Post-exertional malaise and the myth of cardiac deconditioning: rethinking the pathophysiology of long covid, 2026, Charlton, Wüst et al

Andy

Senior Member (Voting rights)

Authors: Braeden T Charlton, Kasper Janssen, David M Systrom, David Putrino, Rob CI Wüst

Post-exertional malaise (PEM): a defining feature of long covid​

While the number of fatal acute SARS-CoV-2 infections has declined since 2020, the proportion of these infections that result in persisting symptoms has not reduced significantly.1 The continuity or development of new symptoms longer than 3 months after an acute SARS-CoV-2 infection is clinically defined as long covid.2 PEM, a hallmark and debilitating feature, is recognised as one of the most frequent manifestations of long covid and is present in ~80% of patients with the condition.3 PEM is a delayed exacerbation (or new onset) of symptoms after physical or cognitive activity above a patient- and time-dependent threshold, which may persist for days, weeks or months or even result in a permanent change in a patient’s baseline.2 The need to screen for PEM in suspected long covid before initiating a rehabilitation strategy has already been recognised by major health authorities, including the WHO, who heavily cautioned against graded exercise therapies for patients experiencing PEM.2

Open access
 
Last edited:
PEM, a hallmark and debilitating feature, is recognised as one of the most frequent manifestations of long covid and is present in ~80% of patients with the condition.3

This is Wüst’s paper. There is nothing about the prevalnece of PEM in LC in general in it. Clinical samples are not representative. This is really basic stuff - when are they going to learn?
PEM is a delayed exacerbation (or new onset) of symptoms after physical or cognitive activity above a patient- and time-dependent threshold, which may persist for days, weeks or months or even result in a permanent change in a patient’s baseline.2

We really need to get rid of the talk about a baseline and thresholds.
The need to screen for PEM in suspected long covid before initiating a rehabilitation strategy has already been recognised by major health authorities, including the WHO, who heavily cautioned against graded exercise therapies for patients experiencing PEM.2
There is a need to screen for evidence of the benefit of rehab before prescribing rehab. And why not cite NICE NG206 here and their review of the research?
 
How do we explain PEM and pacing without them?
For me, the issue is the simplisitic cause–effect language that is used to describe exertion and PEM. It's just not that simple in reality. There seems to be an element of randomness and it's very easy for patients to fall into the trap of over-attributing PEM and crashes to exertion/activity alone, even though roughly the same level of exertion/activty can have wildly different outcomes.
 
There is clearly a huge problem with defining what rehabilitation even means, because it only applies in exceptional cases here, the vast majority of people suffering from any set of LC symptoms have no need for any type of rehabilitation, most of the time the patients know better than the therapists anyway, and I don't know of a single bit of professional-grade insight or skill that professionals can add beyond what patients can learn in 15 minutes.
Stratification of patients by POTS or PEM status allows for tailored rehabilitation plans, prioritising breathing exercises, low-intensity activities and pacing strategies for those experiencing PEM.
"Tailored rehabilitation plans" is way too vague and broad, there is no actual evidence that such 'plans' offer any meaningful benefits, breathing exercises have very little relevance, and what is even the point of "low-intensity activities"? Who needs that?! No one needs professionally-coached "low-intensity activities" because we are not children whose time needs to be managed, or whatever. And "pacing strategies" is not really a thing, pacing is not rehabilitation, it's convalescence, which is basically the opposite of rehabilitation.

Our professional allies will really need to stop pretending like any of this is valid if they ever want to help us. The only valid reason to do this kind of exertional rehabilitation is from severe deconditioning, and even at that most people don't need any such coaching because normal activities of daily living are more than sufficient, and people can do the rest all on their own. I'd be surprised if anything more than 1-2% ever need that, and I genuinely don't think outcomes would be meaningfully worse if no one did.

This kind of stuff is frankly just insulting in a "you people need to learn how to adult" way. The entire premise is that we are idiots suffering from weird phobias and ended up deconditioning ourselves because we stopped doing everything even though we were always capable of it, or whatever, and all of it is junk, there is no need to pretend that the lies have any relevance here.

They even do those mistakes in the paper:
While prolonged rest may initially seem beneficial for symptom management, extended periods of daytime lying or bed rest can induce cardiovascular and skeletal muscle deconditioning.
Almost no one needs to hear that, because almost no one does that, and the vast majority of those who do wouldn't do that in the first place if they weren't neglected and gaslighted in the first place, this is a wholly medicine-manufactured problem that could be eliminated by tomorrow if the motivation was there. Most severe patients who significantly improve manage it on their own anyway, and it's not as if any such coaching would change much, in about 99.9% of cases those people would benefit far more from at-home help, financial support and similar things.
Incorporating PEM into a new conceptual model of long covid cardiac rehabilitation programmes is essential to clinically distinguish it from cardiovascular deconditioning and to safeguard patients from unintended harm.
And again, cardiovascular deconditioning isn't even a secondary problem here, it's even less important than that, and the whole rehabilitation ideology is built around the belief that it's the only thing. Because of all those issues papers like this end up being more harmful than useful, they perpetuate the old debunked myths when we need health care that is based on fact and evidence, not myths and suspension of disbelief.

