COMPARATIVE CHARACTERISTICS OF THE ACCUMULATION OF DIFFERENT VARIANTS OF THE SARS-COV-2 VIRUS (WUHAN, DELTA, OMICRON) IN THE ORGANS OF MODEL ANIMALS

ABSTRACT Background The genotypic variability of the SARS-CoV-2 virus has proven to be extremely high, and the emergence of new strains raises concerns about their possible high virulence, transmissibility, and ability to bypass responses of the body’s immune system induced by previous infection or vaccination. Therefore, one of the main tasks is to study the pathogenesis of various variants of the virus using experimental animal biomodels of SARS-CoV-2 to quickly find methods and approaches to fighting new viruses. Methods 60 humanized mice of the C57BL/6-Tgtn (CAG-human AEC2-IRES-Luciferase-WPRE-polyA) line (hACE2) were used. Mice were infected intranasally at different doses with three variants of the SARS-CoV-2 virus: Wuhan, Delta and Omicron. Results We showed that humanized hACE2 mice, when infected with all three variants of the SARS-CoV-2 virus, showed typical pathological changes in lung consistency comparable to those found in COVID-19 in humans. All mice developed interstitial pneumonia, characterized by inflammatory cell infiltration and thickening of the alveolar septa, characteristic of vascular damage. Conclusions At a dose of 4 lg plaque-forming unit (PFU), all variants showed 100% mortality. A dose-dependent effect was established only for the Wuhan and Delta variants. In a comparative assessment of different variants of the SARS-CoV-2 virus in a humanized mouse model of hACE2, it was found that the Delta variant leads to more severe damage compared to Wuhan or Omicron.