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SARS-CoV-2 infection results in immune responses in the respiratory tract and peripheral blood that suggest mechanisms of disease severity

Author

Listed:
  • Wuji Zhang

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne)

  • Brendon Y. Chua

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne
    Hokkaido University)

  • Kevin J. Selva

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne)

  • Lukasz Kedzierski

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne
    University of Melbourne, Melbourne)

  • Thomas M. Ashhurst

    (Centenary Institute and University of Sydney
    Sydney Institute for Infectious Diseases, University of Sydney)

  • Ebene R. Haycroft

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne)

  • Suzanne K. Shoffner-Beck

    (University of Michigan)

  • Luca Hensen

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne)

  • David F. Boyd

    (St Jude Children’s Research Hospital)

  • Fiona James

    (Department of Infectious Diseases, Austin Health)

  • Effie Mouhtouris

    (Department of Infectious Diseases, Austin Health)

  • Jason C. Kwong

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne
    Department of Infectious Diseases, Austin Health)

  • Kyra Y. L. Chua

    (Department of Infectious Diseases, Austin Health)

  • George Drewett

    (Department of Infectious Diseases, Austin Health)

  • Ana Copaescu

    (Department of Infectious Diseases, Austin Health)

  • Julie E. Dobson

    (Department of Radiology, Austin Health)

  • Louise C. Rowntree

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne)

  • Jennifer R. Habel

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne)

  • Lilith F. Allen

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne)

  • Hui-Fern Koay

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne)

  • Jessica A. Neil

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne)

  • Matthew J. Gartner

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne)

  • Christina Y. Lee

    (University of Michigan)

  • Patiyan Andersson

    (University of Melbourne at the Peter Doherty Institute for Infection and Immunity)

  • Sadid F. Khan

    (Monash University and Alfred Hospital)

  • Luke Blakeway

    (Monash University and Alfred Hospital)

  • Jessica Wisniewski

    (Monash University and Alfred Hospital)

  • James H. McMahon

    (Monash University and Alfred Hospital
    Monash Medical Centre)

  • Erica E. Vine

    (The Westmead Institute for Medical Research
    Faculty of Medicine and Health, University of Sydney
    Faculty of Medicine and Health, University of Sydney)

  • Anthony L. Cunningham

    (The Westmead Institute for Medical Research
    Faculty of Medicine and Health, University of Sydney)

  • Jennifer Audsley

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity)

  • Irani Thevarajan

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity
    The Royal Melbourne Hospital and Doherty Department University of Melbourne, at the Peter Doherty Institute for Infection and Immunity)

  • Torsten Seemann

    (University of Melbourne at the Peter Doherty Institute for Infection and Immunity)

  • Norelle L. Sherry

    (Department of Infectious Diseases, Austin Health
    University of Melbourne at the Peter Doherty Institute for Infection and Immunity)

  • Fatima Amanat

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Florian Krammer

    (Icahn School of Medicine at Mount Sinai)

  • Sarah L. Londrigan

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne)

  • Linda M. Wakim

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne)

  • Nicholas J. C. King

    (Centenary Institute and University of Sydney
    Sydney Institute for Infectious Diseases, University of Sydney
    Faculty of Medicine and Health, University of Sydney
    Charles Perkins Centre, University of Sydney)

  • Dale I. Godfrey

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne)

  • Laura K. Mackay

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne)

  • Paul G. Thomas

    (St Jude Children’s Research Hospital)

  • Suellen Nicholson

    (The Royal Melbourne Hospital at The Peter Doherty Institute for Infection and Immunity)

  • Kelly B. Arnold

    (University of Michigan)

  • Amy W. Chung

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne)

  • Natasha E. Holmes

    (Department of Infectious Diseases, Austin Health
    University of Melbourne
    Austin Health and University of Melbourne
    Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health)

  • Olivia C. Smibert

    (Department of Infectious Diseases, Austin Health
    Peter McCallum Cancer Centre
    National Centre for Infections in Cancer, Peter McCallum Cancer Centre)

  • Jason A. Trubiano

    (Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health
    Peter McCallum Cancer Centre
    National Centre for Infections in Cancer, Peter McCallum Cancer Centre
    Department of Medicine (Austin Health), University of Melbourne)

  • Claire L. Gordon

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne
    Department of Infectious Diseases, Austin Health)

  • Thi H. O. Nguyen

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne)

  • Katherine Kedzierska

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne
    Hokkaido University)

Abstract

Respiratory tract infection with SARS-CoV-2 results in varying immunopathology underlying COVID-19. We examine cellular, humoral and cytokine responses covering 382 immune components in longitudinal blood and respiratory samples from hospitalized COVID-19 patients. SARS-CoV-2-specific IgM, IgG, IgA are detected in respiratory tract and blood, however, receptor-binding domain (RBD)-specific IgM and IgG seroconversion is enhanced in respiratory specimens. SARS-CoV-2 neutralization activity in respiratory samples correlates with RBD-specific IgM and IgG levels. Cytokines/chemokines vary between respiratory samples and plasma, indicating that inflammation should be assessed in respiratory specimens to understand immunopathology. IFN-α2 and IL-12p70 in endotracheal aspirate and neutralization in sputum negatively correlate with duration of hospital stay. Diverse immune subsets are detected in respiratory samples, dominated by neutrophils. Importantly, dexamethasone treatment does not affect humoral responses in blood of COVID-19 patients. Our study unveils differential immune responses between respiratory samples and blood, and shows how drug therapy affects immune responses during COVID-19.

Suggested Citation

  • Wuji Zhang & Brendon Y. Chua & Kevin J. Selva & Lukasz Kedzierski & Thomas M. Ashhurst & Ebene R. Haycroft & Suzanne K. Shoffner-Beck & Luca Hensen & David F. Boyd & Fiona James & Effie Mouhtouris & J, 2022. "SARS-CoV-2 infection results in immune responses in the respiratory tract and peripheral blood that suggest mechanisms of disease severity," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30088-y
    DOI: 10.1038/s41467-022-30088-y
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    References listed on IDEAS

    as
    1. Marios Koutsakos & Katherine Kedzierska, 2020. "A race to determine what drives COVID-19 severity," Nature, Nature, vol. 583(7816), pages 366-368, July.
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