Scientists Identify Specific Gene Variant That Protects Against Severe COVID-19

Researchers have discovered a protective gene variant that seems to shield people from severe cases of COVID-19, and the finding could lead to new breakthroughs in fighting the coronavirus.

Since much earlier in the pandemic, scientists have been busily investigating how patient genetics influence the severity of a SARS-CoV-2 infection, exposing the inherited factors that appear to protect people from – or alternatively predispose them to – severe manifestations of the resulting disease.

Now that effort looks to have uncovered a promising new lead. Building upon 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 gene variant that can confer protection from critical illness.

In 2020, an analysis of genetic data primarily obtained from European people found that a locus of genetic variants in the OAS1/2/3 gene cluster was linked with several antiviral mechanisms. These variants conferred an approximately 23 percent reduced risk of becoming critically ill in cases of SARS-CoV-2 infection, in addition to other factors tied to virus susceptibility.

Nonetheless, it was unclear exactly what it was within this region of largely Neanderthal-inherited DNA that prompted the boosted protection against the coronavirus, meaning a causal gene or genes still remained to be identified – until now.

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

The scientists’ goal was to see if they could narrow the search further within the OAS1/2/3 cluster and determine the same protective signal in the comparatively shorter haplotypes of African people – who don’t carry the same complicated influx of Neanderthal and Denisovan genes in their own DNA, which makes identifying potentially causal variants much more problematic.

The approach worked. In an analysis of 2,787 COVID-19 cases alongside the genetic data of 130,997 individuals of African ancestry, the researchers identified an allele in the gene rs10774671 that confers protection against COVID-19 hospitalization in individuals of African ancestry, corresponding to what had previously been seen in Europeans.

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

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

Given that African ancestries do not usually feature Neanderthal haplotypes – unlike European populations, who adopted Neanderthal genes through breeding with Neanderthals during their long migration out of Africa – the common rs10774671 G variant exists today in both Africans and Europeans “as a result of their…