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. Overall design: HBE cells were maintained >4 weeks on air-liquid interface culture until they are well-ifferentiated. Then the cells were inoculated with SARS-CoV-2 (G614D strain) apically at MON=0.5 for two hours. Cell lysates for bulk RNA-seq were obtained at 1-, 3- 7- and 14-day post inoculation from mock- and virus-inoculated cutures. All samples from GSE210223, which came from 14 donors, were combined with additional samples from 9 donors (GSE299837), and were processed together from the raw FASTQ files to generate combined processed gene expression data and were analyzed as a whole set, which achieved balanced design with regard to age group, and sex. All final statistical analysis of the combined data included batch as a covariate. Therefore, all samples from GSE210223 were re-used in this study. *************************************************************** The table below lists GEO accessions reused/reanalyzed for this study. ***************************************************************