Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19). Little is known about the interplay between preexisting immunity to endemic seasonal coronaviruses and the development of a SARS-CoV-2–specific IgG response. We investigated the kinetics, breadth, magnitude, and level of cross-reactivity of IgG antibodies against SARS-CoV-2 and heterologous seasonal and epidemic coronaviruses at the clonal level in patients with mild or severe COVID-19 as well as in disease control patients. We assessed antibody reactivity to nucleocapsid and spike antigens and correlated this IgG response to SARS-CoV-2 neutralization. Patients with COVID-19 mounted a mostly type-specific SARS-CoV-2 response. Additionally, IgG clones directed against a seasonal coronavirus were boosted in patients with severe COVID-19. These boosted clones showed limited cross-reactivity and did not neutralize SARS-CoV-2. These findings indicate a boost of poorly protective CoV-specific antibodies in patients with COVID-19 that correlated with disease severity, revealing “original antigenic sin.”

doi.org/10.1172/JCI150613, hdl.handle.net/1765/137115
Journal of Clinical Investigation
Erasmus MC: University Medical Center Rotterdam

M (Muriel) Aguilar Bretones, BM (Brenda) Westerhuis, M.P. (Matthijs) Raadsen, E. (Erwin) de Bruin, F.D. (Felicity) Chandler, N.M.A. (Nisreen) Okba, … G.P. (Gijs) van Nierop. (2021). Seasonal coronavirus-specific B cells with limited SARS-CoV-2 cross-reactivity dominate the IgG response in severe COVID-19. Journal of Clinical Investigation, 131(21). doi:10.1172/JCI150613