Walkers wearing masks at Stockport on September 16, 2020 in the UK.

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AFP

Between the loss of taste and smell and going to intensive care, the coronavirus is expressed in several ways depending on the patients.

These very different reactions are due to our genes, believe several researchers.

Nearly 15% of severe forms of Covid-19 disease can be explained by genetic and immune abnormalities leading to the failure of a powerful antiviral molecule naturally produced by the body in the event of infection, according to the work of a team Franco-American.

Genetic abnormalities to detect

Discoveries that could help identify people most at risk of developing a severe form, and better treat them, according to the researchers.

This research more specifically points to a defect in substances of the immune system, type 1 interferons (IFNs), the first line of defense against viral attack.

These conclusions are detailed in two articles published by the American journal

Science

.

"This is a defect in the production or action of type 1 interferons", explains Professor Jean-Laurent Casanova (Imagine Institute in Paris and Rockefeller University in New York), during a press conference in line.

Researchers have demonstrated in some patients genetic abnormalities (mutations of 13 genes) which decrease the production of type I interferons (3-4% of severe forms).

Men more concerned than women

They have also identified in other patients aged 25 to 87 years, a form of autoimmune disease, in this case the presence at very high levels in the blood of misdirected antibodies, called auto- antibody.

These neutralize the antiviral action of type 1 interferons (in at least 10% of severe forms of Covid) instead of attacking the virus.

This anomaly affects more men than women, according to the study, while autoimmune diseases (dysfunction of the immune system that causes it to attack some of its normal constituents) generally affect women much more. .

The study also suggests that the frequency of these antibodies increases with age.

Interferons belong to the family of cytokines, substances produced in particular by cells of the immune system, in response to infection.

The initial lack of type 1 interferon subsequently causes the body to overreact to compensate for this lack.

It thus produces other cytokines causing a fatal inflammatory runaway, "the cytokine storm", observed in very serious cases of Covid.

Medicinal solutions exist

Prof. Casanova led this research with Prof. Laurent Abel (Imagine Institute / Inserm), in collaboration with Helen Su from the American National Institute of Allergies and Infectious Diseases (NIAID / NIH).

These autoantibodies are absent in people who develop a mild form of the disease.

And they are rare in the general population: 0.33% according to an analysis of a sample of more than a thousand healthy people, a frequency fifteen times lower than that observed in patients with severe forms.

The early administration of interferons to these patients could be a therapeutic avenue.

The good news is that these drugs have been available for decades, and seemingly have no noticeable side effects if taken for a short time.

For patients with these bad antibodies, we could use an interferon that they do not neutralize.

They could benefit from plasmapheresis (removal of the liquid part of the blood containing the antibodies in particular), or other treatments that can reduce the production of these antibodies by the B lymphocytes.

These findings are the first published results of the international consortium of the COVID Human Genetic Effort created with the aim of identifying the genetic and immunological factors that can explain the occurrence of severe forms of the disease, in which hospitals in some fifty countries participate.

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