Direct exposure to SARS-CoV-2 and cigarette smoke increases infection severity and alters the stem cell-derived airway repair response

To study the effect of cigarette smoke exposure on Sars-Cov2 infection, we directly exposed mucociliary air-liquid interface (ALI) cultures derived from primary human nonsmoker airway basal stem cells (ABSCs) to short term cigarette smoke and infected them with live SARS-CoV-2. We set out to examine the underlying mechanisms governing the increased susceptibility of cigarette smoke exposed ALI cultures to SARS-CoV-2 infection by usingle cell profiling of the cultures, which showed that interferon response genes were induced in SARS-CoV-2 infected airway epithelial cells in ALI cultures but smoking exposure together with SARS-CoV-2 infection reduced the interferon response. Overall design: Human bronchial airway cells were cultured in air liquid interface for approximately one week. Cells were exposed or not to cigarette smoke for 4 days, then exposed or not to SARS-Covid2 virus for 72 hour. Cultures were then harvested for single cell RNA sequencing.