Evolution of SARS-CoV-2 reshapes upper airway immunity in children
- 1Berlin Insitute of Health at Charité
Abstract
Children were relatively protected from severe COVID-19 during the early pandemic a phenomenon linked to rapid and heightened innate immune responses in the upper-airways. Although adult upper-airway antiviral responses varied across successive SARS-CoV-2 waves, whether viral evolution similarly reshaped pediatric mucosal immunity remains unclear. Here we used single-cell transcriptomics to profile 229,533 upper-airway cells from 68 unvaccinated children including 17 uninfected controls, spanning the wild-type SARS-CoV-2, Alpha, Delta and Omicron waves. Epithelial interferon responses were primarily determined by time since symptom onset but were, unlike in adults, independent of disease severity. During early infection, anti-viral responses differed across variants without following a progressive pattern of attenuation. Alpha and Delta elicited the strongest interferon programs across epithelial and immune cell populations, whereas Omicron exhibited a shift towards macrophage cytokine signaling and T-cell cytotoxicity. These findings reveal variant-specific remodeling of pediatric upper-airway immunity that fundamentally differs from that described in adults.
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BibTeX
@misc{mcewen2026evolution,
title = {{Evolution of SARS-CoV-2 reshapes upper airway immunity in children}},
author = {S. McEwen and J. Roehmel and S. Wisniewski and J. Loske and M. Messingschlager and J. Liebig and R. L. Chua and A. Seegebarth and F. W. Ten and B. Sawitzki and L. E. Sander and C. Conrad and R. Eils and M. A. Mall and I. Lehmann and S. Trump},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.15.759133},
url = {https://www.biorxiv.org/content/10.64898/2026.10.15.759133v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Evolution of SARS-CoV-2 reshapes upper airway immunity in children
AU - S. McEwen
AU - J. Roehmel
AU - S. Wisniewski
AU - J. Loske
AU - M. Messingschlager
AU - J. Liebig
AU - R. L. Chua
AU - A. Seegebarth
AU - F. W. Ten
AU - B. Sawitzki
AU - L. E. Sander
AU - C. Conrad
AU - R. Eils
AU - M. A. Mall
AU - I. Lehmann
AU - S. Trump
PY - 2026
DA - 2026/10/15
PB - bioRxiv
DO - 10.64898/2026.10.15.759133
UR - https://www.biorxiv.org/content/10.64898/2026.10.15.759133v1
AB - Children were relatively protected from severe COVID-19 during the early pandemic a phenomenon linked to rapid and heightened innate immune responses in the upper-airways. Although adult upper-airway antiviral responses varied across successive SARS-CoV-2 waves, whether viral evolution similarly reshaped pediatric mucosal immunity remains unclear. Here we used single-cell transcriptomics to profile 229,533 upper-airway cells from 68 unvaccinated children including 17 uninfected controls, spanning the wild-type SARS-CoV-2, Alpha, Delta and Omicron waves. Epithelial interferon responses were primarily determined by time since symptom onset but were, unlike in adults, independent of disease severity. During early infection, anti-viral responses differed across variants without following a progressive pattern of attenuation. Alpha and Delta elicited the strongest interferon programs across epithelial and immune cell populations, whereas Omicron exhibited a shift towards macrophage cytokine signaling and T-cell cytotoxicity. These findings reveal variant-specific remodeling of pediatric upper-airway immunity that fundamentally differs from that described in adults.
ER -