Characterization of Virus Replication, Pathogenesis, and Cytokine Responses in Syrian Hamsters Inoculated with SARS-CoV-2

Abstract

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus which caused a global respiratory disease pandemic beginning in December 2019. Understanding the pathogenesis of infection and the immune responses in a SARS-CoV-2-infected animal model is urgently needed for vaccine development. Methods Syrian hamsters ( Mesocricetus auratus ) were intranasally inoculated with 10 5 , 5×10 5 , and 10 6 TCID 50 of SARS-CoV-2 per animal and studied for up to 14 days. Body weight, viral load and real-time PCR amplification of the SARS-CoV-2 N gene were measured. On days 3, 6 and 9, lung, blood, liver, pancreas, heart, kidney, and bone marrow were harvested and processed for pathology, viral load, and cytokine expression. Results Body weight loss, increased viral load, immune cell infiltration, upregulated cytokine expression, viral RNA, SARS-CoV-2 nucleoprotein, and mucus were detected in the lungs, particularly on day 3 post-infection. Extremely high expression of the pro-inflammatory cytokines MIP-1 and RANTES was detected in lung tissue, as was high expression of IL-1β, IL-6, IL-12, and PD-L1. The glutamic oxalacetic transaminase/glutamic pyruvic transaminase (GOT/GPT) ratio in blood was significantly increased at 6 days post-infection, and plasma amylase and lipase levels were also elevated in infected hamsters. Conclusion Our results provide new information on immunological cytokines and biological parameters related to the pathogenesis and immune response profile in the Syrian hamster model of SARS-CoV-2 infection.

Dynamic Changes of the Blood Chemistry in Syrian Hamsters Post-Acute COVID-19

“…Consistent with a previous study, the main symptom of intranasal SARS-CoV-2 infection in Syrian hamsters was weight loss and recovery without obvious sequelae ( 8 – 10 , 14 ). Our data demonstrated that weight change can be separated into two stages, namely, the acute onset of rapid weight loss and the recovery course of gradual weight recovery.…”

“…Abnormal liver function was a significant observation in patients with COVID-19 ( 20 , 21 ). A previous study on infected hamsters found that the AST/ALT ratio increased at acute onset, accompanied by structural abnormalities and large vacuoles in the liver ( 14 ). However, we found that the AST of the infection group increased slightly during the long-term monitoring, compared with that of the control group, while other hepatitis-related indicators did not change significantly.…”

“…Therefore, we continued to observe the pathological changes for 20 days after infection in hamsters, equivalent to the long-term changes of 5 years after infection in humans. Virus infection dose affects the lung inflammation severity and weight loss in a hamster model ( 8 , 9 , 11 , 14 ). As in previous studies, 10 5 PFU SARS-CoV-2-infected hamsters were used to study their pathological changes and the effects on blood chemistry.…”

“…When disease recovered, creatine, glucose, ALT, AST, potassium, and LDH levels remained above reference range in more than 10% of patients ( 23 ). In addition to our study, other literature has also analyzed biochemical markers from SARS-CoV-2-infected hamsters ( 14 , 24 ). Small increases in the measurements of amylase, lipase, and ALT were found in hamsters similar to those observed in COVID-19 patients.…”

Experimental Models of COVID-19

“…This is a limitation of the hamster model as it would not be useful to study the extrapulmonary pathologies that are observed in patients associated with COVID-19. Yang et al. (2021) recently used the Syrian hamster model to explore biomarkers of COVID-19.…”