The article, based on modern literature data, provides a comprehensive analysis of the role of human genetic factors in the realization of susceptibility to SARS-CoV-2 infection and the severity of clinical manifestations of COVID-19. The constantly accumulating newest scientific data prove the participation of pathobiological processes at the molecular level (the presence of endotypes) in the mechanisms of development of SARS-CoV-2 infection, which is an important and necessary factor in the implementation of the strategy of personification of the diagnostics and treatment of COVID-19. The problem of studying genetic markers in COVID-19 covers wide areas of knowledge (screening, risk stratification, diagnosis process, assessment of the severity of the disease, control over the course of the disease), identification of phenotypes with the characteristics of the course of the disease, which will optimize the treatment of patients with SARS-CoV-2 infection from the standpoint of personalized therapy. The obtained scientific data indicate that the clinical and genetic approach allows one to approach a deeper understanding of the biological essence of the disease, which is characterized by a high degree of heterogeneity of the disease pattern from mild (outpatient) forms to the most severe manifestations of COVID-19, ending in lethalities. The true severity of the disease is determined by the individual disease pattern of the patient, which is due to the uniqueness of the metabolic processes of each individual, characterized by his genetic status. Therefore, effective treatment requires an individual approach to each patient with multifactorial pathology, an example of which is COVID-19. Further researches to establish the role of various phenotypes is promising both scientifically and practically. The strategy of diagnostics, treatment and prevention of diseases based on the molecular genetic characteristics of the organism is considered today as the basis of personalized medicine. The provided information provided is of great practical importance for practicing physicians.