Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

McNaughton, A. L.; Paton, R. S.; Edmans, M.; Youngs, J.; Wellens, J.; Phalora, P.; Fyfe, A.; Belij-Rammerstorfer, S.; Bolton, J.; Ball, J.; Carnell, G.; Dejnirattisai, W.; Dold, C.; Eyre, D. W.; Hopkins, P.; Howarth, A.; Kooblall, K.; Klim, H.; Leaver, S.; Lee, L.; Lopez-Camacho, C.; Lumley, S. F.; Macallan, D.; Mentzer, A. J.; Provine, N.; Ratcliff, J.; Slon-Compos, J.; Skelly, D.; Stolle, L.; Supasa, P.; Temperton, N.; Walker, C.; Wang, B.; Wyncoll, D.; OPTIC consortium,; SNBTS consortium,; Simmonds, P.; Lambe, T.; Baillie, K.; Semple, M. G.; Openshaw, P. I.; ISARIC4C consortium,; Obol,

It is unclear whether prior endemic coronavirus infections affect COVID-19 severity. Here, we show that in cases of fatal COVID-19, antibody responses to the SARS-COV-2 spike are directed against epitopes shared with endemic beta-coronaviruses in the S2 subunit of the SARS-CoV-2 spike protein. This immune response is associated with the compromised production of a de novo SARS-CoV-2 spike response among individuals with fatal COVID-19 outcomes.