however, at its early stage, lacks a comprehensive survey from a data analytics perspective. In this paper, we review the latest models for analyzing COVID19 related data, conduct post-publication model evaluations and cross-model comparisons, and collect data sources from different projects.", "qid": 35, "docid": "xe0dhx4o", "rank": 79, "score": 0.7534430027008057}, {"content": "Title: Understanding the perception of COVID-19 policies by mining a multilanguage Twitter dataset Content: The objective of this work is to explore popular discourse about the COVID-19 pandemic and policies implemented to manage it. Using Natural Language Processing, Text Mining, and Network Analysis to analyze corpus of tweets that relate to the COVID-19 pandemic, we identify common responses to the pandemic and how these responses differ across time. Moreover, insights as to how information and misinformation were transmitted via Twitter, starting at the early stages of this pandemic, are presented. Finally, this work introduces a dataset of tweets collected from all over the world, in multiple languages, dating back to January 22nd, when the total cases of reported COVID-19 were below 600 worldwide. The insights presented in this work could help inform decision makers in the face of future pandemics, and the dataset introduced can be used to acquire valuable knowledge to help mitigate the COVID-19 pandemic.", "qid": 35, "docid": "uwrotzhk", "rank": 80, "score": 0.7531284093856812}, {"content": "Title: Common Pitfalls in the Interpretation of COVID-19 Data and Statistics Content: Policymakers, experts and the general public heavily rely on the data that are being reported in the context of the coronavirus pandemic. Daily data releases on confirmed COVID-19 cases and deaths provide information on the course of the pandemic.", "qid": 35, "docid": "zbjig3pt", "rank": 81, "score": 0.753043532371521}, {"content": "Title: A Cross-National Design to Estimate Effects of COVID-Induced Non-Pharmacological Interventions Content: We describe a research initiative that will explore the economic and social effects not of the COVID-19 itself but of the policies and information environment that COVID-19 spawned We will exploit the substantial intra and inter-country temporal and geographic variation in non-pharmacological intervention policies induced by the COVID-19 disease We will use data from ongoing household-based panel studies from 10 countries and rich administrative data from an eleventh Six of the ten household panels have already fielded or will shortly field COVID-related questions to their main samples A seventh, the PSID, has fielded questions to samples of the Child Development Supplement and Transition into Adulthood Supplement The PSID and the other three panels will include COVID related questions in their next regular survey All of them will be completed in 2021", "qid": 35, "docid": "u3gju3d6", "rank": 82, "score": 0.7521005868911743}, {"content": "Title: How the world's collective attention is being paid to a pandemic: COVID-19 related 1-gram time series for 24 languages on Twitter Content: In confronting the global spread of the coronavirus disease COVID-19 pandemic we must have coordinated medical, operational, and political responses. In all efforts, data is crucial. Fundamentally, and in the possible absence of a vaccine for 12 to 18 months, we need universal, well-documented testing for both the presence of the disease as well as confirmed recovery through serological tests for antibodies, and we need to track major socioeconomic indices. But we also need auxiliary data of all kinds, including data related to how populations are talking about the unfolding pandemic through news and stories. To in part help on the social media side, we curate a set of 1000 day-scale time series of 1-grams across 24 languages on Twitter that are most `important' for March 2020 with respect to March 2019. We determine importance through our allotaxonometric instrument, rank-turbulence divergence. We make some basic observations about some of the time series, including a comparison to numbers of confirmed deaths due to COVID-19 over time. We broadly observe across all languages a peak for the language-specific word for `virus' in January followed by a decline through February and a recent surge through March. The world's collective attention dropped away while the virus spread out from China. We host the time series on Gitlab, updating them on a daily basis while relevant. Our main intent is for other researchers to use these time series to enhance whatever analyses that may be of use during the pandemic as well as for retrospective investigations.", "qid": 35, "docid": "5uyvn546", "rank": 83, "score": 0.7520966529846191}, {"content": "Title: Development of an openEHR Template for COVID-19 Based on Clinical Guidelines Content: BACKGROUND: The coronavirus disease (COVID-19) was discovered in China in December 2019. It has developed into a threatening international public health emergency. With the exception of China, the number of cases continues to increase worldwide. A number of studies about disease diagnosis and treatment have been carried out, and many clinically proven effective results have been achieved. Although information technology can improve the transferring of such knowledge to clinical practice rapidly, data interoperability is still a challenge due to the heterogeneous nature of hospital information systems. This issue becomes even more serious if the knowledge for diagnosis and treatment is updated rapidly as is the case for COVID-19. An open, semantic-sharing, and collaborative-information modeling framework is needed to rapidly develop a shared data model for exchanging data among systems. openEHR is such a framework and is supported by many open software packages that help to promote information sharing and interoperability. OBJECTIVE: This study aims to develop a shared data model based on the openEHR modeling approach to improve the interoperability among systems for the diagnosis and treatment of COVID-19. METHODS: The latest Guideline of COVID-19 Diagnosis and Treatment in China was selected as the knowledge source for modeling. First, the guideline was analyzed and the data items used for diagnosis and treatment, and management were extracted. Second, the data items were classified and further organized into domain concepts with a mind map. Third, searching was executed in the international openEHR Clinical Knowledge Manager (CKM) to find the existing archetypes that could represent the concepts. New archetypes were developed for those concepts that could not be found. Fourth, these archetypes were further organized into a template using Ocean Template Editor. Fifth, a test case of data exchanging between the clinical data repository and clinical decision support system based on the template was conducted to verify the feasibility of the study. RESULTS: A total of 203 data items were extracted from the guideline in China, and 16 domain concepts (16 leaf nodes in the mind map) were organized. There were 22 archetypes used to develop the template for all data items extracted from the guideline. All of them could be found in the CKM and reused directly. The archetypes and templates were reviewed and finally released in a public project within the CKM. The test case showed that the template can facilitate the data exchange and meet the requirements of decision support. CONCLUSIONS: This study has developed the openEHR template for COVID-19 based on the latest guideline from China using openEHR modeling methodology. It represented the capability of the methodology for rapidly modeling and sharing knowledge through reusing the existing archetypes, which is especially useful in a new and fast-changing area such as with COVID-19.", "qid": 35, "docid": "609eozai", "rank": 84, "score": 0.7520027160644531}, {"content": "Title: Getting Insights from a Large Corpus of Scientific Papers on Specialisted Comprehensive Topics -- the Case of COVID-19 Content: COVID-19 is one of the most important topic these days, specifically on search engines and news. While fake news are easily shared, scientific papers are reliable sources where information can be extracted. With about 24,000 scientific publications on COVID-19 and related research on PUBMED, automatic computer-assisted analysis is required. In this paper, we develop two methodologies to get insights on specific sub-topics of interest and latest research sub-topics. They rely on natural language processing and graph-based visualizations. We run these methodologies on two cases: the virus origin and the uses of existing drugs.", "qid": 35, "docid": "3xwbq8ov", "rank": 85, "score": 0.7519793510437012}, {"content": "Title: COVID-19 publications: Database coverage, citations, readers, tweets, news, Facebook walls, Reddit posts Content: The COVID-19 pandemic requires a fast response from researchers to help address biological, medical and public health issues to minimize its impact. In this rapidly evolving context, scholars, professionals and the public may need to quickly identify important new studies. In response, this paper assesses the coverage of scholarly databases and impact indicators during 21 March to 18 April 2020. The results confirm a rapid increase in the volume of research, which particularly accessible through Google Scholar and Dimensions, and less through Scopus, the Web of Science, PubMed. A few COVID-19 papers from the 21,395 in Dimensions were already highly cited, with substantial news and social media attention. For this topic, in contrast to previous studies, there seems to be a high degree of convergence between articles shared in the social web and citation counts, at least in the short term. In particular, articles that are extensively tweeted on the day first indexed are likely to be highly read and relatively highly cited three weeks later. Researchers needing wide scope literature searches (rather than health focused PubMed or medRxiv searches) should start with Google Scholar or Dimensions and can use tweet and Mendeley reader counts as indicators of likely importance.", "qid": 35, "docid": "6n8ozd36", "rank": 86, "score": 0.7519651651382446}, {"content": "Title: ArCOV-19: The First Arabic COVID-19 Twitter Dataset with Propagation Networks Content: In this paper, we present ArCOV-19, an Arabic COVID-19 Twitter dataset that covers the period from 27th of January till 31st of March 2020. ArCOV-19 is the first publicly-available Arabic Twitter dataset covering COVID-19 pandemic that includes around 748k popular tweets (according to Twitter search criterion) alongside the propagation networks of the most-popular subset of them. The propagation networks include both retweets and conversational threads (i.e., threads of replies). ArCOV-19 is designed to enable research under several domains including natural language processing, information retrieval, and social computing, among others. Preliminary analysis shows that ArCOV-19 captures rising discussions associated with the first reported cases of the disease as they appeared in the Arab world. In addition to the source tweets and the propagation networks, we also release the search queries and the language-independent crawler used to collect the tweets to encourage the curation of similar datasets.", "qid": 35, "docid": "j530ia4u", "rank": 87, "score": 0.7518429756164551}, {"content": "Title: FakeCovid -- A Multilingual Cross-domain Fact Check News Dataset for COVID-19 Content: In this paper, we present a first multilingual cross-domain dataset of 5182 fact-checked news articles for COVID-19, collected from 04/01/2020 to 15/05/2020. We have collected the fact-checked articles from 92 different fact-checking websites after obtaining references from Poynter and Snopes. We have manually annotated articles into 11 different categories of the fact-checked news according to their content. The dataset is in 40 languages from 105 countries. We have built a classifier to detect fake news and present results for the automatic fake news detection and its class. Our model achieves an F1 score of 0.76 to detect the false class and other fact check articles. The FakeCovid dataset is available at Github.", "qid": 35, "docid": "9it9pgq1", "rank": 88, "score": 0.7510663866996765}, {"content": "Title: Scientific solidarity in the face of the COVID-19 pandemic: researchers, publishers, and medical associations Content: In the face of COVID-19, the scientific community has rapidly come together to address this outbreak in an open and collaborative manner to support the global response to this outbreak by rapidly sharing and highlighting research data and relevant findings COVID-19 research is being published at a furious pace Over 6,000 articles have been published as of 20 April 2020, and at least 15 online resource centers/websites for COVID-19 have been created by publishers to enable fast and free access to the latest research, evidence, and data available Moreover, many evidence-based guidelines for COVID-19 have been issued based on academic articles and summaries of the experiences of frontline medical personnel Various academic medical associations are also actively sharing information and providing technical support As an example, 93 guides/proposals/responses to COVID-19 have been issued so far by 50 medical associations in Japan However, few publications and national situation reports have provided information on the number of infected healthcare workers (HCWs) More publications and national situation reports are urgently needed to provide scientific information to devise specific infection prevention and control measures in order to protect HCWs from infection", "qid": 35, "docid": "wkzv1dkd", "rank": 89, "score": 0.7508313655853271}, {"content": "Title: CoAID: COVID-19 Healthcare Misinformation Dataset Content: As the COVID-19 virus quickly spreads around the world, unfortunately, misinformation related to COVID-19 also gets created and spreads like wild fire. Such misinformation has caused confusion among people, disruptions in society, and even deadly consequences in health problems. To be able to understand, detect, and mitigate such COVID-19 misinformation, therefore, has not only deep intellectual values but also huge societal impacts. To help researchers combat COVID-19 health misinformation, therefore, we present CoAID (Covid-19 heAlthcare mIsinformation Dataset), with diverse COVID-19 healthcare misinformation, including fake news on websites and social platforms, along with users' social engagement about such news. CoAID includes 1,896 news, 183,564 related user engagements, 516 social platform posts about COVID-19, and ground truth labels. The dataset is available at: https://github.com/cuilimeng/CoAID.", "qid": 35, "docid": "e2zz90sp", "rank": 90, "score": 0.7506355047225952}, {"content": "Title: Reproducibility and reporting practices in COVID-19 preprint manuscripts Content: The novel coronavirus, COVID-19, has sparked an outflow of scientific research seeking to understand the virus, its spread, and best practices in prevention and treatment. If this international research effort is going to be as swift and effective as possible, it will need to rely on a principle of open science. When researchers share data, code, and software and generally make their work as transparent as possible, it allows other researchers to verify and expand upon their work. Furthermore, it allows public officials to make informed decisions. In this study, we analyzed 535 preprint articles related to COVID-19 for eight transparency criteria and recorded study location and funding information. We found that individual researchers have lined up to help during this crisis, quickly tackling important public health questions, often without funding or support from outside organizations. However, most authors could improve their data sharing and scientific reporting practices. The contrast between the commitment of researchers to doing important research and their reporting practices reveals underlying weaknesses in reporting habits, but not necessarily their science.", "qid": 35, "docid": "x2ky94b0", "rank": 91, "score": 0.7501336336135864}, {"content": "Title: Tracing open data in emergencies: the case of the COVID\u201019 pandemic Content: BACKGROUND: The COVID\u201019 pandemic constitutes an ongoing, burning Public Health Emergency of International Concern (PHEIC). In 2015, the World Health Organization (WHO) adopted an open\u2010data policy recommendation in such situations. OBJECTIVES: The present cross\u2010sectional meta\u2010research study aimed to assess the availability of open data and metrics and of articles pertaining to the COVID\u201019 outbreak in five high\u2010impact journals. METHODS: All articles regarding the SARS\u2010CoV\u20102, published in five high impact journals (Ann Intern Med, BMJ, JAMA, NEJM and Lancet) until March 14, 2020 were retrieved. Meta\u2010data (namely the type of article, number of authors, number of patients, citations, errata, news and social media mentions) were extracted for each article in each journal in a systematic way. Google Scholar and Scopus were used for citations and author metrics respectively, and Altmetrics and PlumX were used for news and social media mentions retrieval. The degree of adherence to the PHEIC open data call was also evaluated. RESULTS: A total of 140 articles were published until March 14, 2020, mostly opinion papers. Sixteen errata followed these publications. The number of authors in each article ranged from 1 to 63, whereas the number of patients with a laboratory\u2010confirmed SARS\u2010CoV\u20102 infection reached 2,645. The impact of these publications reached a total of 4,210 cumulative crude citations and 342,790 news and social media mentions. Only one publication (0.7%) provided complete open data, while 32 (22.9%) included patient data. CONCLUSIONS: Even though a large number of manuscripts was produced since the pandemic, availability of open data remains restricted.", "qid": 35, "docid": "4h2ma00j", "rank": 92, "score": 0.7497811317443848}, {"content": "Title: Mining Coronavirus (COVID-19) Posts in Social Media Content: World Health Organization (WHO) characterized the novel coronavirus (COVID-19) as a global pandemic on March 11th, 2020. Before this and in late January, more specifically on January 27th, while the majority of the infection cases were still reported in China and a few cruise ships, we began crawling social media user postings using the Twitter search API. Our goal was to leverage machine learning and linguistic tools to better understand the impact of the outbreak in China. Unlike our initial expectation to monitor a local outbreak, COVID-19 rapidly spread across the globe. In this short article we report the preliminary results of our study on automatically detecting the positive reports of COVID-19 from social media user postings using state-of-the-art machine learning models.", "qid": 35, "docid": "bhhhslsr", "rank": 93, "score": 0.7493661642074585}, {"content": "Title: Machine Learning to Detect Self-Reporting of Symptoms, Testing Access, and Recovery Associated With COVID-19 on Twitter: Retrospective Big Data Infoveillance Study Content: BACKGROUND: The coronavirus disease (COVID-19) pandemic is a global health emergency with over 6 million cases worldwide as of the beginning of June 2020. The pandemic is historic in scope and precedent given its emergence in an increasingly digital era. Importantly, there have been concerns about the accuracy of COVID-19 case counts due to issues such as lack of access to testing and difficulty in measuring recoveries. OBJECTIVE: The aims of this study were to detect and characterize user-generated conversations that could be associated with COVID-19-related symptoms, experiences with access to testing, and mentions of disease recovery using an unsupervised machine learning approach. METHODS: Tweets were collected from the Twitter public streaming application programming interface from March 3-20, 2020, filtered for general COVID-19-related keywords and then further filtered for terms that could be related to COVID-19 symptoms as self-reported by users. Tweets were analyzed using an unsupervised machine learning approach called the biterm topic model (BTM), where groups of tweets containing the same word-related themes were separated into topic clusters that included conversations about symptoms, testing, and recovery. Tweets in these clusters were then extracted and manually annotated for content analysis and assessed for their statistical and geographic characteristics. RESULTS: A total of 4,492,954 tweets were collected that contained terms that could be related to COVID-19 symptoms. After using BTM to identify relevant topic clusters and removing duplicate tweets, we identified a total of 3465 (<1%) tweets that included user-generated conversations about experiences that users associated with possible COVID-19 symptoms and other disease experiences. These tweets were grouped into five main categories including first- and secondhand reports of symptoms, symptom reporting concurrent with lack of testing, discussion of recovery, confirmation of negative COVID-19 diagnosis after receiving testing, and users recalling symptoms and questioning whether they might have been previously infected with COVID-19. The co-occurrence of tweets for these themes was statistically significant for users reporting symptoms with a lack of testing and with a discussion of recovery. A total of 63% (n=1112) of the geotagged tweets were located in the United States. CONCLUSIONS: This study used unsupervised machine learning for the purposes of characterizing self-reporting of symptoms, experiences with testing, and mentions of recovery related to COVID-19. Many users reported symptoms they thought were related to COVID-19, but they were not able to get tested to confirm their concerns. In the absence of testing availability and confirmation, accurate case estimations for this period of the outbreak may never be known. Future studies should continue to explore the utility of infoveillance approaches to estimate COVID-19 disease severity.", "qid": 35, "docid": "zzaq88ah", "rank": 94, "score": 0.7493482828140259}, {"content": "Title: COVID-19 in people with multiple sclerosis: A global data sharing initiative Content: BACKGROUND: We need high-quality data to assess the determinants for COVID-19 severity in people with MS (PwMS). Several studies have recently emerged but there is great benefit in aligning data collection efforts at a global scale. OBJECTIVES: Our mission is to scale-up COVID-19 data collection efforts and provide the MS community with data-driven insights as soon as possible. METHODS: Numerous stakeholders were brought together. Small dedicated interdisciplinary task forces were created to speed-up the formulation of the study design and work plan. First step was to agree upon a COVID-19 MS core data set. Second, we worked on providing a user-friendly and rapid pipeline to share COVID-19 data at a global scale. RESULTS: The COVID-19 MS core data set was agreed within 48 hours. To date, 23 data collection partners are involved and the first data imports have been performed successfully. Data processing and analysis is an on-going process. CONCLUSIONS: We reached a consensus on a core data set and established data sharing processes with multiple partners to address an urgent need for information to guide clinical practice. First results show that partners are motivated to share data to attain the ultimate joint goal: better understand the effect of COVID-19 in PwMS.", "qid": 35, "docid": "xuuucwgj", "rank": 95, "score": 0.7489968538284302}, {"content": "Title: Crowdsourcing a crisis response for COVID-19 in oncology Content: Crowdsourcing efforts are currently underway to collect and analyze data from patients with cancer who are affected by the COVID-19 pandemic. These community-led initiatives will fill key knowledge gaps to tackle crucial clinical questions on the complexities of infection with the causative coronavirus SARS-Cov-2 in the large, heterogeneous group of vulnerable patients with cancer.", "qid": 35, "docid": "vij7setk", "rank": 96, "score": 0.7487007975578308}, {"content": "Title: Association of COVID-19 Infections in San Francisco in Early March 2020 with Travel to New York and Europe Content: Real-time dissemination of epidemiological survey data from positive COVID-19 cases is critical to support efforts to contain or reduce spread of viral infection in the community. Here we detected a significant association between domestic travel or travel to Europe and the identification of new cases in San Francisco, California, USA. These findings suggest that domestic and European travelers may need to be prioritized for evaluation of acute infection from COVID-19 in the setting of limited testing capacity.", "qid": 35, "docid": "3go7thqh", "rank": 97, "score": 0.7484216690063477}, {"content": "Title: Ranking the explanatory power of factors associated with worldwide new Covid-19 cases Content: Disease spread is a complex phenomenon requiring an interdisciplinary approach. Covid-19 exhibited a global spatial spread in a very short time frame resulting in a global pandemic. Data of new Covid-19 cases per million were analysed worldwide at the spatial scale of a country and time replicated from the end of December 2019 to late May 2020. Data driven analysis of epidemiological, economic, public health, and governmental intervention variables was performed in order to select the optimal variables in explaining new Covid-19 cases across all countries in time. Sequentially, hierarchical variance partitioning of the optimal variables was performed in order to quantify the independent contribution of each variable in the total variance of new Covid-19 cases per million. Results indicated that from the variables available new tests per thousand explained the vast majority of the total variance in new cases (51.6%) followed by the governmental stringency index (15.2%). Availability of hospital beds per 100k inhabitants explained 9% extreme poverty explained 8.8%, hand washing facilities 5.3%, the fraction of the population aged 65 or older explained 3.9%, and other disease prevalence (cardiovascular diseases plus diabetes) explained 2.9%. The percentage of smokers within the population explained 2.6% of the total variance, while population density explained 0.6%.", "qid": 35, "docid": "535cpe5x", "rank": 98, "score": 0.748389720916748}, {"content": "Title: Artificial Intelligence-Powered Search Tools and Resources in the Fight Against COVID-19. Content: Emerging technologies are set to play an important role in our response to the COVID-19 pandemic. This paper explores three prominent initiatives: COVID-19 focused datasets (e.g., CORD-19); Artificial intelligence-powered search tools (e.g., WellAI, SciSight); and contact tracing based on mobile communication technology. We believe that increasing awareness of these tools will be important in future research into the disease, COVID-19, and the virus, SARS-CoV-2.", "qid": 35, "docid": "0p6al1j4", "rank": 99, "score": 0.7483716011047363}, {"content": "Title: Artificial Intelligence-Powered Search Tools and Resources in the Fight Against COVID-19 Content: Emerging technologies are set to play an important role in our response to the COVID-19 pandemic. This paper explores three prominent initiatives: COVID-19 focused datasets (e.g., CORD-19); Artificial intelligence-powered search tools (e.g., WellAI, SciSight); and contact tracing based on mobile communication technology. We believe that increasing awareness of these tools will be important in future research into the disease, COVID-19, and the virus, SARS-CoV-2.", "qid": 35, "docid": "uxhme6r1", "rank": 100, "score": 0.7483716011047363}]}
{"query": "What is the protein structure of the SARS-CoV-2 spike?", "hits": [{"content": "Title: CoV3D: A database of high resolution coronavirus protein structures Content: The SARS-CoV-2 virus is the cause of the current COVID-19 pandemic, and exemplifies the general threat to global health posed by coronaviruses. The urgent need for effective vaccines and therapies is leading to a rapid rise in the number of high resolution structures of SARS-CoV-2 proteins that collectively reveal a map of virus vulnerabilities. To assist structure-based design of vaccines and therapeutics against SARS-CoV-2 and other coronaviruses, we developed CoV3D, a database and molecular viewer of SARS-CoV-2 and other coronavirus protein structures updated weekly. CoV3D annotates structures of coronavirus proteins and their complexes with antibodies, receptors, and small molecules. Additionally, CoV3D provides information on spike glycoprotein sequence variability and polymorphisms, and maps these features onto the spike structure in the integrated molecular viewer. In order to further aid structure-based design and analysis, CoV3D includes viewable and downloadable spike glycoprotein structures with modeled glycosylation from Rosetta. CoV3D is available at: https://cov3d.ibbr.umd.edu.", "qid": 36, "docid": "co27h1kj", "rank": 1, "score": 0.7990635633468628}, {"content": "Title: Molecular architecture of the SARS-CoV-2 virus Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus responsible for the COVID-19 pandemic. Despite recent advances in the structural elucidation of SARS-CoV-2 proteins and the complexes of the spike (S) proteins with the cellular receptor ACE2 or neutralizing antibodies, detailed architecture of the intact virus remains to be unveiled. Here we report the molecular assembly of the authentic SARS-CoV-2 virus using cryo-electron tomography (cryo-ET) and subtomogram averaging (STA). Native structures of the S proteins in both pre- and postfusion conformations were determined to average resolutions of 9-11 \u00c5. Compositions of the N-linked glycans from the native spikes were analyzed by mass spectrometry, which revealed highly similar overall processing states of the native glycans to that of the recombinant glycoprotein glycans. The in situ architecture of the ribonucleoproteins (RNP) and its higher-order assemblies were revealed. These characterizations have revealed the architecture of the SARS-CoV-2 virus to an unprecedented resolution, and shed lights on how the virus packs its ~30 Kb long single-segmented RNA in the ~80 nm diameter lumen. Overall, the results unveiled the molecular architecture and assembly of the SARS-CoV-2 in native context.", "qid": 36, "docid": "oo0pzspi", "rank": 2, "score": 0.7979098558425903}, {"content": "Title: Distinct Structural Flexibility within SARS-CoV-2 Spike Protein Reveals Potential Therapeutic Targets Content: The emergence and rapid worldwide spread of the novel coronavirus disease, COVID-19, has prompted concerted efforts to find successful treatments. The causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), uses its spike (S) protein to gain entry into host cells. Therefore, the S protein presents a viable target to develop a directed therapy. Here, we deployed an integrated artificial intelligence with molecular dynamics simulation approach to provide new details of the S protein structure. Based on a comprehensive structural analysis of S proteins from SARS-CoV-2 and previous human coronaviruses, we found that the protomer state of S proteins is structurally flexible. Without the presence of a stabilizing beta sheet from another protomer chain, two regions in the S2 domain and the hinge connecting the S1 and S2 subunits lose their secondary structures. Interestingly, the region in the S2 domain was previously identified as an immunodominant site in the SARS-CoV-1 S protein. We anticipate that the molecular details elucidated here will assist in effective therapeutic development for COVID-19.", "qid": 36, "docid": "klb8oe9q", "rank": 3, "score": 0.7965153455734253}, {"content": "Title: SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects Content: SARS-CoV-2 is thought to have emerged from bats, possibly via a secondary host. Here, we investigate the relationship of spike (S) glycoprotein from SARS-CoV-2 with the S protein of a closely related bat virus, RaTG13. We determined cryo-EM structures for RaTG13 S and for both furin-cleaved and uncleaved SARS-CoV-2 S; we compared these with recently reported structures for uncleaved SARS-CoV-2 S. We also biochemically characterized their relative stabilities and affinities for the SARS-CoV-2 receptor ACE2. Although the overall structures of human and bat virus S proteins are similar, there are key differences in their properties, including a more stable precleavage form of human S and about 1,000-fold tighter binding of SARS-CoV-2 to human receptor. These observations suggest that cleavage at the furin-cleavage site decreases the overall stability of SARS-CoV-2 S and facilitates the adoption of the open conformation that is required for S to bind to the ACE2 receptor.", "qid": 36, "docid": "3damlwoj", "rank": 4, "score": 0.796148419380188}, {"content": "Title: SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects. Content: SARS-CoV-2 is thought to have emerged from bats, possibly via a secondary host. Here, we investigate the relationship of spike (S) glycoprotein from SARS-CoV-2 with the S protein of a closely related bat virus, RaTG13. We determined cryo-EM structures for RaTG13 S and for both furin-cleaved and uncleaved SARS-CoV-2 S; we compared these with recently reported structures for uncleaved SARS-CoV-2 S. We also biochemically characterized their relative stabilities and affinities for the SARS-CoV-2 receptor ACE2. Although the overall structures of human and bat virus S proteins are similar, there are key differences in their properties, including a more stable precleavage form of human S and about 1,000-fold tighter binding of SARS-CoV-2 to human receptor. These observations suggest that cleavage at the furin-cleavage site decreases the overall stability of SARS-CoV-2 S and facilitates the adoption of the open conformation that is required for S to bind to the ACE2 receptor.", "qid": 36, "docid": "guxbf60n", "rank": 5, "score": 0.796148419380188}, {"content": "Title: Architecture of the SARS coronavirus prefusion spike Content: The emergence in 2003 of a new coronavirus (CoV) responsible for the atypical pneumonia termed severe acute respiratory syndrome (SARS) was a stark reminder that hitherto unknown viruses have the potential to cross species barriers to become new human pathogens. Here we describe the SARS-CoV 'spike' structure determined by single-particle cryo-EM, along with the docked atomic structures of the receptor-binding domain and prefusion core. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nsmb1123) contains supplementary material, which is available to authorized users.", "qid": 36, "docid": "tpn5cg4n", "rank": 6, "score": 0.7935170531272888}, {"content": "Title: Flexibility and mobility of SARS-CoV-2-related protein structures Content: The worldwide CoVid-19 pandemic has led to an unprecedented push across the whole of the scientific community to develop a potent antiviral drug and vaccine as soon as possible. Existing academic, governmental and industrial institutions and companies have engaged in large-scale screening of existing drugs, in vitro, in vivo and in silico. Here, we are using in silico modelling of SARS-CoV-2 drug targets, i.e. SARS-CoV-2 protein structures as deposited on the Protein Databank (PDB). We study their flexibility, rigidity and mobility, an important first step in trying to ascertain their dynamics for further drug-related docking studies. We are using a recent protein flexibility modelling approach, combining protein structural rigidity with possible motion consistent with chemical bonds and sterics. For example, for the SARS-CoV-2 spike protein in the open configuration, our method identifies a possible further opening and closing of the S1 subunit through movement of SB domain. With full structural information of this process available, docking studies with possible drug structures are then possible in silico. In our study, we present full results for the more than 200 thus far published SARS-CoV-2-related protein structures in the PDB.", "qid": 36, "docid": "w62xaa4f", "rank": 7, "score": 0.7916088104248047}, {"content": "Title: In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges Content: The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the major focus for vaccine development. We combine cryo electron tomography, subtomogram averaging and molecular dynamics simulations to structurally analyze S in situ. Compared to recombinant S, the viral S is more heavily glycosylated and occurs predominantly in a closed pre-fusion conformation. We show that the stalk domain of S contains three hinges that give the globular domain unexpected orientational freedom. We propose that the hinges allow S to scan the host cell surface, shielded from antibodies by an extensive glycan coat. The structure of native S contributes to our understanding of SARS-CoV-2 infection and the development of safe vaccines. The large scale tomography data set of SARS-CoV-2 used for this study is therefore sufficient to resolve structural features to below 5 \u00c5ngstrom, and is publicly available at EMPIAR-10453.", "qid": 36, "docid": "otovxksn", "rank": 8, "score": 0.7901723384857178}, {"content": "Title: Distinct conformational states of SARS-CoV-2 spike protein Content: The ongoing SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic has created urgent needs for intervention strategies to control the crisis. The spike (S) protein of the virus forms a trimer and catalyzes fusion between viral and target cell membranes - the first key step of viral infection. Here we report two cryo-EM structures, both derived from a single preparation of the full-length S protein, representing the prefusion (3.1\u00c5 resolution) and postfusion (3.3\u00c5 resolution) conformations, respectively. The spontaneous structural transition to the postfusion state under mild conditions is independent of target cells. The prefusion trimer forms a tightly packed structure with three receptor-binding domains clamped down by a segment adjacent to the fusion peptide, significantly different from recently published structures of a stabilized S ectodomain trimer. The postfusion conformation is a rigid tower-like trimer, but decorated by N-linked glycans along its long axis with almost even spacing, suggesting possible involvement in a mechanism protecting the virus from host immune responses and harsh external conditions. These findings advance our understanding of how SARS-CoV-2 enters a host cell and may guide development of vaccines and therapeutics.", "qid": 36, "docid": "muwwyktk", "rank": 9, "score": 0.7890303134918213}, {"content": "Title: Ligand\u2010centered assessment of SARS\u2010CoV\u20102 drug target models in the Protein Data Bank Content: A bright spot in the SARS\u2010CoV\u20102 (CoV\u20102) coronavirus pandemic has been the immediate mobilization of the biomedical community, working to develop treatments and vaccines for COVID\u201019. Rational drug design against emerging threats depends on well\u2010established methodology, mainly utilizing X\u2010ray crystallography, to provide accurate structure models of the macromolecular drug targets and of their complexes with candidates for drug development. In the current crisis the structural biological community has responded by presenting structure models of CoV\u20102 proteins and depositing them in the Protein Data Bank (PDB), usually without time embargo and before publication. Since the structures from the first\u2010line research are produced in an accelerated mode, there is an elevated chance of mistakes and errors, with the ultimate risk of hindering, rather than speeding\u2010up, drug development. In the present work, we have used model\u2010validation metrics and examined the electron density maps for the deposited models of CoV\u20102 proteins and a sample of related proteins available in the PDB as of 1 April 2020. We present these results with the aim of helping the biomedical community establish a better\u2010validated pool of data. The proteins are divided into groups according to their structure and function. In most cases, no major corrections were necessary. However, in several cases significant revisions in the functionally sensitive area of protein\u2010inhibitor complexes or for bound ions justified correction, re\u2010refinement, and eventually re\u2010versioning in the PDB. The re\u2010refined coordinate files and a tool for facilitating model comparisons are available at https://covid-19.bioreproducibility.org.", "qid": 36, "docid": "0eqn7m73", "rank": 10, "score": 0.7879444360733032}, {"content": "Title: N and O glycosylation of the SARS-CoV-2 spike protein Content: Covid-19 pandemic outbreak is the reason of the current world health crisis. The development of effective antiviral compounds and vaccines requires detailed descriptive studies of the SARS-CoV-2 proteins. The SARS-CoV-2 spike (S) protein mediates virion binding to the human cells through its interaction with the ACE2 cell surface receptor and is one of the prime immunization targets. A functional virion is composed of three S1 and three S2 subunits created by furin cleavage of the spike protein at R682, a polybasic cleavage sites that differs from the SARS-CoV spike protein of 2002. We observe that the spike protein is O-glycosylated on a threonine (T678) near the furin cleavage site occupied by core-1 and core-2 structures. In addition, we have identified eight additional O-glycopeptides on the spike glycoprotein and we confirmed that the spike protein is heavily N-glycosylated. Our recently developed LC-MS/MS methodology allowed us to identify LacdiNAc structural motifs on all occupied N-glycopeptides and polyLacNAc structures on six glycopeptides of the spike protein. In conclusion, our study substantially expands the current knowledge of the spike protein\u2019s glycosylation and enables the investigation of the influence of the O-glycosylation on its proteolytic activation.", "qid": 36, "docid": "ssffvlrl", "rank": 11, "score": 0.7843241691589355}, {"content": "Title: Structure-based Design of Prefusion-stabilized SARS-CoV-2 Spikes Content: The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has led to accelerated efforts to develop therapeutics, diagnostics, and vaccines to mitigate this public health emergency. A key target of these efforts is the spike (S) protein, a large trimeric class I fusion protein that is metastable and difficult to produce recombinantly in large quantities. Here, we designed and expressed over 100 structure-guided spike variants based upon a previously determined cryo-EM structure of the prefusion SARS-CoV-2 spike. Biochemical, biophysical and structural characterization of these variants identified numerous individual substitutions that increased protein yields and stability. The best variant, HexaPro, has six beneficial proline substitutions leading to ~10-fold higher expression than its parental construct and is able to withstand heat stress, storage at room temperature, and multiple freeze-thaws. A 3.2 \u00c5-resolution cryo-EM structure of HexaPro confirmed that it retains the prefusion spike conformation. High-yield production of a stabilized prefusion spike protein will accelerate the development of vaccines and serological diagnostics for SARS-CoV-2.", "qid": 36, "docid": "g81ylcxq", "rank": 12, "score": 0.7831975221633911}, {"content": "Title: Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2 Content: Severe Acute Respiratory Syndrome Coronavirus 2 is rapidly spreading around the world. There is no existing vaccine or proven drug to prevent infections and stop virus proliferation. Although this virus is similar to human and animal SARS- and MERS-CoVs the detailed information about SARS-CoV-2 proteins structures and functions is urgently needed to rapidly develop effective vaccines, antibodies and antivirals. We applied high-throughput protein production and structure determination pipeline at the Center for Structural Genomics of Infectious Diseases to produce SARS-CoV-2 proteins and structures. Here we report the high-resolution crystal structure of endoribonuclease Nsp15/NendoU from SARS-CoV-2 \u2013 a virus causing current world-wide epidemics. We compare this structure with previously reported models of Nsp15 from SARS and MERS coronaviruses.", "qid": 36, "docid": "xq1cxrvf", "rank": 13, "score": 0.7828625440597534}, {"content": "Title: Ligand-centered assessment of SARS-CoV-2 drug target models in the Protein Data Bank Content: A bright spot in the SARS-CoV-2 (CoV-2) coronavirus pandemic has been the immediate mobilization of the biomedical community, working to develop treatments and vaccines for COVID-19. Rational drug design against emerging threats depends on well-established methodology, mainly utilizing X-ray crystallography, to provide accurate structure models of the macromolecular drug targets and of their complexes with candidates for drug development. In the current crisis, the structural biological community has responded by presenting structure models of CoV-2 proteins and depositing them in the Protein Data Bank (PDB), usually without time embargo and before publication. Since the structures from the first-line research are produced in an accelerated mode, there is an elevated chance of mistakes and errors, with the ultimate risk of hindering, rather than speeding up, drug development. In the present work, we have used model-validation metrics and examined the electron density maps for the deposited models of CoV-2 proteins and a sample of related proteins available in the PDB as of April 1, 2020. We present these results with the aim of helping the biomedical community establish a better-validated pool of data. The proteins are divided into groups according to their structure and function. In most cases, no major corrections were necessary. However, in several cases significant revisions in the functionally sensitive area of protein-inhibitor complexes or for bound ions justified correction, re-refinement, and eventually reversioning in the PDB. The re-refined coordinate files and a tool for facilitating model comparisons are available at https://covid-19.bioreproducibility.org. DATABASE: Validated models of CoV-2 proteins are available in a dedicated, publicly accessible web service https://covid-19.bioreproducibility.org.", "qid": 36, "docid": "jt989p2x", "rank": 14, "score": 0.7816270589828491}, {"content": "Title: Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2 Content: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading around the world. There is no existing vaccine or proven drug to prevent infections and stop virus proliferation. Although this virus is similar to human and animal SARS-CoVs and Middle East Respiratory Syndrome coronavirus (MERS-CoVs), the detailed information about SARS-CoV-2 proteins structures and functions is urgently needed to rapidly develop effective vaccines, antibodies, and antivirals. We applied high-throughput protein production and structure determination pipeline at the Center for Structural Genomics of Infectious Diseases to produce SARS-CoV-2 proteins and structures. Here we report two high-resolution crystal structures of endoribonuclease Nsp15/NendoU. We compare these structures with previously reported homologs from SARS and MERS coronaviruses.", "qid": 36, "docid": "vosgahs3", "rank": 15, "score": 0.7764829397201538}, {"content": "Title: Targeting the SARS-CoV-2 spike glycoprotein prefusion conformation: virtual screening and molecular dynamics simulations applied to the identification of potential fusion inhibitors Content: The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a renewed interest in studying the role of the spike S glycoprotein in regulating coronavirus infections in the natural host. Taking advantage of the cryo-electron microscopy structure of SARS-CoV-2 S trimer in the prefusion conformation, we performed a virtual screening simulation with the aim to identify novel molecules that could be used as fusion inhibitors. The spike glycoprotein structure has been completed using modeling techniques and its inner cavity, needful for the postfusion transition of the trimer, has been scanned for the identification of strongly interacting available drugs. Finally, the stability of the protein-drug top complexes has been tested using classical molecular dynamics simulations. The free energy of interaction of the molecules to the spike protein has been evaluated through the MM/GBSA method and per-residue decomposition analysis. Results have been critically discussed considering previous scientific knowledge concerning the selected compounds and sequence alignments have been carried out to evaluate the spike glycoprotein similarity among the betacoronavirus family members. Finally, a cocktail of drugs that may be used as SARS-CoV-2 fusion inhibitors has been suggested.", "qid": 36, "docid": "d4yidznm", "rank": 16, "score": 0.7743147015571594}, {"content": "Title: SARS-CoV-2 mutations and where to find them: An in silico perspective of structural changes and antigenicity of the Spike protein Content: The recent emergence of a novel coronavirus (SARS-CoV-2) is causing a severe global health threat characterized by severe acute respiratory syndrome (Covid-19). At the moment, there is no specific treatment for this disease, and vaccines are still under development. The structural protein Spike is essential for virus infection and has been used as the main target for vaccine and serological diagnosis test development. We analysed 2363 sequences of the Spike protein from SARS-CoV-2 isolates and identified variability in 44 amino acid residues and their worldwide distribution in all continents. We used the three-dimensional structure of the homo-trimer model to predict conformational epitopes of B-cell, and sequence of Spike protein Wuhan-Hu-1 to predict linear epitopes of T-Cytotoxic and T-Helper cells. We identified 45 epitopes with amino acid variations. Finally, we showed the distribution of mutations within the epitopes. Our findings can help researches to identify more efficient strategies for the development of vaccines, therapies, and serological diagnostic tests based on the Spike protein of Sars-Cov-2.", "qid": 36, "docid": "srgi9jc6", "rank": 17, "score": 0.773851752281189}, {"content": "Title: Shielding and Beyond: The Roles of Glycans in SARS-CoV-2 Spike Protein Content: The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 7,000,000 infections and 400,000 deaths worldwide to date. Antibody development efforts mainly revolve around the extensively glycosylated SARSCoV-2 spike (S) protein, which mediates the host cell entry by binding to the angiotensin-converting enzyme 2 (ACE2). In the context of vaccine design, similar to many other viruses, the SARS-CoV-2 spike utilizes a glycan shield to thwart the host immune response. Here, we built a full-length model of glycosylated SARS-CoV-2 S protein, both in the open and closed states, augmenting the available structural and biological data. Multiple microsecond-long, all-atom molecular dynamics simulations were used to provide an atomistic perspective on the glycan shield and the protein structure, stability, and dynamics. End-to-end accessibility analyses outline a complete overview of the vulnerabilities of the glycan shield of SARS-CoV-2 S protein, which can be harnessed for vaccine development. In addition, a dynamic analysis of the main antibody epitopes is provided. Finally, beyond shielding, a possible structural role of N-glycans at N165 and N234 is hypothesized to modulate and stabilize the conformational dynamics of the spike\u2019s receptor binding domain, which is responsible for ACE2 recognition. Overall, this work presents hitherto unseen functional and structural insights into the SARS-CoV-2 S protein and its glycan coat, which may be exploited by therapeutic efforts targeting this essential molecular machine.", "qid": 36, "docid": "1c1k0p93", "rank": 18, "score": 0.7737711071968079}, {"content": "Title: Atlas of coronavirus replicase structure Content: Abstract The international response to SARS-CoV has produced an outstanding number of protein structures in a very short time. This review summarizes the findings of functional and structural studies including those derived from cryoelectron microscopy, small angle X-ray scattering, NMR spectroscopy, and X-ray crystallography, and incorporates bioinformatics predictions where no structural data is available. Structures that shed light on the function and biological roles of the proteins in viral replication and pathogenesis are highlighted. The high percentage of novel protein folds identified among SARS-CoV proteins is discussed.", "qid": 36, "docid": "q5332l0s", "rank": 19, "score": 0.7720333933830261}, {"content": "Title: Solution structure of the severe acute respiratory syndrome-coronavirus heptad repeat 2 domain in the prefusion state. Content: The envelope glycoprotein, termed the spike protein, of severe acute respiratory syndrome coronavirus (SARS-CoV) is known to mediate viral entry. Similar to other class 1 viral fusion proteins, the heptad repeat regions of SARS-CoV spike are thought to undergo conformational changes from a prefusion form to a subsequent post-fusion form that enables fusion of the viral and host membranes. Recently, the structure of a post-fusion form of SARS-CoV spike, which consists of isolated domains of heptad repeats 1 and 2 (HR1 and HR2), has been determined by x-ray crystallography. To date there is no structural information for the prefusion conformations of SARS-CoV HR1 and HR2. In this work we present the NMR structure of the HR2 domain (residues 1141-1193) from SARS-CoV (termed S2-HR2) in the presence of the co-solvent trifluoroethanol. We find that in the absence of HR1, S2-HR2 forms a coiled coil symmetric trimer with a complex molecular mass of 18 kDa. The S2-HR2 structure, which is the first example of the prefusion form of coronavirus envelope, supports the current model of viral membrane fusion and gives insight into the design of structure-based antagonists of SARS.", "qid": 36, "docid": "jfq7820g", "rank": 20, "score": 0.7688086032867432}, {"content": "Title: Conformational Reorganization of the SARS Coronavirus Spike Following Receptor Binding: Implications for Membrane Fusion Content: The SARS coronavirus (SARS-CoV) spike is the largest known viral spike molecule, and shares a similar function with all class 1 viral fusion proteins. Previous structural studies of membrane fusion proteins have largely used crystallography of static molecular fragments, in isolation of their transmembrane domains. In this study we have produced purified, irradiated SARS-CoV virions that retain their morphology, and are fusogenic in cell culture. We used cryo-electron microscopy and image processing to investigate conformational changes that occur in the entire spike of intact virions when they bind to the viral receptor, angiotensin-converting enzyme 2 (ACE2). We have shown that ACE2 binding results in structural changes that appear to be the initial step in viral membrane fusion, and precisely localized the receptor-binding and fusion core domains within the entire spike. Furthermore, our results show that receptor binding and subsequent membrane fusion are distinct steps, and that each spike can bind up to three ACE2 molecules. The SARS-CoV spike provides an ideal model system to study receptor binding and membrane fusion in the native state, employing cryo-electron microscopy and single-particle image analysis.", "qid": 36, "docid": "mcsdem7y", "rank": 21, "score": 0.7686238288879395}, {"content": "Title: Map of SARS-CoV-2 spike epitopes not shielded by glycans Content: The severity of the COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, calls for the urgent development of a vaccine. The primary immunological target is the SARS-CoV-2 spike (S) protein. S is exposed on the viral surface to mediate viral entry into the host cell. To identify possible antibody binding sites not shielded by glycans, we performed multi-microsecond molecular dynamics simulations of a 4.1 million atom system containing a patch of viral membrane with four full-length, fully glycosylated and palmitoylated S proteins. By mapping steric accessibility, structural rigidity, sequence conservation and generic antibody binding signatures, we recover known epitopes on S and reveal promising epitope candidates for vaccine development. We find that the extensive and inherently flexible glycan coat shields a surface area larger than expected from static structures, highlighting the importance of structural dynamics in epitope mapping.", "qid": 36, "docid": "ba7f2mf3", "rank": 22, "score": 0.7671144008636475}, {"content": "Title: Structural features of coronavirus SARS-CoV-2 spike protein: Targets for vaccination Content: Various human pathogenic viruses employ envelope glycoproteins for host cell receptor recognition and binding, membrane fusion and viral entry. The spike (S) glycoprotein of betacoronavirus SARS-CoV-2 is a homotrimeric class I fusion protein that exists in a metastable conformation for cleavage by host cell proteases furin and TMPRSS2, thereby undergoing substantial structural rearrangement for ACE2 host cell receptor binding and subsequent viral entry by membrane fusion. The S protein is densely decorated with N-linked glycans protruding from the trimer surface that affect S protein folding, processing by host cell proteases and the elicitation of humoral immune response. Deep insight into the sophisticated structure of SARS-CoV-2 S protein may provide a blueprint for vaccination strategies, as reviewed herein.", "qid": 36, "docid": "ust578fc", "rank": 23, "score": 0.7664177417755127}, {"content": "Title: Differential Antibody Recognition by Novel SARS-CoV-2 and SARS-CoV Spike Protein Receptor Binding Domains: Mechanistic Insights and Implications for the Design of Diagnostics and Therapeutics Content: The appearance of the novel betacoronavirus SARS-CoV-2 represents a major threat to human health, and its diffusion around the world is causing dramatic consequences. The knowledge of the 3D structures of SARS-CoV-2 proteins can facilitate the development of therapeutic and diagnostic molecules. Specifically, comparative analyses of the structures of SARS-CoV-2 proteins and homologous proteins from previously characterized viruses, such as SARS-CoV, can reveal the common and/or distinctive traits that underlie the mechanisms of recognition of cell receptors and of molecules of the immune system. Herein, we apply our recently developed energy-based methods for the prediction of antibody-binding epitopes and protein-protein interaction regions to the Receptor Binding Domain (RBD) of the Spike proteins from SARS-CoV-2 and SARS-CoV. Our analysis focusses only on the study of the structure of RBDs in isolation, without making use of any previous knowledge of binding properties. Importantly, our results highlight structural and sequence differences among the regions that are predicted to be immunoreactive and bind/elicit antibodies. These results provide a rational basis to the observation that several SARS-CoV RDB-specific monoclonal antibodies fail to appreciably bind the SARS-CoV-2 counterpart. Furthermore, we correctly identify the region of SARS-CoV-2 RBD that is engaged by the cell receptor ACE2 during viral entry into host cells. The data, sequences and structures we present here can be useful for the development of novel therapeutic and diagnostic interventions.", "qid": 36, "docid": "c08ptb1o", "rank": 24, "score": 0.7660361528396606}, {"content": "Title: Site-specific glycan analysis of the SARS-CoV-2 spike Content: The emergence of the betacoronavirus, SARS-CoV-2, the causative agent of COVID-19, represents a significant threat to global human health. Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion. SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion. Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen. This analysis enables mapping of the glycan-processing states across the trimeric viral spike. We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.", "qid": 36, "docid": "kfnq4tv6", "rank": 25, "score": 0.7659842371940613}, {"content": "Title: Crystal structure of Nsp15 endoribonuclease NendoU from SARS\u2010CoV\u20102 Content: Severe Acute Respiratory Syndrome coronavirus 2 (SARS\u2010CoV\u20102) is rapidly spreading around the world. There is no existing vaccine or proven drug to prevent infections and stop virus proliferation. Although this virus is similar to human and animal SARS\u2010CoVs and Middle East Respiratory Syndrome coronavirus (MERS\u2010CoVs), the detailed information about SARS\u2010CoV\u20102 proteins structures and functions is urgently needed to rapidly develop effective vaccines, antibodies, and antivirals. We applied high\u2010throughput protein production and structure determination pipeline at the Center for Structural Genomics of Infectious Diseases to produce SARS\u2010CoV\u20102 proteins and structures. Here we report two high\u2010resolution crystal structures of endoribonuclease Nsp15/NendoU. We compare these structures with previously reported homologs from SARS and MERS coronaviruses.", "qid": 36, "docid": "o0x269k5", "rank": 26, "score": 0.7656171321868896}, {"content": "Title: Site-specific analysis of the SARS-CoV-2 glycan shield Content: The emergence of the betacoronavirus, SARS-CoV-2 that causes COVID-19, represents a significant threat to global human health. Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, that mediates cell entry and membrane fusion. SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in immune evasion and occluding immunogenic protein epitopes. Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen. This analysis enables mapping of the glycan-processing states across the trimeric viral spike. We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.", "qid": 36, "docid": "63j4qc7d", "rank": 27, "score": 0.7651641368865967}, {"content": "Title: Update on the target structures of SARS-CoV-2: A systematic review Content: Knowledge of structural details is very much essential from the drug-design perspective. In the systematic review, we systematically reviewed the structural basis of different target proteins of SARS-corona virus (CoV2) from a viral life cycle and from drug design perspective. We searched four literature (PubMed, EMBASE, NATURE, and Willey online library) databases and one structural database (RCSB.org) with appropriate keywords till April 18, and finally, 26 articles were included in the systematic review. The published literature mainly centered upon the structural details of \"spike protein,\" \"main protease/M Pro/3CL pro,\" \"RNA-dependent RNA polymerase,\" and \"nonstructural protein 15 Endoribonuclease\" of SARS-CoV-2. However, inhibitor bound structures were very less. We need better structures elucidating the interactions between different targets and their inhibitors which will help us in understanding the atomic level importance of different amino acid residues in the functionality of the target structures. To summarize, we need structures with fine resolution, co-crystallized structures with biologically validated inhibitors, and functional characterization of different target proteins. Some other routes of entry of SARS-CoV-2 are also mentioned (e.g., CD147); however, these findings are not structurally validated. This review may pave way for better understanding of SARS-CoV-2 life cycle from structural biology perspective.", "qid": 36, "docid": "wak7ie3q", "rank": 28, "score": 0.7651636600494385}, {"content": "Title: Structural insight into the putative role of novel SARS CoV-2 E protein in viral infection: a potential target for LAV development and therapeutic strategies Content: The outbreak of COVID-19 across the world has posed unprecedented and global challenges on multiple fronts. Most of the vaccine and drug development has focused on the spike proteins and viral RNA-polymerases. Using the bioinformatics and structural modeling approach, we modeled the structure of the envelope (E)-protein of novel SARS-CoV-2. The E-protein of this virus shares sequence similarity with that of SARS-CoV-1, and is highly conserved in the N-terminal regions. Incidentally, compared to spike proteins, E proteins demonstrate lower disparity and mutability among the isolated sequences. Using homology modeling, we found that the most favorable structure could function as a gated proton channel. Combining pocket estimation and docking with water, we determined that GLU 8 and ASN 15 in the N-terminal region were in close proximity to form H-bonds. Additionally, two distinct \u201ccore\u201d structures were visible, the hydrophobic core and the central core, which may regulate the opening/closing of the channel. We propose this as a mechanism of viral proton channeling activity which may play a critical role in viral infection. In addition, it provides a structural basis and additional avenues for LAV development and generating therapeutic interventions against the virus. Significance Statement Structural modeling of the novel SARS-CoV-2 envelope protein (E-protein) demonstrating its possible proton channeling activity", "qid": 36, "docid": "2f1c6h4q", "rank": 29, "score": 0.7648074626922607}, {"content": "Title: Update on the target structures of SARS-CoV-2: A systematic review Content: Knowledge of structural details is very much essential from the drug-design perspective. In the systematic review, we systematically reviewed the structural basis of different target proteins of SARS-corona virus (CoV2) from a viral life cycle and from drug design perspective. We searched four literature (PubMed, EMBASE, NATURE, and Willey online library) databases and one structural database (RCSB.org) with appropriate keywords till April 18, and finally, 26 articles were included in the systematic review. The published literature mainly centered upon the structural details of \u201cspike protein,\u201d \u201cmain protease/M Pro/3CL pro,\u201d \u201cRNA-dependent RNA polymerase,\u201d and \u201cnonstructural protein 15 Endoribonuclease\u201d of SARS-CoV-2. However, inhibitor bound structures were very less. We need better structures elucidating the interactions between different targets and their inhibitors which will help us in understanding the atomic level importance of different amino acid residues in the functionality of the target structures. To summarize, we need structures with fine resolution, co-crystallized structures with biologically validated inhibitors, and functional characterization of different target proteins. Some other routes of entry of SARS-CoV-2 are also mentioned (e.g., CD147); however, these findings are not structurally validated. This review may pave way for better understanding of SARS-CoV-2 life cycle from structural biology perspective.", "qid": 36, "docid": "iyoem0p6", "rank": 30, "score": 0.7647848129272461}, {"content": "Title: On the interactions of the receptor-binding domain of SARS-CoV-1 and SARS-CoV-2 spike proteins with monoclonal antibodies and the receptor ACE2 Content: A new betacoronavirus named SARS-CoV-2 has emerged as a new threat to global health and economy. A promising target for both diagnosis and therapeutics treatments of the new disease named COVID-19 is the coronavirus (CoV) spike (S) glycoprotein. By constant-pH Monte Carlo simulations and the PROCEEDpKa method, we have mapped the electrostatic epitopes for four monoclonal antibodies and the angiotensin-converting enzyme 2 (ACE2) on both SARS-CoV-1 and the new SARS-CoV-2 S receptor binding domain (RBD) proteins. We also calculated free energy of interactions and shown that the S RBD proteins from both SARS viruses binds to ACE2 with similar affinities. However, the affinity between the S RBD protein from the new SARS-CoV-2 and ACE2 is higher than for any studied antibody previously found complexed with SARS-CoV-1. Based on physical chemical analysis and free energies estimates, we can shed some light on the involved molecular recognition processes, their clinical aspects, the implications for drug developments, and suggest structural modifications on the CR3022 antibody that would improve its binding affinities for SARS-CoV-2 and contribute to address the ongoing international health crisis.", "qid": 36, "docid": "4mv6qwpc", "rank": 31, "score": 0.7643134593963623}, {"content": "Title: Continuous flexibility analysis of SARS-CoV-2 Spike prefusion structures Content: With the help of novel processing workflows and algorithms, we have obtained a better understanding of the flexibility and conformational dynamics of the SARS-CoV-2 spike in the prefusion state. We have re-analyzed previous cryo-EM data combining 3D clustering approaches with ways to explore a continuous flexibility space based on 3D Principal Component Analysis. These advanced analyses revealed a concerted motion involving the receptor-binding domain (RBD), N-terminal domain (NTD), and subdomain 1 and 2 (SD1 & SD2) around the previously characterized 1-RBD-up state, which have been modeled as elastic deformations. We show that in this dataset there are not well-defined, stable, spike conformations, but virtually a continuum of states moving in a concerted fashion. We obtained an improved resolution ensemble map with minimum bias, from which we model by flexible fitting the extremes of the change along the direction of maximal variance. Moreover, a high-resolution structure of a recently described biochemically stabilized form of the spike is shown to greatly reduce the dynamics observed for the wild-type spike. Our results provide new detailed avenues to potentially restrain the spike dynamics for structure-based drug and vaccine design and at the same time give a warning of the potential image processing classification instability of these complicated datasets, having a direct impact on the interpretability of the results.", "qid": 36, "docid": "o58kbiqv", "rank": 32, "score": 0.763704240322113}, {"content": "Title: A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV Content: The outbreak of COVID-19, which is caused by SARS-CoV-2 virus, continues to spread globally, but there is currently very little understanding of the epitopes on the virus. In this study, we have determined the crystal structure of the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein in complex with CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient. CR3022 targets a highly conserved epitope that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. Structural modeling further demonstrates that the binding site can only be accessed when at least two RBDs on the trimeric S protein are in the \u201cup\u201d conformation. Overall, this study provides structural and molecular insight into the antigenicity of SARS-CoV-2. ONE SENTENCE SUMMARY Structural study of a cross-reactive SARS antibody reveals a conserved epitope on the SARS-CoV-2 receptor-binding domain.", "qid": 36, "docid": "f03ka7bd", "rank": 33, "score": 0.7634023427963257}, {"content": "Title: A Cryptic Site of Vulnerability on the Receptor Binding Domain of the SARS-CoV-2 Spike Glycoprotein Content: SARS-CoV-2 is a zoonotic virus that has caused a pandemic of severe respiratory disease\u2014COVID-19\u2014 within several months of its initial identification. Comparable to the first SARS-CoV, this novel coronavirus\u2019s surface Spike (S) glycoprotein mediates cell entry via the human ACE-2 receptor, and, thus, is the principal target for the development of vaccines and immunotherapeutics. Molecular information on the SARS-CoV-2 S glycoprotein remains limited. Here we report the crystal structure of the SARS-CoV-2 S receptor-binding-domain (RBD) at a the highest resolution to date, of 1.95 \u00c5. We identified a set of SARS-reactive monoclonal antibodies with cross-reactivity to SARS-CoV-2 RBD and other betacoronavirus S glycoproteins. One of these antibodies, CR3022, was previously shown to synergize with antibodies that target the ACE-2 binding site on the SARS-CoV RBD and reduce viral escape capacity. We determined the structure of CR3022, in complex with the SARS-CoV-2 RBD, and defined a broadly reactive epitope that is highly conserved across betacoronaviruses. This epitope is inaccessible in the \u201cclosed\u201d prefusion S structure, but is accessible in \u201copen\u201d conformations. This first-ever resolution of a human antibody in complex with SARS-CoV-2 and the broad reactivity of this set of antibodies to a conserved betacoronavirus epitope will allow antigenic assessment of vaccine candidates, and provide a framework for accelerated vaccine, immunotherapeutic and diagnostic strategies against SARS-CoV-2 and related betacoronaviruses. HIGHLIGHTS High resolution structure of the SARS-CoV-2 Receptor-Binding-Domain (RBD). Recognition of the SARS-CoV-2 RBD by SARS-CoV antibodies. Structure of the SARS-COV-2 RBD in complex with antibody CR3022. Identification of a cryptic site of vulnerability on the SARS-CoV-2 Spike.", "qid": 36, "docid": "ebbzx8yr", "rank": 34, "score": 0.7626586556434631}, {"content": "Title: Morphology, Genome Organization, Replication, and Pathogenesis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Content: SARS-CoV-2 is a single-stranded RNA virus of ~30 kb genome size which belongs to genus Coronavirus and family Coronaviridae. SARS-CoV-2 has recently emerged and has been declared as a pandemic by the World Health Organization. Genomic characterization of SARS-CoV-2 has shown that it is of zoonotic origin. The structure of SARS-CoV-2 is found to be similar to SARS-CoV with virion size ranging from 70 to 90 nm. Spike, membrane, and envelope surface viral proteins of coronavirus are embedded in host membrane-derived lipid bilayer encapsulating the helical nucleocapsid comprising viral RNA. The genome comprises of 6\u201311 open reading frames (ORFs) with 5\u2032 and 3\u2032 flanking untranslated regions (UTRs). Sequence variation among SARS-CoV-2 and SARS-CoV revealed no significant difference in ORFs and nsps. The nsps includes two viral cysteine proteases including papain-like protease (nsp3), chymotrypsin-like, 3C-like, or main protease (nsp5), RNA-dependent RNA polymerase (nsp12), helicase (nsp13), and others likely to be involved in the transcription and replication of SARS-CoV-2. The structure of spike glycoprotein structure of SARS-CoV-2 resembles that of the spike protein of SARS-CoV with an root-mean-square deviation (RMSD) of 3.8 \u00c5. Like SARS-CoV, SARS-CoV-2 uses the ACE2 receptor for internalization and TMPRSS2 serine proteases for S protein priming. Histopathological investigation of tissues from SARS-CoV-2 infected patients showed virus-induced cytopathic effect with signs of acute respiratory distress syndrome in lung cells. This chapter discusses about the morphology, genome organization, replication, and pathogenesis of SARS-CoV-2 that may help us understand the disease that may leads to identification of effective antiviral drugs and vaccines.", "qid": 36, "docid": "t0cw7l2a", "rank": 35, "score": 0.7619478702545166}, {"content": "Title: Modeling of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Proteins by Machine Learning and Physics-Based Refinement Content: Protein structures are crucial for understanding their biological activities. Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent need to understand the biological behavior of the virus and provide a basis for developing effective therapies. Since the proteome of the virus was determined, some of the protein structures could be determined experimentally, and others were predicted via template-based modeling approaches. However, tertiary structures for several proteins are still not available from experiment nor they could be accurately predicted by template-based modeling because of lack of close homolog structures. Previous efforts to predict structures for these proteins include efforts by DeepMind and the Zhang group via machine learning-based structure prediction methods, i.e. AlphaFold and C-I-TASSER. However, the predicted models vary greatly and have not yet been subjected to refinement. Here, we are reporting new predictions from our in-house structure prediction pipeline. The pipeline takes advantage of inter-residue contact predictions from trRosetta, a machine learning-based method. The predicted models were further improved by applying molecular dynamics simulation-based refinement. We also took the AlphaFold models and refined them by applying the same refinement method. Models based on our structure prediction pipeline and the refined AlphaFold models were analyzed and compared with the C-I-TASSER models. All of our models are available at https://github.com/feiglab/sars-cov-2-proteins.", "qid": 36, "docid": "9qv11m4f", "rank": 36, "score": 0.7613580226898193}, {"content": "Title: Comparing the binding interactions in the receptor binding domains of SARS-CoV-2 and SARS-CoV Content: COVID-19, since emerged in Wuhan, China, has been a major concern due to its high infection rate, leaving more than one million infected people around the world. Huge number of studies tried to reveal the structure of the SARS-CoV-2 compared to the SARS-CoV-1, in order to suppress this high infection rate. Some of these studies showed that the mutations in the SARS-CoV-1 Spike protein might be responsible for its higher affinity to the ACE2 human cell receptor. In this work, we used molecular dynamics simulations and Monte Carlo sampling to compare the binding affinities of the spike proteins of SARS-CoV and SARS-CoV-2 to the ACE2. We found that the SARS-CoV-2 binds to ACE2 stronger than SARS-CoV by 7 kcal/mol, due to enhanced electrostatic interactions. The major contributions to the electrostatic binding energies are resulting from the salt-bridges formed between R426 and ACE2-E329 in case of SARS-CoV and K417 and ACE2-D30 for SARS-CoV2. In addition, there is no significant contribution from a single mutant to the binding energies. However, these mutations induce sophisticated structural changes that enhance the binding energies. Our results also indicate that the SARS-CoV-2 is unlikely a lab engineered virus.", "qid": 36, "docid": "xpbcoipf", "rank": 37, "score": 0.7612590193748474}, {"content": "Title: Closing coronavirus spike glycoproteins by structure-guided design Content: The recent spillover of SARS-CoV-2 in the human population resulted in the ongoing COVID-19 pandemic which has already caused 4.9 million infections and more than 326,000 fatalities. To initiate infection the SARS-CoV-2 spike (S) glycoprotein promotes attachment to the host cell surface, determining host and tissue tropism, and fusion of the viral and host membranes. Although SARS-CoV-2 S is the main target of neutralizing antibodies and the focus of vaccine design, its stability and conformational dynamics are limiting factors for developing countermeasures against this virus. We report here the design of a prefusion SARS-CoV-2 S ectodomain trimer construct covalently stabilized in the closed conformation. Structural and antigenicity analysis showed we successfully shut S in the closed state without otherwise altering its architecture. Finally, we show that this engineering strategy is applicable to other \u03b2-coronavirus S glycoproteins and might become an important tool for vaccine design, structural biology, serology and immunology studies.", "qid": 36, "docid": "c1cm16l8", "rank": 38, "score": 0.760999321937561}, {"content": "Title: Is the Rigidity of SARS-CoV-2 Spike Receptor-Binding Motif the Hallmark for Its Enhanced Infectivity? Insights from All-Atom Simulations Content: The severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic is setting the global health crisis of our time, causing a devastating societal and economic burden. An idiosyncratic trait of coronaviruses is the presence of spike glycoproteins on the viral envelope, which mediate the virus binding to specific host receptor, enabling its entry into the human cells. In spite of the high sequence identity of SARS-CoV-2 with its closely related SARS-CoV emerged in 2002, the atomic-level determinants underlining the molecular recognition of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) receptor and, thus, the rapid virus spread into human body, remain unresolved. Here, multi-microsecond-long molecular dynamics simulations enabled us to unprecedentedly dissect the key molecular traits liable of the higher affinity/specificity of SARS-CoV-2 toward ACE2 as compared to SARS-CoV. This supplies a minute per-residue contact map underlining its stunningly high infectivity. Harnessing this knowledge is pivotal for urgently developing effective medical countermeasures to face the ongoing global health crisis.", "qid": 36, "docid": "6z4kx0y9", "rank": 39, "score": 0.7609704732894897}, {"content": "Title: In silico Proteome analysis of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (2019-nCoV), is a positive-sense, single-stranded RNA coronavirus. The virus is the causative agent of coronavirus disease 2019 (COVID-19) and is contagious through human-to-human transmission. The present study reports sequence analysis, complete coordinate tertiary structure prediction and in silico sequence-based and structure-based functional characterization of full SARS-CoV-2 proteome based on the NCBI reference sequence NC_045512 (29903 bp ss-RNA) which is identical to GenBank entry MN908947 and MT415321. The proteome includes 12 major proteins namely orf1ab polyprotein (includes 15 proteins), surface glycoprotein, ORF3a protein, envelope protein, membrane glycoprotein, ORF6 protein, ORF7a protein, orf7b, ORF8, Nucleocapsid phosphoprotein and ORF10 protein. Each protein of orf1ab polyprotein group has been studied separately. A total of 25 polypeptides have been analyzed out of which 15 proteins are not yet having experimental structures and only 10 are having experimental structures with known PDB IDs. Out of 15 newly predicted structures six (6) were predicted using comparative modeling and nine (09) proteins having no significant similarity with so far available PDB structures were modeled using ab-initio modeling. Structure verification using recent tools QMEANDisCo 4.0.0 and ProQ3 for global and local (per-residue) quality estimates indicate that the all-atom model of tertiary structure of high quality and may be useful for structure-based drug designing targets. The study has identified nine major targets (spike protein, envelop protein, membrane protein, nucleocapsid protein, 2\u2019-O-ribose methyltransferase, endoRNAse, 3\u2019-to-5\u2019 exonuclease, RNA-dependent RNA polymerase and helicase) for which drug design targets could be considered. There are other 16 nonstructural proteins (NSPs), which may also be percieved from the drug design angle. The protein structures have been deposited to ModelArchive. Tunnel analysis revealed the presence of large number of tunnels in NSP3, ORF 6 protein and membrane glycoprotein indicating a large number of transport pathways for small ligands influencing their reactivity.", "qid": 36, "docid": "yaahrjs4", "rank": 40, "score": 0.7609143853187561}, {"content": "Title: Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2 Content: Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome\u2013coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious coronavirus disease 2019 (COVID-19) epidemic. Here, we present cryo\u2013electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B(0)AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 angstroms, with a local resolution of 3.5 angstroms at the ACE2-RBD interface. The ACE2-B(0)AT1 complex is assembled as a dimer of heterodimers, with the collectrin-like domain of ACE2 mediating homodimerization. The RBD is recognized by the extracellular peptidase domain of ACE2 mainly through polar residues. These findings provide important insights into the molecular basis for coronavirus recognition and infection.", "qid": 36, "docid": "g8iz65wm", "rank": 41, "score": 0.7607290744781494}, {"content": "Title: Prefusion spike protein stabilization through computational mutagenesis Content: A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) has emerged as a human pathogen, causing global pandemic and resulting in over 400,000 deaths worldwide. The surface spike protein of SARS-CoV-2 mediates the process of coronavirus entry into human cells by binding angiotensin-converting enzyme 2 (ACE2). Due to the critical role in viral-host interaction and the exposure of spike protein, it has been a focus of most vaccines\u2019 developments. However, the structural and biochemical studies of the spike protein are challenging because it is thermodynamically metastable1. Here, we develop a new pipeline that automatically identifies mutants that thermodynamically stabilize the spike protein. Our pipeline integrates bioinformatics analysis of conserved residues, motion dynamics from molecular dynamics simulations, and other structural analysis to identify residues that significantly contribute to the thermodynamic stability of the spike protein. We then utilize our previously developed protein design tool, Eris, to predict thermodynamically stabilizing mutations in proteins. We validate the ability of our pipeline to identify protein stabilization mutants through known prefusion spike protein mutants. We finally utilize the pipeline to identify new prefusion spike protein stabilization mutants.", "qid": 36, "docid": "86hv27vh", "rank": 42, "score": 0.7602423429489136}, {"content": "Title: The crystal structure of nsp10-nsp16 heterodimer from SARS-CoV-2 in complex with S-adenosylmethionine Content: SARS-CoV-2 is a member of the coronaviridae family and is the etiological agent of the respiratory Coronavirus Disease 2019. The virus has spread rapidly around the world resulting in over two million cases and nearly 150,000 deaths as of April 17, 2020. Since no treatments or vaccines are available to treat COVID-19 and SARS-CoV-2, respiratory complications derived from the infections have overwhelmed healthcare systems around the world. This virus is related to SARS-CoV-1, the virus that caused the 2002-2004 outbreak of Severe Acute Respiratory Syndrome. In January 2020, the Center for Structural Genomics of Infectious Diseases implemented a structural genomics pipeline to solve the structures of proteins essential for coronavirus replication-transcription. Here we show the first structure of the SARS-CoV-2 nsp10-nsp16 2\u2019-O-methyltransferase complex with S-adenosylmethionine at a resolution of 1.80 \u00c5. This heterodimer complex is essential for capping viral mRNA transcripts for efficient translation and to evade immune surveillance.", "qid": 36, "docid": "ywia2ok7", "rank": 43, "score": 0.7601507902145386}, {"content": "Title: Is the Rigidity of SARS-CoV-2 Spike Receptor-Binding Motif the Hallmark for Its Enhanced Infectivity? Insights from All-Atom Simulations Content: [Image: see text] The severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic is setting the global health crisis of our time, causing a devastating societal and economic burden. An idiosyncratic trait of coronaviruses is the presence of spike glycoproteins on the viral envelope, which mediate the virus binding to specific host receptor, enabling its entry into the human cells. In spite of the high sequence identity of SARS-CoV-2 with its closely related SARS-CoV emerged in 2002, the atomic-level determinants underlining the molecular recognition of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) receptor and, thus, the rapid virus spread into human body, remain unresolved. Here, multi-microsecond-long molecular dynamics simulations enabled us to unprecedentedly dissect the key molecular traits liable of the higher affinity/specificity of SARS-CoV-2 toward ACE2 as compared to SARS-CoV. This supplies a minute per-residue contact map underlining its stunningly high infectivity. Harnessing this knowledge is pivotal for urgently developing effective medical countermeasures to face the ongoing global health crisis.", "qid": 36, "docid": "83491vo5", "rank": 44, "score": 0.7600659132003784}, {"content": "Title: Structural basis of SARS-CoV-2 spike protein induced by ACE2 Content: Motivation The recent emergence of the novel SARS-coronavirus 2 (SARS-CoV-2) and its international spread pose a global health emergency. The viral spike (S) glycoprotein binds the receptor (angiotensin-converting enzyme 2) ACE2 and promotes SARS-CoV-2 entry into host cells. The trimeric S protein binds the receptor using the distal receptor-binding domain (RBD) causing conformational changes in S protein that allow priming by host cell proteases. Unravelling the dynamic structural features used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal novel therapeutic targets. Using structures determined by X-ray crystallography and cryo-EM, we performed structural analysis and atomic comparisons of the different conformational states adopted by the SARS-CoV-2-RBD. Results Here, we determined the key structural components induced by the receptor and characterized their intramolecular interactions. We show that \u03ba-helix (also known as polyproline II) is a predominant structure in the binding interface and in facilitating the conversion to the active form of the S protein. We demonstrate a series of conversions between switch-like \u03ba-helix and \u03b2-strand, and conformational variations in a set of short \u03b1-helices which affect the proximal hinge region. This conformational changes lead to an alternating pattern in conserved disulfide bond configurations positioned at the hinge, indicating a possible disulfide exchange, an important allosteric switch implicated in viral entry of various viruses, including HIV and murine coronavirus. The structural information presented herein enables us to inspect and understand the important dynamic features of SARS-CoV-2-RBD and propose a novel potential therapeutic strategy to block viral entry. Overall, this study provides guidance for the design and optimization of structure-based intervention strategies that target SARS-CoV-2.", "qid": 36, "docid": "yfn9vaan", "rank": 45, "score": 0.759758472442627}, {"content": "Title: Genetic variants in TMPRSS2 and Structure of SARS-CoV-2 spike glycoprotein and TMPRSS2 complex Content: SARS-CoV-2, a highly transmittable pathogen has infected over 3.8 million people around the globe. The spike glycoprotein of SARS-CoV-2 engages host ACE2 for adhesion, TMPRSS2 for activation and entry. With the aid of whole-exome sequencing, we report a variant rs12329760 in TMPRSS2 gene and its mutant V160M, which might impede viral entry. Furthermore, we identified TMPRSS2 cleavage sites in S2 domain of spike glycoprotein and report the structure of TMPRSS2 in complex with spike glycoprotein. We also report the structures of protease inhibitors in complex with TMPRSS2, which could hamper the interaction with spike protein. These findings advance our understanding on the role of TMPRSS2 and in the development of potential therapeutics.", "qid": 36, "docid": "alrbutoy", "rank": 46, "score": 0.7595464587211609}, {"content": "Title: The Discovery of a Putative Allosteric Site in the SARS-CoV-2 Spike Protein Using an Integrated Structural/Dynamic Approach Content: SARS-CoV-2 has caused the largest pandemic of the twenty-first century (COVID-19), threatening the life and economy of all countries in the world. The identification of novel therapies and vaccines that can mitigate or control this global health threat is among the most important challenges facing biomedical sciences. To construct a long-term strategy to fight both SARS-CoV-2 and other possible future threats from coronaviruses, it is critical to understand the molecular mechanisms underlying the virus action. The viral entry and associated infectivity stems from the formation of the SARS-CoV-2 spike protein complex with angiotensin-converting enzyme 2 (ACE2). The detection of putative allosteric sites on the viral spike protein molecule can be used to elucidate the molecular pathways that can be targeted with allosteric drugs to weaken the spike-ACE2 interaction and, thus, reduce viral infectivity. In this study, we present the results of the application of different computational methods aimed at detecting allosteric sites on the SARS-CoV-2 spike protein. The adopted tools consisted of the protein contact networks (PCNs), SEPAS (Affinity by Flexibility), and perturbation response scanning (PRS) based on elastic network modes. All of these methods were applied to the ACE2 complex with both the SARS-CoV2 and SARS-CoV spike proteins. All of the adopted analyses converged toward a specific region (allosteric modulation region [AMR]), present in both complexes and predicted to act as an allosteric site modulating the binding of the spike protein with ACE2. Preliminary results on hepcidin (a molecule with strong structural and sequence with AMR) indicated an inhibitory effect on the binding affinity of the spike protein toward the ACE2 protein.", "qid": 36, "docid": "53mu0702", "rank": 47, "score": 0.7594217658042908}, {"content": "Title: Structural Basis of SARS-CoV-2 Spike Protein Priming by TMPRSS2 Content: Entry of SARS-CoV-2, etiological agent of COVID-19, in the host cell is driven by the interaction of its spike protein with human ACE2 receptor and a serine protease, TMPRSS2. Although complex between SARS-CoV-2 spike protein and ACE2 has been structurally resolved, the molecular details of the SARS-CoV-2 and TMPRSS2 complex are still elusive. TMPRSS2 is responsible for priming of the viral spike protein that entails cleavage of the spike protein at two potential sites, Arg685/Ser686 and Arg815/Ser816. The present study aims to investigate the conformational details of complex between TMPRSS2 and SARS-CoV-2 spike protein, in order to discern the finer details of the priming of viral spike and to point candidate drug targets. Briefly, full length structural model of TMPRSS2 was developed and docked against the resolved structure of SARS-CoV-2 spike protein with directional restraints of both cleavage sites. The docking simulations showed that TMPRSS2 interacts with the two different loops of SARS-CoV-2 spike protein, each containing different cleavage sites. Key functional residues of TMPRSS2 (His296, Ser441 and Ser460) were found to interact with immediate flanking residues of cleavage sites of SARS-CoV-2 spike protein. Compared to the N-terminal cleavage site (Arg685/Ser686), TMPRSS2 region that interact with C-terminal cleavage site (Arg815/Ser816) of the SARS-CoV-2 spike protein was predicted as relatively more druggable. In summary, the present study provide structural characteristics of molecular complex between human TMPRSS2 and SARS-CoV-2 spike protein and points to the candidate drug targets that could further be exploited to direct structure base drug designing.", "qid": 36, "docid": "34ljq0qt", "rank": 48, "score": 0.7593339681625366}, {"content": "Title: The search for a structural basis for therapeutic intervention against the SARS coronavirus Content: The 2003 outbreak of severe acute respiratory syndrome (SARS), caused by a previously unknown coronavirus called SARS\u2010CoV, had profound social and economic impacts worldwide. Since then, structure\u2013function studies of SARS\u2010CoV proteins have provided a wealth of information that increases our understanding of the underlying mechanisms of SARS. While no effective therapy is currently available, considerable efforts have been made to develop vaccines and drugs to prevent SARS\u2010CoV infection. In this review, some of the notable achievements made by SARS structural biology projects worldwide are examined and strategies for therapeutic intervention are discussed based on available SARS\u2010CoV protein structures. To date, 12 structures have been determined by X\u2010ray crystallography or NMR from the 28 proteins encoded by SARS\u2010CoV. One key protein, the SARS\u2010CoV main protease (M (pro)), has been the focus of considerable structure\u2010based drug discovery efforts. This article highlights the importance of structural biology and shows that structures for drug design can be rapidly determined in the event of an emerging infectious disease.", "qid": 36, "docid": "6q9h5rpb", "rank": 49, "score": 0.7591474056243896}, {"content": "Title: Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Content: A novel and highly pathogenic coronavirus (SARS-CoV-2) has caused an outbreak in Wuhan city, Hubei province of China since December 2019, and soon spread nationwide and spilled over to other countries around the world1-3. To better understand the initial step of infection at an atomic level, we determined the crystal structure of the SARS-CoV-2 spike receptor-binding domain (RBD) bound to the cell receptor ACE2 at 2.45 \u00c5 resolution. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also utilizes ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are critical for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly argue for convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1-3,5. The epitopes of two SARS-CoV antibodies targeting the RBD are also analysed with the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.", "qid": 36, "docid": "h2zpl0qt", "rank": 50, "score": 0.7589611411094666}, {"content": "Title: Blocking Coronavirus 19 Infection via the SARS-CoV-2 Spike Protein: Initial Steps Content: [Image: see text] Recent crystal structure data for protein\u2013protein interactions featuring the SARS-CoV-2 spike protein will inevitably trigger a new wave of research in this area that was not possible before. This Viewpoint outlines a few of the ways that it is already happening.", "qid": 36, "docid": "908d8bax", "rank": 51, "score": 0.7578765153884888}, {"content": "Title: Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2 Content: Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome-coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious coronavirus disease 2019 (COVID-19) epidemic. Here, we present cryo-electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 angstroms, with a local resolution of 3.5 angstroms at the ACE2-RBD interface. The ACE2-B0AT1 complex is assembled as a dimer of heterodimers, with the collectrin-like domain of ACE2 mediating homodimerization. The RBD is recognized by the extracellular peptidase domain of ACE2 mainly through polar residues. These findings provide important insights into the molecular basis for coronavirus recognition and infection.", "qid": 36, "docid": "86sipee4", "rank": 52, "score": 0.7573062181472778}, {"content": "Title: COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles' heel conserved region to minimize probability of escape mutations and drug resistance Content: This paper continues a recent study of the spike protein sequence of the COVID-19 virus (SARS-CoV-2). It is also in part an introductory review to relevant computational techniques for tackling viral threats, using COVID-19 as an example. Q-UEL tools for facilitating access to knowledge and bioinformatics tools were again used for efficiency, but the focus in this paper is even more on the virus. Subsequence KRSFIEDLLFNKV of the S2' spike glycoprotein proteolytic cleavage site continues to appear important. Here it is shown to be recognizable in the common cold coronaviruses, avian coronaviruses and possibly as traces in the nidoviruses of reptiles and fish. Its function or functions thus seem important to the coronaviruses. It might represent SARS-CoV-2 Achilles' heel, less likely to acquire resistance by mutation, as has happened in some early SARS vaccine studies discussed in the previous paper. Preliminary conformational analysis of the receptor (ACE2) binding site of the spike protein is carried out suggesting that while it is somewhat conserved, it appears to be more variable than KRSFIEDLLFNKV. However compounds like emodin that inhibit SARS entry, apparently by binding ACE2, might also have functions at several different human protein binding sites. The enzyme 11\u00df-hydroxysteroid dehydrogenase type 1 is again argued to be a convenient model pharmacophore perhaps representing an ensemble of targets, and it is noted that it occurs both in lung and alimentary tract. Perhaps it benefits the virus to block an inflammatory response by inhibiting the dehydrogenase, but a fairly complex web involves several possible targets.", "qid": 36, "docid": "8y4j510s", "rank": 53, "score": 0.756999135017395}, {"content": "Title: Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies Content: The recent severe acute respiratory syndrome, known as Corona Virus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim we performed an in silico comparative modeling analysis, which allows to gain new insights about the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor binding domain (RBD), along interactions with human cells angiotensin converting enzyme 2 (ACE2) receptor, that favour human cell invasion. Furthermore, our analysis provides i) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, for preventing interactions with the human ACE2, and ii) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. The proposed antibodies show in silico a high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high affinity antibodies against present and future coronavirus able to invade human cells through interactions of their spike proteins with the human ACE2. More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD-ACE2 interactions for the development of new vaccines, diagnosis kits and other treatments based on the usage or the targeting of SARS-CoV-2 spike protein.", "qid": 36, "docid": "mswmkgl4", "rank": 54, "score": 0.7567794919013977}, {"content": "Title: Spike protein fusion loop controls SARS-CoV-2 fusogenicity and infectivity Content: The Spike is a hallmark coronavirus protein that determines virus fusion, entry and spread in the host, and thus holds clues for the rapid spread of the SARS-CoV-2 pandemic. We have investigated the Spike from six \u03b2-coronaviruses, including the SARS-CoV-2, and find that their surface-exposed fusion peptides constituting the fusion loop are spatially organized contiguous to each other to work synergistically for triggering the virus-host membrane fusion process. The SARS-CoV-2 fusion peptides have unique physicochemical properties, accrued in part from the presence of consecutive prolines that impart backbone rigidity which aids the virus fusogenicity. The specific contribution of these prolines has been inferred from comparative studies of their deletion mutant in a fellow murine \u03b2-coronavirus MHV-A59 that show significantly diminished fusogenicity in vitro and associated pathogenesis in vivo. The Spike cleavage-linked priming and fusogenic conformational transition steered by the fusion loop may be critical for the SARS-CoV-2 spread. Summary The Spike protein on the SARS-CoV-2 surface is the prime mediator of COVID-191 because of its central role in virus-host attachment, virus-entry, and virus-spread2. The contagious nature of SARS-CoV-2 infection has been attributed to dense glycosylation of the Spike glycoprotein3, its high affinity of binding to human ACE2 receptor4, and cleavage5. While these may be imperative, it does not explain the uncontrolled infectivity. Here we show that properties of the fusion peptides constituting the fusion loop of SARS-CoV-2 Spike that triggers the virus fusion, distinguishes it from the other five \u03b2-coronaviruses. The SARS-CoV-2 Spike trimer surface is relatively more hydrophobic, including the surface contributed by the fusion peptides. The fusion peptides are structurally rigid owing to its consecutive prolines, aromatic/hydrophobic clusters, a stretch of consecutive \u03b2-branched amino acids, and the hydrogen bonds. The role of rigidity accrued from the presence of consecutive prolines contributing to virus fusogenicity can be deciphered from our previous murine \u03b2-coronavirus, MHV-A59 studies6. The synergy brought about by the global location of the surface exposed fusion peptides, their physicochemical features, and the fusogenic conformational transition appears to drive the fusion process, which may explain the severity of the infection and widespread nature of the COVID-19 pandemic.", "qid": 36, "docid": "7xd0msyk", "rank": 55, "score": 0.7567424774169922}, {"content": "Title: Comparing the Binding Interactions in the Receptor Binding Domains of SARS-CoV-2 and SARS-CoV Content: SARS-CoV-2, since emerging in Wuhan, China, has been a major concern because of its high infection rate and has left more than six million infected people around the world. Many studies endeavored to reveal the structure of the SARS-CoV-2 compared to the SARS-CoV, in order to find solutions to suppress this high infection rate. Some of these studies showed that the mutations in the SARS-CoV spike (S) protein might be responsible for its higher affinity to the ACE2 human cell receptor. In this work, we used molecular dynamics simulations and Monte Carlo sampling to compare the binding affinities of the S proteins of SARS-CoV and SARS-CoV-2 to the ACE2. Our results show that the protein surface of the ACE2 at the receptor binding domain (RBD) exhibits negative electrostatic potential, while a positive potential is observed for the S proteins of SARS-CoV/SARS-CoV-2. In addition, the binding energies at the interface are slightly higher for SARS-CoV-2 because of enhanced electrostatic interactions. The major contributions to the electrostatic binding energies result from the salt bridges forming between R426 and ACE-2-E329 in the case of SARS-CoV and K417 and ACE2-D30 in the SARS-CoV-2. In addition, our results indicate that the enhancement in the binding energy is not due to a single mutant but rather because of the sophisticated structural changes induced by all these mutations together. This finding suggests that it is implausible for the SARS-CoV-2 to be a lab-engineered virus.", "qid": 36, "docid": "ai7q035z", "rank": 56, "score": 0.7566692233085632}, {"content": "Title: Characterization of the SARS-CoV-2 Spike in an Early Prefusion Conformation Content: Pandemic coronavirus disease 2019 (COVID-19) is caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there are no efficacious vaccines or therapeutics that are urgently needed. We expressed three versions of spike (S) proteins\u2014receptor binding domain (RBD), S1 subunit and S ectodomain\u2014in insect cells. RBD appears monomer in solutions, whereas S1 and S associate into homotrimer with substantial glycosylation. The three proteins confer excellent antigenicity with six convalescent COVID-19 patient sera. Cryo-electron microscopy (cryo-EM) analyses indicate that the SARS-CoV-2 S trimer dominate in a unique conformation distinguished from the classic prefusion conformation of coronaviruses by the upper S1 region at lower position ~15 \u00c5 proximal to viral membrane. Such conformation is proposed as an early prefusion state for the SARS-CoV-2 spike that may broaden the knowledge of coronavirus and facilitate vaccine development.", "qid": 36, "docid": "i9r77o70", "rank": 57, "score": 0.7566055059432983}, {"content": "Title: How the COVID-19 Overcomes the Battle? An Approach to Virus Structure. Content: Coronaviruses primarily cause zoonotic infections, however in the past few decades several interspecies transmissions have occurred, the last one by SARS-CoV-2, causing COVID-19 pandemic, posing serious threat to global health. The SARS-CoV-2 spike (S) protein plays an important role in viral attachment, fusion and entry. However, other structural and non-structural SARS-CoV-2 proteins are potential influencers in virus pathogenicity. Among these proteins; Orf3, Orf8, and Orf10 show the least homology to SARSCoV proteins and therefore should be further studied for their abilities to modulate antiviral and inflammatory responses. Here, we discuss how SARS-COV-2 interacts with our immune system.", "qid": 36, "docid": "5onj6s3n", "rank": 58, "score": 0.7565701603889465}, {"content": "Title: How the COVID-19 Overcomes the Battle? An Approach to Virus Structure Content: Coronaviruses primarily cause zoonotic infections, however in the past few decades several interspecies transmissions have occurred, the last one by SARS-CoV-2, causing COVID-19 pandemic, posing serious threat to global health. The SARS-CoV-2 spike (S) protein plays an important role in viral attachment, fusion and entry. However, other structural and non-structural SARS-CoV-2 proteins are potential influencers in virus pathogenicity. Among these proteins; Orf3, Orf8, and Orf10 show the least homology to SARSCoV proteins and therefore should be further studied for their abilities to modulate antiviral and inflammatory responses. Here, we discuss how SARS-COV-2 interacts with our immune system.", "qid": 36, "docid": "5wakh15h", "rank": 59, "score": 0.7565701007843018}, {"content": "Title: Unexpected free fatty acid binding pocket in the cryo-EM structure of SARS-CoV-2 spike protein Content: COVID-19, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), represents a global crisis. Key to SARS-CoV-2 therapeutic development is unraveling the mechanisms driving high infectivity, broad tissue tropism and severe pathology. Our cryo-EM structure of SARS-CoV-2 spike (S) glycoprotein reveals that the receptor binding domains (RBDs) tightly and specifically bind the essential free fatty acid (FFA) linoleic acid (LA) in three composite binding pockets. The pocket also appears to be present in the highly pathogenic coronaviruses SARS-CoV and MERS-CoV. Lipid metabolome remodeling is a key feature of coronavirus infection, with LA at its core. LA metabolic pathways are central to inflammation, immune modulation and membrane fluidity. Our structure directly links LA and S, setting the stage for interventions targeting LA binding and metabolic remodeling by SARS-CoV-2. One Sentence Summary A direct structural link between SARS-CoV-2 spike and linoleic acid, a key molecule in inflammation, immune modulation and membrane fluidity.", "qid": 36, "docid": "yjsxen4d", "rank": 60, "score": 0.7564334869384766}, {"content": "Title: Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein Content: The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S(1)/S(2) subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.", "qid": 36, "docid": "trlni6iq", "rank": 61, "score": 0.7554532885551453}, {"content": "Title: Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein Content: The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.", "qid": 36, "docid": "im2np7s1", "rank": 62, "score": 0.755014181137085}, {"content": "Title: A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV Content: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has now become a pandemic, but there is currently very little understanding of the antigenicity of the virus. We therefore determined the crystal structure of CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient, in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein at 3.1-angstrom resolution. CR3022 targets a highly conserved epitope, distal from the receptor binding site, that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. Structural modeling further demonstrates that the binding epitope can only be accessed by CR3022 when at least two RBDs on the trimeric S protein are in the \"up\" conformation and slightly rotated. These results provide molecular insights into antibody recognition of SARS-CoV-2.", "qid": 36, "docid": "mo7734w5", "rank": 63, "score": 0.7546327710151672}, {"content": "Title: A pH-dependent switch mediates conformational masking of SARS-CoV-2 spike Content: SARS-CoV-2 has emerged as a global pathogen(1,2), sparking urgent vaccine development efforts with the trimeric spike(3,4). However, the inability of antibodies like CR3022(5), which binds a cryptic spike epitope with nanomolar affinity(6), to neutralize virus, suggests a spike-based means of neutralization escape. Here, we show the SARS-CoV-2 spike to have 10% the unfolding enthalpy of a globular protein at physiological pH, where it is recognized by antibodies like CR3022, and up to 10-times more unfolding enthalpy at endosomal pH, where it sheds such antibodies, suggesting that the spike evades potentially neutralizing antibody through a pH-dependent mechanism of conformational masking. To understand the compatibility of this mechanism with ACE2-receptor interactions, we carried out binding measurements and determined cryo-EM structures of the spike recognizing up to three ACE2 molecules at both physiological and endosomal pH. In the absence of ACE2, cryo-EM analyses indicated lower pH to reduce conformational heterogeneity. Single-receptor binding domain (RBD)-up conformations dominated at pH 5.5, resolving into a locked all-down conformation at lower pH through lowering of RBD and refolding of a pH-dependent switch. Notably, the emerging Asp614Gly strain(7) partially destabilizes the switch that locks RBD down, thereby enhancing functional interactions with ACE2 while reducing evasion by conformational masking.", "qid": 36, "docid": "9rqu018k", "rank": 64, "score": 0.7544727325439453}, {"content": "Title: Adding the missing sugars to coronavirus protein structures Content: Protein structures solved by cryo-electron microscopy (cryo-EM) or X-ray crystallography often miss the sugar molecules known as glycans that cover large swaths of the proteins\u2019 surfaces The recently reported structures of the spike protein on SARS-CoV-2, the novel coronavirus that causes COVID-19, are no different Researchers are now working to fill in some of those sugary blanks to better understand the virus\u2019s biology and to help drugmakers develop vaccines and treatments \u201cPeople usually go for what they can analyze\u201d and focus mostly on the protein components of a structure, says Andrea Thorn, a structural biologist at the Julius Maximilian University of W\u00fcrzburg She is a member of the Coronavirus Structural Task Force, a group of scientists who specialize in modeling and processing crystallographic and cryo-EM data Because structural biology measurements don\u2019t reveal much about glycans on proteins, \u201cwe often fail to recognize what an important part of the structure they", "qid": 36, "docid": "fayr38c7", "rank": 65, "score": 0.7540452480316162}, {"content": "Title: Sars-CoV-2 Envelope and Membrane Proteins: Structural Differences Linked to Virus Characteristics? Content: The Coronavirus Disease 2019 (COVID-19) is a new viral infection caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2). Genomic analyses have revealed that SARS-CoV-2 is related to Pangolin and Bat coronaviruses. In this report, a structural comparison between the Sars-CoV-2 Envelope and Membrane proteins from different human isolates with homologous proteins from closely related viruses is described. The analyses here reported show the high structural similarity of Envelope and Membrane proteins to the counterparts from Pangolin and Bat coronavirus isolates. However, the comparisons have also highlighted structural differences specific of Sars-CoV-2 proteins which may be correlated to the cross-species transmission and/or to the properties of the virus. Structural modelling has been applied to map the variant sites onto the predicted three-dimensional structure of the Envelope and Membrane proteins.", "qid": 36, "docid": "vnwhvi2x", "rank": 66, "score": 0.7529754638671875}, {"content": "Title: Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Content: The spike protein (S) of SARS coronavirus (SARS-CoV) attaches the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2). A defined receptor-binding domain (RBD) on S mediates this interaction. The crystal structure at 2.9 angstrom resolution of the RBD bound with the peptidase domain of human ACE2 shows that the RBD presents a gently concave surface, which cradles the N-terminal lobe of the peptidase. The atomic details at the interface between the two proteins clarify the importance of residue changes that facilitate efficient cross-species infection and human-to-human transmission. The structure of the RBD suggests ways to make truncated disulfide-stabilized RBD variants for use in the design of coronavirus vaccines.", "qid": 36, "docid": "hmswnrgg", "rank": 67, "score": 0.7520562410354614}, {"content": "Title: Structural interactions between pandemic SARS-CoV-2 spike glycoprotein and human Furin protease Content: The SARS-CoV-2 pandemic is an urgent global public health emergency and warrants investigating molecular and structural studies addressing the dynamics of viral proteins involved in host cell adhesion. The recent comparative genomic studies highlight the insertion of Furin protease site in the SARS-CoV-2 spike glycoprotein alerting possible modification in the viral spike protein and its eventual entry to host cell and presence of Furin site implicated to virulence. Here we structurally show how Furin interacts with the SARS-CoV-2 spike glycoprotein homotrimer at S1/S2 region, which underlined the mechanism and mode of action, which is a key for host cell entry. Unravelling the structural features of biding site opens the arena in rising bonafide antibodies targeting to block the Furin cleavage and have great implications in the development of Furin inhibitors or therapeutics.", "qid": 36, "docid": "uuws2nen", "rank": 68, "score": 0.75147944688797}, {"content": "Title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach Content: The newly identified SARS-CoV-2 has now been reported from around 185 countries with more than a million confirmed human cases including more than 120,000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins need to be explored to understand the biology of the virus. Spike glycoprotein is one of the major targets to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment. In this study, 483 unique variations have been identified among the genomes of SARS-CoV-2 including 25 nonsynonymous mutations and one deletion in the spike (S) protein. Among the 26 variations detected in S, 12 variations were located at the N-terminal domain (NTD) and 6 variations at the receptor-binding domain (RBD) which might alter the interaction of S protein with the host receptor angiotensin-converting enzyme 2 (ACE2). Besides, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on results reported herein, potential inhibitors against S protein can be designed by considering these variations and their impact on protein structure.", "qid": 36, "docid": "c5fygzvz", "rank": 69, "score": 0.7513759136199951}, {"content": "Title: COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles\u2019 heel conserved region to minimize probability of escape mutations and drug resistance Content: Abstract This paper continues a recent study of the spike protein sequence of the COVID-19 virus (SARS-CoV-2). It is also in part an introductory review to relevant computational techniques for tackling viral threats, using COVID-19 as an example. Q-UEL tools for facilitating access to knowledge and bioinformatics tools were again used for efficiency, but the focus in this paper is even more on the virus. Subsequence KRSFIEDLLFNKV of the S2\u2032 spike glycoprotein proteolytic cleavage site continues to appear important. Here it is shown to be recognizable in the common cold coronaviruses, avian coronaviruses and possibly as traces in the nidoviruses of reptiles and fish. Its function or functions thus seem important to the coronaviruses. It might represent SARS-CoV-2 Achilles\u2019 Heel, less likely to acquire resistance by mutation, as has happened in some early SARS vaccine studies discussed in the previous paper. Preliminary conformational analysis of the receptor (ACE2) binding site of the spike protein is carried suggesting that while it is somewhat conserved, it appears to be more variable than KRSFIEDLLFNKV. However compounds like emodin that inhibit SARS entry, apparently by binding ACE2, might also have functions at several different human protein binding studies. The enzyme 11\u03b2-hydroxysteroid dehydrogenase type 1 is again argued to be a convenient model pharmacophore perhaps representing an ensemble of targets, and it is noted that it occurs both in lung and alimentary tract. Perhaps it benefits the virus to block an inflammatory response by inhibiting the dehydrogenase, but a fairly complex web involves several possible targets.", "qid": 36, "docid": "xvfl7ycj", "rank": 70, "score": 0.7513248920440674}, {"content": "Title: Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor Content: A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1-3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1-3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.", "qid": 36, "docid": "m3j0kv0t", "rank": 71, "score": 0.7504640221595764}, {"content": "Title: Insights on cross-species transmission of SARS-CoV-2 from structural modeling Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global pandemic that has infected more than 6 million people in more than 180 countries worldwide. Like other coronaviruses, SARS-CoV-2 is thought to have been transmitted to humans from wild animals. Given the scale and widespread geographical distribution of the current pandemic, the question emerges whether human-to-animal transmission is possible and if so, which animal species are most at risk. Here, we investigated the structural properties of several ACE2 orthologs bound to the SARS-CoV-2 spike protein. We found that species known not to be susceptible to SARS-CoV-2 infection have non-conservative mutations in several ACE2 amino acid residues that disrupt key polar and charged contacts with the viral spike protein. Our models also predict affinity-enhancing mutations that could be used to design ACE2 variants for therapeutic purposes. Finally, our study provides a blueprint for modeling viral-host protein interactions and highlights several important considerations when designing these computational studies and analyzing their results.", "qid": 36, "docid": "mtq6yh25", "rank": 72, "score": 0.7503921985626221}, {"content": "Title: The Discovery of a Putative Allosteric Site in the SARS-CoV-2 Spike Protein Using an Integrated Structural/Dynamic Approach Content: [Image: see text] SARS-CoV-2 has caused the largest pandemic of the twenty-first century (COVID-19), threatening the life and economy of all countries in the world. The identification of novel therapies and vaccines that can mitigate or control this global health threat is among the most important challenges facing biomedical sciences. To construct a long-term strategy to fight both SARS-CoV-2 and other possible future threats from coronaviruses, it is critical to understand the molecular mechanisms underlying the virus action. The viral entry and associated infectivity stems from the formation of the SARS-CoV-2 spike protein complex with angiotensin-converting enzyme 2 (ACE2). The detection of putative allosteric sites on the viral spike protein molecule can be used to elucidate the molecular pathways that can be targeted with allosteric drugs to weaken the spike-ACE2 interaction and, thus, reduce viral infectivity. In this study, we present the results of the application of different computational methods aimed at detecting allosteric sites on the SARS-CoV-2 spike protein. The adopted tools consisted of the protein contact networks (PCNs), SEPAS (Affinity by Flexibility), and perturbation response scanning (PRS) based on elastic network modes. All of these methods were applied to the ACE2 complex with both the SARS-CoV2 and SARS-CoV spike proteins. All of the adopted analyses converged toward a specific region (allosteric modulation region [AMR]), present in both complexes and predicted to act as an allosteric site modulating the binding of the spike protein with ACE2. Preliminary results on hepcidin (a molecule with strong structural and sequence with AMR) indicated an inhibitory effect on the binding affinity of the spike protein toward the ACE2 protein.", "qid": 36, "docid": "xy8j5jiv", "rank": 73, "score": 0.7495609521865845}, {"content": "Title: Stabilizing the Closed SARS-CoV-2 Spike Trimer Content: The trimeric spike (S) protein of SARS-CoV-2 is the primary focus of most vaccine design and development efforts. Due to intrinsic instability typical of class I fusion proteins, S tends to prematurely refold to the post-fusion conformation, compromising immunogenic properties and prefusion trimer yields. To support ongoing vaccine development efforts, we report the structure-based design of soluble S trimers, with increased yields and stabilities, based on introduction of single point mutations and disulfide-bridges. We identify two regions in the S-protein critical for the protein\u2019s stability: the heptad repeat region 1 of the S2 subunit and subunit domain 1 at the interface with S2. We combined a minimal selection of mostly interprotomeric mutations to create a stable S-closed variant with a 6.4-fold higher expression than the parental construct while no longer containing a heterologous trimerization domain. The cryo-EM structure reveals a correctly folded, predominantly closed pre-fusion conformation. Highly stable and well producing S protein and the increased understanding of S protein structure will support vaccine development and serological diagnostics.", "qid": 36, "docid": "h90c721k", "rank": 74, "score": 0.749439001083374}, {"content": "Title: Comprehensive characterization of N- and O- glycosylation of SARS-CoV-2 human receptor angiotensin converting enzyme 2 Content: Emergence of COVID-19 pandemic caused by SARS-CoV-2 demanded development of new therapeutic strategies and thus the understanding the mode of viral attachment, entry and replication has become key aspect for such interventions. The coronavirus surface features a trimeric spike (S) protein that is essential in viral attachment, entry and membrane fusion. The S protein of SARS-CoV-2 binds to the human angiotensin converting enzyme 2 (hACE2) for the entry and the serine protease TMPRSS2 for S protein priming. The heavily glycosylated S protein is comprised of two protein subunits (S1 and S2), and the receptor binding domain within S1 subunit binds with to the hACE2 receptor. Even though hACE2 has been known for two decades and has been recognized as the entry point of several human coronaviruses, no comprehensive glycosylation characterization of hACE2 has been reported. Herein, we describe the quantitative glycosylation mapping on hACE2 expressed in human cells by both glycoproteomics and glycomics. We observed heavy glycan occupancy at all the seven possible N-glycosylation sites and surprisingly, detected three novel O-glycosylation sites. In order to deduce the detailed structure of glycan epitopes on hACE2 involved with viral binding, we have characterized the terminal sialic acid linkages, presence of bisecting GlcNAc and also the pattern of N-glycan fucosylation. We have conducted extensive manual interpretation of each glycopeptide and glycan spectra in addition to the use of bioinformatics tools to validate the hACE2 glycosylation. Elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor can aid in understanding the intriguing virus-receptor interactions and help in the development of novel therapeutics to circumvent the viral entry.", "qid": 36, "docid": "1icxzdnm", "rank": 75, "score": 0.7490472793579102}, {"content": "Title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach Content: The newly identified SARS-CoV-2 has now been reported from around 185 countries with more than a million confirmed human cases including more than 120,000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins need to be explored to understand the biology of the virus. Spike glycoprotein is one of the major targets to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment. In this study, 483 unique variations have been identified among the genomes of SARS-CoV-2 including 25 nonsynonymous mutations and one deletion in the spike (S) protein. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction of S protein with the host receptor angiotensin converting enzyme-2 (ACE2). Besides, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on results reported herein, potential inhibitors against S protein can be designed by considering these variations and their impact on protein structure.", "qid": 36, "docid": "w5ytp1q7", "rank": 76, "score": 0.7484575510025024}, {"content": "Title: A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV Content: The outbreak of COVID-19 caused by SARS-CoV-2 virus has now become a pandemic, but there is currently very little understanding of the antigenicity of the virus. We therefore determined the crystal structure of CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient, in complex with the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein to 3.1 \u00c5. CR3022 targets a highly conserved epitope, distal from the receptor-binding site, that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. Structural modeling further demonstrates that the binding epitope can only be accessed by CR3022 when at least two RBD on the trimeric S protein are in the \u201cup\u201d conformation and slightly rotated. Overall, this study provides molecular insights into antibody recognition of SARS-CoV-2.", "qid": 36, "docid": "pkxc2219", "rank": 77, "score": 0.7484532594680786}, {"content": "Title: Architecture and self-assembly of the SARS-CoV-2 nucleocapsid protein Content: The COVID-2019 pandemic is the most severe acute public health threat of the twenty-first century. To properly address this crisis with both robust testing and novel treatments, we require a deep understanding of the life cycle of the causative agent, the SARS-CoV-2 coronavirus. Here, we examine the architecture and self-assembly properties of the SARS-CoV-2 nucleocapsid (N) protein, which binds viral RNA and assembles into a filament that is packaged into new virions. We determined a 1.4 \u00c5 resolution crystal structure of this protein\u2019s N2b domain, revealing a compact, intertwined dimer very similar to that of related coronaviruses SARS-CoV and MERS-CoV. Using size exclusion chromatography and multi-angle light scattering, we find that this domain forms a dimer in solution, and that addition of the C-terminal spacer B/N3 domain mediates tetramer formation. Using hydrogen-deuterium exchange mass spectrometry, we find evidence that at least part of this putatively disordered domain is structured, potentially forming an \u03b1-helix that either self-associates or docks against the N2b domain to mediate tetramer formation. Finally, we map the locations of over 4,400 individual amino acid substitutions in the N protein from (~)17,000 SARS-CoV-2 genome sequences, and find that they are strongly clustered in the protein\u2019s N2a linker domain. The nearly 300 substitutions identified within the N1b and N2b domains cluster away from their functional RNA binding and dimerization interfaces. Overall, this work reveals the architecture and self-assembly properties of a key protein in the SARS-CoV-2 life cycle. As the N protein is a common target of patient antibodies, this work will also benefit ongoing efforts to develop robust and specific serological tests, and could also benefit the analysis of patient-derived antibodies.", "qid": 36, "docid": "afw20ln3", "rank": 78, "score": 0.7482768297195435}, {"content": "Title: Biophysical characterization of the SARS-CoV-2 spike protein binding with the ACE2 receptor and implications for infectivity Content: SARS-CoV-2 is a novel highly virulent pathogen which gains entry to human cells by binding with the cell surface receptor \u2013 angiotensin converting enzyme (ACE2). We computationally contrasted the binding interactions between human ACE2 and coronavirus spike protein receptor binding domain (RBD) of the 2002 epidemic-causing SARS-CoV-1, SARS-CoV-2, and bat coronavirus RaTG13 using the Rosetta energy function. We find that the RBD of the spike protein of SARS-CoV-2 is highly optimized to achieve very strong binding with human ACE2 (hACE2) which is consistent with its enhanced infectivity. SARS-CoV-2 forms the most stable complex with hACE2 compared to SARS-CoV-1 (23% less stable) or RaTG13 (11% less stable) while occupying the greatest number of residues in the ATR1 binding site. Notably, the SARS-CoV-2 RBD out-competes the angiotensin 2 receptor type I (ATR1) which is the native binding partner of ACE2 by 35% in terms of the calculated binding affinity. Strong binding is mediated through strong electrostatic attachments with every fourth residue on the N-terminus alpha-helix (starting from Ser19 to Asn53) as the turn of the helix makes these residues solvent accessible. By contrasting the spike protein SARS-CoV-2 Rosetta binding energy with ACE2 of different livestock and pet species we find strongest binding with bat ACE2 followed by human, feline, equine, canine and finally chicken. This is consistent with the hypothesis that bats are the viral origin and reservoir species. These results offer a computational explanation for the increased infectivity of SARS-CoV-2 and allude to therapeutic modalities by identifying and rank-ordering the ACE2 residues involved in binding with the virus.", "qid": 36, "docid": "lotyldfd", "rank": 79, "score": 0.74821537733078}, {"content": "Title: Enhanced receptor binding of SARS-CoV-2 through networks of hydrogen-bonding and hydrophobic interactions Content: Molecular dynamics and free energy simulations have been carried out to elucidate the structural origin of differential protein\u2013protein interactions between the common receptor protein angiotensin converting enzyme 2 (ACE2) and the receptor binding domains of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [A. E. Gorbalenya et al., Nat. Microbiol. 5, 536\u2013544 (2020)] that causes coronavirus disease 2019 (COVID-19) [P. Zhou et al., Nature 579, 270\u2013273 (2020)] and the SARS coronavirus in the 2002\u20132003 (SARS-CoV) [T. Kuiken et al., Lancet 362, 263\u2013270 (2003)] outbreak. Analysis of the dynamic trajectories reveals that the binding interface consists of a primarily hydrophobic region and a delicate hydrogen-bonding network in the 2019 novel coronavirus. A key mutation from a hydrophobic residue in the SARS-CoV sequence to Lys417 in SARS-CoV-2 creates a salt bridge across the central hydrophobic contact region, which along with polar residue mutations results in greater electrostatic complementarity than that of the SARS-CoV complex. Furthermore, both electrostatic effects and enhanced hydrophobic packing due to removal of four out of five proline residues in a short 12-residue loop lead to conformation shift toward a more tilted binding groove in the complex in comparison with the SARS-CoV complex. On the other hand, hydrophobic contacts in the complex of the SARS-CoV\u2013neutralizing antibody 80R are disrupted in the SARS-CoV-2 homology complex model, which is attributed to failure of recognition of SARS-CoV-2 by 80R.", "qid": 36, "docid": "s10k4s0k", "rank": 80, "score": 0.7481129765510559}, {"content": "Title: High Throughput Designing and Mutational Mapping of RBD-ACE2 Interface Guide Non-Conventional Therapeutic Strategies for COVID-19 Content: Considering the current status of the SARS-CoV-2 pandemic, sequence variations and possibly structural changes in the rapidly evolving SARS-CoV-2 is highly expected in the coming months. The SARS-CoV-2 spike (S) protein is responsible for mediating viral attachment and fusion with cell membranes. Mutations in the receptor-binding domain (RBD) of the S-protein occur at the most variable part of the SARS-CoV-2 genome, and specific sites of S-protein have undergone positive selection impacting the viral pathogenicity. In the present work, we used high-throughput computation to design 100,000 mutants in RBD interfacial residues and identify novel affinity-enhancing and affinity-weakening mutations. Our data suggest that SARS-CoV-2 can establish a higher rate of infectivity and pathogenesis when it acquires combinatorial mutations at the interfacial residues in RBD. Mapping of the mutational landscape of the interaction site suggests that a few of these residues are the hot-spot residues with a very high tendency to undergo positive selection. Knowledge of the affinity-enhancing mutations may guide the identification of potential cold-spots for this mutation as targets for developing a possible therapeutic strategy instead of hot-spots, and vice versa. Understanding of the molecular interactions between the virus and host protein presents a detailed systems view of viral infection mechanisms. The applications of the present research can be explored in multiple antiviral strategies, including monoclonal antibody therapy, vaccine design, and importantly in understanding the clinical pathogenesis of the virus itself. Our work presents research directions for the exploitation of non-conventional solutions for COVID-19.", "qid": 36, "docid": "l7471mik", "rank": 81, "score": 0.7477643489837646}, {"content": "Title: Influence of hydrophobic and electrostatic residues on SARS-coronavirus S2 protein stability: Insights into mechanisms of general viral fusion and inhibitor design Content: Severe acute respiratory syndrome (SARS) is an acute respiratory disease caused by the SARS-coronavirus (SARS-CoV). SARS-CoV entry is facilitated by the spike protein (S), which consists of an N-terminal domain (S1) responsible for cellular attachment and a C-terminal domain (S2) that mediates viral and host cell membrane fusion. The SARS-CoV S2 is a potential drug target, as peptidomimetics against S2 act as potent fusion inhibitors. In this study, site-directed mutagenesis and thermal stability experiments on electrostatic, hydrophobic, and polar residues to dissect their roles in stabilizing the S2 postfusion conformation was performed. It was shown that unlike the pH-independent retroviral fusion proteins, SARS-CoV S2 is stable over a wide pH range, supporting its ability to fuse at both the plasma membrane and endosome. A comprehensive SARS-CoV S2 analysis showed that specific hydrophobic positions at the C-terminal end of the HR2, rather than electrostatics are critical for fusion protein stabilization. Disruption of the conserved C-terminal hydrophobic residues destabilized the fusion core and reduced the melting temperature by 30\u00b0C. The importance of the C-terminal hydrophobic residues led us to identify a 42-residue substructure on the central core that is structurally conserved in all existing CoV S2 fusion proteins (root mean squared deviation = 0.4 \u00c5). This is the first study to identify such a conserved substructure and likely represents a common foundation to facilitate viral fusion. We have discussed the role of key residues in the design of fusion inhibitors and the potential of the substructure as a general target for the development of novel therapeutics against CoV infections.", "qid": 36, "docid": "lgppfs4j", "rank": 82, "score": 0.7474685907363892}, {"content": "Title: Identification of conserved epitopes in SARS-CoV-2 spike and nucleocapsid protein Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first occurred in Wuhan (China) in December 2019, is a novel virus that causes a severe acute respiratory disease. The virus spike glycoproteins and nucleocapsid proteins are the main targets for the development of vaccines and antiviral drugs, to control the disease spread. We herein study the structural order-disorder propensity and the rates of evolution of these two proteins to characterize their B cell and T cell epitopes, previously suggested to contribute to immune response caused by SARS-CoV-2 infections. We first analyzed the rates of evolution along the sequences of spike and nucleocapsid proteins in relation to the spatial locations of their epitopes. For this purpose, we compared orthologs from seven human coronaviruses: SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1. We then focus on the local, structural order-disorder propensities of the protein regions where the SARS-CoV-2 epitopes are located. We show that the vast majority of nucleocapsid protein epitopes overlap the RNA-binding and dimerization domains and some of them are characterized by low rates of evolutions. Similarly, spike protein epitopes are preferentially located in regions that are predicted to be ordered and well-conserved, in correspondence of the heptad repeats 1 and 2. Interestingly, both the receptor-binding motif to ACE2 and the fusion peptide of spike protein are characterized by high rates of evolution, probably to overcome host immunity. In conclusion, our results provide evidence for conserved epitopes that may help to develop long-lasting, broad-spectrum SARS-CoV-2 vaccines.", "qid": 36, "docid": "lg7nnmb6", "rank": 83, "score": 0.7473360300064087}, {"content": "Title: Enhanced receptor binding of SARS-CoV-2 through networks of hydrogen-bonding and hydrophobic interactions Content: Molecular dynamics and free energy simulations have been carried out to elucidate the structural origin of differential protein-protein interactions between the common receptor protein angiotensin converting enzyme 2 (ACE2) and the receptor binding domains of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [A. E. Gorbalenya et al., Nat. Microbiol. 5, 536-544 (2020)] that causes coronavirus disease 2019 (COVID-19) [P. Zhou et al., Nature 579, 270-273 (2020)] and the SARS coronavirus in the 2002-2003 (SARS-CoV) [T. Kuiken et al., Lancet 362, 263-270 (2003)] outbreak. Analysis of the dynamic trajectories reveals that the binding interface consists of a primarily hydrophobic region and a delicate hydrogen-bonding network in the 2019 novel coronavirus. A key mutation from a hydrophobic residue in the SARS-CoV sequence to Lys417 in SARS-CoV-2 creates a salt bridge across the central hydrophobic contact region, which along with polar residue mutations results in greater electrostatic complementarity than that of the SARS-CoV complex. Furthermore, both electrostatic effects and enhanced hydrophobic packing due to removal of four out of five proline residues in a short 12-residue loop lead to conformation shift toward a more tilted binding groove in the complex in comparison with the SARS-CoV complex. On the other hand, hydrophobic contacts in the complex of the SARS-CoV-neutralizing antibody 80R are disrupted in the SARS-CoV-2 homology complex model, which is attributed to failure of recognition of SARS-CoV-2 by 80R.", "qid": 36, "docid": "b0cf3viw", "rank": 84, "score": 0.7471269369125366}, {"content": "Title: Topological analysis of SARS CoV-2 main protease Content: There is an urgent necessity of effective medication against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), which is producing the COVID-19 pandemic across the world. Its main protease (Mpro) represents an attractive pharmacological target due to its involvement in essential viral functions. The crystal structure of free Mpro shows a large structural resemblance with the main protease of SARS CoV (nowadays known as SARS CoV-1). Here, we report that average SARS CoV-2 Mpro is 1900% more sensitive than SARS CoV-1 Mpro in transmitting tiny structural changes across the whole protein through long-range interactions. The largest sensitivity of Mpro to structural perturbations is located exactly around the catalytic site Cys-145 and coincides with the binding site of strong inhibitors. These findings, based on a simplified representation of the protein as a residue network, may help in designing potent inhibitors of SARS CoV-2 Mpro.", "qid": 36, "docid": "eazmemg8", "rank": 85, "score": 0.7471033334732056}, {"content": "Title: Topological analysis of SARS CoV-2 main protease. Content: There is an urgent necessity of effective medication against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), which is producing the COVID-19 pandemic across the world. Its main protease (Mpro) represents an attractive pharmacological target due to its involvement in essential viral functions. The crystal structure of free Mpro shows a large structural resemblance with the main protease of SARS CoV (nowadays known as SARS CoV-1). Here, we report that average SARS CoV-2 Mpro is 1900% more sensitive than SARS CoV-1 Mpro in transmitting tiny structural changes across the whole protein through long-range interactions. The largest sensitivity of Mpro to structural perturbations is located exactly around the catalytic site Cys-145 and coincides with the binding site of strong inhibitors. These findings, based on a simplified representation of the protein as a residue network, may help in designing potent inhibitors of SARS CoV-2 Mpro.", "qid": 36, "docid": "an2za6vj", "rank": 86, "score": 0.7471033334732056}, {"content": "Title: Structural Molecular Insights into SARS Coronavirus Cellular Attachment, Entry and Morphogenesis Content: Coronavirus spikes have the largest mass of any known viral spike molecule. The spike is a type 1 viral fusion protein, a class of trimeric surface glycoprotein proteins from diverse viral families that share many common structural and functional characteristics. Fusion proteins are mainly responsible for host cell receptor recognition and subsequent membrane fusion, and may perform other roles such as virus assembly and release via budding. The conformational changes that occur in the spike of intact SARS coronavirus (SARS-CoV) when it binds to the viral receptor, angiotensin-converting enzyme 2 (ACE2) are described. Clues to the structural/functional relationships of membrane fusion have been made possible by the development of viral purification and inactivation methods, along with cryo-electron microscopy (cryo-EM) and three-dimensional (3D) image processing of many different images containing multiple views of the spikes. These methods have allowed study of the spikes while still attached to virions that are noninfectious, but fusionally competent. The receptor-binding and fusion core domains within the SARS-CoV spike have been precisely localized within the spike. Receptor binding results in structural changes that have been observed in the spike molecule, and these appear to be the initial step in viral membrane fusion. A working model for the stepwise process of receptor binding, and subsequent membrane fusion in SARS-CoV is presented. Uniquely, the large size of the SARS-CoV spike allows structural changes to be observed by cryo-EM in the native state. This provides a useful model for studying the basic process of membrane fusion in general, which forms an essential part of the function of many cellular processes.", "qid": 36, "docid": "w2sbyfy2", "rank": 87, "score": 0.7468876242637634}, {"content": "Title: Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2 Content: The recent emergence of a novel coronavirus (SARS-CoV-2) in China has caused significant public health concerns. Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV. However, atomic details at the binding interface demonstrate that key residue substitutions in SARS-CoV-2-CTD slightly strengthen the interaction and lead to higher affinity for receptor binding than SARS-RBD. Additionally, a panel of murine monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs) against SARS-CoV-S1/receptor-binding domain (RBD) were unable to interact with the SARS-CoV-2 S protein, indicating notable differences in antigenicity between SARS-CoV and SARS-CoV-2. These findings shed light on the viral pathogenesis and provide important structural information regarding development of therapeutic countermeasures against the emerging virus.", "qid": 36, "docid": "bzvaqu08", "rank": 88, "score": 0.7466292977333069}, {"content": "Title: Investigation of the effect of temperature on the structure of SARS-Cov-2 Spike Protein by Molecular Dynamics Simulations Content: Statistical and epidemiological data imply temperature sensitivity of the SARS-CoV-2 coronavirus. However, the molecular level understanding of the virus structure at different temperature is still not clear. Spike protein is the outermost structural protein of the SARS-CoV-2 virus which interacts with the Angiotensin Converting Enzyme 2 (ACE2), a human receptor, and enters the respiratory system. In this study, we performed an all atom molecular dynamics simulation to study the effect of temperature on the structure of the Spike protein. After 200ns of simulation at different temperatures, we came across some interesting phenomena exhibited by the protein. We found that the solvent exposed domain of Spike protein, namely S1, is more mobile than the transmembrane domain, S2. Structural studies implied the presence of several charged residues on the surface of N-terminal Domain of S1 which are optimally oriented at 10-30 \u00b0C. Bioinformatics analyses indicated that it is capable of binding to other human receptors and should not be disregarded. Additionally, we found that receptor binding motif (RBM), present on the receptor binding domain (RBD) of S1, begins to close around temperature of 40 \u00b0C and attains a completely closed conformation at 50 \u00b0C. The closed conformation disables its ability to bind to ACE2, due to the burying of its receptor binding residues. Our results clearly show that there are active and inactive states of the protein at different temperatures. This would not only prove beneficial for understanding the fundamental nature of the virus, but would be also useful in the development of vaccines and therapeutics. Graphical Abstract Highlights Statistical and epidemiological evidence show that external climatic conditions influence the SARS-CoV infectivity, but we still lack a molecular level understanding of the same. Here, we study the influence of temperature on the structure of the Spike glycoprotein, the outermost structural protein, of the virus which binds to the human receptor ACE2. Results show that the Spike\u2019s S1 domain is very sensitive to external atmospheric conditions compared to the S2 transmembrane domain. The N-terminal domain comprises of several solvent exposed charged residues that are capable of binding to human proteins. The region is specifically stable at temperatures ranging around 10-30\u00b0 C. The Receptor Binding Motif adopts a closed conformation at 40\u00b0C and completely closes at higher temperatures making it unsuitable of binding to human receptors", "qid": 36, "docid": "nsp53lv6", "rank": 89, "score": 0.7461792826652527}, {"content": "Title: Mapping active allosteric loci SARS-CoV Spike Proteins by means of Protein Contact Networks Content: Coronaviruses are a class of virus responsible of the recent outbreak of Human Severe Acute Respiratory Syndrome. The molecular machinery behind the viral entry and thus infectivity is based on the formation of the complex of virus spike protein with the angiotensin-converting enzyme 2 (ACE2). The detection of putative allosteric sites on the viral spike protein can trace the path to develop allosteric drugs to weaken the strength of the spike-ACE2 interface and, thus, reduce the viral infectivity. In this work we present results of the application of the Protein Contact Network (PCN) paradigm to the complex SARS-CoV spike - ACE2 relative to both 2003 SARS and the recent 2019 - CoV. Results point to a specific region, present in both structures, that is predicted to act as allosteric site modulating the binding of the spike protein with ACE2.", "qid": 36, "docid": "nrx9wqwg", "rank": 90, "score": 0.7460678815841675}, {"content": "Title: Emerging WuHan (COVID-19) coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26 Content: The recent outbreak of pneumonia-causing COVID-19 in China is an urgent global public health issue with an increase in mortality and morbidity. Here we report our modelled homo-trimer structure of COVID-19 spike glycoprotein in both closed (ligand-free) and open (ligand-bound) conformation, which is involved in host cell adhesion. We also predict the unique N- and O-linked glycosylation sites of spike glycoprotein that distinguish it from the SARS and underlines shielding and camouflage of COVID-19 from the host the defence system. Furthermore, our study also highlights the key finding that the S1 domain of COVID-19 spike glycoprotein potentially interacts with the human CD26, a key immunoregulatory factor for hijacking and virulence. These findings accentuate the unique features of COVID-19 and assist in the development of new therapeutics.", "qid": 36, "docid": "h072om8j", "rank": 91, "score": 0.7458875775337219}, {"content": "Title: Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation Content: The outbreak of a novel betacoronavirus (2019-nCov) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for urgently needed vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure (MCM) development we determined a 3.5 \u00c5-resolution cryo-EM structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also show biophysical and structural evidence that the 2019-nCoV S binds ACE2 with higher affinity than SARS-CoV S. Additionally we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to nCoV-2019 S, suggesting antibody cross-reactivity may be limited between the two virus RBDs. The atomic-resolution structure of 2019-nCoV S should enable rapid development and evaluation of MCMs to address the ongoing public health crisis.", "qid": 36, "docid": "prqeufwg", "rank": 92, "score": 0.7456618547439575}, {"content": "Title: Modeling and Simulation of a Fully-glycosylated Full-length SARS-CoV-2 Spike Protein in a Viral Membrane Content: This technical study describes all-atom modeling and simulation of a fully-glycosylated full-length SARS-CoV-2 spike (S) protein in a viral membrane. First, starting from PDB:6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite. Then, using the recently-determined most occupied glycoforms, 22 N-glycans and 1 O-glycan of each monomer were modeled using Glycan Reader & Modeler in CHARMM-GUI. These fully-glycosylated full-length S protein model structures were assessed and further refined against the low-resolution data in their respective experimental maps using ISOLDE. We then used CHARMM-GUI Membrane Builder to place the S proteins in a viral membrane and performed all-atom molecular dynamics simulations. All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19), so researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.", "qid": 36, "docid": "rd9fy7o1", "rank": 93, "score": 0.7455466985702515}, {"content": "Title: Developing a Fully-glycosylated Full-length SARS-CoV-2 Spike Protein Model in a Viral Membrane Content: This technical study describes all-atom modeling and simulation of a fully-glycosylated full-length SARS-CoV-2 spike (S) protein in a viral membrane. First, starting from PDB:6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite. Then, using the recently-determined most occupied glycoforms, 22 N-glycans and 1 O-glycan of each monomer were modeled using Glycan Reader & Modeler in CHARMM-GUI. These fully-glycosylated full-length S protein model structures were assessed and further refined against the low-resolution data in their respective experimental maps using ISOLDE. We then used CHARMM-GUI Membrane Builder to place the S proteins in a viral membrane and performed all-atom molecular dynamics simulations. All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19), so researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.", "qid": 36, "docid": "9pyubizz", "rank": 94, "score": 0.7455466985702515}, {"content": "Title: Architecture and self-assembly of the SARS-CoV-2 nucleocapsid protein Content: The COVID-2019 pandemic is the most severe acute public health threat of the twenty-first century. To properly address this crisis with both robust testing and novel treatments, we require a deep understanding of the life cycle of the causative agent, the SARS-CoV-2 coronavirus. Here, we examine the architecture and self-assembly properties of the SARS-CoV-2 nucleocapsid protein, which packages viral RNA into new virions. We determined a 1.4 \u00e5 resolution crystal structure of this protein's N2b domain, revealing a compact, intertwined dimer similar to that of related coronaviruses including SARS-CoV. While the N2b domain forms a dimer in solution, addition of the C-terminal spacer B/N3 domain mediates formation of a homotetramer. Using hydrogen-deuterium exchange mass spectrometry, we find evidence that at least part of this putatively disordered domain is structured, potentially forming an &#945;-helix that self-associates and cooperates with the N2b domain to mediate tetramer formation. Finally, we map the locations of amino acid substitutions in the N protein from over 38,000 SARS-CoV-2 genome sequences. We find that these substitutions are strongly clustered in the protein's N2a linker domain, and that substitutions within the N1b and N2b domains cluster away from their functional RNA binding and dimerization interfaces. Overall, this work reveals the architecture and self-assembly properties of a key protein in the SARS-CoV-2 life cycle, with implications for both drug design and antibody-based testing. This article is protected by copyright. All rights reserved.", "qid": 36, "docid": "wfpi0wdo", "rank": 95, "score": 0.7454103231430054}, {"content": "Title: Comparing the Binding Interactions in the Receptor Binding Domains of SARS-CoV-2 and SARS-CoV Content: [Image: see text] SARS-CoV-2, since emerging in Wuhan, China, has been a major concern because of its high infection rate and has left more than six million infected people around the world. Many studies endeavored to reveal the structure of the SARS-CoV-2 compared to the SARS-CoV, in order to find solutions to suppress this high infection rate. Some of these studies showed that the mutations in the SARS-CoV spike (S) protein might be responsible for its higher affinity to the ACE2 human cell receptor. In this work, we used molecular dynamics simulations and Monte Carlo sampling to compare the binding affinities of the S proteins of SARS-CoV and SARS-CoV-2 to the ACE2. Our results show that the protein surface of the ACE2 at the receptor binding domain (RBD) exhibits negative electrostatic potential, while a positive potential is observed for the S proteins of SARS-CoV/SARS-CoV-2. In addition, the binding energies at the interface are slightly higher for SARS-CoV-2 because of enhanced electrostatic interactions. The major contributions to the electrostatic binding energies result from the salt bridges forming between R426 and ACE-2-E329 in the case of SARS-CoV and K417 and ACE2-D30 in the SARS-CoV-2. In addition, our results indicate that the enhancement in the binding energy is not due to a single mutant but rather because of the sophisticated structural changes induced by all these mutations together. This finding suggests that it is implausible for the SARS-CoV-2 to be a lab-engineered virus.", "qid": 36, "docid": "1iq1j47x", "rank": 96, "score": 0.7453672885894775}, {"content": "Title: Structural basis of receptor recognition by SARS-CoV-2 Content: A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans, causing COVID-191,2. A key to tackling this pandemic is to understand the receptor recognition mechanism of the virus, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor-angiotensin-converting enzyme 2 (ACE2)-in humans3,4. Here we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2. In comparison with the SARS-CoV RBD, an ACE2-binding ridge in SARS-CoV-2 RBD has a more compact conformation; moreover, several residue changes in the SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD-ACE2 interface. These structural features of SARS-CoV-2 RBD increase its ACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus that is closely related to SARS-CoV-2, also uses human ACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in ACE2 recognition shed light on the potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies that target receptor recognition by SARS-CoV-2.", "qid": 36, "docid": "nek3celo", "rank": 97, "score": 0.7452865242958069}, {"content": "Title: Structural variations in human ACE2 may influence its binding with SARS-CoV-2 spike protein Content: The recent pandemic of COVID-19, caused by SARS-CoV-2, is unarguably the most fearsome compared with the earlier outbreaks caused by other coronaviruses, SARS-CoV and MERS-CoV. Human ACE2 is now established as a receptor for the SARS-CoV-2 spike protein. Where variations in the viral spike protein, in turn, lead to the cross-species transmission of the virus, genetic variations in the host receptor ACE2 may also contribute to the susceptibility and/or resistance against the viral infection. This study aims to explore the binding of the proteins encoded by different human ACE2 allelic variants with SARS-CoV-2 spike protein. Briefly, coding variants of ACE2 corresponding to the reported binding sites for its attachment with coronavirus spike protein were selected and molecular models of these variants were constructed by homology modeling. The models were then superimposed over the native ACE2 and ACE2-spike protein complex, to observe structural changes in the ACE2 variants and their intermolecular interactions with SARS-CoV-2 spike protein, respectively. Despite strong overall structural similarities, the spatial orientation of the key interacting residues varies in the ACE2 variants compared with the wild-type molecule. Most ACE2 variants showed a similar binding affinity for SARS-CoV-2 spike protein as observed in the complex structure of wild-type ACE2 and SARS-CoV-2 spike protein. However, ACE2 alleles, rs73635825 (S19P) and rs143936283 (E329G) showed noticeable variations in their intermolecular interactions with the viral spike protein. In summary, our data provide a structural basis of potential resistance against SARS-CoV-2 infection driven by ACE2 allelic variants.", "qid": 36, "docid": "4nfxdppt", "rank": 98, "score": 0.7450105547904968}, {"content": "Title: Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies Content: The recent severe acute respiratory syndrome, known as Coronavirus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare a state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, the scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim, we performed an in silico comparative modeling analysis, which allows gaining new insights into the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor-binding domain (RBD), along interactions with human cells angiotensin-converting enzyme 2 (ACE2) receptor, that favor human cell invasion. Furthermore, our analysis provides (1) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, aiming to prevent interactions with the human ACE2, and (2) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. The proposed antibodies show in silico high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high-affinity antibodies against present and future coronaviruses able to invade human cells through interactions of their spike proteins with the human ACE2. More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD-ACE2 interactions for the development of new vaccines, diagnostic kits, and other treatments based on the targeting of SARS-CoV-2 spike protein.", "qid": 36, "docid": "zso57yi7", "rank": 99, "score": 0.7449812889099121}, {"content": "Title: Computational Analysis of Dynamic Allostery and Control in the SARS-CoV-2 Main Protease Content: The dynamics and thermodynamics of the homodimer main protease protein SARS-CoV-2 are analysed at the level of Elastic Network Models (ENM). Correlated motions display a rich and heterogeneous dynamical structure, including allosterically correlated motions between the active sites in the two domains. Exhaustive 1-point and 2-point mutation maps, and their effect on binding free energies and allosteric free energies confirm the susceptibility identified in recent candidate inhibitor assays, but also suggest several new candidate regions for control and inhibition of the protease function, which may assist the development of current fragment binding screens.", "qid": 36, "docid": "5jfpmgfh", "rank": 100, "score": 0.744930624961853}]}
