Pathomorphological changes in lung tissue of guinea pigs in SARS-CoV-2 infection model

Introduction. The main characteristic of pathogenicity of SARS-CoV-2 virus is its ability to cause death in sensitive laboratory animals. The absence of lethal animal infection models requires the search for other approaches to assess pathogenicity. Studying infectious processes in guinea pig lungs allows us to identify the features and patterns of the disease, determine significant histological characteristics, and identify the main pathogenic criteria. We aimed to conduct a comparative pathomorphological study of lung tissue in guinea pigs infected with various SARS-CoV-2 variants using morphometric standardized criteria. Materials and methods. We looked at structural changes in the lungs of 96 outbred guinea pigs depending on COVID-19 pathogenesis. The animals were randomly divided into seven experimental and one control groups of 6 males and 6 females each. The experimental groups were intranasally infected with the following SARS-CoV-2 strains: Wuhan, Alpha, Beta, Gamma, Delta, and Omicron (the last one represented by two genetic lineages BA.5.2 and EG.5). The control group was intranasally injected with 0.9% NaCl. The viral load over time was determined with RT-PCR on nasal flushes and infection titer (on Vero E6 cell culture). The animals that survived were removed from the experiment on day 15. Pathomorphological examination was performed with optical microscopy of histological lung specimens. Results. We detected diffuse alveolar damage as a similar pathological feature in the lungs of both patients with COVID-19 and guinea pigs. Significant differences were revealed in the number of pathomorphological signs caused by various genetic variants of COVID-19. The most considerable pathological effect of SARS-CoV-2 on lung tissue was caused by the Gamma variant. We suppose guinea pig lung dystelectasis to be the main marker of pathogenicity of SARS-CoV-2 strains, since this sign differs significantly in SARS-CoV-2 variants and is associated with excessive cytokine activity. Alveolar hemorrhagic syndrome is characteristic of all the studied coronavirus variants except for Omicron EG.5. The genetic lineages of the omicron variant have a minimal pathological effect on lung tissue and do not cause death in guinea pigs. Conclusion. Guinea pig is an appropriate animal for a SARS-CoV-2 model. Pathomorphological changes in the lungs depend on the SARS-CoV-2 variant causing them. Keywords: SARS-CoV-2, COVID-19, guinea pig, lungs, pathomorphology, SARS-CoV-2 variants