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Background. The incidence of COVID-19 novel coronavirus infection has a wave-like pattern with surges in new cases followed by declines. Viral mutations, changes in viral properties, and new strains continue to emerge and are regularly reported.The aim of the study is to present a comparative analysis of clinical and epidemiological characteristics of hospitalized patients with COVID-19 during different periods of the coronavirus infection pandemic in Moscow.Materials and methods. A two-center, retrospective observational epidemiological study was performed using medical records of patients hospitalized with the confirmed diagnosis of COVID-19 in Moscow from March 2020 to March 2022 (34,354 patients).Results. Within 2 years of the pandemic, there were significant differences in the age structure of hospitalized patients. During the early months (March–June 2020) of the pandemic, age groups of 18–45 and 46–65 yearolds accounted for higher percentages of hospitalizations. Later on (July 2020 – February 2021), the proportion of older age groups demonstrated an upward trend. From spring 2021 (the emergence of the SARS-CoV-2 delta strain) to March 2022 (dominance of the omicron strain), the proportion of hospitalized working-age adults increased once again.The proportion of severe and critically severe cases among the patients hospitalized during different periods remained at steady levels: 7.7% (6.6–8.8%) and 5.5% (4.4–6.6%), respectively. The highest death rates were observed during the delta strain surge, while the lowest death rates were reported for the omicron strain. Throughout the pandemic, the older age and chronic diseases remained risk factors contributing to the severity of the disease and adverse outcomes.Conclusion. The emergence of new variants of SARS-CoV-2 causing a shift of the need for hospitalization towards younger age groups, the persistent high rates of severe cases and death rates among people of retirement age are pressing for the unfailing readiness for implementing preventive and epidemic control measures focusing on the above groups of population.