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July 17th, 2025
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Marsico Lung Institute/Cystic Fibrosis Research Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC
cell biology
biorxiv

Airway Epithelial SARS-CoV-2 Infectious and Repair Responses: Relationships to Age, Sex, and Post-COVID Pulmonary Syndromes

Dang, H.Open in Google Scholar•Edwards, C. E.Open in Google Scholar•Kato, T.Open in Google Scholar•Reidel, B.Open in Google Scholar•Meganck, R. M.Open in Google Scholar•Esther, C. R.Open in Google Scholar•Ehre, C.Open in Google Scholar•Fulcher, M. L.Open in Google Scholar•Bailey, A. B.Open in Google Scholar•Cooley, M. R.Open in Google Scholaret al.

The long-term pulmonary sequelae of SARS-CoV-2 respiratory infections reflect infection severity, innate and adaptive immunity, and respiratory epithelial repair. This study investigated the acute and reparative responses as a function of age and sex in primary human bronchial epithelial (HBE) cultures over a 14-day post-SARS-CoV-2 infection (dpi) protocol. SARS-CoV-2 infection peaked at 3 dpi with an ~ 2 log titer suppression at 14 dpi. SARS-CoV-2 infection induced a series of interferon and interferon-induced gene response and cell damage responses. No age- or sex-dependent effects on SARS-CoV-2 infection were detected. Airway epithelia repaired to an abnormal mucus metaplastic/inflammatory state that reflected potentially beneficial and adverse consequences at 14 dpi. Repair processes were infection severity-dependent, not sex-dependent, and were more robust in young donor cultures. Analyses of long-COVID subjects with persistent pulmonary fibrosis or persistent bronchitic airway diseases exhibited expression of HBE 14 dpi failed repair gene signatures, including ISG gene signatures. Human airway epithelial repair post-SARS-CoV-2 is prolonged and incomplete in vitro over 14 days, and persistently abnormal repair may contribute to phenotypes of people with long-COVID pulmonary syndrome.

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