- Between 1 and 5% of severe patients with coronavirus are young and healthy.
- One of the avenues explored today by research is genetics.
- A study, led by Jean-Laurent Casanova, professor of pediatrics in Necker and New York, is interested in possible genetic mutations which would explain a vulnerability of these young patients in intensive care.
It is a small minority that questions a lot. Why do perfectly healthy children, adolescents, adults under 50 find themselves intubated in intensive care, overnight, because of this coronavirus? One of the explanations, explored in this article, is based on a disproportionate immune response, called "cytokine storm".
But another hypothesis is explored by Jean-Laurent Casanova, his team, but also his network of pediatricians around the world, and she sets out to explore possible genetic causes. Clearly, perhaps some young patients fall seriously ill because they have a genetic mutation in their genome that would make them more vulnerable to Covid-19. 20 Minutes interviewed Jean-Laurent Casanova, immunologist and professor of pediatrics at Necker Hospital (AP-HP) and at Rockefeller University, in New York, where he is currently.
Are you interested in “young” patients with coronavirus, that is to say?
We are interested in patients with severe forms of Covid-19, that is, without oxygen or intensive care, their life prognosis is engaged. In this population, you have 95 to 99% of patients who have risk factors: comorbidities or old age, or both.
The patients we study are those who are less than 50 years old and who have no comorbidity. They can be 15, 30 or 45 years old and run the marathon two weeks before ending up with pneumonia.
What is your study about?
It's a research study into the genetic basis of unexplained severe forms of Covid. Our hypothesis is that some of them carry genetic variations which account for a vulnerability to the coronavirus.
This hypothesis did not come out of a hat. It follows thirty years of work, which has identified dozens of genetic mutations explaining other serious viral infections: viral encephalitis, fulminant viral hepatitis, forms of malignant flu ... We have a problem, a hypothesis. The third step is how we test this hypothesis.
Precisely, how are these patients, quite rare therefore, "recruited"?
We organized, from February, an international network of centers, hospitals, universities, which recruit patients meeting these criteria, and who send blood samples to genome sequencing centers around the world. whole. Although these are rare forms - 1 to 5% of patients - the fact of organizing international recruitment allows us to have enough patients to analyze the genomes and search for "candidate genes".
Was this network of pediatricians around the world, used to study young patients, created during the pandemic? What is it used for ?
This network was pre-existing, but new doctors and new researchers have joined us since the pandemic. This is important for two reasons: there is only one planet and planetary problems require planetary solutions. The second is that as we study the rare forms of severe Covid, we need a recruitment that covers as many countries and hospitals as possible.
If two patients, one in the 15th arrondissement in Paris, and the other in Tokyo, carry the same mutation on the same gene, you cannot realize this if you analyze only the Paris patient or only the patient of Tokyo. In France, for the moment, we have recruited around twenty patients. But it is evolving very quickly.
How are you going to do it?
From a blood sample, we sequence the genome of the patients and look for genetic variations which, perhaps, are responsible for the serious forms of Covid-19. To assert this, it is necessary to establish a causal link between genetic variations and the disease. We are going to carry out a whole series of cellular and immunological studies. Which can take a long time.
If your study concludes with a genetic factor, what can we deduce?
When you understand a disease, it's easier to diagnose it. If your engine breaks down, it's better to understand the fault than tapping the hood. If there are genetic forms, it will shed light on the mechanics of the disease, and therefore it may help prevent or cure. To provide genetic counseling to affected families, too. If you're sick because you don't make a molecule and it can be injected, you can be cured.
Could there be other advances if this study was positive?
Yes, for the 90% of patients who have risk factors. Another hypothesis that interests us is the fact that perhaps, for these forms linked to known risk factors (tobacco, hypertension, overweight, diabetes ...), the cause would not be genetic, but the dysregulation would be even.
Let's take an example: you can break your leg by falling from the first floor or by skiing. In both cases, you have a broken leg, because there was a tension on the bone (mechanism), but it is not the same cause. Imagine that genetically, you make a serious Covid because you do not manufacture a molecule X. Perhaps a hypertensive patient of 90 years, because of old age and hypertension, does not manufacture little or not either same molecule X.
We will therefore seek both if there are genetic mutations that occur in the Covid, and what are these mutations.
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