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

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. Methods: Bulk RNA-seq was performed on well-differentiated human bronchial epithelial (HBE) cell culture lysates with/without SARS-CoV-2 inoculation. Results: SARS-SoV-2 infection peaked at 3 dpi with an ~ 2 log titer suppression at 14 dpi. Airway epithelia repaired to an abnormal mucus metaplastic/inflammatory state that reflected potentially beneficial and adverse consequences at 14 dpi. No age- or sex-dependent effects on SARS-CoV-2 infection were detected. Conclusions: 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.