Covid, who risks the most? What the DNA study says

There are 13 points in the human genome strongly associated with the risk of Coronavirus infection or the severity of Covid. This was stated by one of the largest association studies on the entire Covid genome, published today in the journal ‘Nature’: almost 50,000 Covid patients involved, 2 million checks on non-infected citizens, over 3,500 researchers for 61 sub-studies from 25 countries .

In March 2020, while the lethality of the SARS-CoV-2 virus in Italy is extraordinarily higher than elsewhere, doctors realize that not all people fall ill with the same severity. Hence a question: What genetic factors influence the development of a serious or fatal disease, rather than mild or no symptoms at all? In April 2020, 4 Humanitas researchers publish in open access one of the first studies on the genetics of Covid-19, a work soon deepened thanks to a consortium between Italy, Spain, Germany and Norway. Like them, so many scientists around the world are starting to search genes for an answer to the clinical question. The study published today also encapsulates those early efforts. This major global effort, ‘Covid-19 Host Genomics Initiative’, has made it possible to identify 13 loci, or locations in the human genome, which are strongly associated with the risk of Sars-CoV-2 infection or disease severity. The findings could help identify targets for future therapies and demonstrate the usefulness of genetic studies in understanding infectious diseases.The Covid-19 Host Genomics Initiative was founded in March 2020 by Andrea Ganna, group leader at the Institute for Molecular Medicine Finland (Fimm) of the University of Helsinki, and Mark Daly, director of Fimm and a member of the Broad Institute of MIT and Harvard in Boston, Massachusetts. The initiative has become one of the largest collaborations in the field of human genetics. In the Milan area, in addition to Humanitas, the University of Milan and the University of Milan-Bicocca participated, collaborating in a project called Genius (Genetics Against Coronavirus), also supported by a donation from Intesa Sanpaolo. “We have been much more successful than past experiences in understanding the role of genetic diversity because we have participated in a concerted effort to reach populations around the world,” says Stefano Duga, researcher at Humanitas and professor of molecular biology at Humanitas University. “There is still a lot of work to be done, but we are on the right track to better understand this disease,” he adds. Of the 13 loci identified so far by the global consortium team, two had higher frequencies among East Asian patients. or South Asian than those of European origin. One of these two loci, in particular, is close to the Foxp4 gene, which is linked to lung cancer. The Foxp4 variant associated with clinically severe forms of Covid-19 increases gene expression, suggesting that gene inhibition could be a potential therapeutic strategy. This underlines the importance of analyzing samples from populations with different genetic backgrounds. Other loci associated with severe Covid-19 include Dpp9, a gene also involved in lung cancer and pulmonary fibrosis, and Tyk2, which is implicated in some autoimmune diseases.Although vaccines confer protection against infection, there is still a significant room for improvement in the treatment of Covid-19, which can take advantage of the results of genetic analyzes. “The better we are able to treat Covid-19, the more the medical community will be able to manage the disease and its impact on society – highlights Rosanna Asselta of Humanitas – To this end, the global consortium has made the collected data immediately available to the scientific community, in order to speed up research by other scientists as much as possible. in understanding the molecular mechanisms of the disease, to use already existing drugs (the so-called ‘drug repurposing’) that could lead to rapid mind about new therapies “.

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