Major role of IgM in the neutralizing activity of convalescent plasma against SARS-CoV-2

Romain Gasser; Marc Cloutier; Jérémie Prévost; Corby Fink; Éric Ducas; Shilei Ding; Nathalie Dussault; Patricia Landry; Tony Tremblay; Audrey Laforce-Lavoie; Antoine Lewin; Guillaume Beaudoin-Bussières; Annemarie Laumaea; Halima Medjahed; Catherine Larochelle; Jonathan Richard; Gregory A Dekaban; Jimmy D Dikeakos; Renée Bazin; Andrés Finzi

doi:10.1016/j.celrep.2021.108790

Major role of IgM in the neutralizing activity of convalescent plasma against SARS-CoV-2

Cell Rep. 2021 Mar 2;34(9):108790. doi: 10.1016/j.celrep.2021.108790. Epub 2021 Feb 10.

Authors

Romain Gasser¹, Marc Cloutier², Jérémie Prévost¹, Corby Fink³, Éric Ducas², Shilei Ding¹, Nathalie Dussault², Patricia Landry², Tony Tremblay², Audrey Laforce-Lavoie², Antoine Lewin⁴, Guillaume Beaudoin-Bussières¹, Annemarie Laumaea¹, Halima Medjahed⁵, Catherine Larochelle⁶, Jonathan Richard¹, Gregory A Dekaban³, Jimmy D Dikeakos⁷, Renée Bazin⁸, Andrés Finzi⁹

Affiliations

¹ Centre de recherche du CHUM, Montréal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC H2X 0A9, Canada.
² Héma-Québec, Affaires Médicales et Innovation, Québec, QC G1V 5C3, Canada.
³ Biotherapeutics Research Laboratory, Robarts Research Institute, London, ON NGA 5B7, Canada; Department of Microbiology and Immunology, University of Western Ontario, London, ON N6A 5B7, Canada.
⁴ Héma-Québec, Affaires Médicales et Innovation, Montréal, QC H4R 2W7, Canada; Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
⁵ Centre de recherche du CHUM, Montréal, QC H2X 0A9, Canada.
⁶ Centre de recherche du CHUM, Montréal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC H2X 0A9, Canada; Department of Neurosciences, University of Montreal, Montreal, QC H2X 0A9, Canada.
⁷ Department of Microbiology and Immunology, University of Western Ontario, London, ON N6A 5B7, Canada.
⁸ Héma-Québec, Affaires Médicales et Innovation, Québec, QC G1V 5C3, Canada. Electronic address: renee.bazin@hema-quebec.qc.ca.
⁹ Centre de recherche du CHUM, Montréal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC H2X 0A9, Canada; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada. Electronic address: andres.finzi@umontreal.ca.

Abstract

Characterization of the humoral response to SARS-CoV-2, the etiological agent of COVID-19, is essential to help control the infection. The neutralization activity of plasma from patients with COVID-19 decreases rapidly during the first weeks after recovery. However, the specific role of each immunoglobulin isotype in the overall neutralizing capacity is still not well understood. In this study, we select plasma from a cohort of convalescent patients with COVID-19 and selectively deplete immunoglobulin A, M, or G before testing the remaining neutralizing capacity of the depleted plasma. We find that depletion of immunoglobulin M is associated with the most substantial loss of virus neutralization, followed by immunoglobulin G. This observation may help design efficient antibody-based COVID-19 therapies and may also explain the increased susceptibility to SARS-CoV-2 of autoimmune patients receiving therapies that impair the production of immunoglobulin M (IgM).

Keywords: COVID-19; IgA; IgG; IgM; SARS-CoV-2; convalescent plasma; neutralization; spike glycoprotein.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Antibodies, Neutralizing / immunology
Antibodies, Viral / immunology
COVID-19 / epidemiology
COVID-19 / immunology
COVID-19 / therapy*
COVID-19 Serotherapy
Canada / epidemiology
Cohort Studies
Female
Humans
Immunity, Humoral / immunology
Immunization, Passive / methods
Immunoglobulin A / immunology
Immunoglobulin G / immunology
Immunoglobulin M / blood
Immunoglobulin M / immunology*
Immunoglobulin M / therapeutic use*
Male
Middle Aged
SARS-CoV-2 / immunology*
Spike Glycoprotein, Coronavirus / immunology
Young Adult

Substances

Antibodies, Neutralizing
Antibodies, Viral
Immunoglobulin A
Immunoglobulin G
Immunoglobulin M
Spike Glycoprotein, Coronavirus