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

[V.R.T.]

Of course it's lost in all the 'stress' nonsense

So many important clues are I think, like whatever is going on that makes me get sick from watching intense TV shows now

 

[poetinsf]

I doubt this is the problem.

I was conveying what I was told: it siphons precious little energy they have for little result.

I'm not sure how one can conclude this without any data and patient reports being fairly mixed.

It takes very little to trigger PEM in severely ill cases (signal). And they still have to breathe, eat and go to bathroom (noise). Feel free to point me to the data if you have any, I'll be happy to change my mind.

I suspect it is much more as @InitialConditions describes with randomness and non-linear relationships making the whole thing more complicated then a simple cause and effect language implies.

That's just assumption without proof. We typically attribute what we don't understand to randomness as we do in statistics. There could be actual randomness, but we don't know that until we fully understand the process. And nobody put a serious effort to track and model it yet as far as I know.

if the brain is crucially involved things are likely going to be more complex than the opposite.

Not sure about that either. We know allergies have trigger threshold. So do migraine or PTSD. Some of them do involve brain.

edit: typo

 

[V.R.T.]

There could be some of that, but also decades of exercise studies have pretty much added up to the fact that it takes very little exercise to maintain a healthy body. Not fit, just healthy. Of course the recommendations vary wildly, based on which cherries get picked, but in recent years the shift has been noticeable, making this to be good news, that it pretty much only takes a little movement here and there during the day, that it's actually staying immobile for long periods of time that is the main concern.

Ironically, it could be that it's pacing that helps the most here, as pretty much all of us divide our activities in chunks during the day. I rarely sit down for more than 30 minutes at a time, my very repetitive days are a back-and-forth between sitting down, or taking a nap in late afternoon, and doing a bit here and there, including some light exercises and short walks, basically meeting most of the recommendations for light physical activity. Most people do, unless they are actively lazy, such as always avoiding stairs, always driving to the closest parking spot and just disliking walking or doing anything more exerting than getting up from the couch to grab a snack and back.

And when looking at exercise studies, the amount of exercise that is needed for a healthy level of fitness is also pretty low, anything above it will mainly increase markers of fitness, with little impact outside of showing visible muscle or being better able to compete physically. It's still pretty good to do regular exercise, but the benefits have been wildly exaggerated. The big tell is that people who work physically demanding jobs don't seem to do any better, if they did it would be promoted like a god appearing on toast. Instead, it's all about recreation, hence the shift in recent years from recreational exercise to recreational light activities.

Ironically, by promoting the lie that work is good for health (for most people, the thing they hate the most in their life is work, and the relationship is obviously backwards: being healthy makes it easier to work), the medical profession may have actually made things worse since most people work too much, sitting down for long hours without taking breaks. Plus if exercise were as good as falsely advertised, governments would have long have been subsidizing it to make it free. But not a single one does, because the math doesn't actually math here.

Yes I think a lot of media and health service messaging gaslights people into thinking they are unhealthy because they don't do intense exercise 4 times a week.

Looking back I was probably in better shape than your average office worker when mild, but was convinced I was 'unfit' - mostly because I felt dreadful all the time. And media tells us we feel bad because we're not hitting the gym or running 5k - it's always your fault.

It's frustrating to realise how much common wisdom about health and exercise is bullshit.

 

[InitialConditions]

I disagree. They can’t be listening if they still believe that an individually tailored rehab approach is suitable. Or that PEM is triggered by going past a certain cardiopulmonary threshold (or something of the like).

They are letting their own preconceptions dominate their work.

I think they are seeing things through the lens of exercise science, because most of them are exericse scientists. The focus on physical exercise and rehab is party, I think, because many still think PEM is just about exercise intolerance — this is something I tried to convey in my response.

So much of the functional impairment in ME/CFS/LC and PEM is only minimally related to physical activty/fitness, and I am not convinced that heart rate monitoring and ventilation threshold tracking can change that in most patients.

 

[rvallee]

This possibility was, of course, a bit of snark.

If it were true then we would be self-healing instantly all the time and hence would not be sick!

Actually this made me light up on the fact that the ideologues have always told us they don't even believe in the myth of deconditioning because they also keep saying that we can just get up and live normally if we want to. Most of them have some variation of Garner's story about fixing their fear of exercise, or whatever, in a few minutes and just going on a run and feeling fine for the first time. They would never say this about someone who they genuinely thought were deconditioned, such as recovering from a severe illness requiring hospitalization.

This means it was never about deconditioning, rather the myth was always truly about some imagined fear of... something. Fear of activity, of movement, whatever, doesn't matter. A ghost, unseen and immaterial, but able to influence reality.

