Pathomorphological Features of Lung Damage Caused by Infection with Various Variants of SARS-CoV-2 in Humanized Model Animals

The genotypic variability of the SARS-CoV-2 virus is extremely high, and the emergence of new strains raises concerns about their possible high virulence 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. The study was performed on humanized mice of the C57BL/6-Tgtn line. Mice were infected intranasally at different doses with three variants of the SARS-CoV-2 virus. 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. At a dose of 4 log plaque-forming unit (PFU), all variants showed 100% mortality. In a comparative assessment of different variants of the SARS-CoV-2 virus in hACE2 humanized mouse model, it was found that the Delta variant leads to more severe damage compared to Wuhan or Omicron.