Direct Exposure to SARS-CoV-2 and Cigarette Smoke Increases Infection Severity and Alters the Stem Cell-Derived Airway Repair Response

• DOI: 10.1016/j.stem.2020.11.010
• Publication Date: 2020-11-17T14:19:35Z
• Authors: Arunima Purkayastha; Chandani Sen; Gustavo Garcia; Justin Langerman; David W. Shia; Luisa K. Meneses; Preethi Vijayaraj; Abdo Durra; Caroline R. Koloff; Delilah R. Freund; Justin Chi; Tammy M. Rickabaugh; Apoorva Mulay; Bindu Konda; Myung S. Sim; Barry R. Stripp; Kathrin Plath; Vaithilingaraja A...; Brigitte N. Gomperts
• Keywords: 0301 basic medicine; Biomedical and clinical sciences; Coronaviruses; Medical Biotechnology; Medical and Health Sciences; 2.2 Factors relating to the physical environment; 2.1 Biological and endogenous factors; Innate; mucociliary clearance; Lung; Cells, Cultured; Cultured; cigarette smoke; Brief Report; Stem Cells; Smoking; airway basal stem cells; Biological Sciences; 3. Good health; Biological sciences; Infectious Diseases; interferon response; Respiratory; Molecular Medicine; Infection; injury and repair; Cells; 610; Down-Regulation; Respiratory Mucosa; 03 medical and health sciences; single cell RNA sequencing; Tobacco; 617; Genetics; Humans; Biomedical and Clinical Sciences; Tobacco Smoke and Health; Immunity; Patient Acuity; COVID-19; Cell Biology; Interferon-beta; Stem Cell Research; Immunity, Innate; Emerging Infectious Diseases; Good Health and Well Being; viral infection; Developmental Biology

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.