Year: 2026
Type: preprint
Study design: Observational Study
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-airways¹,². Although adult upper-airway antiviral responses varied across successive SARS-CoV-2 waves³, 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.
Institutions: Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charité – Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Freie Universität Berlin, Technische Universität Berlin, Fudan University, German Center for Lung Research, Deutsches Konsortium für Translationale Krebsforschung
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1147967356, G1159569226, G1254183670, de.NBI - Etablierungsphase - Heidelberg Center for Human Bioinformatics - HD-HuB, G1768462002, G2082019117, de.NBI - Etablierungsphase - Leistungszentrum - BiGi - Bioinformatisches Resourcenzentrum für mikrobielle Genomforschung in Biotechnologie und Medizin, G2502478445, G2511594427, HiGHmed - Medizininformatik-Konsortium - Beitrag Universitätsklinikum Heidelberg, G2649981378, G2813928278, G2920619578, HiGHmed - Medizininformatik - Konsortium - Beitrag UKSH, Campus Lübeck und Universität Lübeck, G378942120, Integrated and standardized NGS workflows for Personalised therapy, G431688250, de.NBI - Etablierungsphase - Leistungszentrum CiBi - Zentrum für integrative Bioinformatik, G4628880003, G5121333388, G5139259834, G524245738, G5576285491, TRR 179: Determinanten und Dynamik der Elimination versus Persistenz bei HepatitisVirusInfektionen, DZKJ Aufbauförderung - Standort Berlin - Neue Ansätze zur Bekämpfung chronischer Erkrankungen im Kindesalter, de.NBI - Etablierungsphase - Leistungszentrum: RBC - RNA Bioinformatic, G627612317, G64039306, G6404758788, G653298664, G6645136632, SFB 1449: Dynamische Hydrogele an Biogrenzflächen, G6769798452, de.NBI - Etablierungsphase - Leistungszentrum - BioInfra.Prot - Bioinformatik der Proteomik, G7614570622, G7807817544, G7989280502, de.NBI - Etablierungsphase - Koordinierungs- und Administrationseinheit - CAU - Geschäftsstelle, G8205150067, de.NBI - Etablierungsphase - Leistungszentrum - BiGi - Bioinformatisches Resourcenzentrum für mikrobielle Genomforschung in Biotechnologie und Medizin, de.NBI - Etablierungsphase-European Molecular Biology Laboratory-HD-HUB
OpenAlex ID: W7222805872