Prevalence and Susceptibility to SARS-CoV-2 in Children

Abstract

Source: Viner RM, Mytton OT, Bonell C, et al. Susceptibility to SARS-CoV-2 infection among children and adolescents compared with adults: a systematic review and meta-analysis [published online ahead of print September 25, 2020]. JAMA Pediatrics. doi: 10.1001/jamapediatrics.2020.4573Investigators from multiple institutions conducted a systematic review and meta-analysis to determine the susceptibility to, and transmission of, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents compared to adults. Investigators searched PubMed and the medical preprint server medRxiv for articles published through July 28, 2020. Studies that provided data on proven SARS-CoV-2 infection and reported either rate of secondary infections in children and adolescents compared to adults (contact-tracing studies) or infection prevalence or seroprevalence in children and adolescents separate from adults (prevalence studies) were included. Studies that reported single-institution outbreaks or only included children were excluded.Identified studies were reviewed for eligibility by 2 investigators. Methodological quality of included studies (categorized as high, medium, low, or uncertain) was assessed independently by 3 investigators, with risk of bias assessed as whether symptomatic contacts or individuals were more likely to participate than asymptomatic ones and whether the obtained sample was >75% of the intended sample. Among included contact-tracing studies, investigators combined data on children and adolescents <20 years old and compared these data with those from adults ≥20 years old, generating pooled odds ratio (OR) estimates of being a child with secondary infections compared with being an adult. Subgroup analyses of contact-tracing studies were performed by child age (<10 years, 10-19 years) compared to adults. Data from prevalence studies was not pooled given heterogeneity among populations and reported as ratios of prevalence of SARS-CoV-2 infection in children compared to adults.There were 32 studies included in analysis involving 41,640 children and adolescents and 268,945 adults. Among included studies, 18 were contact-tracing studies and 14 were prevalence studies. Only 2 studies were determined to be high quality.The pooled OR for all contact-tracing studies was 0.56 (95% CI, 0.37, 0.85), suggesting reduced odds of secondary infections among children compared to adults. For children <10 years old, the pooled OR was 0.52 (95% CI, 0.33, 0.82). In the 14 prevalence studies, the ratios of SARS-CoV-2 prevalence in children and adolescents compared to adults ranged from 0.07 to 0.97, suggesting lower prevalence in children.The authors conclude that children and adolescents have lower odds of being an infected contact and have a lower prevalence of SARS-CoV-2 compared to adults.Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/ device.A total of 792,188 COVID-19 cases in children were reported in the US through October 22, 2020.1 The overall rate has been 1,053 cases per 100,000 children. Children have accounted for 0% to 0.23% of all COVID-19 deaths. Most children with COVID-19 have mild symptoms and a good prognosis. (See AAP Grand Rounds. 2020;44[1]:52 and AAP Grand Rounds. 2020;44[4]:42.3)The current investigators found that children had an OR of 0.56 for being an infected contact compared to adults. Explanations that have been suggested for this lower susceptibility among children include fewer underlying medical conditions, healthier respiratory tracts, and stronger innate immune responses.4,5 A biologically plausible theory also concerns expression of the angiotensin converting enzyme 2 (ACE2) receptor used by SARS-CoV-2 to enter the nasal epithelial cell, usually the first point of contact between the virus and the human body.6 Children have lower ACE2 gene expression in the nasal epithelium as compared to adults, which may decrease infectivity.7The current investigators were not able to determine whether transmission of SARS-CoV-2 by children was lower compared to adults. Three school-based contact-tracing studies found minimal transmission from child or teacher index cases. Population screening studies were not suitable for meta-analysis to compare transmission events between children and adults. A large prospective NIH-funded study of 6,000 people from 2,000 US families in 11 cities, called Human Epidemiology and Response to SARS-CoV-2 (HEROS),8 is in progress to clarify the role of children in the transmission of this novel coronavirus. Wearing masks and social distancing are still best practices.Current evidence suggests that children have a lower susceptibility to SARS-CoV-2 infection and a lower prevalence compared to adults. The role that children play in transmission remains unclear.While we focus, appropriately, on SARS-CoV-2, emerging data suggest that coinfection with other respiratory pathogens may be relatively common in children;9 thus the importance of screening for both SARS-CoV-2 as well as other respiratory pathogens.