New research reveals gene variants that could cause life-threatening Covid-19 illness
Two recent studies that looked at the genomes of people who were hospitalised with Covid-19 have shed more light on why some people become seriously ill.
Study one: Serious illness
The latest results from the GenOMICC study, published in Nature, identify 16 genetic variants that make people who carry them more likely to develop serious or life-threatening illness from SARS-CoV-2 infection.
The study, led by Professor Kenneth Baillie at the University of Edinburgh in partnership with Genomics England, is the largest of its kind, having sequenced whole genomes from almost 7,500 intensive care patients with Covid-19 from hospitals across the UK.
This data was used in a genome-wide association study (GWAS) and compared with genomes from people who had mild Covid-19 symptoms, and with a control group who had not had the virus.
The identified variants were in genes associated with different aspects of the illness, including immune signalling, blood clotting and inflammatory responses.
Study two: Kidney damage
A separate study has identified two genetic variants that can double a person’s risk of kidney complications during SARS-CoV-2 infection. Both variants disproportionately affect people with African ancestry.
The study looked at the genomes of nearly 1,000 US army veterans who had been hospitalised with Covid-19. The researchers found that people with both variants in the apolipoprotein L1 (APOL1) gene had double the chance of developing severe kidney damage than those with one or neither of the variants. Of the patients who carried both variants, over 50% developed acute kidney injury and 19% died.
In undertaking the study, the researchers were aiming to shed light on health disparities associated with Covid-19 outcomes, notably the higher incidence and severity of acute kidney disease in Black patients.
Both APOL1 variants are more common in people with West African ancestry and were already known to be associated with chronic kidney disease. The study found, though, that even patients with no kidney problems prior to developing Covid-19 were at increased risk if they carried both variants.
From genome to clinic
Studies such as these are already having an effect on how Covid-19 is managed and treated, with research from the GenOMICC community having already led to clinical progress.
Last year, the group suggested that a drug called baricitinib, usually used to treat arthritis, could be used to target a gene they had shown was involved in inflammatory organ damage in critically ill Covid-19 patients.
The Randomised Evaluation of Covid-19 Therapy (RECOVERY) clinical trial headed by the University of Oxford has since produced results showing that baricitinib reduces the death rate among hospitalised Covid-19 patients by 13–20%.
As with all GWAS studies, the accuracy of the results can be limited for groups of people who were poorly represented in the dataset used. Genomics England chief medical officer Dr Richard Scott said that this had been a major consideration:
“All those involved in the study went to great efforts to engage with all communities within the UK – including groups that have historically been under-represented in medical studies. The inclusive element of our work has generated meaningful results for everyone in the country.”
Read our article to learn more about the importance of diverse and representative genomic datasets