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 KoayJessica 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, Katherine Kedzierska

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13 Scopus citations


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.

Original languageEnglish
Article number2774
JournalNature Communications
Issue number1
StatePublished - Dec 2022


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