What's especially frustrating is that this is the only context in which this shouldn't work, because facts and coherence should matter to professionals, and yet they clearly have no issue being extremely deceitful not just about what they say, but in excusing being deceitful. It's hard to overstate how important it is to force a change in making it illegal to lie, or even slightly deceive, in health care. This alone would simply kill psychosomatic ideology, which is likely the main reason it's a non-starter, even though it technically already is not allowed, but rules don't matter, only enforcement does.

 

[Mij]

Feeling better or worse randomly is often described as a "fluctuating illness". When I'm going through a 'good streak' I take advantage of it because I know it can reverse at any time for whatever reason.

I don't need anyone telling me how or coaching when to exercise.

 

[InitialConditions]

I don't need anyone telling me how or coaching when to exercise.

Yep. We are perfectly capable of reconditioning ourselves — if only our bodies would allow that.

 

[EndME]

It takes very little to trigger PEM in severely ill cases (signal). And they still have to breathe, eat and go to bathroom (noise). Feel free to point me to the data if you have any, I'll be happy to change my mind.

I'm not quite sure what you mean. I'm suggesting that there is no useful data to make firm conclusions, but at least people on S4ME seem to be saying that things appear more variable than a simple causal language might imply. Which is also what I've been told by clinican who sees ME/CFS patients, but who knows how to interpret that.

That's just assumption without proof. We typically attribute what we don't understand to randomness as we do in statistics. There could be actual randomness, but we don't know that until we fully understand the process. And nobody put a serious effort to track and model it yet as far as I know.

Indeed, that is why I said suspect. Apart from actual randomness one typically models things that are too complex to understand in any other way using probabilistic tools. It is completely unlikely that one ever fully understand all processes and it isn't necessary either. I'm biased but what I've heard from patients is that simple predictions don't seem possible more than perhaps an overall impression gives a somewhat valuable guideline. After all you will find various posts of people describing the difficulty to recognize PEM for numerous years. I suspect that things are roughly as @InitialConditions put it, but I don't know it or claim to have a proof.

Not sure about that either. We know allergies have trigger threshold. So do migraine or PTSD. Some of them do involve brain.

I'm not sure what you mean here. The models I've seen of migraines in humans, which in itself tend to be simplifications and probably useless characterisations, have lacked the simplicity you are talking about here. A friend whose been told to be suffering from pressure migraines cannot make any reasonable threshold predictions, so much as it is debated whether the condition exists in a straightforward manner because causal attibutions seem impossible.

Nobody is suggesting that anybody has to understand some awfully complex dynamics that may never be fully grasped. All that has to happen is to get a decent enough understanding of some overarching picture and being able to zoom in a few specifcs to make one useful prediction. I doubt anybody understands more than that about allergies, PTSD or the majority of medical conditions.

 

[EndME]

Perhaps an analogy:

I think healthy or at least regularly active people can typically predict whether or not they will get DOMS from an activity and they can almost always pinpoint which activity lead to DOMS. I think for PEM things look a bit less straightforward.

 

[Mij]

Also PVFS delayed fatigue/muscle exhaustion can also be unpredictable. I experienced that when I was recovering from Covid infection.

 

[Utsikt]

I think they are seeing things through the lens of exercise science, because most of them are exericse scientists. The focus on physical exercise and rehab is party, I think, because many still think PEM is just about exercise intolerance — this is something I tried to convey in my response.

Yes, but if they still think PEM is exercise intolerance, then they can’t be listening to the patients in any meaningful way. By listening I mean not just hearing the words, but making a good faith and neutral attempt at understanding what the patients are trying to convey to them. If they constantly reframe everything in terms of exercise, they are not listening any more than the BPS folks.

So much of the functional impairment in ME/CFS/LC and PEM is only minimally related to physical activty/fitness, and I am not convinced that heart rate monitoring and ventilation threshold tracking can change that in most patients.

I fully agree.

 

[Sean]

There could be actual randomness, but we don't know that until we fully understand the process.

This is probably correct. At least some of what we might currently perceive as random is just insufficient understanding of the causal relationships driving it all.

I don't need anyone telling me how or coaching when to exercise.

Yep. We are perfectly capable of reconditioning ourselves — if only our bodies would allow that.

This. In fact we do it naturally, without planning, or motivating by an external force.

 

[Medfeb]

Great points raised in the letter by @InitialConditions. I agree. But I'm also wondering if a small part of the issue is in what the authors mean by the term "rehabilitation" in this context?

I expect most of us think of rehab as approaches whose goal is to recover and/or improve performance, function, etc. This could presumably include self-management. Pacing clearly does not fit in that scope.

But could they be including in their definition, rehabilitation approaches whose goal is to stabilize? Are they trying to fit pacing into their toolkit of rehab approaches since rehab is what they do?

Not saying this would be a good thing as the medical community at large will be using the improvement narrative.

 

[poetinsf]

I'm not quite sure what you mean.

