Pediatric T cell and B cell responses to SARS-CoV-2 infection

Understanding age-associated differences in acute and memory adaptive immunity to SARS-CoV-2 and how this contributes to more favorable outcomes in children is critically important. We evaluated SARS-CoV-2-specific T cell, B cell, and antibody responses in 329 peripheral blood samples collected from non-hospitalized children, adolescents, and adults at three timepoints, including acute and memory timepoints. Most children produced robust CD4+ T cell responses during infection and developed memory CD4+ T cells; however, young children <4 years old often had undetectable CD4+ T cell responses compared to older children and adults. Young children also generated reduced frequencies of memory B cells; despite this, they mounted substantial and durable neutralizing antibody responses. CD4+ T cell responses in children were biased towards non-spike epitopes, especially in asymptomatic cases. Memory B cells in children were preferentially classical memory or, paradoxically, CXCR3+. These findings support the concept that the kinetics and composition of T and B cell responses shift across age groups and may be associated with milder COVID-19 outcomes in children.