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

**Authors:** Alex Dulovic, Armin Rabsteyn, Jonathan Remppis, Irene K. E. Gentzcke, Julia Mueller, Nadja Tuecks, Matthias Becker, Daniel Junker, Philipp D. Kaiser, Bjoern Traenkle, Ulrich Rothbauer, Juliane S. Walz, Andreas Peter, Sebastian Hörber, Tina Ganzenmueller, Thomas Iftner, Maximilian Stich, Burkhard Tönshoff, Philipp Henneke, Roland Elling, Klaus-Michael Debatin, Ales Janda, Nicole Schneiderhan-Marra, Axel R. Franz, Peter Lang, Hanna Renk

PMC · DOI: 10.1038/s41598-025-07739-3 · 2025-07-18

## 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.

## Key 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.

## Linked entities

- **Diseases:** SARS-CoV-2 (MONDO:0100096)

## Full-text entities

- **Genes:** IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}
- **Diseases:** SARS-CoV-2 infection (MESH:D000086382), infection (MESH:D007239)
- **Species:** Homo sapiens (human, species) [taxon 9606], Orthocoronavirinae (subfamily) [taxon 2501931], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Gammacoronavirus (genus) [taxon 694013]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12274566/full.md

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Source: https://tomesphere.com/paper/PMC12274566