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

Utsikt said:
All LC patients had ME/CFS (CCC).
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I find this bizzare. I have asked Rob on Twitter whether they actively selected for LC meeting CCC, but it would not surprise me if they didn't, given their insistence that basically everyone with LC has PEM. The fact that this LC group could be considered an LC-ME/CFS group would have implications for how this study's results are interpreted.

However, I was just looking at the CCC again: PEM is not actually mandatory. You can have post-exertional fatigue. I am worried that this could pick up cases of exertional intolerance, from e.g., cardiovascular dysfunction and/or dysautonomia, that isn't strictly PEM. This might explain the really high rates of PEM reported in some LC studies, including by Wust + co.

Screenshot 2026-07-28 at 08.45.29.webp
 
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I'm still a bit confused how 'muscle abnormalities' are being described in these studies. I've experienced flu/viral myalgia many times, but I don't describe this as PEM, and it doesn't affect my cognitive energy.

During post-Covid infection I experienced delayed (13hrs) extreme muscle fatigue in my legs for 6 months after going for a 40 minute when I felt recovered.
 
"Can we conclude that Long COVID is roughly the same as ME/CFS?"

Rob Wust:
"Not based on this study. We don't know if LC and ME are the same thing, but we do suspect a certain overlap. Our ME patients had been ill longer, so possible differences can be explained by a difference in the disease, or a difference in the duration of being ill"
 
But delayed PEM has always been in the pathophysiology process following exercise. It's not based on disease duration. When we understand our limit by pacing, and some of us do, the manifestations of delayed PEM doesn't occur.
 
InitialConditions said:
I find this bizzare. I have asked Rob on Twitter whether they actively selected for LC meeting CCC, but it would not surprise me if they didn't, given their insistence that basically everyone with LC has PEM. The fact that this LC group could be considered an LC-ME/CFS group would have implications for how this study's results are interpreted.

However, I was just looking at the CCC again: PEM is not actually mandatory. You can have post-exertional fatigue. I am worried that this could pick up cases of exertional intolerance, from e.g., cardiovascular dysfunction and/or dysautonomia, that isn't strictly PEM. This might explain the really high rates of PEM reported in some LC studies, including by Wust + co.

View attachment 33443
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Rob Wust replied, stating that they only enrolled LC patients with PEM, which is not quite what I asked but I don't think I'm going to probe much further.Screenshot 2026-07-28 at 19.04.14.webp
 
I think the LC cohort with PEM was selected based on the DSQ-PEM. It's from this study. I don't think they've done any new biopsies.

www.nature.com

Muscle abnormalities worsen after post-exertional malaise in long COVID - Nature Communications

In this longitudinal, case-controlled, cohort design study, authors show that post-exertional malaise is associated with severe exercise-induced myopathy, local and systemic metabolic disturbances and infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID.
www.nature.com www.nature.com
 
InitialConditions said:
exertional intolerance
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When did "exertional intolerance" become a distinct construct from PEM? And in that context, what is exertional intolerance? Just regular fatigue after exercise if you're deconditionied? When the IOM introduced SEID, I remember people mostly hated the name but appreciated that they got the PEM concept into it even though they called it "exertion intolerance." I don't remember people objecting specifically that EI was different from PEM. But maybe they did and I missed it. At the time I was mostly reading US sources.
 
dave30th said:
When did "exertional intolerance" become a distinct construct from PEM? And in that context, what is exertional intolerance? Just regular fatigue after exercise if you're deconditionied? When the IOM introduced SEID, I remember people mostly hated the name but appreciated that they got the PEM concept into it even though they called it "exertion intolerance." I don't remember people objecting specifically that EI was different from PEM. But maybe they did and I missed it. At the time I was mostly reading US sources.
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Exercise intolerance involves any abnormal symptoms during exertion, most notably fatigue, chest pain, rapid heart rate, and shortness of breath. The focus is almost always on physical exertion and it is often attributed to deficits/dysfunction of the cardiopulmonary and respiratory systems — such as those found in cardiac deconditioning — but there are other reasons why one might have exertional intolerance. Exercise intolerance seems to be very common in long covid, and is often present in non-ME/CFS LC patients.

In most of the literature, exertional intolerance and exercise intolerance would be intechangeable terms. It's only really in the ME/CFS literature where exertional intolerance (ala SEID) can mean problems from e.g, cogntive exertion.

PEM is very different. It's delayed for a start, takes much longer to recover from, and can be caused by any form of exertion. It exacerbates all existing symptoms, even those that have nothing to do with physical fitness and the cardiovascular system.

I am concerned that PEM and exercise intolerance are being confused, particularly in the long covid literature.
 
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InitialConditions said:
Exertional intolerance involves any abnormal symptoms during exertion, most notably fatigue, chest pain, rapid heart rate, and shortness of breath. The focus is almost always on physical exertion and it is often attributed to deficits/dysfunction of the cardiopulmonary and respiratory systems — such as those caused by cardiac deconditioning — but there are a whole host of reasons why one might have exertional intolerance. Exercise intolerance seems to be very common in long covid, and is often present in non-ME/CFS LC patients.

In most of the literature, exertional intolerance and exercise intolerance would be intechangeable terms. It's only really in the ME/CFS literature where exertional intolerance (ala SEID) can mean problems from e.g, cogntive exertion.

PEM is very different. It's delayed for a start, takes much longer to recover from, and can be caused by any form of exertion. It exacerbates all existing symptoms, even those that have nothing to do with physical fitness and the cardiovascular system.

I am concerned that PEM and exercise intolerance are being confused, particularly in the long covid literature.
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I wrote about this here (https://bjsm.bmj.com/content/60/8/6...well-to-traditional-rehabilitation-approaches) in response to a paper by Charlton + Wust plus Putrino and Systrom, which itself was a rebuttal of an American Heart Association statement on deconditioning in long covid. I felt like an imposter writing this, but I really think this is a problem that needs addressing.
 
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Isn't this the article that Levinovitz claimed hadn't been published or was having trouble getting published because they had null results? He'd cited the rebuttal of the previous Wust paper and had mentioned this follow-up deconditioning paper.
 
Solve ME has posted a news article about this study:

solvecfs.org

Solve-Funded Study Distinguishes Effects of Long Covid and ME/CFS From Effects of Deconditioning - Solve ME/CFS Initiative

A new Solve-funded study by Dr. Rob Wüst shows how physical inactivity–associated deconditioning cannot fully explain Long Covid– and ME/CFS–associated problems with exercise, laying the groundwork for better treatments.
solvecfs.org solvecfs.org

(please let me know if I've got the study wrong and I'll move or delete this post)
 
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