Genetic susceptibility and severity loci for Covid-19 disease

According to latest research by an international team, there are more than a dozen parts of the genome tied to SARS-CoV-2 infection susceptibility and/or the severity of the Covid-19 disease as revealed in a very recent report published in  Nature. 

Members of the COVID-19 Host Genetics Initiative brought together genetic and clinical data for as many as 49,562 individuals of European, African, Middle Eastern, South Asian, East Asian, or admixed American ancestry who were treated for Covid-19 infections in 19 countries, searching for variants that were overrepresented in these individuals compared to roughly 2 million SARS-CoV-2-free control individuals from the same populations, including research-consented 23andMe customers. The authors of this report highlighted the point that the working model of the present study of massive international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed, for any complex human disease.

Genome-wide association studies (GWAS)

With a handful of genome-wide association study meta-analyses, the team highlighted 13 loci with significant links to SARS-CoV-2 infection, including distinct loci linked to infection susceptibility or to Covid-19 severity. For example, the sites linked to infection in general included the chromosome 9 ABO blood locus, as well as a locus in the chromosome 3p21.31 region, near a locus implicated in Covid-19 disease severity in the past.

The team reported and provided possible clues for targeted therapy options in loci with genome-wide significant ties to Covid-19 tended to turn up in genes or pathways previously implicated in lung cancer or lung functions (such as for example, the FOXP4 gene previously tagged as a Covid-19 severity gene), autoimmune conditions, or inflammatory disease-related processes..

Furthermore, with the help of Mendelian randomization, meanwhile, the investigators saw causal associations between particularly severe Covid-19 cases and factors such as smoking or body mass index. On the other hand, past type 2 diabetes diagnoses did not appear to bump up infected individuals’ risk of severe disease, contrary to prior suggestions.

Ancestry: variation in susceptibility/severity loci

In any case, the better one gets at treating Covid-19, disease, the better equipped the medical community could be to manage the disease. Eventhough the the study included genetically diverse study groups, about 80 percent of the participants were  of European ancestry. In orderer to understand more profoundly this disease on a global scale, studies need to include  a larger number of individuals from other ancestry groups in order to ensure that the results apply to non-Europeans too and to identify other loci that might be associated with risk in people of other ancestries.

In fact, in the international dataset considered so far, the afore mentioned lung cancer-related FOXP4 gene appeared to be found at higher frequencies in individuals from East Asian, admixed American, and Middle Eastern populations compared to individuals of European descent. In addition, investigators are digging into the available data and continuing to collect additional genetic and clinical clues, to better distinguish between susceptibility and severity effects for specific loci, while searching for potential contributors to long-term symptoms in so-called Covid-19 “long-haulers” in an effort to better understand, manage, and treat SARS-CoV-2 infections down the road.

See here a sequence on the genetics of predisposition to and severity of Covid-19 disease: