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Recently, the Franco-American Laboratory of Human Genetics of Infectious Diseases at Institut Imagine (Inserm, University Paris Cité, AP-HP) and the Rockefeller University, led by Professor Jean-Laurent Casanova and Dr. Laurent Abel, published several articles on anti-type I interferon (IFN-I) autoantibodies. These autoantibodies are present in a small proportion of the general population before the age of 65, and cause severe forms of viral infections, such as in encephalitis in response to the West Nile virus. The team is simultaneously trying to understand the genetic factors predisposing to the production of these anti-IFN-I autoantibodies.
Paul Bastard, a medical researcher in the laboratory, focused on the young population. He and the team assessed the presence of these autoantibodies in more than 180 children from nine different countries with severe COVID-19 pneumonia. This study is the first to focus on such a young population. IFN-I neutralizing autoantibodies are found in around 10% of children with severe SARS-CoV-2 pneumonia, which is much higher than the frequency observed in the general population. The presence of anti-IFN-I autoantibodies therefore considerably increases the risk of developing severe SARS-CoV-2 infection, even in children.
There are several different IFN-I (16 in total), and the study also identified a different response depending on which IFN-I was blocked by autoantibodies. In fact, the probability of developing potentially fatal COVID-19 pneumonia is higher in children with autoantibodies against IFN-α than in those with autoantibodies blocking IFN-ω, which nevertheless plays an important role in the immune response to viral infections.
Finally, by measuring autoantibody levels in over 2,000 children who had not been infected with SARS-CoV-2, the authors showed that the frequency of anti-IFN-I autoantibodies in children was close to that in young adults.
This research has enabled us to improve our understanding of the immune response to COVID-19, while highlighting the key role of type I IFNs to fight the virus. The identification of these autoantibodies and an understanding of the molecular and cellular mechanisms leading to their synthesis could enable the prevention of viral infections such as COVID-19 pneumonia or influenza in at-risk populations.
DOI: 10.1084/jem.20231353