• Otávio Santiago

COVID-19 and children


There has been substantial research on adult COVID-19 and how to treat it. But how do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections afflict children? The COVID-19 pandemic has yielded many surprises, not least that children generally develop less severe disease than older adults, which is unusual for a respiratory disease. However, some children can develop serious complications from COVID-19, such as multisystem inflammatory syndrome in children (MIS-C) and Long Covid, even after mild or asymptomatic COVID-19. Why this occurs in some and not others is an important question.


Moreover, when children do contract COVID-19, understanding their role in transmission, especially in schools and at home, is crucial to ensuring effective mitigation measures. Therefore, in addition to nonpharmaceutical interventions, such as improved ventilation, there is a strong case to vaccinate children so as to reduce possible long-term effects from infection and to decrease transmission. But questions remain about whether vaccination might skew immune responses to variants in the long term. As the experts discuss below, more is being learned about these important issues, but much more research is needed to understand the long-term effects of COVID-19 in children. –Gemma K. Alderton


Why is COVID-19 generally milder in children?

By Carl A. Pierce, Kevan C. Herold, and Betsy C. Herold

Why infants and young children have milder clinical courses with COVID-19, accounting for ∼0.1% of deaths, but are more vulnerable to established pathogens has been a key question since the onset of the pandemic. This may be attributed to differences in susceptibility. All segments of the population were naïve to SARS-CoV-2, whereas older children and adults have protective immunity to established viruses because of prior exposures and vaccines. Although the underrepresentation of children in severe COVID-19 cases was initially hypothesized to reflect decreased susceptibility, no age-associated difference in household transmission, expression of angiotensin-converting enzyme 2 (ACE2, the receptor for viral cell entry), antibody titers against other coronaviruses, or SARS-CoV-2 viral loads in nasopharyngeal swabs have been detected (14). These findings, coupled with immunological studies, suggest that the more favorable outcomes likely reflect rapid engagement of the pediatric mucosal immune system.


Studies of immune responses in hospitalized children and adults during the first wave of the COVID-19 pandemic found that pediatric patients had less robust memory T cell responses and lower neutralizing and Fcγ-receptor activating antibody responses than adults (2, 5). Coupled with data showing an age-dependent decrease in serum levels of the cytokines interferon-γ and interleukin-17, these findings suggested that children may mount a more vigorous innate (pathogen nonspecific) response that promotes viral clearance and precludes the robust adaptive immune response to SARS-CoV-2 that contributes to severe disease in adults (2). This hypothesis was strengthened by direct study of mucosal responses at the time of COVID-19 diagnosis: RNA sequencing data and measurement of cytokines demonstrated a brisk innate response in the nasal mucosa of children versus adults (3). These findings may be a consequence of trained immunity resulting from more frequent respiratory infections in children, leading to higher baseline innate activity in pediatric relative to adult nasal mucosae (6, 7).

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