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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.

  • Author(s): 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
  • et al.
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.

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