Direct exposure to SARS-CoV-2 and cigarette smoke increases infection severity and alters the stem cell-derived airway repair response. Purkayastha et al
Most demographic studies are now associating current smoking status with increased risk of severe COVID-19 and mortality from the disease but there remain many questions about how direct cigarette smoke exposure affects SARS-CoV-2 airway cell 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 found an increase in the number of infected airway cells after cigarette smoke exposure as well as an increased number of apoptotic cells. Cigarette smoke exposure alone caused airway injury that resulted in an increased number of ABSCs, which proliferate to repair the airway. However, acute SARS-CoV-2 infection or the combination of exposure to cigarette smoke and SARS-CoV-2 did not induce ABSC proliferation. We set out to examine the underlying mechanisms governing the increased susceptibility of cigarette smoke exposed ALI cultures to SARS-CoV-2 infection. Single cell profiling of the cultures 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. In summary, our data show that acute smoke exposure allows for more severe proximal airway epithelial disease from SARS-CoV-2 by reducing the mucosal innate immune response and ABSC proliferation and has implications for disease spread and severity in people exposed to cigarette smoke. Four groups were examined SARS-CoV-2 only (SCoV2), cigarette smoke only (CS Only), SARS-CoV-2 and cigarette smoke (CS+SCoV2), no SARS-CoV-2, no cigarette smoke (no SCoV2+CS). Genes that are up regulated or down regulated in each group are listed.
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Air liquid interface cultures of airway basal stem cells. Cigarette smoke exposure for 3 minutes a day for 4 days. SARS-CoV-2 infection with MOI 0.1