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

tetano

Editor, Senior Moderator
J Clin Invest


. 2021 Sep 7;150613.
doi: 10.1172/JCI150613. Online ahead of print.
Seasonal coronavirus-specific B-cells with limited SARS-CoV-2 cross-reactivity dominate the IgG response in severe COVID-19 patients


Muriel Aguilar-Bretones[SUP] 1 [/SUP], Brenda M Westerhuis[SUP] 1 [/SUP], Matthijs P Raadsen[SUP] 1 [/SUP], Erwin de Bruin[SUP] 1 [/SUP], Felicity D Chandler[SUP] 1 [/SUP], Nisreen Ma Okba[SUP] 1 [/SUP], Bart L Haagmans[SUP] 1 [/SUP], Thomas Langerak[SUP] 1 [/SUP], Henrik Endeman[SUP] 2 [/SUP], Johannes Pc van den Akker[SUP] 2 [/SUP], Diederik Ampj Gommers[SUP] 2 [/SUP], Eric Cm van Gorp[SUP] 1 [/SUP], Corine H GeurtsvanKessel[SUP] 1 [/SUP], Rory D de Vries[SUP] 1 [/SUP], Ron Am Fouchier[SUP] 1 [/SUP], Barry Hg Rockx[SUP] 1 [/SUP], Marion Pg Koopmans[SUP] 1 [/SUP], Gijsbert P van Nierop[SUP] 1 [/SUP]



Affiliations

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 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.

Keywords: Immunoglobulins; Immunology; Imprinting; Virology.
 
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