The main causes of complications of Covid-19 are based on risk factors such as age, cardiovascular disease or the presence of diabetes. But how to explain the severe forms of the disease in patients under 50 years of age and without any pathology before infection with SARS-CoV-2?
Researchers from Inserm and the University of Strasbourg investigated the genetic pathway to answer this question. how ? By analyzing the medical files of 72 patients, divided into two groups: “One made up of patients in intensive care with acute respiratory distress syndrome and the other for patients hospitalized in the so-called traditional sector, suffering from a less severe form of Covid-19,” the scientists detail. The control group was composed of 22 healthy individuals.
Important point: the strong restriction of the inclusion criteria. “We chose to focus on a small but well-defined group of patients, excluding confounding factors such as age or certain diseases, so that we could study the molecular and genetic mechanisms directly associated with severe forms, which are exclusively associated with viral infection and not with other pre-existing risk factors,” he identifies. Professor Siamak Bahram, one of the study’s authors
600 gin, 5 then 1
Step Two: Identify common genes for patients with COVID-19 complications, using the powers of artificial intelligence***. Thanks to algorithmic recognition, the machine made it possible to isolate “600 genes involved in the evolution towards critical forms of Covid-19”. The exact selection made it possible to keep 5 … and then 1, called ADAM9.
In the laboratory, the scientists then observed the effect of inhibiting the ADAM9 gene, which led to “a decrease in the amounts of SARS-CoV-2 virus in these cells, as well as a decrease in the replication of the virus, confirming its importance in serious diseases. But also its potential as a therapeutic target.”
Further work would be necessary to confirm this point on a larger sample. But the ADAM9 gene is already on the testing platform in other therapeutic areas: “Clinical oncology trials are already underway to test the monoclonal antibodies that exactly inhibit ADAM9. Therefore, longer-term therapeutic repositioning strategies can be considered.”
* Unit U1109 “Molecular Immunology and Rheumatology”
** PU-PH, Director of Unit 1109 at Inserm, Head of the Strasbourg Interdisciplinary Thematic Institute for Precision Medicine and Head of the Department of Biological Immunology at the University Hospitals of Strasbourg
*** Partnership with researchers from Genuity Science (Boston, USA), and University of Southern California (Los Angeles, USA)
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