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]

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



Affiliations

• PMID: 34499051
• DOI: 10.1172/JCI150613

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.