{"query": "What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence?", "hits": [{"content": "Title: A snapshot of SARS-CoV-2 genome availability up to 30th March, 2020 and its implications Content: The SARS-CoV-2 pandemic has been growing exponentially, affecting nearly 900 thousand people and causing enormous distress to economies and societies worldwide. A plethora of analyses based on viral sequences has already been published, in scientific journals as well as through non-peer reviewed channels, to investigate SARS-CoV-2 genetic heterogeneity and spatiotemporal dissemination. We examined full genome sequences currently available to assess the presence of sufficient information for reliable phylogenetic and phylogeographic studies in countries with the highest toll of confirmed cases. Although number of-available full-genomes is growing daily, and the full dataset contains sufficient phylogenetic information that would allow reliable inference of phylogenetic relationships, country-specific SARS-CoV-2 datasets still present severe limitations. Studies assessing within country spread or transmission clusters should be considered preliminary at best, or hypothesis generating. Hence the need for continuing concerted efforts to increase number and quality of the sequences required for robust tracing of the epidemic. Significance Statement Although genome sequences of SARS-CoV-2 are growing daily and contain sufficient phylogenetic information, country-specific data still present severe limitations and should be interpreted with caution.", "qid": 37, "docid": "8vl0okiv", "rank": 1, "score": 0.8248631954193115}, {"content": "Title: A Snapshot of SARS-CoV-2 Genome Availability up to April 2020 and its Implications: Data Analysis Content: BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been growing exponentially, affecting over 4 million people and causing enormous distress to economies and societies worldwide. A plethora of analyses based on viral sequences has already been published both in scientific journals and through non-peer-reviewed channels to investigate the genetic heterogeneity and spatiotemporal dissemination of SARS-CoV-2. However, a systematic investigation of phylogenetic information and sampling bias in the available data is lacking. Although the number of available genome sequences of SARS-CoV-2 is growing daily and the sequences show increasing phylogenetic information, country-specific data still present severe limitations and should be interpreted with caution. OBJECTIVE: The objective of this study was to determine the quality of the currently available SARS-CoV-2 full genome data in terms of sampling bias as well as phylogenetic and temporal signals to inform and guide the scientific community. METHODS: We used maximum likelihood-based methods to assess the presence of sufficient information for robust phylogenetic and phylogeographic studies in several SARS-CoV-2 sequence alignments assembled from GISAID (Global Initiative on Sharing All Influenza Data) data released between March and April 2020. RESULTS: Although the number of high-quality full genomes is growing daily, and sequence data released in April 2020 contain sufficient phylogenetic information to allow reliable inference of phylogenetic relationships, country-specific SARS-CoV-2 data sets still present severe limitations. CONCLUSIONS: At the present time, studies assessing within-country spread or transmission clusters should be considered preliminary or hypothesis-generating at best. Hence, current reports should be interpreted with caution, and concerted efforts should continue to increase the number and quality of sequences required for robust tracing of the epidemic.", "qid": 37, "docid": "dqyjdast", "rank": 2, "score": 0.8237589001655579}, {"content": "Title: A Snapshot of SARS-CoV-2 Genome Availability up to April 2020 and its Implications: Data Analysis Content: BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been growing exponentially, affecting over 4 million people and causing enormous distress to economies and societies worldwide. A plethora of analyses based on viral sequences has already been published both in scientific journals and through non\u2013peer-reviewed channels to investigate the genetic heterogeneity and spatiotemporal dissemination of SARS-CoV-2. However, a systematic investigation of phylogenetic information and sampling bias in the available data is lacking. Although the number of available genome sequences of SARS-CoV-2 is growing daily and the sequences show increasing phylogenetic information, country-specific data still present severe limitations and should be interpreted with caution. OBJECTIVE: The objective of this study was to determine the quality of the currently available SARS-CoV-2 full genome data in terms of sampling bias as well as phylogenetic and temporal signals to inform and guide the scientific community. METHODS: We used maximum likelihood\u2013based methods to assess the presence of sufficient information for robust phylogenetic and phylogeographic studies in several SARS-CoV-2 sequence alignments assembled from GISAID (Global Initiative on Sharing All Influenza Data) data released between March and April 2020. RESULTS: Although the number of high-quality full genomes is growing daily, and sequence data released in April 2020 contain sufficient phylogenetic information to allow reliable inference of phylogenetic relationships, country-specific SARS-CoV-2 data sets still present severe limitations. CONCLUSIONS: At the present time, studies assessing within-country spread or transmission clusters should be considered preliminary or hypothesis-generating at best. Hence, current reports should be interpreted with caution, and concerted efforts should continue to increase the number and quality of sequences required for robust tracing of the epidemic.", "qid": 37, "docid": "hze05jnf", "rank": 3, "score": 0.8236206769943237}, {"content": "Title: Whole genome sequencing of SARS-CoV-2 isolated in Guangdong Province and factors influencing the sequencing/ \u5e7f\u4e1c\u7701\u65b0\u578b\u51a0\u72b6\u75c5\u6bd2\u5168\u57fa\u56e0\u7ec4\u5e8f\u5217\u6d4b\u5b9a\u53ca\u5176\u5f71\u54cd\u56e0\u7d20\u5206\u6790 Content: Objective: To obtain the genome sequences of SARS-CoV-2 in respiratory specimens in Guangdong Province with next-generation sequencing (NGS) and analyze the factors influencing sequencing. Methods: Eight upper and lower respiratory tract specimens were collected from patients with SARS-CoV-2 infection in Guangdong Province in January 2020. RNA library construction was used to obtain the genome sequences of SARS-CoV-2. A bio-informatics software package (CLC Genomics Workbench 12.0) was used to analyze and compare the genomic sequences. Results: Five SARS-CoV-2 genome sequences were obtained from the eight specimens and two were obtained from lower respiratory tract specimens. The nucleotide homology to SARS-CoV-2 was 97.74%-99.90%. The Ct values were lower, while the sequencing depth, coverage, relative abundance and genome integrity were higher in sequencing the SARS-CoV-2 in lower respiratory tract specimens. Conclusions: The low Ct value of SARS-CoV-2 in the samples was good for sequencing.", "qid": 37, "docid": "2k7gckj2", "rank": 4, "score": 0.8219826221466064}, {"content": "Title: Early Phylogenetic Diversification of SARS-CoV-2: Determination of Variants and the Effect on Epidemiology, Immunology, and Diagnostics. Content: The phylogenetic clustering of 95 SARS-CoV-2 sequences from the first 3 months of the pandemic reveals insights into the early evolution of the virus and gives first indications of how the variants are globally distributed. Variants might become a challenge in terms of diagnostics, immunology, and effectiveness of drugs. All available whole genome sequence data from the NCBI database (March 16, 2020) were phylogenetically analyzed, and gene prediction as well as analysis of selected variants were performed. Antigenic regions and the secondary protein structure were predicted for selected variants. While some clusters are presenting the same variant with 100% identical bases, other SARS-CoV-2 lineages show a beginning diversification and phylogenetic clustering due to base substitutions and deletions in the genomes. First molecular epidemiological investigations are possible with the results by adding metadata as travelling history to the presented data. The advantage of variants in source tracing can be a challenge in terms of virulence, immune response, and immunological memory. Variants of viruses often show differences in virulence or antigenicity. This must also be considered in decisions like herd immunity. Diagnostic methods might not work if the variations or deletions are in target regions for the detection of the pathogen. One base substitution was detected in a primer binding site.", "qid": 37, "docid": "3sxlvoxf", "rank": 5, "score": 0.8147257566452026}, {"content": "Title: Unsupervised cluster analysis of SARS-CoV-2 genomes reflects its geographic progression and identifies distinct genetic subgroups of SARS-CoV-2 virus Content: Over 10,000 viral genome sequences of the SARS-CoV-2 virus have been made readily available during the ongoing coronavirus pandemic since the initial genome sequence of the virus was released on the open access Virological website (http://virological.org/) early on January 11. We utilize the published data on the single stranded RNAs of 11, 132 SARS-CoV-2 patients in the GISAID (Elbe and Buckland-Merrett, 2017; Shu and McCauley, 2017) database, which contains fully or partially sequenced SARS-CoV-2 samples from laboratories around the world. Among many important research questions which are currently being investigated, one aspect pertains to the genetic characterization/classification of the virus. We analyze data on the nucleotide sequencing of the virus and geographic information of a subset of 7, 640 SARS-CoV-2 patients without missing entries that are available in the GISAID database. Instead of modelling the mutation rate, applying phylogenetic tree approaches, etc., we here utilize a model-free clustering approach that compares the viruses at a genome-wide level. We apply principal component analysis to a similarity matrix that compares all pairs of these SARS-CoV-2 nucleotide sequences at all loci simultaneously, using the Jaccard index (Jaccard, 1901; Tan et al., 2005; Prokopenko et al., 2016; Schlauch et al., 2017). Our analysis results of the SARS-CoV-2 genome data illustrates the geographic and chronological progression of the virus, starting from the first cases that were observed in China to the current wave of cases in Europe and North America. We also observe that, based on their sequence data, the SARS-CoV-2 viruses cluster in distinct genetic subgroups. It is the subject of ongoing research to examine whether the genetic subgroup could be related to diseases outcome and its potential implications for vaccine development.", "qid": 37, "docid": "xnamt7q4", "rank": 6, "score": 0.8146529197692871}, {"content": "Title: Regaining perspective on SARS-CoV-2 molecular tracing and its implications Content: During the past three months, a new coronavirus (SARS-CoV-2) epidemic has been growing exponentially, affecting over 100 thousand people worldwide, and causing enormous distress to economies and societies of affected countries. A plethora of analyses based on viral sequences has already been published, in scientific journals as well as through non-peer reviewed channels, to investigate SARS-CoV-2 genetic heterogeneity and spatiotemporal dissemination. We examined all full genome sequences currently available to assess the presence of sufficient information for reliable phylogenetic and phylogeographic studies. Our analysis clearly shows severe limitations in the present data, in light of which any finding should be considered, at the very best, preliminary and hypothesis-generating. Hence the need for avoiding stigmatization based on partial information, and for continuing concerted efforts to increase number and quality of the sequences required for robust tracing of the epidemic.", "qid": 37, "docid": "szg12wfa", "rank": 7, "score": 0.8099338412284851}, {"content": "Title: Comparative genomics provides an operational classification system and reveals early emergence and biased spatio-temporal distribution of SARS-CoV-2 Content: Effective systems for the analysis of molecular data are of fundamental importance for real-time monitoring of the spread of infectious diseases and the study of pathogen evolution. While the Nextstrain and GISAID portals offer widely used systems for the classification of SARS-CoV-2 genomes, both present relevant limitations. Here we propose a highly reproducible method for the systematic classification of SARS-CoV-2 viral types. To demonstrate the validity of our approach, we conduct an extensive comparative genomic analysis of more than 20,000 SARS-CoV-2 genomes. Our classification system delineates 12 clusters and 4 super-clusters in SARS-CoV-2, with a highly biased spatio-temporal distribution worldwide, and provides important observations concerning the evolutionary processes associated with the emergence of novel viral types. Based on the estimates of SARS-CoV-2 evolutionary rate and genetic distances of genomes of the early pandemic phase, we infer that SARS-CoV-2 could have been circulating in humans since August-November 2019. The observed pattern of genomic variability is remarkably similar between all clusters and super-clusters, being UTRs and the s2m element, a highly conserved secondary structure element, the most variable genomic regions. While several polymorphic sites that are specific to one or more clusters were predicted to be under positive or negative selection, overall, our analyses also suggest that the emergence of novel genome types is unlikely to be driven by widespread convergent evolution and independent fixation of advantageous substitutions. While, in the absence of rigorous experimental validation, several questions concerning the evolutionary processes and the phenotypic characteristics (increased/decreased virulence) remain open, we believe that the approach outlined in this study can be of relevance for the tracking and functional characterization of different types of SARS-CoV-2 genomes.", "qid": 37, "docid": "yoe84ta7", "rank": 8, "score": 0.8054805994033813}, {"content": "Title: A High-Coverage SARS-CoV-2 Genome Sequence Acquired by Target Capture Sequencing Content: This manuscript is based on the method we developed urgently to deal with the research requirement in the conflict between achieving a complete genome sequence for the evolutionary history of SARS-CoV-2 study and the low viral RNA concentration. Here, in this manuscript, we developed a set of SARS-CoV-2 enrichment probes to increase the sensitivity of sequence-based virus detection and characterization via obtaining the comprehensive genome sequence. Following the CDC health and safety guidelines, we test the concept using the culturing supernatant contain SARS-CoV-2 particles, and its full-length sequence was used for further analysis. The fraction of SARS-CoV-2 endogenous DNA was 93.47% with Cluster Factor about 1.1, which demonstrate that the numbers of mapped reads to SARS-CoV-2 reference sequence significantly increased, compared to metagenomic sequencing technology, following SARS-CoV-2 probe enrichment. Moreover, based on the high-quality sequence, we discussed the heterozygosity and viral expression during replication of coronavirus, and its phylogenetic relationship with other selected high-quality samples from The Genome Variation Map (GVM) (on 2020/03/22). We believe this manuscript is valuable for all the researchers who are interested in using clinical warp samples to obtain the high coverage of SARS-CoV-2 genome sequence with a relatively low concentration of viral particles. This would allow the clinician to correlate the diagnostic data with molecular monitoring in viral evolutional, the most importantly, to track the functional mutation of SARS-CoV-2.", "qid": 37, "docid": "yb6if23t", "rank": 9, "score": 0.8044098615646362}, {"content": "Title: Genomic characterization of a novel SARS-CoV-2 Content: A new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated with human to human transmission and extreme human sickness has been as of late announced from the city of Wuhan in China. Our objectives were to mutation analysis between recently reported genomes at various times and locations and to characterize the genomic structure of SARS-CoV-2 using bioinformatics programs. Information on the variation of viruses is of considerable medical and biological impacts on the prevention, diagnosis, and therapy of infectious diseases. To understand the genomic structure and variations of the SARS-CoV-2. The study analyzed 95 SARS-CoV-2 complete genome sequences available in GenBank, National MicrobiologyData Center (NMDC) and NGDC Genome Warehouse from December-2019 until 05 of April-2020. The genomic signature analysis demonstrates that a strong association between the time of sample collection, location of sample and accumulation of genetic diversity. We found 116 mutations, the three most common mutations were 8782C>T in ORF1ab gene, 28144T>C in ORF8 gene and 29095C>T in the N gene. The mutations might affect the severity and spread of the SARS-CoV-2. The finding heavily supports an intense requirement for additional prompt, inclusive investigations that combine genomic detail, epidemiological information and graph records of the clinical features of patients with COVID-19.", "qid": 37, "docid": "mp3196kj", "rank": 10, "score": 0.8041625022888184}, {"content": "Title: Stability of SARS-CoV-2 Phylogenies Content: The SARS-CoV-2 pandemic has led to unprecedented, nearly real-time genetic tracing due to the rapid community sequencing response. Researchers immediately leveraged these data to infer the evolutionary relationships among viral samples and to study key biological questions, including whether host viral genome editing and recombination are features of SARS-CoV-2 evolution. This global sequencing effort is inherently decentralized and must rely on data collected by many labs using a wide variety of molecular and bioinformatic techniques. There is thus a strong possibility that systematic errors associated with lab-specific practices affect some sequences in the repositories. We find that some recurrent mutations in reported SARS-CoV-2 genome sequences have been observed predominantly or exclusively by single labs, co-localize with commonly used primer binding sites and are more likely to affect the protein coding sequences than other similarly recurrent mutations. We show that their inclusion can affect phylogenetic inference on scales relevant to local lineage tracing, and make it appear as though there has been an excess of recurrent mutation and/or recombination among viral lineages. We suggest how samples can be screened and problematic mutations removed. We also develop tools for comparing and visualizing differences among phylogenies and we show that consistent clade- and tree-based comparisons can be made between phylogenies produced by different groups. These will facilitate evolutionary inferences and comparisons among phylogenies produced for a wide array of purposes. Building on the SARS-CoV-2 Genome Browser at UCSC, we present a toolkit to compare, analyze and combine SARS-CoV-2 phylogenies, find and remove potential sequencing errors and establish a widely shared, stable clade structure for a more accurate scientific inference and discourse. Foreword We wish to thank all groups that responded rapidly by producing these invaluable and essential sequence data. Their contributions have enabled an unprecedented, lightning-fast process of scientific discovery---truly an incredible benefit for humanity and for the scientific community. We emphasize that most lab groups with whom we associate specific suspicious alleles are also those who have produced the most sequence data at a time when it was urgently needed. We commend their efforts. We have already contacted each group and many have updated their sequences. Our goal with this work is not to highlight potential errors, but to understand the impacts of these and other kinds of highly recurrent mutations so as to identify commonalities among the suspicious examples that can improve sequence quality and analysis going forward.", "qid": 37, "docid": "aqkpnz0o", "rank": 11, "score": 0.8030504584312439}, {"content": "Title: Comparative genomic signature representations of the emerging COVID-19 coronavirus and other coronaviruses: High identity and possible recombination between Bat and Pangolin coronaviruses Content: Coronaviruses are responsible on respiratory diseases in animal and human. The combination of numerical encoding techniques and digital signal processing methods are becoming increasingly important in handling large genomic data. In this paper, we propose to analyze the SARS-CoV-2 genomic signature using the combination of different nucleotide representations and signal processing tools in the aim to identify its genetic origin. The sequence of SARS-CoV-2 was compared with 21 relevant sequences including bat, yak and pangolin coronavirus sequences. In addition, we developed a new algorithm to locate the nucleotide modifications. The results show that the Bat and Pangolin coronaviruses were the most related to SARS-CoV-2 with 96% and 86% of identity all along the genome. Within the S gene sequence, the Pangolin sequence presents local highest nucleotide identity. Those findings suggest genesis of SARS-Cov-2 through evolution from bat and pangolin strains. This study offers new ways to automatically characterize viruses.", "qid": 37, "docid": "6ydswv0a", "rank": 12, "score": 0.8018296957015991}, {"content": "Title: Genomic characterization of a novel SARS-CoV-2 Content: Abstract A new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated with human to human transmission and extreme human sickness has been as of late announced from the city of Wuhan in China. Our objectives were to mutation analysis between recently reported genomes at various times and locations and to characterize the genomic structure of SARS-CoV-2 using bioinformatics programs. Information on the variation of viruses is of considerable medical and biological impacts on the prevention, diagnosis, and therapy of infectious diseases. To understand the genomic structure and variations of the SARS-CoV-2. The study analyzed 95 SARS-CoV-2 complete genome sequences available in GenBank, National MicrobiologyData Center (NMDC) and NGDC Genome Warehouse from December-2019 until 05 of April-2020. The genomic signature analysis demonstrates that a strong association between the time of sample collection, location of sample and accumulation of genetic diversity. We found 116 mutations, the three most common mutations were 8782C>T in ORF1ab gene, 28144T>C in ORF8 gene and 29095C>T in the N gene. The mutations might affect the severity and spread of the SARS-CoV-2. The finding heavily supports an intense requirement for additional prompt, inclusive investigations that combine genomic detail, epidemiological information and graph records of the clinical features of patients with COVID-19.", "qid": 37, "docid": "vjfquvlu", "rank": 13, "score": 0.8004368543624878}, {"content": "Title: SARS-CoV Infection Was from at Least Two Origins in the Taiwan Area Content: OBJECTIVE: Severe acute respiratory syndrome (SARS) is caused by a new coronavirus. Genomic sequence analysis will provide the molecular epidemiology and help to develop vaccines. METHODS: We developed a rapid method to amplify and sequence the whole SARS-CoV genome from clinical specimens. The technique employed one-step multiplex RT-PCR to amplify the whole SARS-CoV genome, and then nested PCR was performed to amplify a 2-kb region separately. The PCR products were sequenced. RESULTS: We sequenced the genomes of SARS-CoV from 3 clinical specimens obtained in Taiwan. The sequences were similar to those reported by other groups, except that 17 single nucleotide variations and two 2-nucleotide deletions, and a 1-nucleotide deletion were found. All the variations in the clinical specimens did not alter the amino acid sequence. Of these 17 sequenced variants, two loci (positions 26203 and 27812) were segregated together as a specific genotype-T:T or C:C. Phylogenetic analysis showed two major clusters of SARS patients in Taiwan. CONCLUSION: We developed a very economical and rapid method to sequence the whole genome of SARS-CoV, which can avoid cultural influence. From our results, SARS patients in Taiwan may be infected from two different origins.", "qid": 37, "docid": "79uxm3bg", "rank": 14, "score": 0.7968165278434753}, {"content": "Title: CoV-Seq: SARS-CoV-2 Genome Analysis and Visualization Content: Summary COVID-19 has become a global pandemic not long after its inception in late 2019. SARS-CoV-2 genomes are being sequenced and shared on public repositories at a fast pace. To keep up with these updates, scientists need to frequently refresh and reclean datasets, which is ad hoc and labor-intensive. Further, scientists with limited bioinformatics or programming knowledge may find it difficult to analyze SARS-CoV-2 genomes. In order to address these challenges, we developed CoV-Seq, a webserver to enable simple and rapid analysis of SARS-CoV-2 genomes. Given a new sequence, CoV-Seq automatically predicts gene boundaries and identifies genetic variants, which are presented in an interactive genome visualizer and are downloadable for further analysis. A command-line interface is also available for high-throughput processing. Availability and Implementation CoV-Seq is implemented in Python and Javascript. The webserver is available at http://covseq.baidu.com/ and the source code is available from https://github.com/boxiangliu/covseq. Contact jollier.liu@gmail.com Supplementary information Supplementary information are available at bioRxiv online.", "qid": 37, "docid": "nqfo3qtb", "rank": 15, "score": 0.7959824800491333}, {"content": "Title: Genome analysis of SARS-CoV-2 isolates occurring in India: Present scenario. Content: Background The origin of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still a debatable topic. The association of the virus spread from the market is supported by the close relation of genome sequences of environmental surface samples with virus samples from earliest patients by phylogenetic analysis. Objectives To have an insight into the SARS-CoV-2 genome sequences reported from India for better understanding on their epidemiology and virulence. Methods Genome sequences of Indian isolates of SARS-CoV-2 were analyzed to understand their phylogeny and divergence with respect to other isolates reported from other countries. Amino acid sequences of individual open reading frames (ORFs) from SARS-CoV-2 Indian isolates were aligned with sequences of isolates reported from other countries to identify the mutations occurred in Indian isolates. Results Our analysis suggests that Indian SARS-CoV-2 isolates are closely related to isolates reported from other parts of the world. Most ORFs are highly conserved; mutations were also detected in some ORFs. We found that most isolates reported from India have key mutations at 614th position of the S protein and 84th position of the ORF 8, which has been reported to be associated with high virulence and high transmission rate. Conclusion An attempt was made to understand the SARS-CoV-2 virus reported from India. SARS-CoV-2 reported from India was closely similar to other SARS-CoV-2 reported from other parts of the world, which suggests that vaccines and other therapeutic methods generated from other countries might work well in India. In addition, available sequence data suggest that majority of Indian isolates are capable of high transmission and virulence.", "qid": 37, "docid": "bcx51aci", "rank": 16, "score": 0.7957888245582581}, {"content": "Title: An Analysis of SARS-CoV-2 Using ViReport Content: The ongoing outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in millions of cases and hundreds of thousands of deaths. Given the current lack of treatments or vaccines available, it may be useful to trace the evolu-tion and spread of the virus to better develop methods of preventative intervention. In this study, we analyzed over 4,000 full genome sequences of human SARS-CoV-2 using novel tool ViReport [13], an automated workflow for performing phylogenetic analyses on viral sequences and generating comprehensive molecular epidemiologi-cal reports. The complete ViReport output can be found at https://github.com/mirandajsong/ViReport-SARS-CoV-2.", "qid": 37, "docid": "whmawr4q", "rank": 17, "score": 0.7956448793411255}, {"content": "Title: Comparative genomic signature representations of the emerging COVID-19 coronavirus and other coronaviruses: High identity and possible recombination between Bat and Pangolin coronaviruses Content: Abstract Coronaviruses are responsible on respiratory diseases in animal and human. The combination of numerical encoding techniques and digital signal processing methods are becoming increasingly important in handling large genomic data. In this paper, we propose to analyze the SARS-CoV-2 genomic signature using the combination of different nucleotide representations and signal processing tools in the aim to identify its genetic origin. The sequence of SARS-CoV-2 was compared with 21 relevant sequences including bat, yak and pangolin coronavirus sequences. In addition, we developed a new algorithm to locate the nucleotide modifications. The results show that the Bat and Pangolin coronaviruses were the most related to SARS-CoV-2 with 96% and 86% of identity all along the genome. Within the S gene sequence, the Pangolin sequence presents local highest nucleotide identity. Those findings suggest genesis of SARS-Cov-2 through evolution from bat and pangolin strains. This study offers new ways to automatically characterize viruses.", "qid": 37, "docid": "13ir7swr", "rank": 18, "score": 0.7953038215637207}, {"content": "Title: SARS-CoV-2 sequence typing, evolution and signatures of selection using CoVa, a Python-based command-line utility Content: The current global pandemic COVID-19, caused by SARS-CoV-2, has resulted in millions of infections worldwide in a few months. Global efforts to tackle this situation have produced a tremendous body of genomic data, which can be used for tracing transmission routes, characterization of isolates, and monitoring variants with potential for unusual virulence. Several groups have analyzed these genomes using different approaches. However, as new data become available, the research community needs a pipeline to perform a set of routine analyses, that can quickly incorporate new genome sequences and update the analysis reports. We developed a programmatic tool, CoVa, with this objective. It is a fast, accurate and user-friendly utility to perform a variety of genome analyses on hundreds of SARS-CoV-2 sequences. Using CoVa, we define a modified sequence typing nomenclature and identify sites under positive selection. Further analysis identified some peptides and sites showing geographical patterns of selection. Specifically, we show differences in sequence type distribution between sequences from India and those from the rest of the world. We also show that several sites show signatures of positive selection uniquely in sequences from India. Preliminary evolutionary analysis, using features that will be incorporated into CoVa in the near future, show a mutation rate of 7.4 \u00d7 10\u22124 substitutions/site/year, confirm a temporal signal with a November 2019 origin of SARS-CoV-2, and a heterogeneity in the geographical distribution of Indian samples.", "qid": 37, "docid": "w8vs7s28", "rank": 19, "score": 0.7946818470954895}, {"content": "Title: Genome analysis of SARS-CoV-2 isolates occurring in India: Present scenario Content: Background: The origin of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still a debatable topic. The association of the virus spread from the market is supported by the close relation of genome sequences of environmental surface samples with virus samples from earliest patients by phylogenetic analysis. Objectives: To have an insight into the SARS-CoV-2 genome sequences reported from India for better understanding on their epidemiology and virulence. Methods: Genome sequences of Indian isolates of SARS-CoV-2 were analyzed to understand their phylogeny and divergence with respect to other isolates reported from other countries. Amino acid sequences of individual open reading frames (ORFs) from SARS-CoV-2 Indian isolates were aligned with sequences of isolates reported from other countries to identify the mutations occurred in Indian isolates. Results: Our analysis suggests that Indian SARS-CoV-2 isolates are closely related to isolates reported from other parts of the world. Most ORFs are highly conserved; mutations were also detected in some ORFs. We found that most isolates reported from India have key mutations at 614th position of the S protein and 84th position of the ORF 8, which has been reported to be associated with high virulence and high transmission rate. Conclusion: An attempt was made to understand the SARS-CoV-2 virus reported from India. SARS-CoV-2 reported from India was closely similar to other SARS-CoV-2 reported from other parts of the world, which suggests that vaccines and other therapeutic methods generated from other countries might work well in India. In addition, available sequence data suggest that majority of Indian isolates are capable of high transmission and virulence.", "qid": 37, "docid": "2nvk7glh", "rank": 20, "score": 0.7934110164642334}, {"content": "Title: Molecular characterization of SARS-CoV-2 in the first COVID-19 cluster in France reveals an amino-acid deletion in nsp2 (Asp268Del) Content: We present the first genetic characterization of a COVID-19 cluster in Europe using metagenomic next-generation sequencing (mNGS). Despite low viral loads, the mNGS workflow used herein allowed to characterize the whole genome sequences of SARS-CoV2 isolated from an asymptomatic patient, in 2 clinical samples collected 1 day apart. Comparison of these sequences suggests viral evolution with development of quasispecies. In addition, the present workflow identified a new deletion in nsp2 (Asp268Del) which was found in all 3 samples originating from this cluster as well as in 37 other viruses collected in England and in Netherlands, suggesting the spread of this deletion in Europe. The impact of Asp268Del on SARS-CoV-2 transmission and pathogenicity, as well as on PCR performances and anti-viral strategy should be rapidly evaluated in further studies.", "qid": 37, "docid": "wnh6h9f0", "rank": 21, "score": 0.7926859855651855}, {"content": "Title: Investigating the genomic landscape of novel coronavirus (2019-nCoV) to identify non-synonymous mutations for use in diagnosis and drug design Content: This study presents a comprehensive phylogenetic analysis of SARS-CoV2 isolates to understand discrete mutations that are occurring between patient samples. The analysis unravel various amino acid mutations in the viral proteins which may provide an explanation for varying treatment efficacies of different inhibitory drugs and a future direction towards a combinatorial treatment therapies based on the kind of mutation in the viral genome.", "qid": 37, "docid": "ttte21up", "rank": 22, "score": 0.7924566268920898}, {"content": "Title: Quantification of Intra-Host Genomic Diversity of SARS-CoV-2 Allows a High-Resolution Characterization of Viral Evolution and Reveals Functionally Convergent Variants Content: A global cross-discipline effort is ongoing to characterize the evolution of SARS-CoV-2 virus and generate reliable epidemiological models of its diffusion. To this end, phylogenomic approaches leverage accumulating genomic mutations as barcodes to track the evolutionary history of the virus and can benefit from the surge of sequences deposited in public databases. Yet, such methods typically rely on consensus sequences representing the dominant virus lineage, whereas a complex sublineage architecture is often observed within single hosts. Furthermore, most approaches do not account for variants accumulation processes and might produce inaccurate results in condition of limited sampling, as witnessed in most countries affected by the epidemics. We introduce VERSO (Viral Evolution ReconStructiOn), a new comprehensive framework for the characterization of viral evolution and transmission from sequencing data of viral genomes. our approach accounts for accumulation of clonal mutations and uncertainty in the data, by taking advantage of the achievements of research in cancer evolution, to deliver robust phylogenomic lineage models, and exploits intra-host variant frequency profiles to characterize the sublineage similarity among samples, which may derive from uncovered infection events. The application of our approach to RNA-sequencing data of 162 SARS-CoV-2 samples generates a high-resolution model of evolution and spread, which improves recent findings on viral types and highlights the existence of patterns of co-occurrence of minor variants, revealing likely infection paths among hosts harboring the same viral lineage. The in-depth analysis of the mutational landscape of SARS-CoV-2 confirms a statistically significant increase of genomic diversity in time and identifies a number of variants that are transiting from minor to clonal state in the population. We also show that standard phylogenetic methods can produce unreliable results when handling datasets with noise and sampling limitations, as proven by the further application of VERSO to 12419 consensus sequences included in GISAID database. Notably, VERSO allows to pinpoint minor variants that might be positively or negatively selected across distinct lineages, thus driving the design of treatments and vaccines. In particular, minor variant g.29039A>U, detected in multiple viral lineages and validated on independent samples, shows that SARS-CoV-2 can lose its main Nucleocapsid immunogenic epitopes, raising concerns about the effectiveness of vaccines targeting the C-terminus of this protein. Finally, we here release the likely SARS-CoV-2 ancestral genome, obtained by resolving ambiguous SNPs that distinguish two widely-used reference genomes from human samples, by employing the Pangolin-CoV and the Bat-CoV-RaTG13 genomes. Our results show that the joint application of our framework and data-driven epidemiological models might allow to deliver a high-resolution platform for pathogen surveillance and analysis.", "qid": 37, "docid": "ea78sjcs", "rank": 23, "score": 0.7921410202980042}, {"content": "Title: SARS-CoV-2 Whole Genome Amplification and Sequencing for Effective Population-Based Surveillance and Control of Viral Transmission Content: Background With the gradual reopening of economies and resumption of social life, robust surveillance mechanisms should be implemented to control the ongoing COVID-19 pandemic. Unlike RT-qPCR, SARS-CoV-2 Whole Genome Sequencing (cWGS) has the added advantage of identifying cryptic origins of the virus, and the extent of community-based transmissions versus new viral introductions, which can in turn influence public health policy decisions. However, practical and cost considerations of cWGS should be addressed before it can be widely implemented. Methods We performed shotgun transcriptome sequencing using RNA extracted from nasopharyngeal swabs of patients with COVID-19, and compared it to targeted SARS-CoV-2 full genome amplification and sequencing with respect to virus detection, scalability, and cost-effectiveness. To track virus origin, we used open-source multiple sequence alignment and phylogenetic tools to compare the assembled SARS-CoV-2 genomes to publicly available sequences. Results We show a significant improvement in whole genome sequencing data quality and viral detection using amplicon-based target enrichment of SARS-CoV-2. With enrichment, more than 99% of the sequencing reads mapped to the viral genome compared to an average of 0.63% without enrichment. Consequently, a dramatic increase in genome coverage was obtained using significantly less sequencing data, enabling higher scalability and significant cost reductions. We also demonstrate how SARS-CoV-2 genome sequences can be used to determine their possible origin through phylogenetic analysis including other viral strains. Conclusions SARS-CoV-2 whole genome sequencing is a practical, cost-effective, and powerful approach for population-based surveillance and control of viral transmission in the next phase of the COVID-19 pandemic.", "qid": 37, "docid": "8klkojpo", "rank": 24, "score": 0.7889326810836792}, {"content": "Title: On spatial molecular arrangements of SARS-CoV2 genomes of Indian patients Content: A pandemic caused by the SARS-CoV2 is being experienced by the whole world since December, 2019. A thorough understanding beyond just sequential similarities among the protein coding genes of SARS-CoV2 is important in order to differentiate or relate to the other known CoVs of the same genus. In this study, we compare three genomes namely MT012098 (India-Kerala), MT050493 (India-Kerala), MT358637 (India-Gujrat) from India with NC_045512 (China-Wuhan) to view the spatial as well as molecular arrangements of nucleotide bases of all the genes embedded in these four genomes. Based on different features extracted for each gene embedded in these genomes, corresponding phylogenetic relationships have been built up. Differences in phylogenetic tree arrangement with individual gene suggest that three genomes of Indian origin have come from three different origins or the evolution of viral genome is very fast process. This study would also help to understand the virulence factors, disease pathogenicity, origin and transmission of the SARS-CoV2.", "qid": 37, "docid": "k2juhyex", "rank": 25, "score": 0.7888457179069519}, {"content": "Title: Genomic epidemiology of a densely sampled COVID19 outbreak in China Content: Analysis of genetic sequence data from the pandemic SARS Coronavirus 2 can provide insights into epidemic origins, worldwide dispersal, and epidemiological history. With few exceptions, genomic epidemiological analysis has focused on geographically distributed data sets with few isolates in any given location. Here we report an analysis of 20 whole SARS-CoV 2 genomes from a single relatively small and geographically constrained outbreak in Weifang, People's Republic of China. Using Bayesian model-based phylodynamic methods, we estimate the reproduction number for the outbreak to be 1.99(95% CI:1.48-3.14). We further estimate the number of infections through time and compare these estimates to confirmed diagnoses by the Weifang Centers for Disease Control. We find that these estimates are consistent with reported cases and there is unlikely to be a large undiagnosed burden of infection over the period we studied.", "qid": 37, "docid": "xckkdci1", "rank": 26, "score": 0.7887414693832397}, {"content": "Title: Polymorphism of SARS-CoV Genomes Content: Abstract In this work, severe acute respiratory syndrome associated coronavirus (SARS-CoV) genome BJ202 (AY864806) was completely sequenced. The genome was directly accessed from the stool sample of a patient in Beijing. Comparative genomics methods were used to analyze the sequence variations of 116 SARS-CoV genomes (including BJ202) available in the NCBI Gen-Bank. With the genome sequence of GZ02 as the reference, there were 41 polymorphic sites identified in BJ202 and a total of 278 polymorphic sites present in at least two of the 116 genomes. The distribution of the polymorphic sites was biased over the whole genome. Nearly half of the variations (50.4%, 140/278) clustered in the one third of the whole genome at the 3\u2032 end (19.0 kb-29.7 kb). Regions encoding Orf10\u201311, Orf3/4, E, M and S protein had the highest mutation rates. A total of 15 PCR products (about 6.0 kb of the genome) including 11 fragments containing 12 known polymorphic sites and 4 fragments without identified polymorphic sites were cloned and sequenced. Results showed that 3 unique polymorphic sites of BJ202 (positions 13 804, 15 031 and 20 792) along with 3 other polymorphic sites (26 428, 26 477 and 27 243) all contained 2 kinds of nucleotides. It is interesting to find that position 18379 which has not been identified to be polymorphic in any of the other 115 published SARS-CoV genomes is actually a polymorphic site. The nucleotide composition of this site is A (8) to G (6). Among 116 SARS-CoV genomes, 18 types of deletions and 2 insertions were identified. Most of them were related to a 300 bp region (27 700\u201328 000) which encodes parts of the putative ORF9 and ORF10\u201311. A phylogenetic tree illustrating the divergence of whole BJ202 genome from 115 other completely sequenced SARS-CoVs was also constructed. BJ202 was phylogeneticly closer to BJ01 and LLJ-2004.", "qid": 37, "docid": "6vw88jib", "rank": 27, "score": 0.7885369062423706}, {"content": "Title: Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach Content: The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). However, initial testing of the drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. The present study highlights the genomic, proteomic, pathogenesis, and therapeutic strategies in SARS-CoV-2 infection. We have carried out sequence analysis of potential drug target proteins in SARS-CoV-2 and, compared them with SARS-CoV and MERS viruses. Analysis of mutations in the coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 has also been done. A detailed structural analysis of drug target proteins has been performed to gain insights into the mechanism of pathogenesis, structure-function relationships, and the development of structure-guided therapeutic approaches. The cytokine profiling and inflammatory signalling are different in the case of SARS-CoV-2 infection. We also highlighted possible therapies and their mechanism of action followed by clinical manifestation. Our analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, which makes available drugs ineffective.", "qid": 37, "docid": "1evug4fr", "rank": 28, "score": 0.7881324291229248}, {"content": "Title: Chasing the origin of SARS-CoV-2 in Canada\u2019s COVID-19 cases: A genomics study Content: The emergence and global spread of SARS-CoV-2 has had profound social and economic consequences and has shed light on the importance of continued and additional investment in global health and infectious disease surveillance. Identifying changes in viral genomes provides key insights into viral diversity, how viruses spread within populations, and viral strategies for evasion of host immune systems. Here we report twenty-five SARS-CoV-2 genome sequences collected from some of the first COVID-19 cases in eastern Ontario, Canada (March 18-30, 2020). The reported genomes belong to the S-clade (n=2) and G-clade (n=23) of SARS-CoV-2 and contain 45 polymorphic sites including one shared missense and three unique synonymous variants in the gene encoding the spike protein. A phylogenetic analysis enabled the tracing of viral origin and potential transmission into and within Canada. There may be as many as sixteen unique infection events represented in these samples, including at least three that were likely introduced from Europe and seven from the USA. In addition, four separate genomes are each shared by multiple patients, suggesting a common origin or community spread even during this early stage of infection. These results demonstrate how molecular epidemiology and evolutionary phylogenetics can help local health units track origins and vectors of spread for emerging diseases like SARS-CoV-2. Earlier detection and screening in this way could improve the effectiveness of regional public health interventions to prevent future pandemics.", "qid": 37, "docid": "8gtnbm1c", "rank": 29, "score": 0.7878807783126831}, {"content": "Title: Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach Content: The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). However, initial testing of the drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. The present review looks to highlight the differences in genomic, proteomic, pathogenesis, and therapeutic strategies of SARS-CoV-2. We have carried out sequence analysis of potential drug target proteins in SARS-CoV-2 and, compared them with SARS-CoV-1 and MERS viruses. Analysis of mutations in the coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 has also been done. A detailed structural analysis of drug target proteins was performed to gain insights into the mechanism of pathogenesis, structure-function relationships, and the development of structure-guided therapeutic approaches. The cytokine profiling and inflammatory signalling are different in the case of SARS-CoV-2 infection. We also highlighted possible therapies and their mechanism of action followed by clinical manifestation. Our analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, makes available drugs ineffective.", "qid": 37, "docid": "dfydh7sf", "rank": 30, "score": 0.7875882387161255}, {"content": "Title: Sequence analysis of travel-related SARS-CoV-2 cases in the Greater Geelong region, Australia Content: This study reports the sequence analysis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from infected individuals within the Greater Geelong region, Victoria, Australia. All but one individual had recently returned from travelling abroad, and all had clinical signs consistent with SARS-CoV-2 infection. SARS-CoV-2 belonging to three lineages were detected and represent separate introductions of the virus into the region. Sequence data were consistent with the recent travel history of each case. Full virus genome sequencing can play an important role in supporting local epidemiological tracing and monitoring for community transmission. Quality of the SARS-CoV-2 sequences obtained was highly dependent on appropriate sample collection and handling.", "qid": 37, "docid": "ni7dy8pt", "rank": 31, "score": 0.7871977686882019}, {"content": "Title: MicroGMT: A Mutation Tracker for SARS-CoV-2 and Other Microbial Genome Sequences Content: With the continued spread of SARS-CoV-2 virus around the world, researchers often need to quickly identify novel mutations in newly sequenced SARS-CoV-2 genomes for studying the molecular evolution and epidemiology of the virus. We have developed a Python package, MicroGMT, which takes either raw sequence reads or assembled genome sequences as input and compares against database sequences to identify and characterize indels and point mutations. Although our default setting is optimized for SARS-CoV-2 virus, the package can be also applied to any other microbial genomes. The software is freely available at Github URL https://github.com/qunfengdong/MicroGMT.", "qid": 37, "docid": "ypwo98k7", "rank": 32, "score": 0.7867175340652466}, {"content": "Title: Genome-Wide Identification and Characterization of Point Mutations in the SARS-CoV-2 Genome Content: OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has been rapidly spreading worldwide. Although the causal relationship among mutations and the features of SARS-CoV-2 such as rapid transmission, pathogenicity, and tropism, remains unclear, our results of genomic mutations in SARS-CoV-2 may help to interpret the interaction between genomic characterization in SARS-CoV-2 and infectivity with the host. METHODS: A total of 4,254 genomic sequences of SARS-CoV-2 were collected from the Global Initiative on Sharing all Influenza Data (GISAID). Multiple sequence alignment for phylogenetic analysis and comparative genomic approach for mutation analysis were conducted using Molecular Evolutionary Genetics Analysis (MEGA), and an in-house program based on Perl language, respectively. RESULTS: Phylogenetic analysis of SARS-CoV-2 strains indicated that there were 3 major clades including S, V, and G, and 2 subclades (G.1 and G.2). There were 767 types of synonymous and 1,352 types of non-synonymous mutation. ORF1a, ORF1b, S, and N genes were detected at high frequency, whereas ORF7b and E genes exhibited low frequency. In the receptor-binding domain (RBD) of the S gene, 11 non-synonymous mutations were observed in the region adjacent to the angiotensin converting enzyme 2 (ACE2) binding site. CONCLUSION: It has been reported that the rapid infectivity and transmission of SARS-CoV-2 associated with host receptor affinity are derived from several mutations in its genes. Without these genetic mutations to enhance evolutionary adaptation, species recognition, host receptor affinity, and pathogenicity, it would not survive. It is expected that our results could provide an important clue in understanding the genomic characteristics of SARS-CoV-2.", "qid": 37, "docid": "shn7vx3d", "rank": 33, "score": 0.7858618497848511}, {"content": "Title: Companion vaccine Bioinformatic design tool reveals limited functional genomic variability of SARS-Cov-2 Spike Receptor Binding Domain Content: Tracking the genetic variability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for several reasons, such as to identify target sequences to generate robust vaccines and neutralizing monoclonal antibodies; to track viral genetic temporal and geographic evolution; and to mine for viral variants associated with reduced or increased severity. Several online tools and bioinformatic analyses have been released for this purpose; four main viral clades have been described via phylogenetic analyses. Here, we present an open-source bioinformatic protocol focused on SARS-CoV-2 single mutations and minimal consensus sequence building as a companion vaccine design tool. Results on the whole GISAID sequence dataset at the time of the writing (April\u2013June 2020) confirms no high variability pressure on the viral genome in terms of quality and quantity of mutations. We then focused our analysis on the receptor-binding domain region of the spike protein and only found a few variants associated with particular geographic locations that should be tracked over time. Finally, additional immunogenomic analyses revealed some variation in mutated epitope MHC compatibility and T-cell recognition for most frequent human HLAs.", "qid": 37, "docid": "thwnmobo", "rank": 34, "score": 0.7856858968734741}, {"content": "Title: Genomic analysis of early SARS-CoV-2 strains introduced in Mexico Content: The COVID-19 pandemic has affected most countries in the world. Studying the evolution and transmission patterns in different countries is crucial to implement effective strategies for disease control and prevention. In this work, we present the full genome sequence for 17 SARS-CoV-2 isolates corresponding to the earliest sampled cases in Mexico. Global and local phylogenomics, coupled with mutational analysis, consistently revealed that these viral sequences are distributed within 2 known lineages, the SARS-CoV-2 lineage A/G, containing mostly sequences from North America, and the lineage B/S containing mainly sequences from Europe. Based on the exposure history of the cases and on the phylogenomic analysis, we characterized fourteen independent introduction events. Additionally, three cases with no travel history were identified. We found evidence that two of these cases represent local transmission cases occurring in Mexico during mid-March 2020, denoting the earliest events described in the country. Within this Mexican cluster, we also identified an H49Y amino acid change in the spike protein. This mutation is a homoplasy occurring independently through time and space, and may function as a molecular marker to follow on any further spread of these viral variants throughout the country. Our results depict the general picture of the SARS-CoV-2 variants introduced at the beginning of the outbreak in Mexico, setting the foundation for future surveillance efforts. This work is the result of the collaboration of five institutions into one research consortium: three public health institutes and two universities. From the beginning of this work, it was agreed that the experimental leader of each institution would share the first authorship. Those were the criteria followed to assign first co-first authorship in this manuscript. The order of the other authors was randomly assigned. IMPORTANCE Understanding the introduction, spread and establishment of SARS-CoV-2 within distinct human populations is crucial to implement effective control strategies as well as the evolution of the pandemics. In this work, we describe that the initial virus strains introduced in Mexico came from Europe and the United States and the virus was circulating locally in the country as early as mid-March. We also found evidence for early local transmission of strains having the mutation H49Y in the Spike protein, that could be further used as a molecular marker to follow viral spread within the country and the region.", "qid": 37, "docid": "le0ftbps", "rank": 35, "score": 0.7855536937713623}, {"content": "Title: Genomic analysis and comparative multiple sequences of SARS-CoV2 Content: BACKGROUND: China announced an outbreak of new coronavirus in the city of Wuhan on December 31, 2019; lash to now, the virus transmission has become pandemic worldwide. Severe cases from the Huanan Seafood Wholesale market in Wuhan were confirmed pneumonia with a novel coronavirus (2019-nCoV). Understanding the molecular mechanisms of genome selection and packaging is critical for developing antiviral strategies. Thus, we defined the correlation in 10 severe acute respiratory syndrome coronavirus (SARS-CoV2) sequences from different countries to analyze the genomic patterns of disease origin and evolution aiming for developing new control pandemic processes. METHODS: We apply genomic analysis to observe SARS-CoV2 sequences from GenBank (http://www.ncbi.nim.nih.gov/genebank/): MN 908947 (China, C1), MN985325 (USA: WA, UW), MN996527 (China, C2), MT007544 (Australia: Victoria, A1), MT027064 (USA: CA, UC), MT039890 (South Korea, K1), MT066175 (Taiwan, T1), MT066176 (Taiwan, T2), LC528232 (Japan, J1), and LC528233 (Japan, J2) for genomic sequence alignment analysis. Multiple Sequence Alignment by Clustalw (https://www.genome.jp/tools-bin/clustalw) web service is applied as our alignment tool. RESULTS: We analyzed 10 sequences from the National Center for Biotechnology Information (NCBI) database by genome alignment and found no difference in amino acid sequences within M and N proteins. There are two amino acid variances in the spike (S) protein region. One mutation found from the South Korea sequence is verified. Two possible \"L\" and \"S\" SNPs found in ORF1ab and ORF8 regions are detected. CONCLUSION: We performed genomic analysis and comparative multiple sequences of SARS-CoV2. Studies about the biological symptoms of SARS-CoV2 in clinic animals and humans will manipulate an understanding on the origin of pandemic crisis.", "qid": 37, "docid": "x1evu4w9", "rank": 36, "score": 0.78522789478302}, {"content": "Title: Identification of unique mutations in SARS-CoV-2 strains isolated from India suggests its attenuated pathotype Content: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first reported in Wuhan, China in November 2019 has developed into a pandemic since March 2020, causing substantial human casualties and economic losses. Studies on SARS-CoV-2 are being carried out at an unprecedented rate to tackle this threat. Genomics studies, in particular, are indispensable to elucidate the dynamic nature of the RNA genome of SARS-CoV-2. RNA viruses are marked by their unique ability to undergo high rates of mutation in their genome, much more frequently than their hosts, which diversifies their strengths qualifying them to elude host immune response and amplify drug resistance. In this study, we sequenced and analyzed the genomic information of the SARS-CoV-2 isolates from two infected Indian patients and explored the possible implications of point mutations in its biology. In addition to multiple point mutations, we found a remarkable similarity between relatively common mutations of 36-nucleotide deletion in ORF8 of SARS-CoV-2. Our results corroborate with the earlier reported 29-nucleotide deletion in SARS, which was frequent during the early stage of human-to-human transmission. The results will be useful to understand the biology of SARS-CoV-2 and itsattenuation for vaccine development.", "qid": 37, "docid": "fujejfwb", "rank": 37, "score": 0.785011887550354}, {"content": "Title: Molecular phylogeny of coronaviruses including human SARS-CoV Content: Phylogenetic tree of coronaviruses (CoVs) including the human SARS-associated virus is reconstructed from complete genomes by using our newly developed K-string composition approach. The relation of the human SARS-CoV to other coronaviruses, i.e. the rooting of the tree is suggested by choosing an appropriate outgroup. SARS-CoV makes a separate group closer but still distant from G2 (CoVs in mammalian host). The relation between different isolates of the human SARS virus is inferred by first constructing an ultrametric distance matrix from counting sequence variations in the genomes. The resulting tree is consistent with clinic relations between the SARS-CoV isolates. In addition to a larger variety of coronavirus genomes these results provide phylogenetic knowledge based on independent novel methodology as compared to recent phylogenetic studies on SARS-CoV.", "qid": 37, "docid": "iowyb7xs", "rank": 38, "score": 0.7845818996429443}, {"content": "Title: Unsupervised cluster analysis of SARS-CoV-2 genomes indicates that recent (June 2020) cases in Beijing are from a genetic subgroup that consists of mostly European and South(east) Asian samples, of which the latter are the most recent Content: Research efforts of the ongoing SARS-CoV-2 pandemic have focused on viral genome sequence analysis to understand how the virus spread across the globe. Here, we assess three recently identified SARS-CoV-2 genomes in Beijing from June 2020 and attempt to determine the origin of these genomes, made available in the GISAID database. The database contains fully or partially sequenced SARS-CoV-2 samples from laboratories around the world. Including the three new samples and excluding samples with missing annotations, we analyzed 7, 643 SARS-CoV-2 genomes. Using principal component analysis computed on a similarity matrix that compares all pairs of the SARS-CoV-2 nucleotide sequences at all loci simultaneously, using the Jaccard index, we find that the newly discovered virus genomes from Beijing are in a genetic cluster that consists mostly of cases from Europe and South(east) Asia. The sequences of the new cases are most related to virus genomes from a small number of cases from China (March 2020), cases from Europe (February to early May 2020), and cases from South(east) Asia (May to June 2020). These findings could suggest that the original cases of this genetic cluster originated from China in March 2020 and were re-introduced to China by transmissions from samples from South(east) Asia between April and June 2020.", "qid": 37, "docid": "4oa0gsos", "rank": 39, "score": 0.7839855551719666}, {"content": "Title: Monophyletic Relationship between Severe Acute Respiratory Syndrome Coronavirus and Group 2 Coronaviruses Content: Although primary genomic analysis has revealed that severe acute respiratory syndrome coronavirus (SARS CoV) is a new type of coronavirus, the different protein trees published in previous reports have provided no conclusive evidence indicating the phylogenetic position of SARS CoV. To clarify the phylogenetic relationship between SARS CoV and other coronaviruses, we compiled a large data set composed of 7 concatenated protein sequences and performed comprehensive analyses, using the maximum-likelihood, Bayesian-inference, and maximum-parsimony methods. All resulting phylogenetic trees displayed an identical topology and supported the hypothesis that the relationship between SARS CoV and group 2 CoVs is monophyletic. Relationships among all major groups were well resolved and were supported by all statistical analyses.", "qid": 37, "docid": "005b2j4b", "rank": 40, "score": 0.7839202880859375}, {"content": "Title: WHOLE-GENOME SEQUENCING AND DE NOVO ASSEMBLY OF A 2019 NOVEL CORONAVIRUS (SARS-COV-2) STRAIN ISOLATED IN VIETNAM Content: The pandemic COVID-19 caused by the zoonotic virus SARS-CoV-2 has devastated countries worldwide, infecting more than 4.5 million people and leading to more than 300,000 deaths. Whole genome sequencing (WGS) is an effective tool to monitor emerging strains and provide information for intervention, thus help to inform outbreak control decisions. Here, we reported the first effort to sequence and de novo assemble the whole genome of SARS-CoV-2 using PacBio\u2019s SMRT sequencing technology in Vietnam. We also presented the annotation results and a brief analysis of the variants found in our SARS-CoV-2 strain, which was isolated from a Vietnamese patient. The sequencing was successfully completed and de novo assembled in less than 30 hours, resulting in one contig with no gap and a length of 29,766 bp. All detected variants as compared to the NCBI reference were highly accurate as confirmed by Sanger sequencing. The results have shown the potential of long read sequencing to provide high quality WGS data to support public health responses, and advance understanding of this and future pandemics.", "qid": 37, "docid": "eoa3dkoz", "rank": 41, "score": 0.7833781242370605}, {"content": "Title: Metagenomic Analysis Reveals Clinical SARS-CoV-2 Infection and Bacterial or Viral Superinfection and Colonization Content: BACKGROUND: More than 2 months separated the initial description of SARS-CoV-2 and discovery of its widespread dissemination in the United States. Despite this lengthy interval, implementation of specific quantitative reverse transcription (qRT)-PCR-based SARS-CoV-2 tests in the US has been slow, and testing is still not widely available. Metagenomic sequencing offers the promise of unbiased detection of emerging pathogens, without requiring prior knowledge of the identity of the responsible agent or its genomic sequence. METHODS: To evaluate metagenomic approaches in the context of the current SARS-CoV-2 epidemic, laboratory-confirmed positive and negative samples from Seattle, WA were evaluated by metagenomic sequencing, with comparison to a 2019 reference genomic database created before the emergence of SARS-CoV-2. RESULTS: Within 36 h our results showed clear identification of a novel human Betacoronavirus, closely related to known Betacoronaviruses of bats, in laboratory-proven cases of SARS-CoV-2. A subset of samples also showed superinfection or colonization with human parainfluenza virus 3 or Moraxella species, highlighting the need to test directly for SARS-CoV-2 as opposed to ruling out an infection using a viral respiratory panel. Samples negative for SARS-CoV-2 by RT-PCR were also negative by metagenomic analysis, and positive for Rhinovirus A and C. Unlike targeted SARS-CoV-2 qRT-PCR testing, metagenomic analysis of these SARS-CoV-2 negative samples identified candidate etiological agents for the patients' respiratory symptoms. CONCLUSION: Taken together, these results demonstrate the value of metagenomic analysis in the monitoring and response to this and future viral pandemics.", "qid": 37, "docid": "lsowgp2e", "rank": 42, "score": 0.7831899523735046}, {"content": "Title: Children\u2019s Hospital Los Angeles COVID-19 Analysis Research Database (CARD) - A Resource for Rapid SARS-CoV-2 Genome Identification Using Interactive Online Phylogenetic Tools Content: Effective response to the Coronavirus Disease 2019 (COVID-19) pandemic requires genomic resources and bioinformatics tools for genomic epidemiology and surveillance studies that involve characterizing full-length viral genomes, identifying origins of infections, determining the relatedness of viral infections, performing phylogenetic analyses, and monitoring the continuous evolution of the SARS-CoV-2 viral genomes. The Children\u2019s Hospital, Los Angeles (CHLA) COVID-19 Analysis Research Database (CARD) (https://covid19.cpmbiodev.net/) is a comprehensive genomic resource that provides access to full-length SARS-CoV-2 viral genomes and associated meta-data for over 30,000 (as of May 20, 2020) isolates collected from global sequencing repositories and the sequencing performed at the Center for Personalized Medicine (CPM) at CHLA. Reference phylogenetic trees of global and USA viral isolates were constructed and are periodically updated using selected high quality SARS-CoV-2 genome sequences. These provide the baseline and analytical context for identifying the origin of a viral infection, as well as the relatedness of SARS-CoV-2 genomes of interest. A web-based and interactive Phylogenetic Tree Browser supports flexible tree manipulation and advanced analysis based on keyword search while highlighting time series animation, as well as subtree export for graphical representation or offline exploration. A Virus Genome Tracker accepts complete or partial SARS-CoV-2 genome sequence, compares it against all available sequences in the database (>30,000 at time of writing), detects and annotates the variants, and places the new viral isolate within the global or USA phylogenetic contexts based upon variant profiles and haplotype comparisons, in a few seconds. The generated analysis can potentially aid in genomic surveillance to trace the transmission of any new infection. Using CHLA CARD, we demonstrate the identification of a candidate outbreak point where 13 of 31 CHLA internal isolates may have originated. We also discovered multiple indels of unknown clinical significance in the orf3a gene, and revealed a number of USA-specific variants and haplotypes.", "qid": 37, "docid": "2kbi9drl", "rank": 43, "score": 0.7828604578971863}, {"content": "Title: Genetic Diversity and Genomic Epidemiology of SARS-COV-2 in Morocco Content: COVID-A9 is an infection disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), declared as a pandemic due to its rapid expansion worldwide. In this study we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 using 22 virus genome sequences reported by three different laboratories in Morocco till the date 07/06/2020 as well as (40366) virus genomes from all around the world. The SARS-CoV-2 genomes from Moroccan patients revealed 62 mutations of which 30 were missense mutations. The mutations Spike_D614G and NSP12_P323L were present in all the 22 analyzed sequences, followed by N_G204R and N_R203K which occurred in 9 among the 22 sequences. The mutations NSP10_R134S, NSP15_D335N, NSP16_I169L, NSP3_L431H, NSP3_P1292L and Spike_V6F occurred one time in our sequences with no record in other sequence worldwide. These mutations should be investigated to figure out their potential effects on all around the world virulence. Phylogenetic analyses revealed that Moroccan SARS-CoV-2 genomes included 9 viruses pertaining to clade 20A, 9 to clade 20B and 2 to clade 20C. This finding suggest that the epidemic spread in Morocco did not show a predominant SARS-CoV-2 route. For multiple and unrelated introductions of SARS-CoV-2 into Morocco via different routes have occurred, giving rise to the diversity of virus genomes in the country. Furthermore, very likely, the SARS-CoV-2 virus circulated in cryptic way in Morocco starting from the fifteen January before the discovering of the first case the second of March.", "qid": 37, "docid": "zb1pzdd0", "rank": 44, "score": 0.7824839353561401}, {"content": "Title: Controlling the SARS-CoV-2 outbreak, insights from large scale whole genome sequences generated across the world Content: Background SARS-CoV-2 most likely evolved from a bat beta-coronavirus and started infecting humans in December 2019. Since then it has rapidly infected people around the world, with more than 4.5 million confirmed cases by the middle of May 2020. Early genome sequencing of the virus has enabled the development of molecular diagnostics and the commencement of therapy and vaccine development. The analysis of the early sequences showed relatively few evolutionary selection pressures. However, with the rapid worldwide expansion into diverse human populations, significant genetic variations are becoming increasingly likely. The current limitations on social movement between countries also offers the opportunity for these viral variants to become distinct strains with potential implications for diagnostics, therapies and vaccines. Methods We used the current sequencing archives (NCBI and GISAID) to investigate 15,487 whole genomes, looking for evidence of strain diversification and selective pressure. Results We used 6,294 SNPs to build a phylogenetic tree of SARS-CoV-2 diversity and noted strong evidence for the existence of two major clades and six sub-clades, unevenly distributed across the world. We also noted that convergent evolution has potentially occurred across several locations in the genome, showing selection pressures, including on the spike glycoprotein where we noted a potentially critical mutation that could affect its binding to the ACE2 receptor. We also report on mutations that could prevent current molecular diagnostics from detecting some of the sub-clades. Conclusion The worldwide whole genome sequencing effort is revealing the challenge of developing SARS-CoV-2 containment tools suitable for everyone and the need for data to be continually evaluated to ensure accuracy in outbreak estimations.", "qid": 37, "docid": "tutit2bc", "rank": 45, "score": 0.7823876738548279}, {"content": "Title: Metagenomic analysis reveals clinical SARS-CoV-2 infection and bacterial or viral superinfection and colonization Content: BACKGROUND: More than two months separated the initial description of SARS-CoV-2 and discovery of its widespread dissemination in the United States. Despite this lengthy interval, implementation of specific quantitative reverse transcription (qRT)-PCR-based SARS-CoV-2 tests in the US has been slow, and testing is still not widely available. Metagenomic sequencing offers the promise of unbiased detection of emerging pathogens, without requiring prior knowledge of the identity of the responsible agent or its genomic sequence. METHODS: To evaluate metagenomic approaches in the context of the current SARS-CoV-2 epidemic, laboratory-confirmed positive and negative samples from Seattle, Washington were evaluated by metagenomic sequencing, with comparison to a 2019 reference genomic database created before the emergence of SARS-CoV-2. RESULTS: Within 36 hours our results showed clear identification of a novel human Betacoronavirus, closely related to known Betacoronaviruses of bats, in laboratory-proven cases of SARS-CoV-2. A subset of samples also showed superinfection or colonization with human parainfluenza virus 3 or Moraxella species, highlighting the need to test directly for SARS-CoV-2 as opposed to ruling out an infection using a viral respiratory panel. Samples negative for SARS-CoV-2 by RT-PCR were also negative by metagenomic analysis, and positive for Rhinovirus A and C. Unlike targeted SARS-CoV-2 qRT-PCR testing, metagenomic analysis of these SARS-CoV-2 negative samples identified candidate etiological agents for the patients\u2019 respiratory symptoms. CONCLUSION: Taken together, these results demonstrate the value of metagenomic analysis in the monitoring and response to this and future viral pandemics.", "qid": 37, "docid": "m0fjt483", "rank": 46, "score": 0.7817026972770691}, {"content": "Title: Emergence of multiple variants of SARS-CoV-2 with signature structural changes Content: This study explores the divergence pattern of SARS-CoV-2 using whole genome sequences of the isolates from various COVID-19 affected countries. The phylogenomic analysis indicates the presence of at least four distinct groups of the SARS-CoV-2 genomes. The emergent groups have been found to be associated with signature structural changes in specific proteins. Also, this study reveals the differential levels of divergence patterns for the protein coding regions. Moreover, we have predicted the impact of structural changes on a couple of important viral proteins via structural modelling techniques. This study further advocates for more viral genetic studies with associated clinical outcomes and hosts\u2019 response for better understanding of SARS-CoV-2 pathogenesis enabling better mitigation of this pandemic situation.", "qid": 37, "docid": "bu1bc2bi", "rank": 47, "score": 0.7813501358032227}, {"content": "Title: Phylogenomic proximity and comparative proteomic analysis of SARS-CoV-2 Content: The coronavirus disease (COVID-19) belongs to the family Severe Acute Respiratory Syndrome (SARS-CoV). It can be more severe for some persons and can lead to pneumonia or breathing difficulties resulting in the death of immune-compromised patients. We performed a phylogenomic and phylogeographic tree from the collected datasets. Phylogenomic analysis or sequence-based phylogeny showed an evolutionary relationship between the geographical strains. The phylogenomic tree grouped into two major clades consists of various isolates of SARS-CoV-2 and Bat SARS-like coronavirus, Bat coronavirus, and Pangolin coronavirus. The phylogenetic neighbor of newly sequenced Indian strains (Accession: MT012098.1, MT050493.1) was revealed to identify the variations between the nCoV-19 strains. The results showed keen evidence that SARS-CoV-2 has evolved from Bat SARS-like coronavirus. The evolutionary history and comparative proteomic analysis provide a new avenue for the current scientific research related to the coronavirus.", "qid": 37, "docid": "ltar1aa5", "rank": 48, "score": 0.781314492225647}, {"content": "Title: Genomic Analysis of Early SARS-CoV-2 Variants Introduced in Mexico Content: The COVID-19 pandemic has affected most countries in the world. Studying the evolution and transmission patterns in different countries is crucial to implement effective strategies for disease control and prevention. In this work, we present the full genome sequence for 17 SARS-CoV-2 isolates corresponding to the earliest sampled cases in Mexico. Global and local phylogenomics, coupled with mutational analysis, consistently revealed that these viral sequences are distributed within 2 known lineages, the SARS-CoV-2 lineage A/G, containing mostly sequences from North America, and the lineage B/S containing mainly sequences from Europe. Based on the exposure history of the cases and on the phylogenomic analysis, we characterized fourteen independent introduction events. Additionally, three cases with no travel history were identified. We found evidence that two of these cases represent local transmission cases occurring in Mexico during mid-March 2020, denoting the earliest events described for the country. Within this local transmission cluster, we also identified the H49Y amino acid change in the Spike protein. This mutation is a homoplasy occurring independently through time and space, and may function as a molecular marker to follow on any further spread of these viral variants throughout the country. Our results depict the general picture of the SARS-CoV-2 variants introduced at the beginning of the outbreak in Mexico, setting the foundation for future surveillance efforts.IMPORTANCE Understanding the introduction, spread and establishment of SARS-CoV-2 within distinct human populations is crucial to implement effective control strategies as well as the evolution of the pandemics. In this work, we describe that the initial virus strains introduced in Mexico came from Europe and the United States and the virus was circulating locally in the country as early as mid-March. We also found evidence for early local transmission of strains having the mutation H49Y in the Spike protein, that could be further used as a molecular marker to follow viral spread within the country and the region.", "qid": 37, "docid": "1yf5y06o", "rank": 49, "score": 0.7812095880508423}, {"content": "Title: Genomic Analysis of Early SARS-CoV-2 Variants Introduced in Mexico. Content: The COVID-19 pandemic has affected most countries in the world. Studying the evolution and transmission patterns in different countries is crucial to implement effective strategies for disease control and prevention. In this work, we present the full genome sequence for 17 SARS-CoV-2 isolates corresponding to the earliest sampled cases in Mexico. Global and local phylogenomics, coupled with mutational analysis, consistently revealed that these viral sequences are distributed within 2 known lineages, the SARS-CoV-2 lineage A/G, containing mostly sequences from North America, and the lineage B/S containing mainly sequences from Europe. Based on the exposure history of the cases and on the phylogenomic analysis, we characterized fourteen independent introduction events. Additionally, three cases with no travel history were identified. We found evidence that two of these cases represent local transmission cases occurring in Mexico during mid-March 2020, denoting the earliest events described for the country. Within this local transmission cluster, we also identified the H49Y amino acid change in the Spike protein. This mutation is a homoplasy occurring independently through time and space, and may function as a molecular marker to follow on any further spread of these viral variants throughout the country. Our results depict the general picture of the SARS-CoV-2 variants introduced at the beginning of the outbreak in Mexico, setting the foundation for future surveillance efforts.IMPORTANCE Understanding the introduction, spread and establishment of SARS-CoV-2 within distinct human populations is crucial to implement effective control strategies as well as the evolution of the pandemics. In this work, we describe that the initial virus strains introduced in Mexico came from Europe and the United States and the virus was circulating locally in the country as early as mid-March. We also found evidence for early local transmission of strains having the mutation H49Y in the Spike protein, that could be further used as a molecular marker to follow viral spread within the country and the region.", "qid": 37, "docid": "i29eufyo", "rank": 50, "score": 0.7812095880508423}, {"content": "Title: CoV Genome Tracker: tracing genomic footprints of Covid-19 pandemic Content: Summary Genome sequences constitute the primary evidence on the origin and spread of the 2019-2020 Covid-19 pandemic. Rapid comparative analysis of coronavirus SARS-CoV-2 genomes is critical for disease control, outbreak forecasting, and developing clinical interventions. CoV Genome Tracker is a web portal dedicated to trace Covid-19 outbreaks in real time using a haplotype network, an accurate and scalable representation of genomic changes in a rapidly evolving population. We resolve the direction of mutations by using a bat-associated genome as outgroup. At a broader evolutionary time scale, a companion browser provides gene-by-gene and codon-by-codon evolutionary rates to facilitate the search for molecular targets of clinical interventions. Availability and Implementation CoV Genome Tracker is publicly available at http://cov.genometracker.org and updated weekly with the data downloaded from GISAID (http://gisaid.org). The website is implemented with a custom JavaScript script based on jQuery (https://jquery.com) and D3-force (https://github.com/d3/d3-force). Contact weigang@genectr.hunter.cuny.edu, City University of New York, Hunter College Supplementary Information All supporting scripts developed in JavaScript, Python, BASH, and PERL programming languages are available as Open Source at the GitHub repository https://github.com/weigangq/cov-browser.", "qid": 37, "docid": "abqrh2aw", "rank": 51, "score": 0.7809453010559082}, {"content": "Title: Insights into SARS-CoV-2, the Coronavirus Underlying COVID-19: Recent Genomic Data and the Development of Reverse Genetics Systems Content: The emergence and rapid worldwide spread of a novel pandemic of acute respiratory disease - eventually named coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO) - across the human population has raised great concerns. It prompted a mobilization around the globe to study the underlying pathogen, a close relative of severe acute respiratory syndrome coronavirus (SARS-CoV) called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Numerous genome sequences of SARS-CoV-2 are now available and in-depth analyses are advancing. These will allow detailed characterization of sequence and protein functions, including comparative studies. Care should be taken when inferring function from sequence information alone, and reverse genetics systems can be used to unequivocally identify key features. For example, the molecular markers of virulence, host range and transmissibility of SARS-CoV-2 can be compared to those of related viruses in order to shed light on the biology of this emerging pathogen. Here, we summarize some recent insights from genomic studies and strategies for reverse genetics systems to generate recombinant viruses, which will be useful to investigate viral genome properties and evolution.", "qid": 37, "docid": "lx2kxv3t", "rank": 52, "score": 0.7805300951004028}, {"content": "Title: Insights into SARS-CoV-2, the Coronavirus Underlying COVID-19: Recent Genomic Data and the Development of Reverse Genetics Systems. Content: The emergence and rapid worldwide spread of a novel pandemic of acute respiratory disease - eventually named coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO) - across the human population has raised great concerns. It prompted a mobilization around the globe to study the underlying pathogen, a close relative of severe acute respiratory syndrome coronavirus (SARS-CoV) called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Numerous genome sequences of SARS-CoV-2 are now available and in-depth analyses are advancing. These will allow detailed characterization of sequence and protein functions, including comparative studies. Care should be taken when inferring function from sequence information alone, and reverse genetics systems can be used to unequivocally identify key features. For example, the molecular markers of virulence, host range and transmissibility of SARS-CoV-2 can be compared to those of related viruses in order to shed light on the biology of this emerging pathogen. Here, we summarize some recent insights from genomic studies and strategies for reverse genetics systems to generate recombinant viruses, which will be useful to investigate viral genome properties and evolution.", "qid": 37, "docid": "2qxqq071", "rank": 53, "score": 0.7805300951004028}, {"content": "Title: Assessing uncertainty in the rooting of the SARS-CoV-2 phylogeny Content: The rooting of the SARS-CoV-2 phylogeny is important for understanding the origin and early spread of the virus. Previously published phylogenies have used different rootings that do not always provide consistent results. We use several different strategies for rooting the SARS-CoV-2 tree and provide measures of statistical uncertainty for all methods. We show that methods based on the molecular clock tend to place the root in the B clade, while methods based on outgroup rooting tend to place the root in the A clade. The results from the two approaches are statistically incompatible, possibly as a consequence of deviations from a molecular clock or excess back-mutations. We also show that none of the methods provide strong statistical support for the placement of the root in any particular edge of the tree. Our results suggest that inferences on the origin and early spread of SARS-CoV-2 based on rooted trees should be interpreted with caution.", "qid": 37, "docid": "55loucvc", "rank": 54, "score": 0.7799498438835144}, {"content": "Title: Evolutionary analysis of SARS-CoV-2: how mutation of Non-Structural Protein 6 (NSP6) could affect viral autophagy Content: BACKGROUND: SARS-CoV-2 is a new coronavirus that has spread globally, infecting more than 150000 people, and being declared pandemic by the WHO. We provide here bio-informatic, evolutionary analysis of 351 available sequences of its genome with the aim of mapping genome structural variations and the patterns of selection. METHODS: A Maximum likelihood tree has been built and selective pressure has been investigated in order to find any mutation developed during the SARS-CoV-2 epidemic that could potentially affect clinical evolution of the infection. FINDING: We have found in more recent isolates the presence of two mutations affecting the Non-Structural Protein 6 (NSP6) and the Open Reding Frame10 (ORF 10) adjacent regions. Amino acidic change stability analysis suggests both mutations could confer lower stability of the protein structures. INTERPRETATION: One of the two mutations, likely developed within the genome during virus spread, could affect virus intracellular survival. Genome follow-up of SARS-CoV-2 spread is urgently needed in order to identify mutations that could significantly modify virus pathogenicity.", "qid": 37, "docid": "su5tlg3l", "rank": 55, "score": 0.7798271775245667}, {"content": "Title: Whole genome and phylogenetic analysis of two SARS-CoV-2 strains isolated in Italy in January and February 2020: additional clues on multiple introductions and further circulation in Europe Content: Whole genome sequences of SARS-CoV-2 obtained from two patients, a Chinese tourist visiting Rome and an Italian, were compared with sequences from Europe and elsewhere. In a phylogenetic tree, the Italian patient\u2019s sequence clustered with sequences from Germany while the tourist\u2019s sequence clustered with other European sequences. Some additional European sequences in the tree segregated outside the two clusters containing the patients\u2019 sequences. This suggests multiple SARS-CoV-2 introductions in Europe or virus evolution during circulation.", "qid": 37, "docid": "48ul34xo", "rank": 56, "score": 0.7796057462692261}, {"content": "Title: Molecular analysis of several in-house rRT-PCR protocols for SARS-CoV-2 detection in the context of genetic variability of the virus in Colombia Content: The COVID-19 pandemic caused by SARS-CoV-2 is a public health problem unprecedented in the recent history of humanity. Different in-house real-time RT-PCR (rRT-PCR) methods for SARS-CoV-2 diagnosis and the appearance of genomes with mutations in primer regions have been reported. Hence, whole-genome data from locally-circulating SARS-CoV-2 strains contribute to the knowledge of its global variability and the development and fine tuning of diagnostic protocols. To describe the genetic variability of Colombian SARS-CoV-2 genomes in hybridization regions of oligonucleotides of the main in-house methods for SARS-CoV-2 detection, RNA samples with confirmed SARS-CoV-2 molecular diagnosis were processed through next-generation sequencing. Primers/probes sequences from 13 target regions for SARS-CoV-2 detection suggested by 7 institutions and consolidated by WHO during the early stage of the pandemic were aligned with Muscle tool to assess the genetic variability potentially affecting their performance. Finally, the corresponding codon positions at the 3' end of each primer, the open reading frame inspection was identified for each gene/protein product. Complete SARS-CoV-2 genomes were obtained from 30 COVID-19 cases, representative of the current epidemiology in the country. Mismatches between at least one Colombian sequence and five oligonucleotides targeting the RdRP and N genes were observed. The 3' end of 4 primers aligned to the third codon position, showed high risk of nucleotide substitution and potential mismatches at this critical position. Genetic variability was detected in Colombian SARS-CoV-2 sequences in some of the primer/probe regions for in-house rRT-PCR diagnostic tests available at WHO COVID-19 technical guidelines; its impact on the performance and rates of false-negative results should be experimentally evaluated. The genomic surveillance of SARS-CoV-2 is highly recommended for the early identification of mutations in critical regions and to issue recommendations on specific diagnostic tests to ensure the coverage of locally-circulating genetic variants.", "qid": 37, "docid": "vwzdijgg", "rank": 57, "score": 0.7793850898742676}, {"content": "Title: Whole genome and phylogenetic analysis of two SARS-CoV-2 strains isolated in Italy in January and February 2020: additional clues on multiple introductions and further circulation in Europe Content: Whole genome sequences of SARS-CoV-2 obtained from two patients, a Chinese tourist visiting Rome and an Italian, were compared with sequences from Europe and elsewhere. In a phylogenetic tree, the Italian patient's sequence clustered with sequences from Germany while the tourist's sequence clustered with other European sequences. Some additional European sequences in the tree segregated outside the two clusters containing the patients' sequences. This suggests multiple SARS-CoV-2 introductions in Europe or virus evolution during circulation.", "qid": 37, "docid": "o6rr66kc", "rank": 58, "score": 0.779362678527832}, {"content": "Title: Genomic Analysis and Comparative Multiple Sequence of SARS-CoV2. Content: BACKGROUND China announced an outbreak of new coronavirus in the city of Wuhan on December 31, 2019; lash to now, the virus transmission has become pandemic worldwide. Severe cases from Huanan Seafood Wholesale market in Wuhan were confirmed pneumonia with a novel coronavirus. (2019-nCoV). Understanding the molecular mechanisms of genome selection and packaging is critical for developing antiviral strategies. Thus, we defined the correlation in ten SARS-CoV2 sequences from different countries to analyze the genomic patterns of disease origin and evolution aiming for development new control pandemic processes. METHODS We apply genomic analysis to observe SARS-Co-V2 sequences from GenBank (http:// www.ncbi.nim.nih.gov/genebank/): MN 908947 China, C1), MN985325 (USA:WA, UW), MN996527 (China, C2), MT007544 (Australia:Victoria, A1), MT027064 (USA:CA, UC), MT039890 (South Korea, K1), MT066175 (Taiwan,T1), MT066176 (Taiwan, T2), LC528232 (Japan, J1), and LC528233 (Japan, J2) for genomic sequence alignment an analysis. Multiple Sequence Alignment by Clustalw (https://www.genome.jp/tools-bin/clustalw) web is applied as our alignment tool. RESULTS We analyze ten sequences from NCBI database by genome alignment and find no difference in amino acid sequences within M and N proteins. There are two amino acid variances in Spike protein region. One mutation found from south Korea sequence is verified. Two possible \"L\" and \"S\" SNP found in ORF1ab and ORF8 regions are detected CONCLUSION:: We perform genomic analysis and comparative multiple sequence of SARS-CoV-2. Studies about the biological symptoms of SARS-CoV-2 in clinic animal and humans will manipulate an understanding the origin of pandemic crisis.", "qid": 37, "docid": "zzi2xv3p", "rank": 59, "score": 0.7792105674743652}, {"content": "Title: Molecular analysis of several in-house rRT-PCR protocols for SARS-CoV-2 detection in the context of genetic variability of the virus in Colombia. Content: The COVID-19 pandemic caused by SARS-CoV-2 is a public health problem unprecedented in the recent history of humanity. Different in-house real-time RT-PCR (rRT-PCR) methods for SARS-CoV-2 diagnosis and the appearance of genomes with mutations in primer regions have been reported. Hence, whole-genome data from locally-circulating SARS-CoV-2 strains contribute to the knowledge of its global variability and the development and fine-tuning of diagnostic protocols. To describe the genetic variability of Colombian SARS-CoV-2 genomes in hybridization regions of oligonucleotides of the main in-house methods for SARS-CoV-2 detection, RNA samples with confirmed SARS-CoV-2 molecular diagnosis were processed through next-generation sequencing. Primers/probes sequences from 13 target regions for SARS-CoV-2 detection suggested by 7 institutions and consolidated by WHO during the early stage of the pandemic were aligned with Muscle tool to assess the genetic variability potentially affecting their performance. Finally, the corresponding codon positions at the 3' end of each primer, the open reading frame inspection was identified for each gene/protein product. Complete SARS-CoV-2 genomes were obtained from 30 COVID-19 cases, representative of the current epidemiology in the country. Mismatches between at least one Colombian sequence and five oligonucleotides targeting the RdRP and N genes were observed. The 3' end of 4 primers aligned to the third codon position, showed high risk of nucleotide substitution and potential mismatches at this critical position. Genetic variability was detected in Colombian SARS-CoV-2 sequences in some of the primer/probe regions for in-house rRT-PCR diagnostic tests available at WHO COVID-19 technical guidelines; its impact on the performance and rates of false-negative results should be experimentally evaluated. The genomic surveillance of SARS-CoV-2 is highly recommended for the early identification of mutations in critical regions and to issue recommendations on specific diagnostic tests to ensure the coverage of locally-circulating genetic variants.", "qid": 37, "docid": "gs9zno1d", "rank": 60, "score": 0.7790900468826294}, {"content": "Title: Molecular epidemiology of the coronavirus associated with severe acute respiratory syndrome: a review of data from the Chinese University of Hong Kong. Content: The epidemic of the severe acute respiratory syndrome (SARS) has swept through the globe with more than 8000 reported probable cases. In Hong Kong, the hardest hit areas included our teaching hospital and the Amoy Gardens apartment complex. A novel coronavirus, SARS-coronavirus (SARS-CoV), with a single-stranded plus sense RNA genome, was promptly implicated as the causative agent and subsequently fulfilled Koch's postulates. To aid the understanding of SARS-CoV, groups of investigators rapidly sequenced viral isolates around the world. We were the third group in the world to release the complete SARS-CoV genome sequence (isolate CUHK-W1) on the world-wide web. With other isolates from patients of distinct epidemiological backgrounds, we additionally sequenced four complete (CUHK-Su10, CUHK-AG01, CUHK-AG02, CUHK-AG03) and two partial SARS-CoV genomes. The reviewed data obtained from representative patients from the hospital and community outbreaks has documented the evolution of the virus in this epidemic. Their sequence variations also revealed a remarkable epidemiological correlation. We demonstrate that sequence variations in the SARS-CoV genome can be applied as a powerful molecular tool in tracing the route of transmission, when used adjunctively with standard epidemiology.", "qid": 37, "docid": "f54wxips", "rank": 61, "score": 0.7789856195449829}, {"content": "Title: Molecular analysis of several in-house rRT-PCR protocols for SARS-CoV-2 detection in the context of genetic variability of the virus in Colombia Content: The COVID-19 pandemic caused by SARS-CoV-2 is a public health problem unprecedented in the recent history of humanity. Different in-house real-time RT-PCR (rRT-PCR) methods for SARS-CoV-2 diagnosis and the appearance of genomes with mutations in primer regions have been reported. Hence, whole-genome data from locally-circulating SARS-CoV-2 strains contribute to the knowledge of its global variability and the development and fine tuning of diagnostic protocols. To describe the genetic variability of Colombian SARS-CoV-2 genomes in hybridization regions of oligonucleotides of the main in-house methods for SARS-CoV-2 detection, RNA samples with confirmed SARS-CoV-2 molecular diagnosis were processed through next-generation sequencing. Primers/probes sequences from 13 target regions for SARS-CoV-2 detection suggested by 7 institutions and consolidated by WHO during the early stage of the pandemic were aligned with Muscle tool to assess the genetic variability potentially affecting their performance. Finally, the corresponding codon positions at the 3\u2032 end of each primer, the open reading frame inspection was identified for each gene/protein product. Complete SARS-CoV-2 genomes were obtained from 30 COVID-19 cases, representative of the current epidemiology in the country. Mismatches between at least one Colombian sequence and five oligonucleotides targeting the RdRP and N genes were observed. The 3\u2032 end of 4 primers aligned to the third codon position, showed high risk of nucleotide substitution and potential mismatches at this critical position. Genetic variability was detected in Colombian SARS-CoV-2 sequences in some of the primer/probe regions for in-house rRT-PCR diagnostic tests available at WHO COVID-19 technical guidelines; its impact on the performance and rates of false-negative results should be experimentally evaluated. The genomic surveillance of SARS-CoV-2 is highly recommended for the early identification of mutations in critical regions and to issue recommendations on specific diagnostic tests to ensure the coverage of locally-circulating genetic variants.", "qid": 37, "docid": "kr3y2k25", "rank": 62, "score": 0.7788931131362915}, {"content": "Title: Comparative genomics suggests limited variability and similar evolutionary patterns between major clades of SARS-CoV-2 Content: Phylogenomic analysis of SARS-CoV-2 as available from publicly available repositories suggests the presence of 3 prevalent groups of viral episomes (super-clades), which are mostly associated with outbreaks in distinct geographic locations (China, USA and Europe). While levels of genomic variability between SARS-CoV-2 isolates are limited, to our knowledge, it is not clear whether the observed patterns of variability in viral super-clades reflect ongoing adaptation of SARS-CoV-2, or merely genetic drift and founder effects. Here, we analyze more than 1100 complete, high quality SARS-CoV-2 genome sequences, and provide evidence for the absence of distinct evolutionary patterns/signatures in the genomes of the currently known major clades of SARS-CoV-2. Our analyses suggest that the presence of distinct viral episomes at different geographic locations are consistent with founder effects, coupled with the rapid spread of this novel virus. We observe that while cross species adaptation of the virus is associated with hypervariability of specific protein coding regions (including the RDB domain of the spike protein), the more variable genomic regions between extant SARS-CoV-2 episomes correspond with the 3\u2019 and 5\u2019 UTRs, suggesting that at present viral protein coding genes should not be subjected to different adaptive evolutionary pressures in different viral strains. Although this study can not be conclusive, we believe that the evidence presented here is strongly consistent with the notion that the biased geographic distribution of SARS-CoV-2 isolates should not be associated with adaptive evolution of this novel pathogen.", "qid": 37, "docid": "uubndgio", "rank": 63, "score": 0.7785372138023376}, {"content": "Title: Whole Genome Sequencing of SARS-CoV-2: Adapting Illumina Protocols for Quick and Accurate Outbreak Investigation During a Pandemic Content: The COVID-19 pandemic spread very fast around the world. A few days after the first detected case in South Africa, an infection started a large hospital outbreak in Durban, KwaZulu-Natal. Phylogenetic analysis of SARS-CoV-2 genomes can be used to trace the path of transmission within a hospital. It can also identify the source of the outbreak and provide lessons to improve infection prevention and control strategies. In this manuscript, we outline the obstacles we encountered in order to genotype SARS-CoV-2 in real-time during an urgent outbreak investigation. In this process, we encountered problems with the length of the original genotyping protocol, reagent stockout and sample degradation and storage. However, we managed to set up three different library preparation methods for sequencing in Illumina. We also managed to decrease the hands on library preparation time from twelve to three hours, which allowed us to complete the outbreak investigation in just a few weeks. We also fine-tuned a simple bioinformatics workflow for the assembly of high-quality genomes in real-time. In order to allow other laboratories to learn from our experience, we released all of the library preparation and bioinformatics protocols publicly and distributed them to other laboratories of the South African Network for Genomics Surveillance (SANGS) consortium.", "qid": 37, "docid": "lsqg65ez", "rank": 64, "score": 0.7783544063568115}, {"content": "Title: Genomics of Indian SARS-CoV-2: Implications in genetic diversity, possible origin and spread of virus Content: World Health Organization (WHO) declared COVID-19 as a pandemic disease on March 11, 2020. Comparison of genome sequences from diverse locations allows us to identify the genetic diversity among viruses which would help in ascertaining viral virulence, disease pathogenicity, origin and spread of the SARS-CoV-2 between countries. The aim of this study is to ascertain the genetic diversity among Indian SARS-CoV-2 isolates. Initial examination of the phylogenetic data of SARS-CoV-2 genomes (n=3123) from different continents deposited at GISAID (Global Initiative on Sharing All Influenza Data) revealed multiple origin for Indian isolates. An in-depth analysis of 449 viral genomes derived from samples representing countries from USA, Europe, China, East Asia, South Asia, Oceania, Middle East regions and India revealed that most Indian samples are divided into two clusters (A and B) with cluster A showing more similarity to samples from Oceania and Kuwait and the cluster B grouping with countries from Europe, Middle East and South Asia. Diversity analysis of viral clades, which are characterized by specific non-synonymous mutations in viral proteins, discovered that the cluster A Indian samples belong to I clade (V378I in ORF1ab), which is an Oceania clade with samples having Iran connections and the cluster B Indian samples belong to G clade (D614G in Spike protein), which is an European clade. Thus our study identifies that the Indian SARS-CoV-2 viruses belong to I and G clades with potential origin to be countries mainly from Oceania, Europe, Middle East and South Asia regions, which strongly implying the spread of virus through most travelled countries. The study also emphasizes the importance of pathogen genomics through phylogenetic analysis to discover viral genetic diversity and understand the viral transmission dynamics with eventual grasp on viral virulence and disease pathogenesis.", "qid": 37, "docid": "i758v1vb", "rank": 65, "score": 0.7782133221626282}, {"content": "Title: COVID-19 Variants Database: A repository for Human SARS-CoV-2 Polymorphism Data Content: COVID-19 is a newly communicable disease with a catastrophe outbreak that affects all over the world. We retrieved about 8,781 nucleotide fragments and complete genomes of SARS-CoV-2 reported from sixty-four countries. The CoV-2 reference genome was obtained from the National Genomics Data Center (NGDC), GISAID, and NCBI Genbank. All the sequences were aligned against reference genomes using Clustal Omega and variants were called using in-house built Python script. We intend to establish a user-friendly online resource to visualize the variants in the viral genome along with the Primer Infopedia. After analyzing and filtering the data globally, it was made available to the public. The detail of data available to the public includes mutations from 5688 SARS-CoV-2 sequences curated from 91 regions. This database incorporated 39920 mutations over 3990 unique positions. According to the translational impact, these mutations include 11829 synonymous mutations including 681 synonymous frameshifts and 21701 nonsynonymous mutations including 10 nonsynonymous frameshifts. Development of SARS-CoV-2 mutation genome browsers is a fundamental step obliging towards the virus surveillance, viral detection, and development of vaccine and therapeutic drugs. The SARS-COV-2 mutation browser is available at http://covid-19.dnageography.com.", "qid": 37, "docid": "r0gr0bhl", "rank": 66, "score": 0.7781198024749756}, {"content": "Title: Large scale genomic analysis of 3067 SARS-CoV-2 genomes reveals a clonal geo-distribution and a rich genetic variations of hotspots mutations Content: In late December 2019, an emerging viral infection COVID-19 was identified in Wuhan, China, and became a global pandemic. Characterization of the genetic variants of SARS-CoV-2 is crucial in following and evaluating it spread across countries. In this study, we collected and analyzed 3,067 SARS-CoV-2 genomes isolated from 55 countries during the first three months after the onset of this virus. Using comparative genomics analysis, we traced the profiles of the whole-genome mutations and compared the frequency of each mutation in the studied population. The accumulation of mutations during the epidemic period with their geographic locations was also monitored. The results showed 782 variant sites, of which 512 (65.47%) had a non-synonymous effect. Frequencies of mutated alleles revealed the presence of 38 recurrent non-synonymous mutations, including ten hotspot mutations with a prevalence higher than 0.10 in this population and distributed in six SARS-CoV-2 genes. The distribution of these recurrent mutations on the world map revealed certain genotypes specific to the geographic location. We also found co-occurring mutations resulting in the presence of several haplotypes. Moreover, evolution over time has shown a mechanism of mutation co-accumulation which might affect the severity and spread of the SARS-CoV-2. On the other hand, analysis of the selective pressure revealed the presence of negatively selected residues that could be taken into considerations as therapeutic targets We have also created an inclusive unified database (http://genoma.ma/covid-19/) that lists all of the genetic variants of the SARS-CoV-2 genomes found in this study with phylogeographic analysis around the world.", "qid": 37, "docid": "5mh3ds6y", "rank": 67, "score": 0.776993989944458}, {"content": "Title: Temporal evolution and adaptation of SARS-COV 2 codon usage Content: The outbreak of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has caused an unprecedented pandemic. Since the first sequenced whole-genome of SARS-CoV-2 on January 2020, the identification of its genetic variants has become crucial in tracking and evaluating their spread across the globe. In this study, we compared 15,259 SARS-CoV-2 genomes isolated from 60 countries since the outbreak of this novel coronavirus with the first sequenced genome in Wuhan to quantify the evolutionary divergence of SARS-CoV-2. Thus, we compared the codon usage patterns, every two weeks, of 13 of SARS-CoV-2 genes encoding for the membrane protein (M), envelope (E), spike surface glycoprotein (S), nucleoprotein (N), non-structural 3C-like proteinase (3CLpro), ssRNA-binding protein (RBP), 2\u2019-O-ribose methyltransferase (OMT), endoRNase (RNase), helicase, RNA-dependent RNA polymerase (RdRp), Nsp7, Nsp8, and exonuclease ExoN. As a general rule, we find that SARS-CoV-2 genome tends to diverge over time by accumulating mutations on its genome and, specifically, on the coding sequences for proteins N and S. Interestingly, different patterns of codon usage were observed among these genes. Genes S, Nsp7, NSp8, tend to use a norrower set of synonymous codons that are better optimized to the human host. Conversely, genes E and M consistently use a broader set of synonymous codons, which does not vary with respect to the reference genome. We identified key SARS-CoV-2 genes (S, N, ExoN, RNase, RdRp, Nsp7 and Nsp8) suggested to be causally implicated in the virus adaptation to the human host.", "qid": 37, "docid": "xh41koro", "rank": 68, "score": 0.7768566012382507}, {"content": "Title: Emergence of genomic diversity and recurrent mutations in SARS-CoV-2 Content: SARS-CoV-2 is a SARS-like coronavirus of likely zoonotic origin first identified in December 2019 in Wuhan, the capital of China's Hubei province. The virus has since spread globally, resulting in the currently ongoing COVID-19 pandemic. The first whole genome sequence was published on January 5 2020, and thousands of genomes have been sequenced since this date. This resource allows unprecedented insights into the past demography of SARS-CoV-2 but also monitoring of how the virus is adapting to its novel human host, providing information to direct drug and vaccine design. We curated a dataset of 7666 public genome assemblies and analysed the emergence of genomic diversity over time. Our results are in line with previous estimates and point to all sequences sharing a common ancestor towards the end of 2019, supporting this as the period when SARS-CoV-2 jumped into its human host. Due to extensive transmission, the genetic diversity of the virus in several countries recapitulates a large fraction of its worldwide genetic diversity. We identify regions of the SARS-CoV-2 genome that have remained largely invariant to date, and others that have already accumulated diversity. By focusing on mutations which have emerged independently multiple times (homoplasies), we identify 198 filtered recurrent mutations in the SARS-CoV-2 genome. Nearly 80% of the recurrent mutations produced non-synonymous changes at the protein level, suggesting possible ongoing adaptation of SARS-CoV-2. Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. We additionally provide an interactive user-friendly web-application to query the alignment of the 7666 SARS-CoV-2 genomes.", "qid": 37, "docid": "msggi1p2", "rank": 69, "score": 0.7767378091812134}, {"content": "Title: SARS-CoV-2 detection in nasopharyngeal throat swabs by metagenomics Content: Metagenomics could detect SARS-CoV-2 in all eight nasopharyngeal/throat swabs with high/low viral loads, and rhinovirus in a co-infected patient. The sequenced viruses belonged to lineage B1. Because metagenomics could detect novel pathogen and co-infection, and generate sequence data for epidemiological investigation, it is an attractive approach for infectious-disease diagnosis.", "qid": 37, "docid": "464yfabr", "rank": 70, "score": 0.7767112255096436}, {"content": "Title: Tracking the genomic footprints of SARS-CoV-2 transmission Content: Abstract There is considerable public and scientific interest on the origin, spread and evolution of SARS-CoV-2. A recent study by Lu et al. [1], conducted genomic sequencing and analysis of SARS-CoV-2 in Guangdong, revealing its early transmission out of Hubei and shedding light on the effectiveness of controlling local transmission chains.", "qid": 37, "docid": "o004ggon", "rank": 71, "score": 0.7766969203948975}, {"content": "Title: Genome Analysis of SARS-CoV-2 Isolate from Bangladesh Content: Recently the first genome sequence for a Severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 isolate from Bangladesh became available. The sequencing was carried out by the Child Health Research Foundation and provided the first insight into the genetic details of the viral strain responsible for the SARS-CoV-2 infections in Bangladesh. Here we carried out a comparative study were we explored the phylogenetic relationship between the Bangladeshi isolate with other isolates from different parts of the world. Afterwards we identified single nucleotide variants in the Bangladeshi isolate, using the Wuhan virus reference sequence. We found a total of 9 variants in the Bangladeshi isolate using 2 separate tools. Barring 2, the rest of these variants were also observed in other isolates from different countries. Most of the variants occurred in the ORF1ab gen. Another noteworthy finding was a sequence of three consecutive variants in the N protein gene that were observed in other isolates as well. Lastly the phylogenetic analysis revealed a close relationship between the Bangladeshi isolate and those from Taiwan, Kazakhstan, Greece, California, Spain, Israel, and Sri Lanka.", "qid": 37, "docid": "gygi11gk", "rank": 72, "score": 0.7766717076301575}, {"content": "Title: Analysis of SARS-CoV-2 RNA-Sequences by Interpretable Machine Learning Models Content: We present an approach to investigate SARS-CoV-2 virus sequences based on alignment-free methods for RNA sequence comparison. In particular, we verify a given clustering result for the GISAID data set, which was obtained analyzing the molecular differences in coronavirus populations by phylogenetic trees. For this purpose, we use alignment-free dissimilarity measures for sequences and combine them with learning vector quantization classifiers for virus type discriminant analysis and classification. Those vector quantizers belong to the class of interpretable machine learning methods, which, on the one hand side provide additional knowledge about the classification decisions like discriminant feature correlations, and on the other hand can be equipped with a reject option. This option gives the model the property of self controlled evidence if applied to new data, i.e. the models refuses to make a classification decision, if the model evidence for the presented data is not given. After training such a classifier for the GISAID data set, we apply the obtained classifier model to another but unlabeled SARS-CoV-2 virus data set. On the one hand side, this allows us to assign new sequences to already known virus types and, on the other hand, the rejected sequences allow speculations about new virus types with respect to nucleotide base mutations in the viral sequences. Author summary The currently emerging global disease COVID-19 caused by novel SARS-CoV-2 viruses requires all scientific effort to investigate the development of the viral epidemy, the properties of the virus and its types. Investigations of the virus sequence are of special interest. Frequently, those are based on mathematical/statistical analysis. However, machine learning methods represent a promising alternative, if one focuses on interpretable models, i.e. those that do not act as black-boxes. Doing so, we apply variants of Learning Vector Quantizers to analyze the SARS-CoV-2 sequences. We encoded the sequences and compared them in their numerical representations to avoid the computationally costly comparison based on sequence alignments. Our resulting model is interpretable, robust, efficient, and has a self-controlling mechanism regarding the applicability to data. This framework was applied to two data sets concerning SARS-CoV-2. We were able to verify previously published virus type findings for one of the data sets by training our model to accurately identify the virus type of sequences. For sequences without virus type information (second data set), our trained model can predict them. Thereby, we observe a new scattered spreading of the sequences in the data space which probably is caused by mutations in the viral sequences.", "qid": 37, "docid": "4dbuc91c", "rank": 73, "score": 0.7762328386306763}, {"content": "Title: CoV2ID: Detection and Therapeutics Oligo Database for SARS-CoV-2 Content: The ability to detect the SARS-CoV-2 in a widespread epidemic is crucial for screening of carriers and for the success of quarantine efforts. Methods based on real-time reverse transcription polymerase chain reaction (RT-qPCR) and sequencing are being used for virus detection and characterization. However, RNA viruses are known for their high genetic diversity which poses a challenge for the design of efficient nucleic acid-based assays. The first SARS-CoV-2 genomic sequences already showed novel mutations, which may affect the efficiency of available screening tests leading to false-negative diagnosis or inefficient therapeutics. Here we describe the CoV2ID (http://covid.portugene.com/), a free database built to facilitate the evaluation of molecular methods for detection of SARS-CoV-2 and treatment of COVID-19. The database evaluates the available oligonucleotide sequences (PCR primers, RT-qPCR probes, etc.) considering the genetic diversity of the virus. Updated sequences alignments are used to constantly verify the theoretical efficiency of available testing methods. Detailed information on available detection protocols are also available to help laboratories implementing SARS-CoV-2 testing.", "qid": 37, "docid": "mg2dziuw", "rank": 74, "score": 0.7761677503585815}, {"content": "Title: Evolutionary analysis of SARS-CoV-2: how mutation of Non-Structural Protein 6 (NSP6) could affect viral autophagy Content: Abstract Background SARS-CoV-2 is a new coronavirus that has spread globally, infecting more than 150000 people, and being declared pandemic by the WHO. We provide here bio-informatic, evolutionary analysis of 351 available sequences of its genome with the aim of mapping genome structural variations and the patterns of selection. Methods A Maximum likelihood tree has been built and selective pressure has been investigated in order to find any mutation developed during the SARS-CoV-2 epidemic that could potentially affect clinical evolution of the infection. Finding We have found in more recent isolates the presence of two mutations affecting the Non-Structural Protein 6 (NSP6) and the Open Reding Frame10 (ORF 10) adjacent regions. Amino acidic change stability analysis suggests both mutations could confer lower stability of the protein structures. Interpretation One of the two mutations, likely developed within the genome during virus spread, could affect virus intracellular survival. Genome follow-up of SARS-CoV-2 spread is urgently needed in order to identify mutations that could significantly modify virus pathogenicity.", "qid": 37, "docid": "tldg8c94", "rank": 75, "score": 0.7761214971542358}, {"content": "Title: The novel coronavirus SARS-CoV-2: From a zoonotic infection to coronavirus disease 2019 Content: The novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2 is an international public health emergency. Until now, the intermediate host and mechanisms of the interspecies jump of this virus are unknown. Phylogenetic analysis of all available bat CoV complete genomes was performed to analyze the relationships between bat CoV and SARS-CoV-2. To suggest a possible intermediate host, another phylogenetic reconstruction of CoV genomes obtained from animals that were hypothetically commercialized in the Chinese markets was also carried out. Moreover, mutation analysis was executed to suggest genomic regions that may have permitted the adaptation of SARS-CoV-2 to the human host. The phylogenetic analysis demonstrated that SARS-CoV-2 formed a cluster with the bat CoV isolate RaTG13. Possible CoV interspecies jumps among bat isolates were also observed. The phylogenetic tree reconstructed from CoV strains belonging to different animals demonstrated that SARS-CoV-2, bat RaTG13, and pangolin CoV genomes formed a monophyletic cluster, demonstrating that pangolins may be suggested as SARS-CoV-2 intermediate hosts. Three AA substitutions localized in the S1 portion of the S gene were observed, some of which have been correlated to structural modifications of the S protein which may facilitate SARS-CoV-2 tropism to human cells. Our analysis shows the tight relationship between SARS-CoV-2 and bat SARS-like strains. It also hypothesizes that pangolins might have been possible intermediate hosts of the infection. Some of the observed AA substitutions in the S-binding protein may serve as possible adaptation mutations in humans but more studies are needed to elucidate their function.", "qid": 37, "docid": "5qn5h7p5", "rank": 76, "score": 0.7758741974830627}, {"content": "Title: Analyzing hCov genome sequences: Applying Machine Intelligence and beyond Content: Covid-19 pandemic, caused by the sars-cov-2 strain of coronavirus, has affected millions of people all over the world and taken thousands of lives. It is of utmost importance that the character of this deadly virus be studied and its nature be analysed. We present here an analysis pipeline comprising phylogenetic analysis on strains of this novel virus to track its evolutionary history among the countries uncovering several interesting relationships, followed by a classification exercise to identify the virulence of the strains and extraction of important features from its genetic material that are used subsequently to predict mutation at those interesting sites using deep learning techniques. In a nutshell, we have prepared an analysis pipeline for hCov genome sequences leveraging the power of machine intelligence and uncovered what remained apparently shrouded by raw data.", "qid": 37, "docid": "0x90yubt", "rank": 77, "score": 0.7755913734436035}, {"content": "Title: The phylogeny of SARS coronavirus Content: Different tree-building methods consistently place the SARS corona-virus (SARS-CoV) as a basal Group 2 coronavirus rather than as an ungrouped species as concluded by others. Detailed comparisons of the SARS-CoV genomic sequence with those of six other coronaviruses failed to find evidence of recombination or genomic rearrangement using computational methods designed for that purpose.", "qid": 37, "docid": "wr7vrild", "rank": 78, "score": 0.7752832174301147}, {"content": "Title: The origin and underlying driving forces of the SARS-CoV-2 outbreak Content: The spread of SARS-CoV-2 since December 2019 has become a pandemic and impacted many aspects of human society. Here, we analyzed genetic variation of SARS-CoV-2 and its related coronavirus and found the evidence of intergenomic recombination. After correction for mutational bias, analysis of 137 SARS-CoV-2 genomes as of 2/23/2020 revealed the excess of low frequency mutations on both synonymous and nonsynonymous sites which is consistent with recent origin of the virus. In contrast to adaptive evolution previously reported for SARS-CoV in its brief epidemic in 2003, our analysis of SARS-CoV-2 genomes shows signs of relaxation of selection. The sequence similarity of the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression. Therefore, SARS-CoV-2 might have cryptically circulated within humans for years before being recently noticed. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and reveal critical steps required for effective spreading. Two mutations, 84S in orf8 protein and 251V in orf3 protein, occurred coincidentally with human intervention. The 84S first appeared on 1/5/2020 and reached a plateau around 1/23/2020, the lockdown of Wuhan. 251V emerged on 1/21/2020 and rapidly increased its frequency. Thus, the roles of these mutations on infectivity need to be elucidated. Genetic diversity of SARS-CoV-2 collected from China was two time higher than those derived from the rest of the world. In addition, in network analysis, haplotypes collected from Wuhan city were at interior and have more mutational connections, both of which are consistent with the observation that the outbreak of cov-19 was originated from China. SUMMARY In contrast to adaptive evolution previously reported for SARS-CoV in its brief epidemic, our analysis of SARS-CoV-2 genomes shows signs of relaxation of selection. The sequence similarity of the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression. Therefore, SARS-CoV-2 might have cryptically circulated within humans for years before being recently noticed. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and reveal critical steps required for effective spreading. Two mutations, 84S in orf8 protein and 251V in orf3 protein, occurred coincidentally with human intervention. The 84S first appeared on 1/5/2020 and reached a plateau around 1/23/2020, the lockdown of Wuhan. 251V emerged on 1/21/2020 and rapidly increased its frequency. Thus, the roles of these mutations on infectivity need to be elucidated.", "qid": 37, "docid": "bawgldfi", "rank": 79, "score": 0.7752426266670227}, {"content": "Title: Phylogenetic analysis of the full\u2010length SARS\u2010CoV sequences: Evidence for phylogenetic discordance in three genomic regions Content: The origin of the severe acute respiratory syndrome\u2010coronavirus (SARS\u2010CoV) remains unclear. Evidence based on Bayesian scanning plots and phylogenetic analysis using maximum likelihood (ML) and Bayesian methods indicates that SARS\u2010CoV, for the largest part of the genome (\u223c80%), is more closely related to Group II coronaviruses sequences, whereas in three regions in the ORF1ab gene it shows no apparent similarity to any of the previously characterized groups of coronaviruses. There is discordant phylogenetic clustering of SARS\u2010CoV and coronaviruses sequences, throughout the genome, compatible with either ancient recombination events or altered evolutionary rates in different lineages, or a combination of both. J. Med. Virol. 