GENETIC CHARACTERISTICS OF OMICRON VARIANT STRAINS CIRCULATING IN THE NORTHWESTERN FEDERAL DISTRICT IN 2022–2024

The Omicron variant of SARS-CoV-2 is characterized by high genetic variability, which has facilitated the emergence of a large number of its subvariants, several of which have caused sharp increases in morbidity. Studying the regional features of viral evolution is essential for a deep understanding of pandemic dynamics, epidemiological forecasting, and further control of the COVID-19 infection. The aim of this study was to investigate the genetic characteristics and phylodynamics of Omicron genetic variants in the Northwestern Federal District (NWFD) of Russia during 2022–2024. Whole-genome sequencing was performed on 2,524 SARS-CoV-2 samples, followed by analysis of the mutational profile of dominant lineages, including the calculation of the proportion of typical and atypical non-synonymous substitutions, as well as phylogenetic reconstruction and assessment of the local evolutionary rate. The previously established sequential replacement of dominant lineages using S-gene fragment sequencing was confirmed: BA.1 → BA.2 → BA.5 → XBB (XBB.1.5, XBB.1.9, XBB.1.16) → JN.1 and its "FLiRT" descendants (KS.1, KP.1, KP.3). A persistent presence of over 70 rare lineages and recombinants (XDA, XEC, XEL, etc.) was noted annually. The nucleotide substitution rate was 8.02×10⁻⁴ per site per year, which corresponds to global estimates of the Omicron variant's evolutionary rate and is significantly lower than that of the original virus variant. Despite a high proportion of typical mutations (69.5–100%) in the circulating strains, atypical substitutions affecting receptor binding and immune escape were identified. The highest number of atypical mutations was found within the BA.2 lineage and may result from local viral adaptation.

         Thus, for the first time in the NWFD, a three-year evolutionary picture of the SARS-CoV-2 Omicron variant has been reconstructed. The high genetic diversity and multiplicity of co-circulating variants confirm the key role of St. Petersburg as a transport hub, while the identified atypical mutations indicate possible viral adaptation to local circulation conditions. The obtained data are valuable for forecasting the epidemic process and optimizing genomic surveillance systems.