Despite the stable decline in SARS-CoV-2 virus-caused COVID-19 incidence in most countries worldwide by the end of 2023, spreading of this infection on a global scale remains relevant. Among all known SARS-CoV-2 genovariants, within the last about two years Omicron remains dominant. The distinctive properties of this genovariant are presented by short incubation period (1–5 days), high contagiousness, and a relatively mild disease course due to largest number of genomic mutations among all SARS-CoV-2 genovariants. The first case of Omicron genovariant-caused infection in Russia was recorded in early December 2021. Over many month-monitoring after active spread of the genovariant in Russia, it is obvious that in a number of key characteristics it differs profoundly from previous SARS-CoV-2 genovariants. Analyzing major patterns inherent in COVID-19 epidemic process particularly uncovering geographic features is one of the most crucial activities in COVID-19 surveillance. Here, we provide a comparatively analyzed pattern of Delta and Omicron SARS-CoV-2 genovariant dominated COVID-19 incidence in the population of the Saratov region. For this, there was used statistical reporting from the Office of Rospotrebnadzor for the Saratov Region. The main research method is based on epidemiological analysis. The study data showed that upon Omicron genovariant dominance, an increased percentage in COVID-19 cases among children of varying age, increased rate of infected subjects with unknown source of infection as well as improved clinical disease course were recorded. Regardless of the circulating genovariant, elderly people remain to be in risk group. Thus, after three years of the COVID-19 pandemic, the mutual adaptation for SARS-CoV-2 and human population can be observed, which is accompanied by altered biological properties of the former and the accumulation of herd immunity. Alleviated disease symptoms and decreased mortality rate among Omicron genovariant-infected individuals evidence in favor of further COVID-19 transformation into a seasonal infection.