Organ and tissue damage related to SARS-CoV-2: the biological model for experimental (preclinical) trials on golden hamsters Mesocricetus auratus

Abstract

Introduction. Amid the pandemic of the new coronavirus infection COVID-19, experimental models for screening both newly developed vaccines and drugs, and the already registered active pharmaceutical in-gredients tested for new indications are in high demand. The registration of changes in biometric and mor-phological parameters that are significant for the investigative pathology can be an optimal screening tool for antiviral drugs and vaccines to treat COVID-19. In this regard, the purpose of this study was to describe the changes over time of organ and tissue changes using a biological model of a SARS-CoV-2-associated infection in the golden hamsters Mesocricetus auratus. Materials and methods. We performed the study in golden hamsters Mesocricetus auratus weighing 80–100 g. The animals were infected through intranasal administration of a culture of SARS-CoV-2 virus containing 4 × 104 TCID50/mL. We recorded the animals’ weight before the infection and during the next 14 days and measured the specific gravity of the internal organs and the degree of their moisture saturation on days 3, 7, and 14 after the infection. Additionally, tissue samples were fixed in 10% neutral formalin; the preparation of histological specimens was performed according to the standard procedure. Statistical data processing was carried out using non-parametric tests. Results. In the model of SARS-CoV-2 infection in Mesocricetus auratus, we observed the manifestation of the infectious disease after 3 days. The most pronounced pathological changes in the overall health status of the animals and in the histology of internal organs were seen 7 days after the infection. We determined the weight loss and significant deviations in gravimetric coefficients of lungs, heart, spleen, and kidneys to be the indicators revealing the infectious disease course changes over time. Histologic evaluation showed typical changes in the SARS-CoV-2-associated visceral damage: the formation of polymorphonuclear cell infiltrates in the lung interalveolar septa and patchy dystrophic changes in the neurocytes of the brain screen-type centers with the demyelination of the commissural nerve guides. The detected pathological manifestations corresponded in time to an increase in the virus replicative activity in the lungs. Conclusion. The experimental model of the SARS-CoV-2-associated infection in golden hamsters Mesocricetus auratus can be recommended for screening experimental (preclinical) studies of the promising drugs’ efficacy for pathogenetic and etiotropic therapy of COVID-19. Keywords: SARS-CoV-2, golden hamsters, morphometry, organ and tissue structural damage