74:369\u2013372, 2004. \u00a9 2004 Wiley\u2010Liss, Inc.", "qid": 37, "docid": "arp07mck", "rank": 80, "score": 0.7749610543251038}, {"content": "Title: Close relationship between SARS-coronavirus and group 2 coronavirus. Content: The sudden appearance and potential lethality of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) in humans has resulted in a focusing of new attention on the determination of both its origins and evolution. The relationship existing between SARS-CoV and other groups of coronaviruses was determined via analyses of phylogenetic trees and comparative genomic analyses of the coronavirus genes: polymerase (Orf1ab), spike (S), envelope (E), membrane (M) and nucleocapsid (N). Although the coronaviruses are traditionally classed into 3 groups, with SARS-CoV forming a 4th group, the phylogenetic position and origins of SARS-CoV remain a matter of some controversy. Thus, we conducted extensive phylogenetic analyses of the genes common to all coronavirus groups, using the Neighbor-joining, Maximum-likelihood, and Bayesian methods. Our data evidenced largely identical topology for all of the obtained phylogenetic trees, thus supporting the hypothesis that the relationship existing between SARS-CoV and group 2 coronavirus is a monophyletic one. Additional comparative genomic studies, including sequence similarity and protein secondary structure analyses, suggested that SARS-CoV may bear a closer relationship with group 2 than with the other coronavirus groups. Although our data strongly suggest that group 2 coronaviruses are most closely related with SARS-CoV, further and more detailed analyses may provide us with an increased amount of information regarding the origins and evolution of the coronaviruses, most notably SARS-CoV.", "qid": 37, "docid": "ax6v6ham", "rank": 81, "score": 0.7749472856521606}, {"content": "Title: Insights into The Codon Usage Bias of 13 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Isolates from Different Geo-locations Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of Coronavirus disease 2019 (COVID-19) which is an infectious disease that spread throughout the world and was declared as a pandemic by the World Health Organization (WHO). In the present study, we analyzed genome-wide codon usage patterns in 13 SARS-CoV-2 isolates from different geo-locations (countries) by utilizing different CUB measurements. Nucleotide and di-nucleotide compositions displayed bias toward A/U content in all codon positions and CpU-ended codons preference, respectively. Relative Synonymous Codon Usage (RSCU) analysis revealed 8 common putative preferred codons among all the 13 isolates. Interestingly, all of the latter codons are A/U-ended (U-ended: 7, A-ended: 1). Cluster analysis (based on RSCU values) was performed and showed comparable results to the phylogenetic analysis (based on their whole genome sequences) indicating that the CUB pattern may reflect the evolutionary relationship between the tested isolates. To investigate the force (mutation and/or selection) influencing the pattern of CUB in SARS-CoV-2 coding sequences, we employed the following; (i). Effective number of codons (ENc), (ii). ENc-GC3 plot, (iii). Neutrality plot, and (iv) Codon adaptation index (CAI). According to their results, natural selection and/or other factors (not investigated in this study) may be the dominant force driving SARS-CoV-2 CUB. It is also worth mentioning that, by using the most expressed genes in human lung tissues as a reference set, some viral genes such as Nucleocapsid phosphoprotein, ORF7a protein, and surface glycoprotein had high CAI values which may indicate for selection force acting on their codon usage, as they play important roles in viral assembly and may help viruses avoid the host immune system. The outcome of our study may help in understanding the underlying factors involved in the evolution of SARS-CoV-2 viruses, and the interactions with their host. Also, it may aid in vaccine design strategies.", "qid": 37, "docid": "ooj9yqbx", "rank": 82, "score": 0.7747606039047241}, {"content": "Title: Comprehensive evolution and molecular characteristics of a large number of SARS-CoV-2 genomes revealed its epidemic trend and possible origins Content: Objectives To reveal epidemic trend and possible origins of SARS-CoV-2 by exploring its evolution and molecular characteristics based on a large number of genomes since it has infected millions of people and spread quickly all over the world. Methods Various evolution analysis methods were employed. Results The estimated Ka/Ks ratio of SARS-CoV-2 is 1.008 or 1.094 based on 622 or 3624 SARS-CoV-2 genomes, and the time to the most recent common ancestor (tMRCA) was inferred in late September 2019. Further 9 key specific sites of highly linkage and four major haplotypes H1, H2, H3 and H4 were found. The Ka/Ks, detected population size and development trends of each major haplotype showed H3 and H4 subgroups were going through a purify evolution and almost disappeared after detection, indicating H3 and H4 might have existed for a long time, while H1 and H2 subgroups were going through a near neutral or neutral evolution and globally increased with time. Notably the frequency of H1 was generally high in Europe and correlated to death rate (r>0.37). Conclusions In this study, the evolution and molecular characteristics of more than 16000 genomic sequences provided a new perspective for revealing epidemiology of SARS-CoV-2.", "qid": 37, "docid": "npcu4wq1", "rank": 83, "score": 0.7747348546981812}, {"content": "Title: Has India met this enemy before? From an eternal optimist\u2019s perspective: SARS-CoV-2 Content: OBJECTIVE: We are presently going through a historic and unprecedented crisis for humanity with SARS-CoV-2 causing immense damage to life and world economics. It has been 3 months, since we had the first cluster in China and we felt the need to look into certain regional patterns of transmission of the virus with respect to some distinctive living conditions, incidence of malaria, the genomics of different strains, and its impact on severity. MATERIAL AND METHODS: Data for 107 countries was compiled and correlation analysis was done between incidence of malaria and number of SARS-CoV-2 cases. Possibility of genetic similarity between SARS-CoV-2 and reported zoonotic RNA viruses found associated previously with some Plasmodium species was explored by utilizing NCBI database. RESULTS: We found a significant inverse correlation between SARS-CoV-2 disease burden and incidence of Malaria. Our analysis also showed that a 12 base pair region encoding a part of surface glycoprotein of SARS- CoV-2 aligned with the Plasmodium associated zoonotic viral genome. CONCLUSION: Our analysis suggests a significantly lower SARS-CoV-2 disease burden in Malaria endemic regions and an inverse correlation with incidence of Malaria. The possibility of a pre-existing immunological memory for SARS-CoV-2 in Indians is possible and needs to be explored further", "qid": 37, "docid": "xvosxgl6", "rank": 84, "score": 0.7747198343276978}, {"content": "Title: Dinucleotide repeats in coronavirus SARS-CoV-2 genome: evolutionary implications Content: The ongoing global pandemic of infection disease COVID-19 caused by the 2019 novel coronavirus (SARS-COV-2, formerly 2019-nCoV) presents critical threats to public health and the economy since it was identified in China, December 2019. The genome of SARS-CoV-2 had been sequenced and structurally annotated, yet little is known of the intrinsic organization and evolution of the genome. To this end, we present a mathematical method for the genomic spectrum, a kind of barcode, of SARS-CoV-2 and common human coronaviruses. The genomic spectrum is constructed according to the periodic distributions of nucleotides, and therefore reflects the unique characteristics of the genome. The results demonstrate that coronavirus SARS-CoV-2 exhibits dinucleotide TT islands in the non-structural proteins 3, 4, 5, and 6. Further analysis of the dinucleotide regions suggests that the dinucleotide repeats are increased during evolution and may confer the evolutionary fitness of the virus. The special dinucleotide regions in the SARS-CoV-2 genome identified in this study may become diagnostic and pharmaceutical targets in monitoring and curing the COVID-19 disease.", "qid": 37, "docid": "lnys6iuu", "rank": 85, "score": 0.7745601534843445}, {"content": "Title: Population genomics insights into the recent evolution of SARS-CoV-2 Content: The current coronavirus disease 2019 (COVID-19) pandemic is caused by the SARS-CoV-2 virus and is still spreading rapidly worldwide. Full-genome-sequence computational analysis of the SARS-CoV-2 genome will allow us to understand the recent evolutionary events and adaptability mechanisms more accurately, as there is still neither effective therapeutic nor prophylactic strategy. In this study, we used population genetics analysis to infer the mutation rate and plausible recombination events that may have contributed to the evolution of the SARS-CoV-2 virus. Furthermore, we localized targets of recent and strong positive selection. The genomic regions that appear to be under positive selection are largely co-localized with regions in which recombination from non-human hosts appeared to have taken place in the past. Our results suggest that the pangolin coronavirus genome may have contributed to the SARS-CoV-2 genome by recombination with the bat coronavirus genome. However, we find evidence for additional recombination events that involve coronavirus genomes from other hosts, i.e., Hedgehog and Sparrow. Even though recombination events within human hosts cannot be directly assessed, due to the high similarity of SARS-CoV-2 genomes, we infer that recombinations may have recently occurred within human hosts using a linkage disequilibrium analysis. In addition, we employed an Approximate Bayesian Computation approach to estimate the parameters of a demographic scenario involving an exponential growth of the size of the SARS-CoV-2 populations that have infected European, Asian and Northern American cohorts, and we demonstrated that a rapid exponential growth in population size can support the observed polymorphism patterns in SARS-CoV-2 genomes.", "qid": 37, "docid": "1fxrmuzl", "rank": 86, "score": 0.774258553981781}, {"content": "Title: Coronavirus phylogeny based on base-base correlation. Content: With more and more complete genome sequences having been released, phylogenetic analysis is entering a new era--that of phylogenomics. In this paper, a novel phylogenomic method, named as Base-Base Correlation (BBC), has been proposed to infer phylogenetic relationships from complete genomes, with particular emphasis on coronavirus phylogeny. Following the high-profile publicity of SARS outbreaks, a renewed interest in coronavirus has been promoted and two novel human coronaviruses (NL63 and HKU1) have been identified. Coronavirus phylogenomics based on BBC is well consistent with that of previous studies. BBC, to study genome information structure based on information theory, provides a novel alignment-free phylogenomic methodology in postgenome informatics.", "qid": 37, "docid": "who8l9f9", "rank": 87, "score": 0.7741677761077881}, {"content": "Title: Evidence of Increasing Diversification of Emerging SARS-CoV-2 Strains Content: BACKGROUND: On January 30th, 2020, an outbreak of atypical pneumonia caused by a novel Betacoronavirus (\u00dfCoV), named SARS-CoV-2, was declared a public health emergency of international concern by the World Health Organization. For this reason, a detailed evolutionary analysis of SARS-CoV-2 strains currently circulating in different geographic regions of the world was performed. METHODS: A compositional analysis as well as a Bayesian coalescent analysis of complete genome sequences of SARS-CoV-2 strains recently isolated in Europe, North America, South America and Asia was performed. RESULTS: The results of these studies revealed a diversification of SARS-CoV-2 strains in three different genetic clades. Co-circulation of different clades in different countries, as well as different genetic lineages within different clades were observed. The time of the most recent common ancestor (tMRCA) was established to be around November 1, 2019. A mean rate of evolution of 6.57 x 10-4 substitutions per site per year was found. A significant migration rate per genetic lineage per year from Europe to South America was also observed. CONCLUSION: The results of these studies revealed an increasing diversification of SARS-CoV-2 strains. High evolutionary rates and fast population growth characterizes the population dynamics of SARS-CoV-2 strains. This article is protected by copyright. All rights reserved.", "qid": 37, "docid": "1h1hwbos", "rank": 88, "score": 0.7741259932518005}, {"content": "Title: SARS-CoV-2: virus mutations in specific European populations Content: Abstract The SARS-CoV-2 virus is being intensively studied, particularly, its evolution in the increasingly available sequences between countries/continents with classical phylogenetic tree representation. More recently, certain protein mutations are correlated with specific functional impacts. Our clinical data from patients suggest different clinical symptoms between European countries. Among others, SARS-CoV-2 mutations could explain these disparities. Our analyses point out an association of diverse mutations, including co-evolving ones, in a few SARS-CoV-2 proteins, with specific countries. We therefore suggest combining clinical information from patients and the determination of the associated SARS-CoV-2 genome to better understand the specific symptoms.", "qid": 37, "docid": "y5th0mrf", "rank": 89, "score": 0.7740973234176636}, {"content": "Title: [Analysis of variation and evolution of SARS-CoV-2 genome] Content: OBJECTIVE: To analyze the evolution and variation of SARS-CoV-2 during the epidemic starting at the end of 2019. METHODS: We downloaded the full-length genome sequence of SARS-CoV-2 from the databases of GISAID and NCBI. Using the software for bioinformatics including MEGA-X, BEAST, and TempEst, we constructed the genomic evolution tree, inferred the time evolution signal of the virus, calculated the tMRCA time of the virus and analyzed the selection pressure of the virus during evolution. RESULTS: The phylogenetic tree showed that SARS-CoV-2 belonged to the Sarbecovirus subgenus of \u00df Coronavirus genus together with bat coronavirus BetaCoV/bat/Yunnan/RaTG13/2013, bat-SL-CoVZC45, bat-SL-CoVZXC21 and SARS-CoV. The genomic sequences of SARS-CoV-2 isolated from the ongoing epidemic showed a weak time evolution signal with an average tMRCA time of 73 days (95% CI: 38.9-119.3 days). No positive time evolution signal was found between SARS-CoV-2 and BetaCoV/bat/Yunnan/RaTG13/2013, but the former virus had a strong positive temporal evolution relationship with bat-SL-CoVZC45 and SARS-CoV. The major cause for mutations of SARS-CoV-2 was the pressure of purification selection during the epidemic. CONCLUSIONS: SARS-CoV-2 may have emerged as early as November, 2019, originating most likely from bat-associated coronavirus. This finding may provide evidence for tracing the sources and evolution of the virus.", "qid": 37, "docid": "fofy6whl", "rank": 90, "score": 0.7740029692649841}, {"content": "Title: Coronavirus phylogeny based on 2D graphical representation of DNA sequence Content: A novel coronavirus has been identified as the cause of the outbreak of severe acute respiratory syndrome (SARS). Previous phylogenetic analyses based on sequence alignments show that SARS\u2010CoVs form a new group distantly related to the other three groups of previously characterized coronaviruses. In this aritcle, a new approach based on the 2D graphical representation of the whole genome sequence is proposed to analyze the phylogenetic relationships of coronaviruses. The evolutionary distances are obtained through measuring the differences among the two\u2010dimensional curves. \u00a9 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1196\u20131202, 2006", "qid": 37, "docid": "plsspth8", "rank": 91, "score": 0.7739419937133789}, {"content": "Title: Evidence of Increasing Diversification of Emerging SARS\u2010CoV\u20102 Strains Content: BACKGROUND: On January 30th, 2020, an outbreak of atypical pneumonia caused by a novel Betacoronavirus (\u03b2CoV), named SARS\u2010CoV\u20102, was declared a public health emergency of international concern by the World Health Organization. For this reason, a detailed evolutionary analysis of SARS\u2010CoV\u20102 strains currently circulating in different geographic regions of the world was performed. METHODS: A compositional analysis as well as a Bayesian coalescent analysis of complete genome sequences of SARS\u2010CoV\u20102 strains recently isolated in Europe, North America, South America and Asia was performed. RESULTS: The results of these studies revealed a diversification of SARS\u2010CoV\u20102 strains in three different genetic clades. Co\u2010circulation of different clades in different countries, as well as different genetic lineages within different clades were observed. The time of the most recent common ancestor (tMRCA) was established to be around November 1, 2019. A mean rate of evolution of 6.57 x 10(\u20104) substitutions per site per year was found. A significant migration rate per genetic lineage per year from Europe to South America was also observed. CONCLUSION: The results of these studies revealed an increasing diversification of SARS\u2010CoV\u20102 strains. High evolutionary rates and fast population growth characterizes the population dynamics of SARS\u2010CoV\u20102 strains. This article is protected by copyright. All rights reserved.", "qid": 37, "docid": "ew2kjq5s", "rank": 92, "score": 0.7737146615982056}, {"content": "Title: Phyloevolutionary analysis of SARS-CoV-2 in Nigeria Content: Abstract Background Phyloepidemiologic approaches have given specific insight to understanding emergence and evolution of infection. Knowledge on the outbreak and spread of SARS-CoV-2 in Nigeria would assist in providing preventive measures to reduce transmission among populations at risk. Therefore, this study aimed at investigating the evolution of SARS-CoV-2 in Nigeria. Materials and Method A total of 39 complete genomes of SARS-CoV-2 were retrieved from the GISAID EpiFluTM database on March 29th 2020 to investigate its evolution in Nigeria. Sequences were selected based on the travel history of the patient and the collection date. Other sequences were not selected because they were short, contained artefacts, not from original source or had insufficient information. Evolutionary history was inferred using Maximum Likelihood method based on the General Time Reversible model. Phylogenetic tree was constructed to determine the common ancestor of each strain. Results The phylogenetic analysis showed the strain in Nigeria clustered in a monophyletic clade with a Wuhan sublineage. Nucleotide alignment also showed a 100% similarity indicating a common origin of evolution. Comparative analysis showed 27,972 (93.6%) identical sites and 97.6% pairwise identity with the consensus. Conclusion The study evidently showed the entire outbreak of COVID-19 infection in Nigeria stemmed from a single introduction sharing consensus similarity with the reference SARS-CoV-2 human genome from Wuhan. Preventive measures that can limit the spread of the infection among populations at risk should be implemented.", "qid": 37, "docid": "aejbfk3l", "rank": 93, "score": 0.7735109329223633}, {"content": "Title: Epidemiological and Genomic Analysis of SARS-CoV-2 in Ten Patients from a Mid-sized City outside of Hubei, China Content: A novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing COVID-19 pandemic. In this study, we performed a comprehensive epidemiological and genomic analysis of SARS-CoV-2 genomes from ten patients in Shaoxing, a mid-sized city outside of the epicenter Hubei province, China, during the early stage of the outbreak (late January to early February, 2020). We obtained viral genomes with > 99% coverage and a mean depth of 296X demonstrating that viral genomic analysis is feasible via metagenomics sequencing directly on nasopharyngeal samples with SARS-CoV-2 Real-time PCR Ct values less than 28. We found that a cluster of 4 patients with travel history to Hubei shared the exact same virus with patients from Wuhan, Taiwan, Belgium and Australia, highlighting how quickly this virus spread to the globe. The virus from another cluster of husband and wife without travel history but with a sick contact of a confirmed case from another city outside of Hubei accumulated significantly more mutations (9 SNPs vs average 4 SNPs), suggesting a complex and dynamic nature of this outbreak. We also found 70% patients in this study had the S genotype, consistent with an early study showing a higher prevalence of S genotype out of Hubei than that inside Hubei. We calculated an average mutation rate of 1.37x10-3 nucleotide substitution per site per year, which is similar to that of other coronaviruses. Our findings add to the growing knowledge of the epidemiological and genomic characteristics of SARS-CoV-2 that are important for guiding outbreak containment and vaccine development. The moderate mutation rate of this virus also lends hope that development of an effective, long-lasting vaccine may be possible.", "qid": 37, "docid": "m9k6upe4", "rank": 94, "score": 0.7732335329055786}, {"content": "Title: Genome-wide analysis of Indian SARS-CoV-2 genomes for the identification of genetic mutation and SNP Content: The wave of COVID-19 is a big threat to the human population. Presently, the world is going through different phases of lock down in order to stop this wave of pandemic; India being no exception. We have also started the lock down on 23rd March 2020. In this current situation, apart from social distancing only a vaccine can be the proper solution to serve the population of human being. Thus it is important for all the nations to perform the genome-wide analysis in order to identify the genetic variation in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) so that proper vaccine can be designed. This fast motivated us to analyze publicly available 566 Indian complete or near complete SARS-CoV-2 genomes to find the mutation points as substitution, deletion and insertion. In this regard, we have performed the multiple sequence alignment in presence of reference sequence from NCBI. After the alignment, a consensus sequence is build to analyze each genome in order to identify the mutation points. As a consequence, we have found 933 substitutions, 2449 deletions and 2 insertions, in total 3384 unique mutation points, in 566 genomes across 29.9 K bp. Further, it has been classified into three groups as 100 clusters of mutations (mostly deletions), 1609 point mutations as substitution, deletion and insertion and 64 SNPs. These outcomes are visualized using BioCircos and bar plots as well as plotting entropy value of each genomic location. Moreover, phylogenetic analysis has also been performed to see the evolution of SARS-CoV-2 virus in India. It also shows the wide variation in tree which indeed vivid in genomic analysis. Finally, these SNPs can be the useful target for virus classification, designing and defining the effective dose of vaccine for the heterogeneous population.", "qid": 37, "docid": "lt0uo7q3", "rank": 95, "score": 0.77323317527771}, {"content": "Title: Origin of imported SARS-CoV-2 strains in The Gambia identified from Whole Genome Sequences Content: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a positive-sense single stranded RNA virus with high human transmissibility. This study generated Whole Genome data to determine the origin and pattern of transmission of SARS-CoV-2 from the first six cases tested in The Gambia. Total RNA from SARS-CoV-2 was extracted from inactivated nasopharyngeal-oropharyngeal swabs of six cases and converted to cDNA following the ARTIC COVID-19 sequencing protocol. Libraries were constructed with the NEBNext ultra II DNA library prep kit for Illumina and Oxford Nanopore Ligation sequencing kit and sequenced on Illumina MiSeq and Nanopore GridION, respectively. Sequencing reads were mapped to the Wuhan reference genome and compared to eleven other SARS-CoV-2 strains of Asian, European and American origins. A phylogenetic tree was constructed with the consensus genomes for local and non-African strains. Three of the Gambian strains had a European origin (UK and Spain), two strains were of Asian origin (Japan). In The Gambia, Nanopore and Illumina sequencers were successfully used to identify the sources of SARS-CoV-2 infection in COVID-19 cases.", "qid": 37, "docid": "z14rf85c", "rank": 96, "score": 0.773094654083252}, {"content": "Title: Tracking the Genomic Footprints of SARS-CoV-2 Transmission Content: There is considerable public and scientific interest in the origin, spread, and evolution of SARS-CoV-2. Lu et al. recently conducted genomic sequencing and analysis of SARS-CoV-2 in Guangdong, revealing its early transmission out of Hubei and shedding light on the effectiveness of controlling local transmission chains.", "qid": 37, "docid": "dg5pc3a0", "rank": 97, "score": 0.7728935480117798}, {"content": "Title: Emergence of genomic diversity and recurrent mutations in SARS-CoV-2 Content: Abstract SARS-CoV-2 is a SARS-like coronavirus of likely zoonotic origin first identified in December 2019 in Wuhan, the capital of China's Hubei province. The virus has since spread globally, resulting in the currently ongoing COVID-19 pandemic. The first whole genome sequence was published on January 52,020, and thousands of genomes have been sequenced since this date. This resource allows unprecedented insights into the past demography of SARS-CoV-2 but also monitoring of how the virus is adapting to its novel human host, providing information to direct drug and vaccine design. We curated a dataset of 7666 public genome assemblies and analysed the emergence of genomic diversity over time. Our results are in line with previous estimates and point to all sequences sharing a common ancestor towards the end of 2019, supporting this as the period when SARS-CoV-2 jumped into its human host. Due to extensive transmission, the genetic diversity of the virus in several countries recapitulates a large fraction of its worldwide genetic diversity. We identify regions of the SARS-CoV-2 genome that have remained largely invariant to date, and others that have already accumulated diversity. By focusing on mutations which have emerged independently multiple times (homoplasies), we identify 198 filtered recurrent mutations in the SARS-CoV-2 genome. Nearly 80% of the recurrent mutations produced non-synonymous changes at the protein level, suggesting possible ongoing adaptation of SARS-CoV-2. Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. We additionally provide an interactive user-friendly web-application to query the alignment of the 7666 SARS-CoV-2 genomes.", "qid": 37, "docid": "bsypo08l", "rank": 98, "score": 0.7723280191421509}, {"content": "Title: The establishment of reference sequence for SARS\u2010CoV\u20102 and variation analysis Content: Starting around December 2019, an epidemic of pneumonia, which was named COVID\u201019 by the World Health Organization, broke out in Wuhan, China, and is spreading throughout the world. A new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses was soon found to be the cause. At present, the sensitivity of clinical nucleic acid detection is limited, and it is still unclear whether it is related to genetic variation. In this study, we retrieved 95 full\u2010length genomic sequences of SARAS\u2010CoV\u20102 strains from the National Center for Biotechnology Information and GISAID databases, established the reference sequence by conducting multiple sequence alignment and phylogenetic analyses, and analyzed sequence variations along the SARS\u2010CoV\u20102 genome. The homology among all viral strains was generally high, among them, 99.99% (99.91%\u2010100%) at the nucleotide level and 99.99% (99.79%\u2010100%) at the amino acid level. Although overall variation in open\u2010reading frame (ORF) regions is low, 13 variation sites in 1a, 1b, S, 3a, M, 8, and N regions were identified, among which positions nt28144 in ORF 8 and nt8782 in ORF 1a showed mutation rate of 30.53% (29/95) and 29.47% (28/95), respectively. These findings suggested that there may be selective mutations in SARS\u2010COV\u20102, and it is necessary to avoid certain regions when designing primers and probes. Establishment of the reference sequence for SARS\u2010CoV\u20102 could benefit not only biological study of this virus but also diagnosis, clinical monitoring and intervention of SARS\u2010CoV\u20102 infection in the future.", "qid": 37, "docid": "41ogljo8", "rank": 99, "score": 0.7722581028938293}, {"content": "Title: The complete genome sequence of severe acute respiratory syndrome coronavirus strain HKU-39849 (HK-39). Content: The complete genomic nucleotide sequence (29.7kb) of a Hong Kong severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) strain HK-39 is determined. Phylogenetic analysis of the genomic sequence reveals it to be a distinct member of the Coronaviridae family. 5' RACE assay confirms the presence of at least six subgenomic transcripts all containing the predicted intergenic sequences. Five open reading frames (ORFs), namely ORF1a, 1b, S, M, and N, are found to be homologues to other CoV members, and three more unknown ORFs (X1, X2, and X3) are unparalleled in all other known CoV species. Optimal alignment and computer analysis of the homologous ORFs has predicted the characteristic structural and functional domains on the putative genes. The overall nucleotides conservation of the homologous ORFs is low (<5%) compared with other known CoVs, implying that HK-39 is a newly emergent SARS-CoV phylogenetically distant from other known members. SimPlot analysis supports this finding, and also suggests that this novel virus is not a product of a recent recombinant from any of the known characterized CoVs. Together, these results confirm that HK-39 is a novel and distinct member of the Coronaviridae family, with unknown origin. The completion of the genomic sequence of the virus will assist in tracing its origin.", "qid": 37, "docid": "myhlbq9h", "rank": 100, "score": 0.7719257473945618}]}
{"query": "What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases?", "hits": [{"content": "Title: COVID-19 - toward a comprehensive understanding of the disease. Content: The evidence on the pathophysiology of the novel coronavirus SARS-CoV-2 infection is rapidly growing. Understanding why some patients suffering from COVID-19 are getting so sick, while others are not, has become an informal imperative for researchers and clinicians around the globe. The answer to this question would allow rationalizing the fear surrounding this pandemic. Understanding of the pathophysiology of COVID-19 relies on an understanding of interplaying mechanisms, including SARS-CoV-2 virulence, human immune response, and complex inflammatory reactions with coagulation playing a major role. An interplay with bacterial co-infections, as well as the vascular system and microcirculation affected throughout the body should also be examined. More importantly, a comprehensive understanding of pathological mechanisms of COVID-19 will increase the efficacy of therapy and decrease mortality. Herewith, presented is the current state of knowledge on COVID-19: beginning from the virus, its transmission, and mechanisms of entry into the human body, through the pathological effects on the cellular level, up to immunological reaction, systemic and organ presentation. Last but not least, currently available and possible future therapeutic and diagnostic options are briefly commented on.", "qid": 38, "docid": "msx6n8xu", "rank": 1, "score": 0.8561310172080994}, {"content": "Title: COVID-19 - Toward a comprehensive understanding of the disease Content: The evidence on the pathophysiology of the novel coronavirus SARS-CoV-2 infection is rapidly growing. Understanding why some patients suffering from COVID-19 are getting so sick, while others are not, has become an informal imperative for researchers and clinicians around the globe. The answer to this question would allow rationalizing the fear surrounding this pandemic. Understanding of the pathophysiology of COVID-19 relies on an understanding of interplaying mechanisms, including SARS-CoV-2 virulence, human immune response, and complex inflammatory reactions with coagulation playing a major role. An interplay with bacterial co-infections, as well as the vascular system and microcirculation affected throughout the body should also be examined. More importantly, a compre-hensive understanding of pathological mechanisms of COVID-19 will increase the efficacy of therapy and decrease mortality. Herewith, presented is the current state of knowledge on COVID-19: beginning from the virus, its transmission, and mechanisms of entry into the human body, through the pathological effects on the cellular level, up to immunological reaction, systemic and organ presentation. Last but not least, currently available and possible future therapeutic and diagnostic options are briefly commented on.", "qid": 38, "docid": "edbtz6up", "rank": 2, "score": 0.8552606701850891}, {"content": "Title: A Dynamic Immune Response Shapes COVID-19 Progression Content: The inflammatory response to SARS-coronavirus-2 (SARS-CoV-2) infection is thought to underpin COVID-19 pathogenesis. We conducted daily transcriptomic profiling of three COVID-19 cases and found that the early immune response in COVID-19 patients is highly dynamic. Patient throat swabs were tested daily for SARS-CoV-2, with the virus persisting for 3 to 4 weeks in all three patients. Cytokine analyses of whole blood revealed increased cytokine expression in the single most severe case. However, most inflammatory gene expression peaked after respiratory function nadir, except expression in the IL1 pathway. Parallel analyses of CD4 and CD8 expression suggested that the pro-inflammatory response may be intertwined with T cell activation that could exacerbate disease or prolong the infection. Collectively, these findings hint at the possibility that IL1 and related pro-inflammatory pathways may be prognostic and serve as therapeutic targets for COVID-19. This work may also guide future studies to illuminate COVID-19 pathogenesis and develop host-directed therapies.", "qid": 38, "docid": "xm0n9iu4", "rank": 3, "score": 0.844856858253479}, {"content": "Title: A dynamic immune response shapes COVID-19 progression Content: The inflammatory response to SARS-coronavirus-2 (SARS-CoV-2) infection is thought to underpin COVID-19 pathogenesis We conducted daily transcriptomic profiling of three COVID-19 cases and found that the early immune response in COVID-19 patients is highly dynamic Patient throat swabs were tested daily for SARS-CoV-2 with the virus persisting for 3-4 weeks in all three patients Cytokine analyses of whole blood revealed increased cytokine expression in the single more severe case However, most inflammatory gene expression peaked after respiratory function nadir, except those in the IL1 pathway Parallel analyses of CD4 and CD8 expression suggested that the pro-inflammatory response may be intertwined with T-cell activation that could exacerbate disease or prolong the infection Collectively, these findings hint at the possibility that IL1 and related pro-inflammatory pathways may be prognostic and serve as therapeutic targets for COVID-19 This work may also guide future studies to illuminate COVID-19 pathogenesis and develop host-directed therapies", "qid": 38, "docid": "uxehz43v", "rank": 4, "score": 0.844654381275177}, {"content": "Title: Comprehensive Transcriptomic Analysis of COVID-19 Blood, Lung, and Airway Content: Abstract SARS-CoV2 is a previously uncharacterized coronavirus and causative agent of the COVID-19 pandemic. The host response to SARS-CoV2 has not yet been fully delineated, hampering a precise approach to therapy. To address this, we carried out a comprehensive analysis of gene expression data from the blood, lung, and airway of COVID-19 patients. Our results indicate that COVID-19 pathogenesis is driven by populations of myeloid-lineage cells with highly inflammatory but distinct transcriptional signatures in each compartment. The relative absence of cytotoxic cells in the lung suggests a model in which delayed clearance of the virus may permit exaggerated myeloid cell activation that contributes to disease pathogenesis by the production of inflammatory mediators. The gene expression profiles also identify potential therapeutic targets that could be modified with available drugs. The data suggest that transcriptomic profiling can provide an understanding of the pathogenesis of COVID-19 in individual patients. Graphical Abstract", "qid": 38, "docid": "9gdi5447", "rank": 5, "score": 0.8393808603286743}, {"content": "Title: Pathogenesis of COVID-19 from the Perspective of the Damage-Response Framework Content: The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents the medical community with a significant challenge. COVID-19 is an entirely new disease with disparate clinical manifestations that are difficult to reconcile with a single pathogenic principle. Here, we explain how the flexible paradigm of the \u201cdamage-response framework\u201d (DRF) of microbial pathogenesis can organize the varied manifestations of COVID-19 into a synthesis that accounts for differences in susceptibility of vulnerable populations as well as for differing manifestations of COVID-19 disease. By focusing on mechanisms of host damage, particularly immune-mediated damage, the DRF provides a lens to understand COVID-19 pathogenesis and to consider how potential therapies could alter the outcome of this disease.", "qid": 38, "docid": "ciej6zq9", "rank": 6, "score": 0.834497332572937}, {"content": "Title: Pathogenesis of COVID-19 from the Perspective of the Damage-Response Framework Content: The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents the medical community with a significant challenge. COVID-19 is an entirely new disease with disparate clinical manifestations that are difficult to reconcile with a single pathogenic principle. Here, we explain how the flexible paradigm of the \"damage-response framework\" (DRF) of microbial pathogenesis can organize the varied manifestations of COVID-19 into a synthesis that accounts for differences in susceptibility of vulnerable populations as well as for differing manifestations of COVID-19 disease. By focusing on mechanisms of host damage, particularly immune-mediated damage, the DRF provides a lens to understand COVID-19 pathogenesis and to consider how potential therapies could alter the outcome of this disease.", "qid": 38, "docid": "wje8t562", "rank": 7, "score": 0.8332780003547668}, {"content": "Title: The immune system and COVID-19: Friend or foe? Content: AIM: Coronavirus disease 2019 (COVID-19) is a novel highly contagious infection caused by SARS-CoV-2, which has been became a global public health challenge. The pathogenesis of this virus is not yet clearly understood, but there is evidence of a hyper-inflammatory immune response in critically ill patients, which leads to acute respiratory distress syndrome (ARDS) and multi-organ failure. MATERIAL AND METHODS: A literature review was performed to identify relevant articles on COVID-19 published up to April 30, 2020. The search resulted in 361 total articles. After reviewing the titles and abstracts for inclusion, some irrelevant papers were excluded. Additional relevant articles were identified from a review of citations referenced. KEY FINDINGS: SARS-CoV-2, directly and indirectly, affects the immune system and avoids being eliminated in early stages. On the other hand, the secretion of inflammatory cytokines creates critical conditions that lead to multi-organ failure. SIGNIFICANCE: The immune system which is affected by the virus tries to respond via a cytokine storm and hyperinflammation, which itself leads to further multi-organ damage and even death.", "qid": 38, "docid": "d44coxr1", "rank": 8, "score": 0.8313575387001038}, {"content": "Title: Pharmacological agents under investigation in the treatment of coronavirus disease 2019 and the importance of melatonin Content: Coronavirus disease 2019 (COVID-19) is a life-threatening infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 pandemic causing morbidities and even deaths worldwide revealed that there is urgent need to find pharmacological agents or vaccines. Although there are a lot of agents under investigation, there is no approved agent for the prevention or treatment of the COVID-19 yet. Treatment of patients remains mainly supportive as well as compassionate use of the agents under investigation. It is well established that excessive inflammatory and immune response as well as oxidative injury play a critical role in the pathogenesis of COVID-19. In this review, we aimed to update knowledge about pathogenesis, clinical features and pharmacological treatment of COVID-19 and review the potential beneficial effects of ancient antioxidant, anti-inflammatory and immunomodulatory molecule melatonin for prevention and treatment of COVID-19.", "qid": 38, "docid": "afx2wv9d", "rank": 9, "score": 0.8304325342178345}, {"content": "Title: Pharmacological agents under investigation in the treatment of coronavirus disease 2019 and the importance of melatonin. Content: Coronavirus disease 2019 (COVID-19) is a life-threatening infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 pandemic causing morbidities and even deaths worldwide revealed that there is urgent need to find pharmacological agents or vaccines. Although there are a lot of agents under investigation, there is no approved agent for the prevention or treatment of the COVID-19 yet. Treatment of patients remains mainly supportive as well as compassionate use of the agents under investigation. It is well established that excessive inflammatory and immune response as well as oxidative injury play a critical role in the pathogenesis of COVID-19. In this review, we aimed to update knowledge about pathogenesis, clinical features and pharmacological treatment of COVID-19 and review the potential beneficial effects of ancient antioxidant, anti-inflammatory and immunomodulatory molecule melatonin for prevention and treatment of COVID-19.", "qid": 38, "docid": "rx1k9hu5", "rank": 10, "score": 0.8304325342178345}, {"content": "Title: SARS-CoV-2 infection: the role of cytokines in COVID-19 disease Content: COVID-19 disease, caused by infection with SARS-CoV-2, is related to a series of physiopathological mechanisms that mobilize a wide variety of biomolecules, mainly immunological in nature. In the most severe cases, the prognosis can be markedly worsened by the hyperproduction of mainly proinflammatory cytokines, such as IL-1, IL-6, IL-12, IFN-\u03b3, and TNF-\u03b1, preferentially targeting lung tissue. This study reviews published data on alterations in the expression of different cytokines in patients with COVID-19 who require admission to an intensive care unit. Data on the implication of cytokines in this disease and their effect on outcomes will support the design of more effective approaches to the management of COVID-19.", "qid": 38, "docid": "8u685f45", "rank": 11, "score": 0.8285312652587891}, {"content": "Title: COVID-19 : physiopathologie d'une maladie \u00e0 plusieurs visages./ [COVID-19: Pathogenesis of a multi-faceted disease] Content: SARS-CoV-2 infection, named COVID-19, can lead to a dysregulated immune response and abnormal coagulation responsible for a viral sepsis. In this review, we specify physiopathological mechanisms of each phase of COVID-19 - viral, immune and pro-thrombotic - notably because they involve different treatment. Finally, we specify the physiopathological mechanisms of organ injury.", "qid": 38, "docid": "goordy3i", "rank": 12, "score": 0.8274673223495483}, {"content": "Title: SARS-CoV-2 infection: The role of cytokines in COVID-19 disease Content: COVID-19 disease, caused by infection with SARS-CoV-2, is related to a series of physiopathological mechanisms that mobilize a wide variety of biomolecules, mainly immunological in nature. In the most severe cases, the prognosis can be markedly worsened by the hyperproduction of mainly proinflammatory cytokines, such as IL-1, IL-6, IL-12, IFN-\u00ce\u00b3, and TNF-&#945;, preferentially targeting lung tissue. This study reviews published data on alterations in the expression of different cytokines in patients with COVID-19 who require admission to an intensive care unit. Data on the implication of cytokines in this disease and their effect on outcomes will support the design of more effective approaches to the management of COVID-19.", "qid": 38, "docid": "tgunokrk", "rank": 13, "score": 0.8269480466842651}, {"content": "Title: Early Insights into Immune Responses during COVID-19 Content: Coronavirus disease-2019 (COVID-19) is caused by the newly emerged virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was recently declared as a pandemic by the World Health Organization. In its severe form, the disease is characterized by acute respiratory distress syndrome, and there are no targeted intervention strategies to treat or prevent it. The immune response is thought to both contribute to the pathogenesis of disease and provide protection during its resolution. Thus, understanding the immune response to SARS-CoV-2 is of the utmost importance for developing and testing vaccines and therapeutics. In this review, we discuss the earliest knowledge and hypotheses of the mechanisms of immune pathology in the lung during acute infection as well at the later stages of disease resolution, recovery, and immune memory formation.", "qid": 38, "docid": "pp71jaau", "rank": 14, "score": 0.8263096213340759}, {"content": "Title: Early Insights into Immune Responses during COVID-19. Content: Coronavirus disease-2019 (COVID-19) is caused by the newly emerged virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was recently declared as a pandemic by the World Health Organization. In its severe form, the disease is characterized by acute respiratory distress syndrome, and there are no targeted intervention strategies to treat or prevent it. The immune response is thought to both contribute to the pathogenesis of disease and provide protection during its resolution. Thus, understanding the immune response to SARS-CoV-2 is of the utmost importance for developing and testing vaccines and therapeutics. In this review, we discuss the earliest knowledge and hypotheses of the mechanisms of immune pathology in the lung during acute infection as well at the later stages of disease resolution, recovery, and immune memory formation.", "qid": 38, "docid": "1mhxy9hh", "rank": 15, "score": 0.8263096213340759}, {"content": "Title: SARS-CoV-2 and viral sepsis: observations and hypotheses Content: Since the outbreak of coronavirus disease 2019 (COVID-19), clinicians have tried every effort to understand the disease, and a brief portrait of its clinical features have been identified. In clinical practice, we noticed that many severe or critically ill COVID-19 patients developed typical clinical manifestations of shock, including cold extremities and weak peripheral pulses, even in the absence of overt hypotension. Understanding the mechanism of viral sepsis in COVID-19 is warranted for exploring better clinical care for these patients. With evidence collected from autopsy studies on COVID-19 and basic science research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV, we have put forward several hypotheses about SARS-CoV-2 pathogenesis after multiple rounds of discussion among basic science researchers, pathologists, and clinicians working on COVID-19. We hypothesise that a process called viral sepsis is crucial to the disease mechanism of COVID-19. Although these ideas might be proven imperfect or even wrong later, we believe they can provide inputs and guide directions for basic research at this moment.", "qid": 38, "docid": "jilnno5p", "rank": 16, "score": 0.8256115913391113}, {"content": "Title: A contemporary review on pathogenesis and immunity of COVID-19 infection Content: Emerging of the COVID-19 pandemic has raised interests in the field of biology and pathogenesis of coronaviruses; including interactions between host immune reactions specific, and viral factors. Deep knowledge about the interaction between coronaviruses and the host factors could be useful to provide a better support for the disease sufferers and be advantageous for managing and treatment of the lung infection caused by the virus. At this study, we reviewed the updated information on the pathogenesis of the COVID-19 and the immune responses toward it, with a special focus on structure, genetics, and viral accessory proteins, viral replication, viral receptors, the human immune reactions, cytopathic effects, and host-related factors.", "qid": 38, "docid": "owby50fr", "rank": 17, "score": 0.8237545490264893}, {"content": "Title: Inflammatory and Coagulative Considerations for the Management of Orthopaedic Trauma Patients With COVID-19: A Review of the Current Evidence and Our Surgical Experience Content: Mounting evidence suggests that the pathogenesis of coronavirus disease 2019 (COVID-19) involves a hyperinflammatory response predisposing patients to thromboembolic disease and acute respiratory distress. In the setting of severe blunt trauma, damaged tissues induce a local and systemic inflammatory response through similar pathways to COVID-19. As such, patients with COVID-19 sustaining orthopaedic trauma injuries may have an amplified response to the traumatic insult because of their baseline hyperinflammatory and hypercoagulable states. These patients may have compromised physiological reserve to withstand the insult of surgical intervention before reaching clinical instability. In this article, we review the current evidence regarding pathogenesis of COVID-19 and its implications on the management of orthopaedic trauma patients by discussing a case and the most recent literature.", "qid": 38, "docid": "41gth6o0", "rank": 18, "score": 0.8225364685058594}, {"content": "Title: SARS-CoV-2 and viral sepsis: observations and hypotheses Content: Summary Since the outbreak of coronavirus disease 2019 (COVID-19), clinicians have tried every effort to understand the disease, and a brief portrait of its clinical features have been identified. In clinical practice, we noticed that many severe or critically ill COVID-19 patients developed typical clinical manifestations of shock, including cold extremities and weak peripheral pulses, even in the absence of overt hypotension. Understanding the mechanism of viral sepsis in COVID-19 is warranted for exploring better clinical care for these patients. With evidence collected from autopsy studies on COVID-19 and basic science research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV, we have put forward several hypotheses about SARS-CoV-2 pathogenesis after multiple rounds of discussion among basic science researchers, pathologists, and clinicians working on COVID-19. We hypothesise that a process called viral sepsis is crucial to the disease mechanism of COVID-19. Although these ideas might be proven imperfect or even wrong later, we believe they can provide inputs and guide directions for basic research at this moment.", "qid": 38, "docid": "mrvk9r4w", "rank": 19, "score": 0.8222450613975525}, {"content": "Title: COVID-19 Hyperinflammation: What about Neutrophils? Content: COVID-19 is often related to hyperinflammation that drives lung or multiorgan injury. The immunopathological mechanisms that cause excessive inflammation are under investigation and constantly updated. Here, a gene network approach was used on recently published data sets to identify possible COVID-19 inflammatory mechanisms and bioactive genes. First, network analysis of putative SARS-CoV-2 cellular receptors led to the mining of a neutrophil-response signature and relevant inflammatory genes. Second, analysis of RNA-seq data sets of lung cells infected with SARS-CoV-2 revealed that infected cells expressed neutrophil-attracting chemokines. Third, analysis of RNA-seq data sets of bronchoalveolar lavage fluid cells from COVID-19 patients identified upregulation of neutrophil genes and chemokines. Different inflammatory genes mined here, including TNFR, IL-8, CXCR1, CXCR2, ADAM10, GPR84, MME, ANPEP, and LAP3, might be druggable targets in efforts to limit SARS-CoV-2 inflammation in severe clinical cases. The possible role of neutrophils in COVID-19 inflammation needs to be studied further.", "qid": 38, "docid": "9l5ajo4q", "rank": 20, "score": 0.8196166157722473}, {"content": "Title: Tackle the free radicals damage in COVID-19. Content: COVID-19 is a severe pandemic which has caused a devastating amount of loss in lives around the world, and yet we still don't know how to appropriately treat this disease. We know very little about the pathogenesis of SARS-CoV-2, the virus which induces the COVID-19. However, COVID-19 does share many similar symptoms with SARS and influenza. Previous scientific discoveries learned from lab animal models and clinical practices shed light on possible pathogenic mechanisms in COVID-19. In the past decades, accumulated scientific findings confirmed the pathogenic role of free radicals damage in respiratory virus infection. Astonishingly very few medical professionals mention the crucial role of free radical damage in COVID-19. This hypothesis aims to summarize the crucial pathogenic role of free radical damage in respiratory virus induced pneumonia and suggest an antioxidative therapeutic strategy for COVID-19.", "qid": 38, "docid": "8aiexhdd", "rank": 21, "score": 0.8192342519760132}, {"content": "Title: The renin-angiotensin-aldosterone system: Role in pathogenesis and potential therapeutic target in COVID-19. Content: Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 novel coronavirus, has spread worldwide causing high fatality rates. Neither a vaccine nor specific therapeutic approaches are available, hindering the fight against this disease and making better understanding of its pathogenesis essential. Despite similarities between SARS-CoV-2 and SARS-CoV, the former has unique characteristics which represent a great challenge to physicians. The mechanism of COVID-19 infection and pathogenesis is still poorly understood. In the present review, we highlight possible pathways involved in the pathogenesis of COVID-19 and potential therapeutic targets, focusing on the role of the renin-angiotensin-aldosterone system.", "qid": 38, "docid": "ep73us0e", "rank": 22, "score": 0.8187038898468018}, {"content": "Title: The renin-angiotensin-aldosterone system: Role in pathogenesis and potential therapeutic target in COVID-19 Content: Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 novel coronavirus, has spread worldwide causing high fatality rates. Neither a vaccine nor specific therapeutic approaches are available, hindering the fight against this disease and making better understanding of its pathogenesis essential. Despite similarities between SARS-CoV-2 and SARS-CoV, the former has unique characteristics which represent a great challenge to physicians. The mechanism of COVID-19 infection and pathogenesis is still poorly understood. In the present review, we highlight possible pathways involved in the pathogenesis of COVID-19 and potential therapeutic targets, focusing on the role of the renin-angiotensin-aldosterone system.", "qid": 38, "docid": "bc2wpryp", "rank": 23, "score": 0.818703830242157}, {"content": "Title: COVID-19: pathogenesis, genetic polymorphism, clinical features and laboratory findings Content: COVID-19 caused by a novel agent SARS-CoV-2 progressed to a pandemic condition and resulted in a major public health concern worldwide, leading to social and economic issues at the same time. The pathogenesis of COVID-19 starts with the bonding of the virus to ACE2 receptors expressed in many tissues, and the triggered excessive immune response plays a critical role in the course of the disease. The cytokine storm that occurs upon excessive production of pro-inflammatory cytokines is considered responsible for the severe progression of the disease and the organ damage. However, the accurate pathophysiological mechanism of the disease, which progresses with various clinical presentations, is still substantially unknown. While various studies have been conducted on the effect of genetic polymorphism on the course and severity of the disease, the presence of a significant effect has not been proven yet. The clinical course of the disease is variable, with clinical representation ranging from 81% mild course to 14% severe course along with 5% critical course in patients. Asymptomatic course is considered to be higher than expected, although its frequency is not known exactly. Older adults and those with comorbidities are exposed to a more severe disease course. The disease progress with various symptoms, such as fever, cough, dyspnea, malaise, myalgia, taste and smell dysfunctions, diarrhea, and headache. A range of complications (acute respiratory distress syndrome, thromboembolic conditions, arrhythmia and cardiac events, secondary infections) could be seen during the course of the disease. Varied laboratory tests are vital to determine these verity and prognosis of the disease, along with the condition and exposure of the affected systems during thecourse of COVID-19.", "qid": 38, "docid": "6hzlbpxg", "rank": 24, "score": 0.818313479423523}, {"content": "Title: [The Agreed Experts' Position of the Eurasian Association of Therapists on Some new Mechanisms of COVID-19 Pathways: Focus on Hemostasis, Hemotransfusion Issues and Blood gas Exchange] Content: The article discusses pathogenesis and treatment of COVID-19. The authors presented state-of-the-art insight into hemostatic disorders in patients with COVID-19 and clinical recommendations on prevention of thrombosis and thromboembolism in patients infected with SARS-CoV-2. The article discussed in detail a new hypothesis proposed by Chinese physicians about a new component in the pathogenesis of COVID-19, namely, about the effect of SARS-CoV-2 virus on the hemoglobin beta-chain and the formation of a complex with porphyrin, which results in displacement of the iron ion. Thus, hemoglobin loses the capability for transporting oxygen, which aggravates hypoxia and worsens the prognosis. The article stated rules of hemotransfusion safety in the conditions of COVID-19 pandemic.", "qid": 38, "docid": "kuoq0yuo", "rank": 25, "score": 0.8178317546844482}, {"content": "Title: [The Agreed Experts' Position of the Eurasian Association of Therapists on Some new Mechanisms of COVID-19 Pathways: Focus on Hemostasis, Hemotransfusion Issues and Blood gas Exchange]. Content: The article discusses pathogenesis and treatment of COVID-19. The authors presented state-of-the-art insight into hemostatic disorders in patients with COVID-19 and clinical recommendations on prevention of thrombosis and thromboembolism in patients infected with SARS-CoV-2. The article discussed in detail a new hypothesis proposed by Chinese physicians about a new component in the pathogenesis of COVID-19, namely, about the effect of SARS-CoV-2 virus on the hemoglobin beta-chain and the formation of a complex with porphyrin, which results in displacement of the iron ion. Thus, hemoglobin loses the capability for transporting oxygen, which aggravates hypoxia and worsens the prognosis. The article stated rules of hemotransfusion safety in the conditions of COVID-19 pandemic.", "qid": 38, "docid": "ag7zgycl", "rank": 26, "score": 0.8178317546844482}, {"content": "Title: Inflammatory and Coagulative Considerations for the Management of Orthopaedic Trauma Patients with COVID-19: A Review of the Current Evidence and Our Surgical Experience Content: Mounting evidence suggests that the pathogenesis of coronavirus disease 2019 (COVID-19) involves a hyperinflammatory response predisposing patients to thromboembolic disease and acute respiratory distress. In the setting of severe blunt trauma, damaged tissues induce a local and systemic inflammatory response through similar pathways to COVID-19. As such, patients with COVID-19 sustaining orthopaedic trauma injuries may have an amplified response to the traumatic insult due to their baseline hyperinflammatory and hypercoagulable state. These patients may have compromised physiological reserve to withstand the insult of surgical intervention before reaching clinical instability. Herein, we review the current evidence regarding pathogenesis of COVID-19 and its implications on the management of orthopaedic trauma patients by discussing a case and the most recent literature.", "qid": 38, "docid": "ldjqczvr", "rank": 27, "score": 0.8173670768737793}, {"content": "Title: Devilishly radical NETwork in COVID-19: Oxidative stress, neutrophil extracellular traps (NETs), and T cell suppression Content: Pandemic coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and poses an unprecedented challenge to healthcare systems due to the lack of a vaccine and specific treatment options. Accordingly, there is an urgent need to understand precisely the pathogenic mechanisms underlying this multifaceted disease. There is increasing evidence that the immune system reacts insufficiently to SARS-CoV-2 and thus contributes to organ damage and to lethality. In this review, we suggest that the overwhelming production of reactive oxygen species (ROS) resulting in oxidative stress is a major cause of local or systemic tissue damage that leads to severe COVID-19. It increases the formation of neutrophil extracellular traps (NETs) and suppresses the adaptive arm of the immune system, i.e. T cells that are necessary to kill virus-infected cells. This creates a vicious cycle that prevents a specific immune response against SARS-CoV-2. The key role of oxidative stress in the pathogenesis of severe COVID-19 implies that therapeutic counterbalancing of ROS by antioxidants such as vitamin C or NAC and/or by antagonizing ROS production by cells of the MPS and neutrophil granulocytes and/or by blocking of TNF-\u03b1 can prevent COVID-19 from becoming severe. Controlled clinical trials and preclinical models of COVID-19 are needed to evaluate this hypothesis.", "qid": 38, "docid": "hs2q61gw", "rank": 28, "score": 0.8172050714492798}, {"content": "Title: Hypothesis for potential pathogenesis of SARS-CoV-2 infection--a review of immune changes in patients with viral pneumonia Content: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with droplets and contact as the main means of transmission Since the first case appeared in Wuhan, China, in December 2019, the outbreak has gradually spread nationwide Up to now, according to official data released by the Chinese health commission, the number of newly diagnosed patients has been declining, and the epidemic is gradually being controlled Although most patients have mild symptoms and good prognosis after infection, some patients developed severe and die from multiple organ complications The pathogenesis of SARS-CoV-2 infection in humans remains unclear Immune function is a strong defense against invasive pathogens and there is currently no specific antiviral drug against the virus This article reviews the immunological changes of coronaviruses like SARS, MERS and other viral pneumonia similar to SARS-CoV-2 Combined with the published literature, the potential pathogenesis of COVID-19 is inferred, and the treatment recommendations for giving high-doses intravenous immunoglobulin and low-molecular-weight heparin anticoagulant therapy to severe type patients are proposed", "qid": 38, "docid": "t6gqa48n", "rank": 29, "score": 0.8166635036468506}, {"content": "Title: COVID-19 severity is associated with immunopathology and multi-organ damage Content: COVID-19 is characterised by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand how host responses contribute to COVID-19 pathophysiology, we used a multi-omics approach to identify molecular markers in peripheral blood and plasma samples that distinguish COVID-19 patients experiencing a range of disease severities. A large number of expressed genes, proteins, metabolites and extracellular RNAs (exRNAs) were identified that exhibited strong associations with various clinical parameters. Multiple sets of tissue-specific proteins and exRNAs varied significantly in both mild and severe patients, indicative of multi-organ damage. The continuous activation of IFN-I signalling and neutrophils, as well as a high level of inflammatory cytokines, were observed in severe disease patients. In contrast, COVID-19 in mild patients was characterised by robust T cell responses. Finally, we show that some of expressed genes, proteins and exRNAs can be used as biomarkers to predict the clinical outcomes of SARS-CoV-2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID-19 and will help guide future studies in this area.", "qid": 38, "docid": "o2k8pquk", "rank": 30, "score": 0.8162955045700073}, {"content": "Title: COVID-19: Pathogenesis, Genetic Polymorphism, Clinical Features and Laboratory Findings. Content: COVID-19 caused by a novel agent SARS-CoV-2 progressed to a pandemic condition and resulted in a major public health concern worldwide, leading to social and economic issues at the same time. The pathogenesis of COVID-19 starts with the bonding of the virus to ACE-2 receptors expressed in many tissues, and the triggered excessive immune response plays a critical role in the course of the disease. The cytokine storm that occurs upon excessive production of pro-inflammatory cytokines is considered responsible for the severe progression of the disease and the organ damage. However, the accurate pathophysiological mechanism of the disease, which progresses with various clinical presentations, is still substantially unknown. While various studies have been conducted on the effect of genetic polymorphism on the course and severity of the disease, the presence of a significant effect has not been proven yet. The clinical course of the disease is variable, with clinical representation ranging from 81% mild course to 14% severe course along with 5% critical course in patients. Asymptomatic course is considered to be higher than expected, although its frequency is not known exactly. Older adults and those with comorbidities are exposed to a more severe disease course. The disease progress with various symptoms, such as fever, cough, dyspnea, malaise, myalgia, taste and smell dysfunctions, diarrhea, and headache. A range of complications (Acute Respiratory Distress Syndrome, thromboembolic conditions, arrhythmia and cardiac events, secondary infections) could be seen during the course of the disease. Varied laboratory tests are vital to determine the severity and prognosis of the disease, along with the condition and exposure of the affected systems during the course of COVID-19.", "qid": 38, "docid": "ot5v8n0c", "rank": 31, "score": 0.8160284757614136}, {"content": "Title: The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system Content: In 2019-2020 a new coronavirus named SARS-CoV-2 was identified as the causative agent of a several acute respiratory infection named COVID-19, which is causing a worldwide pandemic. There are still many unresolved questions regarding the pathogenesis of this disease and especially the reasons underlying the extremely different clinical course, ranging from asymptomatic forms to severe manifestations, including the Acute Respiratory Distress Syndrome (ARDS). SARS-CoV-2 showed phylogenetic similarities to both SARS-CoV and MERS-CoV viruses, and some of the clinical features are shared between COVID-19 and previously identified beta-coronavirus infections. Available evidence indicate that the so called \"cytokine storm\" an uncontrolled over-production of soluble markers of inflammation which, in turn, sustain an aberrant systemic inflammatory response, is a major responsible for the occurrence of ARDS. Chemokines are low molecular weight proteins with powerful chemoattractant activity which play a role in the immune cell recruitment during inflammation. This review will be aimed at providing an overview of the current knowledge on the involvement of the chemokine/chemokine-receptor system in the cytokine storm related to SARS-CoV-2 infection. Basic and clinical evidences obtained from previous SARS and MERS epidemics and available data from COVID-19 will be taken into account.", "qid": 38, "docid": "9ch0wti7", "rank": 32, "score": 0.8152577877044678}, {"content": "Title: The Cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system Content: In 2019-2020 a new coronavirus named SARS-CoV-2 was identified as the causative agent of a several acute respiratory infection named COVID-19, which is causing a worldwide pandemic. There are still many unresolved questions regarding the pathogenesis of this disease and especially the reasons underlying the extremely different clinical course, ranging from asymptomatic forms to severe manifestations, including the Acute Respiratory Distress Syndrome (ARDS). SARS-CoV-2 showed phylogenetic similarities to both SARS-CoV and MERS-CoV viruses, and some of the clinical features are shared between COVID-19 and previously identified beta-coronavirus infections. Available evidence indicate that the so called \u201ccytokine storm\u201d an uncontrolled over-production of soluble markers of inflammation which, in turn, sustain an aberrant systemic inflammatory response, is a major responsible for the occurrence of ARDS. Chemokines are low molecular weight proteins with powerful chemoattractant activity which play a role in the immune cell recruitment during inflammation. This review will be aimed at providing an overview of the current knowledge on the involvement of the chemokine/chemokine-receptor system in the cytokine storm related to SARS-CoV-2 infection. Basic and clinical evidences obtained from previous SARS and MERS epidemics and available data from COVID-19 will be taken into account.", "qid": 38, "docid": "ex9nh1yi", "rank": 33, "score": 0.8148702383041382}, {"content": "Title: SARS-CoV2 may evade innate immune response, causing uncontrolled neutrophil extracellular traps formation and multi-organ failure Content: We demonstrate that the general clinical conditions, risk factors and numerous pathological and biological features of COVID-19 are analogous with various disorders caused by the uncontrolled formation of neutrophil extracellular traps and their by-products. Given the rapid evolution of this disease's symptoms and its lethality, we hypothesize that SARS-CoV2 evades innate immune response causing COVID-19 progresses under just such an amplifier loop, leading to a massive, uncontrolled inflammation process. This work allows us to propose new strategies for treating the pandemic.", "qid": 38, "docid": "faz6icy3", "rank": 34, "score": 0.8144598007202148}, {"content": "Title: SARS-CoV2 may evade innate immune response, causing uncontrolled neutrophil extracellular traps formation and multi-organ failure. Content: We demonstrate that the general clinical conditions, risk factors and numerous pathological and biological features of COVID-19 are analogous with various disorders caused by the uncontrolled formation of neutrophil extracellular traps and their by-products. Given the rapid evolution of this disease's symptoms and its lethality, we hypothesize that SARS-CoV2 evades innate immune response causing COVID-19 progresses under just such an amplifier loop, leading to a massive, uncontrolled inflammation process. This work allows us to propose new strategies for treating the pandemic.", "qid": 38, "docid": "va8kg3kb", "rank": 35, "score": 0.8144598007202148}, {"content": "Title: Serum protein profiling reveals a landscape of inflammation and immune signaling in early-stage COVID-19 infection Content: Coronavirus disease 2019 (COVID-19) is a highly contagious infection and threating the human lives in the world. The elevation of cytokines in blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients. However, the comprehensive changes of serum proteins in COVID-19 patients throughout the SARS-CoV-2 infection is unknown. In this work, we developed a high-density antibody microarray and performed an in-depth proteomics analysis of serum samples collected from early COVID-19 (n=15) and influenza (n=13) patients. We identified a large set of differentially expressed proteins (n=125) that participate in a landscape of inflammation and immune signaling related to the SARS-CoV-2 infection. Furthermore, the significant correlations of neutrophil and lymphocyte with the CCL2 and CXCL10 mediated cytokine signaling pathways was identified. These information are valuable for the understanding of COVID-19 pathogenesis, identification of biomarkers and development of the optimal anti-inflammation therapy.", "qid": 38, "docid": "nr7d1zor", "rank": 36, "score": 0.8140110969543457}, {"content": "Title: Hypothesis for potential pathogenesis of SARS-CoV-2 infection\u2013a review of immune changes in patients with viral pneumonia Content: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with droplets and contact as the main means of transmission. Since the first case appeared in Wuhan, China, in December 2019, the outbreak has gradually spread nationwide. Up to now, according to official data released by the Chinese health commission, the number of newly diagnosed patients has been declining, and the epidemic is gradually being controlled. Although most patients have mild symptoms and good prognosis after infection, some patients developed severe and die from multiple organ complications. The pathogenesis of SARS-CoV-2 infection in humans remains unclear. Immune function is a strong defense against invasive pathogens and there is currently no specific antiviral drug against the virus. This article reviews the immunological changes of coronaviruses like SARS, MERS and other viral pneumonia similar to SARS-CoV-2. Combined with the published literature, the potential pathogenesis of COVID-19 is inferred, and the treatment recommendations for giving high-doses intravenous immunoglobulin and low-molecular-weight heparin anticoagulant therapy to severe type patients are proposed.", "qid": 38, "docid": "9iv1krak", "rank": 37, "score": 0.8122842311859131}, {"content": "Title: SARS-CoV-2 pandemic and research gaps: Understanding SARS-CoV-2 interaction with the ACE2 receptor and implications for therapy Content: The COVID-19 pandemic is an emerging threat to global public health. While our current understanding of COVID-19 pathogenesis is limited, a better understanding will help us develop efficacious treatment and prevention strategies for COVID-19. One potential therapeutic target is angiotensin converting enzyme 2 (ACE2). ACE2 primarily catalyzes the conversion of angiotensin I (Ang I) to a nonapeptide angiotensin or the conversion of angiotensin II (Ang II) to angiotensin 1-7 (Ang 1-7) and has direct effects on cardiac function and multiple organs via counter-regulation of the renin-angiotensin system (RAS). Significant to COVID-19, ACE2 is postulated to serve as a major entry receptor for SARS-CoV-2 in human cells, as it does for SARS-CoV. Many infected individuals develop COVID-19 with fever, cough, and shortness of breath that can progress to pneumonia. Disease progression promotes the activation of immune cells, platelets, and coagulation pathways that can lead to multiple organ failure and death. ACE2 is expressed by epithelial cells of the lungs at high level, a major target of the disease, as seen in post-mortem lung tissue of patients who died with COVID-19, which reveals diffuse alveolar damage with cellular fibromyxoid exudates bilaterally. Comparatively, ACE2 is expressed at low level by vascular endothelial cells of the heart and kidney but may also be targeted by the virus in severe COVID-19 cases. Interestingly, SARS-CoV-2 infection downregulates ACE2 expression, which may also play a critical pathogenic role in COVID-19. Importantly, targeting ACE2/Ang 1-7 axis and blocking ACE2 interaction with the S protein of SARS-CoV-2 to curtail SARS-CoV-2 infection are becoming very attractive therapeutics potential for treatment and prevention of COVID-19. Here, we will discuss the following subtopics: 1) ACE2 as a receptor of SARS-CoV-2; 2) clinical and pathological features of COVID-19; 3) role of ACE2 in the infection and pathogenesis of SARS; 4) potential pathogenic role of ACE2 in COVID-19; 5) animal models for pathological studies and therapeutics; and 6) therapeutics development for COVID-19.", "qid": 38, "docid": "iemvifbg", "rank": 38, "score": 0.8122220039367676}, {"content": "Title: Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: A novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis Content: Early clinical evidence suggests that severe cases of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are frequently characterized by hyperinflammation, imbalance of renin-angiotensin-aldosterone system, and a particular form of vasculopathy, thrombotic microangiopathy, and intravascular coagulopathy. In this paper, we present an immunothrombosis model of COVID-19. We discuss the underlying pathogenesis and the interaction between multiple systems, resulting in propagation of immunothrombosis, which through investigation in the coming weeks, may lead to both an improved understanding of COVID-19 pathophysiology and identification of innovative and efficient therapeutic targets to reverse the otherwise unfavorable clinical outcome of many of these patients.", "qid": 38, "docid": "p298vft5", "rank": 39, "score": 0.8121917247772217}, {"content": "Title: Why the immune system fails to mount an adaptive immune response to a Covid -19 infection. Content: The Covid-19 pandemic has already affected many thousands of people and has become the greatest health challenge worldwide [1]. The range of clinical presentations varies from asymptomatic and mild clinical symptoms to acute respiratory-distress syndrome (ARDS) and death. Due to the unknown number of asymptomatic viral-shedding and pauci-symptomatic people in the community, the total number of infections is uncertain. As yet, effective treatment is unavailable. However, the results of preliminary studies and clinical trials are improving our understanding of the pathogenesis and treatment of Covid-19. Herein, we share our personal opinions on the immunopathogenesis of this infection.", "qid": 38, "docid": "z2n51cet", "rank": 40, "score": 0.8117361068725586}, {"content": "Title: Inflammatory markers in Covid-19 Patients: a systematic review and meta-analysis. Content: Introduction Diagnosis of COVID-19 is based on clinical manifestation, history of exposure, positive findings on chest CT and laboratory tests. It has been shown that inflammation plays a role in pathogenesis of COVID-19. Method We used the necessary transformations to convert the median and IQR to mean and SD Random-effect model using Der Simonian, and Laird methods was used if heterogeneity between studies was significant, the homogeneity among studies was assessed with I2 Statistic, values above 50%, and for the chi-square test, P-values <0.1 was supposed statistically significant Results Twelve studies were included in the analysis that all of which were conducted in China in the year 2020. The result of combining 12 articles with 772 participants showed that the pooled estimate of the mean of lymphocyte with 95% CI was (Mean: 1.01; 95% CI (0.76-1.26); p-value<0.001). About WBC the pooled result of 9 studies with 402 participants was (Mean: 5.11; 95% CI (3.90-6.32); p-value<0.001) Also the pooled mean estimate of 9 studies with 513 patients for the ratio of Neutrophil/lymphocyte was (Mean: 3.62; 95% CI (1.48-5.77); p-value=0.001). The pooled mean from the combination of 7 studies with 521 patients on CRP was (Mean: 28.75; 95% CI (8.04-49.46). Conclusion Inflammatory Markers increase in patients with Covid-19, which can be a good indicator to find patients.", "qid": 38, "docid": "9db9dpvd", "rank": 41, "score": 0.8116154670715332}, {"content": "Title: Potential role of endothelial cell surface ectopic redox complexes in COVID-19 disease pathogenesis Content: The novel coronavirus infectious disease (COVID-19) has rapidly spread and poses a great challenge to researchers, both in elucidating its pathogenic mechanism and developing effective treatments. It has been recently proposed that COVID-19 is an endothelial disease. Indeed, the COVID-19 virus binds to angiotensin-converting enzyme type 2 (ACE2), which is expressed in endothelial cells. ACE2 could be implicated in the production of reactive oxygen species (ROS) caused by endothelial dysfunction due to viral damage. Consequently, oxidative stress could prime these cells to acquire a pro-thrombotic and pro-inflammatory phenotype, predisposing patients to thromboembolic and vasculitic events and to disseminated intravascular coagulopathy (DIC). This implies a pivotal role played by oxygen in the pathogenetic mechanism of COVID-19 disease, in that its availability would tune the oxidant state and consequent damage.", "qid": 38, "docid": "2ilinc5k", "rank": 42, "score": 0.8100334405899048}, {"content": "Title: Potential role of endothelial cell surface ectopic redox complexes in COVID-19 disease pathogenesis. Content: The novel coronavirus infectious disease (COVID-19) has rapidly spread and poses a great challenge to researchers, both in elucidating its pathogenic mechanism and developing effective treatments. It has been recently proposed that COVID-19 is an endothelial disease. Indeed, the COVID-19 virus binds to angiotensin-converting enzyme type 2 (ACE2), which is expressed in endothelial cells. ACE2 could be implicated in the production of reactive oxygen species (ROS) caused by endothelial dysfunction due to viral damage. Consequently, oxidative stress could prime these cells to acquire a pro-thrombotic and pro-inflammatory phenotype, predisposing patients to thromboembolic and vasculitic events and to disseminated intravascular coagulopathy (DIC). This implies a pivotal role played by oxygen in the pathogenetic mechanism of COVID-19 disease, in that its availability would tune the oxidant state and consequent damage.", "qid": 38, "docid": "s7u0ct2l", "rank": 43, "score": 0.8100334405899048}, {"content": "Title: Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: A novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis Content: Abstract Early clinical evidence suggests that severe cases of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are frequently characterized by hyperinflammation, imbalance of renin-angiotensin-aldosterone system, and a particular form of vasculopathy, thrombotic microangiopathy, and intravascular coagulopathy. In this paper, we present an immunothrombosis model of COVID-19. We discuss the underlying pathogenesis and the interaction between multiple systems, resulting in propagation of immunothrombosis, which through investigation in the coming weeks, may lead to both an improved understanding of COVID-19 pathophysiology and identification of innovative and efficient therapeutic targets to reverse the otherwise unfavorable clinical outcome of many of these patients.", "qid": 38, "docid": "7vqnqp83", "rank": 44, "score": 0.80992591381073}, {"content": "Title: Immunology of COVID-19: current state of the science Content: Abstract The coronavirus disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide, igniting an unprecedented effort from the scientific community to understand the biological underpinning of COVID19 pathophysiology. In this review, we summarize the current state of knowledge of innate and adaptive immune responses elicited by SARS-CoV-2 infection and the immunological pathways that likely contribute to disease severity and death. We also discuss the rationale and clinical outcome of current therapeutic strategies as well as prospective clinical trials to prevent or treat SARS-CoV-2 infection.", "qid": 38, "docid": "61fmul8c", "rank": 45, "score": 0.8096580505371094}, {"content": "Title: Immunology of COVID-19: Current State of the Science Content: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide, igniting an unprecedented effort from the scientific community to understand the biological underpinning of COVID19 pathophysiology. In this Review, we summarize the current state of knowledge of innate and adaptive immune responses elicited by SARS-CoV-2 infection and the immunological pathways that likely contribute to disease severity and death. We also discuss the rationale and clinical outcome of current therapeutic strategies as well as prospective clinical trials to prevent or treat SARS-CoV-2 infection.", "qid": 38, "docid": "w66gtl3b", "rank": 46, "score": 0.8090295791625977}, {"content": "Title: Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by COVID-19: anti-inflammatory strategies Content: COVID-19 (coronavirus disease-19) involves humans as well as animals and may cause serious damage to the respiratory tract including the lung This pathogenic virus has been identified in swabs performed on the throat and nose of patients who suffer from or are suspected of the disease When COVID-19 infect the upper and lower respiratory tract it can cause mild or highly acute respiratory syndrome with consequent release of pro-inflammatory cytokines, including interleukin (IL)-1b and IL-6 The binding of COVID-19 to the Toll Like Receptor (TLR) causes the release of pro-IL-1b which is cleaved by caspase-1, followed by inflammasome activation and production of active mature IL-1b which is a mediator of lung inflammation, fever and fibrosis Suppression of pro-inflammatory IL-1 family members and IL-6 have been shown to have a therapeutic effect in many inflammatory diseases, including viral infections Cytokine IL-37 has the ability to suppress innate and acquired immune response and also has the capacity to inhibit inflammation by acting on IL-18Ra receptor IL-37 performs its immunosuppressive activity by acting on mTOR and increasing the adenosine monophosphate (AMP) kinase This cytokine inhibits class II histocompatibility complex (MHC) molecules and inflammation in inflammatory diseases by suppressing MyD88 and subsequently IL-1\u03b2, IL-6, TNF and CCL2 The suppression of IL-1b by IL-37 in inflammatory state induced by COVID-19 can have a new therapeutic effect previously unknown Another inhibitory cytokine is IL-38, the newest cytokine of the IL-1 family members, produced by several immune cells including B cells and macrophages IL-38 is also a suppressor cytokine which inhibits IL-1b and other pro-inflammatory IL-family members IL-38 is a potential therapeutic cytokine which inhibits inflammation in viral infections including that caused by COVID-19, providing a new relevant strategy", "qid": 38, "docid": "4gze6w35", "rank": 47, "score": 0.8081663846969604}, {"content": "Title: SARS-CoV-2 COVID-19 susceptibility and lung inflammatory storm by smoking and vaping Content: The current pandemic of COVID-19 has caused severe morbidity and mortality across the globe. People with a smoking history have severe disease outcomes by COVID-19 infection. Epidemiological studies show that old age and pre-existing disease conditions (hypertension and diabetes) result in severe disease outcome and mortality amongst COVID-19 patients. Evidences suggest that the S1 domain of the SARS-CoV-2 (causative agent of COVID-19) membrane spike has a high affinity towards the angiotensin-converting enzyme 2 (ACE2) receptor found on the host\u2019s lung epithelium. Likewise, TMPRSS2 protease has been shown to be crucial for viral activation thus facilitating the viral engulfment. The viral entry has been shown to cause \u2018cytokine storm\u2019 involving excessive production of pro-inflammatory cytokines/chemokines including IL-6, TNF-\u03b1, IFN-\u03b3, IL-2, IL-7, IP-10, MCP-3 or GM-CSF, which is augmented by smoking. Future research could target these inflammatory-immunological responses to develop effective therapy for COVID-19. This mini-review provides a consolidated account on the role of inflammation and immune responses, proteases, and epithelial permeability by smoking and vaping during SARS-CoV2 infection with future directions of research, and provides a list of the potential targets for therapies particularly controlling cytokine storms in the lung.", "qid": 38, "docid": "n0d9b50t", "rank": 48, "score": 0.8075873851776123}, {"content": "Title: Distinct infection process of SARS-CoV-2 in human bronchial epithelial cells line Content: COVID-19, caused by SARS-CoV-2, leads to a series of clinical symptoms of respiratory and pulmonary inflammatory reactions via unknown pathologic mechanisms related to the viral infection process in tracheal or bronchial epithelial cells. Investigation of this viral infection in the human bronchial epithelial cell line (16HBE) suggests that SARS-CoV-2 can enter these cells through interaction between its membrane-localized S protein with the ACE2 molecule on the host cell membrane. Further observation indicates distinct viral replication with a dynamic and moderate increase, whereby viral replication does not lead to a specific cytopathic effect but maintains a continuous release of progeny virions from infected cells. Although mRNA expression of various innate immune signaling molecules is altered in the cells, transcription of IFN&#945;, IFN\u00df and IFN\u00ce\u00b3 is unchanged. Furthermore, expression of some interleukins related to inflammatory reactions, such as IL-6, IL-2 and IL-8, is maintained at low levels, whereas that of interleukins involved in immune regulation is upregulated. Interestingly, IL-22, an interleukin that functions mainly in tissue repair, shows very high expression. Collectively, these data suggest a distinct infection process for this virus in respiratory epithelial cells, which may be linked to its clinicopathological mechanism. This article is protected by copyright. All rights reserved.", "qid": 38, "docid": "k4lfow9h", "rank": 49, "score": 0.8075779676437378}, {"content": "Title: Immunopathology and immunotherapeutic strategies in severe acute respiratory syndrome coronavirus 2 infection. Content: The outbreak of coronavirus disease 2019 (COVID-19) and pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a major concern globally. As of 14 April 2020, more than 1.9 million COVID-19 cases have been reported in 185 countries. Some patients with COVID-19 develop severe clinical manifestations, while others show mild symptoms, suggesting that dysregulation of the host immune response contributes to disease progression and severity. In this review, we have summarized and discussed recent immunological studies focusing on the response of the host immune system and the immunopathology of SARS-CoV-2 infection as well as immunotherapeutic strategies for COVID-19. Immune evasion by SARS-CoV-2, functional exhaustion of lymphocytes, and cytokine storm have been discussed as part of immunopathology mechanisms in SARS-CoV-2 infection. Some potential immunotherapeutic strategies to control the progression of COVID-19, such as passive antibody therapy and use of interferon \u03b1\u03b2 and IL-6 receptor (IL-6R) inhibitor, have also been discussed. This may help us to understand the immune status of patients with COVID-19, particularly those with severe clinical presentation, and form a basis for further immunotherapeutic investigations.", "qid": 38, "docid": "vlse2pzs", "rank": 50, "score": 0.8074476718902588}, {"content": "Title: Transcriptomic profiling of disease severity in patients with COVID-19 reveals role of blood clotting and vasculature related genes Content: COVID-19 caused by SARS-CoV-2 manifests as a range of symptoms. Understanding the molecular mechanisms responsible for immuno-pathogenesis of disease is important for treatment and management of COVID-19. We examined host transcriptomes in moderate and severe COVID-19 cases with a view to identifying pathways that affect its progression. RNA extracted from whole blood of COVID-19 cases was analysed by microarray analysis. Moderate and severe cases were compared with healthy controls and differentially regulated genes (DEGs) categorized into cellular pathways. DEGs in COVID-19 cases were mostly related to host immune activation and cytokine signaling, pathogen uptake, host defenses, blood and vasculature genes, and SARS-CoV-2- and other virus- affected pathways. The DEGs in these pathways were increased in severe compared with moderate cases. In a severe COVID-19 patient with an unfavourable outcome we observed dysregulation of genes in platelet homeostasis and cardiac conduction and fibrin clotting with disease progression.", "qid": 38, "docid": "yrelcfx9", "rank": 51, "score": 0.8073365092277527}, {"content": "Title: The pathogenesis and treatment of the `Cytokine Storm' in COVID-19 Content: Summary Cytokine storm is an excessive immune response to external stimuli. The pathogenesis of the cytokine storm is complex. The disease progresses rapidly, and the mortality is high. Certain evidence shows that, during the coronavirus disease 2019 (COVID-19) epidemic, the severe deterioration of some patients has been closely related to the cytokine storm in their bodies. This article reviews the occurrence mechanism and treatment strategies of the COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.", "qid": 38, "docid": "fqlv35vo", "rank": 52, "score": 0.8072147965431213}, {"content": "Title: Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions Content: The coronavirus disease-19 pandemic (COVID-19), which appeared in China in December 2019 and rapidly spread throughout the world, has forced clinicians and scientists to take up extraordinary challenges. This unprecedented situation led to the inception of numerous fundamental research protocols and many clinical trials. It quickly became apparent that although COVID-19, in the vast majority of cases, was a benign disease, it could also develop a severe form with sometimes fatal outcomes. Cytokines are central to the pathophysiology of COVID-19; while some of them are beneficial (type-I interferon, interleukin-7), others appear detrimental (interleukin-1\u00df, -6, and TNF-&#945;) particularly in the context of the so-called cytokine storm. Yet another characteristic of the disease has emerged: concomitant immunodeficiency, notably involving impaired type-I interferon response, and lymphopenia. This review provides an overview of current knowledge on COVID-19 immunopathology. We discuss the defective type-I IFN response, the theoretical role of IL-7 to restore lymphocyte repertoire, as well as we mention the two patterns observed in severe COVID-19 (i.e. interleukin-1\u00df-driven macrophage activation syndrome vs. interleukin-6-driven immune dysregulation). Next, reviewing current evidence drawn from clinical trials, we examine a number of cytokine and anti-cytokine therapies, including interleukin-1, -6, and TNF inhibitors, as well as less targeted therapies, such as corticosteroids, chloroquine, or JAK inhibitors.", "qid": 38, "docid": "ybuf69f9", "rank": 53, "score": 0.8069744110107422}, {"content": "Title: Histopathology and genetic susceptibility in COVID\u201019 pneumonia Content: The clinical features of COVID\u201019 range from a mild illness to patients with a very severe illness with acute hypoxemic respiratory failure requiring ventilation and Intensive Care Unit admission. Risk factors for a fatal disease include older age, respiratory disease, diabetes mellitus, obesity and hypertension. Little is known about the mechanisms behind observed episodes of sudden deterioration or the infrequent idiosyncratic clinical demise in otherwise healthy and young subjects. As in other diseases, the answer to some of these questions may in time be provided by genotyping as well careful clinical, serological, radiological and histopathological phenotyping, which enable mechanistic insights into the differences in pathogenesis and underlying immunological and tissue regenerative response patterns. We will aim to provide a brief overview of the existing evidence for such differences in host response and outcome, and generate hypotheses for divergent patterns and avenues for future research, by highlighting similarities and differences in histopathological appearance between COVID19 and influenza as well as previous coronavirus outbreaks, and by discussing predisposition through genetics and underlying disease.", "qid": 38, "docid": "mt939rqw", "rank": 54, "score": 0.80633145570755}, {"content": "Title: Immune Response, Inflammation, and the Clinical Spectrum of COVID-19 Content: The current COVID-19 pandemic began in December 2019 in Wuhan (China) and rapidly extended to become a global sanitary and economic emergency. Its etiological agent is the coronavirus SARS-CoV-2. COVID-19 presents a wide spectrum of clinical manifestations, which ranges from an asymptomatic infection to a severe pneumonia accompanied by multisystemic failure that can lead to a patient's death. The immune response to SARS-CoV-2 is known to involve all the components of the immune system that together appear responsible for viral elimination and recovery from the infection. Nonetheless, such immune responses are implicated in the disease's progression to a more severe and lethal process. This review describes the general aspects of both COVID-19 and its etiological agent SARS-CoV-2, stressing the similarities with other severe coronavirus infections, such as SARS and MERS, but more importantly, pointing toward the evidence supporting the hypothesis that the clinical spectrum of COVID-19 is a consequence of the corresponding variable spectrum of the immune responses to the virus. The critical point where progression of the disease ensues appears to center on loss of the immune regulation between protective and altered responses due to exacerbation of the inflammatory components. Finally, it appears possible to delineate certain major challenges deserving of exhaustive investigation to further understand COVID-19 immunopathogenesis, thus helping to design more effective diagnostic, therapeutic, and prophylactic strategies.", "qid": 38, "docid": "pjjrgn05", "rank": 55, "score": 0.8061585426330566}, {"content": "Title: Dysregulation of the immune system as a driver of the critical course of the novel coronavirus disease 2019 Content: Novel coronavirus disease-2019 (COVID-19) is a highly contagious respiratory-related disease induced by the newly emerged virus SARS-CoV-2. Given that inflammatory immune cells may induce severe lung injury, the involvement of immune factors in the pathogenesis of the disease cannot be overestimated. It has been demonstrated that coronaviruses (CoVs) have developed mechanisms of immune evasion, making them invisible to the immune system at an early stage of infection. The mechanism relies on inhibition of the anti-viral response of type I interferons (IFNs), which supports uncontrolled viral replication in epithelial cells. There is growing body of evidence that the fatal hyperinflammation ('cytokine storm') responsible for the severe course of COVID-19 is a consequence of massive SARS-CoV-2 replication rather than inappropriate hyperresponsiveness of the immune system. Therefore, a dampened innate anti-viral immune response seems to be the primary cause of the delayed critical cascade of uncontrolled immune events leading to fulminating systemic inflammation. The occurrence of virus transmission even in asymptomatic subjects infected with SARS-CoV-2 clearly strengthens the evidence for a key role of sufficient immune control of viral replication in a subset of cases (e.g. in children, a population with highly effective innate immune responses). Although administration of immunomodulatory therapeutics is recommended under certain conditions in the guidelines of COVID-19 management, controversies regarding treatment protocols in immunocompromised patients infected with SARS-CoV-2 still exist. Extended knowledge of clinicians on the dysregulated immune response, which is a driver of the COVID-19 outcome, may improve both therapeutic protocols and the prognosis of SARS-CoV-2 infected patients.", "qid": 38, "docid": "5ad4rm3y", "rank": 56, "score": 0.8050815463066101}, {"content": "Title: Dysregulation of the immune system as a driver of the critical course of the novel coronavirus disease 2019. Content: Novel coronavirus disease-2019 (COVID-19) is a highly contagious respiratory-related disease induced by the newly emerged virus SARS-CoV-2. Given that inflammatory immune cells may induce severe lung injury, the involvement of immune factors in the pathogenesis of the disease cannot be overestimated. It has been demonstrated that coronaviruses (CoVs) have developed mechanisms of immune evasion, making them invisible to the immune system at an early stage of infection. The mechanism relies on inhibition of the anti-viral response of type I interferons (IFNs), which supports uncontrolled viral replication in epithelial cells. There is growing body of evidence that the fatal hyperinflammation ('cytokine storm') responsible for the severe course of COVID-19 is a consequence of massive SARS-CoV-2 replication rather than inappropriate hyperresponsiveness of the immune system. Therefore, a dampened innate anti-viral immune response seems to be the primary cause of the delayed critical cascade of uncontrolled immune events leading to fulminating systemic inflammation. The occurrence of virus transmission even in asymptomatic subjects infected with SARS-CoV-2 clearly strengthens the evidence for a key role of sufficient immune control of viral replication in a subset of cases (e.g. in children, a population with highly effective innate immune responses). Although administration of immunomodulatory therapeutics is recommended under certain conditions in the guidelines of COVID-19 management, controversies regarding treatment protocols in immunocompromised patients infected with SARS-CoV-2 still exist. Extended knowledge of clinicians on the dysregulated immune response, which is a driver of the COVID-19 outcome, may improve both therapeutic protocols and the prognosis of SARS-CoV-2 infected patients.", "qid": 38, "docid": "1zq0aels", "rank": 57, "score": 0.8050815463066101}, {"content": "Title: COVID-19 for the Cardiologist: A Current Review of the Virology, Clinical Epidemiology, Cardiac and Other Clinical Manifestations and Potential Therapeutic Strategies Content: The coronavirus disease-2019 (COVID-19), a contagious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), has reached pandemic status. As it spreads across the world, it has overwhelmed healthcare systems, strangled the global economy and led to a devastating loss of life. Widespread efforts from regulators, clinicians and scientists are driving a rapid expansion of knowledge of the SARS-CoV2 virus and the COVID-19 disease. We review the most current data with a focus on our basic understanding of the mechanism(s) of disease and translation to the clinical syndrome and potential therapeutics. We discuss the basic virology, epidemiology, clinical manifestation, multi-organ consequences, and outcomes. With a focus on cardiovascular complications, we propose several mechanisms of injury. The virology and potential mechanism of injury form the basis for a discussion of potential disease-modifying therapies.", "qid": 38, "docid": "w0ex7ynw", "rank": 58, "score": 0.8043864369392395}, {"content": "Title: Coronavirus Disease 2019-related dyspnea cases difficult to interpret using chest computed tomography Content: Patients with Coronavirus Disease 2019 (COVID-19) often have clinical characteristics, such as chest tightness and dyspnea. Continuous, unresolved dyspnea often indicates the progression of lung lesions. The mechanism that underlies the chest distress and dyspnea in patients with COVID-19 is still unclear. Chest CT has a higher sensitivity and can play an essential role in the diagnosis and treatment of the disease. However, our clinical observations showed that although some patients had significant chest distress and dyspnea, the lesions that were observed in the lungs during computed tomography were milder and not completely consistent with clinical symptoms. We analyzed the clinical characteristics, laboratory test results, and imaging findings of these patients. We found that extensive inflammation of the bilateral and respiratory bronchioles in patients with COVID-19 due to excessive activation of proinflammatory cytokines and chemotactic aggregation of T-lymphocytes at the site of inflammation are possible mechanisms underlying chest distress and dyspnea in patients with COVID-19. Short-time and lose-dose use of corticosteroid may be helpful to treat chest tightness and dyspnea in mild COVID-19 patients. Through this study, we aimed to improve our understanding of the pathogenesis of COVID-19.", "qid": 38, "docid": "n0i5t56g", "rank": 59, "score": 0.8043169975280762}, {"content": "Title: Insights into the Use of C-Reactive Protein as a Diagnostic Index of Disease Severity in COVID-19 Infections Content: Approximately 20% of patients infected with SARS-CoV-2 (COVID-19) develop potentially life-threatening pathologies involving hyperinflammation, cytokine storm, septic shock complications, coagulation dysfunction, and multiple organ failure. Blood levels of the prototypic acute phase reactant, C-reactive protein (CRP), which is hepatically synthesized and released in response to interleukin-6 stimulation, is markedly elevated in patients with COVID-19. Markedly high CRP levels correlate with poor prognosis for survival. Insights into CRP structure-function relationships have uncovered both pro- and anti-inflammatory isoforms that may be used to monitor the extent of tissue damage associated with COVID-19 pathologies and prognoses. Herein, rationale is given for interpretation of CRP blood levels as a simple, rapid, and cost-effective way to assess disease severity and help guide therapeutic options in COVID-19 patients.", "qid": 38, "docid": "85xi1s22", "rank": 60, "score": 0.8041151762008667}, {"content": "Title: Insights into the Use of C-Reactive Protein as a Diagnostic Index of Disease Severity in COVID-19 Infections. Content: Approximately 20% of patients infected with SARS-CoV-2 (COVID-19) develop potentially life-threatening pathologies involving hyperinflammation, cytokine storm, septic shock complications, coagulation dysfunction, and multiple organ failure. Blood levels of the prototypic acute phase reactant, C-reactive protein (CRP), which is hepatically synthesized and released in response to interleukin-6 stimulation, is markedly elevated in patients with COVID-19. Markedly high CRP levels correlate with poor prognosis for survival. Insights into CRP structure-function relationships have uncovered both pro- and anti-inflammatory isoforms that may be used to monitor the extent of tissue damage associated with COVID-19 pathologies and prognoses. Herein, rationale is given for interpretation of CRP blood levels as a simple, rapid, and cost-effective way to assess disease severity and help guide therapeutic options in COVID-19 patients.", "qid": 38, "docid": "d56kci3u", "rank": 61, "score": 0.8041151762008667}, {"content": "Title: Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2 Content: To date, no vaccines or effective drugs have been approved to prevent or treat COVID-19 and the current standard care relies on supportive treatments. Therefore, based on the fast and global spread of the virus, urgent investigations are warranted in order to develop preventive and therapeutic drugs. In this regard, treatments addressing the immunopathology of SARS-CoV-2 infection have become a major focus. Notably, while a rapid and well-coordinated immune response represents the first line of defense against viral infection, excessive inflammatory innate response and impaired adaptive host immune defense may lead to tissue damage both at the site of virus entry and at systemic level. Several studies highlight relevant changes occurring both in innate and adaptive immune system in COVID-19 patients. In particular, the massive cytokine and chemokine release, the so-called \u201ccytokine storm\u201d, clearly reflects a widespread uncontrolled dysregulation of the host immune defense. Although the prospective of counteracting cytokine storm is compelling, a major limitation relies on the limited understanding of the immune signaling pathways triggered by SARS-CoV-2 infection. The identification of signaling pathways altered during viral infections may help to unravel the most relevant molecular cascades implicated in biological processes mediating viral infections and to unveil key molecular players that may be targeted. Thus, given the key role of the immune system in COVID-19, a deeper understanding of the mechanism behind the immune dysregulation might give us clues for the clinical management of the severe cases and for preventing the transition from mild to severe stages.", "qid": 38, "docid": "hedpur93", "rank": 62, "score": 0.8038003444671631}, {"content": "Title: The bio-mission of interleukin-6 in the pathogenesis of COVID-19: A brief look at potential therapeutic tactics Content: Interleukin-6 (IL-6), known as an inflammatory cytokine, can be involved in many innate and adaptive immune responses. The role of IL-6 in the pathogenesis of the novel coronavirus disease 2019 (COVID-19) has recently received much more attention due to the spread of the virus and its pandemic potential. Cytokine storm is among the most critical pathological events in patients affected with coronaviruses (CoVs), i.e., severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and COVID-19, causing inflammation-induced lung injury and also occurring as a result of dysregulation of immune responses to the mentioned viruses. IL-6, along with some other inflammatory cytokines, including IL-1 beta (\u03b2), IL-8, and tumor necrosis factor-alpha (TNF-\u03b1), as well as inflammatory chemokines, can significantly contribute to, fever, lymphopenia, coagulation, lung injury, and multi-organ failure (MOF). Therefore, researchers are to explore novel approaches to treat the disease through targeting of IL-6 and its receptors based on prior experience of other disorders. In this review article, the latest findings on the role of IL-6 in the pathogenesis of COVID-19, as well as therapeutic perspectives, were summarized and discussed.", "qid": 38, "docid": "8leknnvc", "rank": 63, "score": 0.8033950328826904}, {"content": "Title: Coronavirus Disease 2019 and Stroke: Clinical Manifestations and Pathophysiological Insights Content: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health threat. Some COVID-19 patients have exhibited widespread neurological manifestations including stroke. Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been reported in patients with COVID-19. COVID-19-associated coagulopathy is increasingly recognized as a result of acute infection and is likely caused by inflammation, including inflammatory cytokine storm. Recent studies suggest axonal transport of SARS-CoV-2 to the brain can occur via the cribriform plate adjacent to the olfactory bulb that may lead to symptomatic anosmia. The internalization of SARS-CoV-2 is mediated by the binding of the spike glycoprotein of the virus to the angiotensin-converting enzyme 2 (ACE2) on cellular membranes. ACE2 is expressed in several tissues including lung alveolar cells, gastrointestinal tissue, and brain. The aim of this review is to provide insights into the pathophysiological stroke mechanisms in COVID-19 patients. SARS-CoV-2 can down-regulate ACE2 and, in turn, over-activate the classical renin-angiotensin system (RAS) axis and decrease the activation of the alternative RAS pathway in the brain. The consequent imbalance in vasodilation, neuroinflammation, oxidative stress, and thrombotic response may contribute to the pathophysiology of stroke during SARS-CoV-2 infection.", "qid": 38, "docid": "7imf6ev8", "rank": 64, "score": 0.8032791614532471}, {"content": "Title: Immunological and inflammatory profiles in mild and severe cases of COVID-19 Content: COVID-19 is associated with 5.1% mortality. Although the virological, epidemiological, clinical, and management outcome features of COVID-19 patients have been defined rapidly, the inflammatory and immune profiles require definition as they influence pathogenesis and clinical expression of COVID-19. Here we show lymphopenia, selective loss of CD4+ T cells, CD8+ T cells and NK cells, excessive T-cell activation and high expression of T-cell inhibitory molecules are more prominent in severe cases than in those with mild disease. CD8+ T cells in patients with severe disease express high levels of cytotoxic molecules. Histochemical studies of lung tissue from one fatality show sub-anatomical distributions of SARS-CoV-2 RNA and massive infiltration of T cells and macrophages. Thus, aberrant activation and dysregulation of CD8+ T cells occur in patients with severe COVID-19 disease, an effect that might be for pathogenesis of SARS-CoV-2 infection and indicate that immune-based targets for therapeutic interventions constitute a promising treatment for severe COVID-19 patients.", "qid": 38, "docid": "j6jb4j3b", "rank": 65, "score": 0.8025826215744019}, {"content": "Title: Neutrophils and Neutrophil Extracellular Traps Drive Necroinflammation in COVID-19 Content: The COVID-19 pandemic is progressing worldwide with an alarming death toll. There is an urgent need for novel therapeutic strategies to combat potentially fatal complications. Distinctive clinical features of severe COVID-19 include acute respiratory distress syndrome, neutrophilia, and cytokine storm, along with severe inflammatory response syndrome or sepsis. Here, we propose the putative role of enhanced neutrophil infiltration and the release of neutrophil extracellular traps, complement activation and vascular thrombosis during necroinflammation in COVID-19. Furthermore, we discuss how neutrophilic inflammation contributes to the higher mortality of COVID-19 in patients with underlying co-morbidities such as diabetes and cardiovascular diseases. This perspective highlights neutrophils as a putative target for the immunopathologic complications of severely ill COVID-19 patients. Development of the novel therapeutic strategies targeting neutrophils may help reduce the overall disease fatality rate of COVID-19.", "qid": 38, "docid": "wtnyynez", "rank": 66, "score": 0.8025697469711304}, {"content": "Title: Neutrophils and Neutrophil Extracellular Traps Drive Necroinflammation in COVID-19. Content: The COVID-19 pandemic is progressing worldwide with an alarming death toll. There is an urgent need for novel therapeutic strategies to combat potentially fatal complications. Distinctive clinical features of severe COVID-19 include acute respiratory distress syndrome, neutrophilia, and cytokine storm, along with severe inflammatory response syndrome or sepsis. Here, we propose the putative role of enhanced neutrophil infiltration and the release of neutrophil extracellular traps, complement activation and vascular thrombosis during necroinflammation in COVID-19. Furthermore, we discuss how neutrophilic inflammation contributes to the higher mortality of COVID-19 in patients with underlying co-morbidities such as diabetes and cardiovascular diseases. This perspective highlights neutrophils as a putative target for the immunopathologic complications of severely ill COVID-19 patients. Development of the novel therapeutic strategies targeting neutrophils may help reduce the overall disease fatality rate of COVID-19.", "qid": 38, "docid": "6ri6bxfc", "rank": 67, "score": 0.8025697469711304}, {"content": "Title: [From SARS to COVID-19: pathogens, receptor, pathogenesis and principles of the treatment]. Content: COVID-19 is an infectious disease caused by 2019-nCoV and characterizes as an atypical pneumonia. Since 2019-nCoV is a newly emerging virus, the pathogenesis of COVID-19 is not well known. Most patients had a self-limited course, and some became severe even death. In this review, the authors compared two coronavirus outbreaks during the past two decades: the SARS-CoV and 2019-nCoV. Among the biological nature of the pathogens, viral receptor distribution on the human cells, and the pathological findings in the targeted organs and clinical features of the patients with the diseases, found similarities and differences between the two diseases. Due to the shared receptor ACE2 and the pathological similarities of the SARS-CoV and 2019-nCoV diseases. They proposed a pathogenesis model for COVID-19. Like the SARS-CoV disease, COVID-19 is a systematic disease and targets the lungs, vasculatures, and the immune system. The basic pathogenesis involves two interlinked processes: a severe lung inflammation and immune deficiency, both of which are related to an inappropriate immune response and over-production of cytokines. Thus, treatment approaches should include antiviral and anti-proinflammatory cytokines, anti-infectious and life support therapies, especially in patients with severe diseases.", "qid": 38, "docid": "qpwu24e8", "rank": 68, "score": 0.8025636672973633}, {"content": "Title: [From SARS to COVID-19: pathogens, receptor, pathogenesis and principles of the treatment] Content: COVID-19 is an infectious disease caused by 2019-nCoV and characterizes as an atypical pneumonia. Since 2019-nCoV is a newly emerging virus, the pathogenesis of COVID-19 is not well known. Most patients had a self-limited course, and some became severe even death. In this review, the authors compared two coronavirus outbreaks during the past two decades: the SARS-CoV and 2019-nCoV. Among the biological nature of the pathogens, viral receptor distribution on the human cells, and the pathological findings in the targeted organs and clinical features of the patients with the diseases, found similarities and differences between the two diseases had been found. Due to the shared receptor ACE2 and the pathological similarities of the SARS-CoV and 2019-nCoV diseases,authors proposed a pathogenesis model for COVID-19. Like the SARS-CoV disease, COVID-19 is a systematic disease and targets the lungs, vasculatures, and the immune system. The basic pathogenesis involves two interlinked processes: a severe lung inflammation and immune deficiency, both of which were related to an inappropriate immune response and over-production of cytokines. Thus, treatment approaches should include antiviral and anti-proinflammatory cytokines, anti-infectious and life support therapies, especially in patients with severe diseases.", "qid": 38, "docid": "a290vxor", "rank": 69, "score": 0.8016641139984131}, {"content": "Title: Potential pathophysiological mechanisms leading to increased COVID-19 susceptibility and severity in obesity Content: As we are facing worldwide pandemic of COVID-19, we aimed to identify potential pathophysiological mechanisms leading to increased COVID-19 susceptibility and severity in obesity. Special emphasis will be given on increased susceptibility to infections due to obesity-related low-grade chronic inflammation, higher expression of angiotensin converting enzyme-2 and pathway-associated components, as well as decreased vitamin D bioavailability, since all of them provide easier ways for the virus to enter into host cells, replicate and stunt adequate immune responses.", "qid": 38, "docid": "h7xf1kxa", "rank": 70, "score": 0.8016015291213989}, {"content": "Title: Immunopathology and immunotherapeutic strategies in severe acute respiratory syndrome coronavirus 2 infection Content: The outbreak of coronavirus disease 2019 (COVID-19) and pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a major concern globally. As of 14 April 2020, more than 1.9 million COVID-19 cases have been reported in 185 countries. Some patients with COVID-19 develop severe clinical manifestations, while others show mild symptoms, suggesting that dysregulation of the host immune response contributes to disease progression and severity. In this review, we have summarized and discussed recent immunological studies focusing on the response of the host immune system and the immunopathology of SARS-CoV-2 infection as well as immunotherapeutic strategies for COVID-19. Immune evasion by SARS-CoV-2, functional exhaustion of lymphocytes, and cytokine storm have been discussed as part of immunopathology mechanisms in SARS-CoV-2 infection. Some potential immunotherapeutic strategies to control the progression of COVID-19, such as passive antibody therapy and use of interferon &#945;\u00df and IL-6 receptor (IL-6R) inhibitor, have also been discussed. This may help us to understand the immune status of patients with COVID-19, particularly those with severe clinical presentation, and form a basis for further immunotherapeutic investigations.", "qid": 38, "docid": "2h8i4pyb", "rank": 71, "score": 0.8014544248580933}, {"content": "Title: Recent Insight into SARS-CoV2 Immunopathology and Rationale for Potential Treatment and Preventive Strategies in COVID-19 Content: As the outbreak of the new coronavirus (SARS-CoV-2) infection is spreading globally, great effort is being made to understand the disease pathogenesis and host factors that predispose to disease progression in an attempt to find a window of opportunity for intervention. In addition to the direct cytopathic effect of the virus, the host hyper-inflammatory response has emerged as a key factor in determining disease severity and mortality. Accumulating clinical observations raised hypotheses to explain why some patients develop more severe disease while others only manifest mild or no symptoms. So far, Covid-19 management remains mainly supportive. However, many researches are underway to clarify the role of antiviral and immunomodulating drugs in changing morbidity and mortality in patients who become severely ill. This review summarizes the current state of knowledge on the interaction between SARS-CoV-2 and the host immune system and discusses recent findings on proposed pharmacologic treatments.", "qid": 38, "docid": "rso3ryl1", "rank": 72, "score": 0.8013230562210083}, {"content": "Title: The innate immune system: fighting on the front lines or fanning the flames of COVID-19? Content: Abstract The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has had devastating global impacts and will continue to have dramatic effects on public health for years to come. A better understanding of the immune response to SARS-CoV-2 will be critical for the application and development of therapeutics. The degree to which the innate immune response confers protection or induces pathogenesis through a dysregulated immune response remains unclear. In this review, we discuss what is known about the role of the innate immune system during SARS-CoV-2 infection, suggest directions for future studies, and evaluate proposed COVID-19 immunomodulating therapeutics.", "qid": 38, "docid": "ebalebqq", "rank": 73, "score": 0.8011480569839478}, {"content": "Title: The cytokine storm and COVID-19 Content: Coronavirus disease 2019 (COVID-19), which began in Wuhan, China in December 2019 has caused a large global pandemic and poses a serious threat to public health. More than four million cases of COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been confirmed as of May 11, 2020. SARS-CoV-2 is a highly pathogenic and transmissible coronavirus that primarily spreads through respiratory droplets and close contact. A growing body of clinical data suggests that a cytokine storm is associated with COVID-19 severity and is also a crucial cause of death from COVID-19. In the absence of antivirals and vaccines for COVID-19, there is an urgent need to understand the cytokine storm in COVID-19. Here, we have reviewed the current understanding of the features of SARS-CoV-2 and the pathological features, pathophysiological mechanisms, and treatments of the cytokine storm induced by COVID-19. Additionally, we suggest that the identification and treatment of the cytokine storm are important components for rescuing patients with severe COVID-19. This article is protected by copyright. All rights reserved.", "qid": 38, "docid": "hqzkzupi", "rank": 74, "score": 0.8009366393089294}, {"content": "Title: Immunologic aspects of characteristics, diagnosis, and treatment of coronavirus disease 2019 (COVID-19) Content: On March 11, 2020, the World Health Organization declared the worldwide spread of the infectious disease COVID-19, caused by a new strain of coronavirus, SARS-CoV-2, as a pandemic. Like in all other infectious diseases, the host immune system plays a key role in our defense against SARS-CoV-2 infection. However, viruses are able to evade the immune attack and proliferate and, in susceptible individuals, cause severe inflammatory response known as cytokine storm, particularly in the lungs. The advancement in our understanding of the mechanisms underlying the host immune responses promises to facilitate the development of approaches for prevention or treatment of diseases. Components of immune system, such as antibodies, can also be used to develop sensitive and specific diagnostic methods as well as novel therapeutic agents. In this review, we summarize our knowledge about how the host mounts immune responses to infection by SARS-CoV-2. We also describe the diagnostic methods being used for COVID-19 identification and summarize the current status of various therapeutic strategies, including vaccination, being considered for treatment of the disease.", "qid": 38, "docid": "nwu4tdgh", "rank": 75, "score": 0.8004454374313354}, {"content": "Title: Functional characterization of SARS-CoV-2 infection suggests a complex inflammatory response and metabolic alterations Content: Covid-19, caused by the SARS-CoV-2 virus, has reached the category of a worldwide pandemic. Even though intensive efforts, no effective treatments or a vaccine are available. Molecular characterization of the transcriptional response in Covid-19 patients could be helpful to identify therapeutic targets. In this study, RNAseq data from peripheral blood mononuclear cell samples from Covid-19 patients and healthy controls was analyzed from a functional point of view using probabilistic graphical models. Two networks were built: one based on genes differentially expressed between healthy and infected individuals and another one based on the 2,000 most variable genes in terms of expression in order to make a functional characterization. In the network based on differentially expressed genes, two inflammatory response nodes with different tendencies were identified, one related to cytokines and chemokines, and another one related to bacterial infections. In addition, differences in metabolism, which were studied in depth using Flux Balance Analysis, were identified. SARS-CoV2-infection caused alterations in glutamate, methionine and cysteine, and tetrahydrobiopterin metabolism. In the network based on 2,000 most variable genes, also two inflammatory nodes with different tendencies between healthy individuals and patients were identified. Similar to the other network, one was related to cytokines and chemokines. However, the other one, lower in Covid-19 patients, was related to allergic processes and self-regulation of the immune response. Also, we identified a decrease in T cell node activity and an increase in cell division node activity. In the current absence of treatments for these patients, functional characterization of the transcriptional response to SARS-CoV-2 infection could be helpful to define targetable processes. Therefore, these results may be relevant to propose new treatments. Author Summary SARS-CoV-2 infection caused Covid-19 which has reached the category of a worldwide pandemic. However, no treatments or vaccines are still available. For this reason, it is still necessary the molecular study of this disease. In this study, we reanalyzed data from peripheral blood mononuclear cells from Covid-19 patients and healthy controls using computational techniques that allow the study of differential biological processes and metabolic pathways. The results suggested a complex inflammatory response, involving genes related to response to bacterial infection and allergic processes, and alterations in metabolic pathways such as glutamate metabolism, cysteine and methionine metabolism or tetrahydrobiopterin metabolism. These processes could be used in the future as therapeutic targets in Covi-19 infection.", "qid": 38, "docid": "108k7gng", "rank": 76, "score": 0.8001704216003418}, {"content": "Title: The Innate Immune System: Fighting on the Front Lines or Fanning the Flames of COVID-19? Content: The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has had devastating global impacts and will continue to have dramatic effects on public health for years to come. A better understanding of the immune response to SARS-CoV-2 will be critical for the application and development of therapeutics. The degree to which the innate immune response confers protection or induces pathogenesis through a dysregulated immune response remains unclear. In this review, we discuss what is known about the role of the innate immune system during SARS-CoV-2 infection, suggest directions for future studies, and evaluate proposed COVID-19 immunomodulating therapeutics.", "qid": 38, "docid": "1309xyi4", "rank": 77, "score": 0.8000309467315674}, {"content": "Title: Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2 Content: To date, no vaccines or effective drugs have been approved to prevent or treat COVID-19 and the current standard care relies on supportive treatments. Therefore, based on the fast and global spread of the virus, urgent investigations are warranted in order to develop preventive and therapeutic drugs. In this regard, treatments addressing the immunopathology of SARS-CoV-2 infection have become a major focus. Notably, while a rapid and well-coordinated immune response represents the first line of defense against viral infection, excessive inflammatory innate response and impaired adaptive host immune defense may lead to tissue damage both at the site of virus entry and at systemic level. Several studies highlight relevant changes occurring both in innate and adaptive immune system in COVID-19 patients. In particular, the massive cytokine and chemokine release, the so-called \"cytokine storm\", clearly reflects a widespread uncontrolled dysregulation of the host immune defense. Although the prospective of counteracting cytokine storm is compelling, a major limitation relies on the limited understanding of the immune signaling pathways triggered by SARS-CoV-2 infection. The identification of signaling pathways altered during viral infections may help to unravel the most relevant molecular cascades implicated in biological processes mediating viral infections and to unveil key molecular players that may be targeted. Thus, given the key role of the immune system in COVID-19, a deeper understanding of the mechanism behind the immune dysregulation might give us clues for the clinical management of the severe cases and for preventing the transition from mild to severe stages.", "qid": 38, "docid": "lv7kt128", "rank": 78, "score": 0.7998661994934082}, {"content": "Title: The pathogenesis and treatment of the `Cytokine Storm' in COVID-19 Content: Cytokine storm is an excessive immune response to external stimuli. The pathogenesis of the cytokine storm is complex. The disease progresses rapidly, and the mortality is high. Certain evidence shows that, during the coronavirus disease 2019 (COVID-19) epidemic, the severe deterioration of some patients has been closely related to the cytokine storm in their bodies. This article reviews the occurrence mechanism and treatment strategies of the COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.", "qid": 38, "docid": "iaatjew2", "rank": 79, "score": 0.7998008728027344}, {"content": "Title: Rationale for targeting complement in COVID-19 Content: A novel coronavirus, SARS-CoV-2, has recently emerged in China and spread internationally, posing a health emergency to the global community. COVID-19 caused by SARS-CoV-2 is associated with an acute respiratory illness that varies from mild to the life-threatening acute respiratory distress syndrome (ARDS). The complement system is part of the innate immune arsenal against pathogens, in which many viruses can evade or employ to mediate cell entry. The immunopathology and acute lung injury orchestrated through the influx of pro-inflammatory macrophages and neutrophils can be directly activated by complement components to prime an overzealous cytokine storm. The manifestations of severe COVID-19 such as the ARDS, sepsis and multiorgan failure have an established relationship with activation of the complement cascade. We have collected evidence from all the current studies we are aware of on SARS-CoV-2 immunopathogenesis and the preceding literature on SARS-CoV-1 and MERS-CoV infection linking severe COVID-19 disease directly with dysfunction of the complement pathways. This information lends support for a therapeutic anti-inflammatory strategy against complement, where a number of clinically ready potential therapeutic agents are available.", "qid": 38, "docid": "niy9fuil", "rank": 80, "score": 0.7995949983596802}, {"content": "Title: COVID-19 & Periodontitis: The cytokine connection Content: COVID-19 is now recognized as a pandemic throughout the world, leading to a scramble in order to gather knowledge as well as evidence regarding the 'novel' corona virus which causes this disease. Chemokines are a family of cytokines which are chemotactic in nature and cause the recruitment of cells of inflammation. Periodontitis has long been attributed to having its pathophysiology rooted in a cytokine response. The recent COVID-19 pandemic has been reported to have adverse outcomes related to the establishment of a cytokine storm, many of the components of which are common with the cytokine expression profile of periodontitis. This communication explores the connection between COVID-19 and periodontal disease through their cytokine connection to form a translational basis for recommending maintenance of oral hygiene in the COVID era and to red flag patients with periodontitis as having an increased risk of exhibiting COVID related adverse outcomes.", "qid": 38, "docid": "do5lt51a", "rank": 81, "score": 0.7992866039276123}, {"content": "Title: COVID-19 & Periodontitis: The cytokine connection. Content: COVID-19 is now recognized as a pandemic throughout the world, leading to a scramble in order to gather knowledge as well as evidence regarding the 'novel' corona virus which causes this disease. Chemokines are a family of cytokines which are chemotactic in nature and cause the recruitment of cells of inflammation. Periodontitis has long been attributed to having its pathophysiology rooted in a cytokine response. The recent COVID-19 pandemic has been reported to have adverse outcomes related to the establishment of a cytokine storm, many of the components of which are common with the cytokine expression profile of periodontitis. This communication explores the connection between COVID-19 and periodontal disease through their cytokine connection to form a translational basis for recommending maintenance of oral hygiene in the COVID era and to red flag patients with periodontitis as having an increased risk of exhibiting COVID related adverse outcomes.", "qid": 38, "docid": "tguq8o5m", "rank": 82, "score": 0.7992866039276123}, {"content": "Title: Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions Content: Abstract The coronavirus disease-19 pandemic (COVID-19), which appeared in China in December 2019 and rapidly spread throughout the world, has forced clinicians and scientists to take up extraordinary challenges. This unprecedented situation led to the inception of numerous fundamental research protocols and many clinical trials. It quickly became apparent that although COVID-19, in the vast majority of cases, was a benign disease, it could also develop a severe form with sometimes fatal outcomes. Cytokines are central to the pathophysiology of COVID-19; while some of them are beneficial (type-I interferon, interleukin-7), others appear detrimental (interleukin-1\u03b2, -6, and TNF-\u03b1) particularly in the context of the so-called cytokine storm. Yet another characteristic of the disease has emerged: concomitant immunodeficiency, notably involving impaired type-I interferon response, and lymphopenia. This review provides an overview of current knowledge on COVID-19 immunopathology. We discuss the defective type-I IFN response, the theoretical role of IL-7 to restore lymphocyte repertoire, as well as we mention the two patterns observed in severe COVID-19 (i.e. interleukin-1\u03b2-driven macrophage activation syndrome vs. interleukin-6-driven immune dysregulation). Next, reviewing current evidence drawn from clinical trials, we examine a number of cytokine and anti-cytokine therapies, including interleukin-1, -6, and TNF inhibitors, as well as less targeted therapies, such as corticosteroids, chloroquine, or JAK inhibitors.", "qid": 38, "docid": "qlv0jttw", "rank": 83, "score": 0.798984169960022}, {"content": "Title: COVID-19 and the Heart. Content: Infection with the novel coronavirus, SARS-CoV-2, produces a clinical syndrome known as COVID-19. When severe, COVID-19 is a systemic illness characterized by hyperinflammation, cytokine storm and elevations of cardiac injury biomarkers. Here we review what is known about the pathophysiology of COVID-19, its cardiovascular manifestations, and emerging therapeutic prospects. In this rapidly moving field, this review was comprehensive as of April 3, 2020.", "qid": 38, "docid": "d4h49d8b", "rank": 84, "score": 0.798636257648468}, {"content": "Title: Novel therapeutic targets for SARS-CoV-2-induced acute lung injury: Targeting a potential IL-1\u03b2/neutrophil extracellular traps feedback loop. Content: Most COVID-19 infected individuals present with mild flu-like symptoms; however, 5-10% of cases suffer from life-threatening pneumonia and respiratory failure. The pathogenesis of SARS-CoV-2 and its pathology of associated acute lung injury (ALI), acute respiratory distress syndrome (ARDS), sepsis, coagulopathy and multiorgan failure is not known. SARS-CoV-2 is an envelope virus with S (spike), M (membrane), N (nucleocapsid) and E (envelop) proteins. In a closely related coronavirus (SARS-CoV), the transmembrane E protein exerts an important role in membrane-ionic transport through viroporins, deletion of which reduced levels of IL-1\u03b2 and a remarkably reduced lung edema compared to wild type. IL-1\u03b2 is generated by macrophages upon activation of intracellular NLRP3 (NOD-like, leucine rich repeat domains, and pyrin domain-containing protein 3), part of the functional NLRP3 inflammasome complex that detects pathogenic microorganisms and stressors, while neutrophils are enhanced by increasing levels of IL-1\u03b2. Expiring neutrophils undergo \"NETosis\", producing thread-like extracellular structures termed neutrophil extracellular traps (NETs), which protect against mild infections and microbes. However, uncontrolled NET production can cause acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), coagulopathy, multiple organ failure, and autoimmune disease. Herein, we present arguments underlying our hypothesis that IL-1\u03b2 and NETs, mediated via NLRP3 inflammasomes, form a feed-forward loop leading to the excessive alveolar and endothelial damage observed in severe cases of COVID-19. Considering such assertions, we propose potential drug candidates that could be used to alleviate such pathologies. Considering that recent efforts to ascertain effective treatments of COVID-19 in severe patients has been less than successful, investigating novel avenues of treating this virus are essential.", "qid": 38, "docid": "3ww5zvij", "rank": 85, "score": 0.7984868288040161}, {"content": "Title: Altered cytokine levels and immune responses in patients with SARS-CoV-2 infection and related conditions Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic in early 2020. The infection has been associated with a wide range of clinical symptoms. In the severely affected patients, it has caused dysregulation of immune responses including over-secretion of inflammatory cytokines and imbalances in the proportion of na\u00efve helper T cells, memory helper T cells and regulatory T cells. Identification of the underlying mechanism of such aberrant function of immune system would help in the prediction of disease course and selection of susceptible patients for more intensive cares. In the current review, we summarize the results of studies which reported alterations in cytokine levels and immune cell functions in patients affected with SARS-CoV-2 and related viruses.", "qid": 38, "docid": "xcnhzxm0", "rank": 86, "score": 0.7984804511070251}, {"content": "Title: Molecular Alterations Prompted by SARS-CoV-2 Infection: Induction of Hyaluronan, Glycosaminoglycan and Mucopolysaccharide Metabolism Content: BACKGROUND: The SARS-CoV-2 is the etiological agent causing COVID-19 which has infected more than 2 million people with more than 200000 deaths since its emergence in December 2019. In the majority of cases patients are either asymptomatic or show mild to moderate symptoms and signs of a common cold. A subset of patients, however, develop a severe atypical pneumonia, with the characteristic ground-glass appearance on chest x-ray and computerized tomography, which evolves into an acute respiratory distress syndrome, that requires mechanical ventilation and eventually results in multiple organ failure and death. The Molecular pathogenesis of COVID-19 is still unknown. AIM OF THE STUDY: In the present work we performed a stringent metanalysis from the publicly available RNAseq data from bronchoalveolar cells and peripheral blood mononuclear cells to elucidate molecular alterations and cellular deconvolution to identify immune cell profiles. RESULTS: Alterations in genes involved in hyaluronan, glycosaminoglycan and mucopolysaccharides metabolism were over-represented in bronchoalveolar cells infected by SARS-CoV-2, as well as potential lung infiltration with neutrophils, T CD4+ cell and macrophages. The blood mononuclear cells presented a proliferative state. Dramatic reduction of NK and T lymphocytes, whereas an exacerbated increase in monocytes. CONCLUSIONS: In summary our results revealed molecular pathogenesis of the SARS-CoV-2 infection to bronchoalveolar cells inducing the hyaluronan and glycosaminoglycan metabolism that could shape partially the components of the ground-glass opacities observed in CT. And the potential immune response profile in COVID-19.", "qid": 38, "docid": "aydh6jvl", "rank": 87, "score": 0.7984707355499268}, {"content": "Title: STAT2 signaling as double-edged sword restricting viral dissemination but driving severe pneumonia in SARS-CoV-2 infected hamsters Content: Since the emergence of SARS-CoV-2 causing COVID-19, the world is being shaken to its core with numerous hospitalizations and hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that productive SARS-CoV-2 infection in the lungs of mice is limited and restricted by early type I interferon responses. In contrast, we show that Syrian hamsters are highly permissive to SARS- CoV-2 and develop bronchopneumonia and a strong inflammatory response in the lungs with neutrophil infiltration and edema. Moreover, we identify an exuberant innate immune response as a key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Finally, we assess SARS-CoV- 2-induced lung pathology in hamsters by micro-CT alike used in clinical practice. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients.", "qid": 38, "docid": "m5u6ryy9", "rank": 88, "score": 0.798464834690094}, {"content": "Title: The case of complement activation in COVID-19 multiorgan impact Content: The novel coronavirus disease COVID-19 originates in the lungs, but it may extend to other organs, causing, in severe cases, multiorgan damage, including cardiac injury and acute kidney injury. In severe cases, the presence of kidney injury is associated with increased risk of death, highlighting the relevance of this organ as a target of SARS-CoV-2 infection. COVID-19-associated tissue injury is not primarily mediated by viral infection, but rather is a result of the inflammatory host immune response, which drives hypercytokinemia and aggressive inflammation that affect lung parenchymal cells, diminishing oxygen uptake, but also endothelial cells, resulting in endotheliitis and thrombotic events and intravascular coagulation. The complement system represents the first response of the host immune system to SARS-CoV-2 infection, but there is growing evidence that unrestrained activation of complement induced by the virus in the lungs and other organs plays a major role in acute and chronic inflammation, endothelial cell dysfunction, thrombus formation, and intravascular coagulation, and ultimately contributes to multiple organ failure and death. In this review, we discuss the relative role of the different complement activation products in the pathogenesis of COVID-19-associated tissue inflammation and thrombosis and propose the hypothesis that blockade of the terminal complement pathway may represent a potential therapeutic option for the prevention and treatment of lung and multiorgan damage.", "qid": 38, "docid": "0mien60n", "rank": 89, "score": 0.7982770204544067}, {"content": "Title: COVID-19: unravelling the clinical progression of nature's virtually perfect biological weapon Content: Coronavirus disease 2019 (COVID-19) pandemic has shocked the world and caused morbidity and mortality on an unprecedented level in the era of modern medicine Evidence generated to-date on the virulence and pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggests that COVID-19 may be considered a perfect storm, caused by a nature's virtually perfect biological weapon This conclusion is supported by an updated analysis of pathogenesis and clinical progression of this infectious disease It is now readily apparent that COVID-19 is not a clear-cut disorder, but is instead a gradually evolving pathology, characterized by a series of stages sustained by different molecular and biological mechanisms The disease can hence be divided in at least five different phases (incubation, respiratory, pro-inflammatory, pro-thrombotic, and death or remission) Whilst the virus triggers direct cytopathic injury during the initial stage of illness, in the following evolving phases, it is the host itself that undergoes an almost suicidal reaction, sustained, amplified and maintained by the immune, complement and hemostatic systems Another peculiar property making SARS-CoV-2 a devious and vicious pathogen is the biophysical structure of its receptor biding domain, which needs to be primed by human proteases, thus being less efficiently targetable by the host immune system The unique pathophysiology of COVID-19 requires the customization of therapy by individual patient characteristics and according to the phase-specific, evolving derangement of the multiple biological pathways", "qid": 38, "docid": "xtomqvs5", "rank": 90, "score": 0.7982762455940247}, {"content": "Title: COVID-19: a collision of complement, coagulation and inflammatory pathways Content: COVID-19 is frequently accompanied by a hypercoagulable inflammatory state with microangiopathic pulmonary changes that can precede the diffuse alveolar damage characteristic of typical ARDS seen in other severe pathogenic infections. Parallels with systemic inflammatory disorders such as atypical haemolytic uraemic syndrome (aHUS) have implicated the complement pathway in the pathogenesis of COVID-19, and particularly the anaphylatoxins C3a and C5a released from cleavage of C3 and C5 respectively. C5a is a potent cell signalling protein that activates a cytokine storm - a hyper-inflammatory phenomenon - within hours of infection and the innate immune response. However, excess C5a can result in a pro-inflammatory environment orchestrated through a plethora of mechanisms, that propagates lung injury, lymphocyte exhaustion and an immune paresis. Furthermore, disruption of the homeostatic interactions between complement and extrinsic and intrinsic coagulation pathways contributes to a net pro-coagulant state in the microvasculature of critical organs. Fatal COVID-19 has been associated with a systemic inflammatory response accompanied by a pro-coagulant state and organ damage, particularly microvascular thrombi in the lungs and kidneys. Pathologic studies report strong evidence of complement activation. C5 blockade reduces inflammatory cytokines and their manifestations in animal studies, and has shown benefits in patients with aHUS, prompting investigation of this approach in the treatment of COVID-19. This review describes the role of the complement pathway and particularly C5a and its aberrations in highly pathogenic virus infections, and therefore its potential as a therapeutic target in COVID-19.", "qid": 38, "docid": "oj0zthe9", "rank": 91, "score": 0.7982339859008789}, {"content": "Title: Distinct infection process of SARS\u2010CoV\u20102 in human bronchial epithelial cells line Content: COVID\u201019, caused by SARS\u2010CoV\u20102, leads to a series of clinical symptoms of respiratory and pulmonary inflammatory reactions via unknown pathologic mechanisms related to the viral infection process in tracheal or bronchial epithelial cells. Investigation of this viral infection in the human bronchial epithelial cell line (16HBE) suggests that SARS\u2010CoV\u20102 can enter these cells through interaction between its membrane\u2010localized S protein with the ACE2 molecule on the host cell membrane. Further observation indicates distinct viral replication with a dynamic and moderate increase, whereby viral replication does not lead to a specific cytopathic effect but maintains a continuous release of progeny virions from infected cells. Although mRNA expression of various innate immune signaling molecules is altered in the cells, transcription of IFN\u03b1, IFN\u03b2 and IFN\u03b3 is unchanged. Furthermore, expression of some interleukins related to inflammatory reactions, such as IL\u20106, IL\u20102 and IL\u20108, is maintained at low levels, whereas that of interleukins involved in immune regulation is upregulated. Interestingly, IL\u201022, an interleukin that functions mainly in tissue repair, shows very high expression. Collectively, these data suggest a distinct infection process for this virus in respiratory epithelial cells, which may be linked to its clinicopathological mechanism. This article is protected by copyright. All rights reserved.", "qid": 38, "docid": "w3ikwu09", "rank": 92, "score": 0.7979346513748169}, {"content": "Title: Potential Causes and Consequences of Gastrointestinal Disorders during a SARS-CoV-2 Infection Content: Coronaviruses cause several human diseases, including severe acute respiratory syndrome. The global coronavirus disease 2019 (COVID-19) pandemic has become a huge threat to humans. Intensive research on the pathogenic mechanisms used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is urgently needed-notably to identify potential drug targets. Clinical studies of patients with COVID-19 have shown that gastrointestinal disorders appear to precede or follow the respiratory symptoms. Here, we review gastrointestinal disorders in patients with COVID-19, suggest hypothetical mechanisms leading to gut symptoms, and discuss the potential consequences of gastrointestinal disorders on the outcome of the disease. Lastly, we discuss the role of the gut microbiota during respiratory viral infections and suggest that targeting gut dysbiosis may help to control the pathogenesis of COVID-19.", "qid": 38, "docid": "ksr4ly35", "rank": 93, "score": 0.7979308366775513}, {"content": "Title: Rationale for targeting Complement in COVID-19 Content: A novel coronavirus, SARS-CoV-2, has recently emerged in China and spread internationally, posing a health emergency to the global community. COVID-19 caused by SARS-CoV-2 is associated with an acute respiratory illness that varies from mild to the life-threatening acute respiratory distress syndrome (ARDS). The complement system is part of the innate immune arsenal against pathogens, which many viruses can evade or employ to mediate cell entry. The immunopathology and acute lung injury orchestrated through the influx of pro-inflammatory macrophages and neutrophils can be directly activated by complement components to prime an overzealous cytokine storm. The manifestations of severe COVID-19 such as the ARDS, sepsis and multiorgan failure have an established relationship with activation of the complement cascade. We have collected evidence from all the current studies we are aware of on SARS-CoV-2 immunopathogenesis and the preceding literature on SARS-CoV-1 and MERS-CoV infection linking severe COVID-19 disease directly with dysfunction of the complement pathways. This information lends support for a therapeutic anti-inflammatory strategy against complement, where a number of clinically ready potential therapeutic agents are available.", "qid": 38, "docid": "l0ukuk4u", "rank": 94, "score": 0.7977519631385803}, {"content": "Title: Type 3 hypersensitivity in COVID-19 vasculitis Content: Coronavirus Disease 2019 (COVID-19) is an ongoing public health emergency and new knowledge about its immunopathogenic mechanisms is deemed necessary in the attempt to reduce the death burden around the world. For the first time in worldwide literature, we provide scientific evidence that in COVID-19 vasculitis a life-threatening escalation from type 2 T-helper immune response (humoral immunity) to type 3 hypersensitivity (immune complex disease) takes place. The subsequent deposition of immune complexes inside the vascular walls is supposed to induce a severe inflammatory state and a cytokine release syndrome, whose interleukin-6 is the key myokine, from the smooth muscle cells of blood vessels.", "qid": 38, "docid": "nj7prvvj", "rank": 95, "score": 0.7977479100227356}, {"content": "Title: Mechanisms of Myocardial Injury in Coronavirus Disease 2019 Content: Coronavirus disease 2019 (COVID-19) predominantly presents with symptoms of fever, fatigue, cough and respiratory failure. However, it appears to have a unique interplay with cardiovascular disease (CVD); patients with pre-existing CVD are at highest risk for mortality from COVID-19, along with the elderly. COVID-19 contributes to cardiovascular complications including arrhythmias, myocardial dysfunction and myocardial inflammation. Although the exact mechanism of myocardial inflammation in patients with COVID-19 is not known, several plausible mechanisms have been proposed based on early observational reports. In this article, the authors summarise the available literature on mechanisms of myocardial injury in COVID-19.", "qid": 38, "docid": "h2xmxwd1", "rank": 96, "score": 0.7974855303764343}, {"content": "Title: COVID-19 for the Cardiologist: A Current Review of the Virology, Clinical Epidemiology, Cardiac and Other Clinical Manifestations and Potential Therapeutic Strategies Content: Summary The coronavirus disease-2019 (COVID-19), a contagious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), has reached pandemic status. As it spreads across the world, it has overwhelmed healthcare systems, strangled the global economy and led to a devastating loss of life. Widespread efforts from regulators, clinicians and scientists are driving a rapid expansion of knowledge of the SARS-CoV2 virus and the COVID-19 disease. We review the most current data with a focus on our basic understanding of the mechanism(s) of disease and translation to the clinical syndrome and potential therapeutics. We discuss the basic virology, epidemiology, clinical manifestation, multi-organ consequences, and outcomes. With a focus on cardiovascular complications, we propose several mechanisms of injury. The virology and potential mechanism of injury form the basis for a discussion of potential disease-modifying therapies.", "qid": 38, "docid": "hf3paocz", "rank": 97, "score": 0.7974127531051636}, {"content": "Title: COVID-19 Sepsis and Microcirculation Dysfunction Content: The spreading of Coronavirus (SARS-CoV-2) pandemic, known as COVID-19, has caused a great number of fatalities all around the World. Up to date (2020 May 6) in Italy we had more than 28,000 deaths, while there were more than 205.000 infected. The majority of patients affected by COVID-19 complained only slight symptoms: fatigue, myalgia or cough, but more than 15% of Chinese patients progressed into severe complications, with acute respiratory distress syndrome (ARDS), needing intensive treatment. We tried to summarize data reported in the last months from several Countries, highlighting that COVID-19 was characterized by cytokine storm (CS) and endothelial dysfunction in severely ill patients, where the progression of the disease was fast and fatal. Endothelial dysfunction was the fundamental mechanism triggering a pro-coagulant state, finally evolving into intravascular disseminated coagulation, causing embolization of several organs and consequent multiorgan failure (MOF). The Italian Society of Clinical Hemorheology and Microcirculation was aimed to highlight the role of microcirculatory dysfunction in the pathogenetic mechanisms of COVID-19 during the spreading of the biggest challenges to the World Health.", "qid": 38, "docid": "dklpifdj", "rank": 98, "score": 0.7972349524497986}, {"content": "Title: Cytokine Storm Induced by SARS-CoV-2 Content: A novel coronavirus disease 2019 (COVID-19) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently spreading globally, causing severe pneumonia and acute lung injury in many patients. Even worse, severe respiratory may develop into acute respiratory distress syndrome and multiple organ dysfunction syndrome in COVID-19. The cytokine storm caused by immune over-activation due to virus infection may be an important cause of death in the late period of progress, but the pathogenesis of cytokine storm is still unclear. This article reviews the mechanisms of SARS-CoV-2-induced cytokine storm in detail based on the current discovered researches, and put forward some valuable medication ideas for the targeted cytokines drug researches and treatment. The goal of this work will be helpful for reducing excessive immune response.", "qid": 38, "docid": "fozglfc8", "rank": 99, "score": 0.7970144152641296}, {"content": "Title: Coronavirus Disease 2019-related dyspnea cases difficult to interpret using chest computed tomography Content: Abstract Patients with Coronavirus Disease 2019 (COVID-19) often have clinical characteristics, such as chest tightness and dyspnea. Continuous, unresolved dyspnea often indicates the progression of lung lesions. The mechanism that underlies the chest distress and dyspnea in patients with COVID-19 is still unclear. Chest CT has a higher sensitivity and can play an essential role in the diagnosis and treatment of the disease. However, our clinical observations showed that although some patients had significant chest distress and dyspnea, the lesions that were observed in the lungs during computed tomography were milder and not completely consistent with clinical symptoms. We analyzed the clinical characteristics, laboratory test results, and imaging findings of these patients. We found that extensive inflammation of the bilateral and respiratory bronchioles in patients with COVID-19 due to excessive activation of proinflammatory cytokines and chemotactic aggregation of T-lymphocytes at the site of inflammation are possible mechanisms underlying chest distress and dyspnea in patients with COVID-19. Short-time and lose-dose use of corticosteroid may be helpful to treat chest tightness and dyspnea in mild COVID-19 patients. Through this study, we aimed to improve our understanding of the pathogenesis of COVID-19.", "qid": 38, "docid": "bioaupeo", "rank": 100, "score": 0.7965714931488037}]}
