MONTREAL, October 12, 2021 – Variants of the SARS-CoV-2 virus are currently of great concern: they are more contagious, more pathogenic and reduce the effectiveness of vaccines. A Montreal research team, led by Professor Étienne Caron at CHU Sainte-Justine and Professor Julie Hussin at the Montreal Heart Institute, wanted to understand how these mutations eluded our immune system during the first year of the pandemic. In their research they discovered that certain groups of individuals carrying the HLA-B7 genetic marker would be more prone to getting sick.

The results of this study are presented today in Cell Systems.

"We analyzed more than 330,000 sequences of the virus from 143 countries to study all mutant forms of the virus between December 2019 and December 2020, that is, before the arrival of the Delta variant and before mass vaccination," notes Étienne Caron, co-author of the study at CHU Sainte-Justine and the Université de Montréal.

"By combining bioinformatics tools, immunology and population genetics, we found that certain populations are more likely to be severely affected by mutated forms of the virus. Specifically, individuals with the HLA-B7 genetic marker, or 35% of the world's population, are more likely to have a less effective immune response to COVID-19," explains David J. Hamelin, a master's student in bioinformatics at the Université de Montréal and first author of the study.

HLA refers to a large family of antigens. Certain types of HLA are associated with autoimmune diseases such as ankylosing spondylitis, reactive arthritis or isolated eye diseases. An individual with these HLAs has a significantly higher risk of developing such diseases. 

"Based on our results, we hypothesize that HLA-B7 carriers have a weaker natural protective immune response against SARS-CoV-2, given the types of mutations that this virus naturally acquires during its evolution," says Julie Hussin of the Montreal Heart Institute and the Université de Montréal and co-author of the study.

As of September 2021, the COVID-19 pandemic has resulted in more than 4.6 million deaths and over 222 million confirmed cases worldwide.

In the global fight against the pandemic, this discovery has the potential to curb the spread of new variants and associated complications. "By better understanding why certain subgroups of individuals are sicker than others, we'll be able to develop and deliver more effective vaccines for these individuals that will trigger immunological memory – to provide protection for a lifetime," concludes Étienne Caron.

About this study

The article "The mutational landscape of SARS-CoV-2 variants diversifies T cell targets in an HLA supertype-dependent manner" by David J. Hamelin et al. was published online on October 2021 in Cell Systems. Étienne Caron is a researcher at CHU Sainte-Justine and assistant professor in the Department of Pathology and Cell Biology at the Université de Montréal. Julie Hussin is a researcher at the Montreal Heart Institute and IVADO Assistant Professor in the Department of Medicine at the Université de Montréal.

The study was funded by the Fonds de recherche du Québec – Santé, the Cole Foundation, the CHU Sainte-Justine Foundation, the Charles-Bruneau Foundation, the Canada Foundation for Innovation, IVADO, the Montreal Heart Institute Foundation, the Natural Sciences and Engineering Research Council of Canada and the Canadian Institutes of Health Research.

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