Why do some people get “severe flu” or “severe COVID”? French researchers have found the answer. More precisely, they have understood the biological mechanism underlying the predisposition to severe viral conditions. “The French-American laboratory at Imagine Institute and Rockefeller University, coordinated by Professor Jean-Laurent Casanova and Dr. Laurent Abel, has long been interested in inter-individual clinical differences during infection, particularly with SARS-CoV-2 (Covid-19),” the researchers explain.
Severe viral infections: the role of type I interferons
Their study, recently published in the journal Nature, looks specifically at the production of autoantibodies that neutralize type I interferons.
Type I interferons are a group of proteins that are rapidly produced by the body’s cells in response to a viral infection and whose primary effect is to inhibit the replication of the virus in the infected cells.
Autoantibodies (antibodies that attack a person’s own body tissues and cells) directed against type I IFNs have been identified in around 15% of patients suffering from critical forms of COVID-19, 5% of severe cases of influenza, and 40% of cases of West Nile virus encephalitis: “By neutralizing the action of type I IFNs, these autoantibodies prevent the body from defending itself against these viruses. It is likely that these autoantibodies are the cause of a large number of other viral diseases,” the report states.
These autoantibodies are found in the general population (0.2 to 1 percent), with the frequency rising sharply from the age of 70, and are found in up to 5 to 10 percent of the elderly. This means that at least 100 million people worldwide are likely to carry autoantibodies that neutralize type I IFNs
Certain rare genetic diseases can lead to the development of these autoantibodies. For example, they are present in all patients with hereditary autoimmune polyendocrinopathy syndrome type 1 (APS-1).
What are the implications of this new research?
“Our work contributes to our understanding of the molecular, cellular, and immunological mechanisms that are defective in individuals suffering from severe viral infections. This was possible thanks to the identification of mutations in their genome that are responsible for a defective immune response. In the case of viral infections, the detection of autoantibodies that neutralize type I IFNs has important direct clinical implications for the diagnosis, treatment, and monitoring of patients,” the researchers conclude.
“The observed increase in the presence of these autoantibodies after age 70 is another related issue, and understanding the underlying mechanisms will benefit from research into the genetic causes responsible for the development of these autoantibodies,” they conclude.
Le Voyer, T., Parent, A.V., Liu, X. et al. Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency. Nature 623, 803–813 (2023). https://doi.org/10.1038/s41586-023-06717-x