{"query": "What is the mechanism of cytokine storm syndrome on the COVID-19?", "hits": [{"content": "Title: Tocilizumab Administration in Patients with SARS\u2010CoV\u20102 Infection: Subcutaneous Injection versus Intravenous Infusion Content: Recent studies have revealed that cytokine storm syndrome, which is caused by the activation of inflammatory cytokines, is a likely underlying pathophysiology in patients with severe COVID\u201019 that has been associated with a high mortality rate(1). This article is protected by copyright. All rights reserved.", "qid": 39, "docid": "me4tdzvl", "rank": 1, "score": 0.8787381649017334}, {"content": "Title: The pathogenesis and treatment of the `Cytokine Storm' in COVID-19 Content: Summary Cytokine storm is an excessive immune response to external stimuli. The pathogenesis of the cytokine storm is complex. The disease progresses rapidly, and the mortality is high. Certain evidence shows that, during the coronavirus disease 2019 (COVID-19) epidemic, the severe deterioration of some patients has been closely related to the cytokine storm in their bodies. This article reviews the occurrence mechanism and treatment strategies of the COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.", "qid": 39, "docid": "fqlv35vo", "rank": 2, "score": 0.8648551106452942}, {"content": "Title: The pathogenesis and treatment of the `Cytokine Storm' in COVID-19 Content: Cytokine storm is an excessive immune response to external stimuli. The pathogenesis of the cytokine storm is complex. The disease progresses rapidly, and the mortality is high. Certain evidence shows that, during the coronavirus disease 2019 (COVID-19) epidemic, the severe deterioration of some patients has been closely related to the cytokine storm in their bodies. This article reviews the occurrence mechanism and treatment strategies of the COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.", "qid": 39, "docid": "iaatjew2", "rank": 3, "score": 0.8629682064056396}, {"content": "Title: [Advances in the research of mechanism and related immunotherapy on the cytokine storm induced by coronavirus disease 2019] Content: Coronavirus disease 2019 (COVID-19) has seriously affected the safety of patients and social stability. Some COVID-19 patients in the later stage of disease may develop into acute respiratory distress syndrome or even multiple organ failure. However, one of the most important mechanisms underlying the deterioration of disease is cytokine storm. At present, some therapies such as interleukin-6 antibody blocker, stem cell therapy, and transfusion of convalescent plasma have been applied to counteract the cytokine storm with some progresses being achieved. This article reviews the influences of cytokine storm syndrome on the COVID-19 and the corresponding immunotherapies to resist cytokine storm.", "qid": 39, "docid": "zukc3lvq", "rank": 4, "score": 0.8445857763290405}, {"content": "Title: Cytokine storm induced by SARS-CoV-2 Content: Coronavirus disease 2019 (COVID-19), caused by the virus designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread widely throughout the world. Despite the strict global outbreak management and quarantine measures that have been implemented, the incidence of COVID-19 continues to rise, resulting in more than 290,000 deaths and representing an extremely serious threat to human life and health. The clinical symptoms of the affected patients are heterogeneous, ranging from mild upper respiratory symptoms to severe pneumonitis and even acute respiratory distress syndrome (ARDS) or death. Systemic immune over activation due to SARS-CoV-2 infection causes the cytokine storm, which is especially noteworthy in severely ill patients with COVID-19. Pieces of evidence from current studies have shown that the cytokine storm may be an important factor in disease progression, even leading to multiple organ failure and death. This review provides an overview of the knowledge on the COVID-19 epidemiological profile, the molecular mechanisms of the SARS-CoV-2-induced cytokine storm and immune responses, the pathophysiological changes that occur during infection, the main antiviral compounds used in treatment strategies and the potential drugs for targeting cytokines, this information is presented to provide valuable guidance for further studies and for a therapeutic reduction of this excessive immune response.", "qid": 39, "docid": "bxfyse59", "rank": 5, "score": 0.8430584669113159}, {"content": "Title: [Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies] Content: Corona Virus Disease 2019 (COVID-19) has seriously affected the treatment of patients and social stability. In the later stage of disease, some COVID-19 patients may develop into acute respiratory distress syndrome or even multiple organ failure. However, one of the most important mechanism underlying the deterioration of disease is cytokine storm. At present, some therapies such as interleukin-6 antibody blocker, stem cell therapy, and transfusion of convalescent plasma have been applied to counteract the cytokine storm and have made some progress. This article reviews the influences of cytokine storm syndrome on the COVID-19 and the corresponding immunotherapies to resist cytokine storm.", "qid": 39, "docid": "3d04p4xp", "rank": 6, "score": 0.8413339257240295}, {"content": "Title: [Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies]. Content: Corona Virus Disease 2019 (COVID-19) has seriously affected the treatment of patients and social stability. In the later stage of disease, some COVID-19 patients may develop into acute respiratory distress syndrome or even multiple organ failure. However, one of the most important mechanism underlying the deterioration of disease is cytokine storm. At present, some therapies such as interleukin-6 antibody blocker, stem cell therapy, and transfusion of convalescent plasma have been applied to counteract the cytokine storm and have made some progress. This article reviews the influences of cytokine storm syndrome on the COVID-19 and the corresponding immunotherapies to resist cytokine storm.", "qid": 39, "docid": "urr5iuy2", "rank": 7, "score": 0.8413339257240295}, {"content": "Title: Cytokine Storm Induced by SARS-CoV-2 Content: A novel coronavirus disease 2019 (COVID-19) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently spreading globally, causing severe pneumonia and acute lung injury in many patients. Even worse, severe respiratory may develop into acute respiratory distress syndrome and multiple organ dysfunction syndrome in COVID-19. The cytokine storm caused by immune over-activation due to virus infection may be an important cause of death in the late period of progress, but the pathogenesis of cytokine storm is still unclear. This article reviews the mechanisms of SARS-CoV-2-induced cytokine storm in detail based on the current discovered researches, and put forward some valuable medication ideas for the targeted cytokines drug researches and treatment. The goal of this work will be helpful for reducing excessive immune response.", "qid": 39, "docid": "fozglfc8", "rank": 8, "score": 0.8312032222747803}, {"content": "Title: 2019 Novel Coronavirus Pandemic: What Do We Know? Content: The pandemic caused by SARS-COV2 Virus/COVID-19, which was initially reported in China in December 2019, has become a major global health concern. COVID-19 can manifest with cytokine storm - an exaggerated systemic inflammatory phenomenon due to over-production of proinflammatory cytokines by immune cells that results in diffuse inflammatory lung disease and acute respiratory distress syndrome. It may be complicated by septic shock and subsequent multi-organ failure. Based on the most recently published evidence, this article will review and discuss comprehensive information on its clinical manifestations, laboratory tests, potential therapeutics, and prevention guidelines.", "qid": 39, "docid": "k3w39apy", "rank": 9, "score": 0.8286728858947754}, {"content": "Title: Weathering the COVID-19 storm: Lessons from hematologic cytokine syndromes Content: A subset of patients with severe COVID-19 develop profound inflammation and multi-organ dysfunction consistent with a \"Cytokine Storm Syndrome\" (CSS). In this review we compare the clinical features, diagnosis, and pathogenesis of COVID-CSS with other hematological CSS, namely secondary hemophagocytic lymphohistiocytosis (sHLH), idiopathic multicentric Castleman disease (iMCD), and CAR-T cell therapy associated Cytokine Release Syndrome (CRS). Novel therapeutics targeting cytokines or inhibiting cell signaling pathways have now become the mainstay of treatment in these CSS. We review the evidence for cytokine blockade and attenuation in these known CSS as well as the emerging literature and clinical trials pertaining to COVID-CSS. Established markers of inflammation as well as cytokine levels are compared and contrasted between these four entities in order to establish a foundation for future diagnostic criteria of COVID-CSS.", "qid": 39, "docid": "2b6l1c0n", "rank": 10, "score": 0.8277974128723145}, {"content": "Title: Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2 Content: To date, no vaccines or effective drugs have been approved to prevent or treat COVID-19 and the current standard care relies on supportive treatments. Therefore, based on the fast and global spread of the virus, urgent investigations are warranted in order to develop preventive and therapeutic drugs. In this regard, treatments addressing the immunopathology of SARS-CoV-2 infection have become a major focus. Notably, while a rapid and well-coordinated immune response represents the first line of defense against viral infection, excessive inflammatory innate response and impaired adaptive host immune defense may lead to tissue damage both at the site of virus entry and at systemic level. Several studies highlight relevant changes occurring both in innate and adaptive immune system in COVID-19 patients. In particular, the massive cytokine and chemokine release, the so-called \u201ccytokine storm\u201d, clearly reflects a widespread uncontrolled dysregulation of the host immune defense. Although the prospective of counteracting cytokine storm is compelling, a major limitation relies on the limited understanding of the immune signaling pathways triggered by SARS-CoV-2 infection. The identification of signaling pathways altered during viral infections may help to unravel the most relevant molecular cascades implicated in biological processes mediating viral infections and to unveil key molecular players that may be targeted. Thus, given the key role of the immune system in COVID-19, a deeper understanding of the mechanism behind the immune dysregulation might give us clues for the clinical management of the severe cases and for preventing the transition from mild to severe stages.", "qid": 39, "docid": "hedpur93", "rank": 11, "score": 0.8269622325897217}, {"content": "Title: Weathering the COVID-19 storm: Lessons from hematologic cytokine syndromes Content: A subset of patients with severe COVID-19 develop profound inflammation and multi-organ dysfunction consistent with a \u201cCytokine Storm Syndrome\u201d (CSS). In this review we compare the clinical features, diagnosis, and pathogenesis of COVID-CSS with other hematological CSS, namely secondary hemophagocytic lymphohistiocytosis (sHLH), idiopathic multicentric Castleman disease (iMCD), and CAR-T cell therapy associated Cytokine Release Syndrome (CRS). Novel therapeutics targeting cytokines or inhibiting cell signaling pathways have now become the mainstay of treatment in these CSS. We review the evidence for cytokine blockade and attenuation in these known CSS as well as the emerging literature and clinical trials pertaining to COVID-CSS. Established markers of inflammation as well as cytokine levels are compared and contrasted between these four entities in order to establish a foundation for future diagnostic criteria of COVID-CSS.", "qid": 39, "docid": "9321dl89", "rank": 12, "score": 0.825149655342102}, {"content": "Title: Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2 Content: To date, no vaccines or effective drugs have been approved to prevent or treat COVID-19 and the current standard care relies on supportive treatments. Therefore, based on the fast and global spread of the virus, urgent investigations are warranted in order to develop preventive and therapeutic drugs. In this regard, treatments addressing the immunopathology of SARS-CoV-2 infection have become a major focus. Notably, while a rapid and well-coordinated immune response represents the first line of defense against viral infection, excessive inflammatory innate response and impaired adaptive host immune defense may lead to tissue damage both at the site of virus entry and at systemic level. Several studies highlight relevant changes occurring both in innate and adaptive immune system in COVID-19 patients. In particular, the massive cytokine and chemokine release, the so-called \"cytokine storm\", clearly reflects a widespread uncontrolled dysregulation of the host immune defense. Although the prospective of counteracting cytokine storm is compelling, a major limitation relies on the limited understanding of the immune signaling pathways triggered by SARS-CoV-2 infection. The identification of signaling pathways altered during viral infections may help to unravel the most relevant molecular cascades implicated in biological processes mediating viral infections and to unveil key molecular players that may be targeted. Thus, given the key role of the immune system in COVID-19, a deeper understanding of the mechanism behind the immune dysregulation might give us clues for the clinical management of the severe cases and for preventing the transition from mild to severe stages.", "qid": 39, "docid": "lv7kt128", "rank": 13, "score": 0.8243012428283691}, {"content": "Title: Extracorporeal blood purification treatment options for COVID-19: The role of immunoadsorption Content: The activation of the innate and adaptive immune systems by SARS-CoV-2 causes the release of several inflammatory cytokines, including IL-6. The inflammatory hypercytokinemia causes immunopathological changes in the lungs including vascular leakage, and alveolar edema. As a result of these changes in the lungs, hypoxia and acute respiratory distress syndrome occur in patients with COVID-19. Even though there are clinical trials on the development of therapeutics and vaccines, there are currently no licensed vaccines or therapeutics for COVID-19. Pharmacological approaches have shown poor results in sepsis-like syndromes caused by the hypercytokinemia. Suppressing the cytokine storm is an important way to prevent the organ damage in patients with COVID-19. Extracorporeal blood purification could be proposed as an adjunctive therapy for sepsis, aiming to control the associated dysregulation of the immune system, which is known to protect organ functions. Several extracorporeal blood purification therapies are now available, and most of them target endotoxins and/or the cytokines and aim improving the immune response. For this purpose, plasmapheresis and immunoadsorption may be an important adjunctive treatment option to manage the complications caused by cytokine storm in critically ill patients with COVID-19.", "qid": 39, "docid": "h1zsb2en", "rank": 14, "score": 0.8234516978263855}, {"content": "Title: Cytokine Storm in COVID19: A Neural Hypothesis Content: Cytokine storm in COVID-19 is characterized by an excessive inflammatory response to SARS-CoV-2 that is caused by a dysregulated immune system of the host. We are proposing a new hypothesis that SARS-CoV-2 mediated inflammation of nucleus tractus solitarius (NTS) may be responsible for the cytokine storm in COVID 19. The inflamed NTS may result in a dysregulated cholinergic anti-inflammatory pathway and hypothalamic-pituitary-adrenal axis.", "qid": 39, "docid": "ynrvowoc", "rank": 15, "score": 0.8230631351470947}, {"content": "Title: Cytokine Storm in COVID19: A Neural Hypothesis. Content: Cytokine storm in COVID-19 is characterized by an excessive inflammatory response to SARS-CoV-2 that is caused by a dysregulated immune system of the host. We are proposing a new hypothesis that SARS-CoV-2 mediated inflammation of nucleus tractus solitarius (NTS) may be responsible for the cytokine storm in COVID 19. The inflamed NTS may result in a dysregulated cholinergic anti-inflammatory pathway and hypothalamic-pituitary-adrenal axis.", "qid": 39, "docid": "e58nciq3", "rank": 16, "score": 0.8230631351470947}, {"content": "Title: The cytokine storm and COVID-19 Content: Coronavirus disease 2019 (COVID-19), which began in Wuhan, China in December 2019 has caused a large global pandemic and poses a serious threat to public health. More than four million cases of COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been confirmed as of May 11, 2020. SARS-CoV-2 is a highly pathogenic and transmissible coronavirus that primarily spreads through respiratory droplets and close contact. A growing body of clinical data suggests that a cytokine storm is associated with COVID-19 severity and is also a crucial cause of death from COVID-19. In the absence of antivirals and vaccines for COVID-19, there is an urgent need to understand the cytokine storm in COVID-19. Here, we have reviewed the current understanding of the features of SARS-CoV-2 and the pathological features, pathophysiological mechanisms, and treatments of the cytokine storm induced by COVID-19. Additionally, we suggest that the identification and treatment of the cytokine storm are important components for rescuing patients with severe COVID-19. This article is protected by copyright. All rights reserved.", "qid": 39, "docid": "hqzkzupi", "rank": 17, "score": 0.819930911064148}, {"content": "Title: On the Alert for Cytokine Storm: Immunopathology in COVID-19 Content: Poor outcomes in COVID-19 correlate with clinical and laboratory features of cytokine storm syndrome. Broad screening for cytokine storm and early, targeted antiinflammatory therapy may prevent immunopathology and could help conserve limited health care resources. While studies are ongoing, extrapolating from clinical experience in cytokine storm syndromes may benefit the multidisciplinary teams caring for patients with severe COVID-19.", "qid": 39, "docid": "6io0zd0z", "rank": 18, "score": 0.819061279296875}, {"content": "Title: Lymphopenia in COVID-19: Therapeutic opportunities Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is uncontrollably spread all over the world. The host immune responses strongly try to confront it with all the potential cells and cytokines. With chronically condition of SARS-CoV-2, natural killer cells and T cells become exhausted and decreasing their count leads to lymphopenia. Inability to eradicate the infected organ makes hyperinitiation of the immune system, which releases the excessive inflammatory cytokines to compensate the exhausted one as well as the low lymphocytes counts; it consequently leads to the cytokine storm syndrome. These mechanisms and the potential therapeutic targeting are discussed in this paper.", "qid": 39, "docid": "cmq2832d", "rank": 19, "score": 0.8171988725662231}, {"content": "Title: On the Alert for Cytokine Storm: Immunopathology in COVID\u201019 Content: Poor outcomes in COVID\u201019 correlate with clinical and laboratory features of cytokine storm syndrome. Broad screening for cytokine storm and early, targeted antiinflammatory therapy may prevent immunopathology and could help conserve limited health care resources. While studies are ongoing, extrapolating from clinical experience in cytokine storm syndromes may benefit the multidisciplinary teams caring for patients with severe COVID\u201019.", "qid": 39, "docid": "y26r9g3m", "rank": 20, "score": 0.8170382976531982}, {"content": "Title: The cytokine storm and COVID\u201019 Content: Coronavirus disease 2019 (COVID\u201019), which began in Wuhan, China in December 2019 has caused a large global pandemic and poses a serious threat to public health. More than four million cases of COVID\u201019, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102), have been confirmed as of May 11, 2020. SARS\u2010CoV\u20102 is a highly pathogenic and transmissible coronavirus that primarily spreads through respiratory droplets and close contact. A growing body of clinical data suggests that a cytokine storm is associated with COVID\u201019 severity and is also a crucial cause of death from COVID\u201019. In the absence of antivirals and vaccines for COVID\u201019, there is an urgent need to understand the cytokine storm in COVID\u201019. Here, we have reviewed the current understanding of the features of SARS\u2010CoV\u20102 and the pathological features, pathophysiological mechanisms, and treatments of the cytokine storm induced by COVID\u201019. Additionally, we suggest that the identification and treatment of the cytokine storm are important components for rescuing patients with severe COVID\u201019. This article is protected by copyright. All rights reserved.", "qid": 39, "docid": "rvrgcugn", "rank": 21, "score": 0.8165701627731323}, {"content": "Title: 2019 Novel Coronavirus Pandemic: What Do We Know? Content: The pandemic caused by SARS-COV2 Virus/COVID-19, which was initially reported in China in December 2019, has become a major global health concern COVID-19 can manifest with cytokine storm - an exaggerated systemic inflammatory phenomenon due to over-production of proinflammatory cytokines by immune cells that results in diffuse inflammatory lung disease and acute respiratory distress syndrome It may be complicated by septic shock and subsequent multi-organ failure Based on the most recently published evidence, this article will review and discuss comprehensive information on its clinical manifestations, laboratory tests, potential therapeutics, and prevention guidelines", "qid": 39, "docid": "8lnb2tnz", "rank": 22, "score": 0.8156788945198059}, {"content": "Title: Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions Content: Abstract The coronavirus disease-19 pandemic (COVID-19), which appeared in China in December 2019 and rapidly spread throughout the world, has forced clinicians and scientists to take up extraordinary challenges. This unprecedented situation led to the inception of numerous fundamental research protocols and many clinical trials. It quickly became apparent that although COVID-19, in the vast majority of cases, was a benign disease, it could also develop a severe form with sometimes fatal outcomes. Cytokines are central to the pathophysiology of COVID-19; while some of them are beneficial (type-I interferon, interleukin-7), others appear detrimental (interleukin-1\u03b2, -6, and TNF-\u03b1) particularly in the context of the so-called cytokine storm. Yet another characteristic of the disease has emerged: concomitant immunodeficiency, notably involving impaired type-I interferon response, and lymphopenia. This review provides an overview of current knowledge on COVID-19 immunopathology. We discuss the defective type-I IFN response, the theoretical role of IL-7 to restore lymphocyte repertoire, as well as we mention the two patterns observed in severe COVID-19 (i.e. interleukin-1\u03b2-driven macrophage activation syndrome vs. interleukin-6-driven immune dysregulation). Next, reviewing current evidence drawn from clinical trials, we examine a number of cytokine and anti-cytokine therapies, including interleukin-1, -6, and TNF inhibitors, as well as less targeted therapies, such as corticosteroids, chloroquine, or JAK inhibitors.", "qid": 39, "docid": "qlv0jttw", "rank": 23, "score": 0.8155015707015991}, {"content": "Title: COVID-19 cytokine storm: The anger of inflammation Content: Patients with COVID-19 who require ICU admission might have the cytokine storm. It is a state of out-of-control release of a variety of inflammatory cytokines. The molecular mechanism of the cytokine storm has not been explored extensively yet. The attachment of SARS-CoV-2 spike glycoprotein with angiotensin-converting enzyme 2 (ACE2), as its cellular receptor, triggers complex molecular events that leads to hyperinflammation. Four molecular axes that may be involved in SARS-CoV-2 driven inflammatory cytokine overproduction are addressed in this work. The virus-mediated down-regulation of ACE2 causes a burst of inflammatory cytokine release through dysregulation of the renin-angiotensin-aldosterone system (ACE/angiotensin II/AT1R axis), attenuation of Mas receptor (ACE2/MasR axis), increased activation of [des-Arg9]-bradykinin (ACE2/bradykinin B1R/DABK axis), and activation of the complement system including C5a and C5b-9 components. The molecular clarification of these axes will elucidate an array of therapeutic strategies to confront the cytokine storm in order to prevent and treat COVID-19 associated acute respiratory distress syndrome.", "qid": 39, "docid": "s82qv18v", "rank": 24, "score": 0.8153824806213379}, {"content": "Title: Extracorporeal Blood Purification Treatment Options for COVID-19: The Role of Immunoadsorption Content: Abstract The activation of theinnate and adaptive immune systems by SARS-CoV-2 causes the release of several inflammatory cytokines, including IL-6. The inflammatory hypercytokinemia causes immunopathological changes in the lungs including vascular leakage, and alveolar edema. As a result of these changes in the lungs, hypoxia and acute respiratory distress syndrome occur in patients with COVID-19. Even though there are clinical trials on the development of therapeutics and vaccines, there are currently no licensed vaccines or therapeutics for COVID-19. Pharmacological approaches have shown poor results in sepsis-like syndromes caused by the hypercytokinemia. Suppressing the cytokine storm is an important way to prevent the organ damage in patients with COVID-19. Extracorporeal blood purification could be proposed as an adjunctive therapy for sepsis, aiming to control the associated dysregulation of the immune system, which is known to protect organ functions. Several extracorporeal blood purification therapies are now available, and most of them target endotoxins and/or the cytokines and aim improving the immune response. For this purpose, plasmapheresis and immunoadsorption may be an important adjunctive treatment option to manage the complications caused by cytokine storm in critically ill patients with COVID-19.", "qid": 39, "docid": "mt49u9ws", "rank": 25, "score": 0.8140708208084106}, {"content": "Title: Lung under attack by COVID-19-induced cytokine storm: pathogenic mechanisms and therapeutic implications Content: The lung is a key target of the cytokine storm that can be triggered by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the widespread clinical syndrome known as coronavirus disease 2019 (COVID-19). Indeed, in some patients, SARS-CoV-2 promotes a dysfunctional immune response that dysregulates the cytokine secretory pattern. Hypercytokinemia underlies the hyperinflammatory state leading to injury of alveolar epithelial cells and vascular endothelial cells, as well as to lung infiltration sustained by neutrophils and macrophages. Within such a pathogenic context, interleukin-6 (IL-6) and other cytokines/chemokines play a pivotal pro-inflammatory role. Therefore, cytokines and their receptors, as well as cytokine-dependent intracellular signalling pathways can be targeted by potential therapies aimed to relieve the heavy burden of cytokine storm. In particular, the anti-IL-6-receptor monoclonal antibody tocilizumab is emerging as one of the most promising pharmacologic treatments. The reviews of this paper are available via the supplemental material section.", "qid": 39, "docid": "o9xh6bqz", "rank": 26, "score": 0.8140141367912292}, {"content": "Title: Targeting JAK-STAT Signaling to Control Cytokine Release Syndrome in COVID-19 Content: Recent advances in the pathophysiologic understanding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has indicated that patients with severe coronavirus disease 2019 (COVID-19) might experience cytokine release syndrome (CRS), characterized by increased interleukin (IL)-6, IL-2, IL-7, IL-10, etc. Therefore, the treatment of cytokine storm has been proposed as a critical part of rescuing severe COVID-19. Several of the cytokines involved in COVID-19 employ a distinct intracellular signaling pathway mediated by Janus kinases (JAKs). JAK inhibition, therefore, presents an attractive therapeutic strategy for CRS, which is a common cause of adverse clinical outcomes in COVID-19. Below, we review the possibilities and challenges of targeting the pathway in COVID-19.", "qid": 39, "docid": "9f6fxd94", "rank": 27, "score": 0.8122625350952148}, {"content": "Title: Lymphopenia in COVID\u201019: Therapeutic opportunities Content: Severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) is uncontrollably spread all over the world. The host immune responses strongly try to confront it with all the potential cells and cytokines. With chronically condition of SARS\u2010CoV\u20102, natural killer cells and T cells become exhausted and decreasing their count leads to lymphopenia. Inability to eradicate the infected organ makes hyperinitiation of the immune system, which releases the excessive inflammatory cytokines to compensate the exhausted one as well as the low lymphocytes counts; it consequently leads to the cytokine storm syndrome. These mechanisms and the potential therapeutic targeting are discussed in this paper.", "qid": 39, "docid": "ep9aqpfs", "rank": 28, "score": 0.8121543526649475}, {"content": "Title: The amount of cytokine-release defines different shades of Sars-Cov2 infection Content: The recent outbreak of coronavirus disease (COVID 19), spreading from China all around the world in early 2020, has led scientists to investigate the immuno-mediated mechanisms underlying the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) infection. Depending on the amount of cytokines released as the result of the immunological activation induced by SARS-CoV2, three major clinical phenotypes can be identified: \"mild\",symbolized as a \"drizzle\" of cytokines, severe as a \"storm\", and critical as a \"hurricane\". In patients with mild symptoms, the release of pro-inflammatory cytokines is balanced to obtain a defense response against the virus which is often self-limiting and overcomes without tissue damage. In severe phenotype, resembling a \"cytokine-release syndrome\", SARS-CoV2 causes the lysis of the immune-mediators leading to a cytokine storm able to induce lung epithelium damage and acute respiratory distress syndrome. In critical patients, the immune response may become uncontrolled, thus the cytokine burst resembles a form of secondary hemophagocytic lymphohistiocytosis which may result in a multi organ failure. In addition to the standard of care, an immune-modulatory therapy tailored to each one of the different phenotypes should be used in order to prevent or reduce the release of cytokines responsible for organ damage and disease progression.", "qid": 39, "docid": "vt56yqel", "rank": 29, "score": 0.8118151426315308}, {"content": "Title: The amount of cytokine-release defines different shades of Sars-Cov2 infection. Content: The recent outbreak of coronavirus disease (COVID 19), spreading from China all around the world in early 2020, has led scientists to investigate the immuno-mediated mechanisms underlying the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) infection. Depending on the amount of cytokines released as the result of the immunological activation induced by SARS-CoV2, three major clinical phenotypes can be identified: \"mild\",symbolized as a \"drizzle\" of cytokines, severe as a \"storm\", and critical as a \"hurricane\". In patients with mild symptoms, the release of pro-inflammatory cytokines is balanced to obtain a defense response against the virus which is often self-limiting and overcomes without tissue damage. In severe phenotype, resembling a \"cytokine-release syndrome\", SARS-CoV2 causes the lysis of the immune-mediators leading to a cytokine storm able to induce lung epithelium damage and acute respiratory distress syndrome. In critical patients, the immune response may become uncontrolled, thus the cytokine burst resembles a form of secondary hemophagocytic lymphohistiocytosis which may result in a multi organ failure. In addition to the standard of care, an immune-modulatory therapy tailored to each one of the different phenotypes should be used in order to prevent or reduce the release of cytokines responsible for organ damage and disease progression.", "qid": 39, "docid": "5rc9x979", "rank": 30, "score": 0.8118151426315308}, {"content": "Title: Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts Content: Clinical evidence indicates that the fatal outcome observed with severe acute respiratory syndrome-coronavirus-2 infection often results from alveolar injury that impedes airway capacity and multi-organ failure-both of which are associated with the hyperproduction of cytokines, also known as a cytokine storm or cytokine release syndrome. Clinical reports show that both mild and severe forms of disease result in changes in circulating leukocyte subsets and cytokine secretion, particularly IL-6, IL-1\u00df, IL-10, TNF, GM-CSF, IP-10 (IFN-induced protein 10), IL-17, MCP-3, and IL-1ra. Not surprising, therapies that target the immune response and curtail the cytokine storm in coronavirus 2019 (COVID-19) patients have become a focus of recent clinical trials. Here we review reports on leukocyte and cytokine data associated with COVID-19 disease in 3939 patients in China and describe emerging data on immunopathology. With an emphasis on immune modulation, we also look at ongoing clinical studies aimed at blocking proinflammatory cytokines; transfer of immunosuppressive mesenchymal stem cells; use of convalescent plasma transfusion; as well as immunoregulatory therapy and traditional Chinese medicine regimes. In examining leukocyte and cytokine activity in COVID-19, we focus in particular on how these levels are altered as the disease progresses (neutrophil NETosis, macrophage, T cell response, etc.) and proposed consequences to organ pathology (coagulopathy, etc.). Viral and host interactions are described to gain further insight into leukocyte biology and how dysregulated cytokine responses lead to disease and/or organ damage. By better understanding the mechanisms that drive the intensity of a cytokine storm, we can tailor treatment strategies at specific disease stages and improve our response to this worldwide public health threat.", "qid": 39, "docid": "nmdko4nl", "rank": 31, "score": 0.8117504119873047}, {"content": "Title: The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system Content: In 2019-2020 a new coronavirus named SARS-CoV-2 was identified as the causative agent of a several acute respiratory infection named COVID-19, which is causing a worldwide pandemic. There are still many unresolved questions regarding the pathogenesis of this disease and especially the reasons underlying the extremely different clinical course, ranging from asymptomatic forms to severe manifestations, including the Acute Respiratory Distress Syndrome (ARDS). SARS-CoV-2 showed phylogenetic similarities to both SARS-CoV and MERS-CoV viruses, and some of the clinical features are shared between COVID-19 and previously identified beta-coronavirus infections. Available evidence indicate that the so called \"cytokine storm\" an uncontrolled over-production of soluble markers of inflammation which, in turn, sustain an aberrant systemic inflammatory response, is a major responsible for the occurrence of ARDS. Chemokines are low molecular weight proteins with powerful chemoattractant activity which play a role in the immune cell recruitment during inflammation. This review will be aimed at providing an overview of the current knowledge on the involvement of the chemokine/chemokine-receptor system in the cytokine storm related to SARS-CoV-2 infection. Basic and clinical evidences obtained from previous SARS and MERS epidemics and available data from COVID-19 will be taken into account.", "qid": 39, "docid": "9ch0wti7", "rank": 32, "score": 0.8111243844032288}, {"content": "Title: Targeting JAK-STAT Signaling to Control Cytokine Release Syndrome in COVID-19 Content: Recent advances in the pathophysiologic understanding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has indicated that patients with severe COVID-19 might experience cytokine release syndrome (CRS), characterized by increased interleukin (IL)-6, IL-2, IL-7, IL-10, etc. Therefore, the treatment of cytokine storm has been proposed as a critical part of rescuing severe COVID-19. Several of the cytokines involved in COVID-19 employ a distinct intracellular signaling pathway mediated by Janus kinases (JAKs). JAK inhibition, therefore, presents an attractive therapeutic strategy for CRS, which is a common cause of adverse clinical outcomes in COVID-19. Below, we review the possibilities and challenges of targeting the pathway in COVID-19.", "qid": 39, "docid": "xb4ld4tr", "rank": 33, "score": 0.8110965490341187}, {"content": "Title: Bilateral anterior uveitis as a part of a multisystem inflammatory syndrome secondary to COVID-19 infection Content: During the ongoing COVID-19 pandemic, there is a global concern about patients presenting with inflammatory syndrome with variable clinical features. Colanfrancesco et al. described COVID-19 systemic inflammatory reaction that are characterized by a life-threatening hyper-inflammation sustained by a cytokines storm which eventually leads to multi-organ failure. This article is protected by copyright. All rights reserved.", "qid": 39, "docid": "vl0has6x", "rank": 34, "score": 0.8099764585494995}, {"content": "Title: COVID-19 gone bad: A new character in the spectrum of the hyperferritinemic syndrome? Content: The severe form of COVID-19 share several clinical and laboratory features with four entities gathered under the term \"hyperferritinemic syndromes\" and including macrophage activation syndrome (MAS), adult-onset Still's disease (AOSD), catastrophic anti-phospholipid syndrome (CAPS) and septic shock. COVID-19 systemic inflammatory reaction and \"hyperferritinemic syndromes\" are all characterized by high serum ferritin and a life-threatening hyper-inflammation sustained by a cytokines storm which eventually leads to multi-organ failure. In this review, we analyze the possible epidemiological and molecular mechanisms responsible for hyper-inflammation in patients with severe COVID-19 and we underline the similarities between this condition and \"hyperferritinemic syndromes\" which would allow considering severe COVID-19 as a fifth member of this spectrum of inflammatory conditions.", "qid": 39, "docid": "qvpjci4y", "rank": 35, "score": 0.8096799850463867}, {"content": "Title: Absence of severe complications from SARS-CoV-2 infection in children with rheumatic diseases treated with biologic drugs Content: We read with interest the Editorial by Cron and Chatam (1) suggesting a cytokine storm syndrome (CSS) occurring in response to SARS-CoV-2 infection and, consequently, a possible role for targeted approaches to blocking inflammatory cytokines.", "qid": 39, "docid": "iffgnr51", "rank": 36, "score": 0.8094234466552734}, {"content": "Title: Absence of severe complications from SARS-CoV-2 infection in children with rheumatic diseases treated with biologic drugs. Content: We read with interest the Editorial by Cron and Chatam (1) suggesting a cytokine storm syndrome (CSS) occurring in response to SARS-CoV-2 infection and, consequently, a possible role for targeted approaches to blocking inflammatory cytokines.", "qid": 39, "docid": "rzfa4ozr", "rank": 37, "score": 0.8094234466552734}, {"content": "Title: The Cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system Content: In 2019-2020 a new coronavirus named SARS-CoV-2 was identified as the causative agent of a several acute respiratory infection named COVID-19, which is causing a worldwide pandemic. There are still many unresolved questions regarding the pathogenesis of this disease and especially the reasons underlying the extremely different clinical course, ranging from asymptomatic forms to severe manifestations, including the Acute Respiratory Distress Syndrome (ARDS). SARS-CoV-2 showed phylogenetic similarities to both SARS-CoV and MERS-CoV viruses, and some of the clinical features are shared between COVID-19 and previously identified beta-coronavirus infections. Available evidence indicate that the so called \u201ccytokine storm\u201d an uncontrolled over-production of soluble markers of inflammation which, in turn, sustain an aberrant systemic inflammatory response, is a major responsible for the occurrence of ARDS. Chemokines are low molecular weight proteins with powerful chemoattractant activity which play a role in the immune cell recruitment during inflammation. This review will be aimed at providing an overview of the current knowledge on the involvement of the chemokine/chemokine-receptor system in the cytokine storm related to SARS-CoV-2 infection. Basic and clinical evidences obtained from previous SARS and MERS epidemics and available data from COVID-19 will be taken into account.", "qid": 39, "docid": "ex9nh1yi", "rank": 38, "score": 0.8086233139038086}, {"content": "Title: COVID-19 gone bad: A new character in the spectrum of the hyperferritinemic syndrome? Content: Abstract The severe form of COVID-19 share several clinical and laboratory features with four entities gathered under the term \u201chyperferritinemic syndrome\u201d and including macrophage activation syndrome (MAS), adult-onset Still's disease (AOSD), catastrophic anti-phospholipid syndrome (CAPS) and septic shock. COVID-19 systemic inflammatory reaction and \u201chyperferritinemic syndromes\u201d are all characterized by high serum ferritin and a life-threatening hyper-inflammation sustained by a cytokines storm which eventually leads to multi-organ failure. In this review, we analyze the possible epidemiological and molecular mechanisms responsible for hyper-inflammation in patients with severe COVID-19 and we underline the similarities between this condition and \u201chyperferritinemic syndromes\u201d which would allow considering this entity as the fifth member of the spectrum of inflammatory conditions.", "qid": 39, "docid": "v7wgb6mr", "rank": 39, "score": 0.8071340918540955}, {"content": "Title: Cytokine storm and leukocyte changes in mild versus severe SARS\u2010CoV\u20102 infection: Review of 3939 COVID\u201019 patients in China and emerging pathogenesis and therapy concepts Content: Clinical evidence indicates that the fatal outcome observed with severe acute respiratory syndrome\u2010coronavirus\u20102 infection often results from alveolar injury that impedes airway capacity and multi\u2010organ failure\u2014both of which are associated with the hyperproduction of cytokines, also known as a cytokine storm or cytokine release syndrome. Clinical reports show that both mild and severe forms of disease result in changes in circulating leukocyte subsets and cytokine secretion, particularly IL\u20106, IL\u20101\u03b2, IL\u201010, TNF, GM\u2010CSF, IP\u201010 (IFN\u2010induced protein 10), IL\u201017, MCP\u20103, and IL\u20101ra. Not surprising, therapies that target the immune response and curtail the cytokine storm in coronavirus 2019 (COVID\u201019) patients have become a focus of recent clinical trials. Here we review reports on leukocyte and cytokine data associated with COVID\u201019 disease in 3939 patients in China and describe emerging data on immunopathology. With an emphasis on immune modulation, we also look at ongoing clinical studies aimed at blocking proinflammatory cytokines; transfer of immunosuppressive mesenchymal stem cells; use of convalescent plasma transfusion; as well as immunoregulatory therapy and traditional Chinese medicine regimes. In examining leukocyte and cytokine activity in COVID\u201019, we focus in particular on how these levels are altered as the disease progresses (neutrophil NETosis, macrophage, T cell response, etc.) and proposed consequences to organ pathology (coagulopathy, etc.). Viral and host interactions are described to gain further insight into leukocyte biology and how dysregulated cytokine responses lead to disease and/or organ damage. By better understanding the mechanisms that drive the intensity of a cytokine storm, we can tailor treatment strategies at specific disease stages and improve our response to this worldwide public health threat.", "qid": 39, "docid": "r4vobu5w", "rank": 40, "score": 0.8068603277206421}, {"content": "Title: Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions Content: The coronavirus disease-19 pandemic (COVID-19), which appeared in China in December 2019 and rapidly spread throughout the world, has forced clinicians and scientists to take up extraordinary challenges. This unprecedented situation led to the inception of numerous fundamental research protocols and many clinical trials. It quickly became apparent that although COVID-19, in the vast majority of cases, was a benign disease, it could also develop a severe form with sometimes fatal outcomes. Cytokines are central to the pathophysiology of COVID-19; while some of them are beneficial (type-I interferon, interleukin-7), others appear detrimental (interleukin-1\u00df, -6, and TNF-&#945;) particularly in the context of the so-called cytokine storm. Yet another characteristic of the disease has emerged: concomitant immunodeficiency, notably involving impaired type-I interferon response, and lymphopenia. This review provides an overview of current knowledge on COVID-19 immunopathology. We discuss the defective type-I IFN response, the theoretical role of IL-7 to restore lymphocyte repertoire, as well as we mention the two patterns observed in severe COVID-19 (i.e. interleukin-1\u00df-driven macrophage activation syndrome vs. interleukin-6-driven immune dysregulation). Next, reviewing current evidence drawn from clinical trials, we examine a number of cytokine and anti-cytokine therapies, including interleukin-1, -6, and TNF inhibitors, as well as less targeted therapies, such as corticosteroids, chloroquine, or JAK inhibitors.", "qid": 39, "docid": "ybuf69f9", "rank": 41, "score": 0.8066099286079407}, {"content": "Title: Storm, typhoon, cyclone or hurricane in patients with COVID-19? Beware of the same storm that has a different origin Content: Some of the articles being published during the severe acute respiratory syndrome-coronavirus (SARS-CoV)-2 pandemic highlight a link between severe forms of coronavirus disease 2019 (COVID-19) and the so-called cytokine storm, also with increased ferritin levels. However, this scenario is more complex than initially thought due to the heterogeneity of hyperinflammation. Some patients with coronavirus 2019 disease (COVID-19) develop a fully blown secondary haemophagocytic lymphohistiocytosis (sHLH), whereas others, despite a consistent release of pro-inflammatory cytokines, do not fulfil sHLH criteria but still show some features resembling the phenotype of the hyperferritinemic syndrome. Despite the final event (the cytokine storm) is shared by various conditions leading to sHLH, the aetiology, either infectious, autoimmune or neoplastic, accounts for the differences in the various phases of this process. Moreover, the evidence of a hyperinflammatory microenvironment provided the rationale to employ immunomodulating agents for therapeutic purposes in severe COVID-19. This viewpoint aims at discussing the pitfalls and issues to be considered with regard to the use of immunomodulating agents in COVID-19, such as timing of treatment based on the viral load and the extent of cytokine/ferritin overexpression. Furthermore, it encompasses recent findings in the paediatric field about a novel multisystem inflammatory disease resembling toxic shock syndrome and atypical Kawasaki disease observed in children with proven SARS-CoV2 infection. Finally, it includes arguments in favour of adding COVID-19 to the spectrum of the recently defined 'hyperferritinemic syndrome', which already includes adult-onset Still's disease, macrophage activation syndrome, septic shock and catastrophic anti-phospholipid syndrome.", "qid": 39, "docid": "l95x70ab", "rank": 42, "score": 0.8063074946403503}, {"content": "Title: Role of Interleukin-6 in Lung Complications in Patients With COVID-19: Therapeutic Implications. Content: COVID-19 is viral respiratory infection with frequently fatal lung complications in the elderly or in people with serious comorbidities. Lung destruction appears to be associated with a cytokine storm related to an increased level of interleukin-6 (IL6). Therapeutic targeting of the interleukin-6 signaling pathway can attenuate such a cytokine storm and can be beneficial for patients with COVID-19 in danger of pulmonary failure. This article demonstrates the importance of IL6 in progression of disease and the possibility of inhibition of IL6 signaling in COVID-19 therapy.", "qid": 39, "docid": "vlykkorp", "rank": 43, "score": 0.8052005171775818}, {"content": "Title: Role of Interleukin-6 in Lung Complications in Patients With COVID-19: Therapeutic Implications Content: COVID-19 is viral respiratory infection with frequently fatal lung complications in the elderly or in people with serious comorbidities. Lung destruction appears to be associated with a cytokine storm related to an increased level of interleukin-6 (IL6). Therapeutic targeting of the interleukin-6 signaling pathway can attenuate such a cytokine storm and can be beneficial for patients with COVID-19 in danger of pulmonary failure. This article demonstrates the importance of IL6 in progression of disease and the possibility of inhibition of IL6 signaling in COVID-19 therapy.", "qid": 39, "docid": "bn8qjliy", "rank": 44, "score": 0.805200457572937}, {"content": "Title: Storm, typhoon, cyclone or hurricane in patients with COVID-19? Beware of the same storm that has a different origin Content: Some of the articles being published during the severe acute respiratory syndrome\u2013coronavirus (SARS-CoV)-2 pandemic highlight a link between severe forms of coronavirus disease 2019 (COVID-19) and the so-called cytokine storm, also with increased ferritin levels. However, this scenario is more complex than initially thought due to the heterogeneity of hyperinflammation. Some patients with coronavirus 2019 disease (COVID-19) develop a fully blown secondary haemophagocytic lymphohistiocytosis (sHLH), whereas others, despite a consistent release of pro-inflammatory cytokines, do not fulfil sHLH criteria but still show some features resembling the phenotype of the hyperferritinemic syndrome. Despite the final event (the cytokine storm) is shared by various conditions leading to sHLH, the aetiology, either infectious, autoimmune or neoplastic, accounts for the differences in the various phases of this process. Moreover, the evidence of a hyperinflammatory microenvironment provided the rationale to employ immunomodulating agents for therapeutic purposes in severe COVID-19. This viewpoint aims at discussing the pitfalls and issues to be considered with regard to the use of immunomodulating agents in COVID-19, such as timing of treatment based on the viral load and the extent of cytokine/ferritin overexpression. Furthermore, it encompasses recent findings in the paediatric field about a novel multisystem inflammatory disease resembling toxic shock syndrome and atypical Kawasaki disease observed in children with proven SARS-CoV2 infection. Finally, it includes arguments in favour of adding COVID-19 to the spectrum of the recently defined \u2018hyperferritinemic syndrome\u2019, which already includes adult-onset Still\u2019s disease, macrophage activation syndrome, septic shock and catastrophic anti-phospholipid syndrome.", "qid": 39, "docid": "qth1y88o", "rank": 45, "score": 0.804975688457489}, {"content": "Title: Amelioration of COVID-19 related cytokine storm syndrome: Parallels to chimeric antigen receptor-T cell cytokine release syndrome Content: Coronavirus disease-2019 (COVID-19) severity appears to parallel the host immune response, with a subset of patients developing COVID-19 cytokine storm syndrome (CSS).(1) Serum inflammatory cytokines are elevated in COVID-19,(2-5) and interleukin (IL)-6 appears to play a central role in COVID-19 related CSS.(6-8) Based on the success of IL-6 receptor blockade for chimeric antigen receptor T-cell therapy associated cytokine release syndrome (CAR T-cell CRS), similar strategies using tocilizumab are being investigated in COVID-19.", "qid": 39, "docid": "jxsj3lg6", "rank": 46, "score": 0.8044543266296387}, {"content": "Title: [Expert consensus on Corona Virus Disease 2019 with special blood purification technology] Content: The outbreak of Corona Virus Disease 2019 (COVID-19) has spread to more than 70 countries worldwide and there was a higher mortality in those who developed serious illness.Cytokine storm syndrome is an important pathophysiological basis for COVID-19 patients developing into severe or critical conditions. It was indicated in the diagnosis and treatment scheme, by the National Health Commission of the People's Republic of China, that blood purifications such as plasma exchange, plasma adsorption, hemoperfusion, hemofiltration and plasmafiltration could be considered for use in the critical patients with cytokine storm syndrome. This expert consensus, proposed by the Chinese Society of Nephrology and the Nephrology Committee of Chinese Research Hospital Association, is to guide and standardize the clinical application of blood purifications in the treatment of severe or critical patients with COVID-19.", "qid": 39, "docid": "euozpliw", "rank": 47, "score": 0.8041939735412598}, {"content": "Title: [Expert consensus on Corona Virus Disease 2019 with special blood purification technology]. Content: The outbreak of Corona Virus Disease 2019 (COVID-19) has spread to more than 70 countries worldwide and there was a higher mortality in those who developed serious illness.Cytokine storm syndrome is an important pathophysiological basis for COVID-19 patients developing into severe or critical conditions. It was indicated in the diagnosis and treatment scheme, by the National Health Commission of the People's Republic of China, that blood purifications such as plasma exchange, plasma adsorption, hemoperfusion, hemofiltration and plasmafiltration could be considered for use in the critical patients with cytokine storm syndrome. This expert consensus, proposed by the Chinese Society of Nephrology and the Nephrology Committee of Chinese Research Hospital Association, is to guide and standardize the clinical application of blood purifications in the treatment of severe or critical patients with COVID-19.", "qid": 39, "docid": "jqtoundb", "rank": 48, "score": 0.8041939735412598}, {"content": "Title: Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Content: Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread across many other countries. While the majority of patients were considered mild, critically ill patients involving respiratory failure and multiple organ dysfunction syndrome are not uncommon, which could result death. We hypothesized that cytokine storm is associated with severe outcome. We enrolled 102 COVID-19 patients who were admitted to Renmin Hospital (Wuhan, China). All patients were classified into moderate, severe and critical groups according to their symptoms. 45 control samples of healthy volunteers were also included. Inflammatory cytokines and C-Reactive Protein (CRP) profiles of serum samples were analyzed by specific immunoassays. Results showed that COVID-19 patients have higher serum level of cytokines (TNF-\u03b1, IFN-\u03b3, IL-2, IL-4, IL-6 and IL-10) and CRP than control individuals. Within COVID-19 patients, serum IL-6 and IL-10 levels are significantly higher in critical group (n = 17) than in moderate (n = 42) and severe (n = 43) group. The levels of IL-10 is positively correlated with CRP amount (r = 0.41, P < 0.01). Using univariate logistic regression analysis, IL-6 and IL-10 are found to be predictive of disease severity and receiver operating curve analysis could further confirm this result (AUC = 0.841, 0.822 respectively). Our result indicated higher levels of cytokine storm is associated with more severe disease development. Among them, IL-6 and IL-10 can be used as predictors for fast diagnosis of patients with higher risk of disease deterioration. Given the high levels of cytokines induced by SARS-CoV-2, treatment to reduce inflammation-related lung damage is critical.", "qid": 39, "docid": "zuchss0s", "rank": 49, "score": 0.8036556243896484}, {"content": "Title: The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of \"inflame-aging\" Content: PURPOSE: Novel Coronavirus disease 2019 (COVID-19), is an acute respiratory distress syndrome (ARDS), which is emerged in Wuhan, and recently become worldwide pandemic. Strangely, ample evidences have been shown that the severity of COVID-19 infections varies widely from children (asymptomatic), adults (mild infection), as well as elderly adults (deadly critical). It has proven that COVID-19 infection in some elderly critical adults leads to a cytokine storm, which is characterized by severe systemic elevation of several pro-inflammatory cytokines. Then, a cytokine storm can induce edematous, ARDS, pneumonia, as well as multiple organ failure in aged patients. It is far from clear till now why cytokine storm induces in only COVID-19 elderly patients, and not in young patients. However, it seems that aging is associated with mild elevated levels of local and systemic pro-inflammatory cytokines, which is characterized by \"inflamm-aging\". It is highly likely that \"inflamm-aging\" is correlated to increased risk of a cytokine storm in some critical elderly patients with COVID-19 infection. METHODS: A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar pre-print database using all available MeSH terms for COVID-19, Coronavirus, SARS-CoV-2, senescent cell, cytokine storm, inflame-aging, ACE2 receptor, autophagy, and Vitamin D. Electronic database searches combined and duplicates were removed. RESULTS: The aim of the present review was to summarize experimental data and clinical observations that linked the pathophysiology mechanisms of \"inflamm-aging\", mild-grade inflammation, and cytokine storm in some elderly adults with severe COVID-19 infection.", "qid": 39, "docid": "w6b1h1of", "rank": 50, "score": 0.8027548789978027}, {"content": "Title: Weathering the Cytokine Storm in COVID-19: Therapeutic Implications Content: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged in Wuhan, Hubei-China, as responsible for the coronavirus disease 2019 (COVID-19) and then spread rapidly worldwide. While most individuals remain asymptomatic or develop only mild symptoms, approximately 5% develop severe forms of COVID-19 characterized by acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF) that usually require intensive-care support and often yield a poor prognosis. SUMMARY: The pathophysiology of COVID-19 is far from being completely understood, and the lack of effective treatments leads to a sense of urgency to develop new therapeutic strategies based on pathophysiological assumptions. The exaggerated cytokine release in response to viral infection, a condition known as cytokine release syndrome (CRS) or cytokine storm, is emerging as the mechanism leading to ARDS and MOF in COVID-19, thus endorsing the hypothesis that properly timed anti-inflammatory therapeutic strategies could improve patients' clinical outcomes and prognosis. KEY MESSAGES: The objective of this article is to explore and comment on the potential role of the promising immunomodulatory therapies using pharmacological and nonpharmacological approaches to overcome the dysregulated proinflammatory response in COVID-19.", "qid": 39, "docid": "lnltoj1n", "rank": 51, "score": 0.8025162816047668}, {"content": "Title: Weathering the Cytokine Storm in COVID-19: Therapeutic Implications Content: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged in Wuhan, Hubei-China, as responsible for the coronavirus disease 2019 (COVID-19) and then spread rapidly worldwide. While most individuals remain asymptomatic or develop only mild symptoms, approximately 5% develop severe forms of COVID-19 characterized by acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF) that usually require intensive-care support and often yield a poor prognosis. SUMMARY: The pathophysiology of COVID-19 is far from being completely understood, and the lack of effective treatments leads to a sense of urgency to develop new therapeutic strategies based on pathophysiological assumptions. The exaggerated cytokine release in response to viral infection, a condition known as cytokine release syndrome (CRS) or cytokine storm, is emerging as the mechanism leading to ARDS and MOF in COVID-19, thus endorsing the hypothesis that properly timed anti-inflammatory therapeutic strategies could improve patients' clinical outcomes and prognosis. Key Messages: The objective of this article is to explore and comment on the potential role of the promising immunomodulatory therapies using pharmacological and nonpharmacological approaches to overcome the dysregulated proinflammatory response in COVID-19.", "qid": 39, "docid": "re7ar8b1", "rank": 52, "score": 0.8025162220001221}, {"content": "Title: Bilateral anterior uveitis as a part of a multisystem inflammatory syndrome secondary to COVID\u201019 infection Content: During the ongoing COVID\u201019 pandemic, there is a global concern about patients presenting with inflammatory syndrome with variable clinical features. Colanfrancesco et al. described COVID\u201019 systemic inflammatory reaction that are characterized by a life\u2010threatening hyper\u2010inflammation sustained by a cytokines storm which eventually leads to multi\u2010organ failure. This article is protected by copyright. All rights reserved.", "qid": 39, "docid": "y2p97hqa", "rank": 53, "score": 0.8019793033599854}, {"content": "Title: Baricitinib, a drug with potential effect to prevent SARS-COV-2 from entering target cells and control cytokine storm induced by COVID-19 Content: In December 2019, a novel coronavirus pneumonia (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suddenly broke out in China and rapidly spread all over the world. Recently, a cell surface protein, known as angiotensin-converting enzyme II (ACE2), has been identified to be involved in receptor-mediated endocytosis for SARS-CoV-2 entry to the cells. Many studies have reported the clinical characteristics of COVID-19: sudden deterioration of disease around 1-2 weeks after onset; much lower level of lymphocytes, especially natural killer (NK) cells in peripheral blood; extremely high pro-inflammatory cytokines and C reactive protein (CRP). About 15.7% of patients develop severe pneumonia, and cytokine storm is an important factor leading to rapid disease progression. Currently, there are no specific drugs for COVID-19 and the cytokine storm it causes. Baricitinib intracellularly inhibits the proinflammatory signal of several cytokines by suppressing Janus kinase (JAK) JAK1/JAK2. It has been demonstrated clinical benefits for the patients with rheumatoid arthritis (RA), active systemic lupus erythematosus and atopic dermatitis with good efficacy and safety records. Baricitinib is expected to interrupt the passage and intracellular assembly of SARS-CoV-2 into the target cells mediated by ACE2 receptor, and treat cytokine storm caused by COVID-19. Several clinical trials are currently investigating the drug, and one of which has been completed with encouraging results. In this paper, we will elaborate the role of cytokine storm mediated by JAK-STAT pathway in severe COVID-19, the possible mechanisms of baricitinib on reducing the viral entry into the target cells and cytokine storm, the key points of pharmaceutical care based on the latest research reports, clinical trials progress and drug instruction from the US FDA, so as to provide reference for the treatment of severe COVID-19.", "qid": 39, "docid": "8mei3fqy", "rank": 54, "score": 0.8014388084411621}, {"content": "Title: SARS-CoV-2 infection: the role of cytokines in COVID-19 disease Content: COVID-19 disease, caused by infection with SARS-CoV-2, is related to a series of physiopathological mechanisms that mobilize a wide variety of biomolecules, mainly immunological in nature. In the most severe cases, the prognosis can be markedly worsened by the hyperproduction of mainly proinflammatory cytokines, such as IL-1, IL-6, IL-12, IFN-\u03b3, and TNF-\u03b1, preferentially targeting lung tissue. This study reviews published data on alterations in the expression of different cytokines in patients with COVID-19 who require admission to an intensive care unit. Data on the implication of cytokines in this disease and their effect on outcomes will support the design of more effective approaches to the management of COVID-19.", "qid": 39, "docid": "8u685f45", "rank": 55, "score": 0.8005989789962769}, {"content": "Title: Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors Content: Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread across many other countries. While the majority of patients were considered mild, critically ill patients involving respiratory failure and multiple organ dysfunction syndrome are not uncommon, which could result death. We hypothesized that cytokine storm is associated with severe outcome. We enrolled 102 COVID-19 patients who were admitted to Renmin Hospital (Wuhan, China). All patients were classified into moderate, severe and critical groups according to their symptoms. 45 control samples of healthy volunteers were also included. Inflammatory cytokines and C-Reactive Protein (CRP) profiles of serum samples were analyzed by specific immunoassays. Results showed that COVID-19 patients have higher serum level of cytokines (TNF-&#945;, IFN-\u00ce\u00b3, IL-2, IL-4, IL-6 and IL-10) and CRP than control individuals. Within COVID-19 patients, serum IL-6 and IL-10 levels are significantly higher in critical group (n = 17) than in moderate (n = 42) and severe (n = 43) group. The levels of IL-10 is positively correlated with CRP amount (r = 0.41, P < 0.01). Using univariate logistic regression analysis, IL-6 and IL-10 are found to be predictive of disease severity and receiver operating curve analysis could further confirm this result (AUC = 0.841, 0.822 respectively). Our result indicated higher levels of cytokine storm is associated with more severe disease development. Among them, IL-6 and IL-10 can be used as predictors for fast diagnosis of patients with higher risk of disease deterioration. Given the high levels of cytokines induced by SARS-CoV-2, treatment to reduce inflammation-related lung damage is critical.", "qid": 39, "docid": "9qahwku6", "rank": 56, "score": 0.8004333972930908}, {"content": "Title: Immunopathology and immunotherapeutic strategies in severe acute respiratory syndrome coronavirus 2 infection. Content: The outbreak of coronavirus disease 2019 (COVID-19) and pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a major concern globally. As of 14 April 2020, more than 1.9 million COVID-19 cases have been reported in 185 countries. Some patients with COVID-19 develop severe clinical manifestations, while others show mild symptoms, suggesting that dysregulation of the host immune response contributes to disease progression and severity. In this review, we have summarized and discussed recent immunological studies focusing on the response of the host immune system and the immunopathology of SARS-CoV-2 infection as well as immunotherapeutic strategies for COVID-19. Immune evasion by SARS-CoV-2, functional exhaustion of lymphocytes, and cytokine storm have been discussed as part of immunopathology mechanisms in SARS-CoV-2 infection. Some potential immunotherapeutic strategies to control the progression of COVID-19, such as passive antibody therapy and use of interferon \u03b1\u03b2 and IL-6 receptor (IL-6R) inhibitor, have also been discussed. This may help us to understand the immune status of patients with COVID-19, particularly those with severe clinical presentation, and form a basis for further immunotherapeutic investigations.", "qid": 39, "docid": "vlse2pzs", "rank": 57, "score": 0.7993171215057373}, {"content": "Title: Immune Status of COVID-19 Patients with Reference to SARS and MERS Content: During this global pandemic of COVID-19 infection, it became well known that morbidity and mortality is especially high at the extreme of life especially in certain racial or ethnic groups like Americans and Africans This is presumed due to low immunity associated with other comorbid conditions like diabetes, hypertension, cardiovascular disease, obesity and metabolic syndrome But the information available on the immune status of COVID-19 patients is limited Attempts must be made to enhance our understanding of the immune status of COVID-19 patients by revisiting our knowledge on the immune mechanisms of already known coronaviruses such as SARS-CoV and MERS-CoV Early elevation of the serum levels of pro-inflammatory cytokines observed in SARS and MERS infection suggests a possible same type of cytokine storm-mediated lung damage in COVID-19 patients too Dysregulation of interferon-1 response and downstream cascade in initial innate immune response at virus entry point has been related to lethal pneumonia in COVID-19 patients Adaptive response of increased CD8+ levels in COVID-19 patients seems to be useful in mild cases where it causes deteriorating effects in progressed severe disease patients resulting in destruction of type 2 pneumocytes hence inability to regenerate the alveolar epithelium A phenomenon called cytokine storm activates violent immunological reactions in the lung tissue resulting in ARDS followed by multiple organ system damages in COVID-19 patients Several immune evading mechanisms are thought to be employed by severe respiratory syndrome virus-2 (SARS-CoV-2) that might have resulted in its extremely increased contagiousness probably related with its frequent RNA mutations Failure to develop adequate virus limiting immune reactions by some cured patients warrant monitoring of all recovered patients This rapid mini review is aimed to enhance our knowledge of the immune status of COVID-19 infected patients with reference to SARS-CoV and MERS-CoV", "qid": 39, "docid": "f37cp6j3", "rank": 58, "score": 0.7992127537727356}, {"content": "Title: COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons Content: ABSTRACT The outbreak of the novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) responsible for coronavirus disease 2019 (COVID-19) has developed into a major health hazard across the globe. The rapid escalation of the COVID-19 and the considerable associated illness leading to death has transformed it into a critical global public health issue. The current clinical investigation in patients with COVID-19 has showed strong upregulation of cytokine and interferon production after critical infection with SARS-CoV2- induced pneumonia. The current research suggests that few groups of patients with COVID-19 might have a cytokine storm syndrome. Thus, identification and treatment of hyperinflammation using existing, approved therapies with proven safety profiles to address the immediate need to reduce the rising mortality. To date, no specific therapeutic drug or vaccine has been discovered to treat this COVID-19. Intensive research is in progress to identify a promising drug therapy. Hence, several options were proposed to control this fast-emerging pandemic, including antiviral drugs, vaccines, small-molecules, monoclonal antibodies, oligonucleotides, peptides, and interferons (IFNs).", "qid": 39, "docid": "3g06zxmx", "rank": 59, "score": 0.797735333442688}, {"content": "Title: Understanding the COVID\u201019 coagulopathy spectrum Content: The SARS\u2010Cov\u20102 (COVID\u201019) pandemic has already claimed over 200,000 lives. Quite early on in this pandemic, it was recognised that the virus triggers the immune system leading to a cytokine storm in some severely ill patients [1]. This hyper\u2010responsiveness has been suggested to be the predominant aetiology for clinical deterioration and mortality in patients with this infection [2]. More recently, there have been several reports of increased thrombotic events in these patients [3\u20106]. From a laboratory perspective, this hypercoagulability is reflected in the marked elevation of the fibrinolytic marker, D\u2010dimer, in almost all hospitalised COVID\u201019 patients [7]. We must, therefore, ask ourselves what is the link between the extremes of the immune system, presenting as cytokine storm, and the extremes of coagulation, presenting as arterial and venous thromboembolism?", "qid": 39, "docid": "343y63e5", "rank": 60, "score": 0.7976592779159546}, {"content": "Title: Biosensors for Managing the COVID-19 Cytokine Storm: Challenges Ahead Content: The global COVID-19 pandemic has oversaturated many intensive care units to the point of collapse, leading to enormous spikes in death counts. Before critical care becomes a necessity, identifying patients who are likely to become critically ill and providing prompt treatment is a strategy to avoid ICU oversaturation. There is a consensus that a hyperinflammatory syndrome or a \"cytokine storm\" is responsible for poor outcomes in COVID-19. Measuring cytokine levels at the point of care is required in order to better understand this process. In this Perspective, we summarize the main events behind the cytokine storm in COVID-19 as well as current experimental treatments. We advocate for a new biosensor-enabled paradigm to personalize the management of COVID-19 and stratify patients. Biosensor-guided dosing and timing of immunomodulatory therapies could maximize the benefits of these anti-inflammatory treatments while minimizing deleterious effects. Biosensors will also be essential in order to detect complications such as coinfections and sepsis, which are common in immunosuppressed patients. Finally, we propose the ideal features of these biosensors using some prototypes from the recent literature as examples. Multisensors, lateral flow tests, mobile biosensors, and wearable biosensors are seen as key players for precision medicine in COVID-19.", "qid": 39, "docid": "w9ge0df6", "rank": 61, "score": 0.7972494959831238}, {"content": "Title: Immunopathology and immunotherapeutic strategies in severe acute respiratory syndrome coronavirus 2 infection Content: The outbreak of coronavirus disease 2019 (COVID-19) and pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a major concern globally. As of 14 April 2020, more than 1.9 million COVID-19 cases have been reported in 185 countries. Some patients with COVID-19 develop severe clinical manifestations, while others show mild symptoms, suggesting that dysregulation of the host immune response contributes to disease progression and severity. In this review, we have summarized and discussed recent immunological studies focusing on the response of the host immune system and the immunopathology of SARS-CoV-2 infection as well as immunotherapeutic strategies for COVID-19. Immune evasion by SARS-CoV-2, functional exhaustion of lymphocytes, and cytokine storm have been discussed as part of immunopathology mechanisms in SARS-CoV-2 infection. Some potential immunotherapeutic strategies to control the progression of COVID-19, such as passive antibody therapy and use of interferon &#945;\u00df and IL-6 receptor (IL-6R) inhibitor, have also been discussed. This may help us to understand the immune status of patients with COVID-19, particularly those with severe clinical presentation, and form a basis for further immunotherapeutic investigations.", "qid": 39, "docid": "2h8i4pyb", "rank": 62, "score": 0.7971458435058594}, {"content": "Title: SARS-CoV-2: Viral Mechanisms and Possible Therapeutic Targets - What to learn from Rheumatologists? Content: It was with great interest that we read the letter from Randy Cron and collaborators (1) linking the cytokine storm syndrome (CSS) seen in macrophage activation syndrome, common in the rheumatological setting, with the CSS postulated to be a background in the novel coronavirus (SARS-CoV-2) infection. Amid the high contagiousness of the virus, science was also infected by an infodemia, compelled to enter a race to find effective therapies studying mechanisms molecular aspects of SARS-CoV-2 concomitant to urgent bedside manage of patients.", "qid": 39, "docid": "55n1ttz4", "rank": 63, "score": 0.7970597743988037}, {"content": "Title: The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of \u201cinflame-aging\u201d Content: PURPOSE: Novel Coronavirus disease 2019 (COVID-19), is an acute respiratory distress syndrome (ARDS), which is emerged in Wuhan, and recently become worldwide pandemic. Strangely, ample evidences have been shown that the severity of COVID-19 infections varies widely from children (asymptomatic), adults (mild infection), as well as elderly adults (deadly critical). It has proven that COVID-19 infection in some elderly critical adults leads to a cytokine storm, which is characterized by severe systemic elevation of several pro-inflammatory cytokines. Then, a cytokine storm can induce edematous, ARDS, pneumonia, as well as multiple organ failure in aged patients. It is far from clear till now why cytokine storm induces in only COVID-19 elderly patients, and not in young patients. However, it seems that aging is associated with mild elevated levels of local and systemic pro-inflammatory cytokines, which is characterized by \u201cinflamm-aging\u201d. It is highly likely that \u201cinflamm-aging\u201d is correlated to increased risk of a cytokine storm in some critical elderly patients with COVID-19 infection. METHODS: A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar pre-print database using all available MeSH terms for COVID-19, Coronavirus, SARS-CoV-2, senescent cell, cytokine storm, inflame-aging, ACE2 receptor, autophagy, and Vitamin D. Electronic database searches combined and duplicates were removed. RESULTS: The aim of the present review was to summarize experimental data and clinical observations that linked the pathophysiology mechanisms of \u201cinflamm-aging\u201d, mild-grade inflammation, and cytokine storm in some elderly adults with severe COVID-19 infection.", "qid": 39, "docid": "7ak53hto", "rank": 64, "score": 0.7968497276306152}, {"content": "Title: SARS-CoV-2 infection: The role of cytokines in COVID-19 disease Content: COVID-19 disease, caused by infection with SARS-CoV-2, is related to a series of physiopathological mechanisms that mobilize a wide variety of biomolecules, mainly immunological in nature. In the most severe cases, the prognosis can be markedly worsened by the hyperproduction of mainly proinflammatory cytokines, such as IL-1, IL-6, IL-12, IFN-\u00ce\u00b3, and TNF-&#945;, preferentially targeting lung tissue. This study reviews published data on alterations in the expression of different cytokines in patients with COVID-19 who require admission to an intensive care unit. Data on the implication of cytokines in this disease and their effect on outcomes will support the design of more effective approaches to the management of COVID-19.", "qid": 39, "docid": "tgunokrk", "rank": 65, "score": 0.796471357345581}, {"content": "Title: Potential Immunotherapeutic Targets For Hypoxia Due to COVI-FLU Content: The world is currently embroiled in a pandemic of coronavirus disease 2019 (COVID-19), a respiratory illness caused by the novel betacoronavirus SARS-CoV-2. The severity of COVID-19 disease ranges from asymptomatic to fatal acute respiratory distress syndrome (ARDS). In few patients, the disease undergoes phenotypic differentiation between 7-14 days of acute illness, either resulting in full recovery or symptom escalation. However, the mechanism of such variation is not clear, but the facts suggest that patient's immune status, co-morbidities, and the systemic effects of the viral infection (potentially depending on the SARS-CoV-2 strain involved) play a key role. Subsequently, patients with the most severe symptoms tend to have poor outcomes, manifest severe hypoxia, and possess elevated levels of pro-inflammatory cytokines (including IL-1\u00df, IL-6, IFN-\u00ce\u00b3, and TNF-&#945;) along with elevated levels of the anti-inflammatory cytokine IL-10, marked lymphopenia, and elevated neutrophil-to-lymphocyte ratios. Based on the available evidence, we propose a mechanism wherein SARS-CoV-2 infection induces direct organ damage while also fueling an IL-6-mediated cytokine release syndrome (CRS) and hypoxia, resulting in escalating systemic inflammation, multi-organ damage, and end-organ failure. Elevated IL-6 and hypoxia together predisposes patients to pulmonary hypertension, and the presence of asymptomatic hypoxia in COVID-19 further compounds this problem. Due to the similar downstream mediators, we discuss the potential synergistic effects and systemic ramifications of SARS-CoV-2 and influenza virus during co-infection, a phenomenon we have termed \"COVI-Flu.\" Additionally, the differences between CRS and cytokine storm are highlighted. Finally, novel management approaches, clinical trials, and therapeutic strategies toward both SARS-CoV-2 and COVI-Flu infection are discussed, highlighting host response optimization and systemic inflammation reduction.", "qid": 39, "docid": "kb6tymdl", "rank": 66, "score": 0.7955212593078613}, {"content": "Title: Potential Immunotherapeutic Targets For Hypoxia Due to COVI-FLU. Content: The world is currently embroiled in a pandemic of coronavirus disease 2019 (COVID-19), a respiratory illness caused by the novel betacoronavirus SARS-CoV-2. The severity of COVID-19 disease ranges from asymptomatic to fatal acute respiratory distress syndrome (ARDS). In few patients, the disease undergoes phenotypic differentiation between 7-14 days of acute illness, either resulting in full recovery or symptom escalation. However, the mechanism of such variation is not clear, but the facts suggest that patient's immune status, co-morbidities, and the systemic effects of the viral infection (potentially depending on the SARS-CoV-2 strain involved) play a key role. Subsequently, patients with the most severe symptoms tend to have poor outcomes, manifest severe hypoxia, and possess elevated levels of pro-inflammatory cytokines (including IL-1\u03b2, IL-6, IFN-\u03b3, and TNF-\u03b1) along with elevated levels of the anti-inflammatory cytokine IL-10, marked lymphopenia, and elevated neutrophil-to-lymphocyte ratios. Based on the available evidence, we propose a mechanism wherein SARS-CoV-2 infection induces direct organ damage while also fueling an IL-6-mediated cytokine release syndrome (CRS) and hypoxia, resulting in escalating systemic inflammation, multi-organ damage, and end-organ failure. Elevated IL-6 and hypoxia together predisposes patients to pulmonary hypertension, and the presence of asymptomatic hypoxia in COVID-19 further compounds this problem. Due to the similar downstream mediators, we discuss the potential synergistic effects and systemic ramifications of SARS-CoV-2 and influenza virus during co-infection, a phenomenon we have termed \"COVI-Flu.\" Additionally, the differences between CRS and cytokine storm are highlighted. Finally, novel management approaches, clinical trials, and therapeutic strategies toward both SARS-CoV-2 and COVI-Flu infection are discussed, highlighting host response optimization and systemic inflammation reduction.", "qid": 39, "docid": "4ch7eq3i", "rank": 67, "score": 0.7951439619064331}, {"content": "Title: COVID-19 - toward a comprehensive understanding of the disease. Content: The evidence on the pathophysiology of the novel coronavirus SARS-CoV-2 infection is rapidly growing. Understanding why some patients suffering from COVID-19 are getting so sick, while others are not, has become an informal imperative for researchers and clinicians around the globe. The answer to this question would allow rationalizing the fear surrounding this pandemic. Understanding of the pathophysiology of COVID-19 relies on an understanding of interplaying mechanisms, including SARS-CoV-2 virulence, human immune response, and complex inflammatory reactions with coagulation playing a major role. An interplay with bacterial co-infections, as well as the vascular system and microcirculation affected throughout the body should also be examined. More importantly, a comprehensive understanding of pathological mechanisms of COVID-19 will increase the efficacy of therapy and decrease mortality. Herewith, presented is the current state of knowledge on COVID-19: beginning from the virus, its transmission, and mechanisms of entry into the human body, through the pathological effects on the cellular level, up to immunological reaction, systemic and organ presentation. Last but not least, currently available and possible future therapeutic and diagnostic options are briefly commented on.", "qid": 39, "docid": "msx6n8xu", "rank": 68, "score": 0.7949775457382202}, {"content": "Title: COVID-19 - Toward a comprehensive understanding of the disease Content: The evidence on the pathophysiology of the novel coronavirus SARS-CoV-2 infection is rapidly growing. Understanding why some patients suffering from COVID-19 are getting so sick, while others are not, has become an informal imperative for researchers and clinicians around the globe. The answer to this question would allow rationalizing the fear surrounding this pandemic. Understanding of the pathophysiology of COVID-19 relies on an understanding of interplaying mechanisms, including SARS-CoV-2 virulence, human immune response, and complex inflammatory reactions with coagulation playing a major role. An interplay with bacterial co-infections, as well as the vascular system and microcirculation affected throughout the body should also be examined. More importantly, a compre-hensive understanding of pathological mechanisms of COVID-19 will increase the efficacy of therapy and decrease mortality. Herewith, presented is the current state of knowledge on COVID-19: beginning from the virus, its transmission, and mechanisms of entry into the human body, through the pathological effects on the cellular level, up to immunological reaction, systemic and organ presentation. Last but not least, currently available and possible future therapeutic and diagnostic options are briefly commented on.", "qid": 39, "docid": "edbtz6up", "rank": 69, "score": 0.7946674823760986}, {"content": "Title: SARS-CoV-2 COVID-19 susceptibility and lung inflammatory storm by smoking and vaping Content: The current pandemic of COVID-19 has caused severe morbidity and mortality across the globe. People with a smoking history have severe disease outcomes by COVID-19 infection. Epidemiological studies show that old age and pre-existing disease conditions (hypertension and diabetes) result in severe disease outcome and mortality amongst COVID-19 patients. Evidences suggest that the S1 domain of the SARS-CoV-2 (causative agent of COVID-19) membrane spike has a high affinity towards the angiotensin-converting enzyme 2 (ACE2) receptor found on the host\u2019s lung epithelium. Likewise, TMPRSS2 protease has been shown to be crucial for viral activation thus facilitating the viral engulfment. The viral entry has been shown to cause \u2018cytokine storm\u2019 involving excessive production of pro-inflammatory cytokines/chemokines including IL-6, TNF-\u03b1, IFN-\u03b3, IL-2, IL-7, IP-10, MCP-3 or GM-CSF, which is augmented by smoking. Future research could target these inflammatory-immunological responses to develop effective therapy for COVID-19. This mini-review provides a consolidated account on the role of inflammation and immune responses, proteases, and epithelial permeability by smoking and vaping during SARS-CoV2 infection with future directions of research, and provides a list of the potential targets for therapies particularly controlling cytokine storms in the lung.", "qid": 39, "docid": "n0d9b50t", "rank": 70, "score": 0.794597864151001}, {"content": "Title: SARS-CoV-2 and viral sepsis: observations and hypotheses Content: Since the outbreak of coronavirus disease 2019 (COVID-19), clinicians have tried every effort to understand the disease, and a brief portrait of its clinical features have been identified. In clinical practice, we noticed that many severe or critically ill COVID-19 patients developed typical clinical manifestations of shock, including cold extremities and weak peripheral pulses, even in the absence of overt hypotension. Understanding the mechanism of viral sepsis in COVID-19 is warranted for exploring better clinical care for these patients. With evidence collected from autopsy studies on COVID-19 and basic science research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV, we have put forward several hypotheses about SARS-CoV-2 pathogenesis after multiple rounds of discussion among basic science researchers, pathologists, and clinicians working on COVID-19. We hypothesise that a process called viral sepsis is crucial to the disease mechanism of COVID-19. Although these ideas might be proven imperfect or even wrong later, we believe they can provide inputs and guide directions for basic research at this moment.", "qid": 39, "docid": "jilnno5p", "rank": 71, "score": 0.7943035960197449}, {"content": "Title: Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: A novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis Content: Early clinical evidence suggests that severe cases of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are frequently characterized by hyperinflammation, imbalance of renin-angiotensin-aldosterone system, and a particular form of vasculopathy, thrombotic microangiopathy, and intravascular coagulopathy. In this paper, we present an immunothrombosis model of COVID-19. We discuss the underlying pathogenesis and the interaction between multiple systems, resulting in propagation of immunothrombosis, which through investigation in the coming weeks, may lead to both an improved understanding of COVID-19 pathophysiology and identification of innovative and efficient therapeutic targets to reverse the otherwise unfavorable clinical outcome of many of these patients.", "qid": 39, "docid": "p298vft5", "rank": 72, "score": 0.7942522168159485}, {"content": "Title: Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? Content: The emergent outbreak of coronavirus disease 2019 (COVID-19) has caused a global pandemic. Acute respiratory distress syndrome (ARDS) and multiorgan dysfunction are among the leading causes of death in critically ill patients with COVID-19. The elevated inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome (CRS), may play a major role in the pathology of COVID-19. However, the efficacy of corticosteroids, commonly utilized antiinflammatory agents, to treat COVID-19-induced CRS is controversial. There is an urgent need for novel therapies to treat COVID-19-induced CRS. Here, we discuss the pathogenesis of severe acute respiratory syndrome (SARS)-induced CRS, compare the CRS in COVID-19 with that in SARS and Middle East respiratory syndrome (MERS), and summarize the existing therapies for CRS. We propose to utilize interleukin-6 (IL-6) blockade to manage COVID-19-induced CRS and discuss several factors that should be taken into consideration for its clinical application.", "qid": 39, "docid": "uzfpv5rd", "rank": 73, "score": 0.7941712141036987}, {"content": "Title: Amelioration of COVID\u201019 related cytokine storm syndrome: Parallels to chimeric antigen receptor\u2010T cell cytokine release syndrome Content: Coronavirus disease\u20102019 (COVID\u201019) severity appears to parallel the host immune response, with a subset of patients developing COVID\u201019 cytokine storm syndrome (CSS).(1) Serum inflammatory cytokines are elevated in COVID\u201019,(2\u20135) and interleukin (IL)\u20106 appears to play a central role in COVID\u201019 related CSS.(6\u20138) Based on the success of IL\u20106 receptor blockade for chimeric antigen receptor T\u2010cell therapy associated cytokine release syndrome (CAR T\u2010cell CRS), similar strategies using tocilizumab are being investigated in COVID\u201019.", "qid": 39, "docid": "i757oxb6", "rank": 74, "score": 0.7936161756515503}, {"content": "Title: The COVID-19 Cytokine Storm; What We Know So Far Content: COVID-19 is a rapidly spreading global threat that has been declared as a pandemic by the WHO. COVID-19 is transmitted via droplets or direct contact and infects the respiratory tract resulting in pneumonia in most of the cases and acute respiratory distress syndrome (ARDS) in about 15 % of the cases. Mortality in COVID-19 patients has been linked to the presence of the so-called \u201ccytokine storm\u201d induced by the virus. Excessive production of proinflammatory cytokines leads to ARDS aggravation and widespread tissue damage resulting in multi-organ failure and death. Targeting cytokines during the management of COVID-19 patients could improve survival rates and reduce mortality.", "qid": 39, "docid": "ne1qvf5g", "rank": 75, "score": 0.7926820516586304}, {"content": "Title: SARS-CoV-2 and viral sepsis: observations and hypotheses Content: Summary Since the outbreak of coronavirus disease 2019 (COVID-19), clinicians have tried every effort to understand the disease, and a brief portrait of its clinical features have been identified. In clinical practice, we noticed that many severe or critically ill COVID-19 patients developed typical clinical manifestations of shock, including cold extremities and weak peripheral pulses, even in the absence of overt hypotension. Understanding the mechanism of viral sepsis in COVID-19 is warranted for exploring better clinical care for these patients. With evidence collected from autopsy studies on COVID-19 and basic science research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV, we have put forward several hypotheses about SARS-CoV-2 pathogenesis after multiple rounds of discussion among basic science researchers, pathologists, and clinicians working on COVID-19. We hypothesise that a process called viral sepsis is crucial to the disease mechanism of COVID-19. Although these ideas might be proven imperfect or even wrong later, we believe they can provide inputs and guide directions for basic research at this moment.", "qid": 39, "docid": "mrvk9r4w", "rank": 76, "score": 0.7926120758056641}, {"content": "Title: The compelling arguments for the need of microvascular investigation in COVID-19 critical patients Content: The burden of pandemic COVID-19 is growing worldwide, as the continuous increases of contagion. Only 10-15% of the entire infected population has the necessity of intensive care unit (ICU) treatments. But, this relatively low rate of patients has absorbed almost the whole availability of ICU during few days, becoming at least in Italy, an emergency for the national health system. In COVID-19 ICU patients massive aggression of lung with severe pulmonary failure, as well as kidney and liver injuries, heart, brain, bowel and spleen damages with lymph nodes necrosis and even cutaneous manifestations have been observed. Moreover, increased levels of cytokines so-called \"cytokines storm (CS), and overt intravascular disseminated coagulation have been also reported. The hypercoagulation and CS would speculate about a microvascular dysfunction. Unfortunately, no specific observations have been performed on microcirculatory dysfunction in COVID-19 patients. Hence the presumed pathophysiological pathways and models about a microvascular involvement can be gathered by sepsis models studies. But despite this lack of evidence, the COVID-19 has emphasized the compelling need for microcirculation monitoring at the bedside in ICU patients.", "qid": 39, "docid": "pzbg163v", "rank": 77, "score": 0.7922793626785278}, {"content": "Title: The compelling arguments for the need for microvascular investigation in COVID-19 critical patients. Content: The burden of pandemic COVID-19 is growing worldwide, as the continuous increases of contagion. Only 10-15% of the entire infected population has the necessity of intensive care unit (ICU) treatments. But, this relatively low rate of patients has absorbed almost the whole availability of ICU during few days, becoming at least in Italy, an emergency for the national health system. In COVID-19 ICU patients massive aggression of lung with severe pulmonary failure, as well as kidney and liver injuries, heart, brain, bowel and spleen damages with lymph nodes necrosis and even cutaneous manifestations have been observed. Moreover, increased levels of cytokines so-called \"cytokines storm (CS), and overt intravascular disseminated coagulation have been also reported. The hypercoagulation and CS would speculate about a microvascular dysfunction. Unfortunately, no specific observations have been performed on microcirculatory dysfunction in COVID-19 patients. Hence the presumed pathophysiological pathways and models about a microvascular involvement can be gathered by sepsis models studies. But despite this lack of evidence, the COVID-19 has emphasized the compelling need for microcirculation monitoring at the bedside in ICU patients.", "qid": 39, "docid": "eyjakux2", "rank": 78, "score": 0.7922793626785278}, {"content": "Title: High IL\u20106/IFN\u2010\u03b3 ratio could be associated with severe disease in COVID\u201019 patients Content: Cytokines are important mediators of the inflammatory response, and during infection with SARS\u2010CoV\u20102 it has been suggested that there is a cytokine storm syndrome. In this study, a meta\u2010analysis was performed to investigate whether the IL\u20106/IFN\u2010\u03b3 ratio can help predict clinical severity in patients with COVID\u201019. This article is protected by copyright. All rights reserved.", "qid": 39, "docid": "z15l4pcq", "rank": 79, "score": 0.7919638752937317}, {"content": "Title: Biochemical indicators of coronavirus disease 2019 exacerbation and the clinical implications Content: Coronavirus Disease 2019 (COVID-19) has sparked a global pandemic, affecting more than 4 million people worldwide. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute lung injury (ALI) and even acute respiratory distress syndrome (ARDS); with a fatality of 7.0 %. Accumulating evidence suggested that the progression of COVID-19 is associated with lymphopenia and excessive inflammation, and a subset of severe cases might exhibit cytokine storm triggered by secondary hemophagocytic lymphohistiocytosis (sHLH). Furthermore, secondary bacterial infection may contribute to the exacerbation of COVID-19. We recommend using both IL-10 and IL-6 as the indicators of cytokine storm, and monitoring the elevation of procalcitonin (PCT) as an alert for initiating antibacterial agents. Understanding the dynamic progression of SARS-CoV-2 infection is crucial to determine an effective treatment strategy to reduce the rising mortality of this global pandemic.", "qid": 39, "docid": "j25rvp1i", "rank": 80, "score": 0.7916909456253052}, {"content": "Title: Pediatric Crohn's Disease and Multisystem Inflammatory Syndrome in Children (MIS-C) and COVID-19 Treated with Infliximab Content: Coronavirus disease 2019 (COVID-19) may lead to a severe inflammatory response referred to as a cytokine storm. We describe a case of severe COVID-19 infection in a recently diagnosed pediatric Crohn's disease patient successfully treated with Tumor Necrosis Factor-alpha (TNF-&#945;) blockade. The patient presented with five days of fever, an erythematous maculopapular facial rash, and abdominal pain without respiratory symptoms. SARS-CoV-2 PCR was positive. Despite inpatient treatment for COVID-19 and a perianal abscess, the patient acutely decompensated, with worsening fever, tachycardia, fluid-refractory hypotension, elevation of liver enzymes, and transformation of the rash into purpura extending from the face to the trunk, upper and lower extremities, including the palmar and plantar surfaces of the hands and feet. Cytokine profile revealed rising levels of interleukin (IL)-6, IL-8, and TNF-&#945;, higher than those described in either inflammatory bowel disease (IBD) or severe COVID-19 alone. The patient was treated with infliximab for TNF-&#945; blockade to address both moderately to severely active Crohn's disease and multisystem inflammatory syndrome in children (MIS-C) temporally related to COVID-19. Within hours of infliximab treatment, fever, tachycardia and hypotension resolved. Cytokine profile improved with normalization of TNF-&#945;, a decrease in IL-6, and IL-8 concentrations. This case supports a role for blockade of TNF-&#945; in the treatment of COVID-19 inflammatory cascade. The role of anti-TNF agents in patients with MIS-C temporally related to COVID-19 requires further investigation.", "qid": 39, "docid": "8656dp79", "rank": 81, "score": 0.7914407253265381}, {"content": "Title: Coronavirus Disease 2019 (COVID-19): Cytokine Storms, Hyper-Inflammatory Phenotypes, and Acute Respiratory Distress Syndrome Content: Abstract Coronavirus Disease 2019 (COVID-19) was first identified in China at the end of 2019. Acute respiratory distress syndrome (ARDS) represents the most common and serious complication of COVID-19. Cytokine storms are a pathophysiological feature of COVID-19 and play an important role in distinguishing hyper-inflammatory subphenotypes of ARDS. Accordingly, in this review, we focus on hyper-inflammatory host responses in ARDS that play a critical role in the differentiated development of COVID-19. Furthermore, we discuss inflammation-related indicators that have the potential to identify hyper-inflammatory subphenotypes of COVID-19, especially for those with a high risk of ARDS. Finally, we explore the possibility of improving the quality of monitoring and treatment of COVID-19 patients and in reducing the incidence of critical illness and mortality via better distinguishing hyper- and hypo-inflammatory subphenotypes of COVID-19.", "qid": 39, "docid": "c5co9cfq", "rank": 82, "score": 0.7912839651107788}, {"content": "Title: The COVID-19 Cytokine Storm; What We Know So Far Content: COVID-19 is a rapidly spreading global threat that has been declared as a pandemic by the WHO. COVID-19 is transmitted via droplets or direct contact and infects the respiratory tract resulting in pneumonia in most of the cases and acute respiratory distress syndrome (ARDS) in about 15 % of the cases. Mortality in COVID-19 patients has been linked to the presence of the so-called \"cytokine storm\" induced by the virus. Excessive production of proinflammatory cytokines leads to ARDS aggravation and widespread tissue damage resulting in multi-organ failure and death. Targeting cytokines during the management of COVID-19 patients could improve survival rates and reduce mortality.", "qid": 39, "docid": "ete5n5pw", "rank": 83, "score": 0.7911942601203918}, {"content": "Title: Could hemophagocytic lymphohistiocytosis be the core issue of severe COVID-19 cases? Content: BACKGROUND: COVID-19, a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), commonly presents as fever, cough, dyspnea, and myalgia or fatigue. Although the majority of patients with COVID-19 have mild symptoms, some are more prone to serious outcomes, including pneumonia, acute respiratory distress syndrome (ARDS), and even death. Hemophagocytic lymphohistiocytosis (HLH) is a severe, life-threatening inflammatory syndrome associated with intense cytokine release (also known as a \u201ccytokine storm\u201d). Similar to COVID-19, HLH is characterized by aggressive course leading to multi-organ failure. MAIN TEXT: The purpose of this review article is to draw attention to the possibility of the complication of HLH in patients with the severe course of COVID-19. Indeed, some of the clinical characteristics observed in the more severe cases of COVID-19 are reminiscent of secondary HLH (which can be triggered by infections, malignancies, rheumatological diseases, or autoimmune/immunodeficiency conditions). The pathogenesis of SARS-CoV-2 infection also suggests that HLH or a similar hyperinflammatory syndrome is the cause of the severe course of the infection. CONCLUSION: The pathogenesis and clinical symptoms of severe COVID-19 indicate that an increased inflammatory response corresponding to HLH is occurring. Therefore, patients with severe COVID-19 should be screened for hyperinflammation using standard laboratory tests to identify those for whom immunosuppressive therapy may improve outcomes.", "qid": 39, "docid": "x1g9u1j2", "rank": 84, "score": 0.7909500598907471}, {"content": "Title: Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? Content: Abstract The emergent outbreak of coronavirus disease 2019 (COVID-19) has caused a global pandemic. Acute respiratory distress syndrome (ARDS) and multiorgan dysfunction are among the leading causes of death in critically ill patients with COVID-19. The elevated inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome (CRS), may play a major role in the pathology of COVID-19. However, the efficacy of corticosteroids, commonly utilized antiinflammatory agents, to treat COVID-19-induced CRS is controversial. There is an urgent need for novel therapies to treat COVID-19-induced CRS. Here, we discuss the pathogenesis of severe acute respiratory syndrome (SARS)-induced CRS, compare the CRS in COVID-19 with that in SARS and Middle East respiratory syndrome (MERS), and summarize the existing therapies for CRS. We propose to utilize interleukin-6 (IL-6) blockade to manage COVID-19-induced CRS and discuss several factors that should be taken into consideration for its clinical application.", "qid": 39, "docid": "6gwnhkn4", "rank": 85, "score": 0.7907049655914307}, {"content": "Title: Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment Content: COVID-19 infection has a heterogenous disease course; it may be asymptomatic or causes only mild symptoms in the majority of the cases, while immunologic complications such as macrophage activation syndrome also known as secondary hemophagocytic lymphohistiocytosis, resulting in cytokine storm syndrome and acute respiratory distress syndrome, may also occur in some patients. According to current literature, impairment of SARS-CoV-2 clearance due to genetic and viral features, lower levels of interferons, increased neutrophil extracellular traps, and increased pyroptosis and probable other unknown mechanisms create a background for severe disease course complicated by macrophage activation syndrome and cytokine storm. Various genetic mutations may also constitute a risk factor for severe disease course and occurrence of cytokine storm in COVID-19. Once, immunologic complications like cytokine storm occur, anti-viral treatment alone is not enough and should be combined with appropriate anti-inflammatory treatment. Anti-rheumatic drugs, which are tried for managing immunologic complications of COVID-19 infection, will also be discussed including chloroquine, hydroxychloroquine, JAK inhibitors, IL-6 inhibitors, IL-1 inhibitors, anti-TNF-\u03b1 agents, corticosteroids, intravenous immunoglobulin (IVIG), and colchicine. Early recognition and appropriate treatment of immunologic complications will decrease the morbidity and mortality in COVID-19 infection, which requires the collaboration of infectious disease, lung, and intensive care unit specialists with other experts such as immunologists, rheumatologists, and hematologists.", "qid": 39, "docid": "r3a3xr8b", "rank": 86, "score": 0.7899661064147949}, {"content": "Title: COVID 19: a clue from innate immunity Content: The recent COVID-19 pandemic has had a significant impact on our lives and has rapidly expanded to reach more than 4 million cases worldwide by May 2020. These cases are characterized by extreme variability, from a mild or asymptomatic form lasting for a few days up to severe forms of interstitial pneumonia that may require ventilatory therapy and can lead to patient death. Several hypotheses have been drawn up to understand the role of the interaction between the infectious agent and the immune system in the development of the disease and the most severe forms; the role of the cytokine storm seems important. Innate immunity, as one of the first elements of guest interaction with different infectious agents, could play an important role in the development of the cytokine storm and be responsible for boosting more severe forms. Therefore, it seems important to study also this important arm of the immune system to adequately understand the pathogenesis of the disease. Research on this topic is also needed to develop therapeutic strategies for treatment of this disease.", "qid": 39, "docid": "n21y5kps", "rank": 87, "score": 0.7897659540176392}, {"content": "Title: COVID 19: a clue from innate immunity Content: The recent COVID-19 pandemic has had a significant impact on our lives and has rapidly expanded to reach more than 4 million cases worldwide by May 2020. These cases are characterized by extreme variability, from a mild or asymptomatic form lasting for a few days up to severe forms of interstitial pneumonia that may require ventilatory therapy and can lead to patient death.Several hypotheses have been drawn up to understand the role of the interaction between the infectious agent and the immune system in the development of the disease and the most severe forms; the role of the cytokine storm seems important.Innate immunity, as one of the first elements of guest interaction with different infectious agents, could play an important role in the development of the cytokine storm and be responsible for boosting more severe forms. Therefore, it seems important to study also this important arm of the immune system to adequately understand the pathogenesis of the disease. Research on this topic is also needed to develop therapeutic strategies for treatment of this disease.", "qid": 39, "docid": "911ozh90", "rank": 88, "score": 0.7897659540176392}, {"content": "Title: Changing dynamics of psychoneuroimmunology during COVID-19 pandemic Content: The Coronavirus Disease-2019 (COVID-19) pandemic has led to a global health care crisis in recent times. Emerging research suggest an unanticipated impact of COVID-19 on mental and/or psychological health of both the general community and affected individuals. The fear of the COVID-19 epidemic and the consequent lockdown and economic crisis has led to globally increased psychological distress. The biological bases of immediate and new onset of psychiatric symptoms in individuals with COVID-19 are not yet known. COVID-19 infection may lead to activated immune-inflammatory pathways and cytokine storm. Activated immune-inflammatory pathways, especially chronic low-grade inflammation, are associated with major psychiatric disorders in at least a subset of individuals. We propose that both the (sub)chronic inflammatory response and cytokine storm might crucially be involved in the immediate manifestation of neuropsychiatric symptoms in individuals with COVID-19 infection as well as heightened expression of psychiatric symptoms in COVID-19 infected individuals with prior psychiatric conditions. These events might expand concepts in psychoneuroimmunology, with the importance of chronic-low grade inflammation augmented by the cytokine storm hypothesis. Additionally, this might augment and refine diagnosis and prognostic management as well as treatment.", "qid": 39, "docid": "yne0dus9", "rank": 89, "score": 0.7896515727043152}, {"content": "Title: Biosensors for Managing the COVID-19 Cytokine Storm: Challenges Ahead Content: [Image: see text] The global COVID-19 pandemic has oversaturated many intensive care units to the point of collapse, leading to enormous spikes in death counts. Before critical care becomes a necessity, identifying patients who are likely to become critically ill and providing prompt treatment is a strategy to avoid ICU oversaturation. There is a consensus that a hyperinflammatory syndrome or a \u201ccytokine storm\u201d is responsible for poor outcomes in COVID-19. Measuring cytokine levels at the point of care is required in order to better understand this process. In this Perspective, we summarize the main events behind the cytokine storm in COVID-19 as well as current experimental treatments. We advocate for a new biosensor-enabled paradigm to personalize the management of COVID-19 and stratify patients. Biosensor-guided dosing and timing of immunomodulatory therapies could maximize the benefits of these anti-inflammatory treatments while minimizing deleterious effects. Biosensors will also be essential in order to detect complications such as coinfections and sepsis, which are common in immunosuppressed patients. Finally, we propose the ideal features of these biosensors using some prototypes from the recent literature as examples. Multisensors, lateral flow tests, mobile biosensors, and wearable biosensors are seen as key players for precision medicine in COVID-19.", "qid": 39, "docid": "op02flb8", "rank": 90, "score": 0.7889647483825684}, {"content": "Title: Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: A novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis Content: Abstract Early clinical evidence suggests that severe cases of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are frequently characterized by hyperinflammation, imbalance of renin-angiotensin-aldosterone system, and a particular form of vasculopathy, thrombotic microangiopathy, and intravascular coagulopathy. In this paper, we present an immunothrombosis model of COVID-19. We discuss the underlying pathogenesis and the interaction between multiple systems, resulting in propagation of immunothrombosis, which through investigation in the coming weeks, may lead to both an improved understanding of COVID-19 pathophysiology and identification of innovative and efficient therapeutic targets to reverse the otherwise unfavorable clinical outcome of many of these patients.", "qid": 39, "docid": "7vqnqp83", "rank": 91, "score": 0.7883670330047607}, {"content": "Title: Inflammation: A bridge between Diabetes and COVID-19, and possible management with sitagliptin Content: Patients with SARS-CoV-2 infections experience lymphopenia and inflammatory cytokine storms in the severe stage of the disease, leading to multi-organ damage. The exact pattern of immune system changes and their condition during the disease process is unclear. The available knowledge has indicated that the NF-kappa-B pathway, which is induced by several mediators, has a significant role in cytokine storm through the various mechanisms. Therefore, identifying the state of the immune cells and the dominant mechanisms for the production of cytokines incorporated in the cytokine storm can be a critical step in the therapeutic approach. On the other hand, some studies identified a higher risk for diabetic patients. Diabetes mellitus exhibits a close association with inflammation and increases the chance of developing COVID-19. Patients with diabetes mellitus have shown to have more virus entry, impaired immunity response, less viral elimination, and dysregulated inflammatory cytokines. The parallel analysis of COVID-19 and diabetes mellitus pathogenesis has proposed that the control of the inflammation through the interfering with the critical points of major signaling pathways may provide the new therapeutic approaches. In recent years, the role of Dipeptidyl Peptidase 4 (DPP4) in chronic inflammation has been proved. Numerous immune cells express the DPP4 protein. DPP4 regulates antibody production, cytokine secretion, and immunoglobulin class switching. DPP4 inhibitors like sitagliptin reduce inflammation intensity in different states. Following the accumulating data, we hypothesize that sitagliptin might reduce COVID-19 severity. Sitagliptin, an available DPP4 inhibitor drug, showed multidimensional anti-inflammatory effects among diabetic patients. It reduces the inflammation mostly by affecting on NF-kappa-B signaling pathway. Under the fact that inflammatory mediators are active in individuals with COVID-19, blocking the predominant pathway could be helpful.", "qid": 39, "docid": "8p5chz08", "rank": 92, "score": 0.7878783941268921}, {"content": "Title: Traditional Chinese medicine for treatment of COVID-19 based on literature mining of targeting cytokine storm/ \u57fa\u4e8e\u5e72\u9884\u7ec6\u80de\u56e0\u5b50\u98ce\u66b4\u6587\u732e\u6316\u6398\u7684\u4e2d\u533b\u836f\u6cbb\u7597\u91cd\u75c7\u65b0\u578b\u51a0\u72b6\u75c5\u6bd2\u80ba\u708e\u63a2\u8ba8 Content: The primary clinical manifestations of coronavirus disease 2019 (COVID-19) are fever, fatigue and dry cough. Several clinical studies reported that some patients with low or medium fever, or even without obvious symptom, rapidly progressed to severe or critical illness, including severe acute respiratory syndrome, septic shock, coagulation disorders and intractable metabolic acidosis. These patients were usually associated with significant elevated serum levels of a profile of cytokines, which is similar to SARS-2003 and MERS-2015, indicating the occurrence of cytokine storm. In the present review, we summarized previous advances in the treatment of severe cases of SARS by using traditional Chinese medicines (TCM), especially those TCM targeting cytokine storm, based on literature mining. By using data mining and network pharmacology, we also investigated underlying mechanisms and biological pathways involved in the inhibitory effects of TCM against cytokine storm. This review not only provides novel insights in the precise application of TCM, appropriate integrative use of TCM in combination with western medicine, but also contributes to the discovery of novel drugs or new therapeutic strategies targeting cytokine storm to suppress progression of COVID-19 and to improve clinical prognosis and outcomes.", "qid": 39, "docid": "ph3z1ha4", "rank": 93, "score": 0.7877867221832275}, {"content": "Title: Cytokine Storm in COVID-19 patients transforms to a Cytokine Super Cyclone in patients with risk factors Content: The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses like SARS-CoV and MERS-CoV, which are established to cause lower respiratory tract infection. The viral infection can be fatal as the disease advances to pneumonia followed by acute respiratory distress syndrome (ARDS). Increasingly higher cytokine concentration on account of over-stimulated immune response against the virus, or the \u2018cytokine storm\u2019, is the reason behind the manifestation of lethal clinical symptoms. In this article, we discuss the immune pathogenesis of cytokine storm and its relation with SARS-CoV2/COVID-19 risk factors. People with underlying risk factors are more susceptible to fatal complications of COVID-19 infection leading to poor clinical outcome. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 to a Cytokine Super Cyclone. We also overviewed antiviral immune response provided by BCG vaccine involving the IL-1\u03b2, IL-6 and TNF-\u03b1 secretion via \u2018trained monocytes\u2019, which confers early protection against SARS-CoV2.", "qid": 39, "docid": "6dq6gm27", "rank": 94, "score": 0.786817729473114}, {"content": "Title: Pediatric Crohn's Disease and Multisystem Inflammatory Syndrome in Children (MIS-C) and COVID-19 Treated with Infliximab Content: Coronavirus disease 2019 (COVID-19) may lead to a severe inflammatory response referred to as a cytokine storm. We describe a case of severe COVID-19 infection in a recently diagnosed pediatric Crohn's disease patient successfully treated with Tumor Necrosis Factor-alpha (TNF-\u03b1) blockade. The patient presented with five days of fever, an erythematous maculopapular facial rash, and abdominal pain without respiratory symptoms. SARS-CoV-2 PCR was positive. Despite inpatient treatment for COVID-19 and a perianal abscess, the patient acutely decompensated, with worsening fever, tachycardia, fluid-refractory hypotension, elevation of liver enzymes, and transformation of the rash into purpura extending from the face to the trunk, upper and lower extremities, including the palmar and plantar surfaces of the hands and feet. Cytokine profile revealed rising levels of interleukin (IL)-6, IL-8, and TNF-\u03b1, higher than those described in either inflammatory bowel disease (IBD) or severe COVID-19 alone. The patient was treated with infliximab for TNF-\u03b1 blockade to address both moderately to severely active Crohn's disease and multisystem inflammatory syndrome in children (MIS-C) temporally related to COVID-19. Within hours of infliximab treatment, fever, tachycardia and hypotension resolved. Cytokine profile improved with normalization of TNF-\u03b1, a decrease in IL-6, and IL-8 concentrations. This case supports a role for blockade of TNF-\u03b1 in the treatment of COVID-19 inflammatory cascade. The role of anti-TNF agents in patients with MIS-C temporally related to COVID-19 requires further investigation.", "qid": 39, "docid": "kgc7lgjp", "rank": 95, "score": 0.7864049077033997}, {"content": "Title: Rheumatologists and Pulmonologists at Temple University weather the COVID-19 storm together. Content: In recent commentaries from Lancet Rheumatology and The Journal of Rhuematology (1-2) the authors eloquently illustrated the connection between COVID-19 infection, the subsequent cytokine storm (CS) that ensues in a number of patients and the potential efficacy of biologics that Rheumatologists routinely use in their practices. Moreover those biologics were originally investigated by Rheumatologists for the treatment of numerous rheumatic conditions, including macrophage activating syndrome (MAS), a similar form of storm that resembles the one occurring in COVID-19 patients (3).", "qid": 39, "docid": "1pujz3em", "rank": 96, "score": 0.7861813306808472}, {"content": "Title: Role of inflammatory markers in corona virus disease (COVID-19) patients: A review. Content: IMPACT STATEMENT In late 2019, a novel virus called SARS-CoV-2, expanded globally from Wuhan, China and was declared a pandemic on 11 March 2020 by the WHO. The mechanism of virus entry inside the host cell depends upon the cellular proteases including cathepsins, HAT, and TMPRSS2, which splits up the spike protein and causes further penetration. MERS coronavirus uses DPP4, while coronavirus HCoV-NL63 and SARS-CoV and SARS-CoV-2 employ ACE-2 as the key receptor. Cytokine storm syndrome was analyzed in critically ill nCOVID-19 patients and it is presented with high inflammatory mediators, systemic inflammation, and multiple organ failure. Among various inflammatory mediators, the level of interleukins (IL-2, IL-7, IL-10), G-CSF, MIP1A, MCP1, and TNF-\u03b1 was reported to be higher in critically ill patients. Understanding this molecular mechanism of ILs, T cells, and dendritic cells will be helpful to design immunotherapy and novel drugs for the treatment of nCOVID-19 infection.", "qid": 39, "docid": "8gzcrrml", "rank": 97, "score": 0.7859184145927429}, {"content": "Title: The bio-mission of interleukin-6 in the pathogenesis of COVID-19: A brief look at potential therapeutic tactics Content: Interleukin-6 (IL-6), known as an inflammatory cytokine, can be involved in many innate and adaptive immune responses. The role of IL-6 in the pathogenesis of the novel coronavirus disease 2019 (COVID-19) has recently received much more attention due to the spread of the virus and its pandemic potential. Cytokine storm is among the most critical pathological events in patients affected with coronaviruses (CoVs), i.e., severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and COVID-19, causing inflammation-induced lung injury and also occurring as a result of dysregulation of immune responses to the mentioned viruses. IL-6, along with some other inflammatory cytokines, including IL-1 beta (\u03b2), IL-8, and tumor necrosis factor-alpha (TNF-\u03b1), as well as inflammatory chemokines, can significantly contribute to, fever, lymphopenia, coagulation, lung injury, and multi-organ failure (MOF). Therefore, researchers are to explore novel approaches to treat the disease through targeting of IL-6 and its receptors based on prior experience of other disorders. In this review article, the latest findings on the role of IL-6 in the pathogenesis of COVID-19, as well as therapeutic perspectives, were summarized and discussed.", "qid": 39, "docid": "8leknnvc", "rank": 98, "score": 0.78580641746521}, {"content": "Title: The immune system and COVID-19: Friend or foe? Content: AIM: Coronavirus disease 2019 (COVID-19) is a novel highly contagious infection caused by SARS-CoV-2, which has been became a global public health challenge. The pathogenesis of this virus is not yet clearly understood, but there is evidence of a hyper-inflammatory immune response in critically ill patients, which leads to acute respiratory distress syndrome (ARDS) and multi-organ failure. MATERIAL AND METHODS: A literature review was performed to identify relevant articles on COVID-19 published up to April 30, 2020. The search resulted in 361 total articles. After reviewing the titles and abstracts for inclusion, some irrelevant papers were excluded. Additional relevant articles were identified from a review of citations referenced. KEY FINDINGS: SARS-CoV-2, directly and indirectly, affects the immune system and avoids being eliminated in early stages. On the other hand, the secretion of inflammatory cytokines creates critical conditions that lead to multi-organ failure. SIGNIFICANCE: The immune system which is affected by the virus tries to respond via a cytokine storm and hyperinflammation, which itself leads to further multi-organ damage and even death.", "qid": 39, "docid": "d44coxr1", "rank": 99, "score": 0.7856499552726746}, {"content": "Title: The kidney in COVID-19: protagonist or figurant? Content: The etiology of injury in COVID-19 patients is diverse and multifactorial. Autopsy and biopsy studies reveal, alongside podocyte and tubular cell anomalies, the presence of virion within the cells. Evidence suggests that, in addition to the direct cytopathic effect of SARS- CoV2 on the glomeruli and renal tubules, there is also the indirect effect of cell-mediated immunity, the cytokines storm and the cross-talk between organs with possible systemic effects of the disease. These mechanisms are interconnected and have profound therapeutic implications involving extracorporeal removal of inflammatory cytokines. Dialysis patients, and children, in particular, should be classified as \"at high risk\" of contracting the disease. Infections are one of the most frequent causes of death in children with chronic renal failure who undergo dialysis. The reasons for this particular susceptibility are to be found in the compromised immune system, secondary to chronic malnutrition, immunosuppressive therapy, and uremia, frequent contact with healthcare personnel and other patients attending the dialysis unit and in need of the presence of other family members during treatment.", "qid": 39, "docid": "h9v5jqfc", "rank": 100, "score": 0.7855608463287354}]}
