Comparison Across Species: SARS‐CoV‐2 Infection Leads to More Significant Myopathological Changes in A Rhesus Monkey Model

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can cause skeletal muscle, myocardial, and gastrointestinal lesions. However, it is currently unclear whether these lesions are caused directly by viral infection or indirectly after infection and whether there are differences between different animal models. Here, we first compared the pathological changes of skeletal muscle, myocardium, and gastrointestinal smooth muscle of different COVID-19 animal models (rhesus monkey, hamster, ferret, hACE2 transgenic mice, hACE2-K18 transgenic mice, mink, and cat), and analyzed the possible mechanism of pathological changes. Within 5-7 days of being infected with SARS-CoV-2, the three types of muscles in these models were all damaged and inflammatory response to varying degrees, and infiltrating inflammatory cells and factors mainly included CD4T, CD8T cells, macrophages, a small amount of B cells, IL-6, TNF-α, and IFN-γ, and so on. Among them, the pathological changes of the three muscle tissues in the rhesus monkey model were the most significant and closely related to clinical manifestations. It was determined that SARS-CoV-2 can infect these three types of muscles through in situ hybridization and electron microscopy analysis. Therefore, the performance of muscle lesions in each model was not completely consistent and may be related to multiple factors after SARS-CoV-2 infection, including animal species, direct virus invasion, systemic inflammation after infection, and immune status of the body. This study provides a foundation for selecting models to study muscle lesion mechanisms and treatment strategies, highlighting the need for clinical attention to muscle tissue involvement in COVID-19 patients.