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)
|
PDF
Publisher pdf
Language: English 
This work is licensed under a Creative Commons Attribution 4.0 International License.
|
|
|
Download this file (PDF/8MB) |
Preview |
| Request a format suitable for use with assistive technology e.g. a screenreader | |
| 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 |
| Institutional Unit: | Schools > Medway School of Pharmacy |
| Former Institutional Unit: |
Divisions > Division of Natural Sciences > Medway School of Pharmacy
|
| Depositing User: | Nigel Temperton |
| Date Deposited: | 24 May 2022 21:47 UTC |
| Last Modified: | 22 Jul 2025 09:10 UTC |
| Resource URI: | https://kar.kent.ac.uk/id/eprint/95167 (The current URI for this page, for reference purposes) |
University of Kent Author Information
Temperton, Nigel J..
| Creator's ORCID: |
 https://orcid.org/0000-0002-7978-3815
|
|---|---|
| CReDIT Contributor Roles: |
- Link to SensusAccess
- Export to:
- RefWorks
- EPrints3 XML
- BibTeX
- CSV
- Depositors only (login required):
Altmetric
Altmetric
