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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 C.W., Wellens, Judith, Phalora, Prabhjeet, Fyfe, Alex, Belij-Rammerstorfer, Sandra, Bolton, Jai S., Ball, Jonathan, and others. (2022) Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses. JCI Insight, . ISSN 2379-3708. (doi:10.1172/jci.insight.156372) (KAR id:95167)

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Official URL:
https://doi.org/10.1172/jci.insight.156372

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.

Item Type: Article
DOI/Identification number: 10.1172/jci.insight.156372
Uncontrolled keywords: COVID-19
Subjects: Q Science > QR Microbiology > QR355 Virology
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Nigel Temperton
Date Deposited: 24 May 2022 21:47 UTC
Last Modified: 25 May 2022 11:34 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/95167 (The current URI for this page, for reference purposes)
Temperton, Nigel J.: https://orcid.org/0000-0002-7978-3815
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