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

McNaughton, Anna L; Paton, Robert S; Edmans, Matthew; Youngs, Jonathan Cw; Wellens, Judith; Phalora, Prabhjeet; Fyfe, Alex; ... Thompson, Craig P; + view all (2022) Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses. JCI Insight , Article e156372. 10.1172/jci.insight.156372. (In press). Green open access

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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 coronavirus disease (COVID-19) outcomes 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 intensive care units (ICU) with fatal COVID-19 outcomes, but not in individuals with non-fatal 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 ICU with fatal and non-fatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an original antigenic sin type-response.

Type: Article
Title: Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1172/jci.insight.156372
Publisher version: https://doi.org/10.1172/jci.insight.156372
Language: English
Additional information: Copyright © 2022, McNaughton et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Adaptive immunity, Immunology, Imprinting, Infectious disease
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10149922
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