Abstract
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.”
Original language | English |
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Article number | e150613 |
Number of pages | 14 |
Journal | Journal of Clinical Investigation |
Volume | 131 |
Issue number | 21 |
DOIs | |
Publication status | Published - 1 Nov 2021 |
Bibliographical note
Acknowledgments:This study was funded by the European Union’s Horizon 2020
research and innovation program under grant agreements
from the Versatile Emerging Infectious Disease Observatory (VEO; 874735), Rapid European COVID-19 Emergency
Response Research (RECoVER; 101003589), and the Netherlands Organization for Health Research and Development (ZonMw; 10150062010008). We acknowledge Berend Jan Bosch,
Chunyan Wang, and Wentao Li (Utrecht University, Netherlands) for generously supplying the SECTO antigens; Katharina S.
Schmitz for technical assistance with the biosafety level 3 work;
and Georges M.G.M. Verjans and Pieter L.A. Fraaij for scientific
discussions (EMC, Rotterdam, Netherlands).