Longitudinal analysis of humoral and cellular immunity in SARS-CoV-2 exposed families

TL;DR

This study compares how children and adults develop antibody and T-cell immune responses to SARS-CoV-2 over time, finding that children often show only T-cell responses.

Contribution

The study reveals discordant humoral and cellular immune responses in children versus adults after SARS-CoV-2 exposure.

Findings

More children had T-cell responses alone compared to adults with combined antibody and T-cell responses.

T-cell response magnitude correlated with symptoms and antibody levels.

SARS-CoV-2 infection boosted responses to other coronaviruses.

Abstract

Identification of previous SARS-CoV-2 infection typically relies on serology, yet T-cells play a key role in the adaptive immune response against SARS-CoV-2. Here, we investigated in parallel the SARS-CoV-2-specific as well as endemic human coronavirus-specific humoral and cross-reactive cellular responses in children and adults. We analyzed clinical data and blood samples from a family cohort of 96 children and 144 adults at 3–4 and 11–12 months after their first contact with SARS-CoV-2. Humoral response was assessed by a multiplex immunoassay with high sensitivity and specificity (MULTICOV-AB). Cellular responses were analyzed by IFN-γ ELISPOT using four different established epitope compositions (ECs) to discriminate between SARS-CoV-2 specific and HCoV cross-reactive T-cell responses. While the majority of adults had a combined serological and T-cell response, relatively more children had a T-cell response alone rather than a combined response. The magnitude of the T-cell response correlated with symptoms and the humoral response. In addition, SARS-CoV-2 infection significantly boosted the endemic coronavirus-specific cellular response. Overall, our data suggest discordant humoral and cellular responses, reflecting either abortive infection, cellular sensitization with rapid viral clearance or rapid antibody waning or a combination of these phenomena. Restricting epidemiologic analysis to SARS-CoV-2 serological data may underestimate rates of infection with or at least exposure to SARS-CoV-2 in children.

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