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Researchers at the University of Edinburgh have identified five genes, some variants of which are associated with the need for intensive care among people infected with COVID. Now that we know these genes, the proteins in question can be targeted with drugs that already exist.
Investigating the links between genetic differences and the course of disease immediately after clinical trials is the second best way to find effective treatments for a disease.
By identifying genes that clearly influence the severity of COVID-19 infection, we can analyze whether there are pre-existing and accepted drugs that target these genes.
And if we can find a drug like this
it may be available much earlier to treat severe COVID patients than any recently developed compound.
“The predisposition to life-threatening infectious diseases and conditions caused by an overactive immune system is known to run in families. In particular, susceptibility to respiratory viral diseases such as influenza is also inherited and is known to be related to certain specific genetic variants, ”write researchers from the University of Edinburgh in an article in the latest issue of the journal Nature.
Five genes that can be the basis of severe symptoms
By studying the DNA of a total of 2,700 patients seen in 208 intensive care units in the UK, the authors of the article identified five genes whose variants were associated with the most severe form of COVID disease. These genes, according to the researchers, function as two molecular processes,
the range of antiviral immunity and pneumonia is grouped.
The discovery will also help us better understand how SARS-CoV2 damages lung tissue.
Researchers from the GenOMICC International Consortium for the Study of the Genetics of Critical Diseases
genetic information in patients with severe COVID-19
compared to healthy subjects enrolled in other studies as controls. Control genomes were obtained from the UK Biobank, Generation Scotland and 100,000 Genomes genomic databases.
GenOMICC (Genetics of Intensive Care Susceptibility and Mortality) is a global consortium of intensive care physicians established in 2015 with the research goal of understanding how genetic factors affect SARS and influenza. , the need for intensive care in patients with sepsis and similar conditions.
This can make COVID nearly asymptomatic or life threatening.
The most notable difference between the genomes of patients in the intensive care unit with COVID and healthy volunteers was at five points: IFNAR2, TYK2, OAS1, DPP9 and CCR2 genes. So which variant of these genes does anyone have?
it may explain, at least in part, the severity of the disease.
As is now apparent, some are essentially asymptomatic through COVID infection, while others are in critical condition, and the reasons for the huge course differences are not entirely apparent.
After identifying key genes, the researchers were able to predict which drug treatment might help patients, since genetic variants can have similar effects to certain drugs that affect that gene.
For example, scientists have shown that a decrease in the activity of the TYK2 gene protects against severe COVID disease,
and anti-inflammatory agents belonging to the class of JAK inhibitors, such as baricitinib, can reproduce this effect.
An increase in the activity of the IFNAR2 gene has also been shown to have a protective effect as well, presumably because it mimics the effect of antiviral protective proteins released by cells of the immune system, interferons. However, for such treatment to be effective, intervention is needed in the early stages of the disease, the authors of the article warn.
It is not the virus but the immune system that damages lung tissue.
Based on their recently published results, the researchers argue that additional clinical trials should focus on drugs that specifically target these antiviral and anti-inflammatory pathways.
“This research beautifully realizes the promise of human genetics in understanding critically severe conditions. Like sepsis and flu
Also in COVID-19 it is our own immune system, not the virus, that damages lung tissue.
Our genetic findings serve as a compass in the forest of immune system signals and show the right path toward key drug targets, ”said Dr. Kenneth Baillie, project manager and critical care consultant at the Roslin Institute of the University of Edinburgh.
Our data provides direct guidance on
which drugs should be placed at the top of the list in planned clinical trials.
Because we can try even a few drugs at the same time, a good decision made early can save thousands of lives. “
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