Severe COVID-19 patients display a back boost of seasonal coronavirus-specific antibodies

Westerhuis, B. M.; Aguilar-Bretones, M.; Raadsen, M. P.; de Bruin, E.; Okba, N. M. A.; Haagmans, B. L.; Langerak, T.; Endeman, H.; van den Akker, J. P. C.; Gommers, D. A. M. P. J.; van Gorp, E. C. M.; Rockx, B. H. G.; Koopmans, M. P. G.; van Nierop, G. P.

Severe acquired respiratory syndrome coronavirus-2 (SARS-CoV-2) is the cause of coronavirus disease (COVID-19). In severe COVID-19 cases, higher antibody titers against seasonal coronaviruses have been observed than in mild cases. To investigate antibody cross-reactivity as potential explanation for severe disease, we determined the kinetics, breadth, magnitude and level of cross-reactivity of IgG against SARS-CoV-2 and seasonal CoV nucleocapsid and spike from 17 severe COVID-19 cases at the clonal level. Although patients mounted a mostly type-specific SARS-CoV-2 response, B-cell clones directed against seasonal CoV dominated and strongly increased over time. Seasonal CoV IgG responses that did not neutralize SARS-CoV-2 were boosted well beyond detectable cross-reactivity, particularly for HCoV-OC43 spike. These findings support a back-boost of poorly protective coronavirus-specific antibodies in severe COVID-19 patients that may negatively impact de novo SARS-CoV-2 immunity, reminiscent of original antigenic sin.