This is a political problem where messaging is crucial and this whole "my opponent is right about x" when actually they are not is just bad politics. We need better than this, the whole approach is wrong and it needs to be said out loud, defiantly.
 
For me, the issue is the simplisitic cause–effect language that is used to describe exertion and PEM. It's just not that simple in reality. There seems to be an element of randomness and it's very easy for patients to fall into the trap of over-attributing PEM and crashes to exertion/activity alone, even though roughly the same level of exertion/activty can have wildly different outcomes.
No I agree, but I don't know if we can totally abandon the concepts without being unable to explain pacing and PEM.
 
Heartsink.

It seems a pity to recommend:
targeted pharmacotherapy for PEM and POTS (including low-dose naltrexone, beta-blockers or pyridostigmine) to reduce symptom burden
when Systrom, a co-author, is currently doing a trial to determine whether LDN +/- pyridostigmine help ME/CFS (includes pwLC).

Imagine if Fluge & Mella had written a piece recommending rituximab before their phase III trial showed it didn't work?

And even more of a pity to be recommending supposedly good rehabilitation rather than the bad rehabilitation that went before, when we've no evidence that:
Using first ventilatory threshold-guided heart rate pacing enables patients to remain within their individual energy envelope, minimising PEM exacerbations while supporting gradual, safe reconditioning.

There are some valid points in here, but those with mild and moderate ME/CFS Sars-CoV-2 infection are still going to be encouraged to recondition and those with severe and very severe ME/CFS are still going to be encouraged to do more than they're able for:
While prolonged rest may initially seem beneficial for symptom management, extended periods of daytime lying or bed rest can induce cardiovascular and skeletal muscle deconditioning. Lying down during the day can be minimised by supported sitting or gentle upright postures and compression garments—provided the patient’s symptoms allow for such a strategy. Encouraging light, tolerance-based activity and postural variation is essential to prevent further functional decline while respecting post-exertional symptom thresholds.10

A simpler message would be:
Don't recommend graded exercise.
Advise people to experiment with being a little more upright a little more often, and stop if it makes them worse. Do not meddle further with people with severe and very severe ME/CFS, and believe them if they say they cannot do something or something makes them worse. Don't make them prove it.
We'll let you know if our trial suggests you should recommend LDN or pyridostigmine.
 
There are some valid points in here, but those with mild and moderate ME/CFS Sars-CoV-2 infection are still going to be encouraged to recondition and those with severe and very severe ME/CFS are still going to be encouraged to do more than they're able for:
This is exactly what’s happening, and worse. Assumptions are being made about what deconditioning is, what role it plays in patients’ symptoms, and patients’ ability to “recondition” that have little basis in science and entirely ignore patients’ lived experience. Here’s a post I made on Twitter about a supposedly tailored exercise program being sold to me as curative for ME patients. The provider in question claimed something like 80-90% return to work or outright recovery:

 
For me, the issue is the simplisitic cause–effect language that is used to describe exertion and PEM. It's just not that simple in reality. There seems to be an element of randomness and it's very easy for patients to fall into the trap of over-attributing PEM and crashes to exertion/activity alone, even though roughly the same level of exertion/activty can have wildly different outcomes.
I think a lot of us easily fall into that trap because we'd like to have an explanation, a cause-and-consequence model, some sort of a guideline, myself included. Someone who is really attuned to my body and spots things like changes in my breathing and eye movement/gaze when I start going beyond my capacity in the moment, pointed out so many times that my cause-consequence explanations don't make sense. As you say, there is more variation and randomness than I can feel in my body and that can be judged by me or someone who lives with me based on how I've been doing lately. Of course, completely ignoring body signals and perceived current capacity leads to a disaster.
 
S Blitshteyn MD, FAAN, Dysautonomia Clinic ® @dysclinic.3h FYI: I will be blocking you if you come attacking me. I practice evidence- based medicine with the goal of improving function and encourage movement via an individualized approach that we outline in our paper. We
don't do GET, we do medications. Peace!


Dr Blitshteyn does not seem to appreciate irony.
It is useful to be clear how she approaches things.
 
