Abstract
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.
Keywords: COVID-19; airway basal stem cells; cigarette smoke; injury and repair; interferon response; mucociliary clearance; single cell RNA sequencing; viral infection.
【저자키워드】 COVID-19, viral infection, Mucociliary clearance, single cell RNA sequencing, cigarette smoke, interferon response, airway basal stem cells, injury and repair, 【초록키워드】 stem cells, SARS-CoV-2, viral infection, innate immune response, severe COVID-19, severity, Infection, interferon, smoking, Mucociliary clearance, airway, RNA, Viral, Culture, Single Cell, cigarette smoke, disease spread, disease, epithelial, interferon response, Air-liquid interface, repair, Injury, proliferation, with infection, short term, potential mechanism, increased risk, cultures, smoke, Affect, ALI cultures, implication, Cell, current, basal stem cells, infected airway cells, lack, reducing, increase in, abrogated, number of infected, was reduced, ALI culture, basal stem cell, 【제목키워드】 SARS-CoV-2, response, cigarette smoke, exposure to, cigarette, Direct, STEM, increase,