Many people living with Long COVID report persistent fatigue, muscle pain, and an inability to recover from even mild exertion. These symptoms are sometimes dismissed as general “deconditioning”, but emerging research paints a far more nuanced and biologically grounded picture.
A major study from 2024, led by Dr Rob Wüst and colleagues at Vrije Universiteit Amsterdam, offers detailed insights into how Long COVID affects muscle tissue and why recovery remains so challenging for many.
What’s Happening Inside the Muscles?
1. Mitochondrial Dysfunction
Mitochondria are the structures in our cells responsible for generating energy, particularly through a process known as oxidative phosphorylation. In individuals with Long COVID, this process appears to be disrupted, leading to poor energy production—even during low-intensity activity.
A 2024 muscle biopsy study found significantly reduced mitochondrial efficiency in people with Long COVID, along with evidence of tissue stress and microdamage. These biological impairments help explain why ordinary tasks can feel exhausting or even impossible.
2. Changes in Muscle Fibre Composition
Healthy muscle contains a mix of slow and fast twitch fibres. In Long COVID, researchers have observed a shift towards a greater proportion of fast twitch (glycolytic) fibres. These are suited to short bursts of activity but tire easily.
This shift may explain why individuals often feel capable at the beginning of an activity, only to experience sudden and disproportionate fatigue shortly afterwards.
3. Post-Exertional Malaise (PEM) and Muscle Injury
PEM is a core symptom of Long COVID and is also well documented in ME/CFS. It refers to a delayed, often severe worsening of symptoms following physical or mental activity.
Recent studies suggest that in Long COVID, even mild exertion can result in:
- Micro-damage to muscle tissue
- Immune cell infiltration into muscle fibres
- Amyloid-like protein build up in affected tissues
These changes may contribute to the extended recovery times reported by many patients after seemingly simple tasks such as climbing stairs or attending a short meeting.
How Do Clinicians Measure Muscle Changes?
Assessment of muscle dysfunction in Long COVID may involve:
- Electromyography (EMG): Measures electrical activity in muscles to detect abnormalities.
- Muscle biopsy: Confirms structural changes, mitochondrial dysfunction, and inflammatory markers.
- Heart Rate Variability (HRV) tracking: A wearable-based method that assesses autonomic nervous system function and can help guide energy expenditure.
HRV is increasingly used as a non-invasive tool to understand pacing thresholds and autonomic dysregulation in people with energy-limiting conditions.
(See: MedRxiv preprint, 2025)
Management and Recovery: What Helps?
There is no one-size-fits-all treatment for Long COVID related muscle dysfunction. However, the following strategies may help reduce symptom burden and support long-term management:
- Pacing: A core approach involving careful activity planning to avoid triggering PEM.
- Nutritional support: Some clinicians suggest nutrients like CoQ10, magnesium, and B-vitamins may support mitochondrial health, though formal evidence remains limited.
- Physiological monitoring: Using HRV or step count thresholds to track activity and maintain sustainable energy use.
- Emerging therapies: Ongoing clinical trials are investigating treatments aimed at improving mitochondrial function and reducing inflammation.
Dr Wüst and his team are also examining whether tailored, low-intensity exercise programmes introduced at the right moment and carefully individualised might offer benefits. However, they stress that any such approach must be applied with caution, and never forced.
(Source: Vrije Universiteit Amsterdam, 2024)
Key Takeaways
- Long COVID causes measurable biological changes in muscle tissue, including mitochondrial impairment and inflammation.
- These findings challenge the idea that symptoms are simply due to inactivity or lack of fitness.
- Management strategies must reflect this complexity, with a focus on pacing, personalisation, and continued research.
- Understanding the biology of muscle dysfunction is essential to developing effective, respectful care pathways.
Long Covid Journey 