Your genes, COVID-19 and you | Coronavirus

I had fever, malaise and vomiting, he says in front of the Montreal restaurant 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 workingremembers 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 unknowns that persists about SARS-CoV-2: people apparently without particular risk factors nevertheless fall seriously ill.

Why someone had 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-19explains Dr. Brent Richards, endocrinologist at the Jewish General Hospital in Montreal.

Dr. Brent Richards, endocrinologist at the Jewish General Hospital in Montreal

Photo: Radio Canada

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

As a clinician, when you saw a 30-year-old young 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-infectiologist 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.

Illustration showing a DNA molecule.

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

Photo: iStock

It allows them to compare the entire genetic codes, or genomes, of large groups of patients. They are looking 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 is whether people with the letter C are more likely to have a severe form of COVID-19 than people with the letter Tsays Dr. Richards.

Using this method, the researchers have so far identified around 20 regions of the genome where variations are associated with being hospitalized due to COVID-19, or which increase the risk of infection by the virus.

Portrait of Guillaume Butler-Laporte.

Dr Guillaume Butler-Laporte microbiologist-infectiologist at McGill University

Photo: Radio Canada

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 coursecomments 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 the example of gastroenteritis. We know that there are families in which gastro strikes. But some people are sick and some aren’t, and that’s because they carry different molecules on their gut cells. […] I’ve been studying these questions for about a decade, but I think COVID brings 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 it 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 body.

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

Dr. Donald Vinh wears the white lab coat.

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

Photo: Radio Canada

With this in mind, among the genetic variants that can influence the risk of suffering complications from COVID-19, Dr. Brent Richards’ team has identified at least one, called OAS1, which seems promising.

It’s 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 find out if we could influence this gene to modify the risk of having severe COVID-19.explains the researcher.

Last March, the company Eiger Biopharmaceuticals, based in California, communicated the results – partial and not yet reviewed by peers – of a clinical trial it is currently conducting to verify the effect of a molecule which influences the 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 visitsrejoices, albeit cautiously, Dr. Richards.

For the moment, it is not a question of choosing who could receive this or that drug according to its 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 neighbor?

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

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

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