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Saturday, January 23, 2021

What genetic alterations discovered by scientists aggravate COVID-19

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One of the latest relevant scientific studies on the new SARS-CoV-2 coronavirus and the disease COVID-19 reveals that people who have alterations in genes related to the immune system are at higher risk of severe forms of COVID-19, by highlighting the genetic variants linked to the development of life-threatening diseases in coronavirus patients.

The study, which involved 2244 UK patients and went published in the prestigious journal Nature, helps scientists and doctors to develop new treatment strategies for people with severe COVID-19 and they suggest some existing drugs that could be useful to treat these critically ill patients. But fundamentally, The investigation seeks to unravel one of the great mysteries of this pandemic: why the coronavirus affects different people so differently, with conditions ranging from asymptomatic infection to death.

“This is a Incredibly interesting article that clarifies why some people are at higher risk of a mild infection turning into a life-threatening illness. Interestingly, at least one of the SNP genes (single nucleotide polymorphisms, the genetic mutation they are exploring) referenced here it is more common in people of Indian and African origin, which is consistent with the observation that people from these ethnic groups are at increased risk of having a poor outcome from COVID-19”Explained Dr. David Strain, senior clinical professor at the University of Exeter and chairman of the British Medical Association’s Medical Academic Staff Committee, who analyzed the published paper.

After a year of pandemic, scientists are still searching for answers on the new coronavirus - REUTERS / Bernadett Szabo

“However, one of the main limitations of this study is that they tried to exclude people who had previously tested positive for coronavirus. Ideally, to differentiate between those with susceptibility to severe disease, all controls would have also been exposed to the Coronavirus, and we would be comparing those who tested positive but only had mild illness with those who were hospitalized. Currently, the implications of this are limited. These data are useful for predicting those who are at risk, However, most of us don’t know what our genes are like. In the near future, however, additional interest may arise from a greater understanding of what these genes do. Knowing what they do can create greater opportunities to develop future treatments. For example, TYK2 gene is associated with inflammatory responses known to cause the ‘cytokine storm’ which is responsible for the death of the youngest patients who contract this condition, added the expert.

“The other area of ​​interest is association between a genetic predictor of adiposity (obesity) and poor outcomes. This suggests that the association may be genetic in origin, so lifestyle measures to address obesity may not be beneficial if this represents a predisposition rather than an effect of obesity itself. The authors themselves highlight the biases in the populations they enrolled in the study and their comparators, however, this is an important consideration in the future ”, Strain remarked.

Immune system functions

Genetic variants in certain ethnicities could favor severe COVID-19

The key to research in which 208 intensive care units in the United Kingdom have participated -more than 95% of those in the country-, resides in analyzing at least two functions of the immune system of our body. On the one hand, defense against viral infections, which has an important protective role in the initial phases of COVID-19. And on the other, inflammation reactions that aggravate the disease in more advanced stages.

Genetics influence the likelihood of severe COVID”, Stated Erola Pairó-Castiñeira, a computational biologist from Barcelona who currently works at the University of Edinburgh and the first author of the research. compared the genomes of critically ill patients with genomes of the general population. This allowed identifying seven genes that present differences between the two groups. Four of these genes (called IFNAR2, OAS1, OAS2 and OAS3) are important in the early phase of the disease, which is characterized by a rapid increase in the amount of virus in the body.

The experts explained that the alterations found in the IFNAR2 gene reduce the activity of interferons, a group of proteins involved in the initial response against viruses. The discovery suggests that an interferon treatment, if given early in the infection, could be effective in preventing COVID-19 from progressing to severe conditions. There are even experimental drugs that can act on the proteins produced by the OAS genes, the authors of the research point out in Nature.

The genetic alterations of COVID-19 would determine the severity of the disease - EFE / Marta Pérez / Archive

The other three genes that were identified (TYK2, CCR2 and DPP9) They appear in advanced stages of the disease, characterized by an excessive inflammatory reaction that damages the body itself. Drugs developed for rheumatoid arthritis that act on the activity of the TYK2 and CCR2 genes, such as baricitinib, have already been tested in combination with the antiviral remdesivir to treat severely COVID patients. According to results presented last week in The New England Journal of Medicine, mortality was 35% lower among patients who received the two drugs than among those who received remdesivir alone. Among survivors, the time from initiation of treatment to recovery was reduced from 18 to 10 days with the combination of the two drugs.

According to statistics, less than 3% of people who suffer serious complications from COCVID-19 have any of these genetic alterations. “This research is relevant to all people with severe COVID-19 because it reveals the molecular mechanisms that lead to complications. We are hopeful that this understanding will help us find drugs to treat all critically ill patients, ”concluded Kenneth Baillie, director of the work, University of Edinburgh.

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