Seasonal coronavirus-specific B-cells with limited SARS-CoV-2 cross-reactivity dominate the IgG response in severe COVID-19 patients.

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 pre-existing immunity towards 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 mild and severe COVID-19 patients and disease control patients. Antibody reactivity towards nucleocapsid and spike antigens was assessed and correlated to SARS-CoV-2 neutralization. COVID-19 patients mounted a mostly type-specific SARS-CoV-2 response. Additionally, IgG clones directed against 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 support a boost of poorly protective coronavirus-specific antibodies in COVID-19 patients that correlates with disease severity, revealing original antigenic sin.