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; Katherine Kedzierska

doi:10.1038/s41467-022-30088-y

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

Nat Commun. 2022 May 19;13(1):2774. doi: 10.1038/s41467-022-30088-y.

Authors

Wuji Zhang¹, Brendon Y Chua^{1

2}, Kevin J Selva¹, Lukasz Kedzierski^{1

3}, Thomas M Ashhurst^{4

5}, Ebene R Haycroft¹, Suzanne K Shoffner-Beck⁶, Luca Hensen¹, David F Boyd⁷, Fiona James⁸, Effie Mouhtouris⁸, Jason C Kwong^{1

8}, Kyra Y L Chua⁸, George Drewett⁸, Ana Copaescu⁸, Julie E Dobson⁹, Louise C Rowntree¹, Jennifer R Habel¹, Lilith F Allen¹, Hui-Fern Koay¹, Jessica A Neil¹, Matthew J Gartner¹, Christina Y Lee⁶, Patiyan Andersson¹⁰, Sadid F Khan¹¹, Luke Blakeway¹¹, Jessica Wisniewski¹¹, James H McMahon^{11

12}, Erica E Vine^{13

14

15}, Anthony L Cunningham^{13

15}, Jennifer Audsley¹⁶, Irani Thevarajan^{16

17}, Torsten Seemann¹⁰, Norelle L Sherry^{8

10}, Fatima Amanat^{18

19}, Florian Krammer¹⁸, Sarah L Londrigan¹, Linda M Wakim¹, Nicholas J C King^{4

5

14

20

21

22}, Dale I Godfrey¹, Laura K Mackay¹, Paul G Thomas⁷, Suellen Nicholson²³, Kelly B Arnold⁶, Amy W Chung¹, Natasha E Holmes^{8

24

25

26}, Olivia C Smibert^{8

27

28}, Jason A Trubiano^#^{29

30

31

32}, Claire L Gordon^#^{33

34}, Thi H O Nguyen^#³⁵, Katherine Kedzierska^#^{36

37}

Affiliations

¹ Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia.
² Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan.
³ Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne, Victoria, 3000, Australia.
⁴ Sydney Cytometry Core Research Facility, Charles Perkins Centre, Centenary Institute and University of Sydney, Sydney, NSW, Australia.
⁵ Sydney Institute for Infectious Diseases, University of Sydney, Sydney, NSW, Australia.
⁶ Department of Biomedical Engineering, University of Michigan, Michigan, USA.
⁷ Department of Immunology, St Jude Children's Research Hospital, Memphis, TN, USA.
⁸ Department of Infectious Diseases, Austin Health, Heidelberg, VIC, Australia.
⁹ Department of Radiology, Austin Health, Heidelberg, VIC, Australia.
¹⁰ Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
¹¹ Department of Infectious Diseases, Monash University and Alfred Hospital, Melbourne, VIC, Australia.
¹² Department of Infectious Diseases, Monash Medical Centre, Melbourne, VIC, Australia.
¹³ Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, NSW, Australia.
¹⁴ School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
¹⁵ Sydney Infectious Diseases, Faculty of Medicine and Health, University of Sydney, Westmead, NSW, Australia.
¹⁶ Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, 3000, Australia.
¹⁷ Victorian Infectious Diseases Services, The Royal Melbourne Hospital and Doherty Department University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, 3000, VIC, Australia.
¹⁸ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁹ Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
²⁰ Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.
²¹ Viral Immunopathology Laboratory, Discipline of Pathology, School of Medical Sciences, University of Sydney, Sydney, NSW, Australia.
²² Sydney Nano, University of Sydney, Sydney, NSW, 2006, Australia.
²³ Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
²⁴ Department of Critical Care, University of Melbourne, Parkville, VIC, Australia.
²⁵ Data Analytics Research and Evaluation (DARE) Centre, Austin Health and University of Melbourne, Heidelberg, VIC, Australia.
²⁶ Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Heidelberg, VIC, Australia.
²⁷ Department of Infectious Diseases, Peter McCallum Cancer Centre, Melbourne, VIC, Australia.
²⁸ National Centre for Infections in Cancer, Peter McCallum Cancer Centre, Melbourne, VIC, Australia.
²⁹ Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Heidelberg, VIC, Australia. [email protected].
³⁰ Department of Infectious Diseases, Peter McCallum Cancer Centre, Melbourne, VIC, Australia. [email protected].
³¹ National Centre for Infections in Cancer, Peter McCallum Cancer Centre, Melbourne, VIC, Australia. [email protected].
³² Department of Medicine (Austin Health), University of Melbourne, Heidelberg, VIC, Australia. [email protected].
³³ Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia. [email protected].
³⁴ Department of Infectious Diseases, Austin Health, Heidelberg, VIC, Australia. [email protected].
³⁵ Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia. [email protected].
³⁶ Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia. [email protected].
³⁷ Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan. [email protected].

^# Contributed equally.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Viral
COVID-19*
Humans
Immunity
Immunoglobulin G
Immunoglobulin M
Respiratory System
SARS-CoV-2
Severity of Illness Index
Spike Glycoprotein, Coronavirus

Substances

Antibodies, Viral
Immunoglobulin G
Immunoglobulin M
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Abstract

Publication types

MeSH terms

Substances

Grants and funding