Myopathy as a cause of Long COVID fatigue: Evidence from quantitative and single fiber EMG and muscle histopathology, April 2023, Hejbøl et al

Myopathy as a cause of Long COVID fatigue: Evidence from quantitative and single fiber EMG and muscle histopathology

Highlights

• Myopathic changes in qEMG and/or increased jitter in sfEMG were seen in 63% of 84 patients with Long COVID neuromuscularsymptoms.
• Low quality of life score correlated with higher mean jitter values in sfEMG but not with qEMG measures.
• Electron microscopy showed damage of terminal nerves and motor endplate.

Objective
To describe neurophysiological abnormalities in Long COVID and correlate quantitative electromyography (qEMG) and single fiber EMG (sfEMG) results to clinical scores and histopathology.

Methods
84 patients with non-improving musculoskeletal Long COVID symptoms were examined with qEMG and sfEMG. Muscle biopsies were taken in a subgroup.

Results
Mean motor unit potential (MUP) duration was decreased in ≥ 1 muscles in 52 % of the patients. Mean jitter was increased in 17 % of the patients in tibialis anterior and 25 % in extensor digitorum communis. Increased jitter was seen with or without myopathic qEMG. Low quality of life score correlated with higher jitter values but not with qEMG measures. In addition to our previously published mitochondrial changes, inflammation, and capillary injury, we show now in muscle biopsies damage of terminal nerves and motor endplate with abundant basal lamina material. At the endplate, axons were present but no vesicle containing terminals. The post-synaptic cleft in areas appeared atrophic with short clefts and coarse crests.

Conclusions
Myopathic changes are common in Long COVID. sfEMG abnormality is less common but may correlate with clinical scores. sfEMG changes may be due to motor endplate pathology.


https://www.sciencedirect.com/science/article/pii/S1388245723000196#b0040

This seems to build on similar work discussed here: https://www.s4me.info/threads/myopa...uscle-histopathology-2022-hejbøl-et-al.27997/.

 

From their 2022 paper —

Which sounds a lot like Mitochondrial abnormalities in the postviral fatigue syndrome (1991, Acta Neuropathologica) —

The other point made in their 2022 paper was —

We keep seeing this.

Rob Wüst presented at the recent Charité conference on LC and said —

In the picture he showed they looked to be where the capillaries would previously have been, so maybe they were in empty capillary basal membranes?

 

Is it right to say that it can't be due to the processing method of the samples? Which is often a criticism of microclots in the blood.

 

This is also what I'd be interested in. Can these dust looking like microclots and similar problems still occur in these muscle biopsies if one is looking inside of skeletal muscles?

 

I guess it'd be a lot clearer if they weren't present in samples from a control group processed at the same time. Haven't the energy to read the article properly, so I'm not sure whether they did this.

 

I don't think that'll be possible since Rob Wüst's findings haven't been published (the article is about a different study). It's more of a question for those that have knowledge of such biopsies without being able to read the study.

 

One of the criticisms about ex vivo microclot demonstration was that blood likes to make clots, particularly at room temperature. Although we only had 12 seconds of video comment, the point was made that these were amyloid deposits, not in blood vessels, therefore not in blood. The image on screen showed these as green fluorescent deposits, so possibly using the amyloid tagging Thioflavin-T that Resia Pretorius has published on. I think it's been said that that can stick to quite a lot of other stuff, so there is still room for it being artifact.

Rob Wüst characterised them as "microclots", but not blocking capillary flow. The question that I hope will be addressed in their upcoming paper is whether they think they were previously in capillaries and so previously obstructed flow — and required the capillary remodelling discussed in this thread's papers. I have no idea whether it would be possible to separate them off and compare their proteomics to the Pretorius findings.

I'll try and ask a pathology colleague about this, though we may need to wait for the paper.