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

TL;DR

Children generally have strong immune responses to SARS-CoV-2, but those under 4 years old show weaker T and B cell responses while still maintaining good antibody levels.

Contribution

The study reveals age-related differences in T and B cell immune responses to SARS-CoV-2 in children.

Findings

Most children produce robust CD4+ T cell and memory B cell responses to SARS-CoV-2.

Children under 4 years old have reduced CD4+ T cell and memory B cell responses but maintain durable neutralizing antibodies.

CD4+ T cell responses in children are biased toward non-spike epitopes, especially in asymptomatic cases.

Abstract

Understanding 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.

We 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.

Most 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+.

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.

NIH 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.

Most children develop robust, multifunctional CD4+ T cell, memory B cell, and humoral responses to SARS-CoV-2 infection whereas children <4 years old have uniquely reduced CD4+ T cell and memory B cell responses yet maintain humoral responses comparable to those in older individuals.

Figures