From the first moment that “Covid-19” came out of China, in January 2020, the eyes of the whole world turned to the rates and categories of deaths, despite the fact that the disease in the vast majority of cases passes without symptoms or like a colder than usual. In about a fifth of cases, hospitalization is required, and a quarter of these cases face critical problems that may eventually lead to death.
Our first information about the risk was related to (1) age and disease category, as it became clear during the first weeks of the spread in China and around the world that those over the age of fifty are more likely to develop serious symptoms of the disease, with rates of severity that escalate with age, especially if the advanced age Coinciding with chronic diseases such as diabetes, high blood pressure, or heart, kidney and liver diseases in general, people with these diseases, even if they are in younger age groups, are more likely to suffer from serious symptoms of the disease, up to death.
Subsequently, there was an association of the serious symptoms of “Covid-19” with other diseases (2), including, of course, most categories of lung diseases from asthma to cancer, and those who suffer from weak immunity for one reason or another (usually receiving immunosuppressive drugs due to a disease Some immune), with all that, incomprehensible relationships have emerged yet, for example, it turns out that the disease is more severe in obese people of all ages, and it has also been found that serious symptoms of the disease affect men in slightly greater proportions than women.
But despite all these results, it represented about 95% of all critical cases and deaths due to “Covid-19”, and the rest were for people other than the main dangerous groups, people belonging to small age groups, completely healthy and perhaps athletes, and did not suffer From any chronic disease, yet the disease was able to kill them, at that specific point geneticists intervened to answer the new question: Can genes play a role in determining the severity of “Covid-19” cases?
Well, DNA is - simply - the code of life, and it consists of a very long line of complex chemical letters that are present in all the cells of your body. Let's imagine that it is a long tape of one of the old videos, along the line of this brown tape the different scenes are recorded, here for example the hero meets With the heroine for the first time, and there he leaves her to travel in search of money, in another piece of the tape he returns to her in great regret.
DNA also consists of codes or codes that you inherited from your parents, here is a code that determines your height, there is another code that determines the color of your eyes, and a third code determines the nature of your hair.
In biology, these codes have a well-known name: genes, which are translated to become the components of your body and its mechanism of action, and therefore any possible tampering with genes is tampering with your body and its working mechanisms.
One of the first to be interested in the hypothesis of the relationship between genes and “Covid-19” was John Laurent Casanova, a professor at the American Rockefeller University, who, for several decades, examined a strange link that no one expected to exist, as we know that there are diseases, such as hemophilia or anemia. falciparum, a person inherits from their parents, but no one would have thought that infectious diseases might have a genetic or hereditary aspect.
According to Casanova, there are a number of imbalances in the genes responsible for the immune system in humans (there are two thousand out of about 25 thousand genes in humans), that can prevent it from dealing with a number of viral infections effectively, which pushes the disease to penetrate more heavily into the patient's body. Here, serious symptoms of disease appear, as well as death. Some of these types Casanova calls "Mendelian Infections" (3).
In a research paper published in September 2020 in the prestigious journal "Science", Casanova, along with a large team of researchers, genetically analyzed (4) the blood samples of more than 650 patients hospitalized with severe pneumonia associated with "Covid- 19” (14% of whom later died), with samples from another group of more than 530 people with asymptomatic “Covid-19” infection.
The team (5) looked for differences between the two groups across 13 genes that play a role in the body's defense against the influenza virus, and they found a clear difference in a number of genes that are actually responsible for the production of a system of 17 proteins called type I interferons, which They play an important, and very early, role in defending against invading viruses and stimulating other immune factors. In some patients, interferons are not produced at all.
This was followed by a research focus on that point that was neglected several months ago due to the chaos of the disease spreading in an accelerating pattern, as a research team (6) examined the last larger sample, consisting of about 1900 people of severe cases infected with the emerging coronavirus in Spanish and Italian hospitals, the study adopted According to previous analyzes, there is an advantage for people with blood type O compared to people with type A, which raises risk rates by 50%.
From this study, it was found that there are several genes, located on a site in the third human chromosome (and chromosomes are - in a simplified way - the shapes that genes take when stored in cells), that are associated with the severity of “Covid-19”, which are the same genes responsible for blood types, which means That there may indeed be a direct relationship between the genes in our DNA and the varying degrees of severity, up to death, in cases of "Covid-19".
Recently, a team from the GenOMICC Consortium - a global collaboration to study the relationship between genetics and serious diseases - identified five genes in particular (7) that are directly related to serious injuries, and they found that the problem is related to two aspects of the physical response, the first is related to With immunity and its ability to repel aggression (virus) appropriately, it is neither more nor less than normal, and the second is related to the inflammatory response to the disease when it comes to the body.
To date, this is the largest sample in this range, as the team examined 2,700 patients in 208 intensive care units in the United Kingdom, and compared their genetic tests with a number of healthy people, to show that defects in the genes called "IFNAR2", "TYK2" and "OAS1". DPP9 and CCR2 may be related to severe and critical symptoms of COVID-19.
This group of genes was really interesting (8), one of them, for example, which is "TYK2", is responsible for the amount of the immune response to the virus, but in terms of virulence, if this gene is defective, the immune response will not be limited to resistance to the virus attacking the body, But it will extend to attacking and damaging the body itself, which causes severe infections associated with the disease in the lung, heart and kidneys, called the “cytokine storm”, and it is now known to be the main cause of death for patients in critical cases of the disease.
On the other hand, the gene called "DPP9" plays a role in determining the amount of inflammation that is produced during the battle between our immune system on the one hand and the virus on the other hand, and the group of genes called "OAS", whose greater representation produces mechanisms that help prevent The virus copies itself inside the body, and the gene "IFNAR2" confirms the Casanova study that we talked about a while ago, as it helps to produce interferon early, which in turn helps to activate the immune system once infection is detected.
Of course, we cannot make a definitive and definitive link between genes and those cases in which “Covid-19” kills families while passing peacefully on other families, due to the complexity of the risk criteria for the disease, which include social and demographic factors, and reach gender and ethnicity. Income and access to quality health care, all of which play key roles in determining how this pandemic affects people.
In addition, even after these results are reached, direct confirmations, that is, linking a particular gene with its specific effect on the course of the disease and its severity, are still lacking, but day after day researchers collect results that tend towards the presence of genetic factors associated with the most symptoms The severity of “Covid-19” and the death rates due to it.
But in the end, the importance of this type of genetics discoveries does not stop only when explaining why some genetic factors may be related to the severity of the infection, but it may also one day be a reason for the production of new drugs that treat the disease, or directing drugs that were It already exists and is used to treat other diseases besides "Covid-19".
At that point, a drug (9) already used in cases such as rheumatoid arthritis, called "Baricitinib", can help as an antidote for severe inflammatory conditions caused by defects in the "TYK2" gene, and interferon therapy may also avoid defects. Currently, the Genomics team is working to direct a group of drugs already used in other diseases at Covid-19 because of their effects that help against defects in these genes.
Although we now have vaccines capable of resistance, obtained by more than a billion people around the world, it will not be the only line of defense against a disease that seems to continue with us for many years as a heavy guest knocking on our lives from time to time, and perhaps even after this pandemic is over That continues to strike our world hard, and relentlessly.
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Sources:
COVID-19: Who's at higher risk of serious symptoms?
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Human genetics of infectious diseases: between proof of principle and paradigm
Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
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Genomewide Association Study of Severe Covid-19 with Respiratory Failure
Genetic mechanisms of critical illness in COVID-19
Covid: Genes hold clues to why some people get severely ill
Genes could be key to new Covid-19 treatments, study finds