Wow, this is terrible. I think pretty much everything they say in the following section is some kind of wrong:
Stratification of patients by POTS or PEM status allows for tailored rehabilitation plans, prioritising breathing exercises, low-intensity activities and pacing strategies for those experiencing PEM.
There is no evidence that low-intensity rehabilitation programmes have any benefit for pwPEM. The domination-fetishes in rehab have to stop.
While prolonged rest may initially seem beneficial for symptom management, extended periods of daytime lying or bed rest can induce cardiovascular and skeletal muscle deconditioning. Lying down during the day can be minimised by supported sitting or gentle upright postures and compression garments—provided the patient’s symptoms allow for such a strategy.
There is no reliable evidence that compression garments are beneficial for pwOI.
Encouraging light, tolerance-based activity and postural variation is essential to prevent further functional decline while respecting post-exertional symptom thresholds.10
Even more dom-fetishes by the rehab people. Leave people alone and let them do what they values the most. And if you want to encourage postural variation you need to understand that it will come at a cost. It’s not just something the body will get used to eventually, and if you do less of something else that will also start costing more. There is always a trade-off.
The repetitive exposure to PEM events may perpetuate the worsening of patient health. Thus, monitoring patient response to various activities can aid in the reduction of PEM episodes, overall improving patient outcomes.
Even more invasivenes and intrusivenes. Patients are usually quite good a figuring out their situation if you explain what PEM is. There is no need for more monitoring.
Wearable heart rate monitors may be a practical method to monitor patient activity levels;11 however, we acknowledge that their use may not be feasible in less-resourced settings.
There are so many potential confounders for HR.
Using first ventilatory threshold-guided heart rate pacing enables patients to remain within their individual energy envelope, minimising PEM exacerbations while supporting gradual, safe reconditioning.
There is no evidence whatsoever for this approach. It’s pure make-believe.
This personalised, data-driven method contrasts with traditional graded exercise therapy, which remains contraindicated for patients with PEM.
It’s fairly similar in that there is no evidence for it, and both seem to believe that PEM is in part caused and maintained by the lack of activtiy.
Activity recommendations must be adjusted in real time to prevent symptom exacerbations.2
The fist thing they’ve said that makes any sense, but prevent is too strong. Try to prevent would be correct. They talk as if PEM is always avoidable and predictable.
Incorporating PEM into a new conceptual model of long covid cardiac rehabilitation programmes is essential to clinically distinguish it from cardiovascular deconditioning and to safeguard patients from unintended harm.
No, it clearly isn’t if you insist on doing rehab.
New programmes should deviate from historical guidelines for ME/CFS and include the latest insights into the pathophysiology of long covid.
Which we know next to nothing about because people keep jumping to conclusions and never learn.
We emphasise the heterogeneous nature of the disease and the need for targeted pharmacotherapy for PEM and POTS (including low-dose naltrexone, beta-blockers or pyridostigmine) to reduce symptom burden.10 12
Even more unevidenced statements.
Such an interdisciplinary approach will assist in personalised exercise and recovery prescriptions to avoid relapses or worsening of symptoms.
This is just the same old rehab garbage.
In conclusion, PEM and cardiac alterations in long covid patients can occur, but these findings are largely independent of cardiac deconditioning. Thus, an individually tailored management strategy, guided by exercise physiology data, for patients with long covid and PEM is recommended.
«We should stop beating you with a shoe, and use a belt instead».
 
I personally find them (threshold, baseline etc) useful simplifications for conceptualising my own illness and for explaining it to others.

But I agree there’s more randomness and variation than they let on.
I also think they are useful in everyday conversation, but they are simplifications that can’t be used to create complete models of care or treatment.

One hidden cost of using them is the expectation that you’ll get back to your baseline, so PEM appears less serious because it’s just a temporary blip. Nothing to worry about.
 
One hidden cost of using them is the expectation that you’ll get back to your baseline, so PEM appears less serious because it’s just a temporary blip. Nothing to worry about.
This is why it really annoys me when PEM is defined just as an increase in symptoms and not also as a loss of function.

Because as a very severe person I have had atleast two dozen episodes of PEM where not only I lost function (I do in nearly every episode), but I never gained it back again.

The symptoms framing makes it too easy to see it as a temporary inconvenience.
 
I don't know if we can totally abandon the concepts without being unable to explain pacing and PEM.

I wonder if we should substitute baseline for severity level, as indicated by FUNCAP scores. The categories are quite broad, but they probably reflect what people with ME/CFS mean when they describe their own severity level.

The aim of pacing is to avoid increasing FUNCAP scores in any domain. Harm reduction, as someone said in another thread.
 
Back
Top Bottom