Question: what are the health outcomes for children who contract COVID-19?

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.

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.

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.

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.

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.

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.

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.

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.

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: â¢ 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: â¢ 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. â¢ However, 57.7% were hospitalized, 11.5% needed some respiratory support, and 6.9% were treated in an intensive care unit.

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.

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.

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.

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.

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

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 ≥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.

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.

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 1â¯day to 17â¯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 0.5â¯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 1â¯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).

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.

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).

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.

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.

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 “novel coronavirus”, “COVID-19” or “SARS-CoV-2”. 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 (59·1%) and cough (55·9%) were the most frequent symptoms 19·3% of children were asymptomatic. Patchy lesions (21·0%) and ground-glass opacities (32·9%) 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 (0·09%) and 11 children (0·14%) 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.

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.

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.

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-α.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.

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‐α.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.

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-CoV2, 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.

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 6–2143 children infected with SARS-CoV‑2, 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.

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.

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 ≤19 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.

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.

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.

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.

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-α 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.

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.

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.

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.

Title: Clinical Features and the Treatment of Children with COVID‐19: A Case Series from Wenzhou, China Content: The clinical features and treatment of children with COVID‐19 is unclear and understudied. Here, three children with COVID‐19 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‐19 infection. This article is protected by copyright. All rights reserved.

Title: Novel Coronavirus Infection (COVID‐19) in Children Younger Than One Year: A Systematic Review of Symptoms, Management and Outcomes Content: AIM: This aim of this systematic review and meta‐analysis 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 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‐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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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-α 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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Title: Pediatric Asthma & Coronavirus (COVID-19)-Clinical Presentation in an Asthmatic Child—Case 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.

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.

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 8·3 [SD 3·5] 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 38·5°C or higher, and nine (25%) had a body temperature of 37·5-38·5°C. 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.

Title: Psychopathological problems related to the COVID‐19 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.

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.

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

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.

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.

Title: Favourable outcome of coronavirus disease 2019 in a 1‐year‐old girl with acute myeloid leukaemia and severe treatment‐induced 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.

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.

Title: Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center’s 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’s 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-γ (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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 0–16 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 8·3 [SD 3·5] 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 38·5°C or higher, and nine (25%) had a body temperature of 37·5–38·5°C. 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.

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.

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.

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.

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.

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 0.39–12.3% 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.

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.

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.

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.

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.

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%5% 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.

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.