Your genes, COVID-19 and you | Coronavirus

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Vos gè nes, COVID-19 and you | Coronavirus

Confronted with COVID-19, some people resist the disease well, while others, despite perfect health, fall seriously ill. Why? The answer would be in our genetic code.

Dominic Domen's health plummeted after catching COVID-19 .

At 37, Dominic Domen does not remember being sick, except for a kidney stone in the 1990s. However, in the spring of 2021, he caught COVID-19 and almost died.

I had a fever, malaise and vomiting, he says in front of the restaurant in Montreal where he cooks specialties from his country of origin, the Philippines. Then his condition deteriorated rapidly. My left lung collapsed, my liver and kidneys stopped working, recalls the former nurse, who has since regained his cheerful air.

According to his doctors, Dominic Domen suffered from a multisystem inflammatory syndrome caused by the virus. A rare complication of the disease.

Why him? This is one of the lingering unknowns about SARS-CoV-2: people with seemingly no particular risk factors do get seriously ill.

Why did someone have a serious illness and another person had almost no symptoms? They are the same age, the same economic situation, the same risk factors such as obesity, diabetes… But despite this, there is a big difference in the severity of COVID-19, explains Dr. Brent Richards, endocrinologist at the Jewish General Hospital in Montreal.

Dr. Brent Richards, Endocrinologist at General Hospital Montreal Jew

Dr. Richards is part of an international consortium of researchers called the COVID-19 Host Genetics Initiative. According to these experts, the explanation may well be in our DNA.

As a clinician, when you saw a 30-year-old man come into intensive care with lungs that were completely white from COVID, the question was always, why did this happen to him?, says his colleague, the microbiologist- infectious disease specialist at McGill University Guillaume Butler-Laporte. In these cases, in general, in medicine, what we say is that there must be something more. If we have eliminated the environment, the epidemiological factors, there is really just genetics.

Researchers have published several papers over the past few months that support the hypothesis that our genes may influence our response to COVID-19. To reach these conclusions, they draw on large biobanks that collect DNA samples from hundreds of thousands of people around the world, including people who have suffered from complications from COVID-19.

A person's genome contains all of their genetic material carried by the DNA located on the 23 pairs of chromosomes.

It allows them to compare the entire genetic codes, or genomes, of large groups of patients. They look in the billions of base pairs, usually represented by the letters A, C, G and T, for small variations that could explain the observed clinical differences.

With this information, we can see for example that a certain percentage of the population has a variation like a letter C in their DNA and the other part of the population has a letter T. And the question we are asking, this& #x27;is whether people with the C are more likely to have severe COVID-19 than people with the letter T, says Dr. Richards.

Thanks to this method, researchers have so far identified about twenty regions of the genome where variations are associated with being hospitalized because of COVID-19, or which increase the risk of infection with the virus.

Dr Guillaume Butler-Laporte microbiologist-infectiologist at McGill University

These are small additive effects. Some areas greatly increase the risk. Other regions increase it a little less. Then each person is somewhere on that spectrum. And then there are people who are very unlucky, of course, comments Dr. Butler-Laporte.

The idea that our genes can influence our response to infectious diseases is not new. Dr. Donald Vinh, microbiologist-infectiologist at the McGill University Health Center, gives an example of gastroenteritis. We know that there are families in which gastro strikes. But some people are sick and some people aren't and that's because they carry different molecules on the cells in their intestines […] I've been studying these questions for about a year. decade, but I think COVID puts them forward for the rest of the world, to recognize that genetics is important for infections in general and for COVID.

In his current work, Dr. Vinh is particularly interested in the luckiest among us – those seemingly impervious to the SARS-CoV-2 virus.

There are people who seem to be completely resistant, that is to say they have done tests, either PCR or rapid, which were always negative, and that is interesting because that suggests that these people are resistant not to disease, but even upstream of that, to infection. And we are looking for genetic or molecular reasons to explain this resistance, hoping that it could eventually give us tools to fight the pandemic, says the researcher.

To achieve this, it is not enough to identify the genes responsible, but also to understand their functions and the mechanisms they regulate in the organism.

The ultimate goal is to It's not just to identify genes or molecules that explain resistance, but to translate them into new treatments or drugs to minimize or prevent infection, adds Dr. Vinh.

Dr. Donald Vinh, microbiologist-infectiologist at the McGill University Health Center

< p class="e-p">With this in mind, among the genetic variants that may influence the risk of suffering complications from COVID-19, Dr. Brent Richards' team has identified at least one, called OAS1, that shows promise .

It is a gene that destroys the RNA of viruses that enter our cells. This is very important because there is a change in this gene that greatly increases its effectiveness in preventing the virus from reproducing […] And now we are working with specialists from a pharmaceutical company to whether we could influence this gene to alter the risk of having severe COVID-19, says the researcher.

Last March, California-based Eiger Biopharmaceuticals released the results – partial and not yet peer-reviewed – of a clinical trial it is currently conducting to test the effect of a molecule that influences OAS1 protein, produced by the gene of the same name.

With just one injection, they noticed a halving of hospital admissions, emergency room and intensive care visits, says Dr. Richards. p>

For the moment, it is not a question of choosing who could receive this or that drug according to their genetic code, but rather of making everyone benefit from the knowledge acquired thanks to our understanding of the influence of genes on our response to COVID-19.

But can we imagine that one day our genetic profile could be used to specify which drugs would be more useful , or more effective, for us in our fight against infection, rather than for our neighbour?

The research is not there yet, but, according to Guillaume Butler-Laporte , that's the next question. It opens the door to finding better therapies for many diseases, many of which have been neglected for a long time, believes the researcher.

The report by Gaëlle Lussiaà-Berdou and Yanic Lapointe is broadcast on the show Découverte on Sundays at 6:30 p.m. on ICI Radio-Canada Télé.

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