Although older people are more likely to suffer a severe or even fatal case of COVID-19 than younger people, they too can become infected with the SARS CoV-2 coronavirus and end up fighting for their lives in intensive care units. On the other hand, there are also people in the so-called “high-risk group” who are infected with SARS-CoV-2 but hardly notice anything. Why this is the case is still largely unexplained even after almost a year of the pandemic.
It seems clear that the individual immune response of the body plays a role, probably also the blood group or even the genes. British researchers have now identified five genes that could be linked to severe cases of COVID-19. They hope that these findings might potentially lead to treatments for the disease.
Damage to the lungs at a molecular level
Experts say that genetic information is the second-best way to determine after clinical trials which treatments for a disease could be successful. For example, existing drugs that are currently known to target gene activities offer clues as to which drugs should be used to treat COVID-19 in clinical trials.
Scientists from the University of Edinburgh, under the direction of the Roslin Institute, together with researchers from the MRC Human Genetics Unit, the Centre for Genomic and Experimental Medicine, and the Edinburgh Clinical Research Facility have now identified genes that are implicated in two molecular processes: Antiviral immunity and pneumonia. The scientists say that this breakthrough and “startling discovery” will help to understand how Covid-19 damages the lung at a molecular level.
“Just like in sepsis and influenza, in Covid-19, damage to the lungs is caused by our own immune system, rather than the virus itself,” says Dr. Kenny Baillie, head of research at the Roslin Institute. “. Our genetic results provide a roadmap through the complexity of immune signals, showing the route to key drug targets.” The findings would immediately reveal which drugs should be at the top of the list for clinical testing. ‘We can only test a few drugs at a time, so making the right choices will save thousands of lives.”
“Major differences in five genes”
As part of their study, GenOMICC consortium researchers examined the DNA of 2,700 patients suffering from severe cases of COVID-19 who had been treated in 208 intensive care units across the UK. They compared the genetic information with samples from healthy volunteers from other studies, such as UK Biobank, Generation Scotland, and the 100,000 Genomes Project. And they found significant differences in five genes of intensive care patients compared to samples from healthy volunteers: “The genes – IFNAR2, TYK2, OAS1, DPP9, and CCR2 – partly explain why some people become critically ill with Covid-19 while others develop hardly any symptoms,” the researchers say. The mutated genes IFNAR2 and OAS1 are linked to the innate immune system, the genes TYK2, DPP9, and CCR2 to severe inflammatory processes.
The researchers were able to predict the effect of medications on patients on the basis of these findings. For example, it was shown that a reduction in the activity of the TYK2 gene provides protection against COVID-19 or a potentially life-threatening disruption of the immune system that might be triggered by it. There is also good news where this is concerned. A drug already approved for the treatment of rheumatoid arthritis, baricitinib, significantly reduces this TYK2 activity.
The scientists also discovered that an increase in the activity of the INFAR2 gene is also likely to protect against COVID-19. This gene is believed to mimic the effect of treatment with interferon, whereby proteins are released by the immune system’s cells to defend against viruses. According to experts, however, the most important aspect of this type of treatment is “that patients need the treatment at an early stage of the disease in order for it to be effective.”
“We now hope that further understanding on Covid-19 will come from studying the genetics of symptom duration and how symptoms change over time in non-hospitalized patients,” said Professor Albert Tenesa, lead researcher at Coronagenes. “For this, it is vital that those that have or have had Covid-19 everywhere in the world join studies such as our parallel study Coronagenes.”
Drawing on the findings published in the journal Nature, the researchers say that clinical trials should focus on drugs targeting these specific antiviral and anti-inflammatory routes.
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