A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection

SARS-CoV-2 infections display tremendous interindividual variability, ranging from asymptomatic infections to life-threatening disease. Inborn errors of, and autoantibodies directed against, type I interferons (IFNs) account for about 20% of critical COVID-19 cases among SARS-CoV-2-infected individuals. By contrast, the genetic and immunological determinants of resistance to infection per se remain unknown. Following the discovery that autosomal recessive deficiency in the DARC chemokine receptor confers resistance to Plasmodium vivax, autosomal recessive deficiencies of chemokine receptor 5 (CCR5) and the enzyme FUT2 were shown to underlie resistance to HIV-1 and noroviruses, respectively. Along the same lines, we propose a strategy for identifying, recruiting, and genetically analyzing individuals who are naturally resistant to SARS-CoV-2 infection.

Automated summary

SARS-CoV-2 infections can vary greatly between individuals, with some being asymptomatic while others experience life-threatening disease. While 20% of critical COVID-19 cases are due to inborn errors or autoantibodies, the genetic and immunological factors for resistance to infection itself remain unknown. Studies have shown that autosomal recessive deficiencies in certain genes or enzymes can confer resistance to diseases, suggesting a potential strategy for identifying individuals naturally resistant to SARS-CoV-2 infection.