{"query": "What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur?", "hits": [{"content": "Title: Large scale genomic analysis of 3067 SARS-CoV-2 genomes reveals a clonal geo-distribution and a rich genetic variations of hotspots mutations Content: In late December 2019, an emerging viral infection COVID-19 was identified in Wuhan, China, and became a global pandemic. Characterization of the genetic variants of SARS-CoV-2 is crucial in following and evaluating it spread across countries. In this study, we collected and analyzed 3,067 SARS-CoV-2 genomes isolated from 55 countries during the first three months after the onset of this virus. Using comparative genomics analysis, we traced the profiles of the whole-genome mutations and compared the frequency of each mutation in the studied population. The accumulation of mutations during the epidemic period with their geographic locations was also monitored. The results showed 782 variant sites, of which 512 (65.47%) had a non-synonymous effect. Frequencies of mutated alleles revealed the presence of 38 recurrent non-synonymous mutations, including ten hotspot mutations with a prevalence higher than 0.10 in this population and distributed in six SARS-CoV-2 genes. The distribution of these recurrent mutations on the world map revealed certain genotypes specific to the geographic location. We also found co-occurring mutations resulting in the presence of several haplotypes. Moreover, evolution over time has shown a mechanism of mutation co-accumulation which might affect the severity and spread of the SARS-CoV-2. On the other hand, analysis of the selective pressure revealed the presence of negatively selected residues that could be taken into considerations as therapeutic targets We have also created an inclusive unified database (http://genoma.ma/covid-19/) that lists all of the genetic variants of the SARS-CoV-2 genomes found in this study with phylogeographic analysis around the world.", "qid": 40, "docid": "5mh3ds6y", "rank": 1, "score": 0.8087823987007141}, {"content": "Title: Characterizations of SARS-CoV-2 mutational profile, spike protein stability and viral transmission Content: The recent pandemic of SARS-CoV-2 infection has affected more than 3.0 million people worldwide with more than 200 thousand reported deaths. The SARS-CoV-2 genome has the capability of gaining rapid mutations as the virus spreads. Whole-genome sequencing data offers a wide range of opportunities to study mutation dynamics. The advantage of an increasing amount of whole-genome sequence data of SARS-CoV-2 intrigued us to explore the mutation profile across the genome, to check the genome diversity, and to investigate the implications of those mutations in protein stability and viral transmission. We have identified frequently mutated residues by aligning ~660 SARS-CoV-2 genomes and validated in 10,000 datasets available in GISAID Nextstrain. We further evaluated the potential of these frequently mutated residues in protein structure stability of spike glycoprotein and their possible functional consequences in other proteins. Among the 11 genes, surface glycoprotein, nucleocapsid, ORF1ab, and ORF8 showed frequent mutations, while envelop, membrane, ORF6, ORF7a and ORF7b showed conservation in terms of amino acid substitutions. Combined analysis with the frequently mutated residues identified 20 viral variants, among which 12 specific combinations comprised more than 97% of the isolates considered for the analysis. Some of the mutations across different proteins showed co-occurrences, suggesting their structural and/or functional interaction among different SARS-COV-2 proteins, and their involvement in adaptability and viral transmission. Analysis of protein structure stability of surface glycoprotein mutants indicated the viability of specific variants and are more prone to be temporally and spatially distributed across the globe. A similar empirical analysis of other proteins indicated the existence of important functional implications of several variants. Identification of frequently mutated variants among COVID-19 patients might be useful for better clinical management, contact tracing, and containment of the disease.", "qid": 40, "docid": "q86nga34", "rank": 2, "score": 0.7999858856201172}, {"content": "Title: SARS-CoV-2 amino acid substitutions widely spread in the human population are mainly located in highly conserved segments of the structural proteins Content: The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic offers a unique opportunity to study the introduction and evolution of a pathogen into a completely na\u00efve human population. We identified and analysed the amino acid mutations that gained prominence worldwide in the early months of the pandemic. Eight mutations have been identified along the viral genome, mostly located in conserved segments of the structural proteins and showing low variability among coronavirus, which indicated that they might have a functional impact. At the moment of writing this paper, these mutations present a varied success in the SARS-CoV-2 virus population; ranging from a change in the spike protein that becomes absolutely prevalent, two mutations in the nucleocapsid protein showing frequencies around 25%, to a mutation in the matrix protein that nearly fades out after reaching a frequency of 20%.", "qid": 40, "docid": "0hldozml", "rank": 3, "score": 0.7991829514503479}, {"content": "Title: Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions Content: Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive and GenBank repositories. Up until 27 March 2020, we downloaded 50 illumina datasets, mostly from China, USA (WA State) and Australia (VIC). A total of 30 datasets (60%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA next-generation sequencing samples. Sequencing samples from North America in GenBank (22 April 2020) present this signature with up to 39% allele frequencies among samples (n = 1,359). Australian variant signatures were more diverse than USA samples, but still, clonal events were found in these samples. Mutations in the helicase, encoded by the ORF1ab gene in SARS-CoV-2 were predominant, among others, suggesting that these regions are actively evolving. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.", "qid": 40, "docid": "0xruezf2", "rank": 4, "score": 0.7986350655555725}, {"content": "Title: Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions Content: Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive repository. Up until March 27, 2020, we downloaded 53 illumina datasets, mostly from China, USA (Washington DC) and Australia (Victoria). Of 30 high quality datasets, 27 datasets (90%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA sequencing samples. Sequencing samples from USA in GenBank present this signature with 50% allele frequencies among samples. Australian mutation signatures were more diverse than USA samples, but still, clonal events were found in those samples. Mutations in the helicase and orf1a coding regions from SARS-CoV-2 were predominant, among others, suggesting that these proteins are prone to evolve by natural selection. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.", "qid": 40, "docid": "gfwqog3x", "rank": 5, "score": 0.7983684539794922}, {"content": "Title: COVID-19 Variants Database: A repository for Human SARS-CoV-2 Polymorphism Data Content: COVID-19 is a newly communicable disease with a catastrophe outbreak that affects all over the world. We retrieved about 8,781 nucleotide fragments and complete genomes of SARS-CoV-2 reported from sixty-four countries. The CoV-2 reference genome was obtained from the National Genomics Data Center (NGDC), GISAID, and NCBI Genbank. All the sequences were aligned against reference genomes using Clustal Omega and variants were called using in-house built Python script. We intend to establish a user-friendly online resource to visualize the variants in the viral genome along with the Primer Infopedia. After analyzing and filtering the data globally, it was made available to the public. The detail of data available to the public includes mutations from 5688 SARS-CoV-2 sequences curated from 91 regions. This database incorporated 39920 mutations over 3990 unique positions. According to the translational impact, these mutations include 11829 synonymous mutations including 681 synonymous frameshifts and 21701 nonsynonymous mutations including 10 nonsynonymous frameshifts. Development of SARS-CoV-2 mutation genome browsers is a fundamental step obliging towards the virus surveillance, viral detection, and development of vaccine and therapeutic drugs. The SARS-COV-2 mutation browser is available at http://covid-19.dnageography.com.", "qid": 40, "docid": "r0gr0bhl", "rank": 6, "score": 0.7964757680892944}, {"content": "Title: Mutation landscape of SARS-CoV-2 reveals three mutually exclusive clusters of leading and trailing single nucleotide substitutions Content: The COVID-19 pandemic has spread across the globe at an alarming rate in the last four months. However, unlike any of the previous global outbreaks the availability of hundreds of SARS-CoV-2 sequences provides us with a unique opportunity to understand viral evolution in real time. We analysed 480 full-length (>29000 nt) sequences from the 1575 SARS-CoV-2 sequences available and identified 37 single-nucleotide substitutions occurring in >1% of the genomes. Majority of the substitutions were C to T or G to A. We identify C/Gs with an upstream TTT trinucleotide motif as hotspots for mutations in the SARS-CoV-2 genome. Interestingly, two of the 37 substitutions occur within highly conserved secondary structures in the 5\u2019 and 3\u2019 untranslated regions that are critical for the virus life cycle. Furthermore, clustering analysis revealed unique geographical distribution of SARS-CoV-2 variants defined by their mutation profile. Of note, we observed several co-occurring mutations that almost never occur individually. We define 3 mutually exclusive lineages (A1, B1 and C1) of SARS-CoV-2 which account for about three quarters of the genomes analysed. We identify lineage-defining leading mutations in the SARS-CoV-2 genome which precede the occurrence of sub-lineage defining trailing mutations. The identification of mutually exclusive lineage-defining mutations with geographically restricted patterns of distribution has potential implications for diagnosis, pathogenesis and vaccine design. Our work provides novel insights on the temporal evolution of SARS-CoV-2.", "qid": 40, "docid": "miujzgtd", "rank": 7, "score": 0.7954896688461304}, {"content": "Title: Characterizations of SARS-CoV-2 mutational profile, spike protein stability and viral transmission Content: The recent pandemic of SARS-CoV-2 infection has affected more than 3.0 million people worldwide with more than 200 thousand reported deaths. The SARS-CoV-2 genome has a capability of gaining rapid mutations as the virus spreads. Whole genome sequencing data offers a wide range of opportunities to study the mutation dynamics. The advantage of increasing amount of whole genome sequence data of SARS-CoV-2 intrigued us to explore the mutation profile across the genome, to check the genome diversity and to investigate the implications of those mutations in protein stability and viral transmission. Four proteins, surface glycoprotein, nucleocapsid, ORF1ab and ORF8 showed frequent mutations, while envelop, membrane, ORF6 and ORF7a proteins showed conservation in terms of amino acid substitutions. Some of the mutations across different proteins showed co-occurrence, suggesting their functional cooperation in stability, transmission and adaptability. Combined analysis with the frequently mutated residues identified 20 viral variants, among which 12 specific combinations comprised more than 97% of the isolates considered for the analysis. Analysis of protein structure stability of surface glycoprotein mutants indicated viability of specific variants and are more prone to be temporally and spatially distributed across the globe. Similar empirical analysis of other proteins indicated existence of important functional implications of several variants. Analysis of co-occurred mutants indicated their structural and/or functional interaction among different SARS-COV-2 proteins. Identification of frequently mutated variants among COVID-19 patients might be useful for better clinical management, contact tracing and containment of the disease.", "qid": 40, "docid": "86byq11c", "rank": 8, "score": 0.7939753532409668}, {"content": "Title: Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2 Content: We have developed an analysis pipeline to facilitate real-time mutation tracking in SARS-CoV-2, focusing initially on the Spike (S) protein because it mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapeutics. To date we have identified thirteen mutations in Spike that are accumulating. Mutations are considered in a broader phylogenetic context, geographically, and over time, to provide an early warning system to reveal mutations that may confer selective advantages in transmission or resistance to interventions. Each one is evaluated for evidence of positive selection, and the implications of the mutation are explored through structural modeling. The mutation Spike D614G is of urgent concern; it began spreading in Europe in early February, and when introduced to new regions it rapidly becomes the dominant form. Also, we present evidence of recombination between locally circulating strains, indicative of multiple strain infections. These finding have important implications for SARS-CoV-2 transmission, pathogenesis and immune interventions.", "qid": 40, "docid": "4hmecfi0", "rank": 9, "score": 0.7890233397483826}, {"content": "Title: Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity Content: Monitoring the mutation dynamics of SARS-CoV-2 is critical for the development of effective approaches to contain the pathogen. By analyzing 106 SARS-CoV-2 and 39 SARS genome sequences, we provided direct genetic evidence that SARS-CoV-2 has a much lower mutation rate than SARS. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. The discrepant phylogenies for the spike protein and its receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARS-CoV-2. Despite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a mutation that leads to weaker receptor binding capability, which concerns a SARS-CoV-2 sample collected on 27th January 2020 from India. This represents the first report of a significant SARS-CoV-2 mutant, and raises the alarm that the ongoing vaccine development may become futile in future epidemic if more mutations were identified. Highlights Based on the currently available genome sequence data, we proved that SARS-COV-2 genome has a much lower mutation rate and genetic diversity than SARS during the 2002-2003 outbreak. The spike (S) protein encoding gene of SARS-COV-2 is found relatively more conserved than other protein-encoding genes, which is a good indication for the ongoing antiviral drug and vaccine development. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. We confirmed a previously reported rearrangement in the S protein arrangement of SARS-COV-2, and propose that this rearrangement should have occurred between human SARS-CoV and a bat SARS-CoV, at a time point much earlier before SARS-COV-2 transmission to human. We provided first evidence that a mutated SARS-COV-2 with reduced human ACE2 receptor binding affinity have emerged in India based on a sample collected on 27th January 2020.", "qid": 40, "docid": "t8q99tlq", "rank": 10, "score": 0.7870306968688965}, {"content": "Title: Mutation density changes in SARS-CoV-2 are related to the pandemic stage but to a lesser extent in the dominant strain with mutations in spike and RdRp Content: Since its emergence in Wuhan, China in late 2019, the origin and evolution of SARS-CoV-2 have been among the most debated issues related to COVID-19. Throughout its spread around the world, the viral genome continued acquiring new mutations and some of them became widespread. Among them, 14408 C>T and 23403 A>G mutations in RdRp and S, respectively, became dominant in Europe and the US, which led to debates regarding their effects on the mutability and transmissibility of the virus. In this study, we aimed to investigate possible differences between time-dependent variation of mutation densities (MDe) of viral strains that carry these two mutations and those that do not. Our analyses at the genome and gene level led to two important findings: First, time-dependent changes in the average MDe of circulating SARS-CoV-2 genomes showed different characteristics before and after the beginning of April, when daily new case numbers started levelling off. Second, this pattern was much delayed or even non-existent for the \u201cmutant\u201d (MT) strain that harbored both 14408 C>T and 23403 A>G mutations. Although these differences were not limited to a few hotspots, it is intriguing that the MDe increase is most evident in two critical genes, S and Orf1ab, which are also the genes that harbor the defining mutations of the MT genotype. The nature of these unexpected relationships warrant further research.", "qid": 40, "docid": "fglghjy6", "rank": 11, "score": 0.7862103581428528}, {"content": "Title: Genomic, geographic and temporal distributions of SARS-CoV-2 mutations Content: The COVID-19 pandemic is the most significant public health issue in recent history. Its causal agent, SARS-CoV-2, has evolved rapidly since its first emergence in December 2019. Mutations in the viral genome have critical impacts on the adaptation of viral strains to the local environment, and may alter the characteristics of viral transmission, disease manifestation, and the efficacy of treatment and vaccination. Using the complete sequences of 1,932 SARS-CoV-2 genomes, we examined the genomic, geographic and temporal distributions of aged, new, and frequent mutations of SARS-CoV-2, and identified six phylogenetic clusters of the strains, which also exhibit a geographic preference in different continents. Mutations in the form of single nucleotide variations (SNVs) provide a direct interpretation for the six phylogenetic clusters. Linkage disequilibrium, haplotype structure, evolutionary process, global distribution of mutations unveiled a sketch of the mutational history. Additionally, we found a positive correlation between the average mutation count and case fatality, and this correlation had strengthened with time, suggesting an important role of SNVs on disease outcomes. This study suggests that SNVs may become an important consideration in virus detection, clinical treatment, drug design, and vaccine development to avoid target shifting, and that continued isolation and sequencing is a crucial component in the fight against this pandemic. Significance Statement Mutation is the driving force of evolution for viruses like SARS-CoV-2, the causal agent of COVID-19. In this study, we discovered that the genome of SARS-CoV-2 is changing rapidly from the originally isolated form. These mutations have been spreading around the world and caused more than 2.5 million of infected cases and 170 thousands of deaths. We found that fourteen frequent mutations identified in this study can characterize the six main clusters of SARS-CoV-2 strains. In addition, we found the mutation burden is positively correlated with the fatality of COVID-19 patients. Understanding mutations in the SARS-CoV-2 genome will provide useful insight for the design of treatment and vaccination.", "qid": 40, "docid": "1vhxcbx7", "rank": 12, "score": 0.7839034795761108}, {"content": "Title: coronapp: A Web Application to Annotate and Monitor SARS-CoV-2 Mutations Content: The avalanche of genomic data generated from the SARS-CoV-2 virus requires the development of tools to detect and monitor its mutations across the World. Here, we present a webtool, coronapp, dedicated to easily processing user-provided SARS-CoV-2 genomic sequences, in order to detect and annotate protein-changing mutations. This results in an up-to-date status of SARS-CoV-2 mutations, both worldwide and in user-selected countries. The tool allows users to highlight and prioritize the most frequent mutations in specific protein regions, and to monitor their frequency in the population over time. The tool is available at http://giorgilab.dyndns.org/coronapp/ and the full code is freely shared at https://github.com/federicogiorgi/giorgilab/tree/master/coronapp", "qid": 40, "docid": "pfhfmck1", "rank": 13, "score": 0.7832449078559875}, {"content": "Title: Identification of unique mutations in SARS-CoV-2 strains isolated from India suggests its attenuated pathotype Content: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first reported in Wuhan, China in November 2019 has developed into a pandemic since March 2020, causing substantial human casualties and economic losses. Studies on SARS-CoV-2 are being carried out at an unprecedented rate to tackle this threat. Genomics studies, in particular, are indispensable to elucidate the dynamic nature of the RNA genome of SARS-CoV-2. RNA viruses are marked by their unique ability to undergo high rates of mutation in their genome, much more frequently than their hosts, which diversifies their strengths qualifying them to elude host immune response and amplify drug resistance. In this study, we sequenced and analyzed the genomic information of the SARS-CoV-2 isolates from two infected Indian patients and explored the possible implications of point mutations in its biology. In addition to multiple point mutations, we found a remarkable similarity between relatively common mutations of 36-nucleotide deletion in ORF8 of SARS-CoV-2. Our results corroborate with the earlier reported 29-nucleotide deletion in SARS, which was frequent during the early stage of human-to-human transmission. The results will be useful to understand the biology of SARS-CoV-2 and itsattenuation for vaccine development.", "qid": 40, "docid": "fujejfwb", "rank": 14, "score": 0.7831985354423523}, {"content": "Title: Mutational dynamics of the SARS coronavirus in cell culture and human populations isolated in 2003 Content: BACKGROUND: The SARS coronavirus is the etiologic agent for the epidemic of the Severe Acute Respiratory Syndrome. The recent emergence of this new pathogen, the careful tracing of its transmission patterns, and the ability to propagate in culture allows the exploration of the mutational dynamics of the SARS-CoV in human populations. METHODS: We sequenced complete SARS-CoV genomes taken from primary human tissues (SIN3408, SIN3725V, SIN3765V), cultured isolates (SIN848, SIN846, SIN842, SIN845, SIN847, SIN849, SIN850, SIN852, SIN3408L), and five consecutive Vero cell passages (SIN2774_P1, SIN2774_P2, SIN2774_P3, SIN2774_P4, SIN2774_P5) arising from SIN2774 isolate. These represented individual patient samples, serial in vitro passages in cell culture, and paired human and cell culture isolates. Employing a refined mutation filtering scheme and constant mutation rate model, the mutation rates were estimated and the possible date of emergence was calculated. Phylogenetic analysis was used to uncover molecular relationships between the isolates. RESULTS: Close examination of whole genome sequence of 54 SARS-CoV isolates identified before 14(th )October 2003, including 22 from patients in Singapore, revealed the mutations engendered during human-to-Vero and Vero-to-human transmission as well as in multiple Vero cell passages in order to refine our analysis of human-to-human transmission. Though co-infection by different quasipecies in individual tissue samples is observed, the in vitro mutation rate of the SARS-CoV in Vero cell passage is negligible. The in vivo mutation rate, however, is consistent with estimates of other RNA viruses at approximately 5.7 \u00d7 10(-6 )nucleotide substitutions per site per day (0.17 mutations per genome per day), or two mutations per human passage (adjusted R-square = 0.4014). Using the immediate Hotel M contact isolates as roots, we observed that the SARS epidemic has generated four major genetic groups that are geographically associated: two Singapore isolates, one Taiwan isolate, and one North China isolate which appears most closely related to the putative SARS-CoV isolated from a palm civet. Non-synonymous mutations are centered in non-essential ORFs especially in structural and antigenic genes such as the S and M proteins, but these mutations did not distinguish the geographical groupings. However, no non-synonymous mutations were found in the 3CLpro and the polymerase genes. CONCLUSIONS: Our results show that the SARS-CoV is well adapted to growth in culture and did not appear to undergo specific selection in human populations. We further assessed that the putative origin of the SARS epidemic was in late October 2002 which is consistent with a recent estimate using cases from China. The greater sequence divergence in the structural and antigenic proteins and consistent deletions in the 3' \u2013 most portion of the viral genome suggest that certain selection pressures are interacting with the functional nature of these validated and putative ORFs.", "qid": 40, "docid": "0gmtnkbh", "rank": 15, "score": 0.7817164659500122}, {"content": "Title: No evidence for increased transmissibility from recurrent mutations in SARS-CoV-2 Content: The COVID-19 pandemic is caused by the coronavirus SARS-CoV-2, which jumped into the human population in late 2019 from a currently uncharacterised reservoir. Due to this extremely recent association with humans, SARS-CoV-2 may not yet be fully adapted to its human host. This has led to speculations that some lineages of SARS-CoV-2 may be evolving towards higher transmissibility. The most plausible candidate mutations under putative natural selection are those which have emerged repeatedly and independently (homoplasies). Here, we formally test whether any of the recurrent mutations that have been observed in SARS-CoV-2 to date are significantly associated with increased viral transmission. To do so, we developed a phylogenetic index to quantify the relative number of descendants in sister clades with and without a specific allele. We apply this index to a carefully curated set of recurrent mutations identified within a dataset of over 23,000 SARS-CoV-2 genomes isolated from patients worldwide. We do not identify a single recurrent mutation in this set convincingly associated with increased viral transmission. Instead, recurrent SARS-CoV-2 mutations currently in circulation appear to be evolutionary neutral. Recurrent mutations also seem primarily induced by the human immune system via host RNA editing, rather than being signatures of adaption to the novel human host. We find no evidence at this stage for the emergence of more transmissible lineages of SARS-CoV-2 due to recurrent mutations.", "qid": 40, "docid": "a51vkiei", "rank": 16, "score": 0.7770146131515503}, {"content": "Title: Evolutionary analysis of SARS-CoV-2: how mutation of Non-Structural Protein 6 (NSP6) could affect viral autophagy Content: BACKGROUND: SARS-CoV-2 is a new coronavirus that has spread globally, infecting more than 150000 people, and being declared pandemic by the WHO. We provide here bio-informatic, evolutionary analysis of 351 available sequences of its genome with the aim of mapping genome structural variations and the patterns of selection. METHODS: A Maximum likelihood tree has been built and selective pressure has been investigated in order to find any mutation developed during the SARS-CoV-2 epidemic that could potentially affect clinical evolution of the infection. FINDING: We have found in more recent isolates the presence of two mutations affecting the Non-Structural Protein 6 (NSP6) and the Open Reding Frame10 (ORF 10) adjacent regions. Amino acidic change stability analysis suggests both mutations could confer lower stability of the protein structures. INTERPRETATION: One of the two mutations, likely developed within the genome during virus spread, could affect virus intracellular survival. Genome follow-up of SARS-CoV-2 spread is urgently needed in order to identify mutations that could significantly modify virus pathogenicity.", "qid": 40, "docid": "su5tlg3l", "rank": 17, "score": 0.7770006656646729}, {"content": "Title: Comprehensive annotations of the mutational spectra of SARS-CoV-2 spike protein: a fast and accurate pipeline Content: In order to explore nonsynonymous mutations and deletions in the spike (S) protein of SARS-CoV-2, we comprehensively analyzed 35,750 complete S protein gene sequences from across six continents and five climate zones around the world, as documented in the GISAID database as of June 24th, 2020. Through a custom Python-based pipeline for analyzing mutations, we identified 27,801 (77.77 % of spike sequences) mutated strains compared to Wuhan-Hu-1 strain. 84.40% of these strains had only single amino-acid (aa) substitution mutations, but an outlier strain from Bosnia and Herzegovina (EPI_ISL_463893) was found to possess six aa substitutions. The D614G variant of the major G clade was found to be predominant across circulating strains in all climates. We also identified 988 unique aa substitution mutations distributed across 660 positions within the spike protein, with eleven sites showing high variability \u2013 these sites had four types of aa variations at each position. Besides, 17 in-frame deletions at four major regions (three in N-terminal domain and one just downstream of the RBD) may have possible impact on attenuation. Moreover, the mutational frequency differed significantly (p= 0.003, Kruskal\u2013Wallis test) among the SARS-CoV-2 strains worldwide. This study presents a fast and accurate pipeline for identifying nonsynonymous mutations and deletions from large dataset for any particular protein coding sequence and presents this S protein data as representative analysis. By using separate multi-sequence alignment with MAFFT, removing ambiguous sequences and in-frame stop codons, and utilizing pairwise alignment, this method can derive nonsynonymus mutations (Reference:Position:Strain). We believe this will aid in the surveillance of any proteins encoded by SARS-CoV-2, and will prove to be crucial in tracking the ever-increasing variation of many other divergent RNA viruses in the future.", "qid": 40, "docid": "1iqg0efn", "rank": 18, "score": 0.7753188610076904}, {"content": "Title: Time-series analyses of directional sequence changes in SARS-CoV-2 genomes and an efficient search method for advantageous mutations for growth in human cells Content: We first conducted time-series analysis of mono- and dinucleotide composition for over 10,000 SARS-CoV-2 genomes, as well as over 1500 Zaire ebolavirus genomes, and found clear time-series changes in the compositions on a monthly basis, which should reflect viral adaptations for efficient growth in human cells. We next developed a sequence alignment free method that extensively searches for advantageous mutations and rank them in an increase level for their intrapopulation frequency. Time-series analysis of occurrences of oligonucleotides of diverse lengths for SARS-CoV-2 genomes revealed seven distinctive mutations that rapidly expanded their intrapopulation frequency and are thought to be candidates of advantageous mutations for the efficient growth in human cells.", "qid": 40, "docid": "0d9hzmyk", "rank": 19, "score": 0.7742981910705566}, {"content": "Title: SARS-CoV-2: virus mutations in specific European populations Content: Abstract The SARS-CoV-2 virus is being intensively studied, particularly, its evolution in the increasingly available sequences between countries/continents with classical phylogenetic tree representation. More recently, certain protein mutations are correlated with specific functional impacts. Our clinical data from patients suggest different clinical symptoms between European countries. Among others, SARS-CoV-2 mutations could explain these disparities. Our analyses point out an association of diverse mutations, including co-evolving ones, in a few SARS-CoV-2 proteins, with specific countries. We therefore suggest combining clinical information from patients and the determination of the associated SARS-CoV-2 genome to better understand the specific symptoms.", "qid": 40, "docid": "y5th0mrf", "rank": 20, "score": 0.773737370967865}, {"content": "Title: Overwhelming mutations or SNPs of SARS-CoV-2: A point of caution Content: The morbidity of SARS-CoV-2 (COVID-19) is reaching 3 Million landmark causing and a serious public health concern globally and it is enigmatic how several antiviral and antibody treatments were not effective in the different period across the globe. With the drastic increasing number of positive cases around the world WHO raised the importance in the assessment of the risk of spread and understanding genetic modifications that could have occurred in the SARS-CoV-2. Using all available deep sequencing data of complete genome from all over the world (NCBI repository), we identified several hundreds of point mutations or SNPs in SARS-CoV-2 all across the genome. This could be the cause for the constant change and differed virulence with an increase in mortality and morbidity. Among the 12 different countries (one sequence from each country) with complete genome sequencing data, we noted the 47 key point mutations or SNPs located along the entire genome that might have impact in the virulence and response to different antivirals against SARS-CoV-2. In this regard, key viral proteins of spike glycoprotein, Nsp1, RdRp and the ORF8 region got heavily mutated within these 3 months via person-to-person passage. We also discuss what could be the possible cause of this rapid mutation in the SARS-CoV-2.", "qid": 40, "docid": "j8sg5n5g", "rank": 21, "score": 0.7728508710861206}, {"content": "Title: Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant Content: BACKGROUND: SARS-CoV-2 is a RNA coronavirus responsible for the pandemic of the Severe Acute Respiratory Syndrome (COVID-19). RNA viruses are characterized by a high mutation rate, up to a million times higher than that of their hosts. Virus mutagenic capability depends upon several factors, including the fidelity of viral enzymes that replicate nucleic acids, as SARS-CoV-2 RNA dependent RNA polymerase (RdRp). Mutation rate drives viral evolution and genome variability, thereby enabling viruses to escape host immunity and to develop drug resistance. METHODS: We analyzed 220 genomic sequences from the GISAID database derived from patients infected by SARS-CoV-2 worldwide from December 2019 to mid-March 2020. SARS-CoV-2 reference genome was obtained from the GenBank database. Genomes alignment was performed using Clustal Omega. Mann-Whitney and Fisher-Exact tests were used to assess statistical significance. RESULTS: We characterized 8 novel recurrent mutations of SARS-CoV-2, located at positions 1397, 2891, 14408, 17746, 17857, 18060, 23403 and 28881. Mutations in 2891, 3036, 14408, 23403 and 28881 positions are predominantly observed in Europe, whereas those located at positions 17746, 17857 and 18060 are exclusively present in North America. We noticed for the first time a silent mutation in RdRp gene in England (UK) on February 9th, 2020 while a different mutation in RdRp changing its amino acid composition emerged on February 20th, 2020 in Italy (Lombardy). Viruses with RdRp mutation have a median of 3 point mutations [range: 2-5], otherwise they have a median of 1 mutation [range: 0-3] (p value < 0.001). CONCLUSIONS: These findings suggest that the virus is evolving and European, North American and Asian strains might coexist, each of them characterized by a different mutation pattern. The contribution of the mutated RdRp to this phenomenon needs to be investigated. To date, several drugs targeting RdRp enzymes are being employed for SARS-CoV-2 infection treatment. Some of them have a predicted binding moiety in a SARS-CoV-2 RdRp hydrophobic cleft, which is adjacent to the 14408 mutation we identified. Consequently, it is important to study and characterize SARS-CoV-2 RdRp mutation in order to assess possible drug-resistance viral phenotypes. It is also important to recognize whether the presence of some mutations might correlate with different SARS-CoV-2 mortality rates.", "qid": 40, "docid": "16lkzgtq", "rank": 22, "score": 0.7727953195571899}, {"content": "Title: Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant Content: BACKGROUND: SARS-CoV-2 is a RNA coronavirus responsible for the pandemic of the Severe Acute Respiratory Syndrome (COVID-19). RNA viruses are characterized by a high mutation rate, up to a million times higher than that of their hosts. Virus mutagenic capability depends upon several factors, including the fidelity of viral enzymes that replicate nucleic acids, as SARS-CoV-2 RNA dependent RNA polymerase (RdRp). Mutation rate drives viral evolution and genome variability, thereby enabling viruses to escape host immunity and to develop drug resistance. METHODS: We analyzed 220 genomic sequences from the GISAID database derived from patients infected by SARS-CoV-2 worldwide from December 2019 to mid-March 2020. SARS-CoV-2 reference genome was obtained from the GenBank database. Genomes alignment was performed using Clustal Omega. Mann\u2013Whitney and Fisher-Exact tests were used to assess statistical significance. RESULTS: We characterized 8 novel recurrent mutations of SARS-CoV-2, located at positions 1397, 2891, 14408, 17746, 17857, 18060, 23403 and 28881. Mutations in 2891, 3036, 14408, 23403 and 28881 positions are predominantly observed in Europe, whereas those located at positions 17746, 17857 and 18060 are exclusively present in North America. We noticed for the first time a silent mutation in RdRp gene in England (UK) on February 9th, 2020 while a different mutation in RdRp changing its amino acid composition emerged on February 20th, 2020 in Italy (Lombardy). Viruses with RdRp mutation have a median of 3 point mutations [range: 2\u20135], otherwise they have a median of 1 mutation [range: 0\u20133] (p value < 0.001). CONCLUSIONS: These findings suggest that the virus is evolving and European, North American and Asian strains might coexist, each of them characterized by a different mutation pattern. The contribution of the mutated RdRp to this phenomenon needs to be investigated. To date, several drugs targeting RdRp enzymes are being employed for SARS-CoV-2 infection treatment. Some of them have a predicted binding moiety in a SARS-CoV-2 RdRp hydrophobic cleft, which is adjacent to the 14408 mutation we identified. Consequently, it is important to study and characterize SARS-CoV-2 RdRp mutation in order to assess possible drug-resistance viral phenotypes. It is also important to recognize whether the presence of some mutations might correlate with different SARS-CoV-2 mortality rates.", "qid": 40, "docid": "ow2aijmj", "rank": 23, "score": 0.7727862596511841}, {"content": "Title: Evolutionary analysis of SARS-CoV-2: how mutation of Non-Structural Protein 6 (NSP6) could affect viral autophagy Content: Abstract Background SARS-CoV-2 is a new coronavirus that has spread globally, infecting more than 150000 people, and being declared pandemic by the WHO. We provide here bio-informatic, evolutionary analysis of 351 available sequences of its genome with the aim of mapping genome structural variations and the patterns of selection. Methods A Maximum likelihood tree has been built and selective pressure has been investigated in order to find any mutation developed during the SARS-CoV-2 epidemic that could potentially affect clinical evolution of the infection. Finding We have found in more recent isolates the presence of two mutations affecting the Non-Structural Protein 6 (NSP6) and the Open Reding Frame10 (ORF 10) adjacent regions. Amino acidic change stability analysis suggests both mutations could confer lower stability of the protein structures. Interpretation One of the two mutations, likely developed within the genome during virus spread, could affect virus intracellular survival. Genome follow-up of SARS-CoV-2 spread is urgently needed in order to identify mutations that could significantly modify virus pathogenicity.", "qid": 40, "docid": "tldg8c94", "rank": 24, "score": 0.7725948095321655}, {"content": "Title: Genomic characterization of a novel SARS-CoV-2 Content: A new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated with human to human transmission and extreme human sickness has been as of late announced from the city of Wuhan in China. Our objectives were to mutation analysis between recently reported genomes at various times and locations and to characterize the genomic structure of SARS-CoV-2 using bioinformatics programs. Information on the variation of viruses is of considerable medical and biological impacts on the prevention, diagnosis, and therapy of infectious diseases. To understand the genomic structure and variations of the SARS-CoV-2. The study analyzed 95 SARS-CoV-2 complete genome sequences available in GenBank, National MicrobiologyData Center (NMDC) and NGDC Genome Warehouse from December-2019 until 05 of April-2020. The genomic signature analysis demonstrates that a strong association between the time of sample collection, location of sample and accumulation of genetic diversity. We found 116 mutations, the three most common mutations were 8782C>T in ORF1ab gene, 28144T>C in ORF8 gene and 29095C>T in the N gene. The mutations might affect the severity and spread of the SARS-CoV-2. The finding heavily supports an intense requirement for additional prompt, inclusive investigations that combine genomic detail, epidemiological information and graph records of the clinical features of patients with COVID-19.", "qid": 40, "docid": "mp3196kj", "rank": 25, "score": 0.7704358100891113}, {"content": "Title: Genome-Wide Identification and Characterization of Point Mutations in the SARS-CoV-2 Genome Content: OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has been rapidly spreading worldwide. Although the causal relationship among mutations and the features of SARS-CoV-2 such as rapid transmission, pathogenicity, and tropism, remains unclear, our results of genomic mutations in SARS-CoV-2 may help to interpret the interaction between genomic characterization in SARS-CoV-2 and infectivity with the host. METHODS: A total of 4,254 genomic sequences of SARS-CoV-2 were collected from the Global Initiative on Sharing all Influenza Data (GISAID). Multiple sequence alignment for phylogenetic analysis and comparative genomic approach for mutation analysis were conducted using Molecular Evolutionary Genetics Analysis (MEGA), and an in-house program based on Perl language, respectively. RESULTS: Phylogenetic analysis of SARS-CoV-2 strains indicated that there were 3 major clades including S, V, and G, and 2 subclades (G.1 and G.2). There were 767 types of synonymous and 1,352 types of non-synonymous mutation. ORF1a, ORF1b, S, and N genes were detected at high frequency, whereas ORF7b and E genes exhibited low frequency. In the receptor-binding domain (RBD) of the S gene, 11 non-synonymous mutations were observed in the region adjacent to the angiotensin converting enzyme 2 (ACE2) binding site. CONCLUSION: It has been reported that the rapid infectivity and transmission of SARS-CoV-2 associated with host receptor affinity are derived from several mutations in its genes. Without these genetic mutations to enhance evolutionary adaptation, species recognition, host receptor affinity, and pathogenicity, it would not survive. It is expected that our results could provide an important clue in understanding the genomic characteristics of SARS-CoV-2.", "qid": 40, "docid": "shn7vx3d", "rank": 26, "score": 0.7702085971832275}, {"content": "Title: Controlling the SARS-CoV-2 outbreak, insights from large scale whole genome sequences generated across the world Content: Background SARS-CoV-2 most likely evolved from a bat beta-coronavirus and started infecting humans in December 2019. Since then it has rapidly infected people around the world, with more than 4.5 million confirmed cases by the middle of May 2020. Early genome sequencing of the virus has enabled the development of molecular diagnostics and the commencement of therapy and vaccine development. The analysis of the early sequences showed relatively few evolutionary selection pressures. However, with the rapid worldwide expansion into diverse human populations, significant genetic variations are becoming increasingly likely. The current limitations on social movement between countries also offers the opportunity for these viral variants to become distinct strains with potential implications for diagnostics, therapies and vaccines. Methods We used the current sequencing archives (NCBI and GISAID) to investigate 15,487 whole genomes, looking for evidence of strain diversification and selective pressure. Results We used 6,294 SNPs to build a phylogenetic tree of SARS-CoV-2 diversity and noted strong evidence for the existence of two major clades and six sub-clades, unevenly distributed across the world. We also noted that convergent evolution has potentially occurred across several locations in the genome, showing selection pressures, including on the spike glycoprotein where we noted a potentially critical mutation that could affect its binding to the ACE2 receptor. We also report on mutations that could prevent current molecular diagnostics from detecting some of the sub-clades. Conclusion The worldwide whole genome sequencing effort is revealing the challenge of developing SARS-CoV-2 containment tools suitable for everyone and the need for data to be continually evaluated to ensure accuracy in outbreak estimations.", "qid": 40, "docid": "tutit2bc", "rank": 27, "score": 0.7687105536460876}, {"content": "Title: Genomic characterization of a novel SARS-CoV-2 Content: Abstract A new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated with human to human transmission and extreme human sickness has been as of late announced from the city of Wuhan in China. Our objectives were to mutation analysis between recently reported genomes at various times and locations and to characterize the genomic structure of SARS-CoV-2 using bioinformatics programs. Information on the variation of viruses is of considerable medical and biological impacts on the prevention, diagnosis, and therapy of infectious diseases. To understand the genomic structure and variations of the SARS-CoV-2. The study analyzed 95 SARS-CoV-2 complete genome sequences available in GenBank, National MicrobiologyData Center (NMDC) and NGDC Genome Warehouse from December-2019 until 05 of April-2020. The genomic signature analysis demonstrates that a strong association between the time of sample collection, location of sample and accumulation of genetic diversity. We found 116 mutations, the three most common mutations were 8782C>T in ORF1ab gene, 28144T>C in ORF8 gene and 29095C>T in the N gene. The mutations might affect the severity and spread of the SARS-CoV-2. The finding heavily supports an intense requirement for additional prompt, inclusive investigations that combine genomic detail, epidemiological information and graph records of the clinical features of patients with COVID-19.", "qid": 40, "docid": "vjfquvlu", "rank": 28, "score": 0.7665249109268188}, {"content": "Title: Decoding SARS-CoV-2 Transmission and Evolution and Ramifications for COVID-19 Diagnosis, Vaccine, and Medicine Content: [Image: see text] Tremendous effort has been given to the development of diagnostic tests, preventive vaccines, and therapeutic medicines for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much of this development has been based on the reference genome collected on January 5, 2020. Based on the genotyping of 15 140 genome samples collected up to June 1, 2020, we report that SARS-CoV-2 has undergone 8309 single mutations which can be clustered into six subtypes. We introduce mutation ratio and mutation h-index to characterize the protein conservativeness and unveil that SARS-CoV-2 envelope protein, main protease, and endoribonuclease protein are relatively conservative, while SARS-CoV-2 nucleocapsid protein, spike protein, and papain-like protease are relatively nonconservative. In particular, we have identified mutations on 40% of nucleotides in the nucleocapsid gene in the population level, signaling potential impacts on the ongoing development of COVID-19 diagnosis, vaccines, and antibody and small-molecular drugs.", "qid": 40, "docid": "13tc3loo", "rank": 29, "score": 0.7660659551620483}, {"content": "Title: Emergence of genomic diversity and recurrent mutations in SARS-CoV-2 Content: SARS-CoV-2 is a SARS-like coronavirus of likely zoonotic origin first identified in December 2019 in Wuhan, the capital of China's Hubei province. The virus has since spread globally, resulting in the currently ongoing COVID-19 pandemic. The first whole genome sequence was published on January 5 2020, and thousands of genomes have been sequenced since this date. This resource allows unprecedented insights into the past demography of SARS-CoV-2 but also monitoring of how the virus is adapting to its novel human host, providing information to direct drug and vaccine design. We curated a dataset of 7666 public genome assemblies and analysed the emergence of genomic diversity over time. Our results are in line with previous estimates and point to all sequences sharing a common ancestor towards the end of 2019, supporting this as the period when SARS-CoV-2 jumped into its human host. Due to extensive transmission, the genetic diversity of the virus in several countries recapitulates a large fraction of its worldwide genetic diversity. We identify regions of the SARS-CoV-2 genome that have remained largely invariant to date, and others that have already accumulated diversity. By focusing on mutations which have emerged independently multiple times (homoplasies), we identify 198 filtered recurrent mutations in the SARS-CoV-2 genome. Nearly 80% of the recurrent mutations produced non-synonymous changes at the protein level, suggesting possible ongoing adaptation of SARS-CoV-2. Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. We additionally provide an interactive user-friendly web-application to query the alignment of the 7666 SARS-CoV-2 genomes.", "qid": 40, "docid": "msggi1p2", "rank": 30, "score": 0.7660123705863953}, {"content": "Title: RdRp mutations are associated with SARS-CoV-2 genome evolution Content: COVID-19, caused by the novel SARS-CoV-2 virus, started in China in late 2019, and soon became a global pandemic. With the help of thousands of viral genome sequences that have been accumulating, it has become possible to track the evolution of viral genome over time as it spread across the world. An important question that still needs to be answered is whether any of the common mutations affect the viral properties, and therefore the disease characteristics. Therefore, we sought to understand the effects of mutations in RNA-dependent RNA polymerase (RdRp), particularly the common 14408C>T mutation, on mutation rate and viral spread. By focusing on mutations in the slowly evolving M or E genes, we aimed to minimize the effects of selective pressure. Our results indicate that 14408C>T mutation increases the mutation rate, while the third-most common RdRp mutation, 15324C>T, has the opposite effect. It is possible that 14408C>T mutation may have contributed to the dominance of its co-mutations in Europe and elsewhere.", "qid": 40, "docid": "i09lh5i6", "rank": 31, "score": 0.7657757997512817}, {"content": "Title: Emergence of genomic diversity and recurrent mutations in SARS-CoV-2 Content: Abstract SARS-CoV-2 is a SARS-like coronavirus of likely zoonotic origin first identified in December 2019 in Wuhan, the capital of China's Hubei province. The virus has since spread globally, resulting in the currently ongoing COVID-19 pandemic. The first whole genome sequence was published on January 52,020, and thousands of genomes have been sequenced since this date. This resource allows unprecedented insights into the past demography of SARS-CoV-2 but also monitoring of how the virus is adapting to its novel human host, providing information to direct drug and vaccine design. We curated a dataset of 7666 public genome assemblies and analysed the emergence of genomic diversity over time. Our results are in line with previous estimates and point to all sequences sharing a common ancestor towards the end of 2019, supporting this as the period when SARS-CoV-2 jumped into its human host. Due to extensive transmission, the genetic diversity of the virus in several countries recapitulates a large fraction of its worldwide genetic diversity. We identify regions of the SARS-CoV-2 genome that have remained largely invariant to date, and others that have already accumulated diversity. By focusing on mutations which have emerged independently multiple times (homoplasies), we identify 198 filtered recurrent mutations in the SARS-CoV-2 genome. Nearly 80% of the recurrent mutations produced non-synonymous changes at the protein level, suggesting possible ongoing adaptation of SARS-CoV-2. Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. We additionally provide an interactive user-friendly web-application to query the alignment of the 7666 SARS-CoV-2 genomes.", "qid": 40, "docid": "bsypo08l", "rank": 32, "score": 0.7655776143074036}, {"content": "Title: Investigating the genomic landscape of novel coronavirus (2019-nCoV) to identify non-synonymous mutations for use in diagnosis and drug design Content: This study presents a comprehensive phylogenetic analysis of SARS-CoV2 isolates to understand discrete mutations that are occurring between patient samples. The analysis unravel various amino acid mutations in the viral proteins which may provide an explanation for varying treatment efficacies of different inhibitory drugs and a future direction towards a combinatorial treatment therapies based on the kind of mutation in the viral genome.", "qid": 40, "docid": "ttte21up", "rank": 33, "score": 0.7651140689849854}, {"content": "Title: SARS-CoV2 envelope protein: Non-synonymous mutations and its consequences Content: In the NCBI database, as on June 6, 2020, total number of available complete genome sequences of SARS-CoV2 across the world is 3617. The envelope protein of SARS-CoV2 possesses several non-synonymous mutations over the transmembrane domain and (C)-terminus in 15 (0.414%) genomes among 3617 available SARS-CoV2 genomes. More precisely, it is to be mentioned that 10(0.386%) out of 2588 genomes from the USA, 3(0.806%) from Asia, 1 (0.348%) from Europe and 1 (0.274%) from Oceania contain the missense mutations over the envelope proteins of SARS-CoV2 genomes. The C-terminus motif DLLV has been changed to DFLV and YLLV in the proteins QJR88103 (Australia: Victoria) and QKI36831 (China: Guangzhou) respectively, which might affect the binding of this motif with the host protein PALS1.", "qid": 40, "docid": "phl6ibbv", "rank": 34, "score": 0.7648568153381348}, {"content": "Title: Whole-Genome Sequences of the Severe Acute Respiratory Syndrome Coronavirus-2 obtained from Romanian patients between March and June of 2020 Content: Impact of mutations on the evolution of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) are needed for ongoing global efforts to track and trace the current pandemic, in order to enact effective prevention and treatment options. SARS-Co-V-2 viral genomes were detected and sequenced from 18 Romanian patients suffering from coronavirus disease-2019. Viral Spike S glycoprotein sequences were used to generate model structures and assess the role of mutations on protein stability. We integrated the phylogenetic tree within the available European SARS-Co-V-2 genomic sequences. We further provide an epidemiological overview of the pre-existing conditions that are lethal in relevant Romanian patients. Non-synonymous mutations in the viral Spike glycoprotein relating to infectivity are constructed in models of protein structures. Continuing search to limit and treat SARS-CoV-2 benefit from our contribution in delineating the viral Spike glycoprotein mutations, as well as from assessment of their role on protein stability or complex formation with human receptor angiotensin-converting enzyme 2. Our results help implement and extend worldwide genomic surveillance of coronavirus disease-2019.", "qid": 40, "docid": "uhru7rn8", "rank": 35, "score": 0.7646490335464478}, {"content": "Title: The novel Coronavirus enigma: Phylogeny and mutation analyses of SARS-CoV-2 viruses circulating in India during early 2020 Content: Background This is a comprehensive analysis of 46 Indian SARS-CoV-2 genome sequences available from the NCBI and GISAID repository during early 2020. Evolutionary dynamics, gene-specific phylogeny and emergence of the novel co-evolving mutations in nine structural and non-structural genes among circulating SARS-CoV-2 strains in ten states of India have been assessed. Materials and methods 46 SARS-CoV-2 nucleotide sequences submitted from India were downloaded from the GISAID (39/46) or from NCBI (7/46) database. Phylogenetic study and analyses of mutation were based on the nine structural and non-structural genes of SARS-CoV-2 strains. Secondary structure of RdRP/NSP12 protein was predicted with respect to the novel A97V mutation. Results Phylogenetic analyses revealed the evolution of \u201cgenome-type clusters\u201d and adaptive selection of \u201cL\u201d type SARS-CoV-2 strains with genetic closeness to the bat SARS-like coronaviruses than pangolin or MERS-CoVs. With regards to the novel co-evolving mutations, 2 groups are seen to circulate in India at present: the \u201cmajor group\u201d (52.2%) and the \u201cminor group\u201d (30.4%), harboring four and five co-existing mutations, respectively. The \u201cmajor group\u201d mutations fall in the A2a clade. All the minor group mutations, except 11083G>T (L37F, NSP6) were unique to the Indian isolates. Conclusion The study highlights rapidly evolving SARS-CoV-2 virus and co-circulation of multiple clades and sub-clades, driving this pandemic worldwide. This comprehensive study is a potential resource for monitoring the novel mutations in the viral genome, changes in viral pathogenesis, for designing vaccines and other therapeutics.", "qid": 40, "docid": "915srotp", "rank": 36, "score": 0.7640478014945984}, {"content": "Title: Mutational Signatures and Heterogeneous Host Response Revealed Via Large-Scale Characterization of SARS-COV-2 Genomic Diversity Content: To dissect the mechanisms underlying the observed inflation of variants in SARS-CoV-2 genome, we present the largest up-to-date analysis of intra-host genomic diversity, which reveals that the majority of samples present a complex sublineage architecture, due to the interplay between host-related mutational processes and transmission dynamics. Strikingly, the deconvolution of the entire set of intra-host variants reveals the existence of mutually exclusive viral mutational signatures, which prove that distinct hosts differently respond to SARS-CoV-2 infections. In particular, two signatures are likely ruled by APOBEC and Reactive Oxygen Species (ROS), which induce hypermutation in a significant number of samples, and appear to be affected by severe purifying selection. Conversely, several mutations linked to low-rate mutational processes appear to transit to clonality in the population, eventually leading to the definition of new viral genotypes and to an increase of overall genomic diversity. Finally, we demonstrate that a high number of variants are observed in samples associated to independent lineages, likely due to signature-related mutational hotspots or to positive selection.", "qid": 40, "docid": "7se14455", "rank": 37, "score": 0.7628751993179321}, {"content": "Title: The genomic variation landscape of globally-circulating clades of SARS-CoV-2 defines a genetic barcoding scheme Content: We describe fifteen major mutation events from 2,058 high-quality SARS-CoV-2 genomes deposited up to March 31st, 2020. These events define five major clades (G, I, S, D and V) of globally-circulating viral populations, representing 85.7% of all sequenced cases, which we can identify using a 10 nucleotide genetic classifier or barcode. We applied this barcode to 4,000 additional genomes deposited between March 31st and April 15th and classified successfully 95.6% of the clades demonstrating the utility of this approach. An analysis of amino acid variation in SARS-CoV-2 ORFs provided evidence of substitution events in the viral proteins involved in both host-entry and genome replication. The systematic monitoring of dynamic changes in the SARS-CoV-2 genomes of circulating virus populations over time can guide therapeutic and prophylactic strategies to manage and contain the virus and, also, with available efficacious antivirals and vaccines, aid in the monitoring of circulating genetic diversity as we proceed towards elimination of the agent. The barcode will add the necessary genetic resolution to facilitate tracking and monitoring of infection clusters to distinguish imported and indigenous cases and thereby aid public health measures seeking to interrupt transmission chains without the requirement for real-time complete genomes sequencing.", "qid": 40, "docid": "drqhuhk4", "rank": 38, "score": 0.762823760509491}, {"content": "Title: Evolutionary and structural analyses of SARS-CoV-2 D614G spike protein mutation now documented worldwide Content: The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared on March 11, 2020 by the World Health Organization. As of the 31st of May, 2020, there have been more than 6 million COVID-19 cases diagnosed worldwide and over 370,000 deaths, according to Johns Hopkins. Thousands of SARS-CoV-2 strains have been sequenced to date, providing a valuable opportunity to investigate the evolution of the virus on a global scale. We performed a phylogenetic analysis of over 1,225 SARS-CoV-2 genomes spanning from late December 2019 to mid-March 2020. We identified a missense mutation, D614G, in the spike protein of SARS-CoV-2, which has emerged as a predominant clade in Europe (954 of 1,449 (66%) sequences) and is spreading worldwide (1,237 of 2,795 (44%) sequences). Molecular dating analysis estimated the emergence of this clade around mid-to-late January (10 - 25 January) 2020. We also applied structural bioinformatics to assess D614G potential impact on the virulence and epidemiology of SARS-CoV-2. In silico analyses on the spike protein structure suggests that the mutation is most likely neutral to protein function as it relates to its interaction with the human ACE2 receptor. The lack of clinical metadata available prevented our investigation of association between viral clade and disease severity phenotype. Future work that can leverage clinical outcome data with both viral and human genomic diversity is needed to monitor the pandemic.", "qid": 40, "docid": "zu46bdpu", "rank": 39, "score": 0.7624744772911072}, {"content": "Title: SARS-CoV2 envelope protein: Non-synonymous mutations and its consequences Content: Abstract In the NCBI database, as on June 6, 2020, total number of available complete genome sequences of SARS-CoV2 across the world is 3617. The envelope protein of SARS-CoV2 possesses several non-synonymous mutations over the transmembrane domain and (C)-terminus in 15 (0.414%) genomes among 3617 available SARS-CoV2 genomes. More precisely, it is to be mentioned that 10(0.386%) out of 2588 genomes from the USA, 3(0.806%) from Asia, 1 (0.348%) from Europe and 1 (0.274%) from Oceania contain the missense mutations over the envelope proteins of SARS-CoV2 genomes. The C-terminus motif DLLV has been changed to DFLV and YLLV in the proteins QJR88103 (Australia: Victoria) and QKI36831 (China: Guangzhou) respectively, which might affect the binding of this motif with the host protein PALS1.", "qid": 40, "docid": "gnrnsxej", "rank": 40, "score": 0.7622435092926025}, {"content": "Title: Comment on \u201cGenetic variants and source of introduction of SARS\u2010CoV\u20102 in South America\u201d Content: I read with great interest a recent study by Poterico and Mestanza1 who described mutations in 30 SARS-CoV-2 genomes from South American countries (Argentina, Brazil, Chile, Colombia, Ecuador, and Peru) This article is protected by copyright. All rights reserved.", "qid": 40, "docid": "09r8xd0u", "rank": 41, "score": 0.7622230052947998}, {"content": "Title: Genetic analysis of SARS-CoV-2 strains collected from North Africa: viral origins and mutational spectrum Content: In Morocco two waves of SARS-CoV-2 infections have been recorded. The first one occurred from March 02, 2020 with infections mostly imported from Europe and the second one dominated by local infections. At the time of writing, the genetic diversity of Moroccan isolates of SARS-CoV-2 has not yet been reported. The present study aimed to analyze first the genomic variation of the twenty-eight Moroccan strains of SARS-CoV-2 isolated from March 03, 2020 to May 15, 2020, to compare their distributions with twelve other viral genomes from North Africa as well as to identify their possible sources. Our finding revealed 61 mutations in the Moroccan genomes of SARS-CoV-2 compared to the reference sequence Wuhan-Hu-1/2019, of them 23 (37.7%) were present in two or more genomes. Focusing on non-synonymous mutations, 29 (47.54%) were distributed in five genes (ORF1ab, spike, membrane, nucleocapsid and ORF3a) with variable frequencies. The non-structural protein coding regions nsp3-Multi domain and nsp12-RdRp of the ORF1ab gene harbored more mutations, with six for each. The comparison of genetic variants of fourty North African strains revealed that two non-synonymous mutations D614G (in spike) and Q57H (in ORF3a) were common in four countries (Morocco, Tunisia, Algeria and Egypt), with a prevalence of 92.5% (n = 37) and 42.5% (n = 17), respectively, of the total genomes. Phylogenetic analysis showed that the Moroccan and Tunisian SARS-CoV-2 strains were closely related to those from different origins (Asia, Europe, North and South America) and distributed in different distinct subclades. This could indicate different sources of infection with no specific strain dominating yet in in these countries. These results have the potential to lead to new comprehensive investigations combining genomic data, epidemiological information and the clinical characteristics of patients with SARS-CoV-2.", "qid": 40, "docid": "8871aifz", "rank": 42, "score": 0.7620159983634949}, {"content": "Title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach Content: The newly identified SARS-CoV-2 has now been reported from around 183 countries with more than a million confirmed human cases including more than 68000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins have gotten substantial attention recently. Spike glycoprotein is widely considered as a possible target to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment tools. In this study, 483 unique variations have been identified among the genomes including 25 non-synonymous mutations and one deletion in the spike protein of SARS-CoV-2. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction with receptor molecules. In addition, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on our findings, potential inhibitors can be designed and tested targeting these proposed sites of variation.", "qid": 40, "docid": "vf32wxkx", "rank": 43, "score": 0.7619578838348389}, {"content": "Title: How fast does the SARS-Cov-2 virus really mutate in heterogeneous populations? Content: We introduce the problem of determining the mutational support of genes in the SARS-Cov-2 virus and estimating the distribution of mutations within different genes using small sample sizes that do not allow for accurate maximum likelihood estimation. The mutational support refers to the unknown number of sites mutated across all strains and individual samples of the SARS-Cov-2 genome; given the high cost and limited availability of real-time polymerase chain reaction (RT-PCR) test kits, especially in early stages of infections when only a small number of genomic samples (\u223c 1000s) are available that do not allow for determining the exact degree of mutations in an RNA virus that comprises roughly 30, 000 nucleotides. Nevertheless, working with small sample sets is required in order to quickly predict the mutation rate of this and other viruses and get an insight into their transformational power. Furthermore, with the small number of samples available, it is hard to estimate the mutational landscape across different age/gender groups and geographical locations which may be of great importance in assessing different risk categories and factors influencing susceptibility to infection. To this end, we use our state-of-the art polynomial estimator techniques and the Good-Turing estimator to obtain estimates based on only roughly 1, 000 samples per category. Our analysis reveals an interesting finding: the mutational support appears to be statistically more significant in patients which appear to have lower infection rates and handle the exposure with milder symptoms, such as women and people of relatively young age (\u2264 55).", "qid": 40, "docid": "or0rfxuu", "rank": 44, "score": 0.7618824243545532}, {"content": "Title: Decoding SARS-CoV-2 Transmission and Evolution and Ramifications for COVID-19 Diagnosis, Vaccine, and Medicine Content: Tremendous effort has been given to the development of diagnostic tests, preventive vaccines, and therapeutic medicines for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much of this development has been based on the reference genome collected on January 5, 2020. Based on the genotyping of 15\u00e2\u0080\u00af140 genome samples collected up to June 1, 2020, we report that SARS-CoV-2 has undergone 8309 single mutations which can be clustered into six subtypes. We introduce mutation ratio and mutation h-index to characterize the protein conservativeness and unveil that SARS-CoV-2 envelope protein, main protease, and endoribonuclease protein are relatively conservative, while SARS-CoV-2 nucleocapsid protein, spike protein, and papain-like protease are relatively nonconservative. In particular, we have identified mutations on 40% of nucleotides in the nucleocapsid gene in the population level, signaling potential impacts on the ongoing development of COVID-19 diagnosis, vaccines, and antibody and small-molecular drugs.", "qid": 40, "docid": "lzrxdi6a", "rank": 45, "score": 0.761789083480835}, {"content": "Title: Insurgence and worldwide diffusion of genomic variants in SARS-CoV-2 genomes Content: The SARS-CoV-2 pandemic that we are currently experiencing is exerting a massive toll both in human lives and economic impact. One of the challenges we must face is to try to understand if and how different variants of the virus emerge and change their frequency in time. Such information can be extremely valuable as it may indicate shifts in aggressiveness, and it could provide useful information to trace the spread of the virus in the population. In this work we identified and traced over time 7 amino acid variants that are present with high frequency in Italy and Europe, but that were absent or present at very low frequencies during the first stages of the epidemic in China and the initial reports in Europe. The analysis of these variants helps defining 6 phylogenetic clades that are currently spreading throughout the world with changes in frequency that are sometimes very fast and dramatic. In the absence of conclusive data at the time of writing, we discuss whether the spread of the variants may be due to a prominent founder effect or if it indicates an adaptive advantage.", "qid": 40, "docid": "odtue60a", "rank": 46, "score": 0.7616252899169922}, {"content": "Title: Implications of SARS-CoV-2 mutations for genomic RNA structure and host microRNA targeting Content: The SARS-CoV-2 virus is a recently-emerged zoonotic pathogen already well adapted to transmission and replication in humans. Although the mutation rate is limited, recently introduced mutations in SARS-CoV-2 have the potential to alter viral fitness. In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson-Crick pairing, with resultant changes in predicted secondary structure. Filtering to targets matching miRNAs expressed in SARS-CoV-2 permissive host cells, we identified twelve separate target sequences in the SARS-CoV-2 genome; eight of these targets have been lost through conserved mutations. A genomic site targeted by the highly abundant miR-197-5p, overexpressed in patients with cardiovascular disease, is lost by a conserved mutation. Our results are compatible with a model that SARS-CoV-2 replication within the human host could be constrained by host miRNA defence. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineered viral attenuation and antigen presentation.", "qid": 40, "docid": "4e3cn50u", "rank": 47, "score": 0.7609705924987793}, {"content": "Title: Decoding the evolution and transmissions of the novel pneumonia coronavirus (SARS-CoV-2 / HCoV-19) using whole genomic data Content: The outbreak of COVID-19 started in mid-December 2019 in Wuhan, China. Up to 29 February 2020, SARS-CoV-2 (HCoV-19 / 2019-nCoV) had infected more than 85 000 people in the world. In this study, we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFlu(TM) database to investigate the evolution and human-to-human transmissions of SARS-CoV-2 in the first two months of the outbreak. We constructed haplotypes of the SARS-CoV-2 genomes, performed phylogenomic analyses and estimated the potential population size changes of the virus. The date of population expansion was calculated based on the expansion parameter tau (\u03c4) using the formula t=\u03c4/2u. A total of 120 substitution sites with 119 codons, including 79 non-synonymous and 40 synonymous substitutions, were found in eight coding-regions in the SARS-CoV-2 genomes. Forty non-synonymous substitutions are potentially associated with virus adaptation. No combinations were detected. The 58 haplotypes (31 found in samples from China and 31 from outside China) were identified in 93 viral genomes under study and could be classified into five groups. By applying the reported bat coronavirus genome (bat-RaTG13-CoV) as the outgroup, we found that haplotypes H13 and H38 might be considered as ancestral haplotypes, and later H1 was derived from the intermediate haplotype H3. The population size of the SARS-CoV-2 was estimated to have undergone a recent expansion on 06 January 2020, and an early expansion on 08 December 2019. Furthermore, phyloepidemiologic approaches have recovered specific directions of human-to-human transmissions and the potential sources for international infected cases.", "qid": 40, "docid": "127c5bve", "rank": 48, "score": 0.7608435153961182}, {"content": "Title: Decoding the evolution and transmissions of the novel pneumonia coronavirus (SARS-CoV-2 / HCoV-19) using whole genomic data Content: The outbreak of COVID-19 started in mid-December 2019 in Wuhan, China. Up to 29 February 2020, SARS-CoV-2 (HCoV-19 / 2019-nCoV) had infected more than 85 000 people in the world. In this study, we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFlu TM database to investigate the evolution and human-to-human transmissions of SARS-CoV-2 in the first two months of the outbreak. We constructed haplotypes of the SARS-CoV-2 genomes, performed phylogenomic analyses and estimated the potential population size changes of the virus. The date of population expansion was calculated based on the expansion parameter tau ( &#964;) using the formula t= &#964;/2 u. A total of 120 substitution sites with 119 codons, including 79 non-synonymous and 40 synonymous substitutions, were found in eight coding-regions in the SARS-CoV-2 genomes. Forty non-synonymous substitutions are potentially associated with virus adaptation. No combinations were detected. The 58 haplotypes (31 found in samples from China and 31 from outside China) were identified in 93 viral genomes under study and could be classified into five groups. By applying the reported bat coronavirus genome (bat-RaTG13-CoV) as the outgroup, we found that haplotypes H13 and H38 might be considered as ancestral haplotypes, and later H1 was derived from the intermediate haplotype H3. The population size of the SARS-CoV-2 was estimated to have undergone a recent expansion on 06 January 2020, and an early expansion on 08 December 2019. Furthermore, phyloepidemiologic approaches have recovered specific directions of human-to-human transmissions and the potential sources for international infected cases.", "qid": 40, "docid": "gy78e87y", "rank": 49, "score": 0.7608269453048706}, {"content": "Title: Mutation Patterns of Human SARS-CoV-2 and Bat RaTG13 Coronavirus Genomes Are Strongly Biased Towards C>U Transitions, Indicating Rapid Evolution in Their Hosts Content: The pandemic caused by the spread of SARS-CoV-2 has led to considerable interest in its evolutionary origin and genome structure. Here, we analyzed mutation patterns in 34 human SARS-CoV-2 isolates and a closely related RaTG13 isolated from Rhinolophus affinis (a horseshoe bat). We also evaluated the CpG dinucleotide contents in SARS-CoV-2 and other human and animal coronavirus genomes. Out of 1136 single nucleotide variations (~4% divergence) between human SARS-CoV-2 and bat RaTG13, 682 (60%) can be attributed to C>U and U>C substitutions, far exceeding other types of substitutions. An accumulation of C>U mutations was also observed in SARS-CoV2 variants that arose within the human population. Globally, the C>U substitutions increased the frequency of codons for hydrophobic amino acids in SARS-CoV-2 peptides, while U>C substitutions decreased it. In contrast to most other coronaviruses, both SARS-CoV-2 and RaTG13 exhibited CpG depletion in their genomes. The data suggest that C-to-U conversion mediated by C deamination played a significant role in the evolution of the SARS-CoV-2 coronavirus. We hypothesize that the high frequency C>U transitions reflect virus adaptation processes in their hosts, and that SARS-CoV-2 could have been evolving for a relatively long period in humans following the transfer from animals before spreading worldwide.", "qid": 40, "docid": "k4l759k2", "rank": 50, "score": 0.7607660293579102}, {"content": "Title: Mutation Patterns of Human SARS-CoV-2 and Bat RaTG13 Coronavirus Genomes Are Strongly Biased Towards C>U Transitions, Indicating Rapid Evolution in Their Hosts. Content: The pandemic caused by the spread of SARS-CoV-2 has led to considerable interest in its evolutionary origin and genome structure. Here, we analyzed mutation patterns in 34 human SARS-CoV-2 isolates and a closely related RaTG13 isolated from Rhinolophus affinis (a horseshoe bat). We also evaluated the CpG dinucleotide contents in SARS-CoV-2 and other human and animal coronavirus genomes. Out of 1136 single nucleotide variations (~4% divergence) between human SARS-CoV-2 and bat RaTG13, 682 (60%) can be attributed to C>U and U>C substitutions, far exceeding other types of substitutions. An accumulation of C>U mutations was also observed in SARS-CoV2 variants that arose within the human population. Globally, the C>U substitutions increased the frequency of codons for hydrophobic amino acids in SARS-CoV-2 peptides, while U>C substitutions decreased it. In contrast to most other coronaviruses, both SARS-CoV-2 and RaTG13 exhibited CpG depletion in their genomes. The data suggest that C-to-U conversion mediated by C deamination played a significant role in the evolution of the SARS-CoV-2 coronavirus. We hypothesize that the high frequency C>U transitions reflect virus adaptation processes in their hosts, and that SARS-CoV-2 could have been evolving for a relatively long period in humans following the transfer from animals before spreading worldwide.", "qid": 40, "docid": "ox7xetlq", "rank": 51, "score": 0.7607659697532654}, {"content": "Title: Temporal evolution and adaptation of SARS-COV 2 codon usage Content: The outbreak of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has caused an unprecedented pandemic. Since the first sequenced whole-genome of SARS-CoV-2 on January 2020, the identification of its genetic variants has become crucial in tracking and evaluating their spread across the globe. In this study, we compared 15,259 SARS-CoV-2 genomes isolated from 60 countries since the outbreak of this novel coronavirus with the first sequenced genome in Wuhan to quantify the evolutionary divergence of SARS-CoV-2. Thus, we compared the codon usage patterns, every two weeks, of 13 of SARS-CoV-2 genes encoding for the membrane protein (M), envelope (E), spike surface glycoprotein (S), nucleoprotein (N), non-structural 3C-like proteinase (3CLpro), ssRNA-binding protein (RBP), 2\u2019-O-ribose methyltransferase (OMT), endoRNase (RNase), helicase, RNA-dependent RNA polymerase (RdRp), Nsp7, Nsp8, and exonuclease ExoN. As a general rule, we find that SARS-CoV-2 genome tends to diverge over time by accumulating mutations on its genome and, specifically, on the coding sequences for proteins N and S. Interestingly, different patterns of codon usage were observed among these genes. Genes S, Nsp7, NSp8, tend to use a norrower set of synonymous codons that are better optimized to the human host. Conversely, genes E and M consistently use a broader set of synonymous codons, which does not vary with respect to the reference genome. We identified key SARS-CoV-2 genes (S, N, ExoN, RNase, RdRp, Nsp7 and Nsp8) suggested to be causally implicated in the virus adaptation to the human host.", "qid": 40, "docid": "xh41koro", "rank": 52, "score": 0.7605058550834656}, {"content": "Title: Mutational patterns correlate with genome organization in SARS and other coronaviruses Content: Abstract Focused efforts by several international laboratories have resulted in the sequencing of the genome of the causative agent of severe acute respiratory syndrome (SARS), novel coronavirus SARS-CoV, in record time. Using cumulative skew diagrams, I found that mutational patterns in the SARS-CoV genome were strikingly different from other coronaviruses in terms of mutation rates, although they were in general agreement with the model of the coronavirus lifecycle. These findings might be relevant for the development of sequence-based diagnostics and the design of agents to treat SARS.", "qid": 40, "docid": "g68g6xxu", "rank": 53, "score": 0.7603905200958252}, {"content": "Title: Decoding SARS-CoV-2 transmission, evolution and ramification on COVID-19 diagnosis, vaccine, and medicine Content: Tremendous effort has been given to the development of diagnostic tests, preventive vaccines, and therapeutic medicines for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much of this development has been based on the reference genome collected on January 5, 2020. Based on the genotyping of 6156 genome samples collected up to April 24, 2020, we report that SARS-CoV-2 has had 4459 alarmingly mutations which can be clustered into five subtypes. We introduce mutation ratio and mutation $h$-index to characterize the protein conservativeness and unveil that SARS-CoV-2 envelope protein, main protease, and endoribonuclease protein are relatively conservative, while SARS-CoV-2 nucleocapsid protein, spike protein, and papain-like protease are relatively non-conservative. In particular, the nucleocapsid protein has more than half its genes changed in the past few months, signaling devastating impacts on the ongoing development of COVID-19 diagnosis, vaccines, and drugs.", "qid": 40, "docid": "u6ewlh16", "rank": 54, "score": 0.7597376108169556}, {"content": "Title: Analysis of SARS-CoV-2 Genomes from Southern California Reveals Community Transmission Pathways in the Early Stage of the US COVID-19 Pandemic Content: Given the higher mortality rate and widespread phenomenon of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) within the United States (US) population, understanding the mutational pattern of SARS CoV-2 has global implications for detection and therapy to prevent further escalation. Los Angeles has become an epicenter of the SARS-CoV-2 pandemic in the US. Efforts to contain the spread of SARS-CoV-2 require identifying its genetic and geographic variation and understanding the drivers of these differences. For the first time, we report genetic characterization of SARS-CoV-2 genome isolates in the Los Angeles population using targeted next generation sequencing (NGS). Samples collected at Cedars Sinai Medical Center were collected from patients with confirmed SARS-CoV-2 infection. We identified and diagnosed 192 patients by our in-house qPCR assay. In this population, the highest frequency variants were in known mutations in the 5'UTR, AA193 protein, RdRp and the spike glycoprotein. SARS-CoV-2 transmission within the local community was tracked by integrating mutation data with patient postal codes with two predominant community spread clusters being identified. Notably, significant viral genomic diversity was identified. Less than 10 percent of the Los Angeles community samples resembled published mutational profiles of SARS-CoV-2 genomes from China, while >50 percent of the isolates shared closely similarities to those from New York State. Based on these findings we conclude SARS-CoV-2 was likely introduced into the Los Angeles community predominantly from New York State but also via multiple other independent transmission routes including but not limited to Washington State and China.", "qid": 40, "docid": "h3ftgzqz", "rank": 55, "score": 0.7595164775848389}, {"content": "Title: Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility. Content: Direct massively parallel sequencing of SARS-CoV-2 genome was undertaken from nasopharyngeal and oropharyngeal swab samples of infected individuals in Eastern India. Seven of the isolates belonged to the A2a clade, while one belonged to the B4 clade. Specific mutations, characteristic of the A2a clade, were also detected, which included the P323L in RNA-dependent RNA polymerase and D614G in the Spike glycoprotein. Further, our data revealed emergence of novel subclones harbouring nonsynonymous mutations, viz. G1124V in Spike (S) protein, R203K, and G204R in the nucleocapsid (N) protein. The N protein mutations reside in the SR-rich region involved in viral capsid formation and the S protein mutation is in the S2 domain, which is involved in triggering viral fusion with the host cell membrane. Interesting correlation was observed between these mutations and travel or contact history of COVID-19 positive cases. Consequent alterations of miRNA binding and structure were also predicted for these mutations. More importantly, the possible implications of mutation D614G (in SD domain) and G1124V (in S2 subunit) on the structural stability of S protein have also been discussed. Results report for the first time a bird's eye view on the accumulation of mutations in SARS-CoV-2 genome in Eastern India.", "qid": 40, "docid": "02cfyuf4", "rank": 56, "score": 0.7591993808746338}, {"content": "Title: Presence of mismatches between diagnostic PCR assays and coronavirus SARS-CoV-2 genome Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2;initially named as 2019-nCoV) is responsible for the recent COVID-19 pandemic and polymerase chain reaction (PCR) is the current standard method for its diagnosis from patient samples This study conducted a reassessment of published diagnostic PCR assays, including those recommended by the World Health Organization (WHO), through the evaluation of mismatches with publicly available viral sequences An exhaustive evaluation of the sequence variability within the primer/probe target regions of the viral genome was performed using more than 17 000 viral sequences from around the world The analysis showed the presence of mutations/mismatches in primer/probe binding regions of 7 assays out of 27 assays studied A comprehensive bioinformatics approach for in silico inclusivity evaluation of PCR diagnostic assays of SARS-CoV-2 was validated using freely available software programs that can be applied to any diagnostic assay of choice These findings provide potentially important information for clinicians, laboratory professionals and policy-makers", "qid": 40, "docid": "a6m76xrn", "rank": 57, "score": 0.7591038346290588}, {"content": "Title: Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting Content: The SARS-CoV-2 virus is a recently-emerged zoonotic pathogen already well adapted to transmission and replication in humans. Although the mutation rate is limited, recently introduced mutations in SARS-CoV-2 have the potential to alter viral fitness. In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson-Crick pairing, with resultant changes in predicted secondary structure. Filtering to targets matching miRNAs expressed in SARS-CoV-2-permissive host cells, we identified ten separate target sequences in the SARS-CoV-2 genome; three of these targets have been lost through conserved mutations. A genomic site targeted by the highly abundant miR-197-5p, overexpressed in patients with cardiovascular disease, is lost by a conserved mutation. Our results are compatible with a model that SARS-CoV-2 replication within the human host is constrained by host miRNA defences. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineering conditional attenuation to vaccine development, as well as providing a better understanding of viral tropism and pathogenesis.", "qid": 40, "docid": "eri92ki6", "rank": 58, "score": 0.7586573362350464}, {"content": "Title: Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting. Content: The SARS-CoV-2 virus is a recently-emerged zoonotic pathogen already well adapted to transmission and replication in humans. Although the mutation rate is limited, recently introduced mutations in SARS-CoV-2 have the potential to alter viral fitness. In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson-Crick pairing, with resultant changes in predicted secondary structure. Filtering to targets matching miRNAs expressed in SARS-CoV-2-permissive host cells, we identified ten separate target sequences in the SARS-CoV-2 genome; three of these targets have been lost through conserved mutations. A genomic site targeted by the highly abundant miR-197-5p, overexpressed in patients with cardiovascular disease, is lost by a conserved mutation. Our results are compatible with a model that SARS-CoV-2 replication within the human host is constrained by host miRNA defences. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineering conditional attenuation to vaccine development, as well as providing a better understanding of viral tropism and pathogenesis.", "qid": 40, "docid": "8cex7qi4", "rank": 59, "score": 0.7586573362350464}, {"content": "Title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach Content: The newly identified SARS-CoV-2 has now been reported from around 185 countries with more than a million confirmed human cases including more than 120,000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins need to be explored to understand the biology of the virus. Spike glycoprotein is one of the major targets to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment. In this study, 483 unique variations have been identified among the genomes of SARS-CoV-2 including 25 nonsynonymous mutations and one deletion in the spike (S) protein. Among the 26 variations detected in S, 12 variations were located at the N-terminal domain (NTD) and 6 variations at the receptor-binding domain (RBD) which might alter the interaction of S protein with the host receptor angiotensin-converting enzyme 2 (ACE2). Besides, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on results reported herein, potential inhibitors against S protein can be designed by considering these variations and their impact on protein structure.", "qid": 40, "docid": "c5fygzvz", "rank": 60, "score": 0.7584526538848877}, {"content": "Title: The origin and underlying driving forces of the SARS-CoV-2 outbreak Content: The spread of SARS-CoV-2 since December 2019 has become a pandemic and impacted many aspects of human society. Here, we analyzed genetic variation of SARS-CoV-2 and its related coronavirus and found the evidence of intergenomic recombination. After correction for mutational bias, analysis of 137 SARS-CoV-2 genomes as of 2/23/2020 revealed the excess of low frequency mutations on both synonymous and nonsynonymous sites which is consistent with recent origin of the virus. In contrast to adaptive evolution previously reported for SARS-CoV in its brief epidemic in 2003, our analysis of SARS-CoV-2 genomes shows signs of relaxation of selection. The sequence similarity of the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression. Therefore, SARS-CoV-2 might have cryptically circulated within humans for years before being recently noticed. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and reveal critical steps required for effective spreading. Two mutations, 84S in orf8 protein and 251V in orf3 protein, occurred coincidentally with human intervention. The 84S first appeared on 1/5/2020 and reached a plateau around 1/23/2020, the lockdown of Wuhan. 251V emerged on 1/21/2020 and rapidly increased its frequency. Thus, the roles of these mutations on infectivity need to be elucidated. Genetic diversity of SARS-CoV-2 collected from China was two time higher than those derived from the rest of the world. In addition, in network analysis, haplotypes collected from Wuhan city were at interior and have more mutational connections, both of which are consistent with the observation that the outbreak of cov-19 was originated from China. SUMMARY In contrast to adaptive evolution previously reported for SARS-CoV in its brief epidemic, our analysis of SARS-CoV-2 genomes shows signs of relaxation of selection. The sequence similarity of the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression. Therefore, SARS-CoV-2 might have cryptically circulated within humans for years before being recently noticed. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and reveal critical steps required for effective spreading. Two mutations, 84S in orf8 protein and 251V in orf3 protein, occurred coincidentally with human intervention. The 84S first appeared on 1/5/2020 and reached a plateau around 1/23/2020, the lockdown of Wuhan. 251V emerged on 1/21/2020 and rapidly increased its frequency. Thus, the roles of these mutations on infectivity need to be elucidated.", "qid": 40, "docid": "bawgldfi", "rank": 61, "score": 0.7582876682281494}, {"content": "Title: Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility Content: Direct massively parallel sequencing of SARS-CoV-2 genome was undertaken from nasopharyngeal and oropharyngeal swab samples of infected individuals in Eastern India. Seven of the isolates belonged to the A2a clade, while one belonged to the B4 clade. Specific mutations, characteristic of the A2a clade, were also detected, which included the P323L in RNA-dependent RNA polymerase and D614G in the Spike glycoprotein. Further, our data revealed emergence of novel subclones harbouring nonsynonymous mutations, viz. G1124V in Spike (S) protein, R203K, and G204R in the nucleocapsid (N) protein. The N protein mutations reside in the SR-rich region involved in viral capsid formation and the S protein mutation is in the S(2) domain, which is involved in triggering viral fusion with the host cell membrane. Interesting correlation was observed between these mutations and travel or contact history of COVID-19 positive cases. Consequent alterations of miRNA binding and structure were also predicted for these mutations. More importantly, the possible implications of mutation D614G (in S(D) domain) and G1124V (in S(2) subunit) on the structural stability of S protein have also been discussed. Results report for the first time a bird\u2019s eye view on the accumulation of mutations in SARS-CoV-2 genome in Eastern India. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12038-020-00046-1) contains supplementary material, which is available to authorized users.", "qid": 40, "docid": "6dsx7pey", "rank": 62, "score": 0.7580541968345642}, {"content": "Title: Quantification of Intra-Host Genomic Diversity of SARS-CoV-2 Allows a High-Resolution Characterization of Viral Evolution and Reveals Functionally Convergent Variants Content: A global cross-discipline effort is ongoing to characterize the evolution of SARS-CoV-2 virus and generate reliable epidemiological models of its diffusion. To this end, phylogenomic approaches leverage accumulating genomic mutations as barcodes to track the evolutionary history of the virus and can benefit from the surge of sequences deposited in public databases. Yet, such methods typically rely on consensus sequences representing the dominant virus lineage, whereas a complex sublineage architecture is often observed within single hosts. Furthermore, most approaches do not account for variants accumulation processes and might produce inaccurate results in condition of limited sampling, as witnessed in most countries affected by the epidemics. We introduce VERSO (Viral Evolution ReconStructiOn), a new comprehensive framework for the characterization of viral evolution and transmission from sequencing data of viral genomes. our approach accounts for accumulation of clonal mutations and uncertainty in the data, by taking advantage of the achievements of research in cancer evolution, to deliver robust phylogenomic lineage models, and exploits intra-host variant frequency profiles to characterize the sublineage similarity among samples, which may derive from uncovered infection events. The application of our approach to RNA-sequencing data of 162 SARS-CoV-2 samples generates a high-resolution model of evolution and spread, which improves recent findings on viral types and highlights the existence of patterns of co-occurrence of minor variants, revealing likely infection paths among hosts harboring the same viral lineage. The in-depth analysis of the mutational landscape of SARS-CoV-2 confirms a statistically significant increase of genomic diversity in time and identifies a number of variants that are transiting from minor to clonal state in the population. We also show that standard phylogenetic methods can produce unreliable results when handling datasets with noise and sampling limitations, as proven by the further application of VERSO to 12419 consensus sequences included in GISAID database. Notably, VERSO allows to pinpoint minor variants that might be positively or negatively selected across distinct lineages, thus driving the design of treatments and vaccines. In particular, minor variant g.29039A>U, detected in multiple viral lineages and validated on independent samples, shows that SARS-CoV-2 can lose its main Nucleocapsid immunogenic epitopes, raising concerns about the effectiveness of vaccines targeting the C-terminus of this protein. Finally, we here release the likely SARS-CoV-2 ancestral genome, obtained by resolving ambiguous SNPs that distinguish two widely-used reference genomes from human samples, by employing the Pangolin-CoV and the Bat-CoV-RaTG13 genomes. Our results show that the joint application of our framework and data-driven epidemiological models might allow to deliver a high-resolution platform for pathogen surveillance and analysis.", "qid": 40, "docid": "ea78sjcs", "rank": 63, "score": 0.7576996684074402}, {"content": "Title: MicroGMT: A Mutation Tracker for SARS-CoV-2 and Other Microbial Genome Sequences Content: With the continued spread of SARS-CoV-2 virus around the world, researchers often need to quickly identify novel mutations in newly sequenced SARS-CoV-2 genomes for studying the molecular evolution and epidemiology of the virus. We have developed a Python package, MicroGMT, which takes either raw sequence reads or assembled genome sequences as input and compares against database sequences to identify and characterize indels and point mutations. Although our default setting is optimized for SARS-CoV-2 virus, the package can be also applied to any other microbial genomes. The software is freely available at Github URL https://github.com/qunfengdong/MicroGMT.", "qid": 40, "docid": "ypwo98k7", "rank": 64, "score": 0.7576770186424255}, {"content": "Title: Rampant C\u2192U Hypermutation in the Genomes of SARS-CoV-2 and Other Coronaviruses: Causes and Consequences for Their Short- and Long-Term Evolutionary Trajectories Content: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has motivated an intensive analysis of its molecular epidemiology following its worldwide spread. To understand the early evolutionary events following its emergence, a data set of 985 complete SARS-CoV-2 sequences was assembled. Variants showed a mean of 5.5 to 9.5 nucleotide differences from each other, consistent with a midrange coronavirus substitution rate of 3 \u00d7 10(\u22124) substitutions/site/year. Almost one-half of sequence changes were C\u2192U transitions, with an 8-fold base frequency normalized directional asymmetry between C\u2192U and U\u2192C substitutions. Elevated ratios were observed in other recently emerged coronaviruses (SARS-CoV, Middle East respiratory syndrome [MERS]-CoV), and decreasing ratios were observed in other human coronaviruses (HCoV-NL63, -OC43, -229E, and -HKU1) proportionate to their increasing divergence. C\u2192U transitions underpinned almost one-half of the amino acid differences between SARS-CoV-2 variants and occurred preferentially in both 5\u2032 U/A and 3\u2032 U/A flanking sequence contexts comparable to favored motifs of human APOBEC3 proteins. Marked base asymmetries observed in nonpandemic human coronaviruses (U \u226b A > G \u226b C) and low G+C contents may represent long-term effects of prolonged C\u2192U hypermutation in their hosts. The evidence that much of sequence change in SARS-CoV-2 and other coronaviruses may be driven by a host APOBEC-like editing process has profound implications for understanding their short- and long-term evolution. Repeated cycles of mutation and reversion in favored mutational hot spots and the widespread occurrence of amino acid changes with no adaptive value for the virus represent a quite different paradigm of virus sequence change from neutral and Darwinian evolutionary frameworks and are not incorporated by standard models used in molecular epidemiology investigations. IMPORTANCE The wealth of accurately curated sequence data for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its long genome, and its low substitution rate provides a relatively blank canvas with which to investigate effects of mutational and editing processes imposed by the host cell. The finding that a large proportion of sequence change in SARS-CoV-2 in the initial months of the pandemic comprised C\u2192U mutations in a host APOBEC-like context provides evidence for a potent host-driven antiviral editing mechanism against coronaviruses more often associated with antiretroviral defense. In evolutionary terms, the contribution of biased, convergent, and context-dependent mutations to sequence change in SARS-CoV-2 is substantial, and these processes are not incorporated by standard models used in molecular epidemiology investigations.", "qid": 40, "docid": "jw6kh8os", "rank": 65, "score": 0.7574714422225952}, {"content": "Title: Genome-wide variations of SARS-CoV-2 infer evolution relationship and transmission route Content: In the epidemic evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the issues of mutation, origin, typing and the effect of mutation on molecular detection remain to be unrevealed. In order to identify the evolutionary relationship of SARS-CoV-2 and evaluate the detection efficiency of primers that are currently used in different countries, we retrieved genomic sequences of 373 SARS-CoV-2 strains from multiple databases and performed genome-wide variation analysis. According to the nucleotide C28144T variation, the SARS-CoV-2 can be divided into group A (117 strains) and group B (256 strains). The spike protein gene (S gene) coding region 1841 (total 23403) A1841G, formed a B1 subgroup (40 strains) in group B, of which 30 strains were from European and American countries in March (especially Washington, USA). These mutations are likely to be influenced by the environment or the immunization selection pressure of different populations. Although the mutation is not in the receptor binding region (RBD) and alkaline cleavage region, it may also affect the ability of transmission and pathogenicity; however, the significance is not yet clear. As the ratio of A / B strains in the epidemic months showed an increasing trend (0.35: 1 in January, 0.62: 1 in February and 0.76: 1 in March), it seems that the transmissibility of group A strains becomes stronger with time. Based on the variation of 11 nucleotide sites during the epidemic process, it is speculated that the Washington strain is more like an ancestor type, and the Wuhan strain is the offspring of the group A virus strain. By comparing the detection capabilities of primers in different countries, the SARS-CoV-2 nucleotide variation may only affect molecular detection of very few strains. The differences in the transmissibility, pathogenicity and clinical manifestations of different types of strains require further investigations.", "qid": 40, "docid": "blqzi69t", "rank": 66, "score": 0.7570413947105408}, {"content": "Title: Decoding the lethal effect of SARS-CoV-2 (novel coronavirus) strains from global perspective: molecular pathogenesis and evolutionary divergence Content: Background COVID-19 is a disease with global public health emergency that have shook the world since its\u2019 first detection in China in December, 2019. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is the pathogen responsible behind this pandemic. The lethality of different viral strains is found to vary in different geographical locations but the molecular mechanism is yet to be known. Methods Available data of whole genome sequencing of different viral strains published by different countries were retrieved and then analysed using Multiple Sequence Alignment and Pair-wise Sequence Alignment leading to Phylogenetic tree construction. Each location and the corresponding genetic variations were screened in depth. Then the variations are analysed at protein level giving special emphasis on Non Synonymous amino acid substitutions. The fatality rates in different countries were matched against the mutation number, rarity of the nucleotide alterations and functional impact of the Non Synonymous changes at protein level, separately and in combination. Findings All the viral strains have been found to evolve from the viral strain of Taiwan (MT192759) which is 100% identical with the ancestor SARS-CoV-2 sequences of Wuhan (NC 045512.2; submitted on 5th Jan, 2020). Transition from C to T (C>T) is the most frequent mutation in this viral genome and mutations A>T, G>A, T>A are the rarest ones, found in countries with maximum fatality rate i.e Italy, Spain and Sweden. 20 Non Synonymous mutations are located in viral genome spanning Orf1ab polyprotein, Surface glycoprotein, Nucleocapsid protein etc. The functional effect on the structure and function of the protein can favourably or unfavourably interact with the host body. Interpretation The fatality outcome depends on three important factors (a) number of mutation (b) rarity of the allelic variation and (c) functional consequence of the mutation at protein level. The molecular divergence, evolved from the ancestral strain (S) lead to extremely lethal (E), lethal(L) and non lethal (N) strains with the involvement of an Intermediate strain(I).", "qid": 40, "docid": "qvz63m93", "rank": 67, "score": 0.7567659616470337}, {"content": "Title: Evidence of Increasing Diversification of Emerging SARS-CoV-2 Strains Content: BACKGROUND: On January 30th, 2020, an outbreak of atypical pneumonia caused by a novel Betacoronavirus (\u00dfCoV), named SARS-CoV-2, was declared a public health emergency of international concern by the World Health Organization. For this reason, a detailed evolutionary analysis of SARS-CoV-2 strains currently circulating in different geographic regions of the world was performed. METHODS: A compositional analysis as well as a Bayesian coalescent analysis of complete genome sequences of SARS-CoV-2 strains recently isolated in Europe, North America, South America and Asia was performed. RESULTS: The results of these studies revealed a diversification of SARS-CoV-2 strains in three different genetic clades. Co-circulation of different clades in different countries, as well as different genetic lineages within different clades were observed. The time of the most recent common ancestor (tMRCA) was established to be around November 1, 2019. A mean rate of evolution of 6.57 x 10-4 substitutions per site per year was found. A significant migration rate per genetic lineage per year from Europe to South America was also observed. CONCLUSION: The results of these studies revealed an increasing diversification of SARS-CoV-2 strains. High evolutionary rates and fast population growth characterizes the population dynamics of SARS-CoV-2 strains. This article is protected by copyright. All rights reserved.", "qid": 40, "docid": "1h1hwbos", "rank": 68, "score": 0.7566310167312622}, {"content": "Title: Molecular analysis of several in-house rRT-PCR protocols for SARS-CoV-2 detection in the context of genetic variability of the virus in Colombia. Content: The COVID-19 pandemic caused by SARS-CoV-2 is a public health problem unprecedented in the recent history of humanity. Different in-house real-time RT-PCR (rRT-PCR) methods for SARS-CoV-2 diagnosis and the appearance of genomes with mutations in primer regions have been reported. Hence, whole-genome data from locally-circulating SARS-CoV-2 strains contribute to the knowledge of its global variability and the development and fine-tuning of diagnostic protocols. To describe the genetic variability of Colombian SARS-CoV-2 genomes in hybridization regions of oligonucleotides of the main in-house methods for SARS-CoV-2 detection, RNA samples with confirmed SARS-CoV-2 molecular diagnosis were processed through next-generation sequencing. Primers/probes sequences from 13 target regions for SARS-CoV-2 detection suggested by 7 institutions and consolidated by WHO during the early stage of the pandemic were aligned with Muscle tool to assess the genetic variability potentially affecting their performance. Finally, the corresponding codon positions at the 3' end of each primer, the open reading frame inspection was identified for each gene/protein product. Complete SARS-CoV-2 genomes were obtained from 30 COVID-19 cases, representative of the current epidemiology in the country. Mismatches between at least one Colombian sequence and five oligonucleotides targeting the RdRP and N genes were observed. The 3' end of 4 primers aligned to the third codon position, showed high risk of nucleotide substitution and potential mismatches at this critical position. Genetic variability was detected in Colombian SARS-CoV-2 sequences in some of the primer/probe regions for in-house rRT-PCR diagnostic tests available at WHO COVID-19 technical guidelines; its impact on the performance and rates of false-negative results should be experimentally evaluated. The genomic surveillance of SARS-CoV-2 is highly recommended for the early identification of mutations in critical regions and to issue recommendations on specific diagnostic tests to ensure the coverage of locally-circulating genetic variants.", "qid": 40, "docid": "gs9zno1d", "rank": 69, "score": 0.7565672993659973}, {"content": "Title: Molecular analysis of several in-house rRT-PCR protocols for SARS-CoV-2 detection in the context of genetic variability of the virus in Colombia Content: The COVID-19 pandemic caused by SARS-CoV-2 is a public health problem unprecedented in the recent history of humanity. Different in-house real-time RT-PCR (rRT-PCR) methods for SARS-CoV-2 diagnosis and the appearance of genomes with mutations in primer regions have been reported. Hence, whole-genome data from locally-circulating SARS-CoV-2 strains contribute to the knowledge of its global variability and the development and fine tuning of diagnostic protocols. To describe the genetic variability of Colombian SARS-CoV-2 genomes in hybridization regions of oligonucleotides of the main in-house methods for SARS-CoV-2 detection, RNA samples with confirmed SARS-CoV-2 molecular diagnosis were processed through next-generation sequencing. Primers/probes sequences from 13 target regions for SARS-CoV-2 detection suggested by 7 institutions and consolidated by WHO during the early stage of the pandemic were aligned with Muscle tool to assess the genetic variability potentially affecting their performance. Finally, the corresponding codon positions at the 3' end of each primer, the open reading frame inspection was identified for each gene/protein product. Complete SARS-CoV-2 genomes were obtained from 30 COVID-19 cases, representative of the current epidemiology in the country. Mismatches between at least one Colombian sequence and five oligonucleotides targeting the RdRP and N genes were observed. The 3' end of 4 primers aligned to the third codon position, showed high risk of nucleotide substitution and potential mismatches at this critical position. Genetic variability was detected in Colombian SARS-CoV-2 sequences in some of the primer/probe regions for in-house rRT-PCR diagnostic tests available at WHO COVID-19 technical guidelines; its impact on the performance and rates of false-negative results should be experimentally evaluated. The genomic surveillance of SARS-CoV-2 is highly recommended for the early identification of mutations in critical regions and to issue recommendations on specific diagnostic tests to ensure the coverage of locally-circulating genetic variants.", "qid": 40, "docid": "vwzdijgg", "rank": 70, "score": 0.7561404705047607}, {"content": "Title: The establishment of reference sequence for SARS\u2010CoV\u20102 and variation analysis Content: Starting around December 2019, an epidemic of pneumonia, which was named COVID\u201019 by the World Health Organization, broke out in Wuhan, China, and is spreading throughout the world. A new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses was soon found to be the cause. At present, the sensitivity of clinical nucleic acid detection is limited, and it is still unclear whether it is related to genetic variation. In this study, we retrieved 95 full\u2010length genomic sequences of SARAS\u2010CoV\u20102 strains from the National Center for Biotechnology Information and GISAID databases, established the reference sequence by conducting multiple sequence alignment and phylogenetic analyses, and analyzed sequence variations along the SARS\u2010CoV\u20102 genome. The homology among all viral strains was generally high, among them, 99.99% (99.91%\u2010100%) at the nucleotide level and 99.99% (99.79%\u2010100%) at the amino acid level. Although overall variation in open\u2010reading frame (ORF) regions is low, 13 variation sites in 1a, 1b, S, 3a, M, 8, and N regions were identified, among which positions nt28144 in ORF 8 and nt8782 in ORF 1a showed mutation rate of 30.53% (29/95) and 29.47% (28/95), respectively. These findings suggested that there may be selective mutations in SARS\u2010COV\u20102, and it is necessary to avoid certain regions when designing primers and probes. Establishment of the reference sequence for SARS\u2010CoV\u20102 could benefit not only biological study of this virus but also diagnosis, clinical monitoring and intervention of SARS\u2010CoV\u20102 infection in the future.", "qid": 40, "docid": "41ogljo8", "rank": 71, "score": 0.7561221122741699}, {"content": "Title: Substitutions in Spike and Nucleocapsid proteins of SARS-CoV-2 circulating in Colombia Content: Introduction: SARS-CoV-2 is a new member of the genus Betacoronavirus, responsible for the COVID-19 pandemics. The virus crossed the species barrier and established in the human population due to its ability to exploit the ACE receptor for virus entry, which is present and abundant in several tissues, including the lung and respiratory tract, gastrointestinal tract and hearth. Virus interaction with the cellular receptor is mediated by the surface protein, known as Spike. Another structural protein of major importance in the Nucleocapsid, directly interacting with the viral RNA to form the ribonucleocapsid, considered a multifunctional protein, and being the target of the most molecular diagnostics assays. Objective: To describe the frequency of substitutions in spike and nucleocapsid proteins of SARS-CoV-2 circulating in Colombia and evaluate the frequency of these substitutions in SARS-CoV-2 sequences from other countries of South America. Materials and methods: Samples of 43 patients were included for viral RNA detection by real-time RT-PCR using the Charite-Berlin protocol for the amplification of the SARS-CoV-2 E and RdRp genes. Genome sequences were obtained through the Oxford Nanopore and Illumina MiSeq technologies, following the artic.network \"nCoV-2019 sequencing protocol\". Available genomes were consulted from GISAID, GenBank, and Genome sequence archive (GSA) and a total of 371 genomes sequences from South America were included. The genome sequences were aligned with the Muscle tool using the MEGA X software. Substitution matrices of the Colombian sequences respect to the reference genome (NC_045512) at the nucleotide and amino acid levels were generated for the spike and nucleocapsid gene. Results: substitution D614G in the amino acid sequence of spike protein was found in 86.7% of the Colombian sequences; substitutions G181V and D936Y in 2.3%, respectively. Five substitutions were found in the nucleocapsid protein, with substitution R203K and G204R being the most frequent (13.95 %) in Colombia. The substitutions D614G in Spike and R203K-G204R in nucleocapsid have a frequency of 83% and 28% respectively in sequences from South America. Conclusion: Non-synonymous substitutions were found in the spike and nucleocapsid proteins in Colombian genomes, the most frequent being D614G in Spike and R203K-G204R in nucleocapsid. These substitutions are frequent in the genomes reported for other South American countries. It is necessary to continue with genomic surveillance of the changes in Spike and Nucleocapsid proteins during the SARS-CoV-2 pandemic in Colombia and South America, even more considering that these proteins are the most commonly used antigen in serological tests.", "qid": 40, "docid": "zb034sbv", "rank": 72, "score": 0.7552751302719116}, {"content": "Title: Identification of common deletions in the spike protein of SARS-CoV-2 Content: SARS-CoV-2 is a novel coronavirus first identified in December 2019. Notable features make SARS-CoV-2 distinct from most other previously-identified Betacoronaviruses, including the receptor binding domain of SARS-CoV-2 and a unique insertion of twelve nucleotide or four amino acids (PRRA) at the S1/S2 boundary. In this study, we identified two deletion variants of SARS-CoV-2 that either directly affect the polybasic cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN). These deletions were verified by multiple sequencing methods. In vitro results showed that the deletion of NSPRRAR likely does not affect virus replication in Vero and Vero-E6 cells, however the deletion of QTQTN may restrict late phase viral replication. The deletion of QTQTN was detected in 3 of 68 clinical samples and half of 24 in vitro isolated viruses, whilst the deletion of NSPRRAR was identified in 3 in vitro isolated viruses. Our data indicate that (i) there may be distinct selection pressures on SARS-CoV-2 replication or infection in vitro and in vivo, (ii) an efficient mechanism for deleting this region from the viral genome may exist, given that the deletion variant is commonly detected after two rounds of cell passage, and (iii) the PRRA insertion, which is unique to SARS-CoV-2, is not fixed during virus replication in vitro These findings provide information to aid further investigation of SARS-CoV-2 infection mechanisms and a better understanding of the NSPRRAR deletion variant observed here.Important notes The spike protein determines the infectivity and host range of coronaviruses. SARS-CoV-2 has two unique features in its spike protein, the receptor binding domain and an insertion of twelve nucleotides at the S1/S2 boundary resulting a furin-like cleavage site. Here, we identified two deletion variants of SARS-CoV-2 that either directly affect the furin-like cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN) and investigated these deletions in cell isolates and clinical samples. The absence of the polybasic cleavage site in SARS-CoV-2 did not affect virus replication in Vero or Vero-E6 cells. Our data indicate the PRRAR and its flanking sites are not fixed in vitro, thus there appears to be distinct selection pressures on SARS-CoV-2 sequences in vitro and in vivo Further investigation of the mechanism of generating these deletion variants and their infectivity in different animal models would improve our understanding of the origin and evolution of this virus.", "qid": 40, "docid": "7htfxqno", "rank": 73, "score": 0.7549656629562378}, {"content": "Title: Identification of common deletions in the spike protein of SARS-CoV-2. Content: SARS-CoV-2 is a novel coronavirus first identified in December 2019. Notable features make SARS-CoV-2 distinct from most other previously-identified Betacoronaviruses, including the receptor binding domain of SARS-CoV-2 and a unique insertion of twelve nucleotide or four amino acids (PRRA) at the S1/S2 boundary. In this study, we identified two deletion variants of SARS-CoV-2 that either directly affect the polybasic cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN). These deletions were verified by multiple sequencing methods. In vitro results showed that the deletion of NSPRRAR likely does not affect virus replication in Vero and Vero-E6 cells, however the deletion of QTQTN may restrict late phase viral replication. The deletion of QTQTN was detected in 3 of 68 clinical samples and half of 24 in vitro isolated viruses, whilst the deletion of NSPRRAR was identified in 3 in vitro isolated viruses. Our data indicate that (i) there may be distinct selection pressures on SARS-CoV-2 replication or infection in vitro and in vivo, (ii) an efficient mechanism for deleting this region from the viral genome may exist, given that the deletion variant is commonly detected after two rounds of cell passage, and (iii) the PRRA insertion, which is unique to SARS-CoV-2, is not fixed during virus replication in vitro These findings provide information to aid further investigation of SARS-CoV-2 infection mechanisms and a better understanding of the NSPRRAR deletion variant observed here.Important notes The spike protein determines the infectivity and host range of coronaviruses. SARS-CoV-2 has two unique features in its spike protein, the receptor binding domain and an insertion of twelve nucleotides at the S1/S2 boundary resulting a furin-like cleavage site. Here, we identified two deletion variants of SARS-CoV-2 that either directly affect the furin-like cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN) and investigated these deletions in cell isolates and clinical samples. The absence of the polybasic cleavage site in SARS-CoV-2 did not affect virus replication in Vero or Vero-E6 cells. Our data indicate the PRRAR and its flanking sites are not fixed in vitro, thus there appears to be distinct selection pressures on SARS-CoV-2 sequences in vitro and in vivo Further investigation of the mechanism of generating these deletion variants and their infectivity in different animal models would improve our understanding of the origin and evolution of this virus.", "qid": 40, "docid": "9v4uqsun", "rank": 74, "score": 0.7549656629562378}, {"content": "Title: Molecular analysis of several in-house rRT-PCR protocols for SARS-CoV-2 detection in the context of genetic variability of the virus in Colombia Content: The COVID-19 pandemic caused by SARS-CoV-2 is a public health problem unprecedented in the recent history of humanity. Different in-house real-time RT-PCR (rRT-PCR) methods for SARS-CoV-2 diagnosis and the appearance of genomes with mutations in primer regions have been reported. Hence, whole-genome data from locally-circulating SARS-CoV-2 strains contribute to the knowledge of its global variability and the development and fine tuning of diagnostic protocols. To describe the genetic variability of Colombian SARS-CoV-2 genomes in hybridization regions of oligonucleotides of the main in-house methods for SARS-CoV-2 detection, RNA samples with confirmed SARS-CoV-2 molecular diagnosis were processed through next-generation sequencing. Primers/probes sequences from 13 target regions for SARS-CoV-2 detection suggested by 7 institutions and consolidated by WHO during the early stage of the pandemic were aligned with Muscle tool to assess the genetic variability potentially affecting their performance. Finally, the corresponding codon positions at the 3\u2032 end of each primer, the open reading frame inspection was identified for each gene/protein product. Complete SARS-CoV-2 genomes were obtained from 30 COVID-19 cases, representative of the current epidemiology in the country. Mismatches between at least one Colombian sequence and five oligonucleotides targeting the RdRP and N genes were observed. The 3\u2032 end of 4 primers aligned to the third codon position, showed high risk of nucleotide substitution and potential mismatches at this critical position. Genetic variability was detected in Colombian SARS-CoV-2 sequences in some of the primer/probe regions for in-house rRT-PCR diagnostic tests available at WHO COVID-19 technical guidelines; its impact on the performance and rates of false-negative results should be experimentally evaluated. The genomic surveillance of SARS-CoV-2 is highly recommended for the early identification of mutations in critical regions and to issue recommendations on specific diagnostic tests to ensure the coverage of locally-circulating genetic variants.", "qid": 40, "docid": "kr3y2k25", "rank": 75, "score": 0.7547082901000977}, {"content": "Title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach Content: The newly identified SARS-CoV-2 has now been reported from around 185 countries with more than a million confirmed human cases including more than 120,000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins need to be explored to understand the biology of the virus. Spike glycoprotein is one of the major targets to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment. In this study, 483 unique variations have been identified among the genomes of SARS-CoV-2 including 25 nonsynonymous mutations and one deletion in the spike (S) protein. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction of S protein with the host receptor angiotensin converting enzyme-2 (ACE2). Besides, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on results reported herein, potential inhibitors against S protein can be designed by considering these variations and their impact on protein structure.", "qid": 40, "docid": "w5ytp1q7", "rank": 76, "score": 0.754660964012146}, {"content": "Title: The establishment of reference sequence for SARS-CoV-2 and variation analysis Content: Starting around December 2019, an epidemic of pneumonia, which was named COVID-19 by the World Health Organization, broke out in Wuhan, China, and is spreading throughout the world. A new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses was soon found to be the cause. At present, the sensitivity of clinical nucleic acid detection is limited, and it is still unclear whether it is related to genetic variation. In this study, we retrieved 95 full-length genomic sequences of SARAS-CoV-2 strains from the National Center for Biotechnology Information and GISAID databases, established the reference sequence by conducting multiple sequence alignment and phylogenetic analyses, and analyzed sequence variations along the SARS-CoV-2 genome. The homology among all viral strains was generally high, among them, 99.99% (99.91%-100%) at the nucleotide level and 99.99% (99.79%-100%) at the amino acid level. Although overall variation in open-reading frame (ORF) regions is low, 13 variation sites in 1a, 1b, S, 3a, M, 8, and N regions were identified, among which positions nt28144 in ORF 8 and nt8782 in ORF 1a showed mutation rate of 30.53% (29/95) and 29.47% (28/95), respectively. These findings suggested that there may be selective mutations in SARS-COV-2, and it is necessary to avoid certain regions when designing primers and probes. Establishment of the reference sequence for SARS-CoV-2 could benefit not only biological study of this virus but also diagnosis, clinical monitoring and intervention of SARS-CoV-2 infection in the future.", "qid": 40, "docid": "g1zxlaer", "rank": 77, "score": 0.7545092105865479}, {"content": "Title: Moderate mutation rate in the SARS coronavirus genome and its implications Content: BACKGROUND: The outbreak of severe acute respiratory syndrome (SARS) caused a severe global epidemic in 2003 which led to hundreds of deaths and many thousands of hospitalizations. The virus causing SARS was identified as a novel coronavirus (SARS-CoV) and multiple genomic sequences have been revealed since mid-April, 2003. After a quiet summer and fall in 2003, the newly emerged SARS cases in Asia, particularly the latest cases in China, are reinforcing a wide-spread belief that the SARS epidemic would strike back. With the understanding that SARS-CoV might be with humans for years to come, knowledge of the evolutionary mechanism of the SARS-CoV, including its mutation rate and emergence time, is fundamental to battle this deadly pathogen. To date, the speed at which the deadly virus evolved in nature and the elapsed time before it was transmitted to humans remains poorly understood. RESULTS: Sixteen complete genomic sequences with available clinical histories during the SARS outbreak were analyzed. After careful examination of multiple-sequence alignment, 114 single nucleotide variations were identified. To minimize the effects of sequencing errors and additional mutations during the cell culture, three strategies were applied to estimate the mutation rate by 1) using the closely related sequences as background controls; 2) adjusting the divergence time for cell culture; or 3) using the common variants only. The mutation rate in the SARS-CoV genome was estimated to be 0.80 \u2013 2.38 \u00d7 10(-3 )nucleotide substitution per site per year which is in the same order of magnitude as other RNA viruses. The non-synonymous and synonymous substitution rates were estimated to be 1.16 \u2013 3.30 \u00d7 10(-3 )and 1.67 \u2013 4.67 \u00d7 10(-3 )per site per year, respectively. The most recent common ancestor of the 16 sequences was inferred to be present as early as the spring of 2002. CONCLUSIONS: The estimated mutation rates in the SARS-CoV using multiple strategies were not unusual among coronaviruses and moderate compared to those in other RNA viruses. All estimates of mutation rates led to the inference that the SARS-CoV could have been with humans in the spring of 2002 without causing a severe epidemic.", "qid": 40, "docid": "fpj5urao", "rank": 78, "score": 0.754477858543396}, {"content": "Title: Snapshot of the evolution and mutation patterns of SARS-CoV-2 Content: The COVID-19 pandemic is the most important public health threat in recent history. Here we study how its causal agent, SARS-CoV-2, has diversified genetically since its first emergence in December 2019. We have created a pipeline combining both phylogenetic and structural analysis to identify possible human-adaptation related mutations in a data set consisting of 4,894 SARS-CoV-2 complete genome sequences. Although the phylogenetic diversity of SARS-CoV-2 is low, the whole genome phylogenetic tree can be divided into five clusters/clades based on the tree topology and clustering of specific mutations, but its branches exhibit low genetic distance and bootstrap support values. We also identified 11 residues that are high-frequency substitutions, with four of them currently showing some signal for potential positive selection. These fast-evolving sites are in the non-structural proteins nsp2, nsp5 (3CL-protease), nsp6, nsp12 (polymerase) and nsp13 (helicase), in accessory proteins (ORF3a, ORF8) and in the structural proteins N and S. Temporal and spatial analysis of these potentially adaptive mutations revealed that the incidence of some of these sites was declining after having reached an (often local) peak, whereas the frequency of other sites is continually increasing and now exhibit a worldwide distribution. Structural analysis revealed that the mutations are located on the surface of the proteins that modulate biochemical properties. We speculate that this improves binding to cellular proteins and hence represents fine-tuning of adaptation to human cells. Our study has implications for the design of biochemical and clinical experiments to assess whether important properties of SARS-CoV-2 have changed during the epidemic.", "qid": 40, "docid": "5od0tegt", "rank": 79, "score": 0.7543313503265381}, {"content": "Title: The origin and underlying driving forces of the SARS-CoV-2 outbreak Content: BACKGROUND: SARS-CoV-2 began spreading in December 2019 and has since become a pandemic that has impacted many aspects of human society. Several issues concerning the origin, time of introduction to humans, evolutionary patterns, and underlying force driving the SARS-CoV-2 outbreak remain unclear. METHOD: Genetic variation in 137 SARS-CoV-2 genomes and related coronaviruses as of 2/23/2020 was analyzed. RESULT: After correcting for mutational bias, the excess of low frequency mutations on both synonymous and nonsynonymous sites was revealed which is consistent with the recent outbreak of the virus. In contrast to adaptive evolution previously reported for SARS-CoV during its brief epidemic in 2003, our analysis of SARS-CoV-2 genomes shows signs of relaxation. The sequence similarity in the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression that occurred approximately 40 years ago. The current outbreak of SARS-CoV-2 was estimated to have originated on 12/11/2019 (95% HPD 11/13/2019\u201312/23/2019). The effective population size of the virus showed an approximately 20-fold increase from the onset of the outbreak to the lockdown of Wuhan (1/23/2020) and ceased to increase afterwards, demonstrating the effectiveness of social distancing in preventing its spread. Two mutations, 84S in orf8 protein and 251 V in orf3 protein, occurred coincidentally with human intervention. The former first appeared on 1/5/2020 and plateaued around 1/23/2020. The latter rapidly increased in frequency after 1/23/2020. Thus, the roles of these mutations on infectivity need to be elucidated. Genetic diversity of SARS-CoV-2 collected from China is two times higher than those derived from the rest of the world. A network analysis found that haplotypes collected from Wuhan were interior and had more mutational connections, both of which are consistent with the observation that the SARS-CoV-2 outbreak originated in China. CONCLUSION: SARS-CoV-2 might have cryptically circulated within humans for years before being discovered. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and determine the critical steps required for effective spreading.", "qid": 40, "docid": "59492sjb", "rank": 80, "score": 0.7541592717170715}, {"content": "Title: Genomic diversity and hotspot mutations in 30,983 SARS-CoV-2 genomes: moving toward a universal vaccine for the \u201cconfined virus\u201d? Content: The Coronavirus disease 19 (COVID-19) pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. To date, the SARS-CoV-2 virus has infected more than 8 million people worldwide and killed over 5% of them. Efforts are being made all over the world to control the spread of the disease and most importantly to develop a vaccine. Understanding the genetic evolution of the virus, its geographic characteristics and stability is particularly important for developing a universal vaccine covering all circulating strains of SARS-CoV-2 and for predicting its efficacy. In this perspective, we analyzed the sequences of 30,983 complete genomes from 80 countries located in six geographical zones (Africa, Asia, Europe, North & South America, and Oceania) isolated from December 24, 2019 to May 13, 2020, and compared them to the reference genome. Our in-depth analysis revealed the presence of 3,206 variant sites compared to the reference Wuhan-Hu-1 genome, with a distribution that is largely uniform over all continents. Remarkably, a low frequency of recurrent mutations was observed; only 182 mutations (5.67%) had a prevalence greater than 1%. Nevertheless, fourteen hotspot mutations (> 10%) were identified at different locations, seven at the ORF1ab gene (in regions coding for nsp2, nsp3, nsp6, nsp12, nsp13, nsp14 and nsp15), three in the nucleocapsid protein, one in the spike protein, one in orf3a, and one in orf8. Moreover, 35 non-synonymous mutations were identified in the receptor-binding domain (RBD) of the spike protein with a low prevalence (<1%) across all genomes, of which only four could potentially enhance the binding of the SARS-CoV-2 spike protein to the human receptor ACE2. These results along with the phylogenetic analysis demonstrate that the virus does not have a significant divergence at the protein level compared to the reference both among and within different geographical areas. Unlike the influenza virus or HIV viruses, the slow rate of mutation of SARS-CoV-2 makes the potential of developing an effective global vaccine very likely.", "qid": 40, "docid": "xbn5ov9s", "rank": 81, "score": 0.7540427446365356}, {"content": "Title: The origin and underlying driving forces of the SARS-CoV-2 outbreak Content: BACKGROUND: SARS-CoV-2 began spreading in December 2019 and has since become a pandemic that has impacted many aspects of human society. Several issues concerning the origin, time of introduction to humans, evolutionary patterns, and underlying force driving the SARS-CoV-2 outbreak remain unclear. METHOD: Genetic variation in 137 SARS-CoV-2 genomes and related coronaviruses as of 2/23/2020 was analyzed. RESULT: After correcting for mutational bias, the excess of low frequency mutations on both synonymous and nonsynonymous sites was revealed which is consistent with the recent outbreak of the virus. In contrast to adaptive evolution previously reported for SARS-CoV during its brief epidemic in 2003, our analysis of SARS-CoV-2 genomes shows signs of relaxation. The sequence similarity in the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression that occurred approximately 40 years ago. The current outbreak of SARS-CoV-2 was estimated to have originated on 12/11/2019 (95% HPD 11/13/2019-12/23/2019). The effective population size of the virus showed an approximately 20-fold increase from the onset of the outbreak to the lockdown of Wuhan (1/23/2020) and ceased to increase afterwards, demonstrating the effectiveness of social distancing in preventing its spread. Two mutations, 84S in orf8 protein and 251 V in orf3 protein, occurred coincidentally with human intervention. The former first appeared on 1/5/2020 and plateaued around 1/23/2020. The latter rapidly increased in frequency after 1/23/2020. Thus, the roles of these mutations on infectivity need to be elucidated. Genetic diversity of SARS-CoV-2 collected from China is two times higher than those derived from the rest of the world. A network analysis found that haplotypes collected from Wuhan were interior and had more mutational connections, both of which are consistent with the observation that the SARS-CoV-2 outbreak originated in China. CONCLUSION: SARS-CoV-2 might have cryptically circulated within humans for years before being discovered. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and determine the critical steps required for effective spreading.", "qid": 40, "docid": "vahud6o5", "rank": 82, "score": 0.7539480924606323}, {"content": "Title: Stability of SARS-CoV-2 Phylogenies Content: The SARS-CoV-2 pandemic has led to unprecedented, nearly real-time genetic tracing due to the rapid community sequencing response. Researchers immediately leveraged these data to infer the evolutionary relationships among viral samples and to study key biological questions, including whether host viral genome editing and recombination are features of SARS-CoV-2 evolution. This global sequencing effort is inherently decentralized and must rely on data collected by many labs using a wide variety of molecular and bioinformatic techniques. There is thus a strong possibility that systematic errors associated with lab-specific practices affect some sequences in the repositories. We find that some recurrent mutations in reported SARS-CoV-2 genome sequences have been observed predominantly or exclusively by single labs, co-localize with commonly used primer binding sites and are more likely to affect the protein coding sequences than other similarly recurrent mutations. We show that their inclusion can affect phylogenetic inference on scales relevant to local lineage tracing, and make it appear as though there has been an excess of recurrent mutation and/or recombination among viral lineages. We suggest how samples can be screened and problematic mutations removed. We also develop tools for comparing and visualizing differences among phylogenies and we show that consistent clade- and tree-based comparisons can be made between phylogenies produced by different groups. These will facilitate evolutionary inferences and comparisons among phylogenies produced for a wide array of purposes. Building on the SARS-CoV-2 Genome Browser at UCSC, we present a toolkit to compare, analyze and combine SARS-CoV-2 phylogenies, find and remove potential sequencing errors and establish a widely shared, stable clade structure for a more accurate scientific inference and discourse. Foreword We wish to thank all groups that responded rapidly by producing these invaluable and essential sequence data. Their contributions have enabled an unprecedented, lightning-fast process of scientific discovery---truly an incredible benefit for humanity and for the scientific community. We emphasize that most lab groups with whom we associate specific suspicious alleles are also those who have produced the most sequence data at a time when it was urgently needed. We commend their efforts. We have already contacted each group and many have updated their sequences. Our goal with this work is not to highlight potential errors, but to understand the impacts of these and other kinds of highly recurrent mutations so as to identify commonalities among the suspicious examples that can improve sequence quality and analysis going forward.", "qid": 40, "docid": "aqkpnz0o", "rank": 83, "score": 0.7534905076026917}, {"content": "Title: Quality control of low-frequency variants in SARS-CoV-2 genomes Content: During the current outbreak of COVID-19, research labs around the globe submit sequences of the local SARS-CoV-2 genomes to the GISAID database to provide a comprehensive analysis of the variability and spread of the virus during the outbreak. We explored the variations in the submitted genomes and found a significant number of variants that can be seen only in one submission (singletons). While it is not completely clear whether these variants are erroneous or not, these variants show lower transition/transversion ratio. These singleton variants may influence the estimations of the viral mutation rate and tree topology. We suggest that genomes with multiple singletons even marked as high-covered should be considered with caution. We also provide a simple script for checking variant frequency against the database before submission.", "qid": 40, "docid": "lkdkdque", "rank": 84, "score": 0.7534289360046387}, {"content": "Title: Genetic Diversity and Genomic Epidemiology of SARS-COV-2 in Morocco Content: COVID-A9 is an infection disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), declared as a pandemic due to its rapid expansion worldwide. In this study we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 using 22 virus genome sequences reported by three different laboratories in Morocco till the date 07/06/2020 as well as (40366) virus genomes from all around the world. The SARS-CoV-2 genomes from Moroccan patients revealed 62 mutations of which 30 were missense mutations. The mutations Spike_D614G and NSP12_P323L were present in all the 22 analyzed sequences, followed by N_G204R and N_R203K which occurred in 9 among the 22 sequences. The mutations NSP10_R134S, NSP15_D335N, NSP16_I169L, NSP3_L431H, NSP3_P1292L and Spike_V6F occurred one time in our sequences with no record in other sequence worldwide. These mutations should be investigated to figure out their potential effects on all around the world virulence. Phylogenetic analyses revealed that Moroccan SARS-CoV-2 genomes included 9 viruses pertaining to clade 20A, 9 to clade 20B and 2 to clade 20C. This finding suggest that the epidemic spread in Morocco did not show a predominant SARS-CoV-2 route. For multiple and unrelated introductions of SARS-CoV-2 into Morocco via different routes have occurred, giving rise to the diversity of virus genomes in the country. Furthermore, very likely, the SARS-CoV-2 virus circulated in cryptic way in Morocco starting from the fifteen January before the discovering of the first case the second of March.", "qid": 40, "docid": "zb1pzdd0", "rank": 85, "score": 0.7532099485397339}, {"content": "Title: Overwhelming Mutations or SNPs of SARS-CoV-2: A Point of Caution Content: \u2022 Mutation studies hits cause for the superior infectious rate of SARS-CoV-2. \u2022 SARS-CoV-2 is evolving rapidly with number of mutations and SNPs. \u2022 Mutations were found in the ACE2 binding region of SARS-CoV-2 spike glycoprotein. \u2022 ORF1ab, ORF8 and spike glycoprotein regions of SARS-CoV-2 are highly mutated. \u2022 Overwhelming mutations or SNPs of SARS-CoV-2 alerts drug treatment options.", "qid": 40, "docid": "sd0ah7k5", "rank": 86, "score": 0.752991795539856}, {"content": "Title: Rampant C\u00e2\u0086\u0092U Hypermutation in the Genomes of SARS-CoV-2 and Other Coronaviruses: Causes and Consequences for Their Short- and Long-Term Evolutionary Trajectories Content: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has motivated an intensive analysis of its molecular epidemiology following its worldwide spread. To understand the early evolutionary events following its emergence, a data set of 985 complete SARS-CoV-2 sequences was assembled. Variants showed a mean of 5.5 to 9.5 nucleotide differences from each other, consistent with a midrange coronavirus substitution rate of 3 \u00d7 10-4 substitutions/site/year. Almost one-half of sequence changes were C\u00e2\u0086\u0092U transitions, with an 8-fold base frequency normalized directional asymmetry between C\u00e2\u0086\u0092U and U\u00e2\u0086\u0092C substitutions. Elevated ratios were observed in other recently emerged coronaviruses (SARS-CoV, Middle East respiratory syndrome [MERS]-CoV), and decreasing ratios were observed in other human coronaviruses (HCoV-NL63, -OC43, -229E, and -HKU1) proportionate to their increasing divergence. C\u00e2\u0086\u0092U transitions underpinned almost one-half of the amino acid differences between SARS-CoV-2 variants and occurred preferentially in both 5' U/A and 3' U/A flanking sequence contexts comparable to favored motifs of human APOBEC3 proteins. Marked base asymmetries observed in nonpandemic human coronaviruses (U \u00e2\u0089\u00ab A > G \u00e2\u0089\u00ab C) and low G+C contents may represent long-term effects of prolonged C\u00e2\u0086\u0092U hypermutation in their hosts. The evidence that much of sequence change in SARS-CoV-2 and other coronaviruses may be driven by a host APOBEC-like editing process has profound implications for understanding their short- and long-term evolution. Repeated cycles of mutation and reversion in favored mutational hot spots and the widespread occurrence of amino acid changes with no adaptive value for the virus represent a quite different paradigm of virus sequence change from neutral and Darwinian evolutionary frameworks and are not incorporated by standard models used in molecular epidemiology investigations.IMPORTANCE The wealth of accurately curated sequence data for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its long genome, and its low substitution rate provides a relatively blank canvas with which to investigate effects of mutational and editing processes imposed by the host cell. The finding that a large proportion of sequence change in SARS-CoV-2 in the initial months of the pandemic comprised C\u00e2\u0086\u0092U mutations in a host APOBEC-like context provides evidence for a potent host-driven antiviral editing mechanism against coronaviruses more often associated with antiretroviral defense. In evolutionary terms, the contribution of biased, convergent, and context-dependent mutations to sequence change in SARS-CoV-2 is substantial, and these processes are not incorporated by standard models used in molecular epidemiology investigations.", "qid": 40, "docid": "14pgap3r", "rank": 87, "score": 0.7528727054595947}, {"content": "Title: Direct Sequencing of SARS-Coronavirus S and N Genes from Clinical Specimens Shows Limited Variation Content: Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged, in November 2002, as a novel agent causing severe respiratory illness. To study sequence variation in the SARS-CoV genome, we determined the nucleic acid sequence of the S and N genes directly from clinical specimens from 10 patients\u20141 specimen with no matched SARS-CoV isolate, from 2 patients; multiple specimens from 3 patients; and matched clinical-specimen/ cell-culture-isolate pairs from 6 patients. We identified 3 nucleotide substitutions that were most likely due to natural variation and 2 substitutions that arose after cell-culture passage of the virus. These data demonstrate the overall stability of the S and N genes of SARS-CoV over 3 months during which a minimum of 4 generations for transmission events occurred. These findings are a part of the expanding investigation of the evolution of how this virus adapts to a new host.", "qid": 40, "docid": "xbu18zdr", "rank": 88, "score": 0.7527633905410767}, {"content": "Title: Evolving geographic diversity in SARS-CoV2 and in silico analysis of replicating enzyme 3CLpro targeting repurposed drug candidates Content: BACKGROUND: Severe acute respiratory syndrome (SARS) has been initiating pandemics since the beginning of the century. In December 2019, the world was hit again by a devastating SARS episode that has so far infected almost four million individuals worldwide, with over 200,000 fatalities having already occurred by mid-April 2020, and the infection rate continues to grow exponentially. SARS coronavirus 2 (SARS-CoV-2) is a single stranded RNA pathogen which is characterised by a high mutation rate. It is vital to explore the mutagenic capability of the viral genome that enables SARS-CoV-2 to rapidly jump from one host immunity to another and adapt to the genetic pool of local populations. METHODS: For this study, we analysed 2301 complete viral sequences reported from SARS-CoV-2 infected patients. SARS-CoV-2 host genomes were collected from The Global Initiative on Sharing All Influenza Data (GISAID) database containing 9 genomes from pangolin-CoV origin and 3 genomes from bat-CoV origin, Wuhan SARS-CoV2 reference genome was collected from GeneBank database. The Multiple sequence alignment tool, Clustal Omega was used for genomic sequence alignment. The viral replicating enzyme, 3-chymotrypsin-like cysteine protease (3CLpro) that plays a key role in its pathogenicity was used to assess its affinity with pharmacological inhibitors and repurposed drugs such as anti-viral flavones, biflavanoids, anti-malarial drugs and vitamin supplements. RESULTS: Our results demonstrate that bat-CoV shares > 96% similar identity, while pangolin-CoV shares 85.98% identity with Wuhan SARS-CoV-2 genome. This in-depth analysis has identified 12 novel recurrent mutations in South American and African viral genomes out of which 3 were unique in South America, 4 unique in Africa and 5 were present in-patient isolates from both populations. Using state of the art in silico approaches, this study further investigates the interaction of repurposed drugs with the SARS-CoV-2 3CLpro enzyme, which regulates viral replication machinery. CONCLUSIONS: Overall, this study provides insights into the evolving mutations, with implications to understand viral pathogenicity and possible new strategies for repurposing compounds to combat the nCovid-19 pandemic.", "qid": 40, "docid": "qc5bhxgj", "rank": 89, "score": 0.7526202201843262}, {"content": "Title: Global genetic diversity patterns and transmissions of SARS-CoV-2 Content: Background: Since it was firstly discovered in China, the SARS-CoV-2 epidemic has caused a substantial health emergency and economic stress in the world. However, the global genetic diversity and transmissions are still unclear. Methods: 3050 SARS-CoV-2 genome sequences were retrieved from GIASID database. After aligned by MAFFT, the mutation patterns were identified by phylogenetic tree analysis. Results: We detected 17 high frequency (>6%) mutations in the 3050 sequences. Based on these mutations, we classed the SARS-CoV-2 into four main groups and 10 subgroups. We found that group A was mainly presented in Asia, group B was primarily detected in North America, group C was prevailingly appeared in Asia and Oceania and group D was principally emerged in Europe and Africa. Additionally, the distribution of these groups was different in age, but was similar in gender. Group A, group B1 and group C2 were declined over time, inversely, group B2, group C3 and group D were rising. At last, we found two apparent expansion stages (late Jan-2020 and late Feb-2020 to early Mar-2020, respectively). Notably, most of groups are quickly expanding, especially group D. Conclusions: We classed the SARS-CoV-2 into four main groups and 10 subgroups based on different mutation patterns at first time. The distribution of the 10 subgroups was different in geography, time and age, but not in gender. Most of groups are rapidly expanding, especially group D. Therefore, we should attach importance to these genetic diversity patterns of SARS-CoV-2 and take more targeted measures to constrain its spread.", "qid": 40, "docid": "r3t4bd78", "rank": 90, "score": 0.7524350881576538}, {"content": "Title: Comparative genomic analysis revealed specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13 Content: The novel coronavirus SARS-CoV-2 (2019-nCoV) is a member of the family coronaviridae and contains a single-stranded RNA genome with positive-polarity. To reveal the evolution mechanism of SARS-CoV-2 genome, we performed comprehensive genomic analysis with newly sequenced SARS-CoV-2 strains and 20 closely related coronavirus strains. Among 98 nucleotide mutations at 93 sites of the genome among different SARS-CoV-2 strains, 58 of them caused amino acid change, indicating a result of neutral evolution. However, the ratio of nucleotide substitutions to amino acid substitutions of spike gene (9.07) between SARS-CoV-2 WIV04 and Bat-SARSr-CoV RaTG13 was extensively higher than those from comparisons between other coronaviruses (range 1.29 - 4.81). The elevated synonymous mutations between SARS-CoV-2 and RaTG13, suggesting they underwent stronger purifying selection. Moreover, their nucleotide substitutions are enriched with T:C transition, which is consistent with the mutation signature caused by deactivity of RNA 3\u2019-to-5\u2019 exoribonuclease (ExoN). The codon usage was similar between SARS-CoV-2 and other strains in beta-coronavirus lineage B, suggesting it had small impact on the mutation pattern. In comparison of SARS-CoV-2 WIV04 with Bat-SARSr-CoV RaTG13, the ratios of non-synonymous to synonymous substitution rates (dN/dS) was the lowest among all performed comparisons, reconfirming the evolution of SARS-CoV-2 under stringent selective pressure. Moreover, some sites of spike protein might be subjected to positive selection. Therefore, our results will help understanding the evolutionary mechanisms contribute to viral pathogenicity and its adaptation with hosts.", "qid": 40, "docid": "3h1o0oz3", "rank": 91, "score": 0.7521882057189941}, {"content": "Title: Evidence of Increasing Diversification of Emerging SARS\u2010CoV\u20102 Strains Content: BACKGROUND: On January 30th, 2020, an outbreak of atypical pneumonia caused by a novel Betacoronavirus (\u03b2CoV), named SARS\u2010CoV\u20102, was declared a public health emergency of international concern by the World Health Organization. For this reason, a detailed evolutionary analysis of SARS\u2010CoV\u20102 strains currently circulating in different geographic regions of the world was performed. METHODS: A compositional analysis as well as a Bayesian coalescent analysis of complete genome sequences of SARS\u2010CoV\u20102 strains recently isolated in Europe, North America, South America and Asia was performed. RESULTS: The results of these studies revealed a diversification of SARS\u2010CoV\u20102 strains in three different genetic clades. Co\u2010circulation of different clades in different countries, as well as different genetic lineages within different clades were observed. The time of the most recent common ancestor (tMRCA) was established to be around November 1, 2019. A mean rate of evolution of 6.57 x 10(\u20104) substitutions per site per year was found. A significant migration rate per genetic lineage per year from Europe to South America was also observed. CONCLUSION: The results of these studies revealed an increasing diversification of SARS\u2010CoV\u20102 strains. High evolutionary rates and fast population growth characterizes the population dynamics of SARS\u2010CoV\u20102 strains. This article is protected by copyright. All rights reserved.", "qid": 40, "docid": "ew2kjq5s", "rank": 92, "score": 0.7521806955337524}, {"content": "Title: Complete Genome Sequences of SARS-CoV-2 Strains Detected in Malaysia Content: We sequenced four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from Malaysia during the second wave of infection and found unique mutations which suggest local evolution. Circulating Malaysian strains represent introductions from different countries, particularly during the first wave of infection. Genome sequencing is important for understanding local epidemiology.", "qid": 40, "docid": "8r6u3e3i", "rank": 93, "score": 0.7518622875213623}, {"content": "Title: Evolving geographic diversity in SARS-CoV2 and in silico analysis of replicating enzyme 3CL(pro) targeting repurposed drug candidates Content: BACKGROUND: Severe acute respiratory syndrome (SARS) has been initiating pandemics since the beginning of the century. In December 2019, the world was hit again by a devastating SARS episode that has so far infected almost four million individuals worldwide, with over 200,000 fatalities having already occurred by mid-April 2020, and the infection rate continues to grow exponentially. SARS coronavirus 2 (SARS-CoV-2) is a single stranded RNA pathogen which is characterised by a high mutation rate. It is vital to explore the mutagenic capability of the viral genome that enables SARS-CoV-2 to rapidly jump from one host immunity to another and adapt to the genetic pool of local populations. METHODS: For this study, we analysed 2301 complete viral sequences reported from SARS-CoV-2 infected patients. SARS-CoV-2 host genomes were collected from The Global Initiative on Sharing All Influenza Data (GISAID) database containing 9 genomes from pangolin-CoV origin and 3 genomes from bat-CoV origin, Wuhan SARS-CoV2 reference genome was collected from GeneBank database. The Multiple sequence alignment tool, Clustal Omega was used for genomic sequence alignment. The viral replicating enzyme, 3-chymotrypsin-like cysteine protease (3CL(pro)) that plays a key role in its pathogenicity was used to assess its affinity with pharmacological inhibitors and repurposed drugs such as anti-viral flavones, biflavanoids, anti-malarial drugs and vitamin supplements. RESULTS: Our results demonstrate that bat-CoV shares > 96% similar identity, while pangolin-CoV shares 85.98% identity with Wuhan SARS-CoV-2 genome. This in-depth analysis has identified 12 novel recurrent mutations in South American and African viral genomes out of which 3 were unique in South America, 4 unique in Africa and 5 were present in-patient isolates from both populations. Using state of the art in silico approaches, this study further investigates the interaction of repurposed drugs with the SARS-CoV-2 3CL(pro) enzyme, which regulates viral replication machinery. CONCLUSIONS: Overall, this study provides insights into the evolving mutations, with implications to understand viral pathogenicity and possible new strategies for repurposing compounds to combat the nCovid-19 pandemic.", "qid": 40, "docid": "d25qfq0f", "rank": 94, "score": 0.7511662244796753}, {"content": "Title: A snapshot of SARS-CoV-2 genome availability up to 30th March, 2020 and its implications Content: The SARS-CoV-2 pandemic has been growing exponentially, affecting nearly 900 thousand people and causing enormous distress to economies and societies worldwide. A plethora of analyses based on viral sequences has already been published, in scientific journals as well as through non-peer reviewed channels, to investigate SARS-CoV-2 genetic heterogeneity and spatiotemporal dissemination. We examined full genome sequences currently available to assess the presence of sufficient information for reliable phylogenetic and phylogeographic studies in countries with the highest toll of confirmed cases. Although number of-available full-genomes is growing daily, and the full dataset contains sufficient phylogenetic information that would allow reliable inference of phylogenetic relationships, country-specific SARS-CoV-2 datasets still present severe limitations. Studies assessing within country spread or transmission clusters should be considered preliminary at best, or hypothesis generating. Hence the need for continuing concerted efforts to increase number and quality of the sequences required for robust tracing of the epidemic. Significance Statement Although genome sequences of SARS-CoV-2 are growing daily and contain sufficient phylogenetic information, country-specific data still present severe limitations and should be interpreted with caution.", "qid": 40, "docid": "8vl0okiv", "rank": 95, "score": 0.7510614991188049}, {"content": "Title: Multiple assays in a real-time RT-PCR SARS-CoV-2 panel can mitigate the risk of loss of sensitivity by new genomic variants during the COVID-19 outbreak Content: OBJECTIVES: In this study, five SARS-CoV-2 PCR assay panels were evaluated against the accumulated genetic variability of the virus to assess the effect on sensitivity of the individual assays. DESIGN OR METHODS: As of week 21, 2020, the complete set of available SARS-CoV-2 genomes from GISAID and GenBank databases were used in this study. SARS-CoV-2 primer sequences from publicly available panels (WHO, CDC, NMDC, and HKU) and QIAstat-Dx were included in the alignment, and accumulated genetic variability affecting any oligonucleotide annealing was annotated. RESULTS: A total of 11,627 (34.38%) genomes included single mutations affecting annealing of any PCR assay. Variations in 8,773 (25.94%) genomes were considered as high risk, whereas additional 2,854 (8.43%) genomes presented low frequent single mutations and were predicted to yield no impact on sensitivity. In case of the QIAstat-Dx SARS-CoV-2 Panel, 99.11% of the genomes matched with a 100% coverage all oligonucleotides, and critical variations were tested in vitro corroborating no loss of sensitivity. CONCLUSIONS: This analysis stresses the importance of targeting more than one region in the viral genome for SARS-CoV-2 detection to mitigate the risk of loss of sensitivity due to the unknown mutation rate during this SARS-CoV-2 outbreak.", "qid": 40, "docid": "ydfe06ua", "rank": 96, "score": 0.7509596347808838}, {"content": "Title: Virus strain from a mild COVID-19 patient in Hangzhou represents a new trend in SARS-CoV-2 evolution potentially related to Furin cleavage site Content: The mutations in the SARS-CoV-2 virus genome during COVID-19 dissemination are unclear. In 788 COVID-19 patients from Zhejiang province, we observed decreased rate of severe/critical cases compared with patients in Wuhan. For mechanisms exploration, we isolated one strain of SARS-CoV-2 (ZJ01) from a mild COVID-19 patient. Thirty-five specific gene mutations were identified. Phylogenetic and relative synonymous codon usage analysis suggested that ZJ01 may be a potential evolutionary branch of SARS-CoV-2. We classified 54 global virus strains based on the base (C or T) at positions 8824 and 28247 while ZJ01 has T at both sites. The prediction of the Furin cleavage site (FCS) and sequence alignment indicated that the FCS may be an important site of coronavirus evolution. ZJ01 mutations identified near the FCS (F1-2) caused changes in the structure and electrostatic distribution of the S surface protein, further affecting the binding capacity of Furin. Single-cell sequencing and ACE2-Furin co-expression results confirmed that the Furin expression was especially higher in glands, liver, kidneys, and colon. The evolutionary pattern of SARS-CoV-2 towards FCS formation may result in its clinical symptom becoming closer to HKU-1 and OC43 caused mild flu-like symptoms, further showing its potential in differentiating into mild COVID-19 subtypes.", "qid": 40, "docid": "iljmhdd1", "rank": 97, "score": 0.750576376914978}, {"content": "Title: A COMPREHENSIVE ANALYSIS OF GENOME COMPOSITION AND CODON USAGE PATTERNS OF EMERGING CORONAVIRUSES Content: Abstract An outbreak of atypical pneumonia caused by a novel Betacoronavirus (\u03b2CoV), named SARS-CoV-2 has been declared a public health emergency of international concern by the World Health Organization. In order to gain insight into the emergence, evolution and adaptation of SARS-CoV-2 viruses, a comprehensive analysis of genome composition and codon usage of \u03b2CoV circulating in China was performed. A biased nucleotide composition was found for SARS-CoV-2 genome. This bias in genomic composition is reflected in its codon and amino acid usage patterns. The overall codon usage in SARS-CoV-2 is similar among themselves and slightly biased. Most of the highly frequent codons are A- and U-ending, which strongly suggests that mutational bias is the main force shaping codon usage in this virus. Significant differences in relative synonymous codon usage frequencies among SARS-CoV-2 and human cells were found. These differences are due to codon usage preferences.", "qid": 40, "docid": "hidirfkv", "rank": 98, "score": 0.7504155039787292}, {"content": "Title: Prediction of amino acid pairs sensitive to mutations in the spike protein from SARS related coronavirus Content: In this study, we analyzed the amino acid pairs affected by mutations in two spike proteins from human coronavirus strains 229E and OC43 by means of random analysis in order to gain some insight into the possible mutations in the spike protein from SARS-CoV. The results demonstrate that the randomly unpredictable amino acid pairs are more sensitive to the mutations. The larger is the difference between actual and predicted frequencies, the higher is the chance of mutation occurring. The effect induced by mutations is to reduce the difference between actual and predicted frequencies. The amino acid pairs whose actual frequencies are larger than their predicted frequencies are more likely to be targeted by mutations, whereas the amino acid pairs whose actual frequencies are smaller than their predicted frequencies are more likely to be formed after mutations. These findings are identical to our several recent studies, i.e. the mutations represent a process of degeneration inducing human diseases.", "qid": 40, "docid": "zmqaigqf", "rank": 99, "score": 0.7501302361488342}, {"content": "Title: Genomic Mutations and Changes in Protein Secondary Structure and Solvent Accessibility of SARS-CoV-2 (COVID-19 Virus) Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic virus that has caused the global COVID-19 pandemic. Tracing the evolution and transmission of the virus is crucial to respond to and control the pandemic through appropriate intervention strategies. This paper reports and analyses genomic mutations in the coding regions of SARS-CoV-2 and their probable protein secondary structure and solvent accessibility changes, which are predicted using deep learning models. Prediction results suggest that mutation D614G in the virus spike protein, which has attracted much attention from researchers, is unlikely to make changes in protein secondary structure and relative solvent accessibility. Based on 6,324 viral genome sequences, we create a spreadsheet dataset of point mutations that can facilitate the investigation of SARS-CoV-2 in many perspectives, especially in tracing the evolution and worldwide spread of the virus. Our analysis results also show that coding genes E, M, ORF6, ORF7a, ORF7b and ORF10 are most stable, potentially suitable to be targeted for vaccine and drug development.", "qid": 40, "docid": "o9oxchq6", "rank": 100, "score": 0.7498867511749268}]}
