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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.
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.
  • Purkayastha A; UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA.
  • Sen C; UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA.
  • Garcia G; Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA 90095, USA.
  • Langerman J; Department of Biological Chemistry, David Geffen School of Medicine at UCLA, UCLA, Los Angeles, CA, USA.
  • Shia DW; UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA; UCLA Medical Scientist Training Program, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA; Molecular Bi
  • Meneses LK; UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA.
  • Vijayaraj P; UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA.
  • Durra A; UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA.
  • Koloff CR; UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA.
  • Freund DR; UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA.
  • Chi J; UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA.
  • Rickabaugh TM; UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA.
  • Mulay A; Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Konda B; Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Sim MS; UCLA Department of Medicine, Statistics Core, UCLA, Los Angeles, CA, USA.
  • Stripp BR; Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Plath K; Department of Biological Chemistry, David Geffen School of Medicine at UCLA, UCLA, Los Angeles, CA, USA; Molecular Biology Institute, UCLA, Los Angeles, CA, 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Stem Cell Research Center, UCLA, Los An
  • Arumugaswami V; Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA. Electronic address: varumugaswami@mednet.ucla.edu.
  • Gomperts BN; UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA; Molecular Biology Institute, UCLA, Los Angeles, CA, 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, C
Cell Stem Cell ; 27(6): 869-875.e4, 2020 12 03.
Article in English | MEDLINE | ID: covidwho-927289
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 ß-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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Stem Cells / Smoking / Respiratory Mucosa / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Cell Stem Cell Year: 2020 Document Type: Article Affiliation country: J.stem.2020.11.010

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Stem Cells / Smoking / Respiratory Mucosa / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Cell Stem Cell Year: 2020 Document Type: Article Affiliation country: J.stem.2020.11.010