The research was conducted by a Franco-American team led jointly by Jean-Laurent Casanova and Laurent Abel within the epidemiology department of Rockefeller University Hospital in New York and the Laboratory of Human Genetics of Infectious Diseases at Institut Imagine in Paris (‘HGID Lab’, Paris University/INSERM, Necker Hospital for Sick Children).
Duration of the project: 2020-2023
The results of the research into the causes of lethal COVID-19 cases, led by Jean-Laurent Casanova, head of the Laboratory of Human Genetics of Infectious Diseases at the Imagine Institute in Paris and Rockefeller University in New York, with the support of the SCOR Foundation for Science, confirm that monogenic inborn errors of immunity (IEI) and monogenic inborn variants of resistance (IVR) explain fatal infections and resilience to infection exposure.
During the COVID-19 pandemic, there has been stunning inter-individual clinical variability among infected individuals, ranging from asymptomatic infection to lethal coronavirus infectious disease-19. The importance of monogenic lesions governing immunity to infection is already well established for lethal viral infections as well as for resistance to infection in humans. The Casanova-Abel research started from the assumption that monogenic inborn errors of immunity (IEI) and monogenic inborn variants of resistance (IVR) may underlie respectively fatal cases and resilience cases.
Based on an international sample of 5500 patients infected with Covid-19 pneumonia, the Casanova-Abel research found that auto-antibodies against type I IFNs explain about 15% of critical COVID-19 pneumonia. These auto-antibodies preexist infection, and provide a major increase in the risk of developing critical COVID-19. The research confirms the role of monogenic inborn errors of immunity (IEI) in life-threatening COVID-19 infections in previously healthy individuals and of monogenic inborn variants of resistance (IVR) resilience to repeated infection exposure. It highlights the key role of type I IFN and of auto-antibodies against type I IFNs in the development of severe COVID-19. It also extends this role to several other severe viral conditions (yellow fever, influenza, West Nile virus encephalitis). These findings open new avenues of prevention and treatment based on large-scale screening of auto-antibodies against type I IFNs, and early treatment in infected subjects based on type I IFN not targeted by auto-antibodies such as IFN-β.
These results have been presented in several reviews and position papers published in high international profile journals, as referenced in the final research report.
The SCOR Foundation for Science is part of the SCOR group's commitment to research and the dissemination of risk-related knowledge, providing support for numerous scientific disciplines, of which epidemiology is a priority.
