The purpose statement is to assess the course of the COVID-19 pandemic and its impact on the epidemics of HIV infection, viral hepatitis C (HCV), tuberculosis, influenza, and acute respiratory infections in the North-Western Federal District (NWFD) of the Russian Federation during two years of spreading COVID-19 from the standpoint of the possible formation of syndemia or interference between pathogens.Materials and methods. Data collection on HIV infection and HCV was carried out by Pasteur Research Institute of Epidemiology and Microbiology at St. Petersburg Medical Information and Analytical Center using data from federal state statistical observation forms and our own research materials. The indicators of excess mortality from all causes for 2020 in the Northwestern Federal District (NWFD) and in the Russian Federation were analyzed according to the data of the Federal State Statistics Service (ROSSTAT). The results of epidemiological surveillance of HIV infection, viral hepatitis C (HCV), and tuberculosis in the Russian Federation and in the NWED in 2020 and 2021 in comparison with previous years are summarized. Studies of influenza and SARS were carried out by Smorodintsev Research Institute of Influenza and Gamaleya National Research Center for Epidemiology and Microbiology in cooperation with regional support bases. PCR detection of ARVI pathogens was carried out.Results and discussion. An analysis of epidemic indicators across the territories of the Northwestern Federal District of the Russian Federation made it possible to identify the following features: heterogeneity of the incidence of COVID-19 in the population in terms of time and intensity; the prevalence of morbidity in the metropolis (St. Petersburg) and industrial northern regions (the republics of Karelia and Komi). In a comparative aspect, the NWFD belongs to regions with high morbidity and mortality in the Russian Federation. St. Petersburg (378 deaths per 100,000 people in 2021) ranks second after Moscow. In turn, the Vologda, Murmansk, and Arkhangelsk regions, as well as the Komi Republic are among the top ten of the most affected subjects of the Russian Federation in the country. In terms of mortality, St. Petersburg was significantly ahead of all other subjects of the Russian Federation and the national average, which had several probable reasons. The first and second years of the pandemic did not reveal significant changes in epidemic rates of morbidity and mortality from other socially significant infections — HIV, HCV, and tuberculosis at the population level characteristic interference of viruses, where SARS-CoV-2 took the place of interfering, and influenza and SARS pretending or interfering pathogens. It took several months until the beginning of winter 2020 to crowd out seasonal respiratory infections by SARS-CoV-2. Then SARS-CoV-2 tightly captured the epidemic space, leaving no room for traditional respiratory infections, which accounted for less than 5% in early 2022.Conclusion. The COVID-19 epidemic had pronounced developmental features with higher morbidity and mortality in the metropolis and other industrial centers. The pandemic did not significantly affect the patterns of the epidemic course of HIV, HCV, and tuberculosis, which rejected the presence of a syndemic between these pathogens. Interference with respiratory infections — influenza and SARS — was revealed with a clear predominance of SARS-CoV-2.