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Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity

Author

Listed:
  • Linh T. Bui

    (Translational Genomics Research Institute)

  • Nichelle I. Winters

    (Vanderbilt University Medical Center)

  • Mei-I Chung

    (Translational Genomics Research Institute)

  • Chitra Joseph

    (University of Nottingham)

  • Austin J. Gutierrez

    (Translational Genomics Research Institute)

  • Arun C. Habermann

    (Vanderbilt University Medical Center)

  • Taylor S. Adams

    (Yale School of Medicine)

  • Jonas C. Schupp

    (Yale School of Medicine)

  • Sergio Poli

    (Brigham and Women’s Hospital, Harvard Medical School)

  • Lance M. Peter

    (Translational Genomics Research Institute)

  • Chase J. Taylor

    (Vanderbilt University Medical Center)

  • Jessica B. Blackburn

    (Vanderbilt University Medical Center)

  • Bradley W. Richmond

    (Vanderbilt University Medical Center
    Department of Veterans Affairs Medical Center)

  • Andrew G. Nicholson

    (Imperial College
    Royal Brompton and Harefield NHS Foundation Trust)

  • Doris Rassl

    (Royal Papworth Hospital NHS Foundation Trust)

  • William A. Wallace

    (Royal Infirmary of Edinburgh
    Edinburgh University Medical School)

  • Ivan O. Rosas

    (Baylor College of Medicine)

  • R. Gisli Jenkins

    (University of Nottingham)

  • Naftali Kaminski

    (Yale School of Medicine)

  • Jonathan A. Kropski

    (Vanderbilt University Medical Center
    Department of Veterans Affairs Medical Center
    Vanderbilt University)

  • Nicholas E. Banovich

    (Translational Genomics Research Institute)

Abstract

Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyze the transcriptomes of 611,398 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observe a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD AT2 cells express higher levels of genes linked directly to the efficiency of viral replication and the innate immune response. Additionally, we identify basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection.

Suggested Citation

  • Linh T. Bui & Nichelle I. Winters & Mei-I Chung & Chitra Joseph & Austin J. Gutierrez & Arun C. Habermann & Taylor S. Adams & Jonas C. Schupp & Sergio Poli & Lance M. Peter & Chase J. Taylor & Jessica, 2021. "Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24467-0
    DOI: 10.1038/s41467-021-24467-0
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    1. Jaber S Alqahtani & Tope Oyelade & Abdulelah M Aldhahir & Saeed M Alghamdi & Mater Almehmadi & Abdullah S Alqahtani & Shumonta Quaderi & Swapna Mandal & John R Hurst, 2020. "Prevalence, Severity and Mortality associated with COPD and Smoking in patients with COVID-19: A Rapid Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 15(5), pages 1-13, May.
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