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

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, Jason C. Kwong, Kyra Y. L. Chua, George Drewett, Ana Copaescu, Julie E. Dobson, Louise C. Rowntree, Jennifer R. Habel, Lilith F. Allen, Hui-Fern Koay, Jessica A. Neil, Matthew J. Gartner, Christina Y. Lee, Patiyan Andersson, Sadid F. Khan, Luke Blakeway, Jessica Wisniewski, James H. McMahon, Erica E. Vine, Anthony L. Cunningham, Jennifer Audsley, Irani Thevarajan, Torsten Seemann, Norelle L. Sherry, Fatima Amanat, Florian Krammer, Sarah L. Londrigan, Linda M. Wakim, Nicholas J. C. King, Dale I. Godfrey, Laura K. Mackay, Paul G. Thomas, Suellen Nicholson, Kelly B. Arnold, Amy W. Chung, Natasha E. Holmes, Olivia C. Smibert, Jason A. Trubiano (), Claire L. Gordon (), Thi H. O. Nguyen () and Katherine Kedzierska ()
Additional contact information
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
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
Thomas M. Ashhurst: Centenary Institute and 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
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
Erica E. Vine: The Westmead Institute for Medical Research
Anthony L. Cunningham: The Westmead Institute for Medical Research
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
Torsten Seemann: University of Melbourne at the Peter Doherty Institute for Infection and Immunity
Norelle L. Sherry: Department of Infectious Diseases, Austin Health
Fatima Amanat: 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
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
Olivia C. Smibert: Department of Infectious Diseases, Austin Health
Jason A. Trubiano: Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health
Claire L. Gordon: University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne
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

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-30088-y

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