A genome-wide association study (GWAS) of 2,244 critically ill patients with COVID-19 identified four new genetic loci associated with severe disease. These loci include genes involved in antiviral defence mechanisms and inflammatory responses. The study found that variants in the IFNAR2 gene, which encodes an interferon receptor, and TYK2, a tyrosine kinase, were associated with increased risk of severe disease. Additionally, high expression of the CCR2 gene, which is involved in monocyte and macrophage recruitment, was linked to severe COVID-19. These findings suggest that targeting these genes with existing drugs may be a potential therapeutic approach. The study also identified a genetic locus on chromosome 3p21.31 associated with hospitalization, which has been previously linked to severe disease. The results highlight the importance of host genetic factors in the development of severe COVID-19 and suggest that genetic studies can provide insights into the mechanisms underlying the disease. The study also emphasizes the need for large-scale clinical trials to validate these findings and determine their therapeutic potential. The research underscores the role of host immunity in the progression of COVID-19 and highlights the potential for repurposing existing drugs to target these mechanisms. The study was conducted in collaboration with multiple research groups and involved a large cohort of patients from the UK. The findings provide a foundation for further research into the genetic basis of severe COVID-19 and may lead to the development of new therapeutic strategies.A genome-wide association study (GWAS) of 2,244 critically ill patients with COVID-19 identified four new genetic loci associated with severe disease. These loci include genes involved in antiviral defence mechanisms and inflammatory responses. The study found that variants in the IFNAR2 gene, which encodes an interferon receptor, and TYK2, a tyrosine kinase, were associated with increased risk of severe disease. Additionally, high expression of the CCR2 gene, which is involved in monocyte and macrophage recruitment, was linked to severe COVID-19. These findings suggest that targeting these genes with existing drugs may be a potential therapeutic approach. The study also identified a genetic locus on chromosome 3p21.31 associated with hospitalization, which has been previously linked to severe disease. The results highlight the importance of host genetic factors in the development of severe COVID-19 and suggest that genetic studies can provide insights into the mechanisms underlying the disease. The study also emphasizes the need for large-scale clinical trials to validate these findings and determine their therapeutic potential. The research underscores the role of host immunity in the progression of COVID-19 and highlights the potential for repurposing existing drugs to target these mechanisms. The study was conducted in collaboration with multiple research groups and involved a large cohort of patients from the UK. The findings provide a foundation for further research into the genetic basis of severe COVID-19 and may lead to the development of new therapeutic strategies.