key: cord-335051-31imf6bv authors: Tsabouri, Sophia; Makis, Alexandros; Kosmeri, Chrysoula; Siomou, Ekaterini title: SPECIAL ARTICLE: Risk factors for severity in children with coronavirus-19 disease (COVID-19): A comprehensive literature review date: 2020-07-30 journal: Pediatr Clin North Am DOI: 10.1016/j.pcl.2020.07.014 sha: doc_id: 335051 cord_uid: 31imf6bv The ongoing coronavirus disease 2019 (COVID-19) pandemic has affected hundreds of thousands of people, including infants and children. We carried out a comprehensive literature review to identify the underlying mechanisms and risk factors for severe COVID-19 in children, in comparison with the other two coronavirus outbreaks in the past, SARS and MERS. Search in the Pubmed and Scopus databases to identify publications between February 26, 2020 and June 10, 2020 identified 23 relevant papers in English. Children have so far accounted for 1.7-2% of the diagnosed cases of COVID-19. They often have milder disease than adults, and child deaths have been rare. The documented risk factors for severe disease in children are young age and underlying comorbidities, although the potentially fatal multisystem inflammatory syndrome (MIS) occurs in older children. It is unclear whether male gender and certain laboratory and imaging findings can also be considered as risk factors, due to current insufficiency of evidence. Reports on other potential factors, such as vitamin D level, responsiveness of the immune system, co-infections and genetic polymorphisms have not yet been published. • The ongoing coronavirus disease 2019 pandemic has affected hundreds of 49 thousands of people. • Children have so far accounted for 1.7-2% of diagnosed cases of • Children often have milder disease than adults, and child deaths have been rare. • Risk factors for severe disease from COVID-19 in children are reported to be young age 53 and underlying comorbidities, although not confirmed in all studies. • It is unclear whether male gender, and certain laboratory and imaging findings can also 55 be considered as risk factors, due to insufficient data. 1% of the cases were in children younger than 10 years and 1% of the cases were in children 103 aged 10 to 19 years. 8 In the USA, among 149,082 reported cases of COVID-19, 1.7% were in 104 children aged under 18 years. 9 From the currently available data it appears that children tend to 105 have asymptomatic or mild disease more commonly than adults, 8,10 but severe cases and even 106 deaths have been reported worldwide in patients younger than 18 years. In a cohort study of 107 32,583 confirmed cases of COVID-19 from Wuhan, China, 4.1% of severe and critical cases 108 were in patients aged < 20 years. 11 According to a large retrospective study conducted in China, 4 HCoVs, 110 HCoV-229E, HCoV-NL63 and HCoV-HKU1, were more common in children, , as their 111 prevalence was 4.3%, and the highest prevalence was among infants aged 7-12 months. 12 Infection by these 4 strains usually causes acute respiratory disease, with severe manifestations 113 in some children. 13 Regarding SARS-CoV, only 6 case series have been reported, including a 114 total of 135 pediatric cases, from Canada, Hong Kong, Taiwan and Singapore. 14 A milder form 115 of the disease was observed in children compared with adults, and no child death was 116 recorded. 15 In the MERS-CoV epidemic, pediatric cases were even fewer, as only two small 117 case series of children were reported, both originating from Saudi Arabia, one of 31 children 118 with a mean age of 10 years 16 and one of 7 children with a mean age of 8 years. 17 In both 119 studies, 42% of the infected children were asymptomatic, 16,17 and in one, 2 of the 7 had severe 120 disease 17 , while in the other, 2 of the 31 children died (6% can predispose to severe disease. In contrast to adults, in whom older age is an independent 387 risk factor for severity and mortality, very young age is considered a risk factor for severity 388 in children, although this has recently been questioned, and MIS occurs in older children. Although a distinct pattern of laboratory findings has not emerged as being associated with 390 severity of the disease in pediatric cases of COVID-19, lymphopenia appears seems to be a Recovery in tracheal organ cultures 416 of novel viruses from patients with respiratory disease. Proceedings of the National Academy 417 of Sciences of the United States of America Characterization and complete genome sequence of a novel 419 coronavirus, coronavirus HKU1, from patients with pneumonia Identification of a novel coronavirus in patients with 422 severe acute respiratory syndrome. The New England journal of medicine Molecular epidemiology, evolution and phylogeny of 425 SARS coronavirus. 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