{"query": "What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population?", "hits": [{"content": "Title: Social Vulnerability and Racial Inequality in COVID-19 Deaths in Chicago Content: Although the current COVID-19 crisis is felt globally, at the local level, COVID-19 has disproportionately affected poor, highly segregated African American communities in Chicago. To understand the emerging pattern of racial inequality in the effects of COVID-19, we examined the relative burden of social vulnerability and health risk factors. We found significant spatial clusters of social vulnerability and risk factors, both of which are significantly associated with the increased COVID-19-related death rate. We also found that a higher percentage of African Americans was associated with increased levels of social vulnerability and risk factors. In addition, the proportion of African American residents has an independent effect on the COVID-19 death rate. We argue that existing inequity is often highlighted in emergency conditions. The disproportionate effects of COVID-19 in African American communities are a reflection of racial inequality and social exclusion that existed before the COVID-19 crisis.", "qid": 41, "docid": "aa9zegjr", "rank": 1, "score": 0.8376217484474182}, {"content": "Title: Social Vulnerability and Racial Inequality in COVID-19 Deaths in Chicago. Content: Although the current COVID-19 crisis is felt globally, at the local level, COVID-19 has disproportionately affected poor, highly segregated African American communities in Chicago. To understand the emerging pattern of racial inequality in the effects of COVID-19, we examined the relative burden of social vulnerability and health risk factors. We found significant spatial clusters of social vulnerability and risk factors, both of which are significantly associated with the increased COVID-19-related death rate. We also found that a higher percentage of African Americans was associated with increased levels of social vulnerability and risk factors. In addition, the proportion of African American residents has an independent effect on the COVID-19 death rate. We argue that existing inequity is often highlighted in emergency conditions. The disproportionate effects of COVID-19 in African American communities are a reflection of racial inequality and social exclusion that existed before the COVID-19 crisis.", "qid": 41, "docid": "gn8uwuca", "rank": 2, "score": 0.8376217484474182}, {"content": "Title: Disproportionate COVID-19 Related Mortality Amongst African Americans in Four Southern States in the United States Content: Background African American have been severely affected by COVID-19 noted with the rising mortality rates within the African American community. Health disparities, health inequities and issues with systemic health access are some of the pre-existing issues African American were subjected to within the southern states in the United States. Second, social distancing is a critical non-pharmacological intervention to reduce the spread of COVID-19. However, social distancing was not practical and presented a challenge within the African American community, specifically, in the southern states. Objective This article assesses the effect of COVID-19 on African American in the southern states. Methodology This short communication queried the publicly available Department of Health statistics on COVID-19 related mortality and underlying health conditions in four southern states (Alabama [AL], Georgia [GA], Louisiana [LA] and Mississippi [MS]) with a high proportion of African American residents. Second, unacast COVID-19 toolkit was used to derive a social distancing (SD) grade for any given state, based on three different metrics: (i) percent change in average distance travelled (ii) percent change in non-essential visits and (iii) decrease in human encounters (compared to national baseline). Results Across the four states, on average, as many as 54% of COVID-19 related deaths are in the African American community, although this minority group comprises only 32% of the population cumulatively. This article finds that all four southern states received a social distancing grade of F. COVID-19 have demonstrated that adverse outcomes are higher in individuals with underlying health conditions such as diabetes, cardiovascular diseases, or pre-existing pulmonary compromise. Conclusion Recognizing that there is a great need for African American representation or diversity in the health workforce would be able to better address the health disparities. In addition, the lack of diversity in the healthcare system causes the morbidity and mortality rates to increase in the African American communities because it is not able to address its primary obligations within the African American communities in the southern states during COVID-19 pandemic. These primary obligations are to restore, protect, improve health and to suppress health disparities and inequalities of COVID-19 within in the African American communities. Keywords: COVID-19; African American; Mortality", "qid": 41, "docid": "8yvu9xhw", "rank": 3, "score": 0.8325754404067993}, {"content": "Title: The impact of COVID-19 on African American communities in the United States Content: IMPORTANCE: The novel Coronavirus Disease 2019 (COVID-19), declared a pandemic in March 2020, may present with disproportionately higher rates in underrepresented racial/ethnic minority populations in the United States, including African American communities who have traditionally been over-represented in negative health outcomes. STUDY OBJECTIVE: To understand the impact of the density of African American communities (defined as the percentage of African Americans in a county) on COVID-19 prevalence and death rate within the three most populous counties in each U.S. state and territory (n=152). Design: An ecological study using linear regression was employed for the study. SETTING: The top three most populous counties of each U.S. state and territory were included in analyses for a final sample size of n=152 counties. PARTICIPANTS: Confirmed COVID-19 cases and deaths that were accumulated between January 22, 2020 and April 12, 2020 in each of the three most populous counties in each U.S. state and territory were included. MAIN OUTCOME MEASURES: Linear regression was used to determine the association between African American density and COVID-19 prevalence (defined as the percentage of cases for the county population), and death rate (defined as number of deaths per 100,000 population). The models were adjusted for median age and poverty. RESULTS: There was a direct association between African American density and COVID-19 prevalence; COVID-19 prevalence increased 5% for every 1% increase in county AA density (p<.01). There was also an association between county AA density and COVID-19 deaths, such; the death rate increased 2 per 100,000 for every percentage increase in county AA density (p=.02). CONCLUSION: These study findings indicate that communities with a high African American density have been disproportionately burdened with COVID-19. Further study is needed to indicate if this burden is related to environmental factors or individual factors such as types of employment or comorbidities that members of these community have.", "qid": 41, "docid": "80w0wu9e", "rank": 4, "score": 0.8269913792610168}, {"content": "Title: Racial demographics and COVID-19 confirmed cases and deaths: a correlational analysis of 2886 US counties Content: BACKGROUND: Recent news reports state that racial minority groups, such as African-Americans, are experiencing a greater COVID-19 burden, as measured by confirmed cases and deaths. Limited racial data is available on a national level. METHODS: We conducted the first nationwide analysis to examine COVID-19 and race on a county level. We obtained datasets on COVID-19 cases and deaths, and racial population totals, by US county. We examined if correlations exist between the racial percentages and percentages of confirmed COVID-19 cases and deaths by county. RESULTS: A positive correlation existed between percentages of African-Americans living in a county and who have COVID-19 (r = 0.254, P < 0.0001), who have died from COVID-19 (r = 0.268, P < 0.0001), and case mortality (r = 0.055, P = 0.003). Positive correlations also existed between percentages of Asian-Americans living in counties and these factors. Negative correlations existed between percentages of Whites living in counties and these factors. CONCLUSIONS: A weak, albeit very significant, positive relationship exists between the percentage of African-Americans living in a county and the percentage of COVID-19 confirmed cases, confirmed deaths and case mortality in the county. This is in support of many city and statewide analyses, and we urge for targeted resources towards work that further examine these racial associations.", "qid": 41, "docid": "ne552y3i", "rank": 5, "score": 0.8196544647216797}, {"content": "Title: Racial demographics and COVID-19 confirmed cases and deaths: a correlational analysis of 2886 US counties Content: BACKGROUND: Recent news reports state that racial minority groups, such as African\u2013Americans, are experiencing a greater COVID-19 burden, as measured by confirmed cases and deaths. Limited racial data is available on a national level. METHODS: We conducted the first nationwide analysis to examine COVID-19 and race on a county level. We obtained datasets on COVID-19 cases and deaths, and racial population totals, by US county. We examined if correlations exist between the racial percentages and percentages of confirmed COVID-19 cases and deaths by county. RESULTS: A positive correlation existed between percentages of African\u2013Americans living in a county and who have COVID-19 (r = 0.254, P < 0.0001), who have died from COVID-19 (r = 0.268, P < 0.0001), and case mortality (r = 0.055, P = 0.003). Positive correlations also existed between percentages of Asian\u2013Americans living in counties and these factors. Negative correlations existed between percentages of Whites living in counties and these factors. CONCLUSIONS: A weak, albeit very significant, positive relationship exists between the percentage of African\u2013Americans living in a county and the percentage of COVID-19 confirmed cases, confirmed deaths and case mortality in the county. This is in support of many city and statewide analyses, and we urge for targeted resources towards work that further examine these racial associations.", "qid": 41, "docid": "58ye9c5a", "rank": 6, "score": 0.8195064067840576}, {"content": "Title: Similarities and differences in COVID-19 awareness, concern, and symptoms by race and ethnicity in the United States: A cross-sectional survey Content: BACKGROUND: Existing health disparities based on race and ethnicity in the United States are contributing to disparities in morbidity and mortality in the COVID-19 pandemic. We conducted an online survey of American adults to assess similarities and differences by race and ethnicity groups with respect to COVID-19 symptoms, estimates of the extent of the pandemic, knowledge of control measures, and stigma. OBJECTIVE: Describe similarities and differences in COVID-19 symptoms, knowledge, and beliefs by race and ethnicity among adults in the US. METHODS: We conducted a cross-sectional survey from March 27, 2020 through April 1, 2020. Participants were recruited on social media platforms and completed the survey on a secure, online survey platform. We used chi square tests to compare characteristics related to COVID-19 by race and ethnicity. Statistical tests were corrected using the Holm Bonferroni correction to account for multiple comparisons. RESULTS: A total of 1,435 (3.6% Asian, 11.0% non-Hispanic Black, 38.2% Hispanic, 40.9% non-Hispanic white, and 6.3% other or multiple races) participants completed the survey. Only one symptom (sore throat) was found to be different based on race and ethnicity (p = 0.003), which was less frequently reported by Asian (5.8%), non-Hispanic Black (5.7%), and other/multiple race (8.9%) participants compared to those who were Hispanic (18.1%) or non-Hispanic white (16.2%). Non-Hispanic white and Asian participants were more likely to estimate that the number of current cases was at least 100,000 (p = 0.004) and were more likely to answer all 14 COVID-19 knowledge scale questions correctly (Asian, 25.0%; non-Hispanic White, 30.7%) compared to Hispanic (19.7%) and non-Hispanic Black (15.8%) participants. CONCLUSIONS: We observed differences with respect to knowledge of appropriate methods to prevent infection by the novel coronavirus that causes COVID-19. Deficits in knowledge of proper control methods might further exacerbate existing race/ethnicity disparities. Additional research is needed to identify trusted sources of information in Hispanic and non-Hispanic Black communities and effective messaging to disseminate correct COVID-19 prevention and treatment information.", "qid": 41, "docid": "y1shr2xa", "rank": 7, "score": 0.8189740180969238}, {"content": "Title: Six feet apart or six feet under: The impact of COVID-19 on the Black community Content: To date, 110,000+ people in the United States have died from the COVID-19 pandemic. In this paper, the authors will discuss COVID-19 relative to Black people and their overrepresentation among those who are infected and died from the disease. Their dying, death, and grief experiences are explored through a cultural and spiritual lens. The physical distancing, social isolation, misinformation, and restrictive burials and cremations now elicited by this unprecedented pandemic have had diminished familial, cultural, emotional, and economic impacts on the Black community. Implications for public health and Black peoples' involvement in the political process are also addressed.", "qid": 41, "docid": "i2b9py8e", "rank": 8, "score": 0.8186354637145996}, {"content": "Title: Six feet apart or six feet under: The impact of COVID-19 on the Black community. Content: To date, 110,000+ people in the United States have died from the COVID-19 pandemic. In this paper, the authors will discuss COVID-19 relative to Black people and their overrepresentation among those who are infected and died from the disease. Their dying, death, and grief experiences are explored through a cultural and spiritual lens. The physical distancing, social isolation, misinformation, and restrictive burials and cremations now elicited by this unprecedented pandemic have had diminished familial, cultural, emotional, and economic impacts on the Black community. Implications for public health and Black peoples' involvement in the political process are also addressed.", "qid": 41, "docid": "phcd8b4m", "rank": 9, "score": 0.8186354637145996}, {"content": "Title: Racial Disparity of Coronavirus Disease 2019 (COVID-19) in African American Communities Content: The COVID-19 pandemic has unveiled unsettling disparities in the outcome of the disease among African Americans. These disparities are not new, but are rooted in structural inequities that must be addressed to adequately care for communities of color. We describe the historical context of these structural inequities, their impact on the progression of COVID-19 in the African American (Black) community, and suggest a multifaceted approach to addressing these healthcare disparities. Of note, terminology from survey data cited for this article varied from Blacks, African Americans or both; for consistency, we use African Americans throughout.", "qid": 41, "docid": "bgpep5lc", "rank": 10, "score": 0.8175025582313538}, {"content": "Title: COVID-19 and the Widening Gap in Health Inequity Content: The coronavirus disease 2019 (COVID-19) pandemic has brought to light significant health inequities that have existed in our society for decades. Blacks, Hispanics, Native Americans, and immigrants are the populations most likely to experience disparities related to burden of disease, health care, and health outcomes. Increasingly, national and state statistics on COVID-19 report disproportionately higher mortality rates in blacks. There has never been a more pressing time for us to enact progressive and far-reaching changes in social, economic, and political policies that will shape programs aimed at improving the health of all people living in the United States.", "qid": 41, "docid": "3omm8wkv", "rank": 11, "score": 0.8168960809707642}, {"content": "Title: COVID-19 and the Widening Gap in Health Inequity. Content: The coronavirus disease 2019 (COVID-19) pandemic has brought to light significant health inequities that have existed in our society for decades. Blacks, Hispanics, Native Americans, and immigrants are the populations most likely to experience disparities related to burden of disease, health care, and health outcomes. Increasingly, national and state statistics on COVID-19 report disproportionately higher mortality rates in blacks. There has never been a more pressing time for us to enact progressive and far-reaching changes in social, economic, and political policies that will shape programs aimed at improving the health of all people living in the United States.", "qid": 41, "docid": "sza8r2e1", "rank": 12, "score": 0.8168960809707642}, {"content": "Title: The COVID-19 Pandemic: a Call to Action to Identify and Address Racial and Ethnic Disparities Content: The Coronavirus disease 2019 (COVID-19) pandemic has significantly impacted and devastated the world. As the infection spreads, the projected mortality and economic devastation are unprecedented. In particular, racial and ethnic minorities may be at a particular disadvantage as many already assume the status of a marginalized group. Black Americans have a long-standing history of disadvantage and are in a vulnerable position to experience the impact of this crisis and the myth of Black immunity to COVID-19 is detrimental to promoting and maintaining preventative measures. We are the first to present the earliest available data in the peer-reviewed literature on the racial and ethnic distribution of COVID-19-confirmed cases and fatalities in the state of Connecticut. We also seek to explode the myth of Black immunity to the virus. Finally, we call for a National Commission on COVID-19 Racial and Ethnic Health Disparities to further explore and respond to the unique challenges that the crisis presents for Black and Brown communities.", "qid": 41, "docid": "orz4be90", "rank": 13, "score": 0.815133810043335}, {"content": "Title: Racial, Economic and Health Inequality and COVID-19 Infection in the United States Content: Abstract Background: There is preliminary evidence of racial and social-economic disparities in the population infected by and dying from COVID-19. The goal of this study is to report the associations of COVID-19 with respect to race, health and economic inequality in the United States. Methods: We performed a cross-sectional study of the associations between infection and mortality rate of COVID-19 and demographic, socioeconomic and mobility variables from 369 counties (total population: 102,178,117 [median: 73,447, IQR: 30,761-256,098]) from the seven most affected states (Michigan, New York, New Jersey, Pennsylvania, California, Louisiana, Massachusetts). Findings: The risk factors for infection and mortality are different. Our analysis shows that counties with more diverse demographics, higher population, education, income levels, and lower disability rates were at a higher risk of COVID-19 infection. However, counties with higher disability and poverty rates had a higher death rate. African Americans were more vulnerable to COVID-19 than other ethnic groups (1,981 African American infected cases versus 658 Whites per million). Data on mobility changes corroborate the impact of social distancing. Interpretation: The observed inequality might be due to the workforce of essential services, poverty, and access to care. Counties in more urban areas are probably better equipped at providing care. The lower rate of infection, but a higher death rate in counties with higher poverty and disability could be due to lower levels of mobility, but a higher rate of comorbidities and health care access. Keywords: Healthcare Disparities, Health Status Disparities, Socioeconomic Factors, COVID-19, Economic Inequality, Racial Disparity, United States, Population-Based Analysis.", "qid": 41, "docid": "alrf67ep", "rank": 14, "score": 0.8126418590545654}, {"content": "Title: Assessing racial and ethnic disparities using a COVID-19 outcomes continuum for New York State Content: PURPOSE: Heightened COVID-19 mortality among Black non-Hispanic and Hispanic communities (relative to white non-Hispanic) is well established. This study aims to estimate the relative contributions to fatality disparities in terms of differences in SARS-CoV-2 infections, diagnoses, and disease severity. METHODS: We constructed COVID-19 outcome continua (similar to the HIV care continuum) for white non-Hispanic, Black non-Hispanic, and Hispanic adults in New York State. For each stage in the COVID-19 outcome continua (population, infection experience, diagnosis, hospitalization, fatality), we synthesized the most recent publicly-available data. We described each continuum using overall percentages, fatality rates, and relative changes between stages, with comparisons between race and ethnicity using risk ratios. RESULTS: Estimated per-population COVID-19 fatality rates were 0.03%, 0.18%, and 0.12% for white non-Hispanic, Black non-Hispanic, and Hispanic adults. The 3.48-fold disparity for Hispanic, relative to white, communities was explained by differences in infection-experience, whereas the 5.38-fold disparity for non-Hispanic Black, relative to white, communities was primarily driven by differences in both infection-experience and in the need for hospitalization, given infection. CONCLUSIONS: These findings suggest the most impactful stages upon which to intervene with programs and policies to build COVID-19 health equity.", "qid": 41, "docid": "k2wojibt", "rank": 15, "score": 0.8121737241744995}, {"content": "Title: Social and psychological consequences of the COVID-19 pandemic in African-American communities: Lessons from Michigan Content: The mental health consequences of the COVID-19 pandemic are particularly relevant in African-American communities because African-Americans have been disproportionately impacted by the disease, yet they are traditionally less engaged in mental health treatment compared with other racial groups. Using the state of Michigan as an example, we describe the social and psychological consequences of the pandemic on African-American communities in the United States, highlighting community members' concerns about contracting the disease, fears of racial bias in testing and treatment, experiences of sustained grief and loss, and retraumatization of already-traumatized communities. Furthermore, we describe the multilevel, community-wide approaches that have been used thus far to mitigate adverse mental health outcomes within our local African-American communities. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "423uero3", "rank": 16, "score": 0.810620903968811}, {"content": "Title: Social and psychological consequences of the COVID-19 pandemic in African-American communities: Lessons from Michigan. Content: The mental health consequences of the COVID-19 pandemic are particularly relevant in African-American communities because African-Americans have been disproportionately impacted by the disease, yet they are traditionally less engaged in mental health treatment compared with other racial groups. Using the state of Michigan as an example, we describe the social and psychological consequences of the pandemic on African-American communities in the United States, highlighting community members' concerns about contracting the disease, fears of racial bias in testing and treatment, experiences of sustained grief and loss, and retraumatization of already-traumatized communities. Furthermore, we describe the multilevel, community-wide approaches that have been used thus far to mitigate adverse mental health outcomes within our local African-American communities. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "zdmoifko", "rank": 17, "score": 0.810620903968811}, {"content": "Title: Social Equity and COVID\u201019: The Case of African Americans Content: Emerging statistics demonstrate that COVID\u201019 disproportionately affects African Americans. The effects of COVID\u201019 for this population are inextricably linked to areas of systemic oppression and disenfranchisement, which are further exacerbated by COVID\u201019: (1) healthcare inequality; (2) segregation, overall health, and food insecurity; (3) underrepresentation in government and the medical profession; and (4) inequalities in participatory democracy and public engagement. Following a discussion of these issues, this article shares early and preliminary lessons and strategies on how public administration scholars and practitioners can lead in crafting equitable responses to this global pandemic to uplift the African American community. This article is protected by copyright. All rights reserved.", "qid": 41, "docid": "yq7enzvm", "rank": 18, "score": 0.8105967044830322}, {"content": "Title: Sickle Cell Trait and The Potential Risk of Severe Coronavirus Disease 2019- A Mini-Review Content: Coronavirus Disease 2019 (COVID-19) pandemic is a rapidly evolving public health problem. The severity of COVID-19 cases reported hitherto has varied greatly from asymptomatic to severe pneumonia and thromboembolism with subsequent mortality. An improved understanding of risk factors for adverse clinical outcomes may shed some light on novel personalized approaches to optimize clinical care in vulnerable populations. Emerging trends in the United States suggest possibly higher mortality rates of COVID-19 amongst African Americans, although detailed epidemiological study data is pending. Sickle Cell Disease (SCD) disproportionately affect Black/African Americans in the United States as well as forebearers from sub-Saharan Africa, the Western Hemisphere (South America, the Caribbean, and Central America) and some Mediterranean countries. The carrier frequency for SCD is high amongst African Americans. This article underscores the putative risks that may be associated with COVID-19 pneumonia in sickle cell trait as well as potential opportunities for individualized medical care in the burgeoning era of personalized medicine.", "qid": 41, "docid": "7z5rkti3", "rank": 19, "score": 0.809428334236145}, {"content": "Title: Sickle cell trait and the potential risk of severe coronavirus disease 2019\u2014A mini\u2010review Content: Coronavirus Disease 2019 (COVID\u201019) pandemic is a rapidly evolving public health problem. The severity of COVID\u201019 cases reported hitherto has varied greatly from asymptomatic to severe pneumonia and thromboembolism with subsequent mortality. An improved understanding of risk factors for adverse clinical outcomes may shed some light on novel personalized approaches to optimize clinical care in vulnerable populations. Emerging trends in the United States suggest possibly higher mortality rates of COVID\u201019 among African Americans, although detailed epidemiological study data is pending. Sickle cell disease (SCD) disproportionately affects Black/African Americans in the United States as well as forebearers from sub\u2010Saharan Africa, the Western Hemisphere (South America, the Caribbean, and Central America), and some Mediterranean countries. The carrier frequency for SCD is high among African Americans. This article underscores the putative risks that may be associated with COVID\u201019 pneumonia in sickle cell trait as well as potential opportunities for individualized medical care in the burgeoning era of personalized medicine.", "qid": 41, "docid": "ubkl52d0", "rank": 20, "score": 0.80926513671875}, {"content": "Title: Comorbidities and Disparities in Outcomes of COVID-19 Among African American and White Patients Content: Initial surveillance data suggests a disproportionately high number of deaths among Black patients with COVID-19. However, high-risk comorbidities are often over-represented in the Black population, and understanding whether the disparity is entirely secondary to them is essential. We performed a retrospective cohort study using real-time analysis of electronic medical records (EMR) of patients from multiple healthcare organizations in the United States. Our results showed that Black patients with COVID-19 have a significantly higher risk of mortality, hospitalization, and invasive mechanical ventilation compared to White patients. The incremental risk of poor outcomes in Blacks persists despite accounting for a higher prevalence of comorbidities. This may point to the disparities in socioeconomic determinants of health affecting Blacks and the need for an improvement in the care of this vulnerable population.", "qid": 41, "docid": "cuo7qdkj", "rank": 21, "score": 0.8077729940414429}, {"content": "Title: Disparities in COVID-19 Reported Incidence, Knowledge, and Behavior Content: Abstract Background: Data from the COVID-19 pandemic in the United States show large differences in hospitalizations and mortality across race and geography. However, there is limited data on health information, beliefs, and behaviors that might indicate different exposure to risk. Methods: A sample of 5,198 respondents in the United States (80% population representative, 20% oversample of hotspot areas in New York City, Seattle, New Orleans, and Detroit) was conducted from March 29th to April 13th to measure differences in knowledge, beliefs and behavior regarding COVID-19. Linear regression was used to understand racial, geographic, political, and socioeconomic differences in COVID-19 reported incidence knowledge, and behaviors after adjusting for state-specific and survey date fixed effects. Results: The largest differences in COVID-19 knowledge and behaviors are associated with race/ethnicity, gender, and age. African-Americans, men, and people <55 years old are less likely to know how the disease is spread, less likely to know symptoms of COVID-19, wash their hands less frequently, and leave the home more often. Differences by income, political orientation, and living in a hotspot area are much smaller. Conclusions: There are wide gaps in COVID-19 reported incidence, knowledge regarding disease spread and symptoms, and in social distancing behavior. The findings suggest more effort is needed to increase accurate information and encourage appropriate behaviors among minority communities, men, and younger people.", "qid": 41, "docid": "92o3dujh", "rank": 22, "score": 0.8075079917907715}, {"content": "Title: Black-White Risk Differentials in COVID-19 (SARS-COV2) Transmission, Mortality and Case Fatality in the United States: Translational Epidemiologic Perspective and Challenges Content: BACKGROUND: Social and health inequities predispose vulnerable populations to adverse morbidity and mortality outcomes of epidemics and pandemics. While racial disparities in cumulative incidence (CmI) and mortality from the influenza pandemics of 1918 and 2009 implicated Blacks with survival disadvantage relative to Whites in the United States, COVID-19 currently indicates comparable disparities. We aimed to: (a) assess COVID-19 CmI by race, (b) determine the Black-White case fatality (CF) and risk differentials, and (c) apply explanatory model for mortality risk differentials. METHODS: COVID-19 data on confirmed cases and deaths by selective states health departments were assessed using a cross-sectional ecologic design. Chi-square was used for CF independence, while binomial regression model for the Black-White risk differentials. RESULTS: The COVID-19 mortality CmI indicated Blacks/AA with 34% of the total mortality in the United States, albeit their 13% population size. The COVID-19 CF was higher among Blacks/AA relative to Whites; Maryland, (2.7% vs. 2.5%), Wisconsin (7.4% vs. 4.8%), Illinois (4.8% vs. 4.2%), Chicago (5.9% vs. 3.2%), Detroit (Michigan), 7.2% and St. John the Baptist Parish (Louisiana), 7.9%. Blacks/AA compared to Whites in Michigan were 15% more likely to die, CmI risk ratio (CmIRR) = 1.15, 95% CI, 1.01-1.32. Blacks/AA relative to Whites in Illinois were 13% more likely to die, CmIRR = 1.13, 95% CI, 0.93-1.39, while Blacks/AA compared to Whites in Wisconsin were 51% more likely to die, CmIRR = 1.51, 95% CI, 1.10-2.10. In Chicago, Blacks/AA were more than twice as likely to die, CmIRR = 2.24, 95% CI, 1.36-3.88. CONCLUSION: Substantial racial/ethnic disparities are observed in COVID-19 CF and mortality with Blacks/AA disproportionately affected across the United States.", "qid": 41, "docid": "9cy1jrw9", "rank": 23, "score": 0.8059338927268982}, {"content": "Title: Disproportionate incidence of COVID-19 in African Americans correlates with dynamic segregation Content: Socio-economic disparities quite often have a central role in the unfolding of large-scale catastrophic events. One of the most concerning aspects of the ongoing COVID-19 pandemics is that it disproportionately affects people from Black and African American backgrounds creating an unexpected infection gap. Interestingly, the abnormal impact on these ethnic groups seem to be almost uncorrelated with other risk factors, including co-morbidity, poverty, level of education, access to healthcare, residential segregation, and response to cures. A proposed explanation for the observed incidence gap is that people from African American backgrounds are more often employed in low-income service jobs, and are thus more exposed to infection through face-to-face contacts, but the lack of direct data has not allowed to draw strong conclusions in this sense so far. Here we introduce the concept of dynamic segregation, that is the extent to which a given group of people is internally clustered or exposed to other groups, as a result of mobility and commuting habits. By analysing census and mobility data on more than 120 major US cities, we found that the dynamic segregation of African American communities is significantly associated with the weekly excess COVID-19 incidence and mortality in those communities. The results confirm that knowing where people commute to, rather than where they live, is much more relevant for disease modelling.", "qid": 41, "docid": "3lkahro8", "rank": 24, "score": 0.8055242300033569}, {"content": "Title: Are Clinicians Contributing to Excess African American COVID-19 Deaths? Unbeknownst to Them, They May Be Content: African Americans are overrepresented among reported coronavirus disease 2019 (COVID-19) cases and deaths. There are a multitude of factors that may explain the African American disparity in COVID-19 outcomes, including higher rates of comorbidities. While individual-level factors predictably contribute to disparate COVID-19 outcomes, systematic and structural factors have not yet been reported. It stands to reason that implicit biases may fuel the racial disparity in COVID-19 outcomes. To address this racial disparity, we must apply a health equity lens and disaggregate data explicitly for African Americans, as well as other populations at risk for biased treatment in the health-care system.", "qid": 41, "docid": "1lw5vbu9", "rank": 25, "score": 0.8047500848770142}, {"content": "Title: Black\u2013White Risk Differentials in COVID-19 (SARS-COV2) Transmission, Mortality and Case Fatality in the United States: Translational Epidemiologic Perspective and Challenges Content: Background: Social and health inequities predispose vulnerable populations to adverse morbidity and mortality outcomes of epidemics and pandemics. While racial disparities in cumulative incidence (CmI) and mortality from the influenza pandemics of 1918 and 2009 implicated Blacks with survival disadvantage relative to Whites in the United States, COVID-19 currently indicates comparable disparities. We aimed to: (a) assess COVID-19 CmI by race, (b) determine the Black\u2013White case fatality (CF) and risk differentials, and (c) apply explanatory model for mortality risk differentials. Methods: COVID-19 data on confirmed cases and deaths by selective states health departments were assessed using a cross-sectional ecologic design. Chi-square was used for CF independence, while binomial regression model for the Black\u2013White risk differentials. Results: The COVID-19 mortality CmI indicated Blacks/AA with 34% of the total mortality in the United States, albeit their 13% population size. The COVID-19 CF was higher among Blacks/AA relative to Whites; Maryland, (2.7% vs. 2.5%), Wisconsin (7.4% vs. 4.8%), Illinois (4.8% vs. 4.2%), Chicago (5.9% vs. 3.2%), Detroit (Michigan), 7.2% and St. John the Baptist Parish (Louisiana), 7.9%. Blacks/AA compared to Whites in Michigan were 15% more likely to die, CmI risk ratio (CmIRR) = 1.15, 95% CI, 1.01\u20131.32. Blacks/AA relative to Whites in Illinois were 13% more likely to die, CmIRR = 1.13, 95% CI, 0.93\u20131.39, while Blacks/AA compared to Whites in Wisconsin were 51% more likely to die, CmIRR = 1.51, 95% CI, 1.10\u20132.10. In Chicago, Blacks/AA were more than twice as likely to die, CmIRR = 2.24, 95% CI, 1.36\u20133.88. Conclusion: Substantial racial/ethnic disparities are observed in COVID-19 CF and mortality with Blacks/AA disproportionately affected across the United States.", "qid": 41, "docid": "96001cps", "rank": 26, "score": 0.8046314120292664}, {"content": "Title: COVID-19 outcomes, risk factors and associations by race: a comprehensive analysis using electronic health records data in Michigan Medicine Content: Importance: Blacks/African-Americans are overrepresented in the number of COVID-19 infections, hospitalizations and deaths. Reasons for this disparity have not been well-characterized but may be due to underlying comorbidities or sociodemographic factors. Objective: To systematically determine patient characteristics associated with racial/ethnic disparities in COVID-19 outcomes. Design: A retrospective cohort study with comparative control groups. Setting: Patients tested for COVID-19 at University of Michigan Medicine from March 10, 2020 to April 22, 2020. Participants: 5,698 tested patients and two sets of comparison groups who were not tested for COVID-19: randomly selected unmatched controls (n = 7,211) and frequency-matched controls by race, age, and sex (n = 13,351). Main Outcomes and Measures: We identified factors associated with testing and testing positive for COVID-19, being hospitalized, requiring intensive care unit (ICU) admission, and mortality (in/out-patient during the time frame). Factors included race/ethnicity, age, smoking, alcohol consumption, healthcare utilization, and residential-level socioeconomic characteristics (SES; i.e., education, unemployment, population density, and poverty rate). Medical comorbidities were defined from the International Classification of Diseases (ICD) codes, and were aggregated into a comorbidity score. Results: Of 5,698 patients, (median age, 47 years; 38% male; mean BMI, 30.1), the majority were non-Hispanic Whites (NHW, 59.2%) and non-Hispanic Black/African-Americans (NHAA, 17.2%). Among 1,119 diagnosed, there were 41.2% NHW and 37.4% NHAA; 44.8% hospitalized, 20.6% admitted to ICU, and 3.8% died. Adjusting for age, sex, and SES, NHAA were 1.66 times more likely to be hospitalized (95% CI, 1.09-2.52; P=.02), 1.52 times more likely to enter ICU (95% CI, 0.92-2.52; P=.10). In addition to older age, male sex and obesity, high population density neighborhood (OR, 1.27 associated with one SD change [95% CI, 1.20-1.76]; P=.02) was associated with hospitalization. Pre-existing kidney disease led to 2.55 times higher risk of hospitalization (95% CI, 1.62-4.02; P<.001) in the overall population and 11.9 times higher mortality risk in NHAA (95% CI, 2.2-64.7, P=.004). Conclusions and Relevance: Pre-existing type II diabetes/kidney diseases and living in high population density areas were associated with high risk for COVID-19 susceptibility and poor prognosis. Association of risk factors with COVID-19 outcomes differed by race. NHAA patients were disproportionately affected by obesity and kidney disease.", "qid": 41, "docid": "zxb8zfep", "rank": 27, "score": 0.8038695454597473}, {"content": "Title: The Disproportionate Impact of COVID-19 on Racial and Ethnic Minorities in the United States Content: The COVID-19 pandemic has disproportionately affected racial and ethnic minority groups, with high rates of death in African American, Native American, and LatinX communities. While the mechanisms of these disparities are being investigated, they can be conceived as arising from biomedical factors as well as social determinants of health. Minority groups are disproportionately affected by chronic medical conditions and lower access to healthcare that may portend worse COVID-19 outcomes. Furthermore, minority communities are more likely to experience living and working conditions that predispose them to worse outcomes. Underpinning these disparities are long-standing structural and societal factors that the COVID-19 pandemic has exposed. Clinicians can partner with patients and communities to reduce the short-term impact of COVID-19 disparities while advocating for structural change.", "qid": 41, "docid": "u7s67aug", "rank": 28, "score": 0.8035158514976501}, {"content": "Title: Assessing Differential Impacts of COVID-19 on Black Communities Content: PURPOSE: Given incomplete data reporting by race, we used data on COVID-19 cases and deaths in US counties to describe racial disparities in COVID-19 disease and death and associated determinants. METHODS: Using publicly available data (accessed April 13, 2020), predictors of COVID-19 cases and deaths were compared between disproportionately (>13%) black and all other (<13% black) counties. Rate ratios were calculated and population attributable fractions (PAF) were estimated using COVID-19 cases and deaths via zero-inflated negative binomial regression model. National maps with county-level data and an interactive scatterplot of COVID-19 cases were generated. RESULTS: Nearly ninety-seven percent of disproportionately black counties (656/677) reported a case and 49% (330/677) reported a death versus 81% (1987/2,465) and 28% (684/ 2465), respectively, for all other counties. Counties with higher proportions of black people have higher prevalence of comorbidities and greater air pollution. Counties with higher proportions of black residents had more COVID-19 diagnoses (RR 1.24, 95% CI 1.17-1.33) and deaths (RR 1.18, 95% CI 1.00-1.40), after adjusting for county-level characteristics such as age, poverty, comorbidities, and epidemic duration. COVID-19 deaths were higher in disproportionally black rural and small metro counties. The PAF of COVID-19 diagnosis due to lack of health insurance was 3.3% for counties with <13% black residents and 4.2% for counties with >13% black residents. CONCLUSIONS: Nearly twenty-two percent of US counties are disproportionately black and they accounted for 52% of COVID-19 diagnoses and 58% of COVID-19 deaths nationally. County-level comparisons can both inform COVID-19 responses and identify epidemic hot spots. Social conditions, structural racism, and other factors elevate risk for COVID-19 diagnoses and deaths in black communities.", "qid": 41, "docid": "kr86wlax", "rank": 29, "score": 0.8035073280334473}, {"content": "Title: Assessing Differential Impacts of COVID-19 on Black Communities Content: Purpose: Given incomplete data reporting by race, we used data on COVID-19 cases and deaths in US counties to describe racial disparities in COVID-19 disease and death and associated determinants. Methods: Using publicly available data (accessed April 13, 2020), predictors of COVID-19 cases and deaths were compared between disproportionately (>13%) black and all other (<13% black) counties. Rate ratios were calculated and population attributable fractions (PAF) were estimated using COVID-19 cases and deaths via zero-inflated negative binomial regression model. National maps with county-level data and an interactive scatterplot of COVID-19 cases were generated. Results: Nearly ninety-seven percent of disproportionately black counties (656/677) reported a case and 49% (330/677) reported a death versus 81% (1987/2,465) and 28% (684/ 2465), respectively, for all other counties. Counties with higher proportions of black people have higher prevalence of comorbidities and greater air pollution. Counties with higher proportions of black residents had more COVID-19 diagnoses (RR 1.24, 95% CI 1.17-1.33) and deaths (RR 1.18, 95% CI 1.00-1.40), after adjusting for county-level characteristics such as age, poverty, comorbidities, and epidemic duration. COVID-19 deaths were higher in disproportionally black rural and small metro counties. The PAF of COVID-19 diagnosis due to lack of health insurance was 3.3% for counties with <13% black residents and 4.2% for counties with >13% black residents. Conclusions: Nearly twenty-two percent of US counties are disproportionately black and they accounted for 52% of COVID-19 diagnoses and 58% of COVID-19 deaths nationally. County-level comparisons can both inform COVID-19 responses and identify epidemic hot spots. Social conditions, structural racism, and other factors elevate risk for COVID-19 diagnoses and deaths in black communities.", "qid": 41, "docid": "dl3vkqas", "rank": 30, "score": 0.8035073280334473}, {"content": "Title: Assessing Differential Impacts of COVID-19 on Black Communities Content: Purpose Given incomplete data reporting by race, we used data on COVID-19 cases and deaths in US counties to describe racial disparities in COVID-19 disease and death and associated determinants. Methods Using publicly available data (accessed April 13, 2020), predictors of COVID-19 cases and deaths were compared between disproportionately (>13%) black and all other (<13% black) counties. Rate ratios were calculated and population attributable fractions (PAF) were estimated using COVID-19 cases and deaths via zero-inflated negative binomial regression model. National maps with county-level data and an interactive scatterplot of COVID-19 cases were generated. Results Nearly ninety-seven percent of disproportionately black counties (656/677) reported a case and 49% (330/677) reported a death versus 81% (1987/2,465) and 28% (684/ 2465), respectively, for all other counties. Counties with higher proportions of black people have higher prevalence of comorbidities and greater air pollution. Counties with higher proportions of black residents had more COVID-19 diagnoses (RR 1.24, 95% CI 1.17-1.33) and deaths (RR 1.18, 95% CI 1.00-1.40), after adjusting for county-level characteristics such as age, poverty, comorbidities, and epidemic duration. COVID-19 deaths were higher in disproportionally black rural and small metro counties. The PAF of COVID-19 diagnosis due to lack of health insurance was 3.3% for counties with <13% black residents and 4.2% for counties with >13% black residents. Conclusions Nearly twenty-two percent of US counties are disproportionately black and they accounted for 52% of COVID-19 diagnoses and 58% of COVID-19 deaths nationally. County-level comparisons can both inform COVID-19 responses and identify epidemic hot spots. Social conditions, structural racism, and other factors elevate risk for COVID-19 diagnoses and deaths in black communities.", "qid": 41, "docid": "p5owyivo", "rank": 31, "score": 0.8033217191696167}, {"content": "Title: Policy Recommendations to Address High Risk of COVID-19 Among Immigrants Content: The health and economic consequences of COVID-19 will be devastatingly widespread, but the populations that will suffer most are those who have experienced longstanding health disparities. For example, emerging evidence strongly suggests that incidence and case fatality rates are higher among Blacks than Whites.1 Immigrants are among the groups most likely to experience disproportionate effects from COVID-19. Unlike race/ethnicity, however, nativity and citizenship status are not included on the Centers for Disease Control and Prevention's (CDC's) coronavirus case report form,2 so data regarding testing and spread across immigrant groups are likely to remain scarce. Information from other health and social surveys-including data that I present in Table 1-suggest that noncitizens experience barriers to physical distancing that will place them at high risk of contracting COVID-19 and have high levels of disadvantage that leave them vulnerable to its economic effects. I recommend three policy changes to address the high health and economic risk among noncitizens, goals that are in the best interest of public health and the broader economy. (Am J Public Health. Published online ahead of print June 25, 2020: e1-e3. doi:10.2105/AJPH.2020.305792).", "qid": 41, "docid": "71rhjy74", "rank": 32, "score": 0.8027575016021729}, {"content": "Title: Policy Recommendations to Address High Risk of COVID-19 Among Immigrants. Content: The health and economic consequences of COVID-19 will be devastatingly widespread, but the populations that will suffer most are those who have experienced longstanding health disparities. For example, emerging evidence strongly suggests that incidence and case fatality rates are higher among Blacks than Whites.1 Immigrants are among the groups most likely to experience disproportionate effects from COVID-19. Unlike race/ethnicity, however, nativity and citizenship status are not included on the Centers for Disease Control and Prevention's (CDC's) coronavirus case report form,2 so data regarding testing and spread across immigrant groups are likely to remain scarce. Information from other health and social surveys-including data that I present in Table 1-suggest that noncitizens experience barriers to physical distancing that will place them at high risk of contracting COVID-19 and have high levels of disadvantage that leave them vulnerable to its economic effects. I recommend three policy changes to address the high health and economic risk among noncitizens, goals that are in the best interest of public health and the broader economy. (Am J Public Health. Published online ahead of print June 25, 2020: e1-e3. doi:10.2105/AJPH.2020.305792).", "qid": 41, "docid": "bb8u9nmj", "rank": 33, "score": 0.8027575016021729}, {"content": "Title: This Time Must Be Different: Disparities During the COVID-19 Pandemic Content: African Americans and Latinos are overrepresented among cases of and deaths from COVID-19 nationally and in many of the U.S. regions hardest hit by the pandemic. The editorialist discusses lessons that we should have learned from prior experiences and strategies to reduce observed disparities.", "qid": 41, "docid": "fsid4a39", "rank": 34, "score": 0.8016392588615417}, {"content": "Title: Why African Americans Are a Potential Target for COVID-19 Infection in the United States Content: Since the World Health Organization declared the coronavirus disease (COVID-19) outbreak a pandemic, significant changes have occurred in the United States as the infection spread reached and passed its exponential phase. A stringent analysis of COVID-19 epidemiologic data requires time and would generally be expected to happen with significant delay after the exponential phase of the disease is over and when the focus of the health care system is diverted away from crisis management. Although much has been said about high-risk groups and the vulnerability of the elderly and patients with underlying comorbidities, the impact of race on the susceptibility of ethnic minorities living in indigent communities has not been discussed in detail worldwide and specifically in the United States. There are currently some data on disparities between African American and Caucasian populations for COVID-19 infection and mortality. While health care authorities are reorganizing resources and infrastructure to provide care for symptomatic COVID-19 patients, they should not shy away from protecting the general public as a whole and specifically the most vulnerable members of society, such as the elderly, ethnic minorities, and people with underlying comorbidities.", "qid": 41, "docid": "wwucpqin", "rank": 35, "score": 0.8001971244812012}, {"content": "Title: COVID-19: A Closer Lens Content: Generations of nurses to come, now called heroes in the media, will have challenges in providing care for persons during this global pandemic. COVID-19 has impacted all demographics, regardless of race, gender, or socioeconomic class globally. African Americans have experienced a disproportionate number of deaths related to COVID-19 in the New Orleans and surrounding Metropolitan areas. According to the Louisiana Department of Health (2020), fifty-seven percent (57.40%) of the deaths in Louisiana related to COVID-19 have been African American (Black) and fifty-five percent (55.2%) have been males as of May 11, 2020. Social determinants of health are the conditions in which people age and the conditions they are born, grow, age and work. These conditions include neighborhoods, schools, and places of employment. These circumstances are shaped by the distribution of money, power, and resources at global, national, and local levels (World Health Organization, 2020). Years later the same community that comprised \"pre-and post-Katrina\" are now facing this pandemic.", "qid": 41, "docid": "peys32ve", "rank": 36, "score": 0.8000626564025879}, {"content": "Title: COVID-19: A Closer Lens. Content: Generations of nurses to come, now called heroes in the media, will have challenges in providing care for persons during this global pandemic. COVID-19 has impacted all demographics, regardless of race, gender, or socioeconomic class globally. African Americans have experienced a disproportionate number of deaths related to COVID-19 in the New Orleans and surrounding Metropolitan areas. According to the Louisiana Department of Health (2020), fifty-seven percent (57.40%) of the deaths in Louisiana related to COVID-19 have been African American (Black) and fifty-five percent (55.2%) have been males as of May 11, 2020. Social determinants of health are the conditions in which people age and the conditions they are born, grow, age and work. These conditions include neighborhoods, schools, and places of employment. These circumstances are shaped by the distribution of money, power, and resources at global, national, and local levels (World Health Organization, 2020). Years later the same community that comprised \"pre-and post-Katrina\" are now facing this pandemic.", "qid": 41, "docid": "b7x39b3m", "rank": 37, "score": 0.8000626564025879}, {"content": "Title: Multivariate Analysis of Black Race and Environmental Temperature on COVID-19 In the US Content: BACKGROUND: There has been much interest in environmental temperature and race as modulators of Coronavirus disease-19 (COVID-19) infection and mortality. However, in the United States race and temperature correlate with various other social determinants of health, comorbidities, and environmental influences that could be responsible for noted effects. This study investigates the independent effects of race and environmental temperature on COVID-19 incidence and mortality in United States counties. METHODS: Data on COVID-19 and risk factors in all United States counties was collected. 661 counties with at least 50 COVID-19 cases and 217 with at least 10 deaths were included in analyses. Upper and lower quartiles for cases/100,000 people and halves for deaths/100,000 people were compared with t-tests. Adjusted linear and logistic regression analyses were performed to evaluate the independent effects of race and environmental temperature. RESULTS: Multivariate regression analyses demonstrated Black race is a risk factor for increased COVID-19 cases (OR=1.22, 95% CI: 1.09-1.40, P=0.001) and deaths independent of comorbidities, poverty, access to health care, and other risk factors. Higher environmental temperature independently reduced caseload (OR=0.81, 95% CI: 0.71-0.91, P=0.0009), but not deaths. CONCLUSIONS: Higher environmental temperatures correlated with reduced COVID-19 cases, but this benefit does not yet appear in mortality models. Black race was an independent risk factor for increased COVID-19 cases and deaths. Thus, many proposed mechanisms through which Black race might increase risk for COVID-19, such as socioeconomic and healthcare-related predispositions, are inadequate in explaining the full magnitude of this health disparity.", "qid": 41, "docid": "0wspp086", "rank": 38, "score": 0.7973336577415466}, {"content": "Title: Absence of Skin of Colour Images in Publications of COVID-19 Skin Manifestations Content: There are now over 1 million confirmed cases of COVID-19 globally with more than 270,000 recorded deaths to date. COVID-19 has been shown to disproportionately impact people of colour both in the United Kingdom and in the United States where blacks make up 13.4% of the population but 30% of COVID-19 cases. Mounting evidence shows that COVID-19 impacts several organ systems, including the skin.", "qid": 41, "docid": "33uqbusb", "rank": 39, "score": 0.7957234382629395}, {"content": "Title: County-Level Proportions of Black and Hispanic populations, and Socioeconomic Characteristics in Association with Confirmed COVID-19 Cases and Deaths in the United States Content: Objectives. The objective of this study was to investigate potential county-level disparities among racial/ethnic and economic groups in COVID-19 burden which was measured using confirmed cases and deaths in 100,000 population. Design. Secondary data analysis Using county-level data for 3,142 US counties was conducted in 2020. Hierarchical linear regression and concentration curve analyses were performed. The combined association of COVID-19 cases and deaths was examined separately by sociodemographic and economic characteristics of the county population. Data from the American Community Survey (ACS) 5-year estimates (2014-2018), Area Health Resources File (AHRF) 2018-2019, and 2020 COVID-19 data from Johns Hopkins University were used in this study. Results. After adjusting for covariates, US counties with a higher proportion of the black population, and a higher proportion of adults with less than high school diploma had disproportionately higher COVID-19 cases and deaths ({beta}>0, p<0.05). A higher proportion of the Hispanic population was associated with higher confirmed cases ({beta}= 1.03, 95% CI= 0.57-1.5), and higher housing cost to household income ratio was associated with higher deaths ({beta}= 3.74, 95% CI= 2.14-5.37). This can potentially aggravate the existing health disparities among these population groups. Conclusions. Identification of disproportionately impacted population groups can pave the way towards narrowing the disparity gaps and guide policymakers and stakeholders in designing and implementing population group-specific interventions to mitigate the negative consequences of COVID-19 pandemic.", "qid": 41, "docid": "qcgttpqq", "rank": 40, "score": 0.7956489324569702}, {"content": "Title: Mental health ramifications of the COVID-19 pandemic for Black Americans: Clinical and research recommendations Content: Mental health clinicians and researchers must be prepared to address the unique needs of Black Americans who have been disproportionately affected by the COVID-19 pandemic. Race-conscious and culturally competent interventions that consider factors such as discrimination, distrust of health care providers, and historical and racial trauma as well as protective factors including social support and culturally sanctioned coping strategies are needed. Research to accurately assess and design treatments for the mental health consequences of COVID-19 among Black Americans is warranted. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "ef494his", "rank": 41, "score": 0.794960618019104}, {"content": "Title: Mental health ramifications of the COVID-19 pandemic for Black Americans: Clinical and research recommendations. Content: Mental health clinicians and researchers must be prepared to address the unique needs of Black Americans who have been disproportionately affected by the COVID-19 pandemic. Race-conscious and culturally competent interventions that consider factors such as discrimination, distrust of health care providers, and historical and racial trauma as well as protective factors including social support and culturally sanctioned coping strategies are needed. Research to accurately assess and design treatments for the mental health consequences of COVID-19 among Black Americans is warranted. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "4q97416a", "rank": 42, "score": 0.794960618019104}, {"content": "Title: Differences in race and other state\u2010level characteristics and associations with mortality from COVID\u201019 infection Content: As reporting of COVID\u201019 at the US state level has become more granular, many states have reported a higher proportion of deaths among African\u2010Americans. In our study, we assessed state level data on race, population density, age, obesity rates, insurance data, GDP, per capita healthcare resources (hospital\u2010beds/ventilators per\u2010capita), median household income and high\u2010school graduation rates. We report a higher death rate among states with a greater proportion of African\u2010American residents despite adjusting for case rates and state\u2010level factors. To the best of our knowledge this is the first study looking at state level data (from across the US) and mortality with COVID\u201019. This article is protected by copyright. All rights reserved.", "qid": 41, "docid": "rxgnrrx8", "rank": 43, "score": 0.7943077087402344}, {"content": "Title: Disparities in Coronavirus 2019 Reported Incidence, Knowledge, and Behavior Among US Adults Content: Importance: Data from the coronavirus disease 2019 (COVID-19) pandemic in the US show large differences in hospitalizations and mortality across race and geography. However, there are limited data on health information, beliefs, and behaviors that might indicate different exposure to risk. Objective: To determine the association of sociodemographic characteristics with reported incidence, knowledge, and behavior regarding COVID-19 among US adults. Design, Setting, and Participants: A US national survey study was conducted from March 29 to April 13, 2020, to measure differences in knowledge, beliefs, and behavior about COVID-19. The survey oversampled COVID-19 hotspot areas. The survey was conducted electronically. The criteria for inclusion were age 18 years or older and residence in the US. Data analysis was performed in April 2020. Main Outcomes and Measures: The main outcomes were incidence, knowledge, and behaviors related to COVID-19 as measured by survey response. Results: The survey included 5198 individuals (mean [SD] age, 48 [18] years; 2336 men [45%]; 3759 white [72%], 830 [16%] African American, and 609 [12%] Hispanic). The largest differences in COVID-19-related knowledge and behaviors were associated with race/ethnicity, sex, and age, with African American participants, men, and people younger than 55 years showing less knowledge than other groups. African American respondents were 3.5 percentage points (95% CI, 1.5 to 5.5 percentage points; P = .001) more likely than white respondents to report being infected with COVID-19, as were men compared with women (3.2 percentage points; 95% CI, 2.0 to 4.4 percentage points; P < .001). Knowing someone who tested positive for COVID-19 was more common among African American respondents (7.2 percentage points; 95% CI, 3.4 to 10.9 percentage points; P < .001), people younger than 30 years (11.6 percentage points; 95% CI, 7.5 to 15.7 percentage points; P < .001), and people with higher incomes (coefficient on earning &#8805;$100\u00e2\u0080\u00af000, 12.3 percentage points; 95% CI, 8.7 to 15.8 percentage points; P < .001). Knowledge of potential fomite spread was lower among African American respondents (-9.4 percentage points; 95% CI, -13.1 to -5.7 percentage points; P < .001), Hispanic respondents (-4.8 percentage points; 95% CI, -8.9 to -0.77 percentage points; P = .02), and people younger than 30 years (-10.3 percentage points; 95% CI, -14.1 to -6.5 percentage points; P < .001). Similar gaps were found with respect to knowledge of COVID-19 symptoms and preventive behaviors. Conclusions and Relevance: In this survey study of US adults, there were gaps in reported incidence of COVID-19 and knowledge regarding its spread and symptoms and social distancing behavior. More effort is needed to increase accurate information and encourage appropriate behaviors among minority communities, men, and younger people.", "qid": 41, "docid": "0iy8stse", "rank": 44, "score": 0.7941815257072449}, {"content": "Title: Disparities in Coronavirus 2019 Reported Incidence, Knowledge, and Behavior Among US Adults Content: IMPORTANCE: Data from the coronavirus disease 2019 (COVID-19) pandemic in the US show large differences in hospitalizations and mortality across race and geography. However, there are limited data on health information, beliefs, and behaviors that might indicate different exposure to risk. OBJECTIVE: To determine the association of sociodemographic characteristics with reported incidence, knowledge, and behavior regarding COVID-19 among US adults. DESIGN, SETTING, AND PARTICIPANTS: A US national survey study was conducted from March 29 to April 13, 2020, to measure differences in knowledge, beliefs, and behavior about COVID-19. The survey oversampled COVID-19 hotspot areas. The survey was conducted electronically. The criteria for inclusion were age 18 years or older and residence in the US. Data analysis was performed in April 2020. MAIN OUTCOMES AND MEASURES: The main outcomes were incidence, knowledge, and behaviors related to COVID-19 as measured by survey response. RESULTS: The survey included 5198 individuals (mean [SD] age, 48 [18] years; 2336 men [45%]; 3759 white [72%], 830 [16%] African American, and 609 [12%] Hispanic). The largest differences in COVID-19\u2013related knowledge and behaviors were associated with race/ethnicity, sex, and age, with African American participants, men, and people younger than 55 years showing less knowledge than other groups. African American respondents were 3.5 percentage points (95% CI, 1.5 to 5.5 percentage points; P = .001) more likely than white respondents to report being infected with COVID-19, as were men compared with women (3.2 percentage points; 95% CI, 2.0 to 4.4 percentage points; P < .001). Knowing someone who tested positive for COVID-19 was more common among African American respondents (7.2 percentage points; 95% CI, 3.4 to 10.9 percentage points; P < .001), people younger than 30 years (11.6 percentage points; 95% CI, 7.5 to 15.7 percentage points; P < .001), and people with higher incomes (coefficient on earning \u2265$100 000, 12.3 percentage points; 95% CI, 8.7 to 15.8 percentage points; P < .001). Knowledge of potential fomite spread was lower among African American respondents (\u22129.4 percentage points; 95% CI, \u221213.1 to \u22125.7 percentage points; P < .001), Hispanic respondents (\u22124.8 percentage points; 95% CI, \u22128.9 to \u22120.77 percentage points; P = .02), and people younger than 30 years (\u221210.3 percentage points; 95% CI, \u221214.1 to \u22126.5 percentage points; P < .001). Similar gaps were found with respect to knowledge of COVID-19 symptoms and preventive behaviors. CONCLUSIONS AND RELEVANCE: In this survey study of US adults, there were gaps in reported incidence of COVID-19 and knowledge regarding its spread and symptoms and social distancing behavior. More effort is needed to increase accurate information and encourage appropriate behaviors among minority communities, men, and younger people.", "qid": 41, "docid": "zz299uk5", "rank": 45, "score": 0.7941461801528931}, {"content": "Title: Similarities and Differences in COVID-19 Awareness, Concern, and Symptoms by Race and Ethnicity in the United States: Cross-Sectional Survey Content: BACKGROUND: Existing health disparities based on race and ethnicity in the United States are contributing to disparities in morbidity and mortality during the coronavirus disease (COVID-19) pandemic. We conducted an online survey of American adults to assess similarities and differences by race and ethnicity with respect to COVID-19 symptoms, estimates of the extent of the pandemic, knowledge of control measures, and stigma. OBJECTIVE: The aim of this study was to describe similarities and differences in COVID-19 symptoms, knowledge, and beliefs by race and ethnicity among adults in the United States. METHODS: We conducted a cross-sectional survey from March 27, 2020 through April 1, 2020. Participants were recruited on social media platforms and completed the survey on a secure web-based survey platform. We used chi-square tests to compare characteristics related to COVID-19 by race and ethnicity. Statistical tests were corrected using the Holm Bonferroni correction to account for multiple comparisons. RESULTS: A total of 1435 participants completed the survey; 52 (3.6%) were Asian, 158 (11.0%) were non-Hispanic Black, 548 (38.2%) were Hispanic, 587 (40.9%) were non-Hispanic White, and 90 (6.3%) identified as other or multiple races. Only one symptom (sore throat) was found to be different based on race and ethnicity (P=.003); this symptom was less frequently reported by Asian (3/52, 5.8%), non-Hispanic Black (9/158, 5.7%), and other/multiple race (8/90, 8.9%) participants compared to those who were Hispanic (99/548, 18.1%) or non-Hispanic White (95/587, 16.2%). Non-Hispanic White and Asian participants were more likely to estimate that the number of current cases was at least 100,000 (P=.004) and were more likely to answer all 14 COVID-19 knowledge scale questions correctly (Asian participants, 13/52, 25.0%; non-Hispanic White participants, 180/587, 30.7%) compared to Hispanic (108/548, 19.7%) and non-Hispanic Black (25/158, 15.8%) participants. CONCLUSIONS: We observed differences with respect to knowledge of appropriate methods to prevent infection by the novel coronavirus that causes COVID-19. Deficits in knowledge of proper control methods may further exacerbate existing race/ethnicity disparities. Additional research is needed to identify trusted sources of information in Hispanic and non-Hispanic Black communities and create effective messaging to disseminate correct COVID-19 prevention and treatment information.", "qid": 41, "docid": "961h5r54", "rank": 46, "score": 0.7928231954574585}, {"content": "Title: COVID-19 and the US response: accelerating health inequities Content: Health inequities have long defined health and the healthcare system in the USA. The clinical and research capacity across the USA is unparalleled, yet compared to other high and even some middle-income countries, the average health indicators of the population remain suboptimal in 2020, a finding at least in part explained by inequity in healthcare access. In this context, COVID-19 has rapidly emerged as a major threat to the public\u2019s health. While it was initially thought that severe acute respiratory syndrome coronavirus 2 would be the great equaliser as it would not discriminate, it is clear that COVID-19 incidence and mortality have rapidly reinforced health disparities drawn by historical and contemporary inequities. Here, we synthesise the data highlighting specific risks among particular marginalised and under-resourced communities including those in jails, prisons and detention centers, immigrants and the undocumented, people with disabilities and people experiencing homelessness across the USA. The drivers of these disparities are pervasive structural risks including limited access to preventive services, inability to comply with physical distancing recommendations, underlying health disparities and intersecting stigmas particularly affecting racial and ethnic minorities across the country, including African Americans, Latinx Americans and Native Americans. Advancing the COVID-19 response, saving lives and restarting the economy necessitate rapidly addressing these inequities rather than ignoring and even reinforcing them.", "qid": 41, "docid": "0ctlde8w", "rank": 47, "score": 0.7925699949264526}, {"content": "Title: COVID-19 and the US response: accelerating health inequities Content: Health inequities have long defined health and the healthcare system in the USA. The clinical and research capacity across the USA is unparalleled, yet compared to other high and even some middle-income countries, the average health indicators of the population remain suboptimal in 2020, a finding at least in part explained by inequity in healthcare access. In this context, COVID-19 has rapidly emerged as a major threat to the public's health. While it was initially thought that severe acute respiratory syndrome coronavirus 2 would be the great equaliser as it would not discriminate, it is clear that COVID-19 incidence and mortality have rapidly reinforced health disparities drawn by historical and contemporary inequities. Here, we synthesise the data highlighting specific risks among particular marginalised and under-resourced communities including those in jails, prisons and detention centers, immigrants and the undocumented, people with disabilities and people experiencing homelessness across the USA. The drivers of these disparities are pervasive structural risks including limited access to preventive services, inability to comply with physical distancing recommendations, underlying health disparities and intersecting stigmas particularly affecting racial and ethnic minorities across the country, including African Americans, Latinx Americans and Native Americans. Advancing the COVID-19 response, saving lives and restarting the economy necessitate rapidly addressing these inequities rather than ignoring and even reinforcing them.", "qid": 41, "docid": "n3wbuxnv", "rank": 48, "score": 0.7925658226013184}, {"content": "Title: Inequity and the disproportionate impact of COVID-19 on communities of color in the United States: The need for a trauma-informed social justice response Content: COVID-19 has had disproportionate contagion and fatality in Black, Latino, and Native American communities and among the poor in the United States. Toxic stress resulting from racial and social inequities have been magnified during the pandemic, with implications for poor physical and mental health and socioeconomic outcomes. It is imperative that our country focus and invest in addressing health inequities and work across sectors to build self-efficacy and long-term capacity within communities and systems of care serving the most disenfranchised, now and in the aftermath of the COVID-19 epidemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "81crwncn", "rank": 49, "score": 0.7884856462478638}, {"content": "Title: Inequity and the disproportionate impact of COVID-19 on communities of color in the United States: The need for a trauma-informed social justice response. Content: COVID-19 has had disproportionate contagion and fatality in Black, Latino, and Native American communities and among the poor in the United States. Toxic stress resulting from racial and social inequities have been magnified during the pandemic, with implications for poor physical and mental health and socioeconomic outcomes. It is imperative that our country focus and invest in addressing health inequities and work across sectors to build self-efficacy and long-term capacity within communities and systems of care serving the most disenfranchised, now and in the aftermath of the COVID-19 epidemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "q7telkky", "rank": 50, "score": 0.7884856462478638}, {"content": "Title: Disparities in Vulnerability to Severe Complications from COVID-19 in the United States Content: This paper provides the first nationally representative estimates of vulnerability to severe complications from COVID-19 overall and across race-ethnicity and socioeconomic status. We use the Panel Study of Income Dynamics (PSID) to examine the prevalence of specific health conditions associated with complications from COVID-19 and to calculate, for each individual, an index of the risk of severe complications from respiratory infections developed by DeCaprio et al. (2020). We show large disparities across race-ethnicity and socioeconomic status in the prevalence of conditions, including hypertension, which are associated with the risk of severe complications from COVID-19. Moreover, we show that these disparities emerge early in life, prior to age 65, leading to higher vulnerability to such complications. Our results suggest particular attention should be paid to the risk of adverse outcomes in midlife for non-Hispanic blacks, adults with a high school degree or less, and low-income Americans.", "qid": 41, "docid": "qk0cyee2", "rank": 51, "score": 0.788211464881897}, {"content": "Title: Sociodemographic predictors of outcomes in COVID-19: examining the impact of ethnic disparities in Northern Nevada Content: Background: On March 11, 2020, the World Health Organization declared coronavirus disease-19 (COVID-19) a pandemic. Nearly five million individuals have since been diagnosed with this increasingly common and potentially lethal viral infection. Emerging evidence suggests a disproportionate burden of illness and death among minority communities. We aimed to evaluate the effect of ethnicity on outcomes among patients diagnosed with COVID-19 in Northern Nevada. Design: Single-center, retrospective observational study Materials and methods: The electronic health records of 172 patients diagnosed with COVID-19 were obtained from a 946-bed tertiary referral center serving Northern Nevada. Demographic and clinical characteristics were compared by ethnic group (Hispanic versus non-Hispanic). Logistic regression was used to determine predictors of mortality. Results: Among 172 patients who were diagnosed with COVID-19 between March 12th and May 8th, 2020, 87 (50.6%) identified as Hispanic and 81 (47.1%) as non-Hispanic. The mean age was 46.0 among Hispanics and 55.8 among non-Hispanics. Comorbidities linked to increased COVID-19-related mortality - hypertension, obesity, and chronic obstructive pulmonary disease - were more common among the non-Hispanic population. Hispanic individuals were significantly more likely to be uninsured and to live in low-income communities as compared to their non-Hispanic counterparts (27.6% versus 8.2% and 52.9% versus 30.6%, respectively). Hispanic patients were also less likely than non-Hispanics to have a primary care provider (42.5% versus 61.2%). However, mortality was significantly higher among the non-Hispanic population (15.3% versus 5.8%). Conclusion: The COVID-19 pandemic has disproportionately affected Hispanic individuals in Northern Nevada, who account for only 25.7% of the population but over half of the confirmed cases. Hispanic individuals were younger and had fewer comorbidities than their non-Hispanic counterparts; consequently, despite considerable socioeconomic disadvantage, mortality was lower among the Hispanic population. The underlying causes of ethnic disparities in COVID-19 incidence remain to be established, but further investigation may lead to more effective community- and systems-based interventions.", "qid": 41, "docid": "39jjedq0", "rank": 52, "score": 0.7878811359405518}, {"content": "Title: Differential expression of COVID-19-related genes in European Americans and African Americans Content: The Coronavirus disease 2019 (COVID-19) pandemic has affected African American populations disproportionately in regards to both morbidity and mortality. A multitude of factors likely account for this discrepancy. Gene expression represents the interaction of genetics and environment. To elucidate whether levels of expression of genes implicated in COVID-19 vary in African Americans as compared to European Americans, we re-mine The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) RNA-Seq data. Multiple genes integral to infection, inflammation and immunity are differentially regulated across the two populations. Most notably, F8A2 and F8A3, which encode the HAP40 protein that mediates early endosome movement in Huntington\u2019s Disease, are more highly expressed by up to 24-fold in African Americans. Such differences in gene expression can establish prognostic signatures and have critical implications for precision treatment of diseases such as COVID-19. We advocate routine inclusion of information such as postal code, education level, and profession (as a proxies for socioeconomic condition) and race in the metadata about each individual sampled for sequencing studies. This relatively simple change would enable large-scale data-driven approaches to dissect relationships among race, socio-economic factors, and disease.", "qid": 41, "docid": "miayce9l", "rank": 53, "score": 0.7876255512237549}, {"content": "Title: Hospitalization and Mortality among Black Patients and White Patients with Covid-19 Content: BACKGROUND: Many reports on coronavirus disease 2019 (Covid-19) have highlighted age- and sex-related differences in health outcomes. More information is needed about racial and ethnic differences in outcomes from Covid-19. METHODS: In this retrospective cohort study, we analyzed data from patients seen within an integrated-delivery health system (Ochsner Health) in Louisiana between March 1 and April 11, 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes Covid-19) on qualitative polymerase-chain-reaction assay. The Ochsner Health population is 31% black non-Hispanic and 65% white non-Hispanic. The primary outcomes were hospitalization and in-hospital death. RESULTS: A total of 3626 patients tested positive, of whom 145 were excluded (84 had missing data on race or ethnic group, 9 were Hispanic, and 52 were Asian or of another race or ethnic group). Of the 3481 Covid-19\u2013positive patients included in our analyses, 60.0% were female, 70.4% were black non-Hispanic, and 29.6% were white non-Hispanic. Black patients had higher prevalences of obesity, diabetes, hypertension, and chronic kidney disease than white patients. A total of 39.7% of Covid-19\u2013positive patients (1382 patients) were hospitalized, 76.9% of whom were black. In multivariable analyses, black race, increasing age, a higher score on the Charlson Comorbidity Index (indicating a greater burden of illness), public insurance (Medicare or Medicaid), residence in a low-income area, and obesity were associated with increased odds of hospital admission. Among the 326 patients who died from Covid-19, 70.6% were black. In adjusted time-to-event analyses, variables that were associated with higher in-hospital mortality were increasing age and presentation with an elevated respiratory rate; elevated levels of venous lactate, creatinine, or procalcitonin; or low platelet or lymphocyte counts. However, black race was not independently associated with higher mortality (hazard ratio for death vs. white race, 0.89; 95% confidence interval, 0.68 to 1.17). CONCLUSIONS: In a large cohort in Louisiana, 76.9% of the patients who were hospitalized with Covid-19 and 70.6% of those who died were black, whereas blacks comprise only 31% of the Ochsner Health population. Black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission.", "qid": 41, "docid": "fm8koqjd", "rank": 54, "score": 0.7875820398330688}, {"content": "Title: Hospitalization and Mortality among Black Patients and White Patients with Covid-19 Content: BACKGROUND: Many reports on coronavirus disease 2019 (Covid-19) have highlighted age- and sex-related differences in health outcomes. More information is needed about racial and ethnic differences in outcomes from Covid-19. METHODS: In this retrospective cohort study, we analyzed data from patients seen within an integrated-delivery health system (Ochsner Health) in Louisiana between March 1 and April 11, 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes Covid-19) on qualitative polymerase-chain-reaction assay. The Ochsner Health population is 31% black non-Hispanic and 65% white non-Hispanic. The primary outcomes were hospitalization and in-hospital death. RESULTS: A total of 3626 patients tested positive, of whom 145 were excluded (84 had missing data on race or ethnic group, 9 were Hispanic, and 52 were Asian or of another race or ethnic group). Of the 3481 Covid-19-positive patients included in our analyses, 60.0% were female, 70.4% were black non-Hispanic, and 29.6% were white non-Hispanic. Black patients had higher prevalences of obesity, diabetes, hypertension, and chronic kidney disease than white patients. A total of 39.7% of Covid-19-positive patients (1382 patients) were hospitalized, 76.9% of whom were black. In multivariable analyses, black race, increasing age, a higher score on the Charlson Comorbidity Index (indicating a greater burden of illness), public insurance (Medicare or Medicaid), residence in a low-income area, and obesity were associated with increased odds of hospital admission. Among the 326 patients who died from Covid-19, 70.6% were black. In adjusted time-to-event analyses, variables that were associated with higher in-hospital mortality were increasing age and presentation with an elevated respiratory rate; elevated levels of venous lactate, creatinine, or procalcitonin; or low platelet or lymphocyte counts. However, black race was not independently associated with higher mortality (hazard ratio for death vs. white race, 0.89; 95% confidence interval, 0.68 to 1.17). CONCLUSIONS: In a large cohort in Louisiana, 76.9% of the patients who were hospitalized with Covid-19 and 70.6% of those who died were black, whereas blacks comprise only 31% of the Ochsner Health population. Black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission.", "qid": 41, "docid": "e76foj38", "rank": 55, "score": 0.7872940301895142}, {"content": "Title: Impact of COVID-19 on 2020 US life expectancy for the Black and Latino populations Content: The Black and Latino populations have experienced a disproportionate burden of COVID-19 morbidity and mortality, reflecting persistent structural inequalities that increase risk of exposure to COVID-19 and risk of death for those infected. According to the National Center for Health Statistics, as of July 4, 2020, deaths to Black and Latino individuals comprised 23% and 17%, respectively, of the approximately 115,000 COVID-19 deaths. COVID-19 mortality is likely to result in a larger decline in life expectancy during 2020 than the US has experienced for decades as well as a particularly large reduction for Black and Latino individuals. We estimate life expectancy at birth and at age 65 for 2020, by race and ethnicity, using four scenarios of deaths-one in which the COVID-19 pandemic had not occurred and three including COVID-19 mortality projections produced by the Institute for Health Metrics and Evaluation. Our most likely estimate indicates a reduction in life expectancy at birth greater than 1.5 years for both the Black and Latino populations, which is one year larger than the reduction for whites. This would imply that the Black-white gap would increase by 30%, from 3.6 to 4.7 years, thereby eliminating progress made in reducing this differential since 2008 and reversing an overall trend of steeper mortality declines among the Black population since the early 1990s. Latinos, who have consistently experienced lower mortality than whites (a phenomenon known as the Latino or Hispanic paradox), would see their survival advantage decline by 36%, equivalent to its magnitude in 2006.", "qid": 41, "docid": "bjvg2ivr", "rank": 56, "score": 0.7868639826774597}, {"content": "Title: Absence of Skin of Colour Images in Publications of COVID\u201019 Skin Manifestations Content: There are now over 1 million confirmed cases of COVID\u201019 globally with more than 270,000 recorded deaths to date. COVID\u201019 has been shown to disproportionately impact people of colour both in the United Kingdom and in the United States where blacks make up 13.4% of the population but 30% of COVID\u201019 cases. Mounting evidence shows that COVID\u201019 impacts several organ systems, including the skin.", "qid": 41, "docid": "epkx1u50", "rank": 57, "score": 0.7864575386047363}, {"content": "Title: Racial and Ethnic Digital Divides in Posting COVID-19 Content on Social Media Among US Adults: Secondary Survey Analysis Content: BACKGROUND: Public health surveillance experts are leveraging user-generated content on social media to track the spread and effects of COVID-19. However, racial and ethnic digital divides, which are disparities among people who have internet access and post on social media, can bias inferences. This bias is particularly problematic in the context of the COVID-19 pandemic because due to structural inequalities, members of racial and ethnic minority groups are disproportionately vulnerable to contracting the virus and to the deleterious economic and social effects from mitigation efforts. Further, important demographic intersections with race and ethnicity, such as gender and age, are rarely investigated in work characterizing social media users; however, they reflect additional axes of inequality shaping differential exposure to COVID-19 and its effects. OBJECTIVE: The aim of this study was to characterize how the race and ethnicity of US adults are associated with their odds of posting COVID-19 content on social media and how gender and age modify these odds. METHODS: We performed a secondary analysis of a survey conducted by the Pew Research Center from March 19 to 24, 2020, using a national probability sample (N=10,510). Respondents were recruited from an online panel, where panelists without an internet-enabled device were given one to keep at no cost. The binary dependent variable was responses to an item asking whether respondents \"used social media to share or post information about the coronavirus.\" We used survey-weighted logistic regressions to estimate the odds of responding in the affirmative based on the race and ethnicity of respondents (white, black, Latino, other race/ethnicity), adjusted for covariates measuring sociodemographic background and COVID-19 experiences. We examined how gender (female, male) and age (18 to 30 years, 31 to 50 years, 51 to 64 years, and 65 years and older) intersected with race and ethnicity by estimating interactions. RESULTS: Respondents who identified as black (odds ratio [OR] 1.29, 95% CI 1.02-1.64; P=.03), Latino (OR 1.66, 95% CI 1.36-2.04; P<.001), or other races/ethnicities (OR 1.33, 95% CI 1.02-1.72; P=.03) had higher odds than respondents who identified as white of reporting that they posted COVID-19 content on social media. Women had higher odds of posting than men regardless of race and ethnicity (OR 1.58, 95% CI 1.39-1.80; P<.001). Among men, respondents who identified as black, Latino, or members of other races/ethnicities were significantly more likely to post than respondents who identified as white. Older adults (65 years or older) had significantly lower odds (OR 0.73, 95% CI 0.57-0.94; P=.01) of posting compared to younger adults (18-29 years), particularly among those identifying as other races/ethnicities. Latino respondents were the most likely to report posting across all age groups. CONCLUSIONS: In the United States, members of racial and ethnic minority groups are most likely to contribute to COVID-19 content on social media, particularly among groups traditionally less likely to use social media (older adults and men). The next step is to ensure that data collection procedures capture this diversity by encompassing a breadth of search criteria and social media platforms.", "qid": 41, "docid": "d6hfczkq", "rank": 58, "score": 0.7851071357727051}, {"content": "Title: Racial and Ethnic Digital Divides in Posting COVID-19 Content on Social Media Among US Adults: Secondary Survey Analysis Content: BACKGROUND: Public health surveillance experts are leveraging user-generated content on social media to track the spread and effects of COVID-19. However, racial and ethnic digital divides, which are disparities among people who have internet access and post on social media, can bias inferences. This bias is particularly problematic in the context of the COVID-19 pandemic because due to structural inequalities, members of racial and ethnic minority groups are disproportionately vulnerable to contracting the virus and to the deleterious economic and social effects from mitigation efforts. Further, important demographic intersections with race and ethnicity, such as gender and age, are rarely investigated in work characterizing social media users; however, they reflect additional axes of inequality shaping differential exposure to COVID-19 and its effects. OBJECTIVE: The aim of this study was to characterize how the race and ethnicity of US adults are associated with their odds of posting COVID-19 content on social media and how gender and age modify these odds. METHODS: We performed a secondary analysis of a survey conducted by the Pew Research Center from March 19 to 24, 2020, using a national probability sample (N=10,510). Respondents were recruited from an online panel, where panelists without an internet-enabled device were given one to keep at no cost. The binary dependent variable was responses to an item asking whether respondents \u201cused social media to share or post information about the coronavirus.\u201d We used survey-weighted logistic regressions to estimate the odds of responding in the affirmative based on the race and ethnicity of respondents (white, black, Latino, other race/ethnicity), adjusted for covariates measuring sociodemographic background and COVID-19 experiences. We examined how gender (female, male) and age (18 to 30 years, 31 to 50 years, 51 to 64 years, and 65 years and older) intersected with race and ethnicity by estimating interactions. RESULTS: Respondents who identified as black (odds ratio [OR] 1.29, 95% CI 1.02-1.64; P=.03), Latino (OR 1.66, 95% CI 1.36-2.04; P<.001), or other races/ethnicities (OR 1.33, 95% CI 1.02-1.72; P=.03) had higher odds than respondents who identified as white of reporting that they posted COVID-19 content on social media. Women had higher odds of posting than men regardless of race and ethnicity (OR 1.58, 95% CI 1.39-1.80; P<.001). Among men, respondents who identified as black, Latino, or members of other races/ethnicities were significantly more likely to post than respondents who identified as white. Older adults (65 years or older) had significantly lower odds (OR 0.73, 95% CI 0.57-0.94; P=.01) of posting compared to younger adults (18-29 years), particularly among those identifying as other races/ethnicities. Latino respondents were the most likely to report posting across all age groups. CONCLUSIONS: In the United States, members of racial and ethnic minority groups are most likely to contribute to COVID-19 content on social media, particularly among groups traditionally less likely to use social media (older adults and men). The next step is to ensure that data collection procedures capture this diversity by encompassing a breadth of search criteria and social media platforms.", "qid": 41, "docid": "fambtykj", "rank": 59, "score": 0.7838225364685059}, {"content": "Title: The disproportionate rise in COVID-19 cases among Hispanic/Latinx in disadvantaged communities of Orange County, California: A socioeconomic case-series Content: Background: Recent epidemiological evidence has demonstrated a higher rate of COVID-19 hospitalizations and deaths among minorities. This pattern of race-ethnic disparities emerging throughout the United States raises the question of what social factors may influence spread of a highly transmissible novel coronavirus. The purpose of this study is to describe race-ethnic and socioeconomic disparities associated with COVID-19 in patients in our community in Orange County, California and understand the role of individual-level factors, neighborhood-level factors, and access to care on outcomes. Methods: This is a case-series of COVID-19 patients from the University of California, Irvine (UCI) across six-weeks between 3/12/2020 and 4/22/2020. Note, California's shelter-in-place order began on 3/19/2020. Individual-level factors included race-ethnicity status were recorded. Neighborhood-level factors from census tracts included median household income, mean household size, proportion without a college degree, proportion working from home, and proportion without health insurance were also recorded. Results: A total of 210-patients tested were COVID-19 positive, of which 73.3% (154/210) resided in Orange County. Hispanic/Latinx patients residing in census tracts below the median income demonstrated exponential growth (rate = 55.9%, R2 = 0.9742) during the study period. In addition, there was a significant difference for both race-ethnic (p < 0.001) and income bracket (p = 0.001) distributions prior to and after California's shelter-in-place. In addition, the percentage of individuals residing in neighborhoods with denser households (p = 0.046), lower levels of college graduation (p < 0.001), health insurance coverage (p = 0.01), and ability to work from home (p < 0.001) significantly increased over the same timeframe. Conclusions and Relevance: Our study examines the race-ethnic disparities in Orange County, CA, and highlights vulnerable populations that are at increased risk for contracting COVID-19. Our descriptive case series illustrates that we also need to consider socioeconomic factors, which ultimately set the stage for biological and social disparities.", "qid": 41, "docid": "de6vwlh5", "rank": 60, "score": 0.7836190462112427}, {"content": "Title: Ethnicity, comorbidity, socioeconomic status, and their associations with COVID-19 infection in England: a cohort analysis of UK Biobank data Content: Objectives: Recent data suggest higher COVID-19 rates and severity in Black, Asian, and minority ethnic (BAME) communities. The mechanisms underlying such associations remain unclear. We aimed to study the association between ethnicity and risk of COVID-19 infection and disentangle any correlation with socioeconomic deprivation or previous comorbidity. Design: Prospective cohort. Setting: UK Biobank linked to Hospital Episode Statistics (HES) and COVID-19 tests until 14 April 2020. Participants: UK Biobank participants from England, excluding drop-outs and deaths. Main measures: COVID-19 infection based on a positive PCR test. Ethnicity was self-reported and classified using Office of National Statistics groups. Socioeconomic status was based on index of multiple deprivation quintiles. Comorbidities were self-reported and completed from HES. Analyses: Multivariable Poisson analysis to estimate incidence rate ratios of COVID-19 infection according to ethnicity, adjusted for socioeconomic status, alcohol drinking, smoking, body mass index, age, sex, and comorbidity. Results: 415,582 participants were included, with 1,416 tested and 651 positive for COVID-19. The incidence of COVID-19 was 0.61% (95% CI: 0.46%-0.82%) in Black/Black British participants, 0.32% (0.19%-0.56%) in other ethnicities, 0.32% (0.23%-0.47%) in Asian/Asian British, 0.30% (0.11%-0.80%) in Chinese, 0.16% (0.06%-0.41%) in mixed, and 0.14% (0.13%-0.15%) in White. Compared with White participants, Black/Black British participants had an adjusted relative risk (RR) of 3.30 (2.39-4.55), Chinese participants 3.00 (1.11-8.06), Asian/Asian British participants 2.04 (1.36-3.07), other ethnicities 1.93 (1.08-3.45), and mixed ethnicities 1.07 (0.40-2.86). Socioeconomic status (adjusted RR 1.93 (1.51-2.46) for the most deprived), obesity (adjusted RR 1.04 (1.02-1.05) per kg/m2) and comorbid hypertension, chronic obstructive pulmonary disease, asthma, and specific renal diseases were also associated with increased risk of COVID-19. Conclusions: COVID-19 rates in the UK are higher in BAME communities, those living in deprived areas, obese patients, and patients with previous comorbidity. Public health strategies are needed to reduce COVID-19 infections among the most susceptible groups.", "qid": 41, "docid": "tjqd1srq", "rank": 61, "score": 0.7835889458656311}, {"content": "Title: Racial and ethnic determinants of Covid-19 risk Content: Background Racial and ethnic minorities have disproportionately high hospitalization rates and mortality related to the novel coronavirus disease 2019 (Covid-19). There are comparatively scant data on race and ethnicity as determinants of infection risk. Methods We used a smartphone application (beginning March 24, 2020 in the United Kingdom [U.K.] and March 29, 2020 in the United States [U.S.]) to recruit 2,414,601 participants who reported their race/ethnicity through May 25, 2020 and employed logistic regression to determine the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for a positive Covid-19 test among racial and ethnic groups. Results We documented 8,858 self-reported cases of Covid-19 among 2,259,841 non-Hispanic white; 79 among 9,615 Hispanic; 186 among 18,176 Black; 598 among 63,316 Asian; and 347 among 63,653 other racial minority participants. Compared with non-Hispanic white participants, the risk for a positive Covid-19 test was increased across racial minorities (aORs ranging from 1.24 to 3.51). After adjustment for socioeconomic indices and Covid-19 exposure risk factors, the associations (aOR [95% CI]) were attenuated but remained significant for Hispanic (1.58 [1.24-2.02]) and Black participants (2.56 [1.93-3.39]) in the U.S. and South Asian (1.52 [1.38-1.67]) and Middle Eastern participants (1.56 [1.25-1.95]) in the U.K. A higher risk of Covid-19 and seeking or receiving treatment was also observed for several racial/ethnic minority subgroups. Conclusions Our results demonstrate an increase in Covid-19 risk among racial and ethnic minorities not completely explained by other risk factors for Covid-19, comorbidities, and sociodemographic characteristics. Further research investigating these disparities are needed to inform public health measures.", "qid": 41, "docid": "lt9748vk", "rank": 62, "score": 0.7827714085578918}, {"content": "Title: Covid-19 by Race and Ethnicity: A National Cohort Study of 6 Million United States Veterans Content: BACKGROUND: There is growing concern that racial and ethnic minority communities around the world are experiencing a disproportionate burden of morbidity and mortality from symptomatic SARS-Cov-2 infection or coronavirus disease 2019 (Covid-19). Most studies investigating racial and ethnic disparities to date have focused on hospitalized patients or have not characterized who received testing or those who tested positive for Covid-19. OBJECTIVE: To compare patterns of testing and test results for coronavirus 2019 (Covid-19) and subsequent mortality by race and ethnicity in the largest integrated healthcare system in the United States. DESIGN: Retrospective cohort study. SETTING: United States Department of Veterans Affairs (VA). PARTICIPANTS: 5,834,543 individuals in care, among whom 62,098 were tested and 5,630 tested positive for Covid-19 between February 8 and May 4, 2020. EXPOSURES: Self-reported race/ethnicity. MAIN OUTCOME MEASURES: We evaluated associations between race/ethnicity and receipt of Covid-19 testing, a positive test result, and 30-day mortality, accounting for a wide range of demographic and clinical risk factors including comorbid conditions, site of care, and urban versus rural residence. RESULTS: Among all individuals in care, 74% were non-Hispanic white (white), 19% non-Hispanic black (black), and 7% Hispanic. Compared with white individuals, black and Hispanic individuals were more likely to be tested for Covid-19 (tests per 1000: white=9.0, [95% CI 8.9 to 9.1]; black=16.4, [16.2 to 16.7]; and Hispanic=12.2, [11.9 to 12.5]). While individuals from minority backgrounds were more likely to test positive (black vs white: OR 1.96, 95% CI 1.81 to 2.12; Hispanic vs white: OR 1.73, 95% CI 1.53 to 1.96), 30-day mortality did not differ by race/ethnicity (black vs white: OR 0.93, 95% CI 0.64 to 1.33; Hispanic vs white: OR 1.07, 95% CI 0.61 to 1.87). CONCLUSIONS: Black and Hispanic individuals are experiencing an excess burden of Covid-19 not entirely explained by underlying medical conditions or where they live or receive care. While there was no observed difference in mortality by race or ethnicity, our findings may underestimate risk in the broader US population as health disparities tend to be reduced in VA.", "qid": 41, "docid": "tnp0lrrh", "rank": 63, "score": 0.7824974656105042}, {"content": "Title: Outcomes and Cardiovascular Comorbidities in a Predominantly African-American Population with COVID-19 Content: Importance: Racial disparities in COVID-19 outcomes have been amplified during this pandemic and reports on outcomes in African-American (AA) populations, known to have higher rates of cardiovascular (CV) comorbidities, remain limited. Objective: To examine prevalence of comorbidities, rates of hospitalization and survival, and incidence of CV manifestations of COVID-19 in a predominantly AA population in south metropolitan Chicago. Design, Setting, Participants: This was an observational cohort study of COVID-19 patients encountered from March 16 to April 16, 2020 at the University of Chicago. Deidentified data were obtained from an institutional data warehouse. Group comparisons and logistic regression modeling based on baseline demographics, clinical characteristics, laboratory and diagnostic testing was performed. Exposures: COVID-19 was diagnosed by nasopharyngeal swab testing and clinical management was at the discretion of treating physicians. Main Outcomes and Measures: Primary outcomes were hospitalization and in-hospital mortality, and secondary outcomes included incident CV manifestations of COVID-19 in the context of overall cardiology service utilization. Results: During the 30 day study period, 1008 patients tested positive for COVID-19 and 689 had available encounter data. Of these, 596 (87%) were AA and 356 (52%) were hospitalized, of which 319 (90%) were AA. Age > 60 years, tobacco use, BMI >40 kg/m2, diabetes mellitus (DM), insulin use, hypertension, chronic kidney disease, coronary artery disease (CAD), and atrial fibrillation (AF) were more common in hospitalized patients. Age > 60 years, tobacco use, CAD, and AF were associated with greater risk of in-hospital mortality along with several elevated initial laboratory markers including troponin, NT-proBNP, blood urea nitrogen, and ferritin. Despite this, cardiac manifestations of COVID-19 were uncommon, coincident with a 69% decrease in cardiology service utilization. For hospitalized patients, median length of stay was 6.2 days (3.4-11.9 days) and mortality was 13%. AA patients were more commonly hospitalized, but without increased mortality. Conclusions and Relevance: In this AA-predominant experience from south metropolitan Chicago, CV comorbidities and chronic diseases were highly prevalent and associated with increased hospitalization and mortality. Insulin-requiring DM and CKD emerged as novel predictors for hospitalization. Despite the highest rate of comorbidities reported to date, CV manifestations of COVID-19 and mortality were relatively low. The unexpectedly low rate of mortality merits further study.", "qid": 41, "docid": "4f6h7agt", "rank": 64, "score": 0.7817635536193848}, {"content": "Title: The association of race and COVID-19 mortality Content: BACKGROUND: COVID-19 mortality disproportionately affects the Black population in the United States (US). To explore this association a cohort study was undertaken. METHODS: We assembled a cohort of 505,992 patients receiving ambulatory care at Bronx Montefiore Health System (BMHS) between 1/1/18 and 1/1/20 to evaluate the relative risk of hospitalization and death in two time-periods, the pre-COVID time-period (1/1/20\u20132/15/20) and COVID time-period (3/1/20\u20134/15/20). COVID testing, hospitalization and mortality were determined with the Black and Hispanic patient population compared separately to the White population using logistic modeling. Evaluation of the interaction of pre-COVID and COVID time periods and race, with respect to mortality was completed. FINDINGS: A total of 9,286/505,992 (1.8%) patients were hospitalized during either or both pre-COVID or COVID periods. Compared to Whites the relative risk of hospitalization of Black patients did not increase in the COVID period (p for interaction=0.12). In the pre- COVID period, compared to Whites, the odds of death for Blacks and Hispanics adjusted for comorbidity was statistically equivalent. In the COVID period compared to Whites the adjusted odds of death for Blacks was 1.6 (95% CI 1.2\u20132.0, p = 0.001). There was a significant increase in Black mortality risk from pre-COVID to COVID periods (p for interaction=0.02). Adjustment for relevant clinical and social indices attenuated but did not fully explain the observed difference in Black mortality. INTERPRETATION: The BMHS COVID experience demonstrates that Blacks do have a higher mortality with COVID incompletely explained by age, multiple reported comorbidities and available metrics of sociodemographic disparity. FUNDING: N/A", "qid": 41, "docid": "ncfo2v89", "rank": 65, "score": 0.7817255258560181}, {"content": "Title: Differential occupational risk for COVID-19 and other infection exposure according to race and ethnicity Content: BACKGROUND: There are racial and ethnic disparities in the risk of contracting COVID-19. This study sought to assess how occupational segregation according to race and ethnicity may contribute to the risk of COVID-19. METHODS: Data about employment in 2019 by industry and occupation and race and ethnicity were obtained from the Bureau of Labor Statistics Current Population Survey. This data was combined with information about industries according to whether they were likely or possibly essential during the COVID-19 pandemic and the frequency of exposure to infections and close proximity to others by occupation. The percentage of workers employed in essential industries and occupations with a high risk of infection and close proximity to others by race and ethnicity was calculated. RESULTS: People of color were more likely to be employed in essential industries and in occupations with more exposure to infections and close proximity to others. Black workers in particular faced an elevated risk for all of these factors. CONCLUSION: Occupational segregation into high-risk industries and occupations likely contributes to differential risk with respect to COVID-19. Providing adequate projection to workers may help to reduce these disparities.", "qid": 41, "docid": "8ffds4yc", "rank": 66, "score": 0.781592071056366}, {"content": "Title: Racial and Ethnic Disparities in Population Level Covid-19 Mortality Content: Background: Current reporting of Covid-19 mortality data by race and ethnicity across the United States could bias our understanding of population-mortality disparities. Moreover, stark differences in age distribution by race and ethnicity groups are seldom accounted for in analyses. Methods: To address these gaps, we conducted a cross-sectional study using publicly-reported Covid-19 mortality data to assess the quality of race and ethnicity data (Black, Latinx, white), and estimated age-adjusted disparities using a random effects meta-analytic approach. Results: We found only 28 states, and NYC, reported race and ethnicity-stratified Covid-19 mortality along with large variation in the percent of missing race and ethnicity data by state. Aggregated relative risk of death estimates for Black compared to the white population was 3.57 (95% CI: 2.84-4.48). Similarly, Latinx population displayed 1.88 (95% CI: 1.61-2.19) times higher risk of death than white patients. Discussion: In states providing race and ethnicity data, we identified significant population-level Covid-19 mortality disparities. We demonstrated the importance of adjusting for age differences across population groups to prevent underestimating disparities in younger population groups. The availability of high-quality and comprehensive race and ethnicity data is necessary to address factors contributing to inequity in Covid-19 mortality.", "qid": 41, "docid": "7kevqevo", "rank": 67, "score": 0.7799153327941895}, {"content": "Title: A case-control and cohort study to determine the relationship between ethnic background and severe COVID-19 Content: Background. People of minority ethnic background may be disproportionately affected by severe COVID-19 for reasons that are unclear. We sought to examine the relationship between ethnic background and (1) hospital admission for severe COVID-19; (2) in-hospital mortality. Methods. We conducted a case-control study of 872 inner city adult residents admitted to hospital with confirmed COVID-19 (cases) and 3,488 matched controls randomly sampled from a primary healthcare database comprising 344,083 people resident in the same region. To examine in-hospital mortality, we conducted a cohort study of 1827 adults consecutively admitted with COVID-19. Data collected included hospital admission for COVID-19, demographics, comorbidities, in-hospital mortality. The primary exposure variable was self-defined ethnicity. Results. The 872 cases comprised 48.1% Black, 33.7% White, 12.6% Mixed/Other and 5.6% Asian patients. In conditional logistic regression analyses, Black and Mixed/Other ethnicity were associated with higher admission risk than white (OR 3.12 [95% CI 2.63-3.71] and 2.97 [2.30- 3.85] respectively). Adjustment for comorbidities and deprivation modestly attenuated the association (OR 2.28 [1.87-2.79] for Black, 2.66 [2.01-3.52] for Mixed/Other). Asian ethnicity was not associated with higher admission risk (OR 1.20 [0.86-1.66]). In the cohort study of 1827 patients, 455 (28.9%) died over a median (IQR) of 8 (4-16) days. Age and male sex, but not Black (adjusted HR 0.84 [0.63-1.11]) or Mixed/Other ethnicity (adjusted HR 0.69 [0.43-1.10]), were associated with in-hospital mortality. Asian ethnicity was associated with higher in-hospital mortality (adjusted HR 1.54 [0.98-2.41]). Conclusions. Black and Mixed ethnicity are independently associated with greater admission risk with COVID-19 and may be risk factors for development of severe disease. Comorbidities and socioeconomic factors only partly account for this and additional ethnicity-related factors may play a large role. The impact of COVID-19 may be different in Asians.", "qid": 41, "docid": "gadui4r7", "rank": 68, "score": 0.7795097827911377}, {"content": "Title: Disparities In Outcomes Among COVID-19 Patients In A Large Health Care System In California. Content: As the coronavirus disease (COVID-19) pandemic spreads throughout the United States, evidence is mounting that racial and ethnic minorities and socioeconomically disadvantaged groups are bearing a disproportionate burden of illness and death. We conducted a retrospective cohort analysis of COVID-19 patients at Sutter Health, a large integrated health care system in northern California, to measure potential disparities. We used Sutter's integrated electronic health record to identify adults with suspected and confirmed COVID-19, and used multivariable logistic regression to assess risk of hospitalization, adjusting for known risk factors, such as race/ethnicity, sex, age, health, and socioeconomic variables. We analyzed 1,052 confirmed cases of COVID-19 from January 1-April 8, 2020. Among our findings, we observed that, compared with non-Hispanic white patients, African Americans had 2.7 times the odds of hospitalization, after adjusting for age, sex, comorbidities, and income. We explore possible explanations for this, including societal factors that either result in barriers to timely access to care or create circumstances in which patients view delaying care as the most sensible option. Our study provides real-world evidence that there are racial and ethnic disparities in the presentation of COVID-19. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].", "qid": 41, "docid": "s0xhfla6", "rank": 69, "score": 0.7783084511756897}, {"content": "Title: Social Vulnerability and Equity: The Disproportionate Impact of COVID\u201019 Content: As the architect of racial disparity, racism shapes the vulnerability of communities. Socially vulnerable communities are less resilient in their ability to respond to and recover from natural and man\u2010made disasters when compared to resourced communities. This essay argues that racism exposes existing practices and structures in public administration that, along with the effects of COVID\u201019, have led to disproportionate infection and death rates of Black people. Using the Centers for Disease Control's Social Vulnerability Index (SVI) authors analyze the ways Black bodies occupy the most vulnerable communities, making them bear the brunt of COVID\u201019\u2019s impact. Findings suggest that existing disparities exacerbate COVID\u201019 outcomes for Black people. Targeted universalism is offered as an administrative framework to meet the needs of all people impacted by COVID\u201019. This article is protected by copyright. All rights reserved.", "qid": 41, "docid": "gbqacbvl", "rank": 70, "score": 0.7777077555656433}, {"content": "Title: Even more to handle: Additional sources of stress and trauma for clients from marginalized racial and ethnic groups in the United States during the COVID-19 pandemic Content: In addition the general stressors occurring as a result of the COVID-19 pandemic, individuals who are members of marginalized racial or ethnic minority groups in the United States may face additional stressors, such as pandemic-related, racially-based prejudice and discrimination and the magnification of pre-existing health disparities and their effects. Such stressors may increase pandemic-related and general health risks both directly and indirectly and increase the risk for both general and traumatic stress. These stressors and their historical and social contexts are discussed, and implications for clinicians are provided.", "qid": 41, "docid": "z3j9sbzf", "rank": 71, "score": 0.7773679494857788}, {"content": "Title: Differential occupational risk for COVID\u201019 and other infection exposure according to race and ethnicity Content: BACKGROUND: There are racial and ethnic disparities in the risk of contracting COVID\u201019. This study sought to assess how occupational segregation according to race and ethnicity may contribute to the risk of COVID\u201019. METHODS: Data about employment in 2019 by industry and occupation and race and ethnicity were obtained from the Bureau of Labor Statistics Current Population Survey. This data was combined with information about industries according to whether they were likely or possibly essential during the COVID\u201019 pandemic and the frequency of exposure to infections and close proximity to others by occupation. The percentage of workers employed in essential industries and occupations with a high risk of infection and close proximity to others by race and ethnicity was calculated. RESULTS: People of color were more likely to be employed in essential industries and in occupations with more exposure to infections and close proximity to others. Black workers in particular faced an elevated risk for all of these factors. CONCLUSION: Occupational segregation into high\u2010risk industries and occupations likely contributes to differential risk with respect to COVID\u201019. Providing adequate projection to workers may help to reduce these disparities.", "qid": 41, "docid": "88s32x0v", "rank": 72, "score": 0.7765403985977173}, {"content": "Title: For us, COVID-19 is personal Content: We are colleagues and friends working together in busy emergency departments in Washington DC. As Black physicians working in urban America, we do not find the recent deluge of news reports chronicling the disproportionate effect that the coronavirus disease (COVID-19) pandemic is having on the disenfranchised and minority populations in our country shocking. We have long been witness to and are in a constant state of alarm over the legal, medical, educational, social and economic inequities faced by the most vulnerable residents of this country.", "qid": 41, "docid": "2djys8ky", "rank": 73, "score": 0.775723934173584}, {"content": "Title: Mental health and COVID-19: is the virus racist? Content: COVID-19 has changed our lives and it appears to be especially harmful for some groups more than others. Black and Asian ethnic minorities are at particular risk and have reported greater mortality and intensive care needs. Mental illnesses are more common among Black and ethnic minorities, as are crisis care pathways including compulsory admission. This editorial sets out what might underlie these two phenomena, explaining how societal structures and disadvantage generate and can escalate inequalities in crises.", "qid": 41, "docid": "aku7m0i5", "rank": 74, "score": 0.7752472758293152}, {"content": "Title: Strong Effects of Population Density and Social Characteristics on Distribution of COVID-19 Infections in the United States Content: Coronavirus disease 2019 (Covid-19) has devastated global populations and has had a large impact in the United States with the number of infections and deaths growing exponentially. Using a smooth generalized additive model with quasipoisson counts for total infections and deaths, we developed a county-level predictive model that included population demographics, social characteristics, social distancing, and testing data. This model strongly predicted the actual US distribution of Covid-19, accounting for 94.8% of spatial-temporal variation in total infections and 99.3% in Covid-19 related fatalities from March 15, 2020. US counties with higher population density, poverty index, civilian population, and minorities, especially African Americans had a higher number of confirmed infections adjusted for county population. Social distancing measured by the change in the rate of human encounter per km2 relative to pre-covid-19 national average was associated with slower rate of Covid-19 infections, whereas higher testing was associated with higher number of infections. The number of people infected was increasing, however, the rate of increase in new infections was starting to show signs of plateauing starting from the second week of April. Our model projects 2.11 million people to test positive for Covid-19 and 122,951 fatalities by June 1, 2020. Importantly, our model suggests strong social differences in the infections and deaths across US communities, and inequities in areas with larger African American minorities and higher poverty index expected to show higher rates of Covid-19 infections and deaths. Preventive steps including social distancing and community closures have been a cornerstone in stopping the transmission and potentially reducing the spread of the disease. Crucial knowledge of the role of social characteristics in the disease transmission is essential to understand current disease distribution, predict future distribution, and plan additional preventive steps.", "qid": 41, "docid": "6wqxcshu", "rank": 75, "score": 0.7750293612480164}, {"content": "Title: Clinical, Behavioral and Social Factors Associated with Racial Disparities in Hospitalized and Ambulatory COVID-19 Patients from an Integrated Health Care System in Georgia Content: Introduction: Racial and ethnic minorities have shouldered a disproportioned burden of coronavirus disease 2019 (COVID-19) infection to date in the US, but data on the various drivers of these disparities is limited. Objectives: To describe the characteristics and outcomes of COVID-19 patients and explore factors associated with hospitalization risk by race. Methods: Case series of 448 consecutive patients with confirmed COVID-19 seen at Kaiser Permanente Georgia (KPGA), an integrated health care system serving the Atlanta metropolitan area, from March 3 to May 12, 2020. KPGA members with laboratory-confirmed COVID-19. Multivariable analyses for hospitalization risk also included an additional 3489 persons under investigation (PUI) with suspected infection. COVID-19 treatment and outcomes, underlying comorbidities and quality of care management metrics, socio-demographic and other individual and community-level social determinants of health (SDOH) indicators. Results: Of 448 COVID-19 positive members, 68,3% was non-Hispanic Black (n=306), 18% non-Hispanic White (n=81) and 13,7% Other race (n=61). Median age was 54 [IQR 43-63) years. Overall, 224 patients were hospitalized, median age 60 (50-69) years. Black race was a significant factor in the Confirmed + PUI, female and male models (ORs from 1.98 to 2.19). Obesity was associated with higher hospitalization odds in the confirmed, confirmed + PUI, Black and male models (ORs from 1.78 to 2.77). Chronic disease control metrics (diabetes, hypertension, hyperlipidemia) were associated with lower odds of hospitalization ranging from 48% to 35% in the confirmed + PUI and Black models. Self-reported physical inactivity was associated with 50% higher hospitalization odds in the Black and Female models. Residence in the Northeast region of Atlanta was associated with lower hospitalization odds in the Confirmed + PUI, White and female models (ORs from 0.22 to 0.64) Conclusions: We found that non-Hispanic Black KPGA members had a disproportionately higher risk of infection and, after adjusting for covariates, twice the risk of hospitalization compared to other race groups. We found no significant differences in clinical outcomes or mortality across race/ethnicity groups. In addition to age, sex and comorbidity burden, pre-pandemic self-reported exercise, metrics on quality of care and control of underlying cardio-metabolic diseases, and location of residence in Atlanta were significantly associated with hospitalization risk by race groups. Beyond well-known physiologic and clinical factors, individual and community-level social indicators and health behaviors must be considered as interventions designed to reduce COVID-19 disparities and the systemic effects of racism are implemented.", "qid": 41, "docid": "ix2cbs4j", "rank": 76, "score": 0.7749239206314087}, {"content": "Title: Improved measurement of racial/ethnic disparities in COVID-19 mortality in the United States Content: Different estimation methods produce diverging accounts of racial/ethnic disparities in COVID-19 mortality in the United States. The Center for Disease Control's decision to present the racial/ethnic distribution of COVID-19 deaths at the state level alongside the weighted racial/ethnic distribution of the counties within each state reporting those death -- in effect, a geographic adjustment -- makes it seem that Whites have the highest death rates. Age adjustment procedures used by others, including the New York City Department of Health and Mental Hygiene, lead to the opposite conclusion that Blacks and Hispanics are dying from COVID-19 at higher rates than Whites. In this paper, we use indirect standardization methods to adjust per capita death rates for both age and geography simultaneously, avoiding the one-sided adjustment procedures currently in use. Using CDC data, we find age-and-place-adjusted COVID-19 death rates are 80% higher for Blacks and over 50% higher for Hispanics, relative to Whites, on a national level. State-specific estimates show wide variation in mortality disparities. Comparison with nonepidemic mortality reveals potential roles for preexisting health disparities and differential rates of infection and care.", "qid": 41, "docid": "fyna1euk", "rank": 77, "score": 0.7746590375900269}, {"content": "Title: Framing a Needed Discourse on Health Disparities and Social Inequities: Drawing Lessons from a Pandemic Content: COVID\u201019 provides numerous opportunities for policymakers to consider matters of social equity in relation to the field of public health. Specifically, by reflecting on health disparities in relation to the disproportionate impact of COVID\u201019 on minority and historically underserved populations, we can leverage a needed discourse on health outcomes for many communities. Grounded in the social determinants of health conceptual framework, this article explores the application of the disproportionate impact of COVID\u201019 on vulnerable populations and communities of color for a discussion on strategies for minimizing health disparities. This article is protected by copyright. All rights reserved.", "qid": 41, "docid": "qpf0s1wm", "rank": 78, "score": 0.774106502532959}, {"content": "Title: Racial segregation, testing sites access, and COVID-19 incidence rate in Massachusetts, USA Content: The U.S. has merely 4% of the world population but 25% of the world's COVID-19 cases. Massachusetts has been in the leading position of total cases since the outbreak in the U.S. Racial residential segregation is a fundamental cause of racial disparities in health. Moreover, disparities of access to health care have a large impact on COVID-19 cases. Thus, this study estimates racial segregation and disparities in testing sites access and employs economic, demographic, and transportation variables at the city/town level in Massachusetts. Spatial regression models are applied to evaluate the relationships between COVID-19 incidence rate and related variables. This is the first study to apply spatial analysis methods across neighborhoods in the U.S. to examine the COVID-19 incidence rate. The findings are: 1) residential segregations of Hispanic and Non-Hispanic Black/African Americans have a significantly positive association with COVID-19 incidence rate, indicating the higher susceptibility of COIVD-19 infections among minority; 2) The Black has the shortest drive time to testing sites, followed by Hispanic, Asian, and Whites. The drive time to testing sites is significantly negatively associated with the COVID-19 incidence rate, implying the importance of testing location being accessed by all populations; 3) Poverty rate and road density are significant explanatory variables. Importantly, overcrowding represented by more than one person per room is a significant variable found to be positively associated with COVID-19 incidence rate, suggesting the effectiveness of social distancing for reducing infection; 4) Different from previous studies, elderly population rate is not statistically significant with incidence rate because the elderly population in Massachusetts is less distributed in the hot spot regions of COVID-19 infections. The findings in this study provide useful insights for policymakers to propose new strategies to contain the COVID-19 transmissions in Massachusetts.", "qid": 41, "docid": "gxjsv896", "rank": 79, "score": 0.7740358114242554}, {"content": "Title: Understanding COVID-19 Risks and Vulnerabilities among Black Communities in America: The Lethal Force of Syndemics Content: Black communities in the United States are bearing the brunt of the COVID-19 pandemic and the underlying conditions that exacerbate its negative consequences. Syndemic theory provides a useful framework for understanding how such interacting epidemics to develop under conditions of health and social disparity. Multiple historical and present-day factors have created the syndemic conditions within which Black Americans experience the lethal force of COVID-19. These factors include racism and its manifestations (e.g., chattel slavery, mortgage redlining, political gerrymandering, lack of Medicaid expansion, employment discrimination, and healthcare provider bias). Improving racial disparities in COVID-19 will require that we implement policies that address structural racism at the root of these disparities.", "qid": 41, "docid": "vs4qb91t", "rank": 80, "score": 0.773594856262207}, {"content": "Title: Identification of Vulnerable Populations and Areas at Higher Risk of COVID-19 Related Mortality in the U.S. Content: Background The role of health-related disparities including sociodemographic, environmental, and critical care capacity in the COVID-19 pandemic are poorly understood. In the present study, we characterized vulnerable populations located in areas at higher risk of COVID-19 related mortality and low critical healthcare capacity in the U.S. Methods Using Bayesian multilevel analysis and small area disease risk mapping, we assessed the spatial variation of COVID-19 related mortality risk for the U.S. in relation with healthcare disparities including race, ethnicity, poverty, air quality, and critical healthcare capacity. Results Overall, highly populated, regional air hub areas, and minorities had an increased risk of COVID-19 related mortality. We found that with an increase of only 1 ug/m3 in long term PM2.5 exposure, the COVID-19 mortality rate increased by 13%. Counties with major air hubs had 18% increase in COVID-19 related death compared to counties with no airport connectivity. Sixty-eight percent of the counties with high COVID-19 related mortality risk were also counties with lower critical care capacity than national average. These counties were primary located at the North- and South-Eastern regions of the country. Conclusion The existing disparity in health and environmental risk factors that exacerbate the COVID-19 related mortality, along with the regional healthcare capacity, determine the vulnerability of populations to COVID-19 related mortality. The results from this study can be used to guide the development of strategies for the identification and targeting preventive strategies in vulnerable populations with a higher proportion of minority groups living in areas with poor air quality and low healthcare capacity.", "qid": 41, "docid": "0j6a5xqc", "rank": 81, "score": 0.7733837962150574}, {"content": "Title: Social Workers Must Address Intersecting Vulnerabilities among Noninstitutionalized, Black, Latinx, and Older Adults of Color during the COVID-19 Pandemic Content: Scant attention has been paid to intersecting vulnerabilities experienced by Black, Latinx, and older adults of color (BLOAC) that increase COVID-19 related risks. Structural inequities have resulted in disproportionate rates of chronic conditions and limited access to care. Media coverage, focused on COVID-19 mortality among institutionalized older adults (OA), has overlooked community-dwelling OA, leaving their unique risks unaddressed in research and intervention efforts. Key vulnerabilities impacting noninstitutionalized BLOAC exacerbating adverse health outcomes during COVID-19 are discussed, and recommendations are given for gerontological social work (GSW) education, training, and practice to meet the needs of BLOAC during the COVID-19 pandemic.", "qid": 41, "docid": "882rmszp", "rank": 82, "score": 0.7719323039054871}, {"content": "Title: Social Workers Must Address Intersecting Vulnerabilities among Noninstitutionalized, Black, Latinx, and Older Adults of Color during the COVID-19 Pandemic. Content: Scant attention has been paid to intersecting vulnerabilities experienced by Black, Latinx, and older adults of color (BLOAC) that increase COVID-19 related risks. Structural inequities have resulted in disproportionate rates of chronic conditions and limited access to care. Media coverage, focused on COVID-19 mortality among institutionalized older adults (OA), has overlooked community-dwelling OA, leaving their unique risks unaddressed in research and intervention efforts. Key vulnerabilities impacting noninstitutionalized BLOAC exacerbating adverse health outcomes during COVID-19 are discussed, and recommendations are given for gerontological social work (GSW) education, training, and practice to meet the needs of BLOAC during the COVID-19 pandemic.", "qid": 41, "docid": "ivjt0eml", "rank": 83, "score": 0.7719323039054871}, {"content": "Title: Ethnic Disparities in Hospitalization for COVID-19: a Community-Based Cohort Study in the UK Content: IMPORTANCE: Differentials in COVID-19 incidence, hospitalization and mortality according to ethnicity are being reported but their origin is uncertain. OBJECTIVE: We aimed to explain any ethnic differentials in COVID-19 hospitalization based on socioeconomic, lifestyle, mental and physical health factors. DESIGN: Prospective cohort study with national registry linkage to hospitalisation for COVID-19. SETTING: Community-dwelling. PARTICIPANTS: 340,966 men and women (mean age 56.2 (SD=8.1) years; 54.3% women) residing in England from the UK Biobank study. EXPOSURES: Ethnicity classified as White, Black, Asian, and Others. MAIN OUTCOME(S) AND MEASURE(S): Cases of COVID-19 serious enough to warrant a hospital admission in England from 16-March-2020 to 26-April-2020. RESULTS: There were 640 COVID-19 cases (571/324,306 White, 31/4,485 Black, 21/5,732 Asian, 17/5,803 Other). Compared to the White study members and after adjusting for age and sex, Black individuals had over a 4-fold increased risk of being hospitalised (odds ratio; 95% confidence interval: =4.32; 3.00-6.23), and there was a doubling of risk in the Asian group (2.12; 1.37, 3.28) and the \u2018other\u2019 non-white group (1.84; 1.13, 2.99). After controlling for 15 confounding factors which included neighbourhood deprivation, education, number in household, smoking, markers of body size, inflammation, and glycated haemoglobin, these effect estimates were attenuated by 33% for Blacks, 52% for Asians and 43% for Other, but remained raised for Blacks (2.66; 1.82, 3.91), Asian (1.43; 0.91, 2.26) and other non-white groups (1.41; 0.87, 2.31). CONCLUSIONS AND RELEVANCE: Our findings show clear ethnic differences in risk of hospitalization for COVID-19 which do not appear to be fully explained by known explanatory factors. If replicated, our results have implications for health policy, including the targeting of prevention advice and vaccination coverage.", "qid": 41, "docid": "7g7yt23q", "rank": 84, "score": 0.7707140445709229}, {"content": "Title: Stay-at-Home Orders, African American Population, Poverty and State-level Covid-19 Infections: Are there associations? Content: Importance: To cope with the continuing COVID-19 pandemic, state and local health officials need information on the effectiveness of policies aimed at curbing contagion, as well as area-specific socio-demographic characteristics that can portend vulnerability to the disease. Objective: To investigate whether state-imposed stay-at-home orders, African American population in the state, state poverty and other state socio-demographic characteristics, were associated with the state-level incidence of COVID-19 infection. Design, Setting, Participants: State-level, aggregated, publicly available data on positive COVID-19 cases and tests were used. The period considered was March 1st -May 4th. All U.S. states except Washington were included. Outcomes of interest were daily cumulative and daily incremental COVID-19 infection rates. Outcomes were log-transformed. Log-linear regression models with a quadratic time-trend and random intercepts for states were estimated. Covariates included log-transformed test-rates, a binary indicator for stay-at-home, percentage of African American, poverty, percentage elderly, state population and prevalence of selected comorbidities. Binary fixed effects for date each state first started reporting test data were included. Results: Stay-at-home orders were associated with decreases in cumulative ({beta}:-1.23; T-stat: -6.84) and daily ({beta}:-0.46; T-stat: -2.56) infection-rates. Predictive analyses indicated that expected cumulative infection rates would be 3 times higher and expected daily incremental rates about 60% higher in absence of stay-at-home orders. Higher African American population was associated with higher cumulative ({beta}: 0.08; T-stat: 4.01) and daily ({beta}: 0.06; T-stat: 3.50) rates. State poverty rates had mixed results and were not robust to model specifications. There was strong evidence of a quadratic daily trend for cumulative and daily rates. Results were largely robust to alternate specifications. Conclusions: We find evidence that stay-at-home orders, which were widely supported by public-health experts, helped to substantially curb COVID-19 infection-rates. As we move to a phased re-opening, continued precautions advised by public-health experts should be adhered to. Also, a larger African American population is strongly associated with incidence of COVID-19 infection. Policies and resources to help mitigate African American vulnerability to COVID-19 is an urgent public health and social justice issue, especially since the ongoing mass protests against police brutality may further exacerbate COVID-19 contagion in this community.", "qid": 41, "docid": "csujgaae", "rank": 85, "score": 0.7705297470092773}, {"content": "Title: Multivariate Analysis of Factors Affecting COVID-19 Case and Death Rate in U.S. Counties: The Significant Effects of Black Race and Temperature Content: Objectives: Coronavirus disease-19 (COVID-19) has spread rapidly around the world, and many risk factors including patient demographics, social determinants of health, environmental variables, underlying health conditions, and adherence to social distancing have been hypothesized to affect case and death rates. However, little has been done to account for the potential confounding effects of these factors. Using a large multivariate analysis, this study illuminates modulators of COVID-19 incidence and mortality in U.S. counties while controlling for risk factors across multiple domains. Methods: Data on COVID-19 and various risk factors in all U.S. counties was collected from publicly available data sources through April 14, 2020. Counties with at least 50 COVID-19 cases were included in case analyses and those with at least 10 deaths were included in mortality models. The 661 counties meeting inclusion criteria for number of cases were grouped into quartiles and comparisons of risk factors were made using t-tests between the highest and lowest quartiles. Similar comparisons for 217 counties were made for above average and below average deaths/100,000. Adjusted linear and logistic regression analyses were performed to evaluate the independent effects of factors that significantly impacted cases and deaths. Results: Univariate analyses demonstrated numerous significant differences between cohorts for both cases and deaths. Risk factors associated with increased cases and/or deaths per 100,000 included increased GDP per capita, decreased social distancing, increased age, increased percent Black, decreased percent Hispanic, decreased percent Asian, decreased health, increased poverty, increased diabetes, increased coronary heart disease, increased physical inactivity, increased alcohol consumption, increased tobacco use, and decreased access to primary care. Multivariate regression analyses demonstrated Black race is a risk factor for worse COVID-19 outcome independent of comorbidities, poverty, access to health care, and other mitigating factors. Lower daily temperatures was also an independent risk factor in case load but not deaths. Conclusions: U.S. counties with a higher proportion of Black residents are associated with increased COVID-19 cases and deaths. However, the various suggested mechanisms, such as socioeconomic and healthcare predispositions, did not appear to drive the effect of race in our model. Counties with higher average daily temperatures are also associated with decreased COVID-19 cases but not deaths. Several theories are posited to explain these findings, including prevalence of vitamin D deficiency. Additional studies are needed to further understand these effects.", "qid": 41, "docid": "vp4kq39i", "rank": 86, "score": 0.7703755497932434}, {"content": "Title: Effect of socioeconomic and ethnic characteristics on COVID-19 infection: The case of the Ultra-Orthodox and the Arab communities in Israel Content: Background. During infectious disease outbreaks the weakest communities are more vulnerable to the infection and its deleterious effects. In Israel, the Arab and Ultra-Orthodox Jewish communities have unique demographic and cultural characteristics that place them at risk for infection. Objective. To examine the socioeconomic and ethnic differences in relation to COVID-19 testing, cases and deaths, and to analyze infection spread patterns in ethnically diverse communities. Methods. Consecutive data on COVID-19 diagnostic testing, confirmed cases and deaths collected from March 31st through May 1st, 2020 in 174 localities across Israel (84% of the population) were analyzed by socioeconomic ranking and ethnicity. Findings. Tests were performed on 331,594 individuals (4.29% of the total population). Of those, 14,865 individuals (4.48%) were positive and 203 died (1.37% of confirmed cases). The percentage of the population tested was 26% and the risk of testing positive was 2.16 times higher in the lowest, compared with the highest socioeconomic category. The proportion of confirmed cases was 4.96 times higher in the Jewish compared with the Arab population. The rate of confirmed cases in 2 Ultra-Orthodox localities increased relatively early and quickly. Other Jewish and Arab localities showed consistently low rates of confirmed COVID-19 cases, regardless of socioeconomic ranking. Interpretation Culturally different communities reacted differently to the COVID-19 outbreak and to government measures, resulting in different outcomes. Therefore, socioeconomic and ethnic variables cannot fully explain communities reaction to the pandemic. Our findings stress the need for designing a culturally adapted approach for dealing with health crises.", "qid": 41, "docid": "3ipnhs8f", "rank": 87, "score": 0.7702510356903076}, {"content": "Title: Ethnic disparities in hospitalisation for COVID-19 in England: The role of socioeconomic factors, mental health, and inflammatory and pro-inflammatory factors in a community-based cohort study Content: BACKGROUND: Differentials in COVID-19 hospitalisations and mortality according to ethnicity have been reported but their origin is uncertain. We examined the role of socioeconomic, mental health, and pro-inflammatory factors in a community-based sample. METHODS: We used data on 340,966 men and women (mean age 56.2 years) from the UK Biobank study, a prospective cohort study with linkage to hospitalisation for COVID-19. Logistic regression models were used to estimate associations between ethnicity and hospitalisation for COVID-19. RESULTS: There were 640 COVID-19 cases (571/324,306 White, 31/4,485 Black, 21/5,732 Asian, 17/5,803 Other). Compared to the White study members and after adjusting for age and sex, Black individuals had over a 4-fold increased risk of COVID-19 infection (odds ratio; 95% confidence interval: 4.32; 3.00-6.23), and there was a doubling of risk in the Asian group (2.12; 1.37, 3.28) and the 'other' non-white group (1.84; 1.13, 2.99). After controlling for potential explanatory factors which included neighbourhood deprivation, household crowding, smoking, body size, inflammation, glycated haemoglobin, and mental illness, these effect estimates were attenuated by 33% for Blacks, 52% for Asians and 43% for Other, but remained raised for Blacks (2.66; 1.82, 3.91), Asian (1.43; 0.91, 2.26) and other non-white groups (1.41; 0.87, 2.31). CONCLUSIONS: There were clear ethnic differences in risk of COVID-19 hospitalisation and these do not appear to be fully explained by measured factors. If replicated, our results have implications for health policy, including the targeting of prevention advice and vaccination coverage.", "qid": 41, "docid": "mqnim7pe", "rank": 88, "score": 0.7698364853858948}, {"content": "Title: A culturally specific mental health and spirituality approach for African Americans facing the COVID-19 pandemic Content: A series of 15-min videos were produced to provide resources to pastors in African-American communities to aid them in conveying accurate public and mental health information about COVID-19. Video presenters included trusted experts in public and mental health and pastors with considerable experience responding to the needs of the African-American community during the COVID-19 pandemic. Four culturally specific core themes to consider when providing care to African Americans who are at increased risk during the pandemic were identified: ritual disruption, negative reactions for not following public health guidelines, trauma, and culture and trust. