@article{McNaughton_A-2022_226615,
title = {Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses},
author = {McNaughton, A. and Paton, R. and Edmans, M. and Youngs, J. and Wellens, J. and Phalora, P. and Fyfe, A. and Belij-Rammerstorfer, S. and Bolton, J. and Ball, J. and Carnell, G. and Dejnirattisai, W. and Dold, C. and Eyre, D. and Hopkins, P. and Howarth, A. and Kooblall, K. and Klim, H. and Leaver, S. and Lee, L. and López-Camacho, C. and Lumley, S. and Macallan, D. and Mentzer, A. and Provine, N. and Ratcliff, J. and Slon-Compos, J. and Skelly, D. and Stolle, L. and Supasa, P. and Temperton, N. and Walker, C. and Wang, B. and Wyncoll, D. and Simmonds, P. and Lambe, T. and Baillie, J. and Semple, M. and Openshaw, P. and Obolski, U. and Turner, M. and Carroll, M. and Mongkolsapaya, J. and Screaton, G. and Kennedy, S. and Jarvis, L. and Barnes, E. and Dunachie, S. and Lourenço, J. and Matthews, P. and Bicanic, T. and Klenerman, P. and Gupta, S. and Thompson, C.},
month = {jul},
year = {2022},
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.},
volume = {7},
issue = {13},
journal = {JCI Insight},
publisher = {American Society for Clinical Investigation},
url = {https://doi.org/10.1172/jci.insight.156372},
}
