Preprint Skeletal muscle properties in long COVID and ME/CFS differ from those induced by bed rest, 2025, Charlton, Wust et al

"A muscle biopsy is performed to assess the musculoskeletal system for abnormalities. Various disease processes can cause muscle weakness or pain. These conditions may be related to problems within the nervous system, connective tissue, vascular system, or musculoskeletal system".

This answers my question as to whether the ME and LC patients studied had pain or not, and if this would make a difference in the outcome.

 

Perhaps you are thinking of this OMF funded multi-site study where Dr Wust will examine the biopsy's? Current status shows 1/3 of patients have been recruited.
https://www.omf.ngo/investigation-into-post-exertional-malaise-between-historical-and-recent-me-cfs/

 

My reference was to work happening directly in the Netherlands. From what I recall they had a cohort of roughly 20 ME/CFS patients from around Amsterdam that completed the CPET procedure and 2 muscle biopsies some time in 2023.

Interesting that the OMF is basically doing a replication of that work. Can't remember now if I had heard about that or not.

 

Rob Wüst has written somewhere on X/Twitter that this is indeed the first data of said cohort and that hopefully they will publish full results sometime this year.

 

This looks interesting: muscle fibre types. If we look at panel C we have pre and post bed rest (pre is white, post is grey). There's not much movement in the four fibre types. rest doesn't seem to change their composition.

But in the final chart of panel B we see controls, long covid (red) and mecfs (blue) showing lower levels of type 1 fibre in mecfs.


Type 1 fibres are 'slow-twitch' and type ii are 'fast-twitch', better for sprinting. So I suppose the question would be: have fibre types changed over the course of the disease or does a difference in fibre type pre-dispose you to mecfs? I was always better at endurance than sprinting as a young man so i'd guess the change is a result of a disease process. Either way though there's a clue!

I am very much appreciating the attention Rob Wust is paying to mecfs! Looking forward to the rest of his studies.

 

I think this is the main finding of the paper but wonder if it may simply be a longer-term consequence of less extreme deconditioning. For example that the longer you remain inactive the more type 1 fibers are affected relative to others.

The bed rest was a short period of extreme inactivity that affected all fiber type equally. ME/CFS patients become less active over a longer period of time and probably still maintain some short but not long-term activities. So it would make sense if type I (used for endurance activities) are then proportionally more affected?

 

Is that unique to pwME/CFS though? Could we possibly find some data sets with sedentary, but otherwise healthy people?

I’m sure you could find some office workers with the same activity levels as mild pwME/CFS.

 

I would actually like to see if compared to chronically ill people with other illnesses who are able to exert much less. Lupus, MS?

Also, what about looking at the muscles in someone who’se been unable to use a limb for a long time? People with lower body paralysis maybe.

Having that sort of data might make it easier to see if there really is anything unique about ME/LC.

 

Maybe people that have had casts on their legs for a long time due to nasty breaks or acl tears or something?

I remember a friend that ended up with her left leg with half the diameter of the right after she busted her knee and had to use a brace for many months.

And maybe NASA has some research in relation to their astronauts? I know they spend a lot of effort on maintaining their bodies while in space - so they might know what they are trying to avoid?

 

I found this paper that says that a transition to less type 1 is normal after denervation from strokes or spinal cord injuries:

https://pmc.ncbi.nlm.nih.gov/articles/PMC4723235/

 

I tore basically every ligament in my knee.

But my experience would be the exact opposite. I was on crutches for a long time and couldn’t walk on it.

But at the same time I was doing intense physiotherapy (9 hours a week) to get the leg functioning again. So I don’t know if that is generalisable, but I definitely wouldn’t have been a good control for a study like this.

 

Yes, I was in plaster from thigh to ankle for a long time when a fracture refused to heal.

That could be a good control at the point the plaster's removed. I hadn't used any of the muscles that bend my leg for over six months, and of course I hadn't used the good leg much either because movement was so hard. Stairs were out of the question, I couldn't use any form of transport very easily, etc.

I'm not sure how common that type of injury is though.

 

I did ART for 5-6 years early in the illness (mostly bed resting), and when I started feeling improved again I was running out of the blocks immediately after all that rest, zero issues with my muscles, but started experiencing delayed PEM for the first time.

 

Similar experience really. I mean like I haven’t walked for 2 years but a month ago there was an emergency and I needed to get to the bathroom quick so I stumbled my way and my legs worked suprisingly well. Had to cut off on basically any mental stimulation for the next couple days tho.
(Usually I use “pee bottles” or rolling desk chair to bathroom)

 

Does the data include how long people have had ME or LC? I had muscle aches from the first day of my ME, so that symptom shouldn't have been from changes to muscle tissue. My ME didn't change my muscle capabilities, but for those who did get weakness or reduced endurance, how long did it take for that to develop?

The study should have included comparisons with other debilitating illnesses. Maybe the changes are common with many chronic immune system changes.

 

We might be able to find data on other illnesses elsewhere.

I found this study on MS:

https://pmc.ncbi.nlm.nih.gov/articles/PMC4180259/

It is not clear if it’s caused by the illness or inactivity or both.

 

Worth noting that this study also finds atrophy in MS patients, and suggests selective type IIa atrophy. The Wüst paper finds no atrophy in patients.

 

Interesting to note this study was funded by the Patient Led Research Collaborative.

 

Continuing from the itaconate discussion, I think this is an interesting point. Tomas mentioned that itaconate is only a weak SDH inhibitor, so two options are either that even itaconate's weak effect is sufficient to create the difference shown in this study, or something other than itaconate is affecting SDH. It also suggests that SDH inhibition might also be contingent on time since disease onset.

 

These points also strike me as interesting, though I would be at a loss to explain what they might all mean functionally. To my amateur eye, it does suggest that any impairment in oxidative phosphorylation is not solely due to SDH inhibition, if it is playing a role. I assume that's why they explored proton leak as well--as an additional mechanism resulting in reduced oxidative phosphorylation capacity. Unfortunately it looks like supplemental figures are not included in the preprint.

[Edit: interestingly, one of the main mediators of proton leak is fatty acids, and there have been a handful of studies showing enhanced reliance on fatty acid oxidation in ME/CFS. Though it's hard to tease apart cause and consequence--fatty acid oxidation may be upregulated to compensate for impaired oxidative phosphorylation in the first place]