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

Purkayastha, Arunima; Sen, Chandani; Garcia, Gustavo; Langerman, Justin; Shia, David W.; Meneses, Luisa K.; Vijayaraj, Preethi; Durra, Abdo; Koloff, Caroline R.; Freund, Delilah R.; Chi, Justin; Rickabaugh, Tammy M.; Mulay, Apoorva; Konda, Bindu; Sim, Myung S.; Stripp, Barry R.; Plath, Kathrin; Arumugaswami, Vaithilingaraja; Gomperts, Brigitte N.

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.