E2 ModerateModerate confidencePEM unclearCross-SectionalPeer-reviewedMachine draft
Functional and Morphological Differences of Muscle Mitochondria in Chronic Fatigue Syndrome and Post-COVID Syndrome.
Bizjak, Daniel Alexander, Ohmayer, Birgit, Buhl, Jasmine Leonike et al. · International journal of molecular sciences · 2024 · DOI
Quick Summary
This study examined the energy-producing structures (mitochondria) inside muscle cells of people with ME/CFS and long COVID, comparing them to healthy people. Researchers found that mitochondria in both conditions work less efficiently and have structural damage, but the patterns differ: long COVID shows more damage to a specific energy-producing pathway, while ME/CFS shows more overall structural wear and tear in the mitochondria themselves.
Why It Matters
This work provides objective biological evidence that mitochondrial dysfunction underlies fatigue in both ME/CFS and long COVID, potentially explaining why patients cannot sustain physical activity. Identifying distinct mitochondrial damage patterns between the two conditions may help clinicians differentiate them and could guide future targeted treatments aimed at restoring energy production in muscle.
Observed Findings
- Complex I oxidative phosphorylation capacity was significantly reduced in PCS compared to healthy controls.
- Subsarcolemmal mitochondrial area, volume per cell, diameter, and perimeter were larger in PCS than in CFS.
- Cristae integrity was higher in both subsarcolemmal and intermyofibrillar mitochondria in PCS compared to CFS.
- No significant differences were found in intermyofibrillar mitochondrial size parameters between CFS and PCS.
- Both CFS and PCS patients exhibited impaired mitochondrial function relative to healthy controls.
Inferred Conclusions
- Post-COVID syndrome is characterized by selective complex I dysfunction, possibly due to direct viral-induced mitochondrial injury.
- Chronic fatigue syndrome shows more advanced morphological degeneration of mitochondria, suggesting prolonged inactivity or unknown molecular processes driving structural changes.
- Despite both conditions causing fatigue and reduced performance, their underlying mitochondrial pathologies differ in pattern and severity, indicating distinct disease mechanisms.
Remaining Questions
- Does mitochondrial dysfunction precede symptom onset, or does it develop secondarily to inactivity and illness?
- What specific viral or molecular mechanisms account for selective complex I impairment in PCS?
What This Study Does Not Prove
This cross-sectional study cannot prove that mitochondrial changes *cause* fatigue or reduced performance—only that they correlate with it. The study does not establish whether mitochondrial damage precedes symptom onset, develops as a consequence of illness or inactivity, or follows a specific disease progression. It also does not prove the proposed mechanism of virus-induced damage in PCS, only that the pattern differs from CFS.
Tags
Symptom:Fatigue
Biomarker:Blood Biomarker
Phenotype:Long COVID Overlap
Method Flag:Weak Case DefinitionSmall SampleMixed Cohort
Metadata
- DOI
- 10.3390/ijms25031675
- PMID
- 38338957
- Review status
- Machine draft
- Evidence level
- Single-study or moderate support from human research
- Last updated
- 8 April 2026
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
Spotted an error in this entry? Report it →