Antibodies COVID-19: Canadian Study Finds That IgM Antibodies Are More Important For Fighting SARS-CoV-2 Coronavirus.
A Canadian study last month led by by Université de Montréal professor Dr Andrés Finzi, holder of a Canada Research Chair in Retroviral Entry, and Dr Renée Bazin, director of innovation at Héma-Québec, showed that the neutralization capacity of antibodies produced by a SARS-CoV-2 infected person declined after six weeks, as the person recovers.
In a new follow study, the same team showed that this decline is related to the disappearance of a family of antibodies called immunoglobulin M or IgM, in blood plasma.
In this new study, the study team 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. The team 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.
The study findings are published on a preprint server and have yet to be peer reviewed. https://www.biorxiv.org/content/10.1101/2020.10.09.333278v1
The study findings shows that IgM antibodies play a key role in SARS-CoV-2 coronavirus neutralization and are part of the arsenal used by the immune system to fight the infection.
In past studies, the study team had observed that the drop in neutralization activity over time correlated with the decrease in antibodies specific to the virus's Spike, the glycoprotein S.
The study team had also noticed that this decrease was more closely associated with the disappearance of IgM, a family of antibodies representing approximately 5% of all antibodies in plasma.
In this new study, the researchers selectively removed IgM from the plasma of 25 volunteers who had recovered from COVID-19 and they tested their neutralization capacity. The observation was clear ie the absence of IgM significantly reduces the neutralization power of the plasma and shows their major role in this immune response.
Present vaccine development currently focuses on stimulating the production of antibodies. Antibodies, including IgM are only one dimension of our immune system that helps us fight viral infections.
Better understanding how our immune system succeeds in getting rid of the virus is important in knowing what types of immune responses the vaccines should elicit.
In the researcher’s laboratories, they also studied how long these immune responses last, because this can provide evidence-based data on whether a booster dose could be needed in the context of a vaccination. In a pandemic, this is crucial information for public health authorities.
The study team is continuing to study the immune response of people infected by SARS-CoV-2 over longer time periods to better understand how long the response lasts. They are also evaluating other mechanisms through wh
ich antibodies could fight this virus.
In terms of development, the team is working on developing monoclonal antibody cocktails that could be administered to COVID-19 patients.
The team also warned that the study results suggest that caution should be taken when using therapeutics that impair the production of IgM. Anti-CD20 antibodies (B cell-depleting agents) are used to treat several inflammatory disorders. Their use is associated with IgM deficiency in a substantial number of patients, while their impact on IgG and IgA levels is more limited. https://pubmed.ncbi.nlm.nih.gov/31917267/
In line with the study data, recent studies reported that anti-CD20 therapy could be associated with a higher susceptibility to contract SARS-CoV-2 and develop severe COVID-19.
Whether this is associated to the preferential depletion of IgM-producing B cells by these treatments remains to be shown. https://pubmed.ncbi.nlm.nih.gov/18163518/
Nevertheless, our results suggest that IgM levels should be investigated as a biomarker to stratify patients on immunosuppressive therapies at higher risk for COVID-19.
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