Histological changes in the lungs and viral load indicators of guinea pigs in a model of SARS-CoV-2 infection

Laboratory animals allow modeling infectious diseases to study pathogenesis and conduct drug trials. The creation of animal models that most accurately reproduce COVID-19 is promising for assessing the effectiveness of drugs and vaccines against the SARS-CoV-2 virus. The aim is to study the histological changes in the lungs and the other indicators of the infectious process in modeling COVID-19 in guinea pigs as a type of laboratory animals susceptible to SARSCoV-2 virus.

Material and methods. The experiments were carried out on 12 guinea pigs of both sexes infected with SARS-CoV-2 alpha variant. The dynamics of the viral load was determined in nasal washes by RT-PCR; SARS-CoV-2 antibody content in the blood serum were measured by ELISA; titers of neutralizing antibodies were estimated in the neutralization reaction in Vero E6 cell culture. As controls, 12 lung autopsies of patients infected with SARS-CoV-2 (confirmed by PCR analysis) and those who died as a result of pneumonia were studied. Structural changes in the lungs of autopsy and experimental samples were studied on paraffin sections stained with haematoxylin and eosin.

Results. After intranasal infection with SARS-CoV-2 alpha variant at a dose of 4 lg TCID₅₀ (the dose infecting 50 % of the cell culture and causing cytopathic effect in 50 % of the cell monolayer), a low level of viral load with high rates of elimination was detected in the nasal cavity and lungs of guinea pigs. On days 3 and 5, the viral load in nasal swab samples was significantly higher in males (p < 0.05). After 7 days, viral RNA was not detected in nasal swabs. Antibodies to SARSCoV-2 were detected in the blood serum of guinea pigs on the 15th day. With a neutralizing antibody titer of 1:100 for all animals, the positivity rate in females was 2 times higher. Histologically confirmed severe viral pneumonia was recorded in dead animals and at the end of the experiment, similar to changes in the autopsy material of patients with COVID-19.

Conclusions. Histological changes in the lungs of guinea pigs during modeling of SARS-CoV-2 infection indicate the susceptibility of this animal species to the studied pathogen with reproduction of the disease in patients, which allows us to consider guinea pigs as a promising animal model for the study and prevention of COVID-19.

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