why rare people vaccinated with two doses have severe forms

It was a scientific and medical enigma. Why do some people develop severe forms of Covid-19 despite a two-dose vaccine? This, despite the fact that this vaccination has induced in his body the production of antibodies capable of neutralizing SARS-CoV-2. For almost a quarter of them, it is an immune deficiency, according to the results ofan international paper published in June in the journal science immunologyY piloted by a French team.

Cases of these patients are, however, very rare. A total of 48 of them were recruited -in Greece, France, Turkey, Macedonia, Ukraine and the United States- in a study coordinated by teams from Inserm, Paris Cité University and the Imagine Institute (Necker-Enfants Malades Hospital AP-HP and Rockefeller University of New York). Aged 20 to 86 years (median age: 53; 34 men and 14 women), all had a severe to critical form of Covid-19 that landed them in intensive care, following infection with the Delta variant, despite two dose of RNA vaccine. .

See the charts: Covid-19: the dashboard of the epidemic

The authors first verified that, in these patients, the vaccine had been effective: the objective was to discover the origin of the severe forms not linked to a failure of the vaccination. Six patients were excluded from the study because the vaccine did not induce neutralizing antibodies in them, either because they were taking immunosuppressive treatments, or because they were infected with HIV or were being treated for lymphoma…

In the remaining 42 patients, the authors looked for the presence of an entirely different category of antibodies: antibodies that target certain molecules in our immune system, the type 1 interferons (IFN-1). In the face of a viral infection, these IFN-1 constitute the first line of defense of our body. In rapid response to a virus attack, they are produced by our cells and inhibit the replication of the virus in our infected cells.

Action of autoantibodies

Why look for these antibodies? A number of previous studies had been conducted in unvaccinated people. Around 20% of cases of severe pneumonia, resulting from SARS-CoV-2 infection, are explained by abnormalities (of genetic or immunological origin) that weaken the immune response carried by type I interferons, they had shown. researchers.

But these were unvaccinated people. What happens to people who have received two doses of vaccine? The authors reveal that 24% of them (10 of 42) present “autoantibodies” neutralizing the action of type 1 interferons (autoantibodies are antibodies that attack an individual’s own components). These autoantibodies were present before SARS-CoV-2 infection. Apart from this peculiarity, these patients had no other immunological deficits or a history of serious viral infection.

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