Our Mission…
The COVID Human Genetic Effort is an international consortium aiming to discover the human genetic and immunological bases of the various clinical forms of SARS-CoV-2 infection. In particular, we search for:
(i) Monogenic (or digenic) inborn errors of immunity (IEI), rare or common, underlying severe forms of COVID-19 in previously healthy individuals, including hypoxemic pneumonia, multisystem inflammatory syndrome in children (MIS-C), Long COVID, COVID Toes, etc.
(ii) Phenocopies of these monogenic IEI, such as auto-antibodies neutralizing gene products of loci whose variants underlie these IEI (e.g. auto-antibodies to type I IFNs mimicking inborn errors of type I IFNs).
(iii) Single-gene variants, rare or common, which make certain individuals resistant to the infection by the SARS-CoV2 itself, despite repeated exposure, or resistant to the development of clinical manifestations despite infection.
With these three projects, the COVID Human Genetic Effort aims to discover truly causative genetic and/or immunological anomalies, rare or common, and decipher in depth the molecular, cellular, and immunological mechanisms by which they underlie resistance to viral infection or disease, or predisposition to one or another form of severe disease (Casanova JL & Su HC Cell 2020; Sancho-Shimizu V Journal of Experimental Medicine 2021; Arkin LM The Journal of Investigative Dermatology 2021; Andreakos E Nature Immunology 2022; Brodin P Nature Medicine 2022).
We have already discovered the genetic and immunological basis of at least 15% of cases of critical COVID-19 pneumonia, due to inborn errors of type I IFNs or auto-antibodies to type I IFNs (Zhang Q et al. Science 2020; Bastard P et al. Science 2020; Bastard P. et al. Science Immunology 2021; Asano T et al. Science Immunology 2021). These discoveries have already led to the development of therapeutic applications and suggest a general mechanism of disease (Casanova JL & Abel L, Science 2021; Zhang Q et al. Nature 2022).
We are originally a group of friends and colleagues in the field of IEI, many of whom have successfully worked together on other challenges for years. We have enthusiastically welcomed the addition of new talents from this and other fields, and look forward to making new friends in these dire times, for the benefit (and glory) of humanity.
“We’re going to find the genetic and immunological determinants of the various severe forms of coronavirus infection.”
— Dr. Jean-Laurent Casanova, Co-Leader
The Rockefeller University, Howard Hughes Medical Institute (HHMI), New York, New York, USA
Necker Hospital for Sick Children & INSERM, Paris, France
“Our challenge is to figure out how a person’s unique genetic makeup could determine if they get severely sick or die from COVID19 infection.”
— Dr. Helen Su, Co-Leader
National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH), Bethesda, Maryland, USA
Not everyone who dies from COVID-19 is elderly or immune-suppressed.
Jean-Laurent Casanova explains how we are using genome sequencing to identify rare mutations that blunt the immune system’s normal defenses against the virus.