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

Area of Science:

• Pathology
• Virology
• Immunology

Background:

• Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is known to cause lesions in skeletal muscle, myocardium, and gastrointestinal tract.
• The direct versus indirect cause of these muscle lesions and variations across animal models remain unclear.

Purpose of the Study:

• To compare pathological changes in skeletal, myocardial, and gastrointestinal smooth muscle across various COVID-19 animal models.
• To analyze the mechanisms underlying these muscle pathologies and determine direct viral involvement.

Main Methods:

• Comparative pathological analysis of muscle tissues from rhesus monkeys, hamsters, ferrets, hACE2 transgenic mice, hACE2-K18 transgenic mice, mink, and cats infected with SARS-CoV-2.
• In situ hybridization and electron microscopy to confirm direct viral infection of muscle tissues.
• Analysis of inflammatory cells (CD4T, CD8T, macrophages, B cells) and cytokines (IL-6, TNF-α, IFN-γ).

Main Results:

• All tested animal models exhibited muscle damage and inflammatory responses within 5-7 days post-infection.
• Rhesus monkeys displayed the most severe muscle pathologies, correlating closely with clinical symptoms.
• SARS-CoV-2 was confirmed to directly infect skeletal, myocardial, and gastrointestinal smooth muscle tissues.
• Inflammatory infiltrates included CD4T and CD8T lymphocytes, macrophages, and B cells, along with elevated IL-6, TNF-α, and IFN-γ.

Conclusions:

• SARS-CoV-2 directly infects and damages skeletal, myocardial, and gastrointestinal muscles.
• Muscle lesion severity varies among animal models due to factors like species, viral invasion, systemic inflammation, and immune status.
• This study provides a basis for selecting appropriate models to investigate muscle lesion mechanisms and therapeutic strategies for COVID-19, emphasizing clinical attention to muscle involvement.