Thread by @RobWust

📢 Long COVID symptoms include fatigue, brain fog, myalgia, and post-exertional malaise (#PEM). This thread dives into our newest literature review exploring skeletal muscle dysfunction as a key factor in reduced exercise capacity for #LongCovid . 🧵cell.com/trends/endocri…

With @BraedenCharlton, @RichieGoulding1, @JaspersLab, we performed a literature review and found that LC patients show reduced aerobic capacity, earlier lactate buildup, and muscle abnormalities. Mitochondrial dysfunction and endothelial issues are major contributors to fatigue.

@BraedenCharlton @RichieGoulding1 @JaspersLab 🧠 What is PEM?
Post-exertional malaise (#PEM) is the hallmark symptom where physical or cognitive exertion worsens symptoms, lasting days to weeks. This is different from simply fatigue/tiredness. It's a diagnostic feature of #MECFS, showing overlap between the two conditions.

@BraedenCharlton @RichieGoulding1 @JaspersLab 💡 Mitochondrial Impairments:
Skeletal muscle mitochondria in long COVID patients show:
-Reduced function.
-Fragmented structures.
-Decreased activity in complex I.
This limits energy production, contributing to fatigue and a lower exercise capacity.

@BraedenCharlton @RichieGoulding1 @JaspersLab 🩸 Capillary Dysfunction:
It is unknown whether capillary structures in skeletal muscle are impaired, but studies find endothelial abnormalities. This could impair oxygen delivery during exercise, exacerbating fatigue and other symptoms.

🧬 Muscle Fiber Shifts:
Patients with long COVID exhibit more glycolytic (type II) muscle fibers than oxidative (type I). This reduces endurance and increases reliance on anaerobic metabolism, leading to faster fatigue during exercise.

🔍 PEM pathophysiology is unknown.
Theories on PEM include:
- Immune cell infiltration after exercise damages muscle tissue.
- Hypoxia-like effects due to microclots or endothelial dysfunction.
- Possible roles of autoimmunity or neurological contributors remain unclear

🔧 Challenges & Opportunities in Long COVID:
Diagnosing PEM relies on clinical questionnaires or two-day exercise tests, which are burdensome. Biomarkers for PEM are urgently needed to better understand and treat this condition.

💊 Therapies &🌟 Future Directions:
No definitive treatments exist yet. Some #PEM trials are ongoing. Understanding skeletal muscle alterations in Long COVID requires new research on pathophysiology & therapies, and is desperately needed.We continue to work on this,with your help

We highlighted various hypotheses that require further study, including deconditioning, autoimmunity and central fatigue.