Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses
Issued Date
2022-07-08
Resource Type
eISSN
23793708
Scopus ID
2-s2.0-85133934302
Pubmed ID
35608920
Journal Title
JCI Insight
Volume
7
Issue
13
Rights Holder(s)
SCOPUS
Bibliographic Citation
JCI Insight Vol.7 No.13 (2022)
Suggested Citation
McNaughton A.L., Paton R.S., Edmans M., Youngs J., Wellens J., Phalora P., Fyfe A., Belij-Rammerstorfer S., Bolton J.S., Ball J., Carnell G.W., Dejnirattisai W., Dold C., Eyre D.W., Hopkins P., Howarth A., Kooblall K., Klim H., Leaver S., Lee L.N., López-Camacho C., Lumley S.F., Macallan D.C., Mentzer A.J., Provine N.M., Ratcliff J., Slon-Compos J., Skelly D., Stolle L., Supasa P., Temperton N., Walker C., Wang B., Wyncoll D., Simmonds P., Lambe T., Baillie J.K., Semple M.G., Openshaw P.J.M., Obolski U., Turner M., Carroll M., Mongkolsapaya J., Screaton G., Kennedy S.H., Jarvis L., Barnes E., Dunachie S., Lourenço J., Matthews P.C., Bicanic T., Klenerman P., Gupta S., Thompson C.P. Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses. JCI Insight Vol.7 No.13 (2022). doi:10.1172/jci.insight.156372 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/85718
Title
Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses
Author(s)
McNaughton A.L.
Paton R.S.
Edmans M.
Youngs J.
Wellens J.
Phalora P.
Fyfe A.
Belij-Rammerstorfer S.
Bolton J.S.
Ball J.
Carnell G.W.
Dejnirattisai W.
Dold C.
Eyre D.W.
Hopkins P.
Howarth A.
Kooblall K.
Klim H.
Leaver S.
Lee L.N.
López-Camacho C.
Lumley S.F.
Macallan D.C.
Mentzer A.J.
Provine N.M.
Ratcliff J.
Slon-Compos J.
Skelly D.
Stolle L.
Supasa P.
Temperton N.
Walker C.
Wang B.
Wyncoll D.
Simmonds P.
Lambe T.
Baillie J.K.
Semple M.G.
Openshaw P.J.M.
Obolski U.
Turner M.
Carroll M.
Mongkolsapaya J.
Screaton G.
Kennedy S.H.
Jarvis L.
Barnes E.
Dunachie S.
Lourenço J.
Matthews P.C.
Bicanic T.
Klenerman P.
Gupta S.
Thompson C.P.
Paton R.S.
Edmans M.
Youngs J.
Wellens J.
Phalora P.
Fyfe A.
Belij-Rammerstorfer S.
Bolton J.S.
Ball J.
Carnell G.W.
Dejnirattisai W.
Dold C.
Eyre D.W.
Hopkins P.
Howarth A.
Kooblall K.
Klim H.
Leaver S.
Lee L.N.
López-Camacho C.
Lumley S.F.
Macallan D.C.
Mentzer A.J.
Provine N.M.
Ratcliff J.
Slon-Compos J.
Skelly D.
Stolle L.
Supasa P.
Temperton N.
Walker C.
Wang B.
Wyncoll D.
Simmonds P.
Lambe T.
Baillie J.K.
Semple M.G.
Openshaw P.J.M.
Obolski U.
Turner M.
Carroll M.
Mongkolsapaya J.
Screaton G.
Kennedy S.H.
Jarvis L.
Barnes E.
Dunachie S.
Lourenço J.
Matthews P.C.
Bicanic T.
Klenerman P.
Gupta S.
Thompson C.P.
Author's Affiliation
Siriraj Hospital
Faculty of Life Sciences & Medicine
Oxford University Hospitals NHS Foundation Trust
Department of Veterinary Medicine
Public Health England
St George's University Hospitals NHS Foundation Trust
KU Leuven– University Hospital Leuven
St George’s, University of London
University of Oxford
University of Edinburgh, Roslin Institute
Scottish National Blood Transfusion Service
University of Liverpool
University of Kent
National Heart and Lung Institute
Nuffield Department of Medicine
John Radcliffe Hospital
Tel Aviv University
Guy's and St Thomas' NHS Foundation Trust
University of Oxford Medical Sciences Division
Warwick Medical School
MESO SCALE DIAGNOSTICS, LLC
Faculty of Life Sciences & Medicine
Oxford University Hospitals NHS Foundation Trust
Department of Veterinary Medicine
Public Health England
St George's University Hospitals NHS Foundation Trust
KU Leuven– University Hospital Leuven
St George’s, University of London
University of Oxford
University of Edinburgh, Roslin Institute
Scottish National Blood Transfusion Service
University of Liverpool
University of Kent
National Heart and Lung Institute
Nuffield Department of Medicine
John Radcliffe Hospital
Tel Aviv University
Guy's and St Thomas' NHS Foundation Trust
University of Oxford Medical Sciences Division
Warwick Medical School
MESO SCALE DIAGNOSTICS, LLC
Other Contributor(s)
Abstract
The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal outcomes with coronavirus disease 2019 (COVID-19) is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to an intensive care unit (ICU) with fatal COVID-19 outcomes, but not in individuals with nonfatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to an ICU with fatal and nonfatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an “original antigenic sin” type response.