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.
| Original language | English |
|---|---|
| Article number | 2774 |
| Number of pages | 18 |
| Journal | Nature Communications |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 19 May 2022 |
Keywords
- Antibodies, Viral *covid-19 Humans Immunity Immunoglobulin G Immunoglobulin M Respiratory System SARS-CoV-2 Severity of Illness Index Spike Glycoprotein, Coronavirus
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In: Nature Communications, Vol. 13, No. 1, 2774, 19.05.2022.
Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - SARS-CoV-2 infection results in immune responses in the respiratory tract and peripheral blood that suggest mechanisms of disease severity
AU - Zhang, Wuji
AU - Chua, Brendon Y.
AU - Selva, Kevin J.
AU - Kedzierski, Lukasz
AU - Ashhurst, Thomas M.
AU - Haycroft, Ebene R.
AU - Shoffner-Beck, Suzanne K.
AU - Hensen, Luca
AU - Boyd, David F.
AU - James, Fiona
AU - Mouhtouris, Effie
AU - Kwong, Jason C.
AU - Chua, Kyra Y.L.
AU - Drewett, George
AU - Copaescu, Ana
AU - Dobson, Julie E.
AU - Rowntree, Louise C.
AU - Habel, Jennifer R.
AU - Allen, Lilith F.
AU - Koay, Hui Fern
AU - Neil, Jessica A.
AU - Gartner, Matthew J.
AU - Lee, Christina Y.
AU - Andersson, Patiyan
AU - Khan, Sadid F.
AU - Blakeway, Luke V.
AU - Wisniewski, Jessica
AU - McMahon, James H.
AU - Vine, Erica E.
AU - Cunningham, Anthony L.
AU - Audsley, Jennifer
AU - Thevarajan, Irani
AU - Seemann, Torsten
AU - Sherry, Norelle L.
AU - Amanat, Fatima
AU - Krammer, Florian
AU - Londrigan, Sarah L
AU - Wakim, Linda M
AU - King, Nicholas J.C.
AU - Godfrey, Dale I.
AU - Mackay, Laura K.
AU - Thomas, Paul G.
AU - Nicholson, Suellen
AU - Arnold, Kelly B.
AU - Chung, Amy W.
AU - Holmes, Natasha E.
AU - Smibert, Olivia C.
AU - Trubiano, Jason A.
AU - Gordon, Claire L.
AU - Nguyen, Thi H.O.
AU - Kedzierska, Katherine
N1 - Funding Information: We acknowledge all DRASTIC (The use of cytokines as a preDictoR of disease Severity in criTically Ill COVID-19) investigators from Austin Health, and thank the participants involved. This project obtained samples from the COVID-19 Biobank based at the Alfred Hospital and acknowledge all its investigators and the participants who contributed samples. We acknowledge Janine Roney’s support for this work and funding from the Lord Mayor’s Charitable Foundation and the Ray William Houston Trust. This research included samples and data from the Sentinel Travelers Research Preparedness Platform for Emerging Infectious Diseases (SETREP-ID). We acknowledge all SETREP-ID investigators and sites, and thank all participants involved. The authors thank Barbara Scher for setting up the ethics and governance for the SETREP-ID platform and the Australian Partnership for Preparedness Research for Infectious Disease Emergencies (APPRISE) for ongoing funding of SETREP-ID, Ajantha Rhodes, Judy Chang, Ashanti Dantanarayana and Rosalyn Cao who contributed to the SETREP-ID biobank. SETREP-ID is supported by funding through the National Health and Medical Research Council Centre of Research Excellence (NHMRC CRE), the Australian Partnership for Preparedness Research on Infectious Disease Emergencies (APPRISE AppID 1116530). Funding Information: We acknowledge all DRASTIC (The use of cytokines as a preDictoR of disease Severity in criTically Ill COVID-19) investigators from Austin Health, and thank the participants involved. This project obtained samples from the COVID-19 Biobank based at the Alfred Hospital and acknowledge all its investigators and the participants who contributed samples. We acknowledge Janine Roney’s