Monogenic basis of resistance to SARS-CoV2 and predisposition to severe COVID-19

Monogenic basis of resistance to SARS-CoV2 and predisposition to severe COVID-19

The research is being 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 (currently underway)


This project aims to discover the human monogenic basis for severe COVID-19 and monogenic resistance to SARS-CoV-2. To this end, its research focuses on two “deviant” groups of people who should be naturally resistant to viral infection and who were in good health prior to infection. The first cohort is made up of young people who have developed a severe form of infection for no apparent reason. The second cohort is made up of people who have been systematically exposed to COVID-19 but remain seronegative. The project is based on researching differences between the two groups through whole-exome sequencing (WES), using a cutting-edge strategy developed in the project’s laboratory to analyze this data. It will then perform in-depth functional studies to characterize the products of candidate genotypes biochemically, and to analyze the corresponding patients’ cells immunologically. Individual susceptibility to infection by the SARS-CoV2 virus varies significantly from one person to another. Establishing why is a key priority in the fight against the disease. The project should make it possible to identify people at risk of developing a severe form of Covid-19, and thus to provide better care for this patient population.

The preliminary results are particularly encouraging. Initial genetic and immunity-related causes have been identified which account for 15% of severe forms of COVID-19. The patients concerned all have one thing in common: impaired activity of type I interferons - immune system molecules that usually play a powerful anti-viral role. These preliminary results were published in Science1 magazine.  


1 Qian Zhang et al.: “Inborn errors of type I IFN immunity in patients with life-threatening COVID-19”, and Paul Bastard et al.: “Auto-antibodies against type I IFNs in patients with life-threatening COVID-19”, Science, September 24th, 2020