COVID: an ancient genetic mutation protects against severe forms

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An international study has identified a specific genetic mutation that protects against severe forms of COVID-19. By involving patients from different genetic backgrounds, the researchers found the protective mutation in Europeans of Neanderthal descent and in Africans from sub-Saharan Africa, who do not have a common genetic heritage with Neanderthals.

The different forms of COVID-19 developed can vary greatly from person to person. To advance the understanding of the disease, genetic studies are essential. Thus, several studies have already shown that there are genetic risk factors in the response to SARS-CoV-2 infection. Another study has identified a group of genes responsible for the disease-linked risk of respiratory failure, inherited from our Neanderthal ancestors.

But there are also protective genes. A study published last year suggested that another set of genes inherited from Neanderthals reduced the risk of developing a severe form of COVID-19 by 22%. But the new study published in Nature Genetics goes further, to find the specific mutation that protects against severe forms. Furthermore, the appearance of the protective mutation dates back to a period before the divergence between our species and Neanderthals.

A genetic mutation shared by a common ancestor of Sapiens and Neanderthals

Among the novelties is a greater diversity of populations studied, in the genetic sense of the term: from Europe and Africa. “This study shows how important it is to include individuals of different ancestry. If we had only studied one group, we would not have been able to identify the gene mutation in this case,” said Hugo Zeberg, corresponding author of the study and assistant professor in the Department of Neuroscience at Karolinska Institutet University.

The analysis looked at a total of 2,787 hospitalized COVID-19 patients of African descent, as well as 130,997 people in a control group, from six cohort studies. In the end, 80% of people of African genetic heritage were carriers of the protective mutation. The results were then compared to those of a larger, earlier study of people of European descent.

Both populations share the same OAS1 gene mutation, called rs10774671-G, which confers better immune protection. “The fact that people of African descent had the same protection allowed us to identify the only DNA mutation that truly protects against SARS-CoV-2 infection,” says Jennifer Huffman, first author of the study and a researcher at VA Boston Healthcare. System in the United States.

How did the researchers come to this conclusion? Individuals from sub-Saharan Africa have almost no Neanderthal heritage in their genomes, while this heritage is frequently found in Europe. Extinct about 30,000 years ago, Neanderthals coexisted in Europe with modern humans in Africa, and sometimes mated there, hence this difference in genetic history. The similar protection observed in the two study populations allows the researchers to conclude that the allele responsible for this protection comes from a common ancestor, prior to the divergence of Neanderthals and Sapiens at least 500,000 years ago.

Towards new treatments against COVID-19

The next step will be to understand precisely what this genetic mutation expresses. According to the researchers, the mutation of the protective gene determines the length of the protein encoded by the OAS1 gene. Previous studies have already shown that the longer mutation of this protein is more efficient at breaking down SARS-CoV-2.

Specific treatments for severe forms of COVID-19 could emerge from this work, as co-author Brent Richards, a professor at McGill University in Canada, points out: “The fact that we are beginning to understand genetic risk factors in detail is essential for the development of new drugs against COVID-19”.

Nature Genetics

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