TY - JOUR
AU - McNaughton, Anna L.
AU - Paton, Robert S.
AU - Edmans, Matthew
AU - Youngs, Jonathan
AU - Wellens, Judith
AU - Phalora, Prabhjeet
AU - Fyfe, Alex
AU - Belij-Rammerstorfer, Sandra
AU - Bolton, Jai S
AU - Ball, Jonathan
AU - Carnell, George W.
AU - Dejnirattisai, Wanwisa
AU - Dold, Christina
AU - Eyre, David W.
AU - Hopkins, Philip
AU - Howarth, Alison
AU - Kooblall, Kreepa
AU - Klim, Hannah
AU - Leaver, Susannah
AU - Lee, Lian Ni
AU - López-Camacho, César
AU - Lumley, Sheila F.
AU - Macallan, Derek C
AU - Mentzer, Alexander J.
AU - Provine, Nicholas M
AU - Ratcliff, Jeremy
AU - Slon-Compos, Jose
AU - Skelly, Donal
AU - Stolle, Lucas
AU - Supasa, Piyada
AU - Temperton, Nigel
AU - Walker, Chris
AU - Wang, Beibei
AU - Wyncoll, Duncan
AU - Simmonds, Peter
AU - Lambe, Teresa
AU - Baillie, J. Kenneth
AU - Semple, Malcolm G.
AU - Openshaw, Peter J.M.
AU - Obolski, Uri
AU - Turner, Marc
AU - Carroll, Miles W.
AU - Mongkolsapaya, Juthathip
AU - Screaton, Gavin
AU - Kennedy, Stephen H
AU - Jarvis, Lisa
AU - Barnes, Eleanor
AU - Dunachie, Susanna
AU - Lourenço, José
AU - Matthews, Philippa C.
AU - Bicanic, Tihana
AU - Klenerman, Paul
AU - Gupta, Sunetra
AU - Thompson, Craig P.
PY - 2022
DA - July
TI - Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses
JO - JCI Insight
VL - 7
IS - 13
DO - https://doi.org/10.1172/jci.insight.156372
AB - 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.
PB - American Society for Clinical Investigation
UR - https://www.research.ed.ac.uk/en/publications/b60ce79d-da31-408a-b84b-5996f482e5b8
KW - Coronavirus (COVID-19)
ER