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "5c6nwrdo", "rank": 89, "score": 0.7696494460105896}, {"content": "Title: A culturally specific mental health and spirituality approach for African Americans facing the COVID-19 pandemic. Content: A series of 15-min videos were produced to provide resources to pastors in African-American communities to aid them in conveying accurate public and mental health information about COVID-19. Video presenters included trusted experts in public and mental health and pastors with considerable experience responding to the needs of the African-American community during the COVID-19 pandemic. Four culturally specific core themes to consider when providing care to African Americans who are at increased risk during the pandemic were identified: ritual disruption, negative reactions for not following public health guidelines, trauma, and culture and trust. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 41, "docid": "juzi9th6", "rank": 90, "score": 0.7696494460105896}, {"content": "Title: Social determinants of COVID-19 mortality at the county level Content: The United States is currently the global epicenter of the COVID-19 pandemic. Emerging data suggests that social determinants of health may be key drivers of the epidemic, and that minorities, migrants, and essential workers may bear a disproportionate degree of risk. We used publicly accessible datasets to build a series of spatial autoregressive models assessing county level associations between COVID-19 mortality and (1) Percentage of Non-English speaking households, (2) percentage of individuals engaged in hired farm work, (3) percentage of uninsured individuals under the age of 65, and (3) percentage of individuals living at or below the poverty line. Across all counties (n=2940), counties with more farmworkers, more residents living in poverty, higher density, and more residents over the age of 65 had significantly higher levels of mortality. In urban counties (n=114), only county density was significantly associated with mortality. In non-urban counties (n=2826), counties with more non-English speaking households and more farm workers had significantly higher levels of mortality, as did counties with higher levels of poverty and more residents over the age of 65. More uninsured residents was significantly associated with decreased reported COVID-19 mortality. Individuals who do not speak English, individuals engaged in farm work, and individuals living in poverty may be at heightened risk for COVID-19 mortality in non-urban counties. Mortality among the uninsured may be being systematically undercounted in county and national level surveillance.", "qid": 41, "docid": "yy3x8yx9", "rank": 91, "score": 0.7693519592285156}, {"content": "Title: Race, Socioeconomic Deprivation, and Hospitalization for COVID-19 in English participants of a National Biobank Content: Preliminary reports suggest that the Coronavirus Disease 2019 (COVID-19) pandemic has led to disproportionate morbidity and mortality among historically disadvantaged populations. The extent to which these disparities are related to socioeconomic versus biologic factors is largely unknown. We investigate the racial and socioeconomic associations of COVID-19 hospitalization among 418,794 participants of the UK Biobank, of whom 549 (0.13%) had been hospitalized. Both black participants (odds ratio 3.4; 95%CI 2.4-4.9) and Asian participants (odds ratio 2.1; 95%CI 1.5-3.2) were at substantially increased risk as compared to white participants. We further observed a striking gradient in COVID-19 hospitalization rates according to the Townsend Deprivation Index - a composite measure of socioeconomic deprivation - and household income. Adjusting for such factors led to only modest attenuation of the increased risk in black participants, adjusted odds ratio 3.1 (95%CI 2.0-4.8). These observations confirm and extend earlier preliminary and lay press reports of higher morbidity in non-white individuals in the context of a large population of participants in a national biobank. The extent to which this increased risk relates to variation in pre-existing comorbidities, differences in testing or hospitalization patterns, or additional disparities in social determinants of health warrants further study.", "qid": 41, "docid": "yw8o3c1l", "rank": 92, "score": 0.7691014409065247}, {"content": "Title: Racial Disparities in COVID-19 Deaths Reveal Harsh Truths About Structural Inequality in America. Content: The Coronavirus disease 2019 (COVID-19) pandemic has unveiled the stark racial disparities that are present in United States (US) and other developed countries today. In recent weeks, several states have released demographic data that highlights the disproportionate rate of COVID-19 infections in racial/ethnic minorities1 . These disparities are likely a result of the structural inequities that minorities face due to factors such as racism, neighborhood segregation, income, housing and education inequality, and poor access to medical care.", "qid": 41, "docid": "a2kjjsq1", "rank": 93, "score": 0.768973708152771}, {"content": "Title: Disparities In Outcomes Among COVID-19 Patients In A Large Health Care System In California Content: As the novel coronavirus disease (COVID-19) pandemic spreads throughout the United States, evidence is mounting that racial and ethnic minorities and socioeconomically disadvantaged groups are bearing a disproportionate burden of illness and death. We conducted a retrospective cohort analysis of COVID-19 patients at Sutter Health, a large integrated health system in northern California, to measure potential disparities. We used Sutter's integrated electronic health record to identify adults with suspected and confirmed COVID-19, and we used multivariable logistic regression to assess risk of hospitalization, adjusting for known risk factors, such as race/ethnicity, sex, age, health, and socioeconomic variables. We analyzed 1,052 confirmed cases of COVID-19 from the period January 1-April 8, 2020. Among our findings, we observed that compared with non-Hispanic white patients, non-Hispanic African American patients had 2.7 times the odds of hospitalization, after adjustment for age, sex, comorbidities, and income. We explore possible explanations for this, including societal factors that either result in barriers to timely access to care or create circumstances in which patients view delaying care as the most sensible option. Our study provides real-world evidence of racial and ethnic disparities in the presentation of COVID-19.", "qid": 41, "docid": "xdy9c88p", "rank": 94, "score": 0.7688188552856445}, {"content": "Title: Ethnic Disparities in Hospitalisation for COVID-19 in England: The Role of Socioeconomic Factors, Mental Health, and Inflammatory and Pro-inflammatory Factors in a Community-based Cohort Study Content: BACKGROUND: Differentials in COVID-19 hospitalisations and mortality according to ethnicity have been reported but their origin is uncertain. We examined the role of socioeconomic, mental health, and pro-inflammatory factors in a community-based sample. METHODS: We used data on 340,966 men and women (mean age 56.2 years) from the UK Biobank study, a prospective cohort study with linkage to hospitalisation for COVID-19. Logistic regression models were used to estimate associations between ethnicity and hospitalisation for COVID-19. RESULTS: There were 640 COVID-19 cases (571/324,306 White, 31/4,485 Black, 21/5,732 Asian, 17/5,803 Other). Compared to the White study members and after adjusting for age and sex, Black individuals had over a 4-fold increased risk of COVID-19 infection (odds ratio; 95% confidence interval: 4.32; 3.00-6.23), and there was a doubling of risk in the Asian group (2.12; 1.37, 3.28) and the \u2018other\u2019 non-white group (1.84; 1.13, 2.99). After controlling for potential explanatory factors which included neighbourhood deprivation, household crowding, smoking, body size, inflammation, glycated haemoglobin, and mental illness, these effect estimates were attenuated by 33% for Blacks, 52% for Asians and 43% for Other, but remained raised for Blacks (2.66; 1.82, 3.91), Asian (1.43; 0.91, 2.26) and other non-white groups (1.41; 0.87, 2.31). CONCLUSIONS: There were clear ethnic differences in risk of COVID-19 hospitalisation and these do not appear to be fully explained by measured factors. If replicated, our results have implications for health policy, including the targeting of prevention advice and vaccination coverage.", "qid": 41, "docid": "qq9nf8dr", "rank": 95, "score": 0.7685233354568481}, {"content": "Title: Coronavirus Disease Health Care Delivery Impact on African Americans Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 1.5 million individuals and led to over 91, 000 deaths in the United States (US) alone as of May 20th, 2020. Minority populations, however, continue to be a high-risk population to contract the SARS-CoV-2 infection. While socioeconomic inequality may help to explain why minority ethnic populations are contracting the SARS-CoV-2 in larger proportions, the reason for elevated mortality rates in African Americans is still unknown. African Americans are less likely than whites to utilize high-quality hospitals, ambulatory care services, and regular primary care providers; this is most likely a result of barriers to accessing high quality treatment, as African Americans have substantially higher uninsured rates. However, previous reports have shown that regardless of insurance status, African Americans are more likely to be directed toward lower quality treatment plans compared to their white counterparts, and that physicians carry implicit biases that negatively impact treatment regimens for these minority populations. While income, education, and access to healthcare should be revised in due time, in the short term physicians should do everything possible to learn about implicit biases that may exist in healthcare, as the first step to minimize implicit biases is to recognize that they exist.", "qid": 41, "docid": "7k4reog4", "rank": 96, "score": 0.768108606338501}, {"content": "Title: Factors Associated with Hospitalization and Disease Severity in a Racially and Ethnically Diverse Population of COVID-19 Patients Content: Background: The coronavirus disease (COVID-19) first identified in Wuhan in December 2019 became a pandemic within a few months of its discovery. The impact of COVID-19 is due to both its rapid spread and its severity, but the determinants of severity have not been fully delineated. Objective: Identify factors associated with hospitalization and disease severity in a racially and ethnically diverse cohort of COVID-19 patients. Methods: We analyzed data from COVID-19 patients diagnosed at the University of Cincinnati health system from March 13, 2020 to May 31, 2020. Severe COVID-19 was defined as admission to intensive care unit or death. Logistic regression modeling adjusted for covariates was used to identify the factors associated with hospitalization and severe COVID-19. Results: Among the 689 COVID-19 patients included in our study, 29.2% were non-Hispanic White, 25.5% were non-Hispanic Black, 32.5% were Hispanic, and 12.8% were of other race/ethnicity. About 31.3% of patients were hospitalized and 13.2% had severe disease. In adjusted analyses, the sociodemographic factors associated with hospitalization and/or disease severity included older age, non-Hispanic Black or Hispanic race/ethnicity (compared non-Hispanic White), and smoking. The following comorbidities: diabetes, hypercholesterolemia, asthma, chronic obstructive pulmonary disease (COPD), chronic kidney disease, cardiovascular diseases, osteoarthritis, and vitamin D deficiency, were associated with hospitalization and/or disease severity. Hematological disorders such as anemia, coagulation disorders, and thrombocytopenia were associated with higher odds of both hospitalization and disease severity. Conclusion: This study confirms race and ethnicity as predictors of severe COVID-19 and identifies clinical risk factors not previously reported such a vitamin D deficiency, hypercholesterolemia, osteoarthritis, and anemia.", "qid": 41, "docid": "7hnh85wy", "rank": 97, "score": 0.7674276232719421}, {"content": "Title: Contemporary and Future Concepts on Hypertension in African Americans: COVID-19 and Beyond Content: BACKGROUND: Cardiovascular disease related mortality is the leading cause of death in the United States, with hypertension being the most prevalent and potent risk factor. For decades hypertension has disproportionately affected African Americans, who also have a higher burden of associated comorbidities including diabetes and heart failure. METHODS: Current literature including guideline reports and newer studies on hypertension in African Americans in PubMed were reviewed. We also reviewed newer publications on the relationship between COVID-19 and cardiovascular disease. FINDINGS: While APOL1 has been theorized in the epidemiology of hypertension, the increased prevalence and associated risks are primarily due to environmental and lifestyle factors. These factors include poor diet, adverse lifestyle, and social determinants. Hypertension control can be achieved by lifestyle modifications such as low sodium diet, weight loss, and adequate physical activity. When lifestyle modifications alone do not adequately control hypertension, a common occurrence among African Americans who suffer with greater prevalence of resistant hypertension, pharmacological intervention is indicated. The efficacy of renal denervation, and the use of sodium-glucose cotransporter 2 and aminopeptidase A inhibitors, have been studied for treatment of resistant hypertension. Furthermore, the recent COVID-19 crisis has been particularly devastating among African Americans who demonstrate increased incidence and poorer health outcomes related to the disease. CONCLUSION: The disparities in outcomes, which are largely attributable to a greater prevalence of comorbidities such as hypertension and obesity, in addition to adverse environmental and socioeconomic factors, highlight the necessity of specialized clinical approaches and programs for African Americans to address longstanding barriers to equitable care.", "qid": 41, "docid": "cn2j9ih4", "rank": 98, "score": 0.7673341035842896}, {"content": "Title: Higher Obesity Trends Among African Americans Are Associated with Increased Mortality in Infected COVID-19 Patients Within the City of Detroit Content: As the city of Detroit raids itself of deaths by shifting from homicides, COVID-19 infection continues to harrow the city with more deaths. From March 19 to May 15, more Detroiters died in 2 months than were killed in 2 years of city homicides. African Americans or Blacks (highest-risk phenotypes) developing COVID-19 infection are more likely to die disproportionately. The confluence of diabetes, hypertension, cardiovascular disease, and the higher prevalence of obesity among Blacks have provided the needed environment for viruses like COVID-19 to thrive and cause serious infections. The purpose of this study is to connect mortality rates from COVID-19 infection to increasing obesity trends among African Americans within the city of Detroit. Statistical analyses were conducted using SPSS ver. 23. Results showed that the highest mortality rates among African Americans occurred more in the obese individuals infected with COVID-19 in the city of Detroit. Out of 1930 deaths from COVID-19 infections, 733 deaths were due to obesity alone in patients without reported comorbid conditions like diabetes, hypertension, and cardiovascular disease. Mortality rate for both male and female African Americans amounted to a total of 11.9%. Thirty-eight percent of reported COVID-19-infected African Americans were obese. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s42399-020-00385-y) contains supplementary material, which is available to authorized users.", "qid": 41, "docid": "753klfdp", "rank": 99, "score": 0.7671874761581421}, {"content": "Title: Health and Demographic Impact on COVID-19 Infection and Mortality in US Counties Content: Introduction With the pandemic of COVID-19, the number of confirmed cases and related deaths are increasing in the US. We aimed to understand the potential impact of health and demographic factors on the infection and mortality rates of COVID-19 at the population level. Methods We collected total number of confirmed cases and deaths related to COVID-19 at the county level in the US from January 21, 2020 to April 23, 2020. We extracted health and demographic measures for each US county. Multivariable linear mixed effects models were used to investigate potential correlations of health and demographic characteristics with the infection and mortality rates of COVID-19 in US counties. Results Our models showed that several health and demographic factors were positively correlated with the infection rate of COVID-19, such as low education level and percentage of Black. In contrast, several factors, including percentage of smokers and percentage of food insecure, were negatively correlated with the infection rate of COVID-19. While the number of days since first confirmed case and the infection rate of COVID-19 were negatively correlated with the mortality rate of COVID-19, percentage of elders (65 and above) and percentage of rural were positively correlated with the mortality rate of COVID-19. Conclusions At the population level, health and demographic factors could impact the infection and mortality rates of COVID-19 in US counties.", "qid": 41, "docid": "632r6uqe", "rank": 100, "score": 0.7668120861053467}]}
{"query": "Does Vitamin D impact COVID-19 prevention and treatment?", "hits": [{"content": "Title: Vitamin D Levels and COVID-19 Susceptibility: Is there any Correlation? Content: Coronavirus disease (COVID-19) is a major pandemic and now a leading cause of death worldwide. Currently, no drugs/vaccine is available for the treatment of this disease. Future preventions and social distancing are the only ways to prevent this disease from community transmission. Vitamin D is an important micronutrient and has been reported to improve immunity and protect against respiratory illness. This short review highlights the important scientific link between Vit D levels and susceptibility to COVID-19 in patients. This review also discusses recommendations for Vit D dose required for healthy as well as COVID-19 susceptible patients for protection and prevention.", "qid": 42, "docid": "bpfwcssk", "rank": 1, "score": 0.8606219291687012}, {"content": "Title: Vitamin D can prevent COVID-19 infection-induced multiple organ damage Content: Vitamin D is an immunomodulator hormone with an anti-inflammatory and antimicrobial effect with a high safety profile. A lot of COVID-19 infected patients develop acute respiratory distress syndrome (ARDS), which may lead to multiple organ damage. These symptoms are associated with a cytokine storm syndrome. The aim of this letter is to note the 5 crucial points that vitamin D could have protective and therapeutic effects against COVID-19. For that reason, COVID-19 infection-induced multiple organ damage might be prevented by vitamin D.", "qid": 42, "docid": "yjx6ejrh", "rank": 2, "score": 0.8564666509628296}, {"content": "Title: Role of vitamin D in preventing of COVID-19 infection, progression and severity Content: The outbreak of COVID-19 has created a global public health crisis. Little is known about the protective factors of this infection. Therefore, preventive health measures that can reduce the risk of infection, progression and severity are desperately needed. This review discussed the possible roles of vitamin D in reducing the risk of COVID-19 and other acute respiratory tract infections and severity. Moreover, this study determined the correlation of vitamin D levels with COVID-19 cases and deaths in 20 European countries as of 20 May 2020. A significant negative correlation (p=0.033) has been observed between mean vitamin D levels and COVID-19 cases per one million population in European countries. However, the correlation of vitamin D with COVID-19 deaths of these countries was not significant. Some retrospective studies demonstrated a correlation between vitamin D status and COVID-19 severity and mortality, while other studies did not find the correlation when confounding variables are adjusted. Several studies demonstrated the role of vitamin D in reducing the risk of acute viral respiratory tract infections and pneumonia. These include direct inhibition with viral replication or with anti-inflammatory or immunomodulatory ways. In the meta-analysis, vitamin D supplementation has been shown as safe and effective against acute respiratory tract infections. Thus, people who are at higher risk of vitamin D deficiency during this global pandemic should consider taking vitamin D supplements to maintain the circulating 25(OH)D in the optimal levels (75-125nmol/L). In conclusion, there is not enough evidence on the association between vitamin D levels and COVID-19 severity and mortality. Therefore, randomized control trials and cohort studies are necessary to test this hypothesis.", "qid": 42, "docid": "8ceblnkz", "rank": 3, "score": 0.8499336838722229}, {"content": "Title: Association of Vitamin D Deficiency and Treatment with COVID-19 Incidence Content: Importance: Vitamin D treatment has been found to decrease incidence of viral respiratory tract infection, especially in vitamin D deficiency. It is unknown whether COVID-19 incidence is associated with vitamin D deficiency and treatment. Objective: To examine whether vitamin D deficiency and treatment are associated with testing positive for COVID-19. Design: Retrospective cohort study Setting: University of Chicago Medicine Participants: Patients tested for COVID-19 from 3/3/2020-4/10/2020. Vitamin D deficiency was defined by the most recent 25-hydroxycholecalciferol <20ng/ml or 1,25-dihydroxycholecalciferol <18pg/ml within 1 year before COVID-19 testing. Treatment was defined by the most recent vitamin D type and dose, and treatment changes between the time of the most recent vitamin D level and time of COVID-19 testing. Vitamin D deficiency and treatment changes were combined to categorize vitamin D status at the time of COVID-19 testing as likely deficient(last-level-deficient/treatment-not-increased), likely sufficient(last-level-not-deficient/treatment-not-decreased), or uncertain deficiency(last-level-deficient/treatment-increased or last-level-not-deficient/treatment-decreased). Main Outcomes and Measures: The main outcome was testing positive for COVID-19. Multivariable analysis tested whether the most recent vitamin D level and treatment changes after that level were associated with testing positive for COVID-19 controlling for demographic and comorbidity indicators. Bivariate analyses of associations of treatment with vitamin D deficiency and COVID-19 were performed. Results: Among 4,314 patients tested for COVID-19, 499 had a vitamin D level in the year before testing. Vitamin D status at the time of COVID-19 testing was categorized as likely deficient for 127(25%) patients, likely sufficient for 291(58%) patients, and uncertain for 81(16%) patients. In multivariate analysis, testing positive for COVID-19 was associated with increasing age(RR(age<50)=1.05,p<0.021;RR(age[\u2265]50)=1.02,p<0.064)), non-white race(RR=2.54,p<0.01) and being likely vitamin D deficient (deficient/treatment-not-increased:RR=1.77,p<0.02) as compared to likely vitamin D sufficient(not-deficient/treatment-not-decreased), with predicted COVID-19 rates in the vitamin D deficient group of 21.6%(95%CI[14.0%-29.2%] ) versus 12.2%(95%CI[8.9%-15.4%]) in the vitamin D sufficient group. Vitamin D deficiency declined with increasing vitamin D dose, especially of vitamin D3. Vitamin D dose was not significantly associated with testing positive for COVID-19. Conclusions and Relevance: Vitamin D deficiency that is not sufficiently treated is associated with COVID-19 risk. Testing and treatment for vitamin D deficiency to address COVID-19 warrant aggressive pursuit and study.", "qid": 42, "docid": "4v71xohx", "rank": 4, "score": 0.8485492467880249}, {"content": "Title: Role of vitamin D in preventing of COVID-19 infection, progression and severity Content: The outbreak of COVID-19 has created a global public health crisis. Little is known about the protective factors of this infection. Therefore, preventive health measures that can reduce the risk of infection, progression and severity are desperately needed. This review discussed the possible roles of vitamin D in reducing the risk of COVID-19 and other acute respiratory tract infections and severity. Moreover, this study determined the correlation of vitamin D levels with COVID-19 cases and deaths in 20 European countries as of 20 May 2020. A significant negative correlation (p = 0.033) has been observed between mean vitamin D levels and COVID-19 cases per one million population in European countries. However, the correlation of vitamin D with COVID-19 deaths of these countries was not significant. Some retrospective studies demonstrated a correlation between vitamin D status and COVID-19 severity and mortality, while other studies did not find the correlation when confounding variables are adjusted. Several studies demonstrated the role of vitamin D in reducing the risk of acute viral respiratory tract infections and pneumonia. These include direct inhibition with viral replication or with anti-inflammatory or immunomodulatory ways. In the meta-analysis, vitamin D supplementation has been shown as safe and effective against acute respiratory tract infections. Thus, people who are at higher risk of vitamin D deficiency during this global pandemic should consider taking vitamin D supplements to maintain the circulating 25(OH)D in the optimal levels 75-125 nmol/L. In conclusion, there not enough evidence on the association between vitamin D levels and COVID-19 severity and mortality. Therefore, randomized control trials and cohort studies are necessary to test this hypothesis.", "qid": 42, "docid": "uz34fjyp", "rank": 5, "score": 0.8459973335266113}, {"content": "Title: Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths Content: The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40-60 ng/mL (100-150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.", "qid": 42, "docid": "9vsi8hfx", "rank": 6, "score": 0.8447626233100891}, {"content": "Title: Vitamin D Supplementation in Influenza and COVID-19 Infections Comment on: \u201cEvidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths\u201d Nutrients 2020, 12(4), 988 Content: There is an ongoing debate on the use of vitamin D supplementation in reducing the risk of influenza and COVID-19 infections and deaths. A recently published article highlights a relationship between vitamin D supplementation and reduced risk of COVID-19 and influenza. This comment aims to discuss the evidence on the use of Vitamin D in people who are at risk of developing COVID-19, focusing on safety issues of the Vitamin D supplementation.", "qid": 42, "docid": "svc2xeh1", "rank": 7, "score": 0.8405143022537231}, {"content": "Title: Vitamin D Supplementation in Influenza and COVID-19 Infections Comment on: \"Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths\" Nutrients 2020, 12(4), 988 Content: There is an ongoing debate on the use of vitamin D supplementation in reducing the risk of influenza and COVID-19 infections and deaths. A recently published article highlights a relationship between vitamin D supplementation and reduced risk of COVID-19 and influenza. This comment aims to discuss the evidence on the use of Vitamin D in people who are at risk of developing COVID-19, focusing on safety issues of the Vitamin D supplementation.", "qid": 42, "docid": "pt1i1au3", "rank": 8, "score": 0.8405143022537231}, {"content": "Title: Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths Content: The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D(3) for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40\u201360 ng/mL (100\u2013150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D(3) doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.", "qid": 42, "docid": "iqe6sdq2", "rank": 9, "score": 0.8400918841362}, {"content": "Title: Double COVID-19 Confirmed Case Fatality Rate in Countries with High Elderly Female Vitamin D Deficiency Prevalence Content: A number of clues point to a possible role of vitamin D in fighting COVID-19: a reduction in case growth speed with solar zenith angle, higher fatality rate in black people, lower fatality rate in populations that spend more time outdoors. Yet a direct demonstration that vitamin D deficiency is associated with COVID-19 fatalities has remained elusive. We show here in a comparison of 32 countries that countries with high prevalence of vitamin D deficiency among elderly females show a confirmed case fatality rate twice as high as those with low prevalence. We then show that this effect cannot be explained by differences in life expectancy between countries. A mechanistic role for vitamin D in the severity of COVID-19 is proposed.", "qid": 42, "docid": "jdrhu6l1", "rank": 10, "score": 0.8322030305862427}, {"content": "Title: Vitamin D deficiency and COVID-19 pandemic Content: \u2022 Vitamin D deficiency is very frequent. \u2022 Controlled trials showed that vitamin D decreases acute respiratory infections. \u2022 Despite a lack of direct evidence of an effect of vitamin D on COVID-19 infection. \u2022 Daily vitamin D supplementation with moderate doses is safe and cheap. \u2022 Even a small decrease in COVID-19 infections would easily justify this intervention.", "qid": 42, "docid": "fe7e60dl", "rank": 11, "score": 0.829947292804718}, {"content": "Title: Vitamin D and COVID-19 Content: Epidemiological data report that several countries with a high prevalence of hypovitaminosis D may have increased susceptibility to complications and mortality due to COVID-19 infection. These reports, however, have limitations given that they derive from observational studies. Nevertheless, while awaiting more robust data, clinicians should treat patients with vitamin D deficiency irrespective of whether or not it has a link with respiratory infections.", "qid": 42, "docid": "kfrhwsjb", "rank": 12, "score": 0.8290603160858154}, {"content": "Title: Vitamin D and Inflammation: Potential Implications for Severity of Covid-19. Content: Background Recent research has indicated that vitamin D may have immune supporting properties through modulation of both the adaptive and innate immune system through cytokines and regulation of cell signalling pathways. We hypothesize that vitamin D status may influence the severity of responses to Covid-19 and that the prevalence of vitamin D deficiency in Europe will be closely aligned to Covid-19 mortality. Methods We conducted a literature search on PubMed (no language restriction) of vitamin D status (for older adults) in countries/areas of Europe affected by Covid-19 infection. Countries were selected by severity of infection (high and low) and were limited to national surveys or where not available, to geographic areas within the country affected by infection. Covid-19 infection and mortality data was gathered from the World Health Organisation. Results Counter-intuitively, lower latitude and typically 'sunny' countries such as Spain and Italy (particularly Northern Italy), had low mean concentrations of 25(OH)D and high rates of vitamin D deficiency. These countries have also been experiencing the highest infection and death rates in Europe. The northern latitude countries (Norway, Finland, Sweden) which receive less UVB sunlight than Southern Europe, actually had much higher mean 25(OH)D concentrations, low levels of deficiency and for Norway and Finland, lower infection and death rates. The correlation between 25(OH)D concentration and mortality rate reached conventional significance (P=0.046) by Spearman's Rank Correlation. Conclusions Optimising vitamin D status to recommendations by national and international public health agencies will certainly have benefits for bone health and potential benefits for Covid-19. There is a strong plausible biological hypothesis and evolving epidemiological data supporting a role for vitamin D in Covid-19.", "qid": 42, "docid": "jvyr7pq4", "rank": 13, "score": 0.8271543979644775}, {"content": "Title: The D-side of COVID-19: musculoskeletal benefits of vitamin D and beyond Content: Coronavirus 2019 disease (COVID-19) mostly adversely affects the elderly, a population at higher risk for low serum 25-hydroxyvitamin D (25(OH)D) levels. In this viewpoint, we highlight the well-known musculoskeletal properties of vitamin D, which are particularly relevant in the context of COVID-19, suggesting further potential benefits through extra-skeletal effects. Maintaining optimal 25(OH)D is crucial to prevent falls, frailty and fractures in elderly patients, with low activity levels due to lockdown, or who are relatively immobilized during hospitalization and after discharge for prolonged periods of time. Hypovitaminosis D is also associated with susceptibility to respiratory infections, admissions to the intensive care unit, and mortality. We underscore the importance of achieving desirable serum 25(OH)D in COVID-19 elderly patients, to ensure beneficial musculoskeletal effects and possibly respiratory effects of vitamin D, in the context of COVID-19.", "qid": 42, "docid": "dqqrulyx", "rank": 14, "score": 0.8268846869468689}, {"content": "Title: Perspective: Vitamin D deficiency and COVID-19 severity - plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2, and thrombosis (R1) Content: BACKGROUND: SARS-CoV-2 coronavirus infection ranges from asymptomatic through to fatal COVID-19 characterised by a \"cytokine storm\" and lung failure. Vitamin D deficiency has been postulated as a determinant of severity. OBJECTIVES: To review the evidence relevant to vitamin D and COVID-19 METHODS: Narrative review RESULTS: Regression modelling shows that more northerly countries in the Northern Hemisphere are currently (May 2020) showing relatively high COVID-19 mortality, with an estimated 4.4% increase in mortality for each 1 degree latitude north of 28 degrees North (P=0.031) after adjustment for age of population. This supports a role for ultraviolet B acting via vitamin D synthesis. Factors associated with worse COVID-19 prognosis include old age, ethnicity, male sex, obesity, diabetes and hypertension and these also associate with deficiency of vitamin D or its response. Vitamin D deficiency is also linked to severity of childhood respiratory illness. Experimentally, vitamin D increases the ratio of angiotensin converting enzyme 2 (ACE2) to ACE, thus increasing angiotensin II hydrolysis and reducing subsequent inflammatory cytokine response to pathogens and lung injury. CONCLUSIONS: Substantial evidence supports a link between vitamin D deficiency and COVID-19 severity but it is all indirect. Community-based placebo-controlled trials of vitamin D supplementation may be difficult. Further evidence could come from study of COVID-19 outcomes in large cohorts with information on prescribing data for vitamin D supplementation or assay of serum unbound 25(OH) vitamin D levels. Meanwhile vitamin D supplementation should be strongly advised for people likely to be deficient.", "qid": 42, "docid": "8fu7w0be", "rank": 15, "score": 0.8266445398330688}, {"content": "Title: Can Vitamin D and L-Cysteine Co-Supplementation Reduce 25(OH)-Vitamin D Deficiency and the Mortality Associated with COVID-19 in African Americans? Content: Early reports indicate an association between the severity of the COVID-19 infection and the widespread 25-hydroxy vitamin D deficiency known to exist in populations around the world. Vitamin D deficiency is extremely common among African American (AA) communities, where the COVID-19 infection rate is three-fold higher, and the mortality rate nearly six-fold higher, compared with rates in predominantly white communities. COVID-19 infection primarily affects the lungs and airways. Previous reports have linked 25-hydroxy vitamin D deficiency with subclinical interstitial lung disease. AA are at risk for lower cellular glutathione (GSH) levels, and GSH deficiency epigenetically impairs VD biosynthesis pathway genes. Compared with vitamin D alone, co-supplementation of vitamin D and L-cysteine (a GSH precursor) showed a better efficacy in improving levels of GSH and VD-regulatory genes at the cellular/tissue level, increasing 25(OH) vitamin D levels, and reducing inflammation biomarkers in the blood in mice studies. We propose that randomized clinical trials are needed to examine the potential of co-supplementation with anti-inflammatory antioxidants, vitamin D and L-cysteine in correcting the 25(OH)VD deficiency and preventing the 'cytokine storm,' one of the most severe consequences of infection with COVID-19, thereby preventing the adverse clinical effects of COVID-19 infection in the vulnerable AA population.", "qid": 42, "docid": "q0tu1pja", "rank": 16, "score": 0.8244632482528687}, {"content": "Title: Does Vitamin D play a role in the management of Covid-19 in Brazil? Content: The study discusses the possible role of adequate vitamin D status in plasma or serum for preventing acute respiratory infections during the Covid-19 pandemic. Our arguments respond to an article, published in Italy, that describes the high prevalence of hypovitaminosis D in older Italian women and raises the possible preventive and therapeutic role of optimal vitamin D levels. Based on literature review, we highlight the findings regarding the protective role of vitamin D for infectious diseases of the respiratory system. However, randomized controlled trials are currently lacking. Adequate vitamin D status is obtained from sun exposure and foods rich in vitamin D. Studies in Brazil have shown that hypovitaminosis D is quite common in spite of high insolation. Authors recommend ecological, epidemiological and randomized controlled trials studies to verify this hypothesis.", "qid": 42, "docid": "x4ietehr", "rank": 17, "score": 0.8241677284240723}, {"content": "Title: 25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2 Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), with a clinical outcome ranging from mild to severe, including death. To date, it is unclear why some patients develop severe symptoms. Many authors have suggested the involvement of vitamin D in reducing the risk of infections; thus, we retrospectively investigated the 25-hydroxyvitamin D (25(OH)D) concentrations in plasma obtained from a cohort of patients from Switzerland. In this cohort, significantly lower 25(OH)D levels (p = 0.004) were found in PCR-positive for SARS-CoV-2 (median value 11.1 ng/mL) patients compared with negative patients (24.6 ng/mL); this was also confirmed by stratifying patients according to age >70 years. On the basis of this preliminary observation, vitamin D supplementation might be a useful measure to reduce the risk of infection. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations and to confirm our preliminary observation.", "qid": 42, "docid": "xsaj0fzu", "rank": 18, "score": 0.8224672675132751}, {"content": "Title: Possible role of vitamin D in Covid-19 infection in pediatric population Content: PURPOSE: Covid-19 is a pandemic of unprecedented proportion, whose understanding and management is still under way. In the emergency setting new or available therapies to contrast the spread of COVID-19 are urgently needed. Elderly males, especially those affected by previous diseases or with comorbidities, are more prone to develop interstitial pneumonia that can deteriorate evolving to ARDS (acute respiratory distress syndrome) that require hospitalization in Intensive Care Units (ICUs). Even children and young patients are not spared by SARS-CoV 2 infection, yet they seem to develop a milder form of disease. In this setting the immunomodulatory role of Vitamin D, should be further investigated. Methods: We reviewed the literature about the immunomodulatory role of Vitamin D collecting data from the databases Medline and Embase. RESULTS: Vitamin D proved to interact both with the innate immune system, by activating Toll-like receptors (TLRs) or increasing the levels of cathelicidins and \u03b2-defensins, and adaptive immune system, by reducing immunoglobulin secretion by plasma cells and pro-inflammatory cytokines production, thus modulating T cells function. Promising results have been extensively described as regards the supplementation of vitamin D in respiratory tract infections, autoimmune diseases and even pulmonary fibrosis. CONCLUSIONS: In this review, we suggest that vitamin D supplementation might play a role in the prevention and/or treatment to SARS-CoV-2 infection disease, by modulating the immune response to the virus both in the adult and pediatric population.", "qid": 42, "docid": "rvwxysvc", "rank": 19, "score": 0.8215049505233765}, {"content": "Title: Vitamin D and inflammation: Potential implications for severity of Covid-19 Content: Background Recent research has indicated that vitamin D may have immune supporting properties through modulation of both the adaptive and innate immune system through cytokines and regulation of cell signalling pathways We hypothesize that vitamin D status may influence the severity of responses to Covid-19 and that the prevalence of vitamin D deficiency in Europe will be closely aligned to Covid-19 mortality Methods We conducted a literature search on PubMed (no language restriction) of vitamin D status (for older adults) in countries/areas of Europe affected by Covid-19 infection Countries were selected by severity of infection (high and low) and were limited to national surveys or where not available, to geographic areas within the country affected by infection Covid-19 infection and mortality data was gathered from the World Health Organisation Results Counter-intuitively, lower latitude and typically \u2018sunny\u2019 countries such as Spain and Italy (particularly Northern Italy), had low mean concentrations of 25(OH)D and high rates of vitamin D deficiency These countries have also been experiencing the highest infection and death rates in Europe The northern latitude countries (Norway, Finland, Sweden) which receive less UVB sunlight than Southern Europe, actually had much higher mean 25(OH)D concentrations, low levels of deficiency and for Norway and Finland, lower infection and death rates The correlation between 25(OH)D concentration and mortality rate reached conventional significance (P=0 046) by Spearman's Rank Correlation Conclusions Optimising vitamin D status to recommendations by national and international public health agencies will certainly have benefits for bone health and potential benefits for Covid-19 There is a strong plausible biological hypothesis and evolving epidemiological data supporting a role for vitamin D in Covid-19", "qid": 42, "docid": "lo6u1buy", "rank": 20, "score": 0.8203895688056946}, {"content": "Title: Strong Correlation Between Prevalence of Severe Vitamin D Deficiency and Population Mortality Rate from COVID-19 in Europe Content: Background: SARS-CoV-2 virus causes a very wide range of COVID-19 disease severity in humans: from completely asymptomatic to fatal, and the reasons behind it are often not understood. There is some data that Vitamin D may have protective effect, so authors decided to analyze European country-wide data to determine if Vitamin D levels are associated with COVID-19 population death rate. Methods: To retrieve the Vitamin D levels data, authors analyzed the Vitamin D European population data compiled by 2019 ECTS Statement on Vitamin D Status published in the European Journal of Endocrinology. For the data set to used for analysis, only recently published data, that included general adult population of both genders ages 40-65 or wider, and must have included the prevalence of Vitamin D deficiency. Results: There were 10 countries data sets that fit the criteria and were analyzed. Severe Vitamin D deficiency was defined as 25(OH)D less than 25 nmol/L (10 ng/dL). Pearson correlation analysis between death rate per million from COVID-19 and prevalence of severe Vitamin D deficiency shows a strong correlation with r = 0.76, p = 0.01, indicating significant correlation. Correlation remained significant, even after adjusting for age structure of the population. Additionally, over time, correlation strengthened, and r coefficient asymptoticaly increased. Conclusions: Authors recommend universal screening for Vitamin D deficiency, and further investigation of Vitamin D supplementation in randomized control studies, which may lead to possible treatment or prevention of COVID-19.", "qid": 42, "docid": "67gsn4sy", "rank": 21, "score": 0.820056676864624}, {"content": "Title: Possible role of vitamin D in Covid-19 infection in pediatric population Content: PURPOSE: Covid-19 is a pandemic of unprecedented proportion, whose understanding and management is still under way. In the emergency setting new or available therapies to contrast the spread of COVID-19 are urgently needed. Elderly males, especially those affected by previous diseases or with comorbidities, are more prone to develop interstitial pneumonia that can deteriorate evolving to ARDS (acute respiratory distress syndrome) that require hospitalization in Intensive Care Units (ICUs). Even children and young patients are not spared by SARS-CoV 2 infection, yet they seem to develop a milder form of disease. In this setting the immunomodulatory role of Vitamin D, should be further investigated. METHODS: We reviewed the literature about the immunomodulatory role of Vitamin D collecting data from the databases Medline and Embase. RESULTS: Vitamin D proved to interact both with the innate immune system, by activating Toll-like receptors (TLRs) or increasing the levels of cathelicidins and \u00df-defensins, and adaptive immune system, by reducing immunoglobulin secretion by plasma cells and pro-inflammatory cytokines production, thus modulating T cells function. Promising results have been extensively described as regards the supplementation of vitamin D in respiratory tract infections, autoimmune diseases and even pulmonary fibrosis. CONCLUSIONS: In this review, we suggest that vitamin D supplementation might play a role in the prevention and/or treatment to SARS-CoV-2 infection disease, by modulating the immune response to the virus both in the adult and pediatric population.", "qid": 42, "docid": "46aln4tk", "rank": 22, "score": 0.8200339078903198}, {"content": "Title: COVID-19 breakthroughs: separating fact from fiction Content: The newly recognised coronavirus SARS-CoV-2, causative agent of COVID-19, has caused a pandemic with huge ramifications for human interactions around the globe. As expected, research efforts to understand the virus and curtail the disease are moving at a frantic pace alongside the spread of rumours, speculations and falsehoods. In this article, we aim to clarify the current scientific view behind several claims or controversies related to COVID-19. Starting with the origin of the virus, we then discuss the effect of ibuprofen and nicotine on the severity of the disease. We highlight the knowledge on fomites and SARS-CoV-2 and discuss the evidence and explications for a disproportionately stronger impact of COVID-19 on ethnic minorities, including a potential protective role for vitamin D. We further review what is known about the effects of SARS-CoV-2 infection in children, including their role in transmission of the disease, and conclude with the science on different mortality rates between different countries and whether this hints at the existence of more pathogenic cohorts of SARS-CoV-2.", "qid": 42, "docid": "l2wzr3w1", "rank": 23, "score": 0.8197450041770935}, {"content": "Title: Perspective: Vitamin D deficiency and COVID\u201019 severity \u2013 plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2, and thrombosis (R1) Content: BACKGROUND: SARS\u2010CoV\u20102 coronavirus infection ranges from asymptomatic through to fatal COVID\u201019 characterised by a \u201ccytokine storm\u201d and lung failure. Vitamin D deficiency has been postulated as a determinant of severity. OBJECTIVES: To review the evidence relevant to vitamin D and COVID\u201019 METHODS: Narrative review RESULTS: Regression modelling shows that more northerly countries in the Northern Hemisphere are currently (May 2020) showing relatively high COVID\u201019 mortality, with an estimated 4.4% increase in mortality for each 1 degree latitude north of 28 degrees North (P=0.031) after adjustment for age of population. This supports a role for ultraviolet B acting via vitamin D synthesis. Factors associated with worse COVID\u201019 prognosis include old age, ethnicity, male sex, obesity, diabetes and hypertension and these also associate with deficiency of vitamin D or its response. Vitamin D deficiency is also linked to severity of childhood respiratory illness. Experimentally, vitamin D increases the ratio of angiotensin converting enzyme 2 (ACE2) to ACE, thus increasing angiotensin II hydrolysis and reducing subsequent inflammatory cytokine response to pathogens and lung injury. CONCLUSIONS: Substantial evidence supports a link between vitamin D deficiency and COVID\u201019 severity but it is all indirect. Community\u2010based placebo\u2010controlled trials of vitamin D supplementation may be difficult. Further evidence could come from study of COVID\u201019 outcomes in large cohorts with information on prescribing data for vitamin D supplementation or assay of serum unbound 25(OH) vitamin D levels. Meanwhile vitamin D supplementation should be strongly advised for people likely to be deficient.", "qid": 42, "docid": "mspxtag1", "rank": 24, "score": 0.8193890452384949}, {"content": "Title: Potential Role of Vitamin D in the Elderly to Resist COVID-19 and to Slow Progression of Parkinson\u2019s Disease Content: While we are still learning more about COVID-19, caused by the novel SARS-CoV-2 virus, finding alternative and already available methods to reduce the risk and severity of the disease is paramount. One such option is vitamin D, in the form of vitamin D(3) (cholecalciferol) supplementation, due to its potential antiviral properties. It has become apparent that older individuals have a greater risk of developing severe COVID-19, and compared to younger adults, the elderly have lower levels of vitamin D due to a variety of biological and behavioral factors. Older adults are also more likely to be diagnosed with Parkinson\u2019s disease (PD), with advanced age being the single greatest risk factor. In addition to its immune-system-modulating effects, it has been suggested that vitamin D supplementation plays a role in slowing PD progression and improving PD-related quality of life. We completed a review of the literature to determine the relationship between vitamin D, PD, and COVID-19. We concluded that the daily supplementation of 2000\u20135000 IU/day of vitamin D(3) in older adults with PD has the potential to slow the progression of PD while also potentially offering additional protection against COVID-19.", "qid": 42, "docid": "wfz010d5", "rank": 25, "score": 0.8192551136016846}, {"content": "Title: Short Communication: Vitamin D and COVID-19 infection and mortality in UK Biobank Content: Purpose Vitamin D has been proposed as a potential causal factor in COVID-19 risk. We aimed to establish whether blood 25-hydroxyvitamin D (25(OH)D) concentration was associated with COVID-19 mortality, and inpatient confirmed COVID-19 infection, in UK Biobank participants. Methods UK Biobank recruited 502,624 participants aged 37-73 years between 2006 and 2010. Baseline exposure data, including 25(OH)D concentration, were linked to COVID-19 mortality. Univariable and multivariable Cox proportional hazards regression analyses were performed for the association between 25(OH)D and COVID-19 death, and poisson regression analyses for the association between 25(OH)D and severe COVID-19 infection. Results Complete data were available for 341,484 UK Biobank participants, of which 656 had inpatient confirmed COVID-19 infection and 203 died of COVID-19 infection. Vitamin D was associated with severe COVID-19 infection and mortality univariably (mortality HR=0.99; 95% CI 0.98-0.998; p=0.016), but not after adjustment for confounders (mortality HR=0.998; 95% CI=0.99-1.01; p=0.696). Conclusions Our findings do not support a potential link between vitamin D concentrations and risk of severe COVID-19 infection and mortality. Recommendations for vitamin D supplementation to lessen COVID-19 risks may provide false reassurance.", "qid": 42, "docid": "npk92gra", "rank": 26, "score": 0.8190008997917175}, {"content": "Title: Letter: low population mortality from COVID\u201019 in countries south of latitude 35\u00b0 North supports vitamin D as a factor determining severity\u2014authors\u2019 reply Content: We thank Dr Mansur for his interest in our editorial in which we highlighted the association between northern latitude and increased COVID-19 mortality1 and for his helpful comments about the potential importance of vitamin D effects on cathelicidin and on the renin-angiotensin system, which could be important in protecting against severe COVID-19.2 Vitamin D is a secosteroid hormone, derived like cortisol and sex hormones from cholesterol, so not surprisingly it has a broad range of actions reflecting the several hundred or more genes that are vitamin D-responsive.3,4.", "qid": 42, "docid": "3m8ekphy", "rank": 27, "score": 0.8175379037857056}, {"content": "Title: Spurious Correlation? A review of the relationship between Vitamin D and Covid-19 infection and mortality Content: The study reviews the evidence presented in a recent study linking vitamin D levels and Covid-19 infection and mortality. It was argued that correlation alone may not be useful in establishing a relationship between vitamin D levels and Covid-19 infections and mortality. Appropriate controls need to be included for improved understanding of the relationship. We proposed life expectancy as a potential control. Including this control in a regression model, we find that vitamin D levels are not a statistically significant predictor of Covid-19 infections or mortality. Life expectancy, on the other hand, was found to be statistically significant predictor of infections and mortality at country level.", "qid": 42, "docid": "hevwcofh", "rank": 28, "score": 0.8173598051071167}, {"content": "Title: Vitamin D concentrations and COVID-19 infection in UK Biobank Content: Abstract Background and aims COVID-19 and low levels of vitamin D appear to disproportionately affect black and minority ethnic individuals. We aimed to establish whether blood 25-hydroxyvitamin D (25(OH)D) concentration was associated with COVID-19 risk, and whether it explained the higher incidence of COVID-19 in black and South Asian people. Methods UK Biobank recruited 502,624 participants aged 37\u201373 years between 2006 and 2010. Baseline exposure data, including 25(OH)D concentration and ethnicity, were linked to COVID-19 test results. Univariable and multivariable logistic regression analyses were performed for the association between 25(OH)D and confirmed COVID-19, and the association between ethnicity and both 25(OH)D and COVID-19. Results Complete data were available for 348,598 UK Biobank participants. Of these, 449 had confirmed COVID-19 infection. Vitamin D was associated with COVID-19 infection univariably (OR = 0.99; 95% CI 0.99\u20130.999; p = 0.013), but not after adjustment for confounders (OR = 1.00; 95% CI = 0.998\u20131.01; p = 0.208). Ethnicity was associated with COVID-19 infection univariably (blacks versus whites OR = 5.32, 95% CI = 3.68\u20137.70, p-value<0.001; South Asians versus whites OR = 2.65, 95% CI = 1.65\u20134.25, p-value<0.001). Adjustment for 25(OH)D concentration made little difference to the magnitude of the association. Conclusions Our findings do not support a potential link between vitamin D concentrations and risk of COVID-19 infection, nor that vitamin D concentration may explain ethnic differences in COVID-19 infection.", "qid": 42, "docid": "0oxy9b1p", "rank": 29, "score": 0.8157920837402344}, {"content": "Title: Vitamin D concentrations and COVID-19 infection in UK Biobank Content: BACKGROUND AND AIMS: COVID-19 and low levels of vitamin D appear to disproportionately affect black and minority ethnic individuals. We aimed to establish whether blood 25-hydroxyvitamin D (25(OH)D) concentration was associated with COVID-19 risk, and whether it explained the higher incidence of COVID-19 in black and South Asian people. METHODS: UK Biobank recruited 502,624 participants aged 37-73 years between 2006 and 2010. Baseline exposure data, including 25(OH)D concentration and ethnicity, were linked to COVID-19 test results. Univariable and multivariable logistic regression analyses were performed for the association between 25(OH)D and confirmed COVID-19, and the association between ethnicity and both 25(OH)D and COVID-19. RESULTS: Complete data were available for 348,598 UK Biobank participants. Of these, 449 had confirmed COVID-19 infection. Vitamin D was associated with COVID-19 infection univariably (OR = 0.99; 95% CI 0.99-0.999; p = 0.013), but not after adjustment for confounders (OR = 1.00; 95% CI = 0.998-1.01; p = 0.208). Ethnicity was associated with COVID-19 infection univariably (blacks versus whites OR = 5.32, 95% CI = 3.68-7.70, p-value<0.001; South Asians versus whites OR = 2.65, 95% CI = 1.65-4.25, p-value<0.001). Adjustment for 25(OH)D concentration made little difference to the magnitude of the association. CONCLUSIONS: Our findings do not support a potential link between vitamin D concentrations and risk of COVID-19 infection, nor that vitamin D concentration may explain ethnic differences in COVID-19 infection.", "qid": 42, "docid": "gitj540h", "rank": 30, "score": 0.8155117034912109}, {"content": "Title: COVID\u201019 breakthroughs: separating fact from fiction Content: The newly recognised coronavirus SARS\u2010CoV\u20102, causative agent of COVID\u201019, has caused a pandemic with huge ramifications for human interactions around the globe. As expected, research efforts to understand the virus and curtail the disease are moving at a frantic pace alongside the spread of rumours, speculations and falsehoods. In this article, we aim to clarify the current scientific view behind several claims or controversies related to COVID\u201019. Starting with the origin of the virus, we then discuss the effect of ibuprofen and nicotine on the severity of the disease. We highlight the knowledge on fomites and SARS\u2010CoV\u20102 and discuss the evidence and explications for a disproportionately stronger impact of COVID\u201019 on ethnic minorities, including a potential protective role for vitamin D. We further review what is known about the effects of SARS\u2010CoV\u20102 infection in children, including their role in transmission of the disease, and conclude with the science on different mortality rates between different countries and whether this hints at the existence of more pathogenic cohorts of SARS\u2010CoV\u20102.", "qid": 42, "docid": "ipl6189w", "rank": 31, "score": 0.8128167390823364}, {"content": "Title: COVID-19 breakthroughs: separating fact from fiction Content: The newly recognised coronavirus SARS-CoV-2, causative agent of coronavirus disease (COVID-19), has caused a pandemic with huge ramifications for human interactions around the globe. As expected, research efforts to understand the virus and curtail the disease are moving at a frantic pace alongside the spread of rumours, speculations and falsehoods. In this article, we aim to clarify the current scientific view behind several claims or controversies related to COVID-19. Starting with the origin of the virus, we then discuss the effect of ibuprofen and nicotine on the severity of the disease. We highlight the knowledge on fomites and SARS-CoV-2 and discuss the evidence and explications for a disproportionately stronger impact of COVID-19 on ethnic minorities, including a potential protective role for vitamin D. We further review what is known about the effects of SARS-CoV-2 infection in children, including their role in transmission of the disease, and conclude with the science on different mortality rates between different countries and whether this hints at the existence of more pathogenic cohorts of SARS-CoV-2.", "qid": 42, "docid": "41378qru", "rank": 32, "score": 0.8124390244483948}, {"content": "Title: Lungs as target of COVID-19 infection: Protective common molecular mechanisms of vitamin D and melatonin as a new potential synergistic treatment Content: COVID-19 pandemic has a high mortality rate and is affecting practically the entire world population. The leading cause of death is severe acute respiratory syndrome as a consequence of exacerbated inflammatory response accompanied by uncontrolled oxidative stress as well as the inflammatory reaction at the lung level. Until now, there is not a specific and definitive treatment for this pathology that worries the world population, especially the older adults who constitute the main risk group. In this context, it results in a particular interest in the evaluation of the efficacy of existing pharmacological agents that may be used for overcoming or attenuating the severity of this pulmonary complication that has ended the lives of many people worldwide. Vitamin D and melatonin could be good options for achieving this aim, taking into account that they have many shared underlying mechanisms that are able to modulate and control the immune adequately and oxidative response against COVID-19 infection, possibly even through a synergistic interaction. The renin-angiotensin system exaltation with consequent inflammatory response has a leading role in the physiopathology of COVID-19 infection; and it may be down-regulated by vitamin D and melatonin in many organs. Therefore, it is also essential to analyze this potential therapeutic association and their relation with RAS as part of this new approach.", "qid": 42, "docid": "o8c1i5c2", "rank": 33, "score": 0.8119152784347534}, {"content": "Title: What is the role of supplementation with ascorbic acid, zinc, vitamin D, or N-acetylcysteine for prevention or treatment of COVID-19? Content: Several agents intended to supplement dietary intake or endogenous molecules may have a theoretical role in preventing or treating COVID-19. Because of their potential to influence immune response, ascorbic acid (vitamin C), zinc, vitamin D, and N-acetylcysteine have been hypothesized to be useful for prevention or treatment of COVID-19. The authors outline the biologic plausibility, applicable clinical data, and potential role of each of these agents.", "qid": 42, "docid": "waujy98e", "rank": 34, "score": 0.8100906610488892}, {"content": "Title: The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality Content: WHO declared SARS-CoV-2 a global pandemic. The present aim was to propose an hypothesis that there is a potential association between mean levels of vitamin D in various countries with cases and mortality caused by COVID-19. The mean levels of vitamin D for 20 European countries and morbidity and mortality caused by COVID-19 were acquired. Negative correlations between mean levels of vitamin D (average 56 mmol/L, STDEV 10.61) in each country and the number of COVID-19 cases/1 M (mean 295.95, STDEV 298.7, and mortality/1 M (mean 5.96, STDEV 15.13) were observed. Vitamin D levels are severely low in the aging population especially in Spain, Italy and Switzerland. This is also the most vulnerable group of the population in relation to COVID-19. It should be advisable to perform dedicated studies about vitamin D levels in COVID-19 patients with different degrees of disease severity.", "qid": 42, "docid": "jak0gx9k", "rank": 35, "score": 0.8095313310623169}, {"content": "Title: The Role of Vitamin D in The Age of COVID-19: A Systematic Review and Meta-Analysis Along with an Ecological Approach Content: Background: Following emerge of a novel coronavirus from Wuhan, China, in December 2019, it has affected the whole world and after months of efforts by the medical communities, there is still no specific approach for prevention and treatment against the Coronavirus Disease 2019 (COVID-19). Evidence recommends that vitamin D might be an important supportive agent for the immune system, mainly in cytokine response regulation against COVID-19. Hence, we carried out a rapid systematic review and meta-analysis along with an ecological investigation in order to maximize the use of everything that exists about the role of vitamin D in the COVID-19. Methods: A systematic search was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science and Google Scholar (intitle) as well as preprint database of medRxiv, bioRxiv, Research Square, preprints.org, search engine of ScienceDirect and a rapid search through famous journals up to May 26, 2020. Studies focused on the role of vitamin D in confirmed COVID-19 patients were entered into the systematic review. Along with our main aim, to find the second objective: correlation of global vitamin D status and COVID-19 recovery and mortality we carried out a literature search in PubMed database to identify the national or regional studies reported the vitamin D status globally. CMA v. 2.2.064 and SPSS v.16 were used for data analysis. Results: Out of nine studies entered into our systematic review, six studies containing 3,822 participants entered into the meta-analysis. The meta-analysis indicated that 46.5% of COVID-19 patients were suffering from vitamin D deficiency (95% CI, 28.2%-65.8%) and in 43.3% of patients, levels of vitamin D were insufficient (95% CI, 27.4%-60.8%). In regard to our ecological investigation on 51 countries including 408,748 participants, analyses indicated no correlation between vitamin D levels and recovery rate (r= 0.041) as well as mortality rate (r=-0.073) globally. However, given latitude, a small reverse correlation between mortality rate and vitamin D status was observed throughout the globe (r= -0.177). In Asia, a medium direct correlation was observed for recovery rate (r= 0.317) and a significant reveres correlation for mortality rate (r= -0.700) with vitamin D status in such patients. In Europe, there were no correlations for both recovery (r= 0.040) and mortality rate (r= -0.035). In Middle East, the recovery rate (r= 0.267) and mortality rate (r= -0.217) showed a medium correlation. In North and Sought America, surprisingly, both recovery and mortality rate demonstrated a direct correlation respectively (r= 1.000, r=0.500). In Oceania, unexpectedly, recovery (r= -1.000) and mortality (r= -1.000) rates were in considerable reverse correlation with vitamin D levels. Conclusion: In this systematic review and meta-analysis with an ecological approach, we found a high percentage of COVID-19 patients who suffer from vitamin D deficiency or insufficiency. Much more important, our ecological investigation resulted in substantial direct and reverse correlations between recovery and mortality rates of COVID-19 patients with vitamin D status in different countries. Considering latitudes, a small reverse correlation between vitamin D status and mortality rate was found globally. It seems that populations with lower levels of vitamin D might be more susceptible to the novel coronavirus infection. Nevertheless, due to multiple limitations, if this study does not allow to quantify a value of the Vitamin D with full confidence, it allows at least to know what the Vitamin D might be and that it would be prudent to invest in this direction through comprehensive large randomized clinical trials.", "qid": 42, "docid": "8hvve871", "rank": 36, "score": 0.8090142607688904}, {"content": "Title: Does vitamin D deficiency increase the severity of COVID-19? Content: The severity of coronavirus 2019 infection (COVID-19) is determined by the presence of pneumonia, severe acute respiratory distress syndrome (SARS-CoV-2), myocarditis, microvascular thrombosis and/or cytokine storms, all of which involve underlying inflammation. A principal defence against uncontrolled inflammation, and against viral infection in general, is provided by T regulatory lymphocytes (Tregs). Treg levels have been reported to be low in many COVID-19 patients and can be increased by vitamin D supplementation. Low vitamin D levels have been associated with an increase in inflammatory cytokines and a significantly increased risk of pneumonia and viral upper respiratory tract infections. Vitamin D deficiency is associated with an increase in thrombotic episodes, which are frequently observed in COVID-19. Vitamin D deficiency has been found to occur more frequently in patients with obesity and diabetes. These conditions are reported to carry a higher mortality in COVID-19. If vitamin D does in fact reduce the severity of COVID-19 in regard to pneumonia/ARDS, inflammation, inflammatory cytokines and thrombosis, it is our opinion that supplements would offer a relatively easy option to decrease the impact of the pandemic.", "qid": 42, "docid": "m22h669g", "rank": 37, "score": 0.8067569732666016}, {"content": "Title: Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalised with COVID-19 are associated with greater disease severity Content: OBJECTIVES: Vitamin D deficiency (VDD) has been proposed to play a role in Coronavirus Disease 2019 (COVID-19) pathophysiology. We aim to evaluate our implementation of a local protocol for treatment of VDD among patients hospitalized for COVID-19; to assess the prevalence of VDD among COVID-19 inpatients, and examine potential associations with disease severity and fatality. DESIGN AND PARTICIPANTS: We conducted a retrospective interim audit of a local clinical care pathway for 134 inpatients with COVID-19. Prevalence of VDD, compliance with local treatment protocol and relationship of baseline serum 25(OH)D with markers of COVID-19 severity and fatality were analysed. RESULTS: 55.8% of eligible patients received Colecalciferol replacement, albeit not all according to the suggested protocol. Patients admitted to ITU were younger than those managed on medical wards (61.1 years \u00b1 11.8 vs. 76.4 years \u00b1 14.9, respectively, p<0.001), with greater prevalence of hypertension, higher baseline respiratory rate, National Early Warning Score-2 and C-Reactive protein level. While mean serum 25(OH)D levels were comparable (p=0.3), only 19% of ITU patients had 25(OH)D levels greater than 50 nmol/L vs. 39.1% of non-ITU patients (p=0.02). However, there was no association with fatality, potentially due to small sample size and prompt diagnosis and treatment of VDD. CONCLUSIONS: Higher prevalence of VDD was observed in patients requiring ITU admission compared to patients managed on medical wards. Larger prospective studies and/or clinical trials are needed to validate and extend our observations.", "qid": 42, "docid": "rtkb45lx", "rank": 38, "score": 0.8064395189285278}, {"content": "Title: Letter: does vitamin D have a potential role against COVID\u201019? Authors' reply Content: We thank Kumar et al for their comments on our review article and the letter connected with that by Panarese and Shahini.(1,2) We agree that there is a complicated effect of vitamin D in preventing the severity of COVID\u201019, while this mechanism is not exactly the same as that of influenza.", "qid": 42, "docid": "s7pwtw9j", "rank": 39, "score": 0.8057004809379578}, {"content": "Title: Vitamin D Deficiency and Air Pollution Exacerbate COVID-19 Through Suppression of Antiviral Peptide LL37 Content: Vitamin D deficiency and insufficiency (VDD) are widely recognized as risk factors for respiratory tract infections. Vitamin D influences expression of many genes with well-established relevance to airway infections and relevant to immune system function. Recently, VDD has been shown to be a risk factor for acquisition and severity of COVID-19. Thus, treating VDD presents a safe and inexpensive opportunity for modulating the severity of the disease. VDD is common in those over 60 years of age, many with co-morbid conditions and in people with skin pigmentation sufficient to reduce synthesis of vitamin D. Exposure to fine particulate air pollution is also associated with worse outcomes from COVID19. Vitamin D stimulates transcription of cathelicidin which is cleaved to generate LL37. LL37 is an innate antimicrobial with demonstrated activity against a wide range of microbes including envelope viruses. LL37 also modulates cytokine signaling at the site of infections. Fine particles in air pollution can interfere with LL37 destruction of viruses and may reduce effective immune signaling modulation by LL37. While vitamin D influences transcription of many immune related genes, the weakened antimicrobial response of those with VDD against SARS-CoV-2 may be in part due to reduced LL37. Conclusion: Vitamin D plays an important role reducing the impact of viral lung disease processes. VDD is an acknowledged public health threat that warrants population-wide action to reduce COVID-19 morbidity and mortality. While vitamin D influences transcription of many immune related genes, the weakened antimicrobial response of those with VDD against SARS-CoV-2 may be in part due to reduced LL37. Action is needed to address COVID-19 associated risks of air pollution from industry, transportation, domestic sources and from primary and second hand tobacco smoke.", "qid": 42, "docid": "wr9hkvd3", "rank": 40, "score": 0.8052166700363159}, {"content": "Title: Vitamin D deficiency as risk factor for severe COVID-19: a convergence of two pandemics Content: Importance: Vitamin D deficiency increases the incidence of respiratory virus infections. More than 1 billion people worldwide are vitamin D deficient. If vitamin D deficiency is associated to incidence or severity of SARS-CoV-2 infection, a global call could be made for vitamin D supplementation to mitigate the pandemic. Objective: to determine if lower serum 25-hydroxyvitamin D (25(OH)D) levels are correlated to the risk for COVID-19 and its severity as measured by CT Design: single-center observational study Setting: AZ Delta general hospital Participants: 186 consecutive patients with PCR-confirmed SARS-CoV-2 infection hospitalized for COVID-19 from March 1, 2020 to April 7, 2020 Main outcome and measures: comparative analysis of 25(OH)D levels in patients hospitalized for COVID-19 at various radiological stages and a season/age/sex-matched diseased control population Results: we report on 186 SARS-CoV-2 infected patients requiring hospitalization for severe COVID-19: 109 males (median age 68 years, IQR 53-79 years) and 77 females (median age 71 years, IQR 65-74 years). At admission patients were screened by CT to determine temporal changes of COVID-19 lung disease and classified as stage 1 (ground glass opacities), 2 (crazy paving pattern) and 3 (consolidation). At intake, 25(OH)D levels were measured and compared to a season-matched population of 2717 diseased controls, consisting of 999 males (median age 69 years, IQR 53-81 years) and 1718 females (median age 68 years, IQR 43-83 years). Male and female COVID-19 patients combined showed lower median 25(OH)D than controls (18.6 ng/mL, IQR 12.6-25.3, versus 21.5 ng/mL, IQR 13.9-30.8; P=0.0016) and a higher fraction of vitamin D deficiency (58.6% versus 45.2%, P=0.0005). A strong sexual dimorphism was found: female patients had comparable vitamin D status as control females. Male COVID-19 patients, however, showed markedly higher percentage of vitamin D deficiency than controls (67.0% versus 49.2%, P=0.0006) and this effect was more pronounced with advanced radiological stage ranging from 55.2% in stage 1 to 74% in stage 3. Conclusions and relevance: vitamin D deficiency is a possible risk factor for severe SARS-CoV-2 infection in males. Vitamin D supplementation might be an inexpensive, accessible and safe mitigation for the SARS-CoV-2 pandemic.", "qid": 42, "docid": "rpmmadqc", "rank": 41, "score": 0.8047478199005127}, {"content": "Title: COVID-19 in Parkinson's Disease Patients Living in Lombardy, Italy Content: BACKGROUND: It is unknown whether patients with PD are at greater risk of COVID-19, what their risk factors are, and whether their clinical manifestations differ from the general population. OBJECTIVES: The study aimed to address all these issues. METHODS: In a case-controlled survey, we interviewed 1,486 PD patients attending a single tertiary center in Lombardy, Italy and 1,207 family members (controls). RESULTS: One hundred five (7.1%) and 92 controls (7.6%) were identified as COVID-19 cases. COVID-19 patients were younger, more likely to suffer from chronic obstructive pulmonary disease, to be obese, and vitamin D nonsupplemented than unaffected patients. Six patients (5.7%) and 7 family members (7.6%) died from COVID-19. Patients were less likely to report shortness of breath and require hospitalization. CONCLUSIONS: In an unselected large cohort of nonadvanced PD patients, COVID-19 risk and mortality did not differ from the general population, but symptoms appeared to be milder. The possible protective role of vitamin D supplementation warrants future studies. \u00a9 2020 International Parkinson and Movement Disorder Society.", "qid": 42, "docid": "dfqqogqp", "rank": 42, "score": 0.8033968210220337}, {"content": "Title: Vitamin D deficiency in patients with diabetes and COVID- 19 infection Content: BACKGROUND AND AIMS: Data show that vitamin D deficiency may play a role in patients with diabetes mellitus and COVID-19 infection. In this article, we review evidence of vitamin D deficiency and COVID-19 infection in context of diabetes mellitus. METHODS: A literature search was carried out by using the key term \u2018COVID 19\u2019 combined with \u2018Diabetes\u2019, \u2018Vitamin D\u2019, \u2018Extra skeletal effects\u2019, \u2018immunity\u2019, \u2018infection\u2019, \u2018India\u2019 from Pub Med (National Library of Medicine, Bethesda, MD and Google Scholar from December 2019 to May 2020. A manual search of the references was also carried out. RESULTS: Vitamin D deficiency has been linked to increased morbidity and mortality in COVID -19 infections but convincing data on diabetic subgroup of patients in particular is still awaited. CONCLUSION: Robust studies are required to ascertain if Vitamin D supplementation could be beneficial in patients with diabetes and COVID-19.", "qid": 42, "docid": "ktzx5lz6", "rank": 43, "score": 0.8027901649475098}, {"content": "Title: Evidence of Protective Role of Ultraviolet-B (UVB) Radiation in Reducing COVID-19 Deaths Content: Background: Research is ongoing to identify an effective way to prevent or treat COVID-19, but thus far these efforts have not yet identified a possible solution. Prior studies indicate the protective role of Ultraviolet-B (UVB) radiation in human health, mediated by vitamin D synthesis. In this study, we empirically outline a negative association of UVB radiation as measured by the ultraviolet index (UVI) with the number of deaths attributed to COVID-19 (COVID-19 deaths). Methods: We carry out an observational study, applying a fixed-effect log-linear regression model to a panel dataset of 64 countries over a period of 78 days (n=4992). We use the cumulative number of COVID-19 deaths and case-fatality rate (CFR) as the main dependent variables to test our hypothesis and isolate UVI effect from potential confounding factors such as underlying time trends, country-specific time-constant and time-varying factors such as weather. Findings: After controlling for time-constant and time-varying factors, we find that a permanent unit increase in UVI is associated with a 2.2 percentage points decline in daily growth rates of cumulative COVID-19 deaths [p < 0.01], as well as a 1.9 percentage points, decline in the daily growth rates of CFR [p < 0.05]. These results represent a significant percentage reduction in terms of the daily growth rates of cumulative COVID-19 deaths (-22.92%) and CFR (-73.08%). Our results are consistent across different model specifications. Interpretation: We find a significant negative association between UVI and COVID-19 deaths, indicating evidence of the protective role of UVB in mitigating COVID-19 deaths. If confirmed via clinical studies, then the possibility of mitigating COVID-19 deaths via sensible sunlight exposure or vitamin D intervention will be very attractive because it is cost-effective and widely available.", "qid": 42, "docid": "6u3kepat", "rank": 44, "score": 0.8025115728378296}, {"content": "Title: Low serum 25\u2010hydroxyvitamin D (25[OH]D) levels in patients hospitalised with COVID\u201019 are associated with greater disease severity Content: OBJECTIVES: Vitamin D deficiency (VDD) has been proposed to play a role in Coronavirus Disease 2019 (COVID\u201019) pathophysiology. We aim to evaluate our implementation of a local protocol for treatment of VDD among patients hospitalized for COVID\u201019; to assess the prevalence of VDD among COVID\u201019 inpatients, and examine potential associations with disease severity and fatality. DESIGN AND PARTICIPANTS: We conducted a retrospective interim audit of a local clinical care pathway for 134 inpatients with COVID\u201019. Prevalence of VDD, compliance with local treatment protocol and relationship of baseline serum 25(OH)D with markers of COVID\u201019 severity and fatality were analysed. RESULTS: 55.8% of eligible patients received Colecalciferol replacement, albeit not all according to the suggested protocol. Patients admitted to ITU were younger than those managed on medical wards (61.1 years \u00b1 11.8 vs. 76.4 years \u00b1 14.9, respectively, p<0.001), with greater prevalence of hypertension, higher baseline respiratory rate, National Early Warning Score\u20102 and C\u2010Reactive protein level. While mean serum 25(OH)D levels were comparable (p=0.3), only 19% of ITU patients had 25(OH)D levels greater than 50 nmol/L vs. 39.1% of non\u2010ITU patients (p=0.02). However, there was no association with fatality, potentially due to small sample size and prompt diagnosis and treatment of VDD. CONCLUSIONS: Higher prevalence of VDD was observed in patients requiring ITU admission compared to patients managed on medical wards. Larger prospective studies and/or clinical trials are needed to validate and extend our observations.", "qid": 42, "docid": "tw6f5h2q", "rank": 45, "score": 0.8019061088562012}, {"content": "Title: Vitamin D deficiency in patients with diabetes and COVID- 19 infection Content: BACKGROUND AND AIMS: Data show that vitamin D deficiency may play a role in patients with diabetes mellitus and COVID-19 infection. In this article, we review evidence of vitamin D deficiency and COVID-19 infection in context of diabetes mellitus. METHODS: A literature search was carried out by using the key term 'COVID 19' combined with 'Diabetes', 'Vitamin D', 'Extra skeletal effects', 'immunity', 'infection', 'India' from Pub Med (National Library of Medicine, Bethesda, MD and Google Scholar from December 2019 to May 2020. A manual search of the references was also carried out. RESULTS: Vitamin D deficiency has been linked to increased morbidity and mortality in COVID -19 infections but convincing data on diabetic subgroup of patients in particular is still awaited. CONCLUSION: Robust studies are required to ascertain if Vitamin D supplementation could be beneficial in patients with diabetes and COVID-19.", "qid": 42, "docid": "99zkwrso", "rank": 46, "score": 0.801262617111206}, {"content": "Title: Covid-19, cocooning and vitamin d intake requirements Content: The purpose of this report is to clarify what constitutes best practice on vitamin D supplement use, particularly among older adults, who are at highest risk of Covid-19 On Friday 3rd April, three reports were published on how vitamin D may protect against Covid-19 Two reports are aligned with national and international guidelines on vitamin intake requirements for health: one looked at the importance of vitamin D adequacy in protecting children from respiratory illness but included important advice cautioning against high dose vitamin D;the other is from The Irish Longitudinal Study on Ageing (TILDA) that looked at specific \u2019at risk\u2019 groups for vitamin D deficiency in those over 50 years in a representative sample from the 26 counties TILDA provides a strong evidence base for intervening in older adults with supplemental vitamin D (10 \u00b5g to 20 \u00b5g daily) A third report advises that every adult should take high doses of vitamin D (20 \u00b5g to 50 \u00b5g daily) in order to protect against Covid-19 The authors make no mention about other sources of vitamin D in adults This creates confusion at a time when there is widespread fear and anxiety about the Covid-19 pandemic The following provides a review of the evidence and summarises best practice regarding vitamin D nutrition to protect against Covid-19", "qid": 42, "docid": "ipm58ohm", "rank": 47, "score": 0.8001687526702881}, {"content": "Title: Vitamin D: A simpler alternative to tocilizumab for trial in COVID-19? Content: There is anecdotal evidence that tocilizumab, an immunosuppressant drug, may be a potential therapeutic option for patients with severe manifestations of coronavirus disease 2019 (COVID-19). Like tocilizumab, Vitamin D appears to modulate the activity of an interleukin (IL-6), which may explain the seasonal variation in prevalence of influenza. While most cases of COVID-19 have, thus far, occurred in the Northern Hemisphere winter, limiting the ability to assess seasonal variation, there remains substantial variation in the severity of this condition that has yet to be explained. A retrospective comparison of Vitamin D levels in previously obtained blood samples between survivors and confirmed fatalities could establish a rationale for implementation of widespread Vitamin D supplementation. This would be far cheaper and simpler than tocilizumab as a therapeutic option to trial.", "qid": 42, "docid": "eu7m99a3", "rank": 48, "score": 0.7995496988296509}, {"content": "Title: Can vitamins and/or supplements provide hope against coronavirus? Content: Severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) quickly became a global pandemic and has been responsible, so far, for infecting 5.8 million and claiming the lives of more than 350,000. While certain medications initially garnered attention as potential treatment options, further studies failed to demonstrate great promise but did demonstrate the need to reduce the cytokine storm experienced by patients with this potentially life-threatening virus. Unfortunately, there is no cure on the horizon, but members of the medical community are beginning to evaluate the potential role of vitamins and supplements as potential treatment options or addition to other treatments. The goal of this narrative review is to evaluate current and ongoing clinical trials of vitamins and supplements, alone or in combination with each other or other therapies, for the treatment of coronavirus disease-2019 (COVID-19).", "qid": 42, "docid": "wp7593di", "rank": 49, "score": 0.7984945178031921}, {"content": "Title: Vitamin D Insufficiency is Prevalent in Severe COVID-19 Content: Background: COVID-19 is a major pandemic that has killed more than 196,000 people. The COVID-19 disease course is strikingly divergent. Approximately 80-85% of patients experience mild or no symptoms, while the remainder develop severe disease. The mechanisms underlying these divergent outcomes are unclear. Emerging health disparities data regarding African American and homeless populations suggest that vitamin D insufficiency (VDI) may be an underlying driver of COVID-19 severity. To better define the VDI-COVID-19 link, we determined the prevalence of VDI among our COVID-19 intensive care unit (ICU) patients. Methods: In an Institutional Review Board approved study performed at a single, tertiary care academic medical center, the medical records of COVID-19 patients were retrospectively reviewed. Subjects were included for whom serum 25-hydroxycholecalcifoerol (25OHD) levels were determined. COVID-19-relevant data were compiled and analyzed. We determined the frequency of VDI among COVID-19 patients to evaluate the likelihood of a VDI-COVID-19 relationship. Results: Twenty COVID-19 patients with serum 25OHD levels were identified; 65.0% required ICU admission.The VDI prevalence in ICU patients was 84.6%, vs. 57.1% in floor patients. Strikingly, 100% of ICU patients less than 75 years old had VDI. Coagulopathy was present in 62.5% of ICU COVID-19 patients, and 92.3% were lymphocytopenic. Conclusions: VDI is highly prevalent in severe COVID-19 patients. VDI and severe COVID-19 share numerous associations including hypertension, obesity, male sex, advanced age, concentration in northern climates, coagulopathy, and immune dysfunction. Thus, we suggest that prospective, randomized controlled studies of VDI in COVID-19 patients are warranted.", "qid": 42, "docid": "3ajeiteq", "rank": 50, "score": 0.7920989990234375}, {"content": "Title: COVID\u201019 in Parkinson's Disease Patients Living in Lombardy, Italy Content: BACKGROUND: It is unknown whether patients with Parkinson's disease (PD) are at greater risk of COVID\u201019, what their risk factors are and whether their clinical manifestations differ from the general population. METHODS: In a case\u2010controlled survey, we interviewed 1486 PD patients attending a single tertiary centre in Lombardy, Italy and 1207 family members (controls). RESULTS: 105 (7.1%) and 92 controls (7.6%) were identified as COVID\u201019 cases. COVID\u201019 patients were younger, more likely to suffer from chronic obstructive pulmonary disease, to be obese and vitamin D non\u2010supplemented than unaffected patients. Six patients (5.7%) and seven family members (7.6%) died from COVID\u201019. Patients were less likely to report shortness of breath and require hospitalization. CONCLUSIONS: In an unselected large cohort of non\u2010advanced PD patients, COVID\u201019 risk and mortality did not differ from the general population but symptoms appeared to be milder. The possible protective role of vitamin D supplementation warrants future studies. This article is protected by copyright. All rights reserved.", "qid": 42, "docid": "4pij0x9q", "rank": 51, "score": 0.7891608476638794}, {"content": "Title: Myth Busters: Dietary Supplements and COVID-19 Content: News and social media platforms have implicated dietary supplements in the treatment and prevention of coronavirus disease 2019 (COVID-19). During this pandemic when information quickly evolves in the presence of contradicting messages and misinformation, the role of the pharmacist is essential. Here, we review theoretical mechanisms and evidence related to efficacy and safety of select supplements in the setting of COVID-19, including vitamin C, vitamin D, zinc, elderberry, and silver. Evidence evaluating these supplements in COVID-19 patients is lacking, and providers and patients should not rely on dietary supplements to prevent or treat COVID-19. Rather, reference to evidence-based guidelines should guide treatment decisions.", "qid": 42, "docid": "gu5vrd2v", "rank": 52, "score": 0.7870883941650391}, {"content": "Title: Myth Busters: Dietary Supplements and COVID-19. Content: News and social media platforms have implicated dietary supplements in the treatment and prevention of coronavirus disease 2019 (COVID-19). During this pandemic when information quickly evolves in the presence of contradicting messages and misinformation, the role of the pharmacist is essential. Here, we review theoretical mechanisms and evidence related to efficacy and safety of select supplements in the setting of COVID-19, including vitamin C, vitamin D, zinc, elderberry, and silver. Evidence evaluating these supplements in COVID-19 patients is lacking, and providers and patients should not rely on dietary supplements to prevent or treat COVID-19. Rather, reference to evidence-based guidelines should guide treatment decisions.", "qid": 42, "docid": "jykb5thv", "rank": 53, "score": 0.7870883941650391}, {"content": "Title: Viramina D e coronavirus: un nuovo campo di impiego?/ [Vitamin D and coronavirus: a new field of use?] Content: Given the succession of communications in scientific and popular circuits, tending to take for granted a role for vitamin D in the control of the coronavirus pandemic, the authors conducted an analysis of the literature currently available in order to recognize what is supported by opinions personal and what evidence of effectiveness. At the end of the bibliographic survey there is the current absence of evidence of efficacy in favor of vitamin D in the treatment of coronavirus infection in its various expressions. The diffusion of personal opinions as if they were evidence can be a disturbing factor for adequate assistance and for correct research.", "qid": 42, "docid": "gfyx3nz2", "rank": 54, "score": 0.7869173288345337}, {"content": "Title: [Vitamin D and coronavirus: a new field of use?] Content: Given the succession of communications in scientific and popular circuits, tending to take for granted a role for vitamin D in the control of the coronavirus pandemic, the authors conducted an analysis of the literature currently available in order to recognize what is supported by opinions personal and what evidence of effectiveness. At the end of the bibliographic survey there is the current absence of evidence of efficacy in favor of vitamin D in the treatment of coronavirus infection in its various expressions. The diffusion of personal opinions as if they were evidence can be a disturbing factor for adequate assistance and for correct research.", "qid": 42, "docid": "34f1ie66", "rank": 55, "score": 0.7869173288345337}, {"content": "Title: Evidence Supports a Causal Model for Vitamin D in COVID-19 Outcomes Content: We analyse global data for COVID-19 deaths and recoveries and show that outbreak severity displays a striking latitude relationship with a northern hemisphere bias. Transmission rates can be explained by seasonal weather conditions, but this does not account for observed variations in fatality rates. Many factors point to Vitamin D as a candidate explanation but historical controversy surrounding Vitamin D studies and the lack of a coherent framework for causal inference has hampered acceptance of this explanation despite a wealth of evidence in its favour. We analyse global COVID-19 data using Causal Inference, constructing two contrasting directed acyclic graph (DAG) models, one causal and one acausal, and set out clearly multiple predictions made by each model. We show that observed data strongly match predictions made by the causal model but largely contradict those of the acausal model. We explore historic evidence further supporting the causal model. We review biochemical mechanisms that may explain the various ways in which vitamin D acts. We detail the mechanisms by which the SARS-Cov-2 virus causes the disease and known pathways that involve Vitamin D and show how these both protect against viral infection, as well as ameliorating disease symptoms in COVID-19 and other respiratory diseases. We examine the factors that govern confidence in causal inference models and conclude that a high level of confidence in a causal beneficial role for Vitamin D is justified.", "qid": 42, "docid": "rwh56zhg", "rank": 56, "score": 0.7863093614578247}, {"content": "Title: Vitamin D Receptor stimulation to reduce Acute Respiratory Distress Syndrome (ARDS) in patients with Coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166 Content: Coronavirus infection is a serious health problem awaiting an effective vaccine and/or antiviral treatment. The major complication of coronavirus disease 2019 (COVID-19), the Acute Respiratory Distress syndrome (ARDS), is due to a variety of mechanisms including cytokine storm, dysregulation of the renin-angiotensin system, neutrophil activation and increased (micro)coagulation. Based on many preclinical studies and observational data in humans, ARDS may be aggravated by vitamin D deficiency and tapered down by activation of the vitamin D receptor. Several randomized clinical trials using either oral vitamin D or oral Calcifediol (25OHD) are ongoing. Based on a pilot study, oral calcifediol may be the most promising approach. These studies are expected to provide guidelines within a few months.", "qid": 42, "docid": "5rfxis6f", "rank": 57, "score": 0.7836061716079712}, {"content": "Title: Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166 Content: Coronavirus infection is a serious health problem awaiting an effective vaccine and/or antiviral treatment. The major complication of coronavirus disease 2019 (COVID-19), the Acute Respiratory Distress syndrome (ARDS), is due to a variety of mechanisms including cytokine storm, dysregulation of the renin-angiotensin system, neutrophil activation and increased (micro)coagulation. Based on many preclinical studies and observational data in humans, ARDS may be aggravated by vitamin D deficiency and tapered down by activation of the vitamin D receptor. Several randomized clinical trials using either oral vitamin D or oral Calcifediol (25OHD) are ongoing. Based on a pilot study, oral calcifediol may be the most promising approach. These studies are expected to provide guidelines within a few months.", "qid": 42, "docid": "cb2j9i53", "rank": 58, "score": 0.7836061716079712}, {"content": "Title: Reviews of Science for Science Librarians: Vitamins and Trace Elements that May Be Preventive or Ameliorating in This Age of Contagion Content: Prompted by COVID-19, many laypersons now seek information on nutritional support to ward off or help shorten the effects of serious infectious diseases, and are attracted to practices and substances that lack a serious scientific basis. This paper scanned peer-reviewed medical literature to prove a concept: That diets or supplements rich in some vitamins or minerals may indeed be important in managing threats to health caused by a variety of infectious diseases in the past and compares these findings to the current recommendations of the Academy of Nutrition and Dietetics and to research by Zhang and Liu, two China-based pioneers in countering COVID-19. Vitamins A, D, and zinc, are common to both groups and are well supported in the literature. Vitamin C is also a common denominator but has a mixed record of efficacy in dealing with prior infectious outbreaks. Iron has support and do some other vitamins and trace elements. Health science librarians should emphasize that while experts can disagree on particular micronutrients they tend to agree that decisions on protective or curative supplements or diets or should have some basis in fact.", "qid": 42, "docid": "5uo2bxiv", "rank": 59, "score": 0.7818185091018677}, {"content": "Title: A Comprehensive Literature Review on the Clinical Presentation, and Management of the Pandemic Coronavirus Disease 2019 (COVID-19) Content: Coronavirus disease 2019 (COVID-19) is a declared global pandemic. There are multiple parameters of the clinical course and management of the COVID-19 that need optimization. A hindrance to this development is the vast amount of misinformation present due to scarcely sourced manuscript preprints and social media. This literature review aims to presents accredited and the most current studies pertaining to the basic sciences of SARS-CoV-2, clinical presentation and disease course of COVID-19, public health interventions, and current epidemiological developments. The review on basic sciences aims to clarify the jargon in virology, describe the virion structure of SARS-CoV-2 and present pertinent details relevant to clinical practice. Another component discussed is the brief history on the series of experiments used to explore the origins and evolution of the phylogeny of the viral genome of SARS-CoV-2. Additionally, the clinical and epidemiological differences between COVID-19 and other infections causing outbreaks (SARS, MERS, H1N1) are elucidated. Emphasis is placed on evidence-based medicine to evaluate the frequency of presentation of various symptoms to create a stratification system of the most important epidemiological risk factors for COVID-19. These can be used to triage and expedite risk assessment. Furthermore, the limitations and statistical strength of the diagnostic tools currently in clinical practice are evaluated. Criteria on rapid screening, discharge from hospital and discontinuation of self-quarantine are clarified. Epidemiological factors influencing the rapid rate of spread of the SARS-CoV-2 virus are described. Accurate information pertinent to improving prevention strategies is also discussed. The penultimate portion of the review aims to explain the involvement of micronutrients such as vitamin C and vitamin D in COVID19 treatment and prophylaxis. Furthermore, the biochemistry of the major candidates for novel therapies is briefly reviewed and a summary of their current status in the clinical trials is presented. Lastly, the current scientific data and status of governing bodies such as the Center of Disease Control (CDC) and the WHO on the usage of controversial therapies such as angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs) (Ibuprofen), and corticosteroids usage in COVID-19 are discussed. The composite collection of accredited studies on each of these subtopics of COVID-19 within this review will enable clarification and focus on the current status and direction in the planning of the management of this global pandemic.", "qid": 42, "docid": "vpodtbjk", "rank": 60, "score": 0.781153678894043}, {"content": "Title: Vitamin D status, body mass index, ethnicity and COVID-19: Initial analysis of the first-reported UK Biobank COVID-19 positive cases (n 580) compared with negative controls (n 723) Content: In this short report we present a preliminary assessment of the serum 25-hydroxyvitamin D status (25(OH)D), body mass index (BMI), ethnicity and other lifestyle factors in the first-reported UK Biobank COVID-19 positive cases (n 580) compared with negative controls (n 723). The COVID-19 cases include those who have been treated as a hospital in-patient as well as those who have not, and are from England only. Mean (SD) for age was 57.5 (8.7) in positive cases and 57.9 (8.7) in negative controls.", "qid": 42, "docid": "jx15ib8v", "rank": 61, "score": 0.7801006436347961}, {"content": "Title: Low plasma 25(OH) vitamin D3 level is associated with increased risk of COVID-19 infection: an Israeli population-based study Content: Aim: To evaluate associations of plasma 25(OH)D status with the likelihood of coronavirus disease (COVID-19) infection and hospitalization. Methods: The study population included the 14,000 members of Leumit Health Services who were tested for COVID-19 infection from February 1st to April 30th, 2020, and who had at least one previous blood test for plasma 25(OH)D level. \"Suboptimal\" or \"low\" plasma 25(OH)D level was defined as plasma 25-hydroxyvitamin D, or 25(OH)D, concentration below 30 ng/mL. Results: Of 7,807 individuals, 782 (10.1%) were COVID-19-positive, and 7,025 (89.9%) COVID-19-negative. The mean plasma vitamin D level was significantly lower among those who tested positive than negative for COVID-19 [19.00 ng/mL (95% confidence interval [CI] 18.41-19.59) vs. 20.55 (95% CI 20.32-20.78)]. Univariate analysis demonstrated an association between low plasma 25(OH)D level and increased likelihood of COVID-19 infection [crude odds ratio (OR) of 1.58 (95% CI 1.24-2.01, p<0.001)], and of hospitalization due to the SARS-CoV-2 virus [crude OR of 2.09 (95% CI 1.01-4.30, p<0.05)]. In multivariate analyses that controlled for demographic variables and psychiatric and somatic disorders, the adjusted OR of COVID-19 infection [1.45 (95% CI 1.08-1.95, p<0.001)], and of hospitalization due to the SARS-CoV-2 virus [1.95 (95% CI 0.98-4.845, p=0.061)] were preserved. In the multivariate analyses, age over 50 years, male gender and low-medium socioeconomic status were also positively associated with the risk of COVID-19 infection; age over 50 years was positively associated with the likelihood of hospitalization due to COVID-19.", "qid": 42, "docid": "5xhc3h0z", "rank": 62, "score": 0.7798070907592773}, {"content": "Title: Ultraviolet and COVID-19 pandemic Content: BACKGROUND: COVID-19 virus causes coronavirus disease. AIMS: It is a highly contagious viral infection. PATIENTS/METHODS/RESULTS/CONCLUSION: In this article, we will discuss the potential phototherapy problems and also alternative options for dermatologists, ultraviolet treatment against COVID-19 virus, and vitamin D-associated problems in these coronavirus days.", "qid": 42, "docid": "w143rf7h", "rank": 63, "score": 0.7797828316688538}, {"content": "Title: Nutrition in times of Covid-19, how to trust the deluge of scientific information Content: The Covid-19 pandemic has daunted the world with its enormous impact on healthcare, economic recession, and psychological distress. Nutrition is an integral part of every person life care, and should also be mandatorily integrated to patient care under the Covid-19 pandemic. It is crucial to understand how the Covid-19 does develop and which risk factors are associated with negative outcomes and death. Therefore, it is of utmost importance to have studies that respect the basic tenets of the scientific method in order to be trusted. The goal of this review is to discuss the deluge of scientific data and how it might influence clinical reasoning and practice. RECENT FINDINGS: A large number of scientific manuscripts are daily published worldwide, and the Covid-19 makes no exception. Up to now, data on Covid-19 have come from countries initially affected by the disease and mostly pertain either epidemiological observations or opinion papers. Many of them do not fulfil the essential principles characterizing the adequate scientific method. SUMMARY: It is crucial to be able to critical appraise the scientific literature, in order to provide adequate nutrition therapy to patients, and in particular, to Covid-19 infected individuals.", "qid": 42, "docid": "ube5pd4y", "rank": 64, "score": 0.7775634527206421}, {"content": "Title: Does Lockdown Decrease the Protective Role of ultraviolet-B (UVB) Radiation in Reducing COVID-19 Deaths? Content: Background: Nations are imposing unprecedented measures at large-scale to contain the spread of COVID-19 pandemic. Recent studies indicate that measures such as lockdowns may have slowed down the growth of COVID-19. However, in addition to substantial economic and social costs, these measures also limit the exposure to Ultraviolet-B radiation (UVB). Emerging observational evidence indicate the protective role of UVB and vitamin D in reducing the severity and mortality of COVID-19 deaths. In this observational study, we empirically outline the independent protective roles of lockdown and UVB exposure as measured by ultraviolet index (UVI), whilst also examining whether the severity of lockdown is associated with a reduction in the protective role. Methods. We apply a log-linear fixed-effects model to a panel dataset of 162 countries over a period of 108 days (n=6049). We use the cumulative number of COVID-19 deaths as the dependent variable and isolate the mitigating influence of lockdown severity on the association between UVI and growth-rates of COVID-19 deaths from time-constant country-specific and time-varying country-specific potentially confounding factors. Findings: After controlling for time-constant and time-varying factors, we find that a unit increase in UVI and lockdown severity are independently associated with 17% [-1.8 percentage points] and 77% [-7.9 percentage points] decline in COVID-19 deaths growth rate, indicating their respective protective roles. However, the widely utilized and least severe lockdown (recommendation to not leave the house) already fully mitigates the protective role of UVI by 95% [1.8 percentage points] indicating its downside. Interpretation: We find that lockdown severity and UVI are independently associated with a slowdown in the daily growth rates of cumulative COVID-19 deaths. However, we find consistent evidence that increase in lockdown severity is associated with a significant reduction in the protective role of UVI in reducing COVID-19 deaths. Our results suggest that lockdowns in conjunction with adequate exposure to UVB radiation might have provided even more substantial health benefits, than lockdowns alone. For example, we estimate that there would be 21% fewer deaths on average with sufficient UVB exposure while people were recommended not to leave their house. Therefore, our study outlines the importance of considering UVB exposure, especially while implementing lockdowns and may support policy decision making in countries imposing such measures.", "qid": 42, "docid": "z6cp42aa", "rank": 65, "score": 0.7774074077606201}, {"content": "Title: Nutritional management and support in COVID-19: Emerging nutrivigilance Content: Corona virus disease (COVID-19) emerged as an epidemic from China, with quick spread globally. The disease can lead to serious problems, like pneumonia or even death especially among vulnerable people with existing health conditions. Its treatment and management require huge efforts from medical professionals often at the cost of their own health and life. Nutrition is the epicenter for the management of such diseases which works synergistically with the medical treatment for quick and better recovery. It has been associated with great human and economic toll and it is still not contained. Currently over two million people are affected and over 300,000 deaths globally. However, due to its newness and unfamiliarity, the understanding of this novel virus is still evolving. This viral infection poses numerous metabolic challenges to those severely affected and addressing them is a key to better outcomes. Medical nutritional therapy is thus among the mainstay of core components of comprehensive treatment measures for patients with COVID-19. This manuscript therefore aims to highlight the role of nutritional management and support in covid-19 disease.", "qid": 42, "docid": "dh71u7uw", "rank": 66, "score": 0.7773430347442627}, {"content": "Title: Nutritional management and support in COVID-19: Emerging nutrivigilance. Content: Corona virus disease (COVID-19) emerged as an epidemic from China, with quick spread globally. The disease can lead to serious problems, like pneumonia or even death especially among vulnerable people with existing health conditions. Its treatment and management require huge efforts from medical professionals often at the cost of their own health and life. Nutrition is the epicenter for the management of such diseases which works synergistically with the medical treatment for quick and better recovery. It has been associated with great human and economic toll and it is still not contained. Currently over two million people are affected and over 300,000 deaths globally. However, due to its newness and unfamiliarity, the understanding of this novel virus is still evolving. This viral infection poses numerous metabolic challenges to those severely affected and addressing them is a key to better outcomes. Medical nutritional therapy is thus among the mainstay of core components of comprehensive treatment measures for patients with COVID-19. This manuscript therefore aims to highlight the role of nutritional management and support in covid-19 disease.", "qid": 42, "docid": "6tzlhzg8", "rank": 67, "score": 0.7773430347442627}, {"content": "Title: 'Scientific Strabismus' or two related pandemics: coronavirus disease and vitamin D deficiency Content: The WHO has announced the novel coronavirus disease (COVID-19) outbreak to be a global pandemic. The distribution of community outbreaks shows seasonal patterns along certain latitude, temperature and humidity, that is, similar to the behaviour of seasonal viral respiratory tract infections. COVID-19 displays significant spread in northern mid-latitude countries with an average temperature of 5\u00ad11\u00b0C and low humidity. Vitamin D deficiency has also been described as pandemic, especially in Europe. Regardless of age, ethnicity and latitude, recent data showed that 40 % of Europeans are vitamin D deficient (25-hydroxyvitamin D (25(OH)D) levels <50 nmol/l), and 13 % are severely deficient (25(OH)D < 30 nmol/l). A quadratic relationship was found between the prevalences of vitamin D deficiency in most commonly affected countries by COVID-19 and the latitudes. Vitamin D deficiency is more common in the subtropical and mid-latitude countries than the tropical and high-latitude countries. The most commonly affected countries with severe vitamin D deficiency are from the subtropical (Saudi Arabia 46 %; Qatar 46 %; Iran 33\u00b74 %; Chile 26\u00b74 %) and mid-latitude (France 27\u00b73 %; Portugal 21\u00b72 %; Austria 19\u00b73 %) regions. Severe vitamin D deficiency was found to be nearly 0 % in some high-latitude countries (e.g. Norway, Finland, Sweden, Denmark and Netherlands). Accordingly, we would like to call attention to the possible association between severe vitamin D deficiency and mortality pertaining to COVID-19. Given its rare side effects and relatively wide safety, prophylactic vitamin D supplementation and/or food fortification might reasonably serve as a very convenient adjuvant therapy for these two worldwide public health problems alike.", "qid": 42, "docid": "lj4mq31p", "rank": 68, "score": 0.7765904664993286}, {"content": "Title: Mechanism of inflammatory response in associated comorbidities in COVID-19 Content: BACKGROUND AND AIMS: The outbreak of the new coronavirus, SARS-CoV-2, causes a respiratory disease and individuals with pre-existing cardiometabolic disorders display worse prognosis through the infection course. The aim of this minireview is to present epidemiological data related to metabolic comorbidities in association with the SARS-CoV-2. METHODS: This is a narrative mini-review with Pubmed search until April 23, 2020 using the keywords COVID-19, SARS-CoV-2, treatment of coronavirus and following terms: diabetes mellitus, obesity, arterial hypertension, ACE-inhibitors, cytokine storm, immune response and vitamin D. RESULTS: Studies indicate that obese individuals are more likely to develop infections, and that adipose tissue serves as a pathogen reservoir. In diabetic individuals higher rate of inflammatory processes is seen due to constant glucose recognition by C type lectin receptors. Hypertensive individuals, usually grouped with other conditions, are treated with drugs to reduce blood pressure mostly through ACEi and ARB, that leads to increased ACE2 expression, used by SARS-CoV-2 for human's cell entry. Until now, the studies have shown that individuals with those conditions and affected by COVID-19 present an uncontrolled release of pro-inflammatory cytokines and an unbalanced immune response, leading to the cytokine storm phenomenon. Vitamin D is highlighted as a potential therapeutic target, because in addition to acting on the immune system, it plays an important role in the control of cardiometabolic diseases. CONCLUSION: Currently, since there is no proven and effective antiviral therapy for SARS-CoV-2, the efforts should focus on controlling inflammatory response and reduce the risks of associated complications.", "qid": 42, "docid": "cn3bpmwj", "rank": 69, "score": 0.7753729224205017}, {"content": "Title: The Use of IV vitamin C for patients with COVID-19: a single center observational study. Content: BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has affected almost 2.5 million people worldwide with almost 170 000 deaths reported to date. So far, there is scarce evidence for the current treatment options available for COVID-19. Vitamin C has previously been used for treatment of severe sepsis and septic shock. We reviewed the feasibility of using vitamin C in the setting of COVID-19 in a series of patients. METHODS We sequentially identified a series of patients who were requiring at least 30% of FiO2 or more who received IV vitamin C as part of the COVID-19 treatment and analyzed their demographic and clinical characteristics. We compared inflammatory markers pre and post treatment including D-dimer and ferritin. RESULTS We identified a total of 17 patients who received IV vitamin C for COVID-19. The inpatient mortality rate in this series was 12% with 17.6% rates of intubation and mechanical ventilation. We noted a significant decrease in inflammatory markers, including ferritin and D-dimer, and a trend to decreasing FiO2 requirements, after vitamin C administration. CONCLUSION The use of IV vitamin C in patients with moderate to severe COVID-19 disease may be feasible.", "qid": 42, "docid": "vbj4ki20", "rank": 70, "score": 0.774922251701355}, {"content": "Title: COVID-19: is there a role for immunonutrition, particularly in the over 65s? Content: In late December 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in Wuhan, Hubei, China, resulting in the potentially fatal COVID-19. It went on to be officially recognised as a pandemic by the World Health Organisation on 11 March 2020. While many public health strategies have evolved, there has been little mention of the immune system and how this could be strengthened to help protect against viral infections such as SARS-CoV-2. The present paper evaluates the current evidence base relating to immunonutrition, with a particular focus on respiratory viruses. Within the nutrition sector a promising body of evidence studying inter-relationships between certain nutrients and immune competence already exists. This could potentially be an important player in helping the body to deal with the coronavirus, especially among elders. Evidence for vitamins C, D and zinc and their roles in preventing pneumonia and respiratory infections (vitamins C and D) and reinforcing immunity (zinc) appears to look particularly promising. Ongoing research within this important field is urgently needed.", "qid": 42, "docid": "479wkesk", "rank": 71, "score": 0.7744181156158447}, {"content": "Title: COVID-19 Fatalities, Latitude, Sunlight, and Vitamin D Content: BACKGROUND: Since Vitamin D is known to be vital in regulating the immune system, and sunlight UV radiation exposure on the skin produces Vitamin D and UV intensity is highest nearest the equator, a study was done to examine the correlation between the latitude and COVID-19 fatality rates for countries. METHODS: Eighty-eight countries were selected based on their likelihood of providing reliable data. Using death rates/million for each country from the \"worldometer\" web site, a correlation analysis was done between death rates and a country's latitude. RESULTS: A highly significant, positive correlation was found between lower death rates and a country's proximity to the equator (Pearson r\u00e2\u0080\u00af=\u00e2\u0080\u00af.40 p<.0001, two-tailed t-test). The R squared of .16 means that 16% of the variation in death rates among nations is accounted for by the latitude of the country. Evidence is presented suggesting a direct correlation between sunlight exposure and reduced mortality. DISCUSSION: This study is the first to document a statistically significant correlation between a country's latitude and its COVID-19 mortality and is consistent with other research regarding latitude, Vitamin D deficiency, and COVID-19 fatalities. Limitations of this study are noted. CONCLUSION: Further research is needed to confirm the correlation between latitude and COVID-19 fatalities, and to determine the optimum amounts of safe sunlight exposure and/or vitamin D oral supplementation to reduce COVID-19 fatalities in populations that are at high risk for vitamin D deficiency.", "qid": 42, "docid": "jy45c2pk", "rank": 72, "score": 0.7738028168678284}, {"content": "Title: Dietary recommendations during the COVID-19 pandemic Content: Optimal nutrition can improve well-being and might mitigate the risk and morbidity associated with coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review summarizes nutritional guidelines to support dietary counseling provided by dietitians and health-related professionals. The majority of documents encouraged the consumption of fruits, vegetables, and whole grain foods. Thirty-one percent of the guidelines highlighted the importance of minerals and vitamins such as zinc and vitamins C, A, and D to maintain a well-functioning immune system. Dietary supplementation has not been linked to COVID-19 prevention. However, supplementation with vitamins C and D, as well as with zinc and selenium, was highlighted as potentially beneficial for individuals with, or at risk of, respiratory viral infections or for those in whom nutrient deficiency is detected. There was no convincing evidence that food or food packaging is associated with the transmission of COVID-19, but good hygiene practices for handling and preparing foods were recommended. No changes to breastfeeding recommendations have been made, even in women diagnosed with COVID-19.", "qid": 42, "docid": "wbspn2zm", "rank": 73, "score": 0.7731087803840637}, {"content": "Title: Dietary recommendations during the COVID-19 pandemic. Content: Optimal nutrition can improve well-being and might mitigate the risk and morbidity associated with coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review summarizes nutritional guidelines to support dietary counseling provided by dietitians and health-related professionals. The majority of documents encouraged the consumption of fruits, vegetables, and whole grain foods. Thirty-one percent of the guidelines highlighted the importance of minerals and vitamins such as zinc and vitamins C, A, and D to maintain a well-functioning immune system. Dietary supplementation has not been linked to COVID-19 prevention. However, supplementation with vitamins C and D, as well as with zinc and selenium, was highlighted as potentially beneficial for individuals with, or at risk of, respiratory viral infections or for those in whom nutrient deficiency is detected. There was no convincing evidence that food or food packaging is associated with the transmission of COVID-19, but good hygiene practices for handling and preparing foods were recommended. No changes to breastfeeding recommendations have been made, even in women diagnosed with COVID-19.", "qid": 42, "docid": "zrlqzbss", "rank": 74, "score": 0.7731086611747742}, {"content": "Title: Nutrition in times of Covid-19, how to trust the deluge of scientific information Content: PURPOSE OF REVIEW: The Covid-19 pandemic has daunted the world with its enormous impact on healthcare, economic recession, and psychological distress. Nutrition is an integral part of every person life care, and should also be mandatorily integrated to patient care under the Covid-19 pandemic. It is crucial to understand how the Covid-19 does develop and which risk factors are associated with negative outcomes and death. Therefore, it is of utmost importance to have studies that respect the basic tenets of the scientific method in order to be trusted. The goal of this review is to discuss the deluge of scientific data and how it might influence clinical reasoning and practice. RECENT FINDINGS: A large number of scientific manuscripts are daily published worldwide, and the Covid-19 makes no exception. Up to now, data on Covid-19 have come from countries initially affected by the disease and mostly pertain either epidemiological observations or opinion papers. Many of them do not fulfil the essential principles characterizing the adequate scientific method. SUMMARY: It is crucial to be able to critical appraise the scientific literature, in order to provide adequate nutrition therapy to patients, and in particular, to Covid-19 infected individuals.", "qid": 42, "docid": "1k1p76wv", "rank": 75, "score": 0.7730223536491394}, {"content": "Title: COVID-19 Fatalities, Latitude, Sunlight, and Vitamin D Content: BACKGROUND: Since Vitamin D is known to be vital in regulating the immune system, and sunlight UV radiation exposure on the skin produces Vitamin D and UV intensity is highest nearest the equator, a study was done to examine the correlation between the latitude and COVID-19 fatality rates for countries. METHODS: Eighty-eight countries were selected based on their likelihood of providing reliable data. Using death rates/million for each country from the \u201cworldometer\u201d web site, a correlation analysis was done between death rates and a country's latitude. RESULTS: A highly significant, positive correlation was found between lower death rates and a country's proximity to the equator (Pearson r = .40 p<.0001, two-tailed t-test). The R squared of .16 means that 16% of the variation in death rates among nations is accounted for by the latitude of the country. Evidence is presented suggesting a direct correlation between sunlight exposure and reduced mortality. DISCUSSION: This study is the first to document a statistically significant correlation between a country's latitude and its COVID-19 mortality and is consistent with other research regarding latitude, Vitamin D deficiency, and COVID-19 fatalities. Limitations of this study are noted. CONCLUSION: Further research is needed to confirm the correlation between latitude and COVID-19 fatalities, and to determine the optimum amounts of safe sunlight exposure and/or vitamin D oral supplementation to reduce COVID-19 fatalities in populations that are at high risk for vitamin D deficiency.", "qid": 42, "docid": "l8bsoqbx", "rank": 76, "score": 0.772530198097229}, {"content": "Title: Clinical Pharmacology Considerations for Developing Small-Molecule Treatments for COVID-19 Content: Numerous drugs are being investigated for the treatment of COVID-19, including antivirals and therapies targeting complications related to COVID-19. The clinical presentation of COVID-19 varies from mild fever, cough, and dyspnea in the early stages of disease to severe complications such as acute respiratory distress syndrome, systemic hyperinflammation, and sepsis. A thorough understanding of the disease pathogenesis and the disease complications is essential to developing effective therapies to treat this potentially life-threatening disease. This review offers key clinical pharmacology considerations involved in the development of small molecules for the treatment of COVID-19. They are based on the major observed disease complications that impact drug absorption, distribution, metabolism, and elimination. We also address considerations regarding potential drug interactions, alternative routes and methods of administration, and dosing in patients on hemodialysis.", "qid": 42, "docid": "s0c9odzd", "rank": 77, "score": 0.7704799175262451}, {"content": "Title: Functional Role of Dietary Intervention to Improve the Outcome of COVID-19: A Hypothesis of Work Content: Background: On the 31 December 2019, the World Health Organization (WHO) was informed of a cluster of cases of pneumonia of unknown origin detected in Wuhan City, Hubei Province, China. The infection spread first in China and then in the rest of the world, and on the 11th of March, the WHO declared that COVID-19 was a pandemic. Taking into consideration the mortality rate of COVID-19, about 5\u20137%, and the percentage of positive patients admitted to intensive care units being 9\u201311%, it should be mandatory to consider and take all necessary measures to contain the COVID-19 infection. Moreover, given the recent evidence in different hospitals suggesting IL-6 and TNF-\u03b1 inhibitor drugs as a possible therapy for COVID-19, we aimed to highlight that a dietary intervention could be useful to prevent the infection and/or to ameliorate the outcomes during therapy. Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-\u03b1, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes.", "qid": 42, "docid": "6r6qs4pp", "rank": 78, "score": 0.7701797485351562}, {"content": "Title: Ultraviolet and COVID\u201019 pandemic Content: BACKGROUND: COVID\u201019 virus causes coronavirus disease. AIMS: It is a highly contagious viral infection. PATIENTS/METHODS/RESULTS/CONCLUSION: In this article, we will discuss the potential phototherapy problems and also alternative options for dermatologists, ultraviolet treatment against COVID\u201019 virus, and vitamin D\u2013associated problems in these coronavirus days.", "qid": 42, "docid": "c2gll4d1", "rank": 79, "score": 0.7699415683746338}, {"content": "Title: Pharmacological agents under investigation in the treatment of coronavirus disease 2019 and the importance of melatonin Content: Coronavirus disease 2019 (COVID-19) is a life-threatening infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 pandemic causing morbidities and even deaths worldwide revealed that there is urgent need to find pharmacological agents or vaccines. Although there are a lot of agents under investigation, there is no approved agent for the prevention or treatment of the COVID-19 yet. Treatment of patients remains mainly supportive as well as compassionate use of the agents under investigation. It is well established that excessive inflammatory and immune response as well as oxidative injury play a critical role in the pathogenesis of COVID-19. In this review, we aimed to update knowledge about pathogenesis, clinical features and pharmacological treatment of COVID-19 and review the potential beneficial effects of ancient antioxidant, anti-inflammatory and immunomodulatory molecule melatonin for prevention and treatment of COVID-19.", "qid": 42, "docid": "afx2wv9d", "rank": 80, "score": 0.7696911096572876}, {"content": "Title: Pharmacological agents under investigation in the treatment of coronavirus disease 2019 and the importance of melatonin. Content: Coronavirus disease 2019 (COVID-19) is a life-threatening infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 pandemic causing morbidities and even deaths worldwide revealed that there is urgent need to find pharmacological agents or vaccines. Although there are a lot of agents under investigation, there is no approved agent for the prevention or treatment of the COVID-19 yet. Treatment of patients remains mainly supportive as well as compassionate use of the agents under investigation. It is well established that excessive inflammatory and immune response as well as oxidative injury play a critical role in the pathogenesis of COVID-19. In this review, we aimed to update knowledge about pathogenesis, clinical features and pharmacological treatment of COVID-19 and review the potential beneficial effects of ancient antioxidant, anti-inflammatory and immunomodulatory molecule melatonin for prevention and treatment of COVID-19.", "qid": 42, "docid": "rx1k9hu5", "rank": 81, "score": 0.7696911096572876}, {"content": "Title: Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19) Content: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) represents an emergent global threat which is straining worldwide healthcare capacity. As of May 27th, the disease caused by SARS-CoV-2 (COVID-19) has resulted in more than 340,000 deaths worldwide, with 100,000 deaths in the US alone. It is imperative to study and develop pharmacological treatments suitable for the prevention and treatment of COVID-19. Ascorbic acid is a crucial vitamin necessary for the correct functioning of the immune system. It plays a role in stress response and has shown promising results when administered to the critically ill. Quercetin is a well-known flavonoid whose antiviral properties have been investigated in numerous studies. There is evidence that vitamin C and quercetin co-administration exerts a synergistic antiviral action due to overlapping antiviral and immunomodulatory properties and the capacity of ascorbate to recycle quercetin, increasing its efficacy. Safe, cheap interventions which have a sound biological rationale should be prioritized for experimental use in the current context of a global health pandemic. We present the current evidence for the use of vitamin C and quercetin both for prophylaxis in high-risk populations and for the treatment of COVID-19 patients as an adjunct to promising pharmacological agents such as Remdesivir or convalescent plasma.", "qid": 42, "docid": "ajla989m", "rank": 82, "score": 0.7690294981002808}, {"content": "Title: The key role of zinc in elderly immunity: A possible approach in the COVID-19 crisis Content: BACKGROUND & AIMS: The COVID-19 infection can lead to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mainly affecting patients aged 60 and older. Preliminary data suggest that the nutritional status can change the course of the infection, and on the matter, zinc is crucial for growth, development, and the maintenance of immune function. In the absence of treatment for this virus, there is an urgent need to find alternative methods that can contribute to control of disease. The aim of this paper is to establish the relation between zinc and COVID-19. METHODS AND RESULTS: From the prior scientific knowledge, we have performed a review of the literature and examine the role of zinc in immune function in the infection by COVID-19. Our findings are that the zinc as an anti-inflammatory agent may help to optimize immune function and reduce the risk of infection. CONCLUSIONS: Zinc supplementation can be a useful strategy to reduce the global burden of infection in the elderly, there is a need the increased reporting to improve our understanding of COVID-19 and the care of affected patients.", "qid": 42, "docid": "0uim5xl8", "rank": 83, "score": 0.7685233354568481}, {"content": "Title: El suplemento con altas dosis de vitamina D podr\u00eda representar una alternativa promisoria para prevenir o tratar la infecci\u00f3n por COVID-19 Content: Resumen Si bien carecemos de suficiente evidencia que justifique suplementar con vitamina D en la prevenci\u00f3n y/o tratamiento de la infecci\u00f3n por COVID-19, a la fecha resulta cada vez m\u00e1s factible que esta hip\u00f3tesis sea v\u00e1lida. Dos mecanismos b\u00e1sicos generales deber\u00edan ser considerados. Uno ser\u00eda la acci\u00f3n anti-infecciosa e inmuno-moduladora que ejerce mejorando las barreras intercelulares por est\u00edmulo de la inmunidad innata, as\u00ed tambi\u00e9n por modulaci\u00f3n de la inmunidad adaptativa. Tambi\u00e9n, la vitamina D reduce la producci\u00f3n de citoquinas inflamatorias como IL-2 e interfer\u00f3n gamma (INF\u03b3). M\u00e1s recientemente se han demostrado m\u00faltiples efectos pleiotr\u00f3picos sobre las acciones de vitamina D a nivel anti-inflamatorio e inmuno-modulador. Esto explica resultados positivos en estudios con influenza, coronavirus y otras infecciones respiratorias. Se ha descripto relaci\u00f3n inversa entre niveles s\u00e9ricos de vitamina D y prevalencia de patolog\u00eda infecciosa respiratoria. De inter\u00e9s, otro abordaje mecan\u00edstico responde a considerar la inhibici\u00f3n del sistema renina-angiotensina-aldosterona, que se exacerba en la infecci\u00f3n por COVID-19 debido a que el virus se une a la enzima ECA2, quedando disponible m\u00e1s angiotensina II para causar da\u00f1o. La vitamina D inhibe mediadores del SRAA -presente en todas las c\u00e9lulas del organismo-, y por inhibir la actividad ECA y aumentar la ECA2, disminuye los niveles de angiotensina II. Presentamos estudios con propuestas de dosis recomendadas de vitamina D y aunque no quede concretada una \u00fanica gu\u00eda, los posibles beneficios son promisorios. Finalmente, el prop\u00f3sito de la presente revisi\u00f3n es compartir esta idea con profesionales de la salud para encender el debate y llamar a la reflexi\u00f3n cr\u00edtica, de modo tal que se pueda contribuir con el emprendimiento de dise\u00f1os cl\u00ednicos adecuados para validar los beneficios de utilizar altas dosis de vitamina D en beneficio de la salud p\u00fablica y sobre todo en tiempos de esta emergencia por COVID-19. Abstract Although we lack enough evidence to justify supplementing with vitamin D in the prevention and treatment of COVID-19 infection, it is increasingly feasible that this hypothesis is valid. Two general underlying mechanisms should be considered. One would be the anti-infectious and immunomodulatory action that it exerts by improving intercellular barriers by stimulating innate immunity, as well as by modulating adaptive immunity. Also, vitamin D reduces the production of inflammatory cytokines, such as IL-2 and interferon-gamma (INF\u03b3). More recently, multiple pleiotropic effects have been demonstrated on the actions of vitamin D at the anti-inflammatory and immunomodulatory level with positive results in studies with influenza, coronavirus, and other respiratory infections. An inverse relationship between serum vitamin D levels and the prevalence of the respiratory infectious disease has been described. Of interest, another mechanistic approach responds to considering the inhibition of the renin-angiotensin-aldosterone system (RAAS), which is exacerbated in COVID-19 infection because the virus binds to the enzyme ACE2, making more angiotensin II available to cause damage. Vitamin D inhibits mediators of RAAS -present in all cells of the body- and by inhibiting ACE activity and increasing ACE2, it lowers angiotensin II levels. We present studies with proposals for recommended doses of vitamin D, and although a single guideline is not specified, the possible benefits are promising. Finally, the purpose of this review is to share this idea with health professionals to ignite the debate and call for critical reflection, so that it can contribute to the undertaking of more and better clinical designs to validate the benefits of using high doses of vitamin D for the benefit of public health and especially in times of crisis for COVID-19.", "qid": 42, "docid": "1b7viy5o", "rank": 84, "score": 0.7681747674942017}, {"content": "Title: Manejo nutricional del paciente hospitalizado cr\u00edticamente enfermo con COVID-19. Una revisi\u00f3n narrativa./ [Nutritional management of the critically ill inpatient with COVID-19. A narrative review] Content: The current COVID-19 pandemic mainly affects older people, those with obesity or other coexisting chronic diseases such as type-2 diabetes and high blood pressure. It has been observed that about 20 % of patients will require hospitalization, and some of them will need the support of invasive mechanical ventilation in intensive care units. Nutritional status appears to be a relevant factor influencing the clinical outcome of critically ill patients with COVID-19. Several international guidelines have provided recommendations to ensure energy and protein intake in people with COVID-19, with safety measures to reduce the risk of infection in healthcare personnel. The purpose of this review is to analyze the main recommendations related to adequate nutritional management for critically ill patients with COVID-19 in order to improve their prognosis and clinical outcomes.", "qid": 42, "docid": "nivcea89", "rank": 85, "score": 0.7675046920776367}, {"content": "Title: [Nutritional management of the critically ill inpatient with COVID-19. A narrative review]. Content: The current COVID-19 pandemic mainly affects older people, those with obesity or other coexisting chronic diseases such as type-2 diabetes and high blood pressure. It has been observed that about 20 % of patients will require hospitalization, and some of them will need the support of invasive mechanical ventilation in intensive care units. Nutritional status appears to be a relevant factor influencing the clinical outcome of critically ill patients with COVID-19. Several international guidelines have provided recommendations to ensure energy and protein intake in people with COVID-19, with safety measures to reduce the risk of infection in healthcare personnel. The purpose of this review is to analyze the main recommendations related to adequate nutritional management for critically ill patients with COVID-19 in order to improve their prognosis and clinical outcomes.", "qid": 42, "docid": "h6xtavaf", "rank": 86, "score": 0.7675046920776367}, {"content": "Title: Integrative pharmacological mechanism of vitamin C combined with glycyrrhizic acid against COVID-19: findings of bioinformatics analyses. Content: OBJECTIVE Coronavirus disease 2019 (COVID-19) is a fatal and fast-spreading viral infection. To date, the number of COVID-19 patients worldwide has crossed over six million with over three hundred and seventy thousand deaths (according to the data from World Health Organization; updated on 2 June 2020). Although COVID-19 can be rapidly diagnosed, efficient clinical treatment of COVID-19 remains unavailable, resulting in high fatality. Some clinical trials have identified vitamin C (VC) as a potent compound pneumonia management. In addition, glycyrrhizic acid (GA) is clinically as an anti-inflammatory medicine against pneumonia-induced inflammatory stress. We hypothesized that the combination of VC and GA is a potential option for treating COVID-19. METHODS The aim of this study was to determine pharmacological targets and molecular mechanisms of VC + GA treatment for COVID-19, using bioinformational network pharmacology. RESULTS We uncovered optimal targets, biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of VC + GA against COVID-19. Our findings suggested that combinatorial VC and GA treatment for COVID-19 was associated with elevation of immunity and suppression of inflammatory stress, including activation of the T cell receptor signaling pathway, regulation of Fc gamma R-mediated phagocytosis, ErbB signaling pathway and vascular endothelial growth factor signaling pathway. We also identified 17 core targets of VC + GA, which suggest as antimicrobial function. CONCLUSIONS For the first time, our study uncovered the pharmacological mechanism underlying combined VC and GA treatment for COVID-19. These results should benefit efforts to address the most pressing problem currently facing the world.", "qid": 42, "docid": "3cz34tk4", "rank": 87, "score": 0.7670583724975586}, {"content": "Title: Cancer therapy and treatments during COVID-19 era Content: The COVID-19 pandemic has put a serious strain on health treatments as well at the economies of many nations. Unfortunately, there is not currently available vaccine for SARS-Cov-2/COVID-19. Various types of patients have delayed treatment or even routine check-ups and we are adapting to a virtual world. In many cases, surgeries are delayed unless they are essential. This is also true with regards to cancer treatments and screening. Interestingly, some existing drugs and nutraceuticals have been screened for their effects on COVID-19. Certain FDA approved drugs, vitamin, natural products and trace minerals may be repurposed to treat or improve the prevention of COVID-19 infections and disease progression. This review article will summarize how the treatments of various cancer patients has changed during the COVID-19 era as well as discuss the promise of some existing drugs and other agents to be repurposed to treat this disease.", "qid": 42, "docid": "i90x2r7t", "rank": 88, "score": 0.7669058442115784}, {"content": "Title: Nutrients in prevention, treatment, and management of viral infections; special focus on Coronavirus Content: BACKGROUND: The coronavirus disease 2019 (COVID-19) is a pandemic caused by coronavirus with mild to severe respiratory symptoms. This paper aimed to investigate the effect of nutrients on the immune system and their possible roles in the prevention, treatment, and management of COVID-19 in adults. METHODS: This Systematic review was designed based on the guideline of the Preferred Reporting for Systematic Reviews (PRISMA). The articles that focussed on nutrition, immune system, viral infection, and coronaviruses were collected by searching databases for both published papers and accepted manuscripts from 1990 to 2020. Irrelevant papers and articles without English abstract were excluded from the review process. RESULTS: Some nutrients are actively involved in the proper functioning and strengthening of the human immune system against viral infections including dietary protein, omega-3 fatty acids, vitamin A, vitamin D, vitamin E, vitamin B1, vitamin B6, vitamin B12, vitamin C, iron, zinc, and selenium. Few studies were done on the effect of dietary components on prevention of COVID-19, but supplementation with these nutrients may be effective in improving the health status of patients with viral infections. CONCLUSION: Following a balanced diet and supplementation with proper nutrients may play a vital role in prevention, treatment, and management of COVID-19. However, further clinical trials are needed to confirm these findings and presenting the strong recommendations against this pandemic.", "qid": 42, "docid": "jk0ysuy4", "rank": 89, "score": 0.7662191390991211}, {"content": "Title: Effects of Micronutrients or Conditional Amino Acids on COVID-19 Related Outcomes: An Evidence Analysis Center Scoping Review Content: Abstract Recent narrative reviews have described the potential efficacy of providing individuals infected with COVID-19 with additional micronutrients to reduce disease severity. While there are compelling reasons why providing additional micronutrients or conditional amino acids may affect COVID-19-related outcomes, evidence is lacking. The objective of this scoping review is to explore and describe the literature examining the effect of providing additional micronutrients or conditional amino acids (glutamine, arginine) in adults with conditions or infections similar to COVID-19 infection on COVID-19 related health outcomes. A literature search of the MEDLINE database and hand-search of Cochrane Database of systematic reviews retrieved 1,423 unique studies, and eight studies were included in this scoping review. Four studies examined a target population with ventilator-related pneumonia and acute respiratory distress syndrome, while the other four studies included patients who were at risk for ventilator-associated pneumonia. Interventions included intravenous vitamin C, intramuscular vitamin D, enteral and intramuscular vitamin E, enteral zinc sulfate, and oral and parenteral glutamine. In six of the eight included studies, baseline status of the nutrient of interest was not reported and, thus, it is uncertain how outcomes may vary in the context of nutrient deficiency or insufficiency compared to sufficiency. In the absence of direct evidence examining efficacy of providing additional micronutrients or conditional amino acids to standard care, registered dietitian nutritionists (RDNs) must rely on clinical expertise, and indirect evidence to guide medical nutrition therapy (MNT) for patients infected with COVID-19.", "qid": 42, "docid": "82myb5ao", "rank": 90, "score": 0.7659620046615601}, {"content": "Title: The angiotensin-converting enzyme 2 (ACE2) receptor in the prevention and treatment of COVID-19 are distinctly different paradigms Content: There is current debate concerning the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers (ARBs), for hypertension management, during COVID-19 infection. Specifically, the suggestion has been made that ACE inhibitors or ARBs could theoretically contribute to infection via increasing ACE2 receptor expression and hence increase viral load. The ACE2 receptor is responsible for binding the SAR-CoV2 viral spike and causing COVID-19 infection. What makes the argument somewhat obtuse for ACE inhibitors or ARBs is that ACE2 receptor expression can be increased by compounds that activate or increase the expression of SIRT1. Henceforth common dietary interventions, vitamins and nutrients may directly or indirectly influence the cellular expression of the ACE2 receptor. There are many common compounds that can increase the expression of the ACE2 receptor including Vitamin C, Metformin, Resveratrol, Vitamin B3 and Vitamin D. It is important to acknowledge that down-regulation or blocking the cellular ACE2 receptor will likely be pro-inflammatory and may contribute to end organ pathology and mortality in COVID-19. In conclusion from the perspective of the ACE2 receptor, COVID-19 prevention and treatment are distinctly different. This letter reflects on this current debate and suggests angiotensin-converting enzyme inhibitors and ARBs are likely beneficial during COVID-19 infection for hypertensive and normotensive patients.", "qid": 42, "docid": "ux844b25", "rank": 91, "score": 0.7657016515731812}, {"content": "Title: Functional Role of Dietary Intervention to Improve the Outcome of COVID-19: A Hypothesis of Work Content: BACKGROUND: On the 31 December 2019, the World Health Organization (WHO) was informed of a cluster of cases of pneumonia of unknown origin detected in Wuhan City, Hubei Province, China. The infection spread first in China and then in the rest of the world, and on the 11th of March, the WHO declared that COVID-19 was a pandemic. Taking into consideration the mortality rate of COVID-19, about 5-7%, and the percentage of positive patients admitted to intensive care units being 9-11%, it should be mandatory to consider and take all necessary measures to contain the COVID-19 infection. Moreover, given the recent evidence in different hospitals suggesting IL-6 and TNF-&#945; inhibitor drugs as a possible therapy for COVID-19, we aimed to highlight that a dietary intervention could be useful to prevent the infection and/or to ameliorate the outcomes during therapy. Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-&#945;, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes.", "qid": 42, "docid": "uj8gwfdo", "rank": 92, "score": 0.7656728029251099}, {"content": "Title: Can Vitamins, as Epigenetic Modifiers, Enhance Immunity in COVID-19 Patients with Non-communicable Disease? Content: PURPOSE OF REVIEW: The highly infectious transmissible disease, the novel SARS-CoV-2, causing the coronavirus disease (COVID-19), has a median incubation time of 5 to 15 days. The symptoms vary from person to person and many are \u201chidden carriers.\u201d Few people experience immediate reaction and even death within 48 h of infection. However, many show mild to chronic symptoms and recover. Nevertheless, the death rate due to COVID-19 transmission is high especially among patients with non-communicable diseases. The purpose of this review is to provide evidence to consider vitamins as epigenetic modifiers to enhance immunity and reduce inflammatory response in COVID-19 patients with non-communicable diseases. RECENT FINDINGS: Clinical evidence has suggested the risk of getting infected is high among individuals with non-communicable diseases such as cardiovascular disease, type-2 diabetes, cancer, acute respiratory distress syndrome, and renal disease, as well as the elderly with high mortality rate among the cohort. The impact is due to an already compromised immune system of patients. Every patient has a different response to COVID-19, which shows that the ability to combat the deadly virus varies individually. Thus, treatment can be personalized and adjusted to help protect and combat COVID-19 infections, especially in individuals with non-communicable diseases. SUMMARY: Based on current published scientific and medical evidence, the suggestions made in this article for combination of vitamin therapy as epigenetic modifiers to control the unregulated inflammatory and cytokine marker expressions, further needs to be clinically proven. Future research and clinical trials can apply the suggestions given in this article to support metabolic activities in patients and enhance the immune response.", "qid": 42, "docid": "n6x0r58i", "rank": 93, "score": 0.765520453453064}, {"content": "Title: Comorbid Chronic Diseases and Acute Organ Injuries Are Strongly Correlated with Disease Severity and Mortality among COVID-19 Patients: A Systemic Review and Meta-Analysis Content: The recent outbreak of COVID-19 has been rapidly spreading on a global scale. To date, there is no specific vaccine against the causative virus, SARS-CoV-2, nor is there an effective medicine for treating COVID-19, thus raising concerns with respect to the effect of risk factors such as clinical course and pathophysiological parameters on disease severity and outcome in patients with COVID-19. By extracting and analyzing all available published clinical data, we identified several major clinical characteristics associated with increased disease severity and mortality among patients with COVID-19. Specifically, preexisting chronic conditions such as hypertension, cardiovascular disease, chronic kidney disease, and diabetes are strongly associated with an increased risk of developing severe COVID-19; surprisingly, however, we found no correlation between chronic liver disease and increased disease severity. In addition, we found that both acute cardiac injury and acute kidney injury are highly correlated with an increased risk of COVID-19-related mortality. Given the high risk of comorbidity and the high mortality rate associated with tissue damage, organ function should be monitored closely in patients diagnosed with COVID-19, and this approach should be included when establishing new guidelines for managing these high-risk patients. Moreover, additional clinical data are needed in order to determine whether a supportive therapy can help mitigate the development of severe, potentially fatal complications, and further studies are needed to identify the pathophysiology and the mechanism underlying this novel coronavirus-associated infectious disease. Taken together, these findings provide new insights regarding clinical strategies for improving the management and outcome of patients with COVID-19.", "qid": 42, "docid": "mez1k8t0", "rank": 94, "score": 0.7642069458961487}, {"content": "Title: Combating COVID-19 and Building Immune Resilience: A Potential Role for Magnesium Nutrition? Content: BACKGROUND In December 2019, the viral pandemic of respiratory illness caused by COVID-19 began sweeping its way across the globe. Several aspects of this infectious disease mimic metabolic events shown to occur during latent subclinical magnesium deficiency. Hypomagnesemia is a relatively common clinical occurrence that often goes unrecognized since magnesium levels are rarely monitored in the clinical setting. Magnesium is the second most abundant intracellular cation after potassium. It is involved in >600 enzymatic reactions in the body, including those contributing to the exaggerated immune and inflammatory responses exhibited by COVID-19 patients. METHODS A summary of experimental findings and knowledge of the biochemical role magnesium may play in the pathogenesis of COVID-19 is presented in this perspective. The National Academy of Medicine's Standards for Systematic Reviews were independently employed to identify clinical and prospective cohort studies assessing the relationship of magnesium with interleukin-6, a prominent drug target for treating COVID-19. RESULTS Clinical recommendations are given for prevention and treatment of COVID-19. Constant monitoring of ionized magnesium status with subsequent repletion, when appropriate, may be an effective strategy to influence disease contraction and progression. The peer-reviewed literature supports that several aspects of magnesium nutrition warrant clinical consideration. Mechanisms include its \"calcium-channel blocking\" effects that lead to downstream suppression of nuclear factor-K\u03b2, interleukin-6, c-reactive protein, and other related endocrine disrupters; its role in regulating renal potassium loss; and its ability to activate and enhance the functionality of vitamin D, among others. CONCLUSION As the world awaits an effective vaccine, nutrition plays an important and safe role in helping mitigate patient morbidity and mortality. Our group is working with the Academy of Nutrition and Dietetics to collect patient-level data from intensive care units across the United States to better understand nutrition care practices that lead to better outcomes.", "qid": 42, "docid": "l76bqsn0", "rank": 95, "score": 0.7640141248703003}, {"content": "Title: Are patients with inflammatory bowel disease at increased risk for Covid-19 infection? Content: Crohn's disease (CD)] and ulcerative colitis (UC), the main inflammatory bowel diseases (IBD) in human beings, are chronic, immune-inflammatory diseases, whose pathogenesis implicates a complex interaction between environmental factors and genetic susceptibility. These disabling conditions affect millions of individuals and, together with the drugs used to treat them, can put patients at risk of developing complications and other conditions. This is particularly relevant nowadays, as coronavirus disease (Covid-19) has rapidly spread from China to countries where IBD are more prevalent and there is convincing evidence that Covid-19-mediated morbidity and mortality are higher in subjects with comorbidities. The primary objectives of this Viewpoint are to provide a focused overview of the factors and mechanisms by which the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects the cells and to illustrate the link between such determinants and the intestinal inflammation. We also provide clues about the reasons why the overall IBD population might have no increased risk to be infected with SARS-CoV-2 and highlight the potential of cytokine blockers, used to treat IBD patients, to prevent Covid-driven pneumonia.", "qid": 42, "docid": "zwvutq57", "rank": 96, "score": 0.7638106346130371}, {"content": "Title: Combating COVID-19 and Building Immune Resilience: A Potential Role for Magnesium Nutrition? Content: BACKGROUND: In December 2019, the viral pandemic of respiratory illness caused by COVID-19 began sweeping its way across the globe. Several aspects of this infectious disease mimic metabolic events shown to occur during latent subclinical magnesium deficiency. Hypomagnesemia is a relatively common clinical occurrence that often goes unrecognized since magnesium levels are rarely monitored in the clinical setting. Magnesium is the second most abundant intracellular cation after potassium. It is involved in >600 enzymatic reactions in the body, including those contributing to the exaggerated immune and inflammatory responses exhibited by COVID-19 patients. METHODS: A summary of experimental findings and knowledge of the biochemical role magnesium may play in the pathogenesis of COVID-19 is presented in this perspective. The National Academy of Medicine's Standards for Systematic Reviews were independently employed to identify clinical and prospective cohort studies assessing the relationship of magnesium with interleukin-6, a prominent drug target for treating COVID-19. RESULTS: Clinical recommendations are given for prevention and treatment of COVID-19. Constant monitoring of ionized magnesium status with subsequent repletion, when appropriate, may be an effective strategy to influence disease contraction and progression. The peer-reviewed literature supports that several aspects of magnesium nutrition warrant clinical consideration. Mechanisms include its \"calcium-channel blocking\" effects that lead to downstream suppression of nuclear factor-K\u00df, interleukin-6, c-reactive protein, and other related endocrine disrupters; its role in regulating renal potassium loss; and its ability to activate and enhance the functionality of vitamin D, among others. CONCLUSION: As the world awaits an effective vaccine, nutrition plays an important and safe role in helping mitigate patient morbidity and mortality. Our group is working with the Academy of Nutrition and Dietetics to collect patient-level data from intensive care units across the United States to better understand nutrition care practices that lead to better outcomes.", "qid": 42, "docid": "uc8vm79c", "rank": 97, "score": 0.7629905939102173}, {"content": "Title: Let food be the medicine, but not for coronavirus: Nutrition and food science, telling myths from facts Content: The entire globe is facing a dangerous pandemic due to the coronavirus disease (COVID-19). The medical and scientific community is trying to figure out and adopt effective strategies that can lead to (i) preventing virus expansion; (ii) identifying medications for the management of critical care and reducing rates of mortality; and (iii) finally discovering the highly anticipated vaccine. Nutritional interventions have attained considerable scientific evidence in disease prevention and treatment. The main question, \u201cWhat is the role of nutrition and food science in this scenario?\u201d requires urgent answer as many theories suggesting that specific food or dietary supplements can fight coronavirus infection have received extensive coverage in most popular social media platforms. In this editorial, we focus on some frequent statements on the role of nutrition and food science in the battle against COVID-19, distinguishing between myths and facts. We highlight that social distancing and hygiene precautions are the best practices for reducing the risk of COVID-19 transmission. We further underline the importance of nutrition in its wholistic concept, pointing out the risk of unproven dietary options that could lead individuals to weaken effective precautionary measures.", "qid": 42, "docid": "3mcl83nz", "rank": 98, "score": 0.762706995010376}, {"content": "Title: Challenging Issues in the Management of Cardiovascular Risk Factors in Diabetes During the COVID-19 Pandemic: A Review of Current Literature Content: The COVID-19 outbreak was declared a pandemic on March 2020. Many patients with SARS-CoV-2 infection have underlying chronic medical conditions such as diabetes, cardiovascular disease (CVD), and hypertension. Patient-related outcomes are worse if there are associated comorbidities. We do not have enough evidence regarding the most appropriate management of patients with diabetes during COVID-19 infection. Insulin resistance and CVD together increase the inflammatory state of the body, which can contribute to and perhaps mediate the increase of COVID-19 severity. Hence, in addition to management of dysglycemia, other CVD risk factors should be targeted. We explore the possible pathophysiologic links between diabetes and COVID-19 and discuss various options to treat dysglycemia, hypertension, and dyslipidemia in the era of COVID-19.", "qid": 42, "docid": "ntv2g7ne", "rank": 99, "score": 0.7622950077056885}, {"content": "Title: Examining Social Determinants of Health, Stigma, and COVID-19 Disparities Content: There is growing attention to disparities in the incidence, prevalence, and mortality associated with COVID-19 (Coronavirus disease 2019) in racial/ethnic communities. The conditions leading to these disparities may be a function of social determinants of health and stigma linked to the disease. It is important to examine how these factors may be implicated in COVID-19 onset, treatment, and outcomes. A brief overview of these issues allows for a cursory examination of the role of social determinants of health and stigma in COVID-19. Consideration is given to how understanding COVID-19 in the context of social determinants and stigma may be included in interventions to mitigate its transmission within vulnerable populations.", "qid": 42, "docid": "6ptrilhm", "rank": 100, "score": 0.7621885538101196}]}
