Skeletal muscle adaptions and post-exertional malaise in Long Covid, 2024, Rob C.I. Wüst, et al

Opinion piece:

Highlights
Long COVID occurs when symptoms persist for more than 3 months after acute SARS-CoV-2 infection. Symptoms include fatigue, brain fog, myalgia, and post-exertional malaise (PEM), which worsens with physical, mental, or cognitive exertion.

Long COVID shares many characteristics with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), particularly PEM, which is necessary for ME/CFS diagnosis.

Long COVID is associated with intrinsic skeletal muscle mitochondrial dysfunction, endothelial abnormalities, and a shift towards more glycolytic muscle fibers, which contribute to a lower exercise capacity.

Several potential mechanisms may explain skeletal muscle abnormalities in long COVID, including local hypoxia, deconditioning, autoimmunity, electrophysiological changes, and central fatigue.

There are no treatments for long COVID or PEM, but ongoing trials include immunoadsorption, dietary supplements, and anti-inflammatory/antiviral drugs.

Abstract
When acute SARS-CoV-2 infections cause symptoms that persist longer than 3 months, this condition is termed long COVID. Symptoms experienced by patients often include myalgia, fatigue, brain fog, cognitive impairments, and post-exertional malaise (PEM), which is the worsening of symptoms following mental or physical exertion. There is little consensus on the pathophysiology of exercise-induced PEM and skeletal-muscle-related symptoms. In this opinion article we highlight intrinsic mitochondrial dysfunction, endothelial abnormalities, and a muscle fiber type shift towards a more glycolytic phenotype as main contributors to the reduced exercise capacity in long COVID. The mechanistic trigger for physical exercise to induce PEM is unknown, but rapid skeletal muscle tissue damage and intramuscular infiltration of immune cells contribute to PEM-related symptoms.
LINK

 

Long COVID symptoms include fatigue, brain fog, myalgia, and post-exertional malaise. This thread dives into our newest literature review exploring skeletal muscle dysfunction as a key factor in reduced exercise capacity for LC
https://twitter.com/user/status/1869409724581728666

 

What is PEM? Post-exertional malaise 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 ME/CFS showing overlap between the two conditions.

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.

https://twitter.com/user/status/1869410696871694384

 

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
https://twitter.com/user/status/1869411187592720423

 

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.

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.
https://twitter.com/user/status/1869413269720670716

 

Full thread by corresponding author:
https://threadreaderapp.com/thread/1869409724581728666.html

 

Summary for laypeople:
"Solve-Funded Researcher Reviews How Long Covid Changes Muscle Tissues To Increase Post-Exertional Malaise (PEM)"
https://solvecfs.org/solve-funded-r...sues-to-increase-post-exertional-malaise-pem/

 

Response to the above paper:

Recognizing the role of fibromyalgia in post-exertional malaise

Alessandro Giollo, Mariangela Salvato, Andrea Doria

[Line breaks added]

Abstract
The recent opinion by Charlton et al. published in Trends in Endocrinology & Metabolism [1] provides a thought-provoking discussion of the overlap between long coronavirus disease (long-COVID) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), emphasizing the centrality of post-exertional malaise (PEM) as a shared mechanism.

Here, we suggest that fibromyalgia should be included in the discussion, given the established role of PEM in this condition [2]. In addition, fibromyalgia not only shares symptomatic and mechanistic overlaps with ME/CFS, but also offers a complementary perspective on the pathophysiology of PEM.

Considering that PEM is a key symptom in both fibromyalgia and long COVID, exploring skeletal muscle function in fibromyalgia could provide complementary insights into the muscle-specific alterations that contribute to this debilitating phenomenon.

Link (Trends in Endocrinology & Metabolism) [Paywall]

 

The basis of this claim is this paper, Pain-related post-exertional malaise in (ME/CFS) and Fibromyalgia: A systematic review and three-level meta-analysis, 2021, Barhorst et al

"People with ME/CFS and FM experience small-to-moderate increases in pain severity following exercise which confirms pain as a component of PEM and emphasizes its debilitating impact in ME/CFS and FM."