Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses.
McNaughton AL., Paton RS., Edmans M., Youngs JC., Wellens J., Phalora P., Fyfe A., Belij-Rammerstorfer S., Bolton JS., Ball J., Carnell GW., Dejnirattisai W., Dold C., Eyre DW., Hopkins P., Howarth A., Kooblall K., Klim H., Leaver S., Lee LN., López-Camacho C., Lumley SF., Macallan DC., Mentzer AJ., Provine NM., Ratcliff J., Slon-Campos JL., Skelly DT., Stolle LB., Supasa P., Temperton N., Walker C., Wang B., Wyncoll D., Simmonds P., Lambe T., Ballie JK., Semple MG., Openshaw PJ., Obolski U., Turner M., Carroll M., Mongkolsapaya J., Screaton G., Kennedy SH., Jarvis LM., Barnes E., Dunachie S., Lourenço J., Matthews PC., Bicanic T., Klenerman P., Gupta S., Thompson CP.
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.