What I meant was that it's hard to attribute PEM to any single exertion, or set of exertions, in severely ill cases because the PEM threshold is so low and therefore it could well look random. It's much easier to establish the relationship in milder cases since it takes more than walking to bathroom to induce PEM. (I'm struggling with excess fatigue today and I'm pretty sure that's because I walked 120 steps/min yesterday to keep up with crowds on the streets of NYC).

I'm suggesting that there is no useful data to make firm conclusions,

We agree on that point. Without data, it's mostly speculation and anecdote. We need a deep phenotyping of PEM with more than just "worsening of symptoms after exertion". That would at least fend off PEM minimizers who doubt the link between exertion and PEM and thinks pacing is responsible for fatigue. It could prove to be further useful by providing some clues of PEM mechanism, as well as making pacing more scientific.

 

[Felis Catus]

What I meant was that it's hard to attribute PEM to any single exertion, or set of exertions, in severely ill cases because the PEM threshold is so low and therefore it could well look random. It's much easier to establish the relationship in milder cases since it takes more than walking to bathroom to induce PEM. (I'm struggling with excess fatigue today and I'm pretty sure that's because I walked 120 steps/min yesterday to keep up with crowds on the streets of NYC).

Can you always predict the amount of excess fatigue and how hard PEM will hit you? I mean, has it ever happened that you did something or had a busy day/week and the pay-off was not as harsh as anticipated or perhaps it hit you harder than you thought it would?

You mentioned excess fatigue. Certain food hits me with immediate fatigue so strong that I fall asleep. There is no way for me to know if the food for which I think is ok for me is giving me excess fatigue and to which extent because I have no reference point - the issue came with the illness.

 

[Utsikt]

But could they be including in their definition, rehabilitation approaches whose goal is to stabilize?

They are very clear about trying to improve the underlying health issue, and not just making it easier to live with.

Are they trying to fit pacing into their toolkit of rehab approaches since rehab is what they do?

WHO actually essentially includes pacing in their definition of rehab:

a set of interventions designed to optimize functioning and reduce disability in individuals with health conditions in interaction with their environment

But the rehab people are too obsessed with their own perceived ability to treat health issues, that they forget that sometimes the only thing one can do is to adapt and make the best of a bad hand.

The «father of rehab», Howard Rusk, said that «to believe in rehabilitation is to believe in humanity», and that every person has an «ability to rehabilitate himself».

 

[Evergreen]

Which raises the question of why. Either patients:

1) are not sufficiently inactive for deconditioning to happen, for which we have good evidence from various activity tracking and deconditioning studies over the years, including one of Wust's own recent studies on deconditioning, or

2) are sufficiently inactive to induce clinically significant classical deconditioning but something is preventing or at least substantially mitigating that deconditioning, or

3) possess some miraculous ability to instantly reverse serious deconditioning without any accompanying active rehabilitation program.

I've been thinking about this idea that you and @SNT Gatchaman were discussing above. I thought how clotting risk works might be relevant (and if someone understands this better and can explain this better, pitch in!): People are at risk of clots from inactivity when there has been a sudden big change in their activity level, for example, because they break their leg or they're hospitalised. But I was told that in people like me, ie with long-term low activity level due to ME/CFS, the cardiovascular system adjusts, and so I'm not at a particularly high risk of clots. This seems true - otherwise we'd expect people with very severe ME/CFS to be getting clots all the time, whereas I haven't come across reports of that.

So for your point 2) above, perhaps the cardiovascular system adjusts to our low level of activity. So yes, all of us with lower levels of activity than when we were healthy are likely to have some degree of deconditioning, but perhaps not as much as the deconditioning catastrophisers predict.

If it were true then we would be self-healing instantly all the time and hence would not be sick!

That would only be the case if severe deconditioning were the root of ME/CFS though, right? I think we'd still be sick. And if exercise is indeed our kryptonite, potentially sicker.

 

[Andy]

I have just subitted the following rapid response. Not sure how often this journal publishes RRs, and this might be too off-topic for a sports medicine journal, so I'm posting here. It was helpful to get my thoughts in order, but now I need a break.

--
Post-exertional malaise cannot be reduced to exercise intolerance and often does not respond well to traditional rehabilitation approaches

I applaud Charlton et al. [1] for challenging the assertion that cardiovascular deconditioning plays a significant role in the development and persistence of long covid and that patients can be rehabilitated through appropriately tailored exercise training [2].

Charlton et al. instead argue that deconditioning alone is not sufficient to explain known cardiac alterations in all long covid patients, and that a growing body of evidence of biological abnormalities and pathophysiological findings in long covid (some of which replicate previous findings in ME/CFS) point to different mechanisms. This, they argue, has implications for the treatment and care of long covid patients, particularly in how rehabilitative strategies are designed and implemented.