support for this work and funding from the Lord Mayor’s Charitable Foundation and the Ray William Houston Trust. This research included samples and data from the Sentinel Travelers Research Preparedness Platform for Emerging Infectious Diseases (SETREP-ID). We acknowledge all SETREP-ID investigators and sites, and thank all participants involved. The authors thank Barbara Scher for setting up the ethics and governance for the SETREP-ID platform and the Australian Partnership for Preparedness Research for Infectious Disease Emergencies (APPRISE) for ongoing funding of SETREP-ID, Ajantha Rhodes, Judy Chang, Ashanti Dantanarayana and Rosalyn Cao who contributed to the SETREP-ID biobank. SETREP-ID is supported by funding through the National Health and Medical Research Council Centre of Research Excellence (NHMRC CRE), the Australian Partnership for Preparedness Research on Infectious Disease Emergencies (APPRISE AppID 1116530), the Snow Medical Foundation, the Jack Ma Foundation and the A2 Milk Company. We thank Austin Health Foundation for support of the study. We acknowledge Francesca L. Mordant and Kanta Subbarao for their contributions to the microneutralization assay. We acknowledge Adam K. Wheatley for kindly providing SARS-CoV-2 and HKU-1 spike trimers and Bruce D. Wines and P. Mark Hogarth for kindly providing FcγR dimers. The RBD proteins were produced under HHSN272201400008C and obtained through BEI Resources, NIAID, NIH: Spike Glycoprotein RBD from SARS-Related Coronavirus 2, Wuhan-Hu-1 with C-Terminal Histidine Tag, Recombinant from HEK293F Cells, NR-52366. We thank the staff at the diagnostic microbiology laboratories at Austin Pathology, Melbourne Pathology, Dorevitch Pathology, 4Cyte Pathology, Microbiological Diagnostic Unit Public Health Laboratory, Northern Pathology Victoria, Eastern Health Pathology for performing initial diagnostic testing for the detection of SARS-CoV-2 nucleic acid. We acknowledge Bridie Clemens for reviewing our manuscript. This work was supported by the NHMRC Leadership Investigator Grant to KK (#1173871), Research Grants Council of the Hong Kong Special Administrative Region, China (#T11-712/19-N) to KK, the MRFF Award (#1202445) to KK and AWC, NIH contract CIVC-HRP (HHS-NIH-NIAID-BAA2018) to PGT and KK, NHMRC Senior Principal Research Fellowship (#1117766) to DIG, NHMRC Emerging Leadership Level 1 Investigator Grant to THON (#1194036) and NHMRC Early Career Fellowships to HFK (#1160333), CLG (#1160963) and JAT (#1139902). PGT is supported by NIH NIAID R01 AI136514-03 and ALSAC at St. Jude. WZ and JRH are supported by the Melbourne Research Scholarship from The University of Melbourne. LH is supported by the Melbourne International Research Scholarship (MIRS) and the Melbourne International Fee Remission Scholarship (MIFRS) from The University of Melbourne. We acknowledge the Melbourne Cytometry Platform (Peter Doherty Institute and Melbourne Brain Centre nodes) for provision of flow cytometry services. Publisher Copyright: © 2022, The Author(s).
PY - 2022/5/19
Y1 - 2022/5/19
N2 - 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.
AB - 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.
KW - Antibodies, Viral covid-19 Humans Immunity Immunoglobulin G Immunoglobulin M Respiratory System SARS-CoV-2 Severity of Illness Index Spike Glycoprotein, Coronavirus
UR - http://www.scopus.com/inward/record.url?scp=85130320222&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-30088-y
DO - 10.1038/s41467-022-30088-y
M3 - Article
C2 - 35589689
AN - SCOPUS:85130320222
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2774
ER -