Pediatric T cell and B cell responses to SARS-CoV-2 infection
L. Benjamin Hills, … , Matthew S. Kelly, Shane Crotty
L. Benjamin Hills, … , Matthew S. Kelly, Shane Crotty
Published September 4, 2025
Citation Information: JCI Insight. 2025;10(20):e196032. https://doi.org/10.1172/jci.insight.196032.
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Clinical Research and Public Health Clinical Research Immunology Infectious disease

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

Abstract

BACKGROUND 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.METHODS 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.RESULTS 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+.CONCLUSION 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.FUNDING 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.

Authors

L. Benjamin Hills, Numana Bhat, Jillian H. Hurst, Amber Myers, Thomas W. Burke, Micah T. McClain, Elizabeth Petzold, Alexandre T. Rotta, Nicholas A. Turner, Alba Grifoni, Daniela Weiskopf, Yvonne Dogariu, Genevieve G. Fouda, Sallie R. Permar, Alessandro Sette, Christopher W. Woods, Matthew S. Kelly, Shane Crotty

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Figure 6

SARS-CoV-2–specific cTFH and antibody response in children.

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SARS-CoV-2–specific cTFH and antibody response in children. (A) Represen...
(A) Representative flow cytometry plots showing SARS-CoV-2–specific CD4+ T cells (blue) overlaid on total CD4+ T cells (gray); CXCR5+ gate represents cTFH cells. Numbers in blue indicate frequencies of SARS-CoV-2–specific cTFH among total CD4+ T cells. PD-1, programmed cell death 1. (B) Frequencies of spike-specific and (C) non-spike-specific cTFH cells. (D) Paired longitudinal spike- (left) and non-spike-specific (right) cTFH responses. (E) Bar graph indicating peak responses at acute or 2-month time points, tabulating spike- and non-spike-specific cTFH responses from 12 children and 6 adults (n = 21, n = 12 responses, respectively). (F) Correlations of spike- (left) and non-spike-specific (right) cTFH frequencies at acute phase of infection with age in children (top) and adults (bottom). Triangles represent asymptomatic donors. (G) Frequencies of spike-specific (left) and non-spike-specific (right) cTFH cells. Each connecting line represents the GeoMean; numbers below the graphs denote number of donors for each time point. Center lines and error bars in B and C represent the GeoMean ± geometric SD. Dotted line in B–D, F, and G indicates the LOQ; solid gray line indicates the lower LOD. Uninfected participants indicated as Un; 2-month and 6-month time points as 2m and 6m. AIM+ denotes frequencies of OX40+CD40L+ cells among total CD4+ T cells. N, %, and Gm in B and C represent number of donors, percent responders, and GeoMean for each group, respectively. Ped in E represents the pediatric group. P values for B and C were calculated by Kruskal-Wallis test with Dunn’s correction for comparisons within pediatric and adult groups and by Mann-Whitney test with Holm-Šídák correction for comparisons across age groups, for D by Wilcoxon’s test, and for E by Fisher’s exact test, indicated as *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. r in F indicates Spearman correlation coefficient.