Abstract
BACKGROUNDUnderstanding age-associated differences in acute and memory adaptive immunity to SARS-CoV-2 and how they contribute to more favorable outcomes in children is critically important.METHODSWe evaluated SARS-CoV-2-specific T cell, B cell, and antibody responses in 329 peripheral blood samples collected from nonhospitalized children, adolescents, and adults at 3 time points, including acute and memory time points.RESULTSMost children produced robust CD4+ T cell responses during infection and developed memory CD4+ T cells; however, young children less than 4 years old often had undetectable CD4+ T cell responses compared with 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 toward non-spike epitopes, especially in asymptomatic cases. Memory B cells in children were preferentially classical memory or, paradoxically, CXCR3+.CONCLUSIONThese 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.FUNDINGNIH National Institute of Allergy and Infectious Diseases (NIAID) award AI142742, the Duke University School of Medicine, and grants from the Children's Miracle Network Hospitals, the Translating Duke Health Children's Health and Discovery Initiative, the NIH NIAID (R01-AI161008-02), and the Defense Advanced Research Projects Agency N66001-09-C-2082. NIH Career Development Awards (K23-AI135090 and K01-AI173398). NIH contract 75N93019C00065.