{"query": "How has the COVID-19 pandemic impacted violence in society, including violent crimes?", "hits": [{"content": "Title: JAACAP's Role in Advancing the Science of Pediatric Mental Health and Promoting the Care of Youth and Families During the COVID-19 Pandemic Content: As we pen these words, the COVID-19 pandemic is having profound impacts on human society. Based on decades of research, we know that the accompanying illness,1 death,2 social isolation,3,4 and malnutrition5 will have deep and lasting impacts on our children and adolescents, their families, and the communities in which they develop. The pandemic is exposing, with terrible clarity, the disparities in human society-racism,6 poverty,7,8 domestic violence,9,10 and child maltreatment and neglect11-and tragically will likely amplify the negative impacts that each has on child development and mental health.", "qid": 43, "docid": "77dtxxd4", "rank": 1, "score": 0.8188481330871582}, {"content": "Title: When Stay-at-Home Orders Leave Victims Unsafe at Home: Exploring the Risk and Consequences of Intimate Partner Violence during the COVID-19 Pandemic Content: The novel coronavirus pandemic (hereafter COVID-19) is likely to have unprecedented impacts on the incidence and impacts of crime and violence globally. This includes impacts to the risk, consequences, and decision-making of women experiencing violence by an intimate partner (hereafter IPV). Most importantly, the COVID-19 pandemic, and its impact on the risk of IPV is likely to differentially impact vulnerable populations, including minority women and those with long histories of victimization and mental health issues. This review paper explores the potential short- and long-term implications of COVID-19 on the risk of IPV, highlighting some of the most recent preliminary data. The economic impact of the COVID-19 pandemic, record levels of male unemployment, added stressors in the home, including the care and home schooling of children, and the social distancing measures required by the epidemiological response, may serve to undermine the decades of progress made in keeping women and children safe at home. Victim police reporting, help-seeking decisions, and social service utilization during the pandemic are likely to be impacted by stay-at-home orders and social distancing requirements. The paper concludes with a discussion of the implications for providing safety planning and self-care for victims and their children.", "qid": 43, "docid": "ekajojon", "rank": 2, "score": 0.8148255348205566}, {"content": "Title: Show me a man or a woman alone and I'll show you a saint: Changes in the frequency of criminal incidents during the COVID-19 pandemic Content: OBJECTIVES: To investigate the effect of the COVID-19 pandemic on the frequency of various crime types (property, violent, and mischief) in Vancouver, Canada. METHODS: Crime data representing residential burglary, commercial burglary, theft of vehicle, theft from vehicle, theft, violence, and mischief are analysed at the city level using interrupted time series techniques. RESULTS: While COVID-19 has not had an impact on all crime types, statistically significant change has been identified in a number of cases. Depending on the crime type, the magnitude and direction of the change in frequency varies. It is argued that (mandated) social restrictions, shifted activity patterns and opportunity structures which are responsible for these findings. CONCLUSIONS: We find support for changes in the frequency of particular crime types during the COVID-19 pandemic. This is important for criminal justice and social service practitioners when operating within an extraordinary event.", "qid": 43, "docid": "ssv1arr1", "rank": 3, "score": 0.8128148317337036}, {"content": "Title: Cybercrime in America amid COVID-19: the Initial Results from a Natural Experiment Content: The COVID-19 pandemic has radically altered life, killing hundreds of thousands of people and leading many countries to issue \u201cstay-at-home\u201d orders to contain the virus\u2019s spread. Based on insights from routine activity theory (Cohen & Felson 1979), it is likely that COVID-19 will influence victimization rates as people alter their routines and spend more time at home and less time in public. Yet, the pandemic may affect victimization differently depending on the type of crime as street crimes appear to be decreasing while domestic crimes may be increasing. We consider a third type of crime: cybercrime. Treating the pandemic as a natural experiment, we investigate how the pandemic has affected rates of cybervictimization. We compare pre-pandemic rates of victimization with post-pandemic rates of victimization using datasets designed to track cybercrime. After considering how the pandemic may alter routines and affect cybervictimization, we find that the pandemic has not radically altered cyberroutines nor changed cybervictimization rates. However, a model using routine activity theory to predict cybervictimization offers clear support for the theory\u2019s efficacy both before and after the pandemic. We conclude by considering plausible explanations for our findings.", "qid": 43, "docid": "gjdza9bh", "rank": 4, "score": 0.8121155500411987}, {"content": "Title: Crime Rates in a Pandemic: the Largest Criminological Experiment in History Content: The COVID-19 pandemic of 2020 has impacted the world in ways not seen in generations. Initial evidence suggests one of the effects is crime rates, which appear to have fallen drastically in many communities around the world. We argue that the principal reason for the change is the government ordered stay-at-home orders, which impacted the routine activities of entire populations. Because these orders impacted countries, states, and communities at different times and in different ways, a naturally occurring, quasi-randomized control experiment has unfolded, allowing the testing of criminological theories as never before. Using new and traditional data sources made available as a result of the pandemic criminologists are equipped to study crime in society as never before. We encourage researchers to study specific types of crime, in a temporal fashion (following the stay-at-home orders), and placed-based. The results will reveal not only why, where, when, and to what extent crime changed, but also how to influence future crime reduction.", "qid": 43, "docid": "lcmkribq", "rank": 5, "score": 0.8117643594741821}, {"content": "Title: Has COVID-19 Changed Crime? Crime Rates in the United States during the Pandemic Content: In response to the COVID-19 pandemic, state-level governments across the United States issued mandatory stay-at-home orders around the end of March 2020. Though intended to stop the spread of the COVID-19 virus, the lockdowns have had sweeping impacts on life in ways which were not originally planned. This study\u2019s purpose is to investigate the extent to which governmental responses to COVID-19 have impacted crime rates in the U.S. Compared to the pre-pandemic year of 2019, crime \u2013 as measured by calls for service to law enforcement \u2013 has decreased markedly. However, there are multiple indications that the crime drop is being driven by decreases in minor offenses which are typically committed in peer groups. At the same time, serious crimes which are generally not committed with co-offenders (namely homicide and intimate partner violence) have either remained constant or increased. As such, the crime drop appears to be hiding a very disturbing trend where homicides remain unchanged and intimate partner batteries are increasing. Since many offenders would presumably be committing less serious crimes in a non-pandemic world, we raise attention to the possibility that mandatory lockdown orders may have taken minor offenders and placed them into situations where there is rampant opportunity for intimate partner violence, serious batteries, and homicides. While crime in the U.S. appears to be down overall, this good news should not blind us to a troubling co-occurring reality \u2013 a reality that paints a dim picture of unintended consequences to public health and criminal justice finances as a result of COVID-19 lockdowns.", "qid": 43, "docid": "daxggfj5", "rank": 6, "score": 0.8100842237472534}, {"content": "Title: When \"Shelter-in-Place\" Isn't Shelter That's Safe: A Rapid Analysis of Domestic Violence Case Differences During the COVID-19 Pandemic and Stay-at-Home Orders Content: Purpose: This study explored the COVID-19 pandemic's impacts on domestic violence (DV) with the following research questions: 1) Did DV occurring during the pandemic differ on certain variables from cases occurring on a typical day the previous year? 2) Did DV occurring after the implementation of shelter-in-place orders differ (on these same variables) from cases occurring prior to shelter-in-place orders? Methods: Two logistic regression models were developed to predict DV case differences before and during the pandemic. DV reports (N=4618) were collected from the Chicago Police Department. Cases from March 2019 and March 2020 were analyzed based on multiple variables. One model was set to predict case differences since the pandemic began, and another model was set to predict case differences during the shelter-in-place period later that month. Results: Both models were significant with multiple significant predictors. During the pandemic period, cases with arrests were 3% less likely to have occurred, and cases at residential locations were 22% more likely to have occurred. During the shelter-in-place period, cases at residential locations were 64% more likely to have occurred, and cases with child victims were 67% less likely to have occurred. Conclusions: This study offers a rapid analysis of DV case differences since the pandemic and shelter-in-place began. Additional variables and data sources could improve model explanatory power. Research, policy, and practice in this area must pivot to focus on protecting children whose access to mandated reporters has decreased and moving victims out of dangerous living situations into safe spaces.", "qid": 43, "docid": "c3xcmkuc", "rank": 7, "score": 0.8092780709266663}, {"content": "Title: Coronavirus and Quarantine: Catalysts of Domestic Violence Content: The pandemic of COVID-19 has resulted in quarantines imposed all around the world; these and other restrictions could produce an increase in domestic violence.", "qid": 43, "docid": "luef3iok", "rank": 8, "score": 0.8088115453720093}, {"content": "Title: Coronavirus and Quarantine: Catalysts of Domestic Violence. Content: The pandemic of COVID-19 has resulted in quarantines imposed all around the world; these and other restrictions could produce an increase in domestic violence.", "qid": 43, "docid": "427mkwsj", "rank": 9, "score": 0.8088115453720093}, {"content": "Title: The pandemic paradox: The consequences of COVID\u201019 on domestic violence Content: COVID-19 (the new strain of coronavirus) has been declared a global pandemic. Measures announced over recent weeks to tackle it have seen people's day-to-day life drastically altered. These changes are essential to beat coronavirus and protect health systems (UK Home Office 2020). However, there are unintended, negative consequences. As the virus continues to spread across the world, it brings with it multiple new stresses, including physical and psychological health risks, isolation and loneliness, the closure of many schools and businesses, economic vulnerability and job losses. Through all of that, children (and their mothers) are particularly vulnerable (End Violence against Children, 2020) to the risk of domestic violence. Domestic violence refers to a range of violations that happen within a domestic space. It is a broad term that encompasses intimate partner violence (IPV), a form of abuse that is perpetrated by a current or ex-partner.", "qid": 43, "docid": "1uwdekl3", "rank": 10, "score": 0.8079324960708618}, {"content": "Title: The Impact of Covid-19 on Community-Based Violence Interventions Content: This paper examines the impact of Covid-19 on community-based violence interventions, especially hospital-based violence interventions and street outreach organizations. Guided by our work in Rochester, New York, we explore how the emergence of covid-19, and the subsequent social restrictions, have hampered the ability of community-based organizations to respond to violence. We also examine ways that community-based organizations can adapt to the challenges associated with Covid-19 and continue providing services to the community.", "qid": 43, "docid": "urlsn7vv", "rank": 11, "score": 0.8040744662284851}, {"content": "Title: It\u2019s F**ing Chaos: COVID-19\u2019s Impact on Juvenile Delinquency and Juvenile Justice Content: An early examination of the impact of COVID-19 on juvenile delinquency and juvenile justice in America, this review provides initial scholarship to rapidly evolving areas of research. Our appraisals of these topics are made after nearly 2 months of national COVID-19 mitigation measures, like social distancing and limited \u201cnon-essential\u201d movement outside the home but also as states are gradually lifting stricter directives and reopening economic sectors. We consider the impact of these pandemic-related changes on twenty-first century youths, their behaviors, and their separate justice system. To forecast the immediate future, we draw from decades of research on juvenile delinquency and the justice system, as well as from reported patterns of reactions and responses to an unprecedented and ongoing situation. As post-pandemic studies on juvenile delinquency and juvenile justice proliferate, we urge careful consideration as to how they might influence societal and the system responses to youths\u2019 delinquency. Additional practical implications are discussed.", "qid": 43, "docid": "judp4703", "rank": 12, "score": 0.8032606840133667}, {"content": "Title: COVID-19: The forgotten priorities of the pandemic Content: The zoonotic virus now named SARS-CoV-2 first infected humans in China, and COVID-19 has rapidly become pandemic. To mitigate its impact on societies, health systems and economies, countries have adopted non-pharmacological preventive practices such as 'spatial' or 'social' distancing, the use of protective masks, and handwashing; these have been widely implemented. However, measures aimed at protecting physical health and healthcare systems have side-effects that might have a big impact on individuals' wellbeing. As the pandemic reaches low- and middle-income countries, weaker health systems, limited resources and the lower socioeconomic status of their populations make halting the pandemic more challenging. In this article, we explore the impact of COVID-19 and its prevention measures on the wellbeing of vulnerable populations. Special attention must be given to homeless, indigenous, migrant and imprisoned populations, as well as people living with disabilities and the elderly. More than just resolute governmental action will be required to overcome the pandemic. Links between science and political actions have to be strengthened. Fighting COVID-19 is a collective endeavour and community action, on a global scale, is of paramount importance.", "qid": 43, "docid": "9v5vfd26", "rank": 13, "score": 0.7963372468948364}, {"content": "Title: COVID-19: The forgotten priorities of the pandemic Content: Abstract The zoonotic virus now named SARS-CoV-2 first infected humans in China, and COVID-19 has rapidly become pandemic. To mitigate its impact on societies, health systems and economies, countries have adopted non-pharmacological preventive practices such as \u2018spatial\u2019 or \u2018social\u2019 distancing, the use of protective masks, and handwashing; these have been widely implemented. However, measures aimed at protecting physical health and healthcare systems have side-effects that might have a big impact on individuals\u2019 wellbeing. As the pandemic reaches low- and middle-income countries, weaker health systems, limited resources and the lower socioeconomic status of their populations make halting the pandemic more challenging. In this article, we explore the impact of COVID-19 and its prevention measures on the wellbeing of vulnerable populations. Special attention must be given to homeless, indigenous, migrant and imprisoned populations, as well as people living with disabilities and the elderly. More than just resolute governmental action will be required to overcome the pandemic. Links between science and political actions have to be strengthened. Fighting COVID-19 is a collective endeavour and community action, on a global scale, is of paramount importance.", "qid": 43, "docid": "5cm6122n", "rank": 14, "score": 0.793930172920227}, {"content": "Title: The impact of the Covid-19 pandemic in the precipitation of intimate partner violence Content: Intimate Partner Violence (IPV) is a global pandemic and many have been victims of it long before Covid-19. International organizations have documented an increase in IPV reports during the current pandemic, raising awareness of the potential causes for such an increase. Reflecting on risk factors associated with IPV, and the underlying need of the perpetrators to exert control over the victims, it becomes increasingly important to understand how the current policies of social distancing, self-isolation, and lockdown can precipitate episodes of IPV. Furthermore, access to specialized services and health care can be compromised, and health care professionals face new challenges and demands imposed by the pandemic while managing IPV cases. This article begins by examining the main risk factors more commonly associated with IPV in the literature. It proceeds by reflecting on how these risk factors may be exacerbated during the Covid-19 pandemic, which can explain the increased number of reports. Finally, it emphasizes the new challenges faced by health care professionals, while assisting IPV victims during the pandemic and provides possible recommendations on actions to implement during and beyond the Covid-19 pandemic to prevent such cases.", "qid": 43, "docid": "0einpgeu", "rank": 15, "score": 0.7926731109619141}, {"content": "Title: Family violence and COVID\u201019: Increased vulnerability and reduced options for support Content: Family violence refers to threatening or other violent behaviour within families that may be physical, sexual, psychological, or economic, and can include child abuse and intimate partner violence (Peterman et al. 2020, van Gelder et al. 2020). Family violence during pandemics is associated with a range of factors including economic stress, disaster-related instability, increased exposure to exploitative relationships, and reduced options for support (Peterman et al. 2020). Due to the social isolation measures implemented across the globe to help reduce the spread of COVID-19, people living in volatile situations of family violence are restricted to their homes. Social isolation exacerbates personal and collective vulnerabilities while limiting accessible and familiar support options (van Gelder et al. 2020). In many countries, including Australia, we have already seen an increase in demand for domestic violence services and reports of increased risk for children not attending schools (Duncan, 2020); a pattern similar to previous episodes of social isolation associated with epidemics and pandemics (Boddy, Young & O'Leary 2020).", "qid": 43, "docid": "4jjuwc9r", "rank": 16, "score": 0.7907257080078125}, {"content": "Title: Impact of COVID-19 pandemic on socioeconomic and mental health aspects in Nepal. Content: BACKGROUND Public health concern is increasing with recent rise in the number of COVID-19 cases in Nepal. To curb this pandemic, Nepal is facing some forms of lockdown, encouraging people to implement social distancing so as to reduce interactions between people which could eventually reduce the possibilities of new infection; however, it has affected the overall physical, mental, social and spiritual health of the people. METHODS Published articles related to psychosocial effects due to COVID-19 and other outbreaks were searched and reviewed. CONCLUSION While many countries are supporting their citizens with sophisticated health safety-nets and various relief funds, some developing countries have unique challenges with vulnerable populations and limited resources to respond to the pandemic. This review presents the consequences of pandemic and lockdown on socioeconomic, mental health and other aspects in Nepalese society.", "qid": 43, "docid": "5ut7d32k", "rank": 17, "score": 0.7895029783248901}, {"content": "Title: Impact of COVID-19 pandemic on socioeconomic and mental health aspects in Nepal Content: BACKGROUND: Public health concern is increasing with recent rise in the number of COVID-19 cases in Nepal. To curb this pandemic, Nepal is facing some forms of lockdown, encouraging people to implement social distancing so as to reduce interactions between people which could eventually reduce the possibilities of new infection; however, it has affected the overall physical, mental, social and spiritual health of the people. METHODS: Published articles related to psychosocial effects due to COVID-19 and other outbreaks were searched and reviewed. CONCLUSION: While many countries are supporting their citizens with sophisticated health safety-nets and various relief funds, some developing countries have unique challenges with vulnerable populations and limited resources to respond to the pandemic. This review presents the consequences of pandemic and lockdown on socioeconomic, mental health and other aspects in Nepalese society.", "qid": 43, "docid": "ly5x1thg", "rank": 18, "score": 0.7890089750289917}, {"content": "Title: Caring for patients with posttraumatic stress and substance use disorders during the COVID-19 pandemic Content: Although COVID-19 is a physical illness, it has had large impacts on mental health. For many individuals, social distancing has led to social isolation; individuals with posttraumatic stress disorder and substance use disorders are at a particular risk for negative outcomes due to the global pandemic. Here, we discuss the impacts we have noticed and procedures we have implemented to care for this population during the pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "pfrnlvda", "rank": 19, "score": 0.7885130643844604}, {"content": "Title: Caring for patients with posttraumatic stress and substance use disorders during the COVID-19 pandemic. Content: Although COVID-19 is a physical illness, it has had large impacts on mental health. For many individuals, social distancing has led to social isolation; individuals with posttraumatic stress disorder and substance use disorders are at a particular risk for negative outcomes due to the global pandemic. Here, we discuss the impacts we have noticed and procedures we have implemented to care for this population during the pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "7uodxlrz", "rank": 20, "score": 0.7885130643844604}, {"content": "Title: Pandemic Pulse: Unraveling and Modeling Social Signals during the COVID-19 Pandemic Content: We present and begin to explore a collection of social data that represents part of the COVID-19 pandemic's effects on the United States. This data is collected from a range of sources and includes longitudinal trends of news topics, social distancing behaviors, community mobility changes, web searches, and more. This multimodal effort enables new opportunities for analyzing the impacts such a pandemic has on the pulse of society. Our preliminary results show that the number of COVID-19-related news articles published immediately after the World Health Organization declared the pandemic on March 11, and that since that time have steadily decreased---regardless of changes in the number of cases or public policies. Additionally, we found that politically moderate and scientifically-grounded sources have, relative to baselines measured before the beginning of the pandemic, published a lower proportion of COVID-19 news than more politically extreme sources. We suggest that further analysis of these multimodal signals could produce meaningful social insights and present an interactive dashboard to aid further exploration.", "qid": 43, "docid": "71qh6yjr", "rank": 21, "score": 0.7876702547073364}, {"content": "Title: Mental Health and Psychosocial Challenges in the COVID-19 Pandemic: Food for Thought for Cardiovascular Health Care Professionals Content: Background The coronavirus disease (COVID-19) pandemic has produced substantial health challenges from the perspective of both its direct health complications and the disruption to delivery of standard care for individuals with a range of acute and chronic health issues. In parallel, the widespread application of social isolation initiatives in most countries raises the potential for significant mental health consequences and psychosocial impacts. This has major implications for cardiovascular health care professionals and the management of their patients. Challenges The COVID-19 pandemic and associated physical isolation practices are likely to result in a range of mental health and psychosocial challenges. In addition to an increasing incidence of anxiety, depression, suicidal ideation and post-traumatic stress, the pandemic may also witness an increase in substance abuse, domestic violence and relationship discord. The consequences of these complications will be further magnified, when considering their potential effect on cardiovascular disease and its management. Purpose This statement aims to summarise some of the potential mental health and psychosocial challenges that may arise in the setting of the COVID-19 pandemic.", "qid": 43, "docid": "pf1f9fhc", "rank": 22, "score": 0.7871127128601074}, {"content": "Title: Crime, Justice & the COVID-19 Pandemic: Toward a National Research Agenda Content: The novel corona virus COVID-19 has become a worldwide public health pandemic that has induced anomic conditions impacting daily routines. COVID-19 response measures specifically alter regular schedules and both restrict and expand opportunities for various types of crime while presenting unprecedented challenges for the criminal justice system. For criminologists and criminal justice scientists, the virus also presents natural experiment conditions allowing for real-world theory tests and observation of the relative effectiveness of practice and policy options under weighty conditions. Toward synthesizing scientific discourse and forthcoming empirical work, we suggest the benefits of a COVID-19 crime and justice research program and offer some anchoring concepts. Contagion, containment measures (social distancing, facemasks, shelter-in-place, economic shutdown, virtual work and schooling, banned group gatherings), and social ordinance compliance (voluntary or enforced) posture a conceptual framework from which to align research on crime, justice, and victimization during the virus. After observing crime trends and justice system challenges, we suggest how the pandemic presents opportunities for review of various criminal justice, especially incarceration, policies. System change is a recurring theme across this special issue of the American Journal of Criminal Justice that features twenty additional contributions from a wide range of authoritative crime and justice scholars. These articles on traditional crime during the virus, virus specific hate crime and domestic violence, and the challenges posed by COVID-19 to law enforcement, the courts, and corrections will hopefully provide initial commentary toward deeper inquiry.", "qid": 43, "docid": "7eksp1sj", "rank": 23, "score": 0.786744236946106}, {"content": "Title: Responding to the accumulation of adverse childhood experiences in the wake of the COVID-19 pandemic: implications for practice Content: In early 2020, the world as we knew it began to change dramatically and rapidly with the COVID-19 outbreak. Social distancing restrictions and lockdown measures have been the most effective course of action and an inarguably imperative approach at this time. However, in trying to keep the global population safe, social distancing measures unwittingly placed children already experiencing maltreatment and disadvantage in harm\u2019s way. This paper will consider the evidence base which attests to the importance of considering the accumulation of adversity when seeking to understand risk and impact of child maltreatment and disadvantage. Given the unique and unprecedented circumstances which have accompanied the COVID-19 outbreak, and the dearth of research pertaining to the impact of pandemics on child welfare, the paper draws on an emerging body of literature about the effect of natural disasters, conflict and significant global events on child maltreatment. The paper synthesises the research to date in order to call attention to the cumulative impact of the COVID-19 pandemic on children already experiencing abuse and neglect. The paper concludes with an outline of the implications for practice in the helping professions.", "qid": 43, "docid": "yv7c5xlb", "rank": 24, "score": 0.7864750027656555}, {"content": "Title: Impact of social distancing during COVID-19 pandemic on crime in Los Angeles and Indianapolis Content: Governments have implemented social distancing measures to address the ongoing COVID-19 pandemic. The measures include instructions that individuals maintain social distance when in public, school closures, limitations on gatherings and business operations, and instructions to remain at home. Social distancing may have an impact on the volume and distribution of crime. Crimes such as residential burglary may decrease as a byproduct of increased guardianship over personal space and property. Crimes such as domestic violence may increase because of extended periods of contact between potential offenders and victims. Understanding the impact of social distancing on crime is critical for ensuring the safety of police and government capacity to deal with the evolving crisis. Understanding how social distancing policies impact crime may also provide insights into whether people are complying with public health measures. Examination of the most recently available data from both Los Angeles, CA, and Indianapolis, IN, shows that social distancing has had a statistically significant impact on a few specific crime types. However, the overall effect is notably less than might be expected given the scale of the disruption to social and economic life.", "qid": 43, "docid": "po2c65nb", "rank": 25, "score": 0.7847837805747986}, {"content": "Title: Twin public health emergencies: Covid-19 and domestic violence Content: While a virus is hardly \"choosy\" in finding a host, the consequences of government responses to a pandemic, such as to Covid-19, have deep implications for those already-marginalised, such as women and girls. In the absence of a systematic database examining the details of the impact, this comment synthesises existing opinions, reviews and the limited available data to show how, not only the outbreak, but particularly our response to it, are increasing the incidence of domestic violence (DV) across the globe, including in India. Despite tackling a much higher Covid caseload and mortality rate than India has, countries such as France and Spain have prioritised responding to DV in their respective societies, working out contingent mitigation mechanisms. Admittedly, low resource settings (LRS) such as India, have a bevy of additional infrastructure and budgetary challenges; but would that imply we do not respond to DV? This comment argues that in reality we have two public health emergencies to confront, the Covid-19 and domestic violence. It builds on the author's observations in the course of working on DV in an LRS context in India, and concludes with a set of recommendations on better responding to DV during Covid/lockdown times. Keywords Domestic violence, gender-based violence, Covid-19, lockdown, pandemic, low resource settings.", "qid": 43, "docid": "clt4l6wz", "rank": 26, "score": 0.7843371033668518}, {"content": "Title: Twin public health emergencies: Covid-19 and domestic violence. Content: While a virus is hardly \"choosy\" in finding a host, the consequences of government responses to a pandemic, such as to Covid-19, have deep implications for those already-marginalised, such as women and girls. In the absence of a systematic database examining the details of the impact, this comment synthesises existing opinions, reviews and the limited available data to show how, not only the outbreak, but particularly our response to it, are increasing the incidence of domestic violence (DV) across the globe, including in India. Despite tackling a much higher Covid caseload and mortality rate than India has, countries such as France and Spain have prioritised responding to DV in their respective societies, working out contingent mitigation mechanisms. Admittedly, low resource settings (LRS) such as India, have a bevy of additional infrastructure and budgetary challenges; but would that imply we do not respond to DV? This comment argues that in reality we have two public health emergencies to confront, the Covid-19 and domestic violence. It builds on the author's observations in the course of working on DV in an LRS context in India, and concludes with a set of recommendations on better responding to DV during Covid/lockdown times. Keywords Domestic violence, gender-based violence, Covid-19, lockdown, pandemic, low resource settings.", "qid": 43, "docid": "1h5a4bit", "rank": 27, "score": 0.7843371033668518}, {"content": "Title: The impact of the Covid-19 pandemic on domestic violence: The dark side of home isolation during quarantine Content: Domestic violence is a global public health problem. It takes many different forms and leads to significant physical and psychological consequences for the victim and the whole family. Situations that may prompt episodes of violence in the family include stress, emotional disappointment, economic factors, bad and cramped housing, and alcohol or drug abuse. How does the government's forced home isolation to contain Covid-19 infections impact on this type of abuse? Numerous articles have reported a decrease in reports of domestic violence since quarantine began but how reliable is these data? Is it a potential wake-up call for public institutions? We discuss the risks associated with quarantine measures during the pandemic and suggest the measures to prevent and improve the reporting of abuse cases.", "qid": 43, "docid": "onxosato", "rank": 28, "score": 0.7843104004859924}, {"content": "Title: The impact of the Covid-19 pandemic on domestic violence: The dark side of home isolation during quarantine. Content: Domestic violence is a global public health problem. It takes many different forms and leads to significant physical and psychological consequences for the victim and the whole family. Situations that may prompt episodes of violence in the family include stress, emotional disappointment, economic factors, bad and cramped housing, and alcohol or drug abuse. How does the government's forced home isolation to contain Covid-19 infections impact on this type of abuse? Numerous articles have reported a decrease in reports of domestic violence since quarantine began but how reliable is these data? Is it a potential wake-up call for public institutions? We discuss the risks associated with quarantine measures during the pandemic and suggest the measures to prevent and improve the reporting of abuse cases.", "qid": 43, "docid": "miem1poh", "rank": 29, "score": 0.7843104004859924}, {"content": "Title: Gambling during the COVID-19 crisis - A cause for concern? Content: : The COVID-19 pandemic has the potential to worsen mental health problems in the general population, including increasing engagement in addictive behaviors. Here, we describe observations suggesting that the current crisis and its sequelae may worsen problem gambling. The current pandemic may impact financial and psychological well-being due to social isolation during spatial distancing, and these stressors in conjunction with substantial changes in gambling markets (land-based, online) during the pandemic may significantly influence gambling behaviors. This situation calls for rapid research initiatives in this area and preventive and regulatory measures by multiple stakeholders.", "qid": 43, "docid": "3mzvv6l3", "rank": 30, "score": 0.7839769124984741}, {"content": "Title: Psychiatric Symptoms Related to the COVID-19 Pandemic Content: The COVID-19 pandemic and the consequential societal changes are likely to have major health consequences way beyond those caused by the virus infection. One of the medical fields that may experience significant consequences of the pandemic is that of psychiatry. Importantly, individuals who already live with mental disorders may be particularly vulnerable to the psychological stress associated with the pandemic. However, data on how the COVID-19 pandemic affects this group of people is largely absent from the literature. Here, we report data from a quality development project conducted at the psychiatric services of the Central Denmark Region (CDR), which has a catchment area of approximately 1.3 million people covered by five psychiatric hospitals providing inpatient and outpatient treatment of all types of mental disorders. Based on a manual screening of all clinical notes from the period from February 1st to March 23rd 2020 that contained at least one of the following words: corona, COVID, virus, epidemic, pandemic, and contaminate/contamination (including compound words), we found 1357 notes from 918 adult patients that described pandemic-related psychopathology (symptoms that appeared to be caused/deteriorated by the pandemic and/or its societal consequences). To our knowledge, this is the first investigation of COVID-19 pandemic-related psychopathology from a large psychiatric treatment setting. The results clearly suggest that this phenomenon exists among individuals with mental illness. However, as the data from this investigation stems from standard clinical practice where the patients were not systematically assessed for pandemic-related psychopathology, we cannot speak to its overall prevalence. Nevertheless, we believe that our findings underline the necessity of taking urgent action to mitigate the negative effects of the COVID-19 pandemic on patients with mental disorders. A low-cost intervention would be to simply discuss the ongoing pandemic and its societal consequences with patients seeking care in psychiatric settings - as this may lead to relief of pandemic-related symptoms via general comforting, and clarification of misunderstandings/false beliefs regarding the pandemic.", "qid": 43, "docid": "gy90nvir", "rank": 31, "score": 0.782018780708313}, {"content": "Title: Gambling during the COVID-19 crisis - A cause for concern? Content: The COVID-19 pandemic has the potential to worsen mental health problems in the general population, including increasing engagement in addictive behaviors. Here, we describe observations suggesting that the current crisis and its sequelae may worsen problem gambling. The current pandemic may impact financial and psychological well-being due to social isolation during spatial distancing, and these stressors in conjunction with substantial changes in gambling markets (land-based, online) during the pandemic may significantly influence gambling behaviors. This situation calls for rapid research initiatives in this area and preventive and regulatory measures by multiple stakeholders.", "qid": 43, "docid": "rvcrya5i", "rank": 32, "score": 0.7806413173675537}, {"content": "Title: Covid-19 emergency in prison: Current management and forensic perspectives Content: The Covid-19 pandemic is currently a major worldwide public health problem. Contagion within prisons and in other custodial settings will need to be addressed promptly, but the management of preventive measures will be difficult due to overcrowding and inmates and officers' close physical contact. There may also be less access to care than in community settings. Accordingly, prisons are particularly vulnerable to outbreaks of infection, and in addition to the likely greater risks of contagion attention must be paid to the psychological problems that the pandemic can have on the prison population. Riots and episodes of violence have already taken place in various prisons. With the inevitable restrictions on social contact and family meetings, prisoners who already are at increased risk of mental illness and suicide are more susceptible to adverse psychological repercussions. From a forensic point of view, therefore, we stress the need for the development of a strong support network by mental health workers for the prison population.", "qid": 43, "docid": "nvmp6cql", "rank": 33, "score": 0.7806337475776672}, {"content": "Title: Covid-19 emergency in prison: Current management and forensic perspectives. Content: The Covid-19 pandemic is currently a major worldwide public health problem. Contagion within prisons and in other custodial settings will need to be addressed promptly, but the management of preventive measures will be difficult due to overcrowding and inmates and officers' close physical contact. There may also be less access to care than in community settings. Accordingly, prisons are particularly vulnerable to outbreaks of infection, and in addition to the likely greater risks of contagion attention must be paid to the psychological problems that the pandemic can have on the prison population. Riots and episodes of violence have already taken place in various prisons. With the inevitable restrictions on social contact and family meetings, prisoners who already are at increased risk of mental illness and suicide are more susceptible to adverse psychological repercussions. From a forensic point of view, therefore, we stress the need for the development of a strong support network by mental health workers for the prison population.", "qid": 43, "docid": "ymzigce5", "rank": 34, "score": 0.7806337475776672}, {"content": "Title: Cyber Security in the Age of COVID-19: A Timeline and Analysis of Cyber-Crime and Cyber-Attacks during the Pandemic Content: The COVID-19 pandemic was a remarkable unprecedented event which altered the lives of billions of citizens globally resulting in what became commonly referred to as the new-normal in terms of societal norms and the way we live and work. Aside from the extraordinary impact on society and business as a whole, the pandemic generated a set of unique cyber-crime related circumstances which also affected society and business. The increased anxiety caused by the pandemic heightened the likelihood of cyber-attacks succeeding corresponding with an increase in the number and range of cyber-attacks. This paper analyses the COVID-19 pandemic from a cyber-crime perspective and highlights the range of cyber-attacks experienced globally during the pandemic. Cyber-attacks are analysed and considered within the context of key global events to reveal the modus-operandi of cyber-attack campaigns. The analysis shows how following what appeared to be large gaps between the initial outbreak of the pandemic in China and the first COVID-19 related cyber-attack, attacks steadily became much more prevalent to the point that on some days, 3 or 4 unique cyber-attacks were being reported. The analysis proceeds to utilise the UK as a case study to demonstrate how cyber-criminals leveraged key events and governmental announcements to carefully craft and design cyber-crime campaigns.", "qid": 43, "docid": "j0qperwz", "rank": 35, "score": 0.7804731130599976}, {"content": "Title: Impact of the COVID-19 pandemic on the sexual behavior of the population. The vision of the east and the west Content: The COVID-19 pandemic has radically changed the way of life around the World. The state of alarm has forced the population to stay at home, radically changing both interpersonal and partner relationships; work at home, social distancing, the continued presence of children at home, fear of infection and not being able to physically meet with others have changed most people's sexual habits. We conducted a review by exploring the impact of the COVID-19 pandemic on sexual behavior in the population from three different countries: Iran, Italy and Spain from each country's perspective. The impact of the coronavirus will be very important in the sexual life of the people and we will attend in the next months or years, to some changes in the relationships at all the levels. The pandemic will negatively affect sexual behaviors due to multiple contact restrictions. In the future, we will be able to assess these effects in more detail.", "qid": 43, "docid": "1cg6wnpj", "rank": 36, "score": 0.7800735235214233}, {"content": "Title: Impact of the COVID-19 pandemic on the sexual behavior of the population. The vision of the east and the west. Content: The COVID-19 pandemic has radically changed the way of life around the World. The state of alarm has forced the population to stay at home, radically changing both interpersonal and partner relationships; work at home, social distancing, the continued presence of children at home, fear of infection and not being able to physically meet with others have changed most people's sexual habits. We conducted a review by exploring the impact of the COVID-19 pandemic on sexual behavior in the population from three different countries: Iran, Italy and Spain from each country's perspective. The impact of the coronavirus will be very important in the sexual life of the people and we will attend in the next months or years, to some changes in the relationships at all the levels. The pandemic will negatively affect sexual behaviors due to multiple contact restrictions. In the future, we will be able to assess these effects in more detail.", "qid": 43, "docid": "6lan923i", "rank": 37, "score": 0.7800735235214233}, {"content": "Title: Initial evidence on the relationship between the coronavirus pandemic and crime in the United States Content: The COVID-19 pandemic led to substantial changes in the daily activities of millions of Americans, with many businesses and schools closed, public events cancelled and states introducing stay-at-home orders. This article used police-recorded open crime data to understand how the frequency of common types of crime changed in 16 large cities across the United States in the early months of 2020. Seasonal auto-regressive integrated moving average (SARIMA) models of crime in previous years were used to forecast the expected frequency of crime in 2020 in the absence of the pandemic. The forecasts from these models were then compared to the actual frequency of crime during the early months of the pandemic. There were no significant changes in the frequency of serious assaults in public or (contrary to the concerns of policy makers) any change to the frequency of serious assaults in residences. In some cities, there were reductions in residential burglary but little change in non-residential burglary. Thefts of motor vehicles decreased in some cities while there were diverging patterns of thefts from motor vehicles. These results are used to make suggestions for future research into the relationships between the coronavirus pandemic and different crimes.", "qid": 43, "docid": "tkqufxv8", "rank": 38, "score": 0.7797912359237671}, {"content": "Title: Living with PTSD amid a global pandemic Content: The COVID-19 pandemic has demonstrated itself to be a considerable stressor, especially for those individuals coping with a preexisting mental health disorder. This article contains clinical observations and reflections from two practicing psychologists regarding the impact of the COVID-19 pandemic and associated social conditions on clients with posttraumatic stress disorder. Observations include changes in trauma-related symptom manifestations and therapeutic process issues, particularly in response to social isolation. The authors encourage specific therapeutic considerations and offer suggestions for adapting treatment with regard to these early observations. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "247r7fd3", "rank": 39, "score": 0.7796711921691895}, {"content": "Title: Living with PTSD amid a global pandemic. Content: The COVID-19 pandemic has demonstrated itself to be a considerable stressor, especially for those individuals coping with a preexisting mental health disorder. This article contains clinical observations and reflections from two practicing psychologists regarding the impact of the COVID-19 pandemic and associated social conditions on clients with posttraumatic stress disorder. Observations include changes in trauma-related symptom manifestations and therapeutic process issues, particularly in response to social isolation. The authors encourage specific therapeutic considerations and offer suggestions for adapting treatment with regard to these early observations. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "zn0m48q4", "rank": 40, "score": 0.7796711921691895}, {"content": "Title: Domestic violence against women and the COVID-19 pandemic: What is the role of psychiatry? Content: A heightened risk of domestic violence has been associated with infection-reducing measures undertaken by governments during the COVID-19 pandemic. Psychiatric services can play a key role in addressing this issue by (a) addressing certain risk factors for perpetration of domestic violence through, for example, assertive identification and management of substance misuse; (b) providing support, advocacy and treatment services for victims of domestic violence; and (c) multi-agency working to strengthen medical and social responses to domestic violence. At a time like this, it is important that multi-disciplinary mental health services are strengthened, rather than depleted, in order to address the pressing issues at hand.", "qid": 43, "docid": "slfyv0cu", "rank": 41, "score": 0.7793711423873901}, {"content": "Title: Mental Health and Psychosocial Challenges in the COVID-19 Pandemic: Food for Thought for Cardiovascular Health Care Professionals Content: BACKGROUND: The coronavirus disease (COVID-19) pandemic has produced substantial health challenges from the perspective of both its direct health complications and the disruption to delivery of standard care for individuals with a range of acute and chronic health issues. In parallel, the widespread application of social isolation initiatives in most countries raises the potential for significant mental health consequences and psychosocial impacts. This has major implications for cardiovascular health care professionals and the management of their patients. CHALLENGES: The COVID-19 pandemic and associated physical isolation practices are likely to result in a range of mental health and psychosocial challenges. In addition to an increasing incidence of anxiety, depression, suicidal ideation and post-traumatic stress, the pandemic may also witness an increase in substance abuse, domestic violence and relationship discord. The consequences of these complications will be further magnified, when considering their potential effect on cardiovascular disease and its management. PURPOSE: This commentary aims to summarise some of the potential mental health and psychosocial challenges that may arise in the setting of the COVID-19 pandemic.", "qid": 43, "docid": "d7vo3l8e", "rank": 42, "score": 0.7791671752929688}, {"content": "Title: Effects of COVID-19 on Business and Research Content: Abstract The COVID-19 outbreak is a sharp reminder that pandemics, like other rarely occurring catastrophes, have happened in the past and will continue to happen in the future. Even if we cannot prevent dangerous viruses from emerging, we should prepare to dampen their effects on society. The current outbreak has had severe economic consequences across the globe, and it does not look like any country will be unaffected. This not only has consequences for the economy; all of society is affected, which has led to dramatic changes in how businesses act and consumers behave. This special issue is a global effort to address some of the pandemic-related issues affecting society. In total, there are 12 papers that cover different industry sectors (e.g., tourism, retail, higher education), changes in consumer behavior and businesses, ethical issues, and aspects related to employees and leadership.", "qid": 43, "docid": "7ofgekoj", "rank": 43, "score": 0.778943657875061}, {"content": "Title: COVID-19 and mental health: A review of the existing literature Content: The COVID-19 pandemic is a major health crisis affecting several nations, with over 720,000 cases and 33,000 confirmed deaths reported to date. Such widespread outbreaks are associated with adverse mental health consequences. Keeping this in mind, existing literature on the COVID-19 outbreak pertinent to mental health was retrieved via a literature search of the PubMed database. Published articles were classified according to their overall themes and summarized. Preliminary evidence suggests that symptoms of anxiety and depression (16-28%) and self-reported stress (8%) are common psychological reactions to the COVID-19 pandemic, and may be associated with disturbed sleep. A number of individual and structural variables moderate this risk. In planning services for such populations, both the needs of the concerned people and the necessary preventive guidelines must be taken into account. The available literature has emerged from only a few of the affected countries, and may not reflect the experience of persons living in other parts of the world. In conclusion, subsyndromal mental health problems are a common response to the COVID-19 pandemic. There is a need for more representative research from other affected countries, particularly in vulnerable populations.", "qid": 43, "docid": "6gtgohci", "rank": 44, "score": 0.7786953449249268}, {"content": "Title: Home is not always a haven: The domestic violence crisis amid the COVID-19 pandemic Content: The novel coronavirus (SARS-CoV-2) and the associated disease it causes, COVID-19, have caused unprecedented social disruption. Due to sweeping stay-at-home orders across the United States and internationally, many victims and survivors of domestic violence (DV), now forced to be isolated with their abusers, run the risk of new or escalating violence. Numerous advocates, organizations, and service centers anticipated this: Upticks in domestic violence were reported in many regions soon after stay-at-home directives were announced. In this commentary, we delineate some of the recent events leading up to the reported spike in DV; review literature on previously documented disaster-related DV surges; and discuss some of the unique challenges, dilemmas, and risks victims and survivors face during this pandemic. We conclude with recommendations to allocate resources to DV front-liners and utilize existing DV guidelines for disaster preparedness, response, and recovery. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "ypzpui37", "rank": 45, "score": 0.7778551578521729}, {"content": "Title: Home is not always a haven: The domestic violence crisis amid the COVID-19 pandemic. Content: The novel coronavirus (SARS-CoV-2) and the associated disease it causes, COVID-19, have caused unprecedented social disruption. Due to sweeping stay-at-home orders across the United States and internationally, many victims and survivors of domestic violence (DV), now forced to be isolated with their abusers, run the risk of new or escalating violence. Numerous advocates, organizations, and service centers anticipated this: Upticks in domestic violence were reported in many regions soon after stay-at-home directives were announced. In this commentary, we delineate some of the recent events leading up to the reported spike in DV; review literature on previously documented disaster-related DV surges; and discuss some of the unique challenges, dilemmas, and risks victims and survivors face during this pandemic. We conclude with recommendations to allocate resources to DV front-liners and utilize existing DV guidelines for disaster preparedness, response, and recovery. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "54mxjzfc", "rank": 46, "score": 0.7778551578521729}, {"content": "Title: COVID-19 and mental health: A review of the existing literature Content: Abstract The COVID-19 pandemic is a major health crisis affecting several nations, with over 720,000 cases and 33,000 confirmed deaths reported to date. Such widespread outbreaks are associated with adverse mental health consequences. Keeping this in mind, existing literature on the COVID-19 outbreak pertinent to mental health was retrieved via a literature search of the PubMed database. Published articles were classified according to their overall themes and summarized. Preliminary evidence suggests that symptoms of anxiety and depression (16\u201328%) and self-reported stress (8%) are common psychological reactions to the COVID-19 pandemic, and may be associated with disturbed sleep. A number of individual and structural variables moderate this risk. In planning services for such populations, both the needs of the concerned people and the necessary preventive guidelines must be taken into account. The available literature has emerged from only a few of the affected countries, and may not reflect the experience of persons living in other parts of the world. In conclusion, subsyndromal mental health problems are a common response to the COVID-19 pandemic. There is a need for more representative research from other affected countries, particularly in vulnerable populations.", "qid": 43, "docid": "o72unm3q", "rank": 47, "score": 0.7778247594833374}, {"content": "Title: Crime in Italy at the time of the pandemic. Content: BACKGROUND The beginning of 2020 has been marked by a historic event of worldwide importance: the Coronavirus pandemic. This emergency has resulted in severe global problems affecting areas such as healthcare and the social and economic fields. What about crime? PURPOSE OF THE WORK The purpose of this work is to reflect about Italy and its crime rate at the time of Coronavirus. METHODS Some crimes will be analysed (the \"conventional\" ones only, ruling out health-related offences) in the light of data resulting from Ministries and Europol reports, as well as from newspapers and news. RESULTS AND CONCLUSIONS The outcome will be explained, and some criminological remarks will be added.", "qid": 43, "docid": "0jv5mnnl", "rank": 48, "score": 0.7777626514434814}, {"content": "Title: Utilization of Teleconsultation: Mitigation in Handling Mental Disorders in the COVID-19 Era Content: The COVID-19 pandemic has caused many undesirable effects, including death. The COVID-19 outbreak occurred suddenly, and many countries were ill prepared to face it. Community behaviour has been altered due to the pandemic. Uncertainty surrounding the disease triggered panic buying; public panic caused additional worry about limited food supplies, and thus demand increased. World economies have also felt the impacts of the COVID-19 outbreak. Owing to the measures put in place to address the spread of COVID-19, many service providers and industries were closed, resulting in financial losses, and the risk of unemployment was elevated, which inevitably increased negative emotions in individuals. A psychosocial consequence of the COVID-19 pandemic is worldwide fear. Because psychological defence is a supporting factor for the recovery of COVID-19 patients, it is important to encourage prevention of mental stress. Psychotherapy is able to provide counselling services to the community through teleconsultation. Strengthening psychological defences can help countries fight against this disease.", "qid": 43, "docid": "7vowrme2", "rank": 49, "score": 0.777319073677063}, {"content": "Title: Geographies of Covid-19: how space and virus shape each other Content: This paper contributes to a geographically-informed preliminary assessment of the diverse and uneven immediate impacts of the Covid-19 pandemic, and outlines an agenda for geographical studies of its longer term effects. Intrigued by the apparent tendency of an inverse relationship between a country\u2019s health security capacities and Covid-19 mortalities, the paper explores the significance of a range of geographically situated contextual factors in the realms of the economy, governance and culture as mediators of the public health impacts of Covid-19, and questions how these realms may also be reshaped by this viral pandemic. The paper concludes with reflections on the path dependency and state centrality of pandemic response, and the potential post-pandemic reconfiguration of state-market-society relationships.", "qid": 43, "docid": "7hqai3wj", "rank": 50, "score": 0.777113676071167}, {"content": "Title: Adolescent psychiatric disorders during the COVID-19 pandemic and lockdown Content: The aim of this paper was to review the literature on adolescent psychiatric disorders related to the COVID-19 pandemic and lockdown. Stressful life events, extended home confinement, brutal grief, intrafamilial violence, overuse of the Internet and social media are factors that could influence the mental health of adolescents during this period. The COVID-19 pandemic could result in increased psychiatric disorders such as Post-Traumatic Stress, Depressive, and Anxiety Disorders, as well as grief-related symptoms. Adolescents with psychiatric disorders are at risk of a break or change in their care and management; they may experience increased symptoms. The COVID-19 pandemic and lockdown may have a negative impact on the mental health of adolescents, although there is still no data on the long term impact of this crisis. Adolescents' individual, familial, and social vulnerability, as well as individual and familial coping abilities, are factors related to adolescent mental health in times of crisis. Adolescents are often vulnerable and require careful consideration by caregivers and healthcare system adaptations to allow for mental health support despite the lockdown. Research on adolescent psychiatric disorders in times of pandemics is necessary, as such a global situation could be prolonged or repeated.", "qid": 43, "docid": "2uaylezt", "rank": 51, "score": 0.7767313718795776}, {"content": "Title: Adolescent psychiatric disorders during the COVID-19 pandemic and lockdown Content: The aim of this paper was to review the literature on adolescent psychiatric disorders related to the COVID-19 pandemic and lockdown. Stressful life events, extended home confinement, brutal grief, intrafamilial violence, overuse of the Internet and social media are factors that could influence the mental health of adolescents during this period. The COVID-19 pandemic could result in increased psychiatric disorders such as Post-Traumatic Stress, Depressive, and Anxiety Disorders, as well as grief-related symptoms. Adolescents with psychiatric disorders are at risk of a break or change in their care and management; they may experience increased symptoms. The COVID-19 pandemic and lockdown may have a negative impact on the mental health of adolescents, although there is still no data on the long term impact of this crisis. Adolescents\u2019 individual, familial, and social vulnerability, as well as individual and familial coping abilities, are factors related to adolescent mental health in times of crisis. Adolescents are often vulnerable and require careful consideration by caregivers and healthcare system adaptations to allow for mental health support despite the lockdown. Research on adolescent psychiatric disorders in times of pandemics is necessary, as such a global situation could be prolonged or repeated.", "qid": 43, "docid": "h8s1c5my", "rank": 52, "score": 0.7767310738563538}, {"content": "Title: Mental Health Consequences during the Initial Stage of the 2020 Coronavirus Pandemic (COVID-19) in Spain Content: The pandemic caused by Covid-19 has been an unprecedented social and health emergency worldwide. This is the first study in the scientific literature reporting the psychological impact of the Covid-19 outbreak in a sample of the Spanish population. A cross-sectional study was conducted through an online survey of 3480 people. The presence of depression, anxiety and post-traumatic stress disorder (PTSD) was evaluated with screening tests from 14 March. Sociodemographic and Covid-19-related data was collected. Additionally, spiritual well-being, loneliness, social support, discrimination and sense of belonging were assessed. Descriptive analyses were carried out and linear regression models compiled. The 18.7% of the sample revealed depressive, 21.6% anxiety and 15.8% PTSD symptoms. Being in the older age group, having economic stability and the belief that adequate information had been provided about the pandemic were negatively related to depression, anxiety and PTSD. However, female gender, previous diagnoses of mental health problems or neurological disorders, having symptoms associated with the virus, or those with a close relative infected were associated with greater symptomatology in all three variables. Predictive models revealed that the greatest protector for symptomatology was spiritual well-being, while loneliness was the strongest predictor of depression, anxiety and PTSD. The impact on our mental health caused by the pandemic and the measures adopted during the first weeks to deal with it are evident. In addition, it is possible to identify the need of greater psychological support in general and in certain particularly vulnerable groups.", "qid": 43, "docid": "h0ex5siq", "rank": 53, "score": 0.776305615901947}, {"content": "Title: Mental health consequences during the initial stage of the 2020 Coronavirus pandemic (COVID-19) in Spain Content: The pandemic caused by Covid-19 has been an unprecedented social and health emergency worldwide. This is the first study in the scientific literature reporting the psychological impact of the Covid-19 outbreak in a sample of the Spanish population. A cross-sectional study was conducted through an online survey of 3480 people. The presence of depression, anxiety and post-traumatic stress disorder (PTSD) was evaluated with screening tests from 14 March. Sociodemographic and Covid-19-related data was collected. Additionally, spiritual well-being, loneliness, social support, discrimination and sense of belonging were assessed. Descriptive analyses were carried out and linear regression models compiled. The 18.7% of the sample revealed depressive, 21.6% anxiety and 15.8% PTSD symptoms. Being in the older age group, having economic stability and the belief that adequate information had been provided about the pandemic were negatively related to depression, anxiety and PTSD. However, female gender, previous diagnoses of mental health problems or neurological disorders, having symptoms associated with the virus, or those with a close relative infected were associated with greater symptomatology in all three variables. Predictive models revealed that the greatest protector for symptomatology was spiritual well-being, while loneliness was the strongest predictor of depression, anxiety and PTSD. The impact on our mental health caused by the pandemic and the measures adopted during the first weeks to deal with it are evident. In addition, it is possible to identify the need of greater psychological support in general and in certain particularly vulnerable groups.", "qid": 43, "docid": "n2pw9uts", "rank": 54, "score": 0.776305615901947}, {"content": "Title: COVID-19 and people with intellectual disability: impacts of a pandemic Content: The impacts of the COVID-19 pandemic affect all groups in society. People with intellectual disability (ID) are especially vulnerable to the physical, mental and social effects of the pandemic. Cognitive impairments can limit understanding of information to protect them relying on carers to be vigilant on their behalf during quarantine. Restrictions on usual activities are likely to induce mental stress especially among those who are autistic leading to an escalation in challenging behaviours, risk of placement breakdown and increased the use of psychotropic medication. People with ID are vulnerable to exploitation by others where the usual community supports no longer function to protect them. In future pandemics, it is important that lessons are learned from the impacts COVID-19 have on people with ID. Collecting the evidence through a rigorous approach should help to empower people with ID and their carers to face future outbreaks of infectious diseases.", "qid": 43, "docid": "03aubqeb", "rank": 55, "score": 0.7762730717658997}, {"content": "Title: Effects of the COVID-19 Outbreak on Elder Mistreatment and Response in New York City: Initial Lessons Content: New York City is currently experiencing an outbreak of COVID-19, a highly contagious and potentially deadly virus, which is particularly dangerous for older adults. This pandemic has led to public health policies including social distancing and stay-at-home orders. We explore here the impact of this unique crisis on victims of elder mistreatment and people at risk of victimization. The COVID-19 outbreak has also had a profound impact on the organizations from many sectors that typically respond to protect and serve victims of elder mistreatment. We examine this impact and describe creative solutions developed by these organizations and initial lessons learned in New York City to help inform other communities facing this pandemic and provide guidance for future crises.", "qid": 43, "docid": "wkjsxjcp", "rank": 56, "score": 0.7762582302093506}, {"content": "Title: \u2018What is Inconvenient for You is Life-saving for Me\u2019: How Health Inequities are playing out during the COVID-19 Pandemic Content: The COVID-19 pandemic has had a significant impact globally. Most affected, however, are those individuals and groups routinely disadvantaged by the social injustice created by the misdistribution of power, money, and resources. Simple measures that prevent the spread of COVID-19, such as frequent hand washing and social distancing, are unavailable to millions of people in the wealthiest of nations and in the poorest of nations. Disadvantaged groups are impacted more directly and in disproportionately higher numbers due to existing poor health, and the disruption of services central to securing an income and an education will have lasting consequences for their futures. The unintended effect of exclusionary government policies is that privileged citizens and healthcare systems are also at greater risk. This paper seeks to highlight the impact of COVID-19 on those already suffering health inequities through consideration of some of the social determinants of health on groups in affluent and poorer nations. It also highlights some of the factors that may assist in tackling health inequities as we emerge from this pandemic.", "qid": 43, "docid": "3ly4f8dy", "rank": 57, "score": 0.7761940360069275}, {"content": "Title: 'What is Inconvenient for You is Life-saving for Me': How Health Inequities are playing out during the COVID-19 Pandemic Content: The COVID-19 pandemic has had a significant impact globally. Most affected, however, are those individuals and groups routinely disadvantaged by the social injustice created by the misdistribution of power, money, and resources. Simple measures that prevent the spread of COVID-19, such as frequent hand washing and social distancing, are unavailable to millions of people in the wealthiest of nations and in the poorest of nations. Disadvantaged groups are impacted more directly and in disproportionately higher numbers due to existing poor health, and the disruption of services central to securing an income and an education will have lasting consequences for their futures. The unintended effect of exclusionary government policies is that privileged citizens and healthcare systems are also at greater risk. This paper seeks to highlight the impact of COVID-19 on those already suffering health inequities through consideration of some of the social determinants of health on groups in affluent and poorer nations. It also highlights some of the factors that may assist in tackling health inequities as we emerge from this pandemic.", "qid": 43, "docid": "hwlr3qfz", "rank": 58, "score": 0.7761940360069275}, {"content": "Title: The impact of the COVID-19 pandemic on suicide rates Content: Multiple lines of evidence indicate that the COVID-19 pandemic has profound psychological and social effects. The psychological sequelae of the pandemic will probably persist for months and years to come. Studies indicate that the COVID-19 pandemic is associated with distress, anxiety, fear of contagion, depression, and insomnia in the general population and among health care professionals. Social isolation, anxiety, fear of contagion, uncertainty, chronic stress, and economic difficulties may lead to the development or exacerbation of depressive, anxiety, substance use, and other psychiatric disorders in vulnerable populations including individuals with pre-existing psychiatric disorders and people who reside in high COVID-19 prevalence areas. Stress-related psychiatric conditions including mood and substance use disorders are associated with suicidal behavior. COVID-19 survivors may also be at elevated suicide risk. The COVID-19 crisis may increase suicide rates during and after the pandemic. Mental health consequences of the COVID-19 crisis including suicidal behavior are likely to be present for a long time and peak later than the actual pandemic. To reduce suicides during the COVID-19 crisis it is imperative to decrease stress, anxiety, fears and loneliness in the general population. There should be traditional and social media campaigns to promote mental health and reduce distress. Active outreach is necessary, especially for people with a history of psychiatric disorders, COVID-19 survivors, and older adults. Research studies are needed of how mental health consequences can be mitigated during and after the COVID-19 pandemic.", "qid": 43, "docid": "y9vx7coj", "rank": 59, "score": 0.7757693529129028}, {"content": "Title: Psychopathological problems related to the COVID\u201019 pandemic and possible prevention with music therapy Content: COVID-19 is having a profound effect on societies worldwide and the impact that it is having on children cannot be underestimated. Although Brodin (1) stated that the disease tends to be mild in children, psychopathological considerations allow us to assume that the pandemic will have a high risk of long-term paediatric psychiatric sequelae and interdisciplinary preventative measures are needed.", "qid": 43, "docid": "0mxv8h06", "rank": 60, "score": 0.7757296562194824}, {"content": "Title: Debate: COVID-19 and children in India Content: The COVID-19 pandemic impact on children is a growing concern. The United Nations and its agencies (the World Health Organization and UNICEF), Indian Association For Child and Adolescent Mental Health and National Institute of Mental Health and Neuroscience in India warn about the broader impacts on children and call for urgent action to support the world's children amidst the pandemic which may have lasting consequences. The COVID-19 pandemic and unprecedented control measures to prevent its spread have disrupted nearly every aspect of children's lives - their health, development, learning, behaviour and their families' economic security, including protection from violence and abuse. Given this background, there is an urgent need for action through screening to minimize the mental health issues of children in India who constitute a substantial proportion of the population.", "qid": 43, "docid": "swgb2tzx", "rank": 61, "score": 0.7755749225616455}, {"content": "Title: Letter to the editor in response to: COVID-19 pandemic and challenges for socio-economic issues, healthcare and national programs in India (Gopalan and Misra) Content: Article by Gopalan and Misra is very informative and covers the current challenges arising due to COVID-19. Further, authors has attempted to explore the various socioeconomic and medical aspects affected during this COVID-19 pandemic. It starts with the economic issues, social impacts, cultural influences, and the health related national programs which are regularly getting impacted owing to the ongoing epidemic. The paper throws light on how the pandemic has strongly affected the jobs, businesses transportation, travel, and other sectors which ultimately influence the social-economic balance of the society. This has further led to the decrease in the GDP of the country. The daily wagers and the local business personnel are the most affected ones during this period.", "qid": 43, "docid": "380sajt9", "rank": 62, "score": 0.7754678726196289}, {"content": "Title: Police Stress, Mental Health, and Resiliency during the COVID-19 Pandemic Content: The COVID-19 pandemic created social upheaval and altered norms for all members of society, but its effects on first responders have been particularly profound. Law enforcement officers have been expected to coordinate local shutdowns, encourage social distancing, and enforce stay-at-home mandates all while completing the responsibilities for which they are already understaffed and underfunded. The impact of the COVID-19 pandemic on officer stress, mental health, resiliency, and misconduct is explored drawing insight from reactions to the HIV epidemic over two decades earlier and the terrorist attacks of September 11, 2001. COVID-19 policing is hypothesized to serve as a significant stressor for officers and compound the general and organizational stress associated with the occupation. Avenues for providing officer support are discussed and recommendations for research into the phenomenon presented.", "qid": 43, "docid": "e44nuhh9", "rank": 63, "score": 0.775177001953125}, {"content": "Title: Early impacts of the COVID-19 pandemic on mental health care and on people with mental health conditions: framework synthesis of international experiences and responses Content: Purpose The COVID-19 pandemic has many potential impacts on people with mental health conditions and on mental health care, including direct consequences of infection, effects of infection control measures and subsequent societal changes. We aimed to map early impacts of the pandemic on people with pre-existing mental health conditions and services they use, and to identify individual and service-level strategies adopted to manage these. Methods We searched for relevant material in the public domain published before 30 April 2020, including papers in scientific and professional journals, published first person accounts, media articles, and publications by governments, charities and professional associations. Search languages were English, French, German, Italian, Spanish, and Mandarin Chinese. Relevant content was retrieved and summarised via a rapid qualitative framework synthesis approach. Results We found 872 eligible sources from 29 countries. Most documented observations and experiences rather than reporting research data. We found many reports of deteriorations in symptoms, and of impacts of loneliness and social isolation and of lack of access to services and resources, but sometimes also of resilience, effective self-management and peer support. Immediate service challenges related to controlling infection, especially in inpatient and residential settings, and establishing remote working, especially in the community. We summarise reports of swiftly implemented adaptations and innovations, but also of pressing ethical challenges and concerns for the future. Conclusion Our analysis captures the range of stakeholder perspectives and experiences publicly reported in the early stages of the COVID-19 pandemic in several countries. We identify potential foci for service planning and research.", "qid": 43, "docid": "uyebygdm", "rank": 64, "score": 0.7741570472717285}, {"content": "Title: Impact of the COVID-19 pandemic on patients with pre-existing anxiety disorders attending secondary care Content: OBJECTIVES: To examine the psychological and social impact of the COVID-19 pandemic on patients with established anxiety disorders during a period of stringent mandated social restrictions. METHODS: Semi-structured interviews were conducted with 30 individuals attending the Galway-Roscommon Mental Health Services with an International Classification of Diseases diagnosis of an anxiety disorder to determine the impact of the COVID-19 restrictions on anxiety and mood symptoms, social and occupational functioning and quality of life. RESULTS: Twelve (40.0%) participants described COVID-19 restrictions as having a deleterious impact on their anxiety symptoms. Likert scale measurements noted that the greatest impact of COVID-19 related to social functioning (mean = 4.5, SD = 2.9), with a modest deleterious effect on anxiety symptoms noted (mean = 3.8, SD = 2.9). Clinician rated data noted that 8 (26.7%) participants had disimproved and 14 (46.7%) participants had improved since their previous clinical review, prior to commencement of COVID-19 restrictions. Conditions associated with no 'trigger', such as generalised anxiety disorder, demonstrated a non-significant increase in anxiety symptoms compared to conditions with a 'trigger', such as obsessive compulsive disorder. Psychiatric or physical comorbidity did not substantially impact on symptomatology secondary to COVID-19 mandated restrictions. CONCLUSIONS: The psychological and social impact of COVID-19 restrictions on individuals with pre-existing anxiety disorders has been modest with only minimal increases in symptomatology or social impairment noted.", "qid": 43, "docid": "hcyoshrs", "rank": 65, "score": 0.772911787033081}, {"content": "Title: Crime and coronavirus: social distancing, lockdown, and the mobility elasticity of crime Content: Governments around the world restricted movement of people, using social distancing and lockdowns, to help stem the global coronavirus (COVID-19) pandemic. We examine crime effects for one UK police force area in comparison to 5-year averages. There is variation in the onset of change by crime type, some declining from the WHO \u2018global pandemic\u2019 announcement of 11 March, others later. By 1 week after the 23 March lockdown, all recorded crime had declined 41%, with variation: shoplifting (\u2212 62%), theft (\u2212 52%), domestic abuse (\u2212 45%), theft from vehicle (\u2212 43%), assault (\u2212 36%), burglary dwelling (\u2212 25%) and burglary non-dwelling (\u2212 25%). We use Google Covid-19 Community Mobility Reports to calculate the mobility elasticity of crime for four crime types, finding shoplifting and other theft inelastic but responsive to reduced retail sector mobility (MEC = 0.84, 0.71 respectively), burglary dwelling elastic to increases in residential area mobility (\u2212 1), with assault inelastic but responsive to reduced workplace mobility (0.56). We theorise that crime rate changes were primarily caused by those in mobility, suggesting a mobility theory of crime change in the pandemic. We identify implications for crime theory, policy and future research.", "qid": 43, "docid": "kzpbjvy5", "rank": 66, "score": 0.772600531578064}, {"content": "Title: Impact of the COVID-19 pandemic on patients with pre-existing anxiety disorders attending secondary care Content: OBJECTIVES: To examine the psychological and social impact of the COVID-19 pandemic on patients with established anxiety disorders during a period of stringent mandated social restrictions. METHODS: Semi-structured interviews were conducted with 30 individuals attending the Galway-Roscommon Mental Health Services with an International Classification of Diseases diagnosis of an anxiety disorder to determine the impact of the COVID-19 restrictions on anxiety and mood symptoms, social and occupational functioning and quality of life. RESULTS: Twelve (40.0%) participants described COVID-19 restrictions as having a deleterious impact on their anxiety symptoms. Likert scale measurements noted that the greatest impact of COVID-19 related to social functioning (mean = 4.5, SD = 2.9), with a modest deleterious effect on anxiety symptoms noted (mean = 3.8, SD = 2.9). Clinician rated data noted that 8 (26.7%) participants had disimproved and 14 (46.7%) participants had improved since their previous clinical review, prior to commencement of COVID-19 restrictions. Conditions associated with no \u2018trigger\u2019, such as generalised anxiety disorder, demonstrated a non-significant increase in anxiety symptoms compared to conditions with a \u2018trigger\u2019, such as obsessive compulsive disorder. Psychiatric or physical comorbidity did not substantially impact on symptomatology secondary to COVID-19 mandated restrictions. CONCLUSIONS: The psychological and social impact of COVID-19 restrictions on individuals with pre-existing anxiety disorders has been modest with only minimal increases in symptomatology or social impairment noted.", "qid": 43, "docid": "o3qipyqw", "rank": 67, "score": 0.7722748517990112}, {"content": "Title: The Epidemiological Implications of Incarceration Dynamics in Jails for Community, Corrections Officer, and Incarcerated Population Risks from COVID-19 Content: COVID-19 challenges the daily function of nearly every institution of society. It is the duty of any society to be responsive to such challenges by relying on the best tools and logic available to analyze the costs and benefits of any mitigative action. We here provide a mathematical model to explore the epidemiological consequences of allowing standard intake and unaltered within-jail operational dynamics to be maintained during the ongoing COVID-19 pandemic, and contrast this with proposed interventions to reduce the burden of negative health outcomes. In this way, we provide estimates of the infection risks, and likely loss of life, that arise from current incarceration practices. We provide estimates for in-custody deaths and show how the within-jail dynamics lead to spill-over risks, not only affecting the incarcerated people, but increasing the exposure, infection, and death rates for both corrections officers with whom they interact within the jail system, and the broader community beyond the justice system. We show that, given a typical jail-community dynamic, operating in a business as usual way will result in significant and rapid loss of life. Large scale reductions in arrest and speeding of releases are likely to save the lives of incarcerated people, staff and the community at large.", "qid": 43, "docid": "5lauop7l", "rank": 68, "score": 0.7720628976821899}, {"content": "Title: Commentary on the coronavirus pandemic: Anticipating a fourth wave in the opioid epidemic Content: Experiencing the COVID-19 pandemic simultaneously with the U.S. opioid epidemic is anticipated to have a profound mental health impact on some of our most vulnerable populations. Recent federal and state regulatory changes have been made under the state of emergency in order to ameliorate the some of the challenges faced in maintaining access to substance use and addiction services during such times. There are currently considerable limitations in quantifying the impact of COVID-19 among those with substance use disorders, however, it is imperative that health care systems continue to serve this population in order to prevent associated morbidity and mortality. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "h6gb99fw", "rank": 69, "score": 0.7711446285247803}, {"content": "Title: Commentary on the coronavirus pandemic: Anticipating a fourth wave in the opioid epidemic. Content: Experiencing the COVID-19 pandemic simultaneously with the U.S. opioid epidemic is anticipated to have a profound mental health impact on some of our most vulnerable populations. Recent federal and state regulatory changes have been made under the state of emergency in order to ameliorate the some of the challenges faced in maintaining access to substance use and addiction services during such times. There are currently considerable limitations in quantifying the impact of COVID-19 among those with substance use disorders, however, it is imperative that health care systems continue to serve this population in order to prevent associated morbidity and mortality. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "41rn0fdg", "rank": 70, "score": 0.7711446285247803}, {"content": "Title: Three challenges that the COVID-19 pandemic represents for psychiatry Content: The evolving COVID-19 pandemic and its likely consequences add to the already substantial psychosocial burden caused by global problems, existential threats and heightened uncertainty, which are increasingly confronting communities worldwide. Here we briefly outline three challenges for clinical psychiatry and research, related to coping with the social epidemiology of negative moods, stress and socially mediated traumatic experiences brought on by these adverse developments.", "qid": 43, "docid": "62yih8td", "rank": 71, "score": 0.7709379196166992}, {"content": "Title: Firearm Purchasing and Firearm Violence in the First Months of the Coronavirus Pandemic in the United States Content: Importance. Firearm violence is a significant public health and safety problem in the United States. A surge in firearm purchases following the onset of the coronavirus pandemic may increase rates of firearm violence. Objective. To estimate the association between changes in firearm purchasing and interpersonal firearm violence during the coronavirus pandemic. Design. Cross-sectional time series study. We estimate the difference between observed rates of firearm purchases and those predicted by seasonal autoregressive integrated moving average models. Using negative binomial models, we then estimate the association between excess firearm purchases and rates of interpersonal firearm violence within states, controlling for confounders. Setting. The 48 contiguous states and the District of Columbia. Hawaii and Alaska are excluded due to missing or incomplete data. Exposure. The difference between observed and expected rates of firearm purchases in March through May 2020, approximated by National Instant Criminal Background Check System records. Main Outcome and Measure. Fatal and nonfatal injuries from interpersonal firearm violence, recorded in the Gun Violence Archive. Results. We estimate that there were 2.1 million excess firearm purchases from March through May 2020--a 64.3% increase over expected volume, and an increase of 644.4 excess purchases per 100,000 population. We estimate a relative rate of death and injury from firearm violence of 1.015 (95% Confidence Interval (CI): 1.005 to 1.025) for every 100 excess purchases per 100,000, in models that incorporate variation in purchasing across states and control for effects of the pandemic common to all states. This reflects an increase of 776 fatal and nonfatal injuries (95% CI: 216 to 1,335) over the number expected had no increase in purchasing occurred. Conclusions and Relevance. We find a significant increase in firearm violence in the United States associated with the coronavirus pandemic-related surge in firearm purchasing. Our findings are consistent with existing research. Firearm violence prevention strategies may be particularly important during the pandemic.", "qid": 43, "docid": "bmqt33yw", "rank": 72, "score": 0.7707686424255371}, {"content": "Title: Daily emotional well-being during the COVID-19 pandemic Content: The COVID-19 outbreak has become one of the largest public health crises of our time. Governments have responded by implementing self-isolation and physical distancing measures that have profoundly impacted daily life throughout the world. In this study, we aimed to investigate how people experience the activities, interactions, and settings of their lives during the pandemic. The sample (N = 604) was assessed in Ireland on the 25 March 2020, following the closure of schools and non-essential businesses. We examined within-person variance in emotional well-being and how people spend their time. We found that while most time was spent in the home (74%), time spent outdoors (8%) was associated with markedly raised positive affect and reduced negative emotions. Exercising, going for walks, gardening, pursuing hobbies, and taking care of children were the activities associated with the greatest affective benefits. Home-schooling children and obtaining information about COVID-19 were ranked lowest of all activities in terms of emotional experience. These findings highlight activities that may play a protective role in relation to well-being during the pandemic, the importance of setting limits for exposure to COVID-19-related media coverage, and the need for greater educational supports to facilitate home-schooling during this challenging period.", "qid": 43, "docid": "rhgfmqgu", "rank": 73, "score": 0.770635724067688}, {"content": "Title: Psychological Impact and Associated Factors During the Initial Stage of the Coronavirus (COVID-19) Pandemic Among the General Population in Spain Content: The outbreak of COVID-19 in Spain started at the end of February. By 9th April 2020 Spain was the second country in confirmed cases and in deaths. On March 14, 2020, the Spanish Government declared the state of alarm to limit viral transmission. During such state, citizens must stay confined at home with few justified exceptions. This whole situation drastically changed the life of the population, which can cause a wide range of psychosocial impacts. This study explored the psychological impact of the COVID-19 pandemic in the general adult population (N = 3055) during the first stages of the outbreak in Spain, as well as their anxiety, stress and depression levels. We also examined the extent to which the following variables were associated to participants\u2019 mental health: (1) demographics; (2) degree of concern about the pandemic; (3) environmental conditions during the home confinement, (4) changes in daily life as a consequence of the pandemic; (5) contact with the COVID-19 disease; (6) actual and perceived severity of the crisis; (7) information about the COVID-19, (8) perceived health status and (9) leisure activities conducted within the last 24 h. Our results show that Spanish consider the current COVID-19 health crisis as fairly severe, and the majority felt that the COVID-19 crisis had greatly impacted on their daily life, including changes in their daily routines and cancelation of important activities. About 36% of the participants reported moderate to severe psychological impact, 25% showed mild to severe levels of anxiety, 41% reported depressive symptoms, and 41% felt stressed. Women, young, and those who that lost their job during the health crisis showed the strongest negative psychological symptoms. What worried Spaniards the most was the likelihood of suffering an economic crisis derived from the pandemic. We found factors associated with better mental health, such as being satisfied with the information received about the health crisis, conducting leisure activities, and the perception of being in good health. These findings can be used to design psychological interventions to help coping with COVID-19 pandemic, both in Spain and other countries.", "qid": 43, "docid": "7j98rhr8", "rank": 74, "score": 0.7705245018005371}, {"content": "Title: The Impact of COVID-19 on HIV Treatment and Research: A Call to Action Content: The impact of the COVID-19 pandemic is far reaching, with devastating effects on individuals, communities, and societies across the world. People with chronic health conditions may be at greater risk of contracting or experiencing complications from COVID-19. In addition to illness or death for those who contract the virus, the physical distancing required to flatten the curve of new cases is having a negative impact on the economy, the effects of which intersect with mental health and other existing health concerns, thus affecting marginalized communities. Given that HIV also has a disproportionate impact on marginalized communities, COVID-19 is affecting people with HIV (PWH) in unique ways and will continue to have an impact on HIV research and treatment after the COVID-19 crisis passes. Using the biopsychosocial framework to contextualize the impact of COVID-19 on PWH, the purpose of this review article is to: (1) outline the similarities and differences between the COVID-19 and HIV pandemics; (2) describe the current and future impact of COVID-19 on PWH; and (3) outline a call to action for scientists and practitioners to respond to the impact of COVID-19 on HIV prevention and treatment.", "qid": 43, "docid": "53b4lrk2", "rank": 75, "score": 0.7699904441833496}, {"content": "Title: COVID-19: A global transplant perspective on successfully navigating a pandemic Content: The COVID-19 pandemic has rapidly evolved and changed our way of life in an unprecedented manner. The emergence of COVID-19 has impacted transplantation worldwide. The impact has not been just restricted to issues pertaining to donors or recipients, but also health-care resource utilization as the intensity of cases in certain jurisdictions exceeds available capacity. Here we provide a personal viewpoint representing different jurisdictions from around the world in order to outline the impact of the current COVID-19 pandemic on organ transplantation. Based on our collective experience, we discuss mitigation strategies such as donor screening, resource planning, and a staged approach to transplant volume considerations as local resource issues demand. We also discuss issues related to transplant-related research during the pandemic, the role of transplant infectious diseases, and the influence of transplant societies for education and disseminating current information.", "qid": 43, "docid": "2xt8b0vp", "rank": 76, "score": 0.7697737216949463}, {"content": "Title: COVID-19, children and anxiety in 2020. Content: The ongoing economic and social impacts of the COVID-19 pandemic are likely to produce significant ongoing stresses for children and families.", "qid": 43, "docid": "y7nup1qa", "rank": 77, "score": 0.768796443939209}, {"content": "Title: COVID-19, children and anxiety in 2020 Content: The ongoing economic and social impacts of the COVID-19 pandemic are likely to produce significant ongoing stresses for children and families.", "qid": 43, "docid": "9ocgsfbf", "rank": 78, "score": 0.7687963843345642}, {"content": "Title: An increasing risk of family violence during the Covid-19 pandemic: Strengthening community collaborations to save lives Content: Abstract Though necessary to slow the spread of the novel Coronavirus (Covid-19), actions such as social-distancing, sheltering in-place, restricted travel, and closures of key community foundations are likely to dramatically increase the risk for family violence around the globe. In fact many countries are already indicating a dramatic increase in reported cases of domestic violence. While no clear precedent for the current crisis exists in academic literature, exploring the impact of natural disasters on family violence reports may provide important insight for family violence victim-serving professionals. Improving collaborations between human welfare and animal welfare agencies, expanding community partnerships, and informing the public of the great importance of reporting any concerns of abuse are all critical at this time.", "qid": 43, "docid": "v9fdn4uu", "rank": 79, "score": 0.7681565284729004}, {"content": "Title: Traffic Impacts of the COVID-19 Pandemic: Statewide Analysis of Social Separation and Activity Restriction Content: The COVID-19 pandemic resulted in significant social and economic impacts throughout the world In addition to the health consequences, the impacts on travel behavior have also been sudden and wide ranging This study describes the drastic changes in human behavior using the analysis of highway volume data as a representation of personal activity and interaction Same-day traffic volumes for 2019 and 2020 across Florida were analyzed to identify spatial and temporal changes in behavior resulting from the disease or fear of it and statewide directives to limit person-to-person interaction Compared to similar days in 2019, overall statewide traffic volume dropped by 47 5% Although decreases were evident across the state, there were also differences between rural and urban areas and between highways and arterials both in terms of the timing and extent The data and analyses help to demonstrate the early impacts of the pandemic and may be useful for operational and strategic planning of recovery efforts and for dealing with future pandemics", "qid": 43, "docid": "wszd5kqk", "rank": 80, "score": 0.767985463142395}, {"content": "Title: Flattening the mental ill-health curve: the importance of primary prevention in managing the mental health impacts of COVID19 Content: The COVID19 pandemic is one the biggest challenges the global community has faced. The threat of the virus coupled with the impacts of the social and economic shut-down measures required to slow its spread, already appear to be impacting on people's mental health and wellbeing. Over the weeks, months and years ahead it is likely that many countries will experience a \u2018wave\u2019 of COVID19 related mental disorders as a result of an increase in risk factors linked to the pandemic such as social isolation; child-maltreatment; intimate partner violence; unemployment; housing and income stress; workplace trauma; and grief and loss. The \u2018two-pronged\u2019 approach used to deal with COVID19, provides an excellent blueprint for managing its mental health impacts as well. Nations must focus on preventing the occurrence of new cases of mental disorders as well as strengthening their mental healthcare response to support people who become mentally unwell. A focus on primary prevention is particularly important to \u2018flatten the curve\u2019 and avoid a surge in incidence of mental disorders stemming from the COVID19 pandemic. Many evidence-based interventions designed to prevent common disorders are already available and should be scaled-up. These interventions include parenting programs, social and emotional learning programs, self-care strategies, and workplace mental wellbeing programs, among others.", "qid": 43, "docid": "pl5hyzwp", "rank": 81, "score": 0.7679758071899414}, {"content": "Title: Flexible employment relationships and careers in times of the COVID-19 pandemic Content: The COVID-19 pandemic represents a crisis that affects several aspects of people's lives around the globe. Most of the affected countries took several measures, like lockdowns, business shutdowns, hygiene regulations, social distancing, school and university closings, or mobility tracking as a means of slowing down the distribution of COVID-19. These measures are expected to show short-term and long-term effects on people's working lives. However, most media reports focused on the effects of the COVID-19 pandemic on changes in work arrangements (e.g., short-time work, flexible location and hours) for workers in a regular employment relationship. We here focus on workers in flexible employment relationships (e.g. temporary agency work and other forms of subcontracted labor, as well as new forms of working, such as in the gig economy). Specifically, we will discuss (a) how the work and careers of individuals in flexible employment relationships might get affected by the COVID-19 pandemic; (b) outline ideas how to examine period effects of the COVID-19 pandemic on the work and careers of those individuals, and (c) outline how the pandemic can contribute to the ramification of flexible employment relationships.", "qid": 43, "docid": "9sbyha2v", "rank": 82, "score": 0.7673348784446716}, {"content": "Title: The effects of COVID-19 on the health and socio-economic security of sex workers in Nairobi, Kenya: Emerging intersections with HIV Content: The COVID-19 pandemic, and its attendant responses, has led to massive health, social, and economic challenges on a global scale. While, so far, having a relatively low burden of COVID-19 infection, it is the response in lower- and middle- income countries that has had particularly dire consequences for impoverished populations such as sex workers, many of whom rely on regular income in the informal economic sector to survive. This commentary captures the challenges in Kenya posed by daily curfews and lost economic income, coupled with further changes to sex work that increase potential exposure to infection, stigmatisation, violence, and various health concerns. It also highlights the ways in which communities and programmes have demonstrated resourcefulness in responding to this unprecedented disruption in order to emerge healthy when COVID-19, and the measures to contain it, subside.", "qid": 43, "docid": "euno7cgb", "rank": 83, "score": 0.7673296928405762}, {"content": "Title: The effects of COVID-19 on the health and socio-economic security of sex workers in Nairobi, Kenya: Emerging intersections with HIV. Content: The COVID-19 pandemic, and its attendant responses, has led to massive health, social, and economic challenges on a global scale. While, so far, having a relatively low burden of COVID-19 infection, it is the response in lower- and middle- income countries that has had particularly dire consequences for impoverished populations such as sex workers, many of whom rely on regular income in the informal economic sector to survive. This commentary captures the challenges in Kenya posed by daily curfews and lost economic income, coupled with further changes to sex work that increase potential exposure to infection, stigmatisation, violence, and various health concerns. It also highlights the ways in which communities and programmes have demonstrated resourcefulness in responding to this unprecedented disruption in order to emerge healthy when COVID-19, and the measures to contain it, subside.", "qid": 43, "docid": "3fw915m3", "rank": 84, "score": 0.7673295140266418}, {"content": "Title: The SARS-CoV-2 pandemic impact on rhinology research: A survey of the American Rhinologic Society Content: BACKGROUND: The COVID-19 pandemic has radically shifted healthcare operations within hospitals and universities across the globe. However, the effect of the COVID-19 pandemic on research endeavors and clinical trials is unclear. OBJECTIVE: This study investigates the impact of the COVID-19 pandemic on basic science and clinical research within the rhinology community. METHODS: A cross-sectional study was designed utilizing an 8-question survey to identify changes to rhinology research. Questions evaluated the impact of the COVID-19 pandemic on administrative research support and staffing, basic science research, clinical trials and resident research involvement. RESULTS: Seventy-one participants responded to the survey (8.5% response rate). Most respondents noted changes in IACUC/IRB approval (faster, 33%; slower, 31%). Of those who employed laboratory personnel, 64% were able to continue staff employment with full salary. The majority of animal research and in vitro studies were halted (64% and 56%, respectively), but animal care and cell line maintenance were allowed to continue. Clinical trial enrollment was most commonly limited to COVID derived studies (51%). Forty-seven percent of respondents noted increased resident research participation. CONCLUSION: The rapid spread of the SARS-CoV-2 virus has markedly impacted rhinology-related research. Maintaining safe workplace practices as restrictions are lifted will hopefully mitigate the spread of the virus and allow research productivity to resume.", "qid": 43, "docid": "t8l32052", "rank": 85, "score": 0.7668890357017517}, {"content": "Title: What lies ahead: Elevated concerns for the ongoing suicide pandemic Content: The genesis and global spread of coronavirus disease 2019 (COVID-19) has resulted in significant health concerns amid societies that were ill-equipped for such a formidable opponent. The COVID-19 pandemic has illuminated systemic health disparities and weaknesses within our health care and political systems. With aggressive but necessary interventions to thwart the instantaneous reproduction number, we have simultaneously introduced risk factors for new and exacerbated mental health concerns. Suicide, an ongoing pandemic whose rates are higher than they have been in the past 50 years, is one of these concerns as we navigate COVID-19 deaths and fears surrounding its spread. This article aims to briefly describe in retrospect some of the historical pandemics and their downstream consequences as well as present what may lie ahead in terms of anxiety, depression, and suicidal behaviors. This applies not only to frontline health care workers but also the public at large, who may very well experience long-term stressor- and trauma-related consequences through ongoing exposure to a virus that is not only potentially fatal but may have taken the lives of loved ones. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "h2tcrh1q", "rank": 86, "score": 0.7667374610900879}, {"content": "Title: What lies ahead: Elevated concerns for the ongoing suicide pandemic. Content: The genesis and global spread of coronavirus disease 2019 (COVID-19) has resulted in significant health concerns amid societies that were ill-equipped for such a formidable opponent. The COVID-19 pandemic has illuminated systemic health disparities and weaknesses within our health care and political systems. With aggressive but necessary interventions to thwart the instantaneous reproduction number, we have simultaneously introduced risk factors for new and exacerbated mental health concerns. Suicide, an ongoing pandemic whose rates are higher than they have been in the past 50 years, is one of these concerns as we navigate COVID-19 deaths and fears surrounding its spread. This article aims to briefly describe in retrospect some of the historical pandemics and their downstream consequences as well as present what may lie ahead in terms of anxiety, depression, and suicidal behaviors. This applies not only to frontline health care workers but also the public at large, who may very well experience long-term stressor- and trauma-related consequences through ongoing exposure to a virus that is not only potentially fatal but may have taken the lives of loved ones. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "tfx7tx9i", "rank": 87, "score": 0.7667374610900879}, {"content": "Title: Flexible employment relationships and careers in times of the COVID-19 pandemic Content: Abstract The COVID-19 pandemic represents a crisis that affects several aspects of people's lives around the globe. Most of the affected countries took several measures, like lockdowns, business shutdowns, hygiene regulations, social distancing, school and university closings, or mobility tracking as a means of slowing down the distribution of COVID-19. These measures are expected to show short-term and long-term effects on people's working lives. However, most media reports focused on the effects of the COVID-19 pandemic on changes in work arrangements (e.g., short-time work, flexible location and hours) for workers in a regular employment relationship. We here focus on workers in flexible employment relationships (e.g. temporary agency work and other forms of subcontracted labor, as well as new forms of working, such as in the gig economy). Specifically, we will discuss (a) how the work and careers of individuals in flexible employment relationships might get affected by the COVID-19 pandemic; (b) outline ideas how to examine period effects of the COVID-19 pandemic on the work and careers of those individuals, and (c) outline how the pandemic can contribute to the ramification of flexible employment relationships.", "qid": 43, "docid": "jxzvyfwx", "rank": 88, "score": 0.766494631767273}, {"content": "Title: The German COVID-19 Survey on Mental Health: Primary Results Content: Abstract First cases of COVID-19 were reported in Wuhan, China in early December 2019. Preliminary data from China indicated a substantial impact on mental health by the pandemic and its associated lockdown measures. Such measures are unprecedented for the majority of people and may affect their lives tremendously. The current survey was developed to assess mental health in response to the lockdown in Germany. Methods We conducted a web-based self-report survey including various aspects of mental health (e.g. PHQ-D, PHQ-4, WHO-5 and comparative questions on a 5-point Likert scale concerning sleep, irritability & interpersonal violence). First wave data were taken during the height of lockdown measures in Germany from 1 April to 15 April 2020. Results A total of 3,545 volunteers took part in this cross-sectional survey. Mean age was 40.36 years (SD = 11.70; 83.1% female, 15.2% male). Acute or chronic disease was reported by 36.7% (physical) and 24.7% (mental) of subjects. Participants scored mild severity distress in the PHQ stress module. Depression and anxiety as assessed by PHQ-4 was significantly higher than in reference samples. The mean well-being score (WHO-5) was 50.7, thus pointing towards possible signs of depression. Furthermore, we found significant gender differences for anxiety and depression with women showing higher levels. 45.3% of participants reported worsened sleep, increased levels of irritation, anger and aggression compared to pre-pandemic times. Most importantly, 5% of all participants reported experiencing interpersonal violence (IPV). Discussion This is one of the first and largest surveys on mental health during the COVID-19 pandemic in a European society reflecting a relatively well educated and financially secure sample. Yet, there is evidence for a substantial mental burden with increased levels of stress, anxiety, depressive symptoms, sleep disturbance and irritability. Most importantly and also most concerning is the finding of a one-month prevalence of 5% IPV. We think it is of vital importance to continuously monitor the mental health of the general public during this pandemic and its aftermath and to carefully screen for IPV and its risk factors such as stress, sleep problems and anger.", "qid": 43, "docid": "ov0x3dho", "rank": 89, "score": 0.7663131952285767}, {"content": "Title: The coronavirus (COVID-19) pandemic's impact on mental health Content: Throughout the world, the public is being informed about the physical effects of SARS-CoV-2 infection and steps to take to prevent exposure to the coronavirus and manage symptoms of COVID-19 if they appear. However, the effects of this pandemic on one's mental health have not been studied at length and are still not known. As all efforts are focused on understanding the epidemiology, clinical features, transmission patterns, and management of the COVID-19 outbreak, there has been very little concern expressed over the effects on one's mental health and on strategies to prevent stigmatization. People's behavior may greatly affect the pandemic's dynamic by altering the severity, transmission, disease flow, and repercussions. The present situation requires raising awareness in public, which can be helpful to deal with this calamity. This perspective article provides a detailed overview of the effects of the COVID-19 outbreak on the mental health of people.", "qid": 43, "docid": "5cmcri6u", "rank": 90, "score": 0.7662642002105713}, {"content": "Title: Impact on mental health care and on mental health service users of the COVID-19 pandemic: a mixed methods survey of UK mental health care staff Content: Purpose: The COVID-19 pandemic has potential to disrupt and burden the mental health care system, and to magnify inequalities experienced by mental health service users. Methods: We investigated staff reports regarding the impact of the COVID-19 pandemic in its early weeks on mental health care and mental health service users in the UK using a mixed methods online survey. Recruitment channels included professional associations and networks, charities and social media. Quantitative findings were reported with descriptive statistics, and content analysis conducted for qualitative data. Results: 2,180 staff from a range of sectors, professions and specialties participated. Immediate infection control concerns were highly salient for inpatient staff, new ways of working for community staff. Multiple rapid adaptations and innovations in response to the crisis were described, especially remote working. This was cautiously welcomed but found successful in only some clinical situations. Staff had specific concerns about many groups of service users, including people whose conditions are exacerbated by pandemic anxieties and social disruptions; people experiencing loneliness, domestic abuse and family conflict; those unable to understand and follow social distancing requirements; and those who cannot engage with remote care. Conclusion: This overview of staff concerns and experiences in the early COVID-19 pandemic suggests directions for further research and service development: we suggest that how to combine infection control and a therapeutic environment in hospital, and how to achieve effective and targeted tele-health implementation in the community, should be priorities. The limitations of our convenience sample must be noted.", "qid": 43, "docid": "mfetvz49", "rank": 91, "score": 0.7659350633621216}, {"content": "Title: Daily emotional well\u2010being during the COVID\u201019 pandemic Content: The COVID\u201019 outbreak has become one of the largest public health crises of our time. Governments have responded by implementing self\u2010isolation and physical distancing measures that have profoundly impacted daily life throughout the world. In this study, we aimed to investigate how people experience the activities, interactions, and settings of their lives during the pandemic. The sample (N = 604) was assessed in Ireland on the 25 March 2020, following the closure of schools and non\u2010essential businesses. We examined within\u2010person variance in emotional well\u2010being and how people spend their time. We found that while most time was spent in the home (74%), time spent outdoors (8%) was associated with markedly raised positive affect and reduced negative emotions. Exercising, going for walks, gardening, pursuing hobbies, and taking care of children were the activities associated with the greatest affective benefits. Home\u2010schooling children and obtaining information about COVID\u201019 were ranked lowest of all activities in terms of emotional experience. These findings highlight activities that may play a protective role in relation to well\u2010being during the pandemic, the importance of setting limits for exposure to COVID\u201019\u2010related media coverage, and the need for greater educational supports to facilitate home\u2010schooling during this challenging period.", "qid": 43, "docid": "n276aksa", "rank": 92, "score": 0.7651302814483643}, {"content": "Title: The COVID\u201019 pandemic is a crisis and opportunity for bipolar disorder Content: The ongoing COVID\u201019 pandemic has to date infected more than one million people and led to tens of thousands of deaths across the globe. Thus, many governments have imposed regional or national mass shelters\u2010in\u2010place in an effort to slow its rapid spread. In this global health emergency, special attention should be paid to the potential impact of the measures taken to combat the pandemic on patients with bipolar disorders (BDs).", "qid": 43, "docid": "ttir73l5", "rank": 93, "score": 0.764611005783081}, {"content": "Title: COVID-19 and cancer research Content: The COVID-19 pandemic has had a devastating effect on human lives and society. The accompanying editorial summarises some of the major effects on cancer patients and impacts on cancer research. These may be mitigated by appropriate responses from governments, research funders, charities, universities, industry and the public. It is already clear that different approaches to management have drastically different outcomes.", "qid": 43, "docid": "boyxyt88", "rank": 94, "score": 0.7643455266952515}, {"content": "Title: Debate: COVID\u201019 and children in India Content: The COVID\u201019 pandemic impact on children is a growing concern. The United Nations and its agencies (the World Health Organization and UNICEF), Indian Association For Child and Adolescent Mental Health and National Institute of Mental Health and Neuroscience in India warn about the broader impacts on children and call for urgent action to support the world\u2019s children amidst the pandemic which may have lasting consequences. The COVID\u201019 pandemic and unprecedented control measures to prevent its spread have disrupted nearly every aspect of children\u2019s lives \u2013 their health, development, learning, behaviour and their families\u2019 economic security, including protection from violence and abuse. Given this background, there is an urgent need for action through screening to minimize the mental health issues of children in India who constitute a substantial proportion of the population.", "qid": 43, "docid": "8bu6xadf", "rank": 95, "score": 0.7643186450004578}, {"content": "Title: Taking control amidst the chaos: Emotion regulation during the COVID-19 pandemic Content: The COVID-19 pandemic represents a major global health crisis that continues to threaten public health and safety. Although the pandemic is still unfolding, measures to reduce the spread of the virus have spawned significant challenges to people's current work as well as their careers more generally. In this commentary, we discuss the implications of COVID-19 for maintaining one's psychological well-being and employment security, and also managing family and work responsibilities. We also bring forth evidence from the emotion regulation literature to help mitigate the downstream negative consequences of COVID-19 on people's work lives. Finally, we offer several suggestions for future scholarly investigation into how this pandemic impacts vocational behavior.", "qid": 43, "docid": "snisvk47", "rank": 96, "score": 0.7632762789726257}, {"content": "Title: Commentary on COVID-19 situation in Poland: Practical and empirical evaluation of current state Content: This commentary describes some of the aspects of the COVID-19 pandemic in Poland. The 1st part of the text covers issues related to actions introduced by the Polish government to minimize the risk of infection as well as statistics and difficulties resulting from the restrictions introduced. In the 2nd part, we present the results of our own research, including predictors of posttraumatic stress disorder symptom severity associated with the pandemic situation, and we discuss the results. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "7d2r9jcs", "rank": 97, "score": 0.7627837657928467}, {"content": "Title: Commentary on COVID-19 situation in Poland: Practical and empirical evaluation of current state. Content: This commentary describes some of the aspects of the COVID-19 pandemic in Poland. The 1st part of the text covers issues related to actions introduced by the Polish government to minimize the risk of infection as well as statistics and difficulties resulting from the restrictions introduced. In the 2nd part, we present the results of our own research, including predictors of posttraumatic stress disorder symptom severity associated with the pandemic situation, and we discuss the results. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "qid": 43, "docid": "kadgppks", "rank": 98, "score": 0.7627837657928467}, {"content": "Title: Mapping population mental health concerns related to COVID-19 and the consequences of physical distancing: a Google trends analysis Content: Background: The 2020 Coronavirus pandemic is a major international public health challenge. Governments have taken public health protection measures to reduce the spread of the virus through non-pharmalogical measures. The impact of the pandemic and the public health response on individual and population mental health is unknown. Methods: We used Google Trends data (1 Jan 2020 - 30 Mar 2020) to investigate the impact of the pandemic and government measures to curb it on people\u2019s concerns, as indexed by changes in search frequency for topics indicating mental distress, social and economic stressors and mental health treatment-seeking. We explored the changes of key topics in Google trends in Italy, Spain, USA, UK, and Worldwide in relation to sentinel events during the pandemic. Results: Globally there appears to be significant concerns over the financial and work-related consequences of the pandemic, with some evidence that levels of fear are rising. Conversely relative searching for topics related to depression and suicide fell after the pandemic was announced, with some evidence that searches for the latter have risen recently. Concerns over education and access to medication appear to be particular social stressors. Whilst searches for face-to-face treatments have declined, those for self-care have risen. Conclusions: Monitoring Google trends shows promise as a means of tracking changing public concerns. In weeks to come it may enable policy makers to assess the impact of their interventions including those aiming to limit negative consequences, such as government funded financial safety nets.", "qid": 43, "docid": "9659rpgy", "rank": 99, "score": 0.7620193362236023}, {"content": "Title: The coronavirus (COVID\u201019) pandemic's impact on mental health Content: Throughout the world, the public is being informed about the physical effects of SARS\u2010CoV\u20102 infection and steps to take to prevent exposure to the coronavirus and manage symptoms of COVID\u201019 if they appear. However, the effects of this pandemic on one's mental health have not been studied at length and are still not known. As all efforts are focused on understanding the epidemiology, clinical features, transmission patterns, and management of the COVID\u201019 outbreak, there has been very little concern expressed over the effects on one's mental health and on strategies to prevent stigmatization. People's behavior may greatly affect the pandemic's dynamic by altering the severity, transmission, disease flow, and repercussions. The present situation requires raising awareness in public, which can be helpful to deal with this calamity. This perspective article provides a detailed overview of the effects of the COVID\u201019 outbreak on the mental health of people.", "qid": 43, "docid": "0n5n7p4b", "rank": 100, "score": 0.7617641687393188}]}