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

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.

Anti-SARS-CoV-2 neutralizing monoclonal antibodies: clinical pipeline

“…Despite IgM, IgG and IgA are all capable of mediating neutralization, virus neutralization test titers correlated better with the binding levels of IgM and IgA1 than IgG. 64,65 The lack of evidence about the efficacy of IgG formulations (either polyclonal or monoclonal) against any respiratory pathogen 66,67 could theoretically be attributed to the lack of IgA. For this reason, Phase 3 trials testing IgG mAbs for COVID-19 prevention are eagerly awaited.…”

Comparison of SARS-CoV-2 IgM and IgG seroconversion profiles among hospitalized patients in two US cities

“…Studies have also demonstrated associations between neutralizing antibody titers correlated with those of IgG in patients with more severe COVID-19 symptoms [ 25 , 27 ] and in elderly and middle-aged patients relative to younger patients [26] . Interestingly, a recent study implied a crucial role of circulating IgM for SARS-CoV-2 neutralization [28] . While further studies are needed, the seroconversion kinetics demonstrated here may have important implications for demonstrating duration and efficacy of immunity, evaluation of convalescent plasma, and vaccine development [26] .…”

Immune responses to SARS-CoV-2 infection in Humans and ACE2 humanized mice

“…Similarly, the dynamics of the antibody profile in COVID-19 patients showed that IgG responses were detected in most patients, including both the severe and mild groups, between 8 and 12 days post onset; SARS-CoV-2 IgM and IgG response reached a peak in about 2 and 3 weeks 34 , remained at a high level for over 60 days, then declined within 90 days 35 . IgM plays a dominate role in the neutralizing titer early in the infection 36 ; compared with severe patients, the mild group showed much lower IgM response. Antibodies cross-reactive to SARS-CoV and SARS-CoV-2 were detected in patients with COVID-19 but not in patients with MERS.…”