Severe symptoms of COVID-19 reduced by a genetic variant

symptoms of COVID-19

A new Swedish meta-study has discovered that a particular gene variant can protect against severe symptoms of COVID-19.

The research, pioneered by experts at the Karolinska Institutet, identified a specific gene variant that mitigated symptoms of COVID-19 from severe infection through analysing people from various ancestries. The team said their research demonstrates the importance of conducting clinical trials with people of mixed descent.

The study’s findings are published in Nature Genetics.

How genetics influence symptoms of COVID-19

Genetics play an essential role in how our bodies respond to a plethora of underlying diseases, including COVID-19, and influence how mild or severe the symptoms of the condition may be. Multiple studies on people predominantly of European ancestry identified that people carrying a specific segment of DNA have a 20% lower risk of developing a critical COVID-19 infection. This DNA segment encodes genes in the immune system inherited from Neanderthals in around 50% of all people outside of Africa.

However, this region of DNA is infused with numerous genetic variants making it challenging to distinguish the exact protective variant that may be a target of medical treatment for combating severe symptoms of COVID-19.

Searching for gene variants

To identify the special gene variant, the researchers looked for individuals carrying only parts of this DNA segment. Because the Neanderthal inheritance happened after the ancient migration out of Africa, the team saw an opportunity to focus on individuals with African ancestry who do not have Neanderthal heritage, meaning they do not have the majority of this DNA segment. However, a small piece of this DNA region is the same for both people of African and European ancestries.

The research discovered that people of mainly African ancestry had the same protection as those of European ancestry, enabling them to pinpoint a specific gene variant of particular interest.

Jennifer Huffman, the first author of the study and a researcher at the VA Boston Healthcare System in the US, said: “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.”

To conduct their study, the researchers examined 2,797 hospitalised patients of African ancestry and 130,997 people in a control group from six cohort studies; 80% of the people with African ancestry carried the protective variant. Subsequently, the results were compared to a previous, extensive meta-study of individuals of European heritage.

The team identified that the protective gene variant – rs10774671-G- determines the length of the protein encoded by the OAS1 gene. Previous studies showed that the longer variant of the protein is more effective at breaking down SARS-CoV-2 and therefore mitigates severe symptoms of COVID-19.

Co-author Brent Richards, the senior investigator at the Lady Davis Institute of the Jewish General Hospital and professor at McGill University in Canada, commented: “We are beginning to understand the genetic risk factors in detail, which is key to developing new drugs against COVID-19.”

Enhancing clinical research

Although the COVID-19 pandemic has inspired collaboration between experts worldwide, enhancing research into genetic risk factors in a wider diversity than in previous studies, most clinical research is still conducted on people of predominantly European descent.

Hugo Zeberg, the study’s corresponding author and assistant professor at the Department of Neuroscience at Karolinska Institutet, said: “This study shows how important it is to include individuals of different ancestries. If we had only studied one group, we would not have been successful in identifying the gene variant in this case.”


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