The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has brought distinct challenges to the care of children and adolescents globally. Unusually for a respiratory viral infection, children and adolescents are at much lower risk from symptomatic coronavirus disease 2019 (COVID-19) than any other age group. The near-global closure of schools in response to the pandemic reflected the reasonable expectation from previous respiratory virus outbreaks that children would be a key component of the transmission chain. However, emerging evidence suggests that this is most likely not the case. A minority of children experience a postinfectious inflammatory syndrome, the pathology and long-term outcomes of which are poorly understood. However, relative to their risk of contracting disease, children and adolescents have been disproportionately affected by lockdown measures, and advocates of child health need to ensure that children's rights to health and social care, mental health support, and education are protected throughout subsequent pandemic waves.

Evidence from contact-tracing studies suggest that children and teenagers are less susceptible to SARS-CoV-2 infection than adults; however, community swabbing and seroprevalence studies conducted outside of outbreak settings suggest that infection rates are similar to those in older age groups (1–3). Only half of children and teenagers with antibodies against SARS-CoV-2 have experienced symptoms, and there is growing evidence that there is a broad range of presentations, emphasizing the limitations of community-based prevalence studies based on testing only children with respiratory symptoms. Hospitalization for severe acute COVID-19 in children is rare, but among these pediatric inpatients, respiratory symptoms are more apparent than in infected children in the community (4). Case fatality in hospitalized children is, fortunately, relatively low at 1% (compared with 27% across all ages) (4).

The reason for the lower burden of symptomatic disease in children is not yet clear. Upper airway expression of angiotensin-converting enzyme 2 (ACE2), a receptor for the SARS-CoV-2 spike protein, increases with age, and higher ACE2 expression correlates with being positive for SARS-CoV-2 genomic RNA in swabs of upper respiratory tracts from symptomatic children, but not with viral load (5). An alternative proposal is the absence in children of maladaptive immune responses that lead to acute respiratory distress syndrome (ARDS) in older age groups (6), but there are likely other unidentified mechanisms.