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Direct Exposure to SARS-CoV-2 and Cigarette Smoke Increases Infection Severity and Alters the Stem Cell-Derived Airway Repair Response
Cell Stem Cell ( IF 19.8 ) Pub Date : 2020-11-17 , DOI: 10.1016/j.stem.2020.11.010
Arunima Purkayastha 1 , Chandani Sen 1 , Gustavo Garcia 2 , Justin Langerman 3 , David W Shia 4 , Luisa K Meneses 1 , Preethi Vijayaraj 1 , Abdo Durra 1 , Caroline R Koloff 1 , Delilah R Freund 1 , Justin Chi 1 , Tammy M Rickabaugh 1 , Apoorva Mulay 5 , Bindu Konda 5 , Myung S Sim 6 , Barry R Stripp 5 , Kathrin Plath 7 , Vaithilingaraja Arumugaswami 8 , Brigitte N Gomperts 9
Affiliation  

Current smoking is associated with increased risk of severe COVID-19, but it is not clear how cigarette smoke (CS) exposure affects SARS-CoV-2 airway cell infection. We directly exposed air-liquid interface (ALI) cultures derived from primary human nonsmoker airway basal stem cells (ABSCs) to short term CS and then infected them with SARS-CoV-2. We found an increase in the number of infected airway cells after CS exposure with a lack of ABSC proliferation. Single-cell profiling of the cultures showed that the normal interferon response was reduced after CS exposure with infection. Treatment of CS-exposed ALI cultures with interferon β-1 abrogated the viral infection, suggesting one potential mechanism for more severe viral infection. Our data show that acute CS exposure allows for more severe airway epithelial disease from SARS-CoV-2 by reducing the innate immune response and ABSC proliferation and has implications for disease spread and severity in people exposed to CS.



中文翻译:


直接暴露于 SARS-CoV-2 和香烟烟雾会增加感染严重程度并改变干细胞衍生的气道修复反应



目前吸烟与严重 COVID-19 的风险增加有关,但尚不清楚香烟烟雾 (CS) 暴露如何影响 SARS-CoV-2 气道细胞感染。我们直接将源自人类非吸烟者气道基底干细胞 (ABSC) 的气液界面 (ALI) 培养物直接暴露于短期 CS,然后用 SARS-CoV-2 感染它们。我们发现接触 CS 后受感染的气道细胞数量增加,但 ABSC 增殖缺乏。培养物的单细胞分析表明,在接触CS并感染后,正常的干扰素反应降低。用干扰素β-1处理暴露于CS的ALI培养物消除了病毒感染,这表明更严重的病毒感染的一种潜在机制。我们的数据表明,急性 CS 暴露会降低先天免疫反应和 ABSC 增殖,导致 SARS-CoV-2 导致更严重的气道上皮疾病,并对暴露于 CS 的人的疾病传播和严重程度产生影响。

更新日期:2020-12-03
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