Scientists identify specific genetic variant that protects against severe COVID-19

Researchers have discovered a variant of the protective gene that appears to protect people against severe cases of COVID-19, and this discovery could lead to new breakthroughs in the fight against the coronavirus.

Since much earlier in the pandemic, scientists have been actively studying the influence of patient genetics on the severity of a SARS-CoV-2 infection, exposing the hereditary factors that appear to protect people against – or predispose them to – – severe manifestations of the resulting disease .

Now that effort seems to have uncovered a promising new lead. Building on findings from late 2020 that revealed numerous genetic mechanisms linked to life-threatening cases of COVID-19, an international team of researchers has identified a specific genetic variant that may confer protection against serious disease.

In 2020, an analysis of genetic data primarily obtained from Europeans revealed that a genetic variant locus in the OAS1/2/3 gene cluster was linked to several antiviral mechanisms. These variants conferred an approximately 23% reduced risk of becoming seriously ill if infected with SARS-CoV-2, in addition to other factors related to susceptibility to the virus.

Nevertheless, it was unclear exactly what it was in this region of DNA largely inherited from Neanderthals that prompted the enhanced protection against the coronavirus, meaning that a causative gene or genes had yet to be identified – until now.

In a new study, researchers compared information from people of different ancestries – looking at genetic data sets of people from African and European lineages.

The scientists’ goal was to see if they could further refine the search in the OAS1/2/3 group and determine the same protective signal in the relatively shorter haplotypes of Africans – who do not carry the same complicated Neanderthal influx. and Denisovan. genes in their own DNA, which makes the identification of potentially causal variants much more problematic.

The approach worked. In an analysis of 2,787 COVID-19 cases alongside genetic data from 130,997 people of African descent, researchers identified an allele in the rs10774671 gene that confers protection against COVID-19 hospitalization in people of African descent, consistent with what had been seen previously. among Europeans.

“The fact that people of African descent have the same protection allowed us to identify the single DNA variant that actually protects against COVID-19 infection,” says first author and genomics researcher Jennifer Huffman. of the VA Boston Healthcare System.

The variant in question – called rs10774671 G – confers protection against COVID-19 severity independent of other associated alleles in non-African populations, the researchers say, and their analysis suggests it is likely the only causative variant. behind the protective effect.

Since African ancestors generally do not exhibit Neanderthal haplotypes – unlike European populations, which adopted Neanderthal genes by interbreeding with Neanderthals during their long migration out of Africa – the common variant rs10774671 G exists today among Africans and Europeans today “as a result of their heritage”. of the common ancestral population of modern humans and Neanderthals,” the researchers write in their paper.

“Such variants have existed in modern humans for about half a million years and therefore co-segregate with different variants than when derived from gene flow from Neanderthals to modern humans who s was produced about 60,000 years ago.”

Although the variant appears to have been carried by humans for a very long time, it would not have been easy to find, given the complexity of genetic analyzes like this – unless populations of different types are compared, c is to say.

“This study shows how important it is to include individuals of different ancestry,” says lead researcher and evolutionary geneticist Hugo Zeberg of the Karolinska Institute in Sweden.

“If we had only studied one group, we would not have been able to identify the gene variant in this case.”

Although much remains to be studied around rs10774671 G, the researchers suggest that the protective effect is due to the variant’s effect on the OAS1 gene, encoding a longer OAS1 protein that is more efficient at breaking down the SARS-CoV-2 than the unmodified form.

If they’re right, this discovery could be an important step towards new types of treatment that could boost the immune response in the same way.

“The fact that we are beginning to understand genetic risk factors in detail is essential for developing new drugs against COVID-19,” says lead researcher and geneticist Brent Richards of McGill University in Canada.

The findings are reported in Natural genetics.

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