A review paper summarizing the latest genome-wide association (GWAS) and transcriptomic studies that identified two groups of candidates associated with severe COVID-19. These relate to polymorphisms in the ACE2 gene (rs2285666 G) and the host IFN-related antiviral pathway (IFITM3 rs12252C allele). Interestingly, the authors point out that the severity of COVID-19 may change as the virus evolves. This means that genetic findings from the early pandemic may not be strictly applicable to new variants like Omicron. Therefore, further research on the genetic predisposition to severe COVID-19 is needed, which will contribute to a better definition of risk groups. The paper published in Trends in Genetics.