key: cord-302920-jkr438p9 authors: Gasser, Romain; Cloutier, Marc; Prévost, Jérémie; Fink, Corby; Ducas, Éric; Ding, Shilei; Dussault, Nathalie; Landry, Patricia; Tremblay, Tony; Laforce-Lavoie, Audrey; Lewin, Antoine; Beaudoin-Bussières, Guillaume; Laumaea, Annemarie; Medjahed, Halima; Larochelle, Catherine; Richard, Jonathan; Dekaban, Gregory A.; Dikeakos, Jimmy D.; Bazin, Renée; Finzi, Andrés title: Major role of IgM in the neutralizing activity of convalescent plasma against SARS-CoV-2 date: 2020-10-09 journal: bioRxiv DOI: 10.1101/2020.10.09.333278 sha: doc_id: 302920 cord_uid: jkr438p9 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. should be performed early after disease recovery. Second, our results suggest that caution 121 should be taken when using therapeutics that impair the production of IgM. Anti-CD20 122 antibodies (B cell-depleting agents) are used to treat several inflammatory disorders. Their use 123 is associated with IgM deficiency in a substantial number of patients, while their impact on IgG 124 and IgA levels is more limited (Kridin and Ahmed, 2020) . In line with our data, recent studies 125 reported that anti-CD20 therapy could be associated with a higher susceptibility to contract An In Vitro Microneutralization 406 Assay for SARS-CoV-2 Serology and Drug Screening Decline of humoral 409 responses against SARS-CoV-2 Spike in convalescent individuals Potent neutralizing 413 antibodies from COVID-19 patients define multiple targets of vulnerability Rituximab for granulomatosis with 416 polyangiitis in the pandemic of covid-19: lessons from a case with severe pneumonia Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor COVID-19 in persons with multiple sclerosis 423 treated with ocrelizumab -A pharmacovigilance case series Post-rituximab immunoglobulin M (IgM) 426 hypogammaglobulinemia intracytoplasmic tyrosine residue of HIV-1 envelope glycoprotein is critical for basolateral 429 targeting of viral budding in MDCK cells