The heterogeneity of the clinical manifestation of COVID-19 may be associated with the characteristics of the genome of both humans and the virus. A combination of allelic variants of genes associated with viral life cycle can determine susceptibility to SARS-CoV-2 infection. Allelic variants in genes ACE1, ACE2, TMPRSS2, IL6, SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, and XCR1 can determine the severity of COVID-19. Analysis of the genomes of COVID-19 patients with different clinical course and development on their basis of model for stratification of people according to the degree of susceptibility and severity of manifestation will allow to develop a personalized approach for the prevention and treatment of COVID-19.