Why do some young people end up in intensive care because of Covid-19 when other people of the same age do not even realize they have been infected? The answer is partly written in our genes and an immense international collaboration is in the process of unveiling it. This is the Covid-19 Hosts Genomics Initiative (COVID-19 Host Genomics Initiative), a group of researchers from around the world who were interested not in the genomics of Sars-CoV-2 but in that of people infected with the coronavirus. They pooled data from 46 studies, done in 19 different countries by a total of 3,300 researchers, in a study published on July 8 in the newspaper Nature. They reveal 13 genetic mutations that would increase the risk of being infected with the virus or developing severe forms of the disease.
13 mutations revealed
“Even though infectious diseases are not heritable, the way we respond to infection may depend on our genetics ” explain to Sciences and the Future Andrea Ganna, geneticist at the Institute of Molecular Medicine of Finland (FIVE) and coordinator of this initiative. In order to understand the reasons why the severity of Covid-19 can vary so much between people with the same risk factors, the researchers studied the genomes of 49,562 patients with Covid-19 (three quarters of whom are of Caucasian origin) . And they compared them to two million healthy subjects, from other studies or from genomics companies like 23andMe.
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They thus found 13 mutations that could have an impact on Covid-19: nine mutations with a plausible biological mechanism to influence the severity of Covid-19, such as mutations in the DPP9 and FOXP4 genes which have already been recognized to increase the risk of developing lung disease, or a mutation in the TYK2 gene, linked to autoimmune diseases. And four other mutations that would rather have an impact on the probability of being infected with the virus. According to Andrea Ganna, the initiative will continue to add sequences to its analysis as long as there are cases to study, in particular to understand the genetic factors behind the long Covid.
Leads for new treatments
Even though the detection of these mutations could help identify the patients most at risk of developing severe forms of the disease, Andrea Ganna does not believe that this knowledge could be used for this short-term goal: “Healthcare facilities don’t necessarily have the necessary equipment for this type of detection, and there are other factors that are easier to measure clinically to predict a patient’s risk, so I don’t think we are. will use it for this during this pandemic ”, he admits. On the other hand, this knowledge can be useful for the repositioning of drugs already known to treat conditions linked to these mutations, such as certain pulmonary or autoimmune diseases. “Being realistic, it is very likely that Covid-19 will remain a major health problem for a long time, regretted Mark Daly, director of FIMM and co-director of the initiative in a Press release. So any therapeutic approach that we develop this year, for example by repositioning drugs thanks to this genetic knowledge, could have a very big impact ”.
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