Journal article

Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

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.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

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., … Thompson, C. P. (2022). Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses. JCI Insight, 7(13).

MLA Style

McNaughton, A. L., et al. “Fatal COVID-19 Outcomes Are Associated with an Antibody Response Targeting Epitopes Shared with Endemic Coronaviruses.” JCI Insight, vol. 7, no. 13, American Society for Clinical Investigation, 2022.

Chicago Style

McNaughton, AL, RS Paton, M Edmans, J Youngs, J Wellens, P Phalora, A Fyfe, et al. 2022. “Fatal COVID-19 Outcomes Are Associated with an Antibody Response Targeting Epitopes Shared with Endemic Coronaviruses.” JCI Insight 7 (13).
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Files:: McNaughton_et_al_2022_Fatal_COVID-19_outcomes_are_associated.pdf

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Publisher copy:: 10.1172/jci.insight.156372

Authors

+ McNaughton, AL More by this author

Institution:: University of Oxford
Division:: MSD
Department:: NDM
Research group:: Peter Medawar Building for Pathogen Research
Role:: Author
ORCID:: 0000-0002-7436-8727

+ Paton, RS More by this author

Institution:: University of Oxford
Division:: MPLS
Department:: Zoology
Research group:: Peter Medawar Building for Pathogen Research
Role:: Author

+ Edmans, M More by this author

Institution:: University of Oxford
Division:: MSD
Department:: NDM
Research group:: Peter Medawar Building for Pathogen Research, Department of Zoology
Role:: Author

+ Youngs, J More by this author

Role:: Author

+ Wellens, J More by this author

Institution:: University of Oxford
Division:: MSD
Department:: NDM
Sub department:: NDM Experimental Medicine
Research group:: Peter Medawar Building for Pathogen Research; Translational Gastroenterology Unit
Role:: Author

More authors...

Contributors

+ Oxford Protective T Cell Immunology for COVID-19 (OPTIC) consortium

Role:: Contributor

+ Scottish National Blood Transfusion Service (SNBTS) consortium

Role:: Contributor

+ International Severe Acute Respiratory and emerging Infection Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) investigators

Role:: Contributor

+ Wellcome Trust More from this funder

Grant:: 109965/Z/15/Z; 222426/Z/21/Z

+ National Institute for Health Research More from this funder

Grant:: NF-SI-0617-10139; NF-SI-0515-10005; NIHR300791

+ Medical Research Council More from this funder

+ Wellcome Trust Principal Fellowship More from this funder

+ Georg and Emily Von Opel Foundation More from this funder

Publisher:: American Society for Clinical Investigation
Journal:: JCI Insight More from this journal
Volume:: 7
Issue:: 13
Article number:: e156372
Publication date:: 2022-05-24
Acceptance date:: 2022-05-18
DOI:: 10.1172/jci.insight.156372
ISSN:: 2379-3708

Language:: English
Keywords:: SNBTS consortium

epitopes

spike glycoprotein

FFR

OPTIC consortium

antibody formation

viral antibodies

COVID-19

ISARIC4C investigators

SARS-CoV-2
Subjects:: immunology

infectious disease
Pubs id:: 1178278
Local pid:: pubs:1178278
Deposit date:: 2022-08-04

Terms of use

Copyright holder:: McNaughton et al.
Copyright date:: 2022
Rights statement:: © 2022 McNaughton et al. This work is licensed under the Creative Commons Attribution 4.0 International License.

Licence:: CC Attribution (CC BY)

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