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.

众多流行病学研究目前将当前吸烟状态与严重COVID-19的风险增加以及疾病死亡率联系起来，然而关于直接接触香烟烟雾如何影响SARS-CoV-2气道细胞感染的问题仍存在许多疑问。本研究直接将源自原发性非吸烟者气道基底干细胞（ABSCs）的粘液纤毛气-液界面（ALI）培养物暴露于短期香烟烟雾，并感染了活性的SARS-CoV-2。我们发现，在香烟烟雾暴露后，感染气道细胞数量增加，以及凋亡细胞数量也相应增加。单独的香烟烟雾暴露导致气道损伤，从而增加了ABSCs的数量，这些细胞通过增殖来修复气道。然而，急性SARS-CoV-2感染或香烟烟雾与SARS-CoV-2暴露的结合并未诱导ABSC增殖。本研究旨在探讨支配香烟烟雾暴露的ALI培养物对SARS-CoV-2感染易感性增加的潜在机制。对培养物的单细胞分析显示，在ALI培养物中感染的SARS-CoV-2气道上皮细胞中诱导了干扰素反应基因，但香烟暴露与SARS-CoV-2感染共同作用降低了干扰素反应。总之，我们的数据显示，急性烟雾暴露通过降低粘膜先天免疫反应和ABSC增殖，使SARS-CoV-2引起的近端气道上皮疾病更为严重，这对吸烟者疾病的传播和严重程度具有深远影响。研究共分为四组：仅SARS-CoV-2组（SCoV2）、仅香烟烟雾组（CS Only）、SARS-CoV-2与香烟烟雾组（CS+SCoV2）、无SARS-CoV-2和无香烟烟雾组（no SCoV2+CS）。列出每组中上调或下调的基因。