🦠 Some serious viral infections explained by... an abnormality

Why, after an apparently mild viral infection, do some patients still develop severe forms?

Researchers show that the presence, in some patients, of a particular type of antibody disrupts the antiviral response. This study, published in the journal Cell, is part of an international collaboration involving a total of 60 doctors or researchers, and has identified the immune cells responsible for producing anti-type I interferon antibodies in these patients.


Type I interferons are essential proteins for antiviral defense. Some patients with severe forms of infectious diseases have high blood levels of antibodies directed against type I interferons. These autoantibodies are found in more than 10% of patients who develop severe pneumonia due to SARS-CoV2 infection (COVID-19).

Through the joint work of a consortium combining a unique mix of expertise in structural biology, protein-protein interaction modeling, and fine analysis of B lymphocytes, the researchers demonstrated that these immune cells producing autoantibodies are not induced in the context of COVID-19 but are already present before infection with SARS-CoV-2.

These cells also exhibit characteristics similar to those observed in certain genetic diseases affecting immune tolerance, particularly in their molecular targets on type I interferons and their ability to disrupt the antiviral response.

"These results suggest the existence, in otherwise healthy individuals, of an immune system abnormality that may promote the development of severe forms of certain viral infections. This discovery opens the way to new screening and prevention strategies to better identify people at risk and adapt their management," explains Matthieu Mahévas, last author of this study and researcher at the Institut Necker-Enfants Malades.