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

TLDR: It is found that depletion of immunoglobulin M was associated with the most substantial loss of virus neutralization, followed by immunoglOBulin G, which 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 IgM.

Abstract: Characterization of the humoral response to SARS-CoV-2, the etiological agent of Covid-19, is essential to help control the infection. In this regard, we and others recently reported that the neutralization activity of plasma from COVID-19 patients 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 selected plasma from a cohort of Covid-19 convalescent patients and selectively depleted immunoglobulin A, M or G before testing the remaining neutralizing capacity of the depleted plasma. We found that depletion of immunoglobulin M was 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 IgM.

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Table 1. COVID convalescent plasma donor’s characteristics 217

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Major role of IgM in the neutralizing activity of convalescent plasma 1 against SARS-CoV-2 2 3 4 Romain Gasser, Marc Cloutier, Jérémie Prévost, Corby Fink, Éric Ducas, Shilei 5 Ding, Nathalie Dussault, Patricia Landry, Tony Tremblay, Audrey Laforce-Lavoie, 6 Antoine Lewin, Guillaume Beaudoin-Bussières, Annemarie Laumaea, Halima 7 Medjahed, Catherine Larochelle, Jonathan Richard, Gregory A. Dekaban, Jimmy D. 8 Dikeakos, Renée Bazin, Andrés Finzi 9 10 11 1 Centre de recherche du CHUM, Montréal, QC H2X 0A9, Canada 12 2 Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, 13 Montréal, QC H2X 0A9, Canada 14 3 Héma-Québec, Affaires Médicales et Innovation, Québec, QC G1V 5C3, Canada 15 4 Biotherapeutics Research Laboratory, Robarts Research Institute, London, Ontario, NGA 16 5B7, Canada 17 5 Department of Microbiology and Immunology, University of Western Ontario, London, 18 Ontario, N6A 5B7, Canada 19 6 Héma-Québec, Affaires Médicales et Innovation, Montréal, QC H4R 2W7, Canada 20 7 Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, QC 21 J1H 5N4, Canada 22 8 Department of Neurosciences, University of Montreal, Montreal, QC H2X 0A9, Canada 23 9 Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, 24 Canada 25 10 These authors contributed equally 26 27 * Correspondence: renee. bazin @ hema-quebec. qc. ca ; andres. finzi @ umontreal.