Respiratory SARS-CoV-2 Infection Causes Skeletal Muscle Atrophy and Long-Lasting Energy Metabolism Suppression

Area of Science:

• * Molecular Biology
• * Pathology
• * Immunology

Background:

• * Muscle fatigue is a common long-term COVID-19 symptom with unclear causes.
• * Skeletal muscle changes in SARS-CoV-2 infection require detailed investigation.

Purpose of the Study:

• * To investigate histopathological and transcriptional alterations in skeletal muscle following SARS-CoV-2 infection.
• * To compare SARS-CoV-2 effects with influenza A virus (IAV) infection in a hamster model.
• * To elucidate the mechanisms underlying COVID-19-associated muscle dysfunction.

Main Methods:

• * Longitudinal study of hamster leg muscles at 3, 30, and 60 days post-infection.
• * Histopathological examination and bulk RNA sequencing.
• * In vitro experiments using C2C12 myotubes treated with cytokines (IFN-γ, TNF-α).

Main Results:

• * SARS-CoV-2 infection led to myofiber atrophy without direct viral invasion.
• * Persistent downregulation of genes involved in muscle structure, protein synthesis, and mitochondrial energy metabolism was observed.
• * SARS-CoV-2 induced TNF-α/NF-κB signaling, unlike IAV, and combined IFN-γ/TNF-α impaired myotube mitochondrial function.

Conclusions:

• * Respiratory SARS-CoV-2 infection causes skeletal muscle atrophy and sustained suppression of energy metabolism.
• * These effects are likely mediated by systemic immune responses (interferon and TNF-α) during the acute phase.
• * The findings suggest a mechanism contributing to persistent muscle fatigue after COVID-19.