Interestingly, despite seeing only a limited role for deconditioning, Charlton et al. reach similar conclusions to the AHA statement and recommend individually tailored rehabilitation strategies, albeit with the addition of certain safeguards to mitigate the harms (i.e., symptom exacerbation and further loss of function) associated with post-exertional malaise (PEM).

The focus placed by Charlton et al on PEM — the cardinal and defining feature of ME/CFS — is warranted, because it is found in a sizeable subset of long covid patients. The authors provide a prevalence rate of 80%, but this is considerably higher than other estimates, including those from systematic reviews and meta-analyses, [3, 4] and likely reflects unrepresentative clinical data.

Presence of PEM, much like absence of deconditioning, has important implications for how long covid is understood and treated. Presence of PEM in long covid helps define a specific ME/CFS(-like) phenotype describing patients with a highly debilitating, perverse reaction to exertion that is not seen in other patients.

Reading the long covid literature, I have noticed that PEM is still widely misunderstood and too frequently mischaracterised. Charlton et al. present a better understanding of PEM than most, but simplistic models based on ‘baselines’ and ‘thresholds’ do not fully capture PEM's inexorability and unpredictability. Further, the incessant focus on physical fitness/activity minimises the role of mental and cognitive exertion in triggering PEM and the significant role that ‘cognitive/neurological’ and ‘immune’ symptoms play in determining overall symptom burden and function capacity in these patients. The presence of these symptoms is generally independent of cardiovascular fitness or physical activity; this in itself should provide a clear rebuttal of the deconditioning myth.

Matters are further complicated by conflation of PEM and exercise intolerance, including in many long covid studies. The AHA long covid statement is really a statement about identifying and treating exercise intolerance (as per its title), not PEM. Confusingly, exercise intolerance might be present in long covid patients in the absence of PEM, and, in some patients, might well be explained by deconditioning and therefore respond well to physical rehabilitation.

I am concerned that many of the mistakes made in ME/CFS research are being repeated in long covid patient populations, particularly in trials of exercise and rehabilitation. Some of these mistakes include: complete ignorance of PEM [5]; poor identification and monitoring of PEM status (and associated harms) in patients; and/or exclusion of the most severely ill patients from research and clinical trials. Because of these mistakes, there remains an absence of evidence that these interventions improve patient outcomes and do not lead to deterioration or other harms, particularly in the most severely ill patients.

I therefore have doubts about the promotion of ‘tailored rehabilitation plans’ for patients with (correctly identified) PEM, particularly if there is no evidence of deconditioning. After all, reversing apparent deconditioning has always been the primary justification for exercise-based programmes in post-infectious chronic conditions. PEM and growing evidence of associated pathophysiological mechanisms can help explain why rehabilitative approaches very rarely ‘shift the dial’ in these conditions, and why many patients report them to be inaccessible, inefficacious, and counterproductive.

Acknowledgments: Comments from members of the Science for ME (S4ME) forum helped shape this response.

[1] Charlton BT, Janssen K, Systrom DM, et al. Post-exertional malaise and the myth of cardiac deconditioning: rethinking the pathophysiology of long covid. British Journal of Sports Medicine Published Online First: 10 February 2026. doi:10.1136/bjsports-2025-111387

[2] Cornwell III WK, Levine BD, Baptiste D, et al. Exercise Intolerance and Response to Training in Patients With Postacute Sequelae of SARS-CoV2 (Long COVID): A Scientific Statement From the American Heart Association. Circulation. 2025 Aug 5;152(5):e50-62. doi:10.1161/CIR.0000000000001348

[3] Li X, Zhang Y, Li J, et al. Prevalence and measurement of post-exertional malaise in post-acute COVID-19 syndrome: a systematic review and meta-analysis. Gen Hosp Psychiatry 2025;92:1-10. doi:10.1016/j.genhosppsych.2024.10.011

[4] Pouliopoulou DV, Hawthorne M, MacDermid JC, et al. Prevalence and impact of postexertional malaise on recovery in adults with post-COVID-19 condition: a systematic review with meta-analysis. Arch Phys Med Rehabil 2025;106(8):1267-1278. doi:10.1016/j.apmr.2025.01.471

[5] Spichak S. Less than 20% of Long COVID trials involving exercise even mention post-exertional malaise. The Sick Times. 2025 Nov 21. Available from: https://thesicktimes.org/2025/11/21...xercise-even-mention-post-exertional-malaise/.

Now published

 

[Evergreen]

Something that concerns me in the Charlton et al. piece (and many others at the moment) is that POTS is presented in a way that makes it sound very common.

Here's the first mention of POTS in Charlton et al.:

Healthcare providers should systematically screen for long covid aetiology, exclude other pathologies, and quantify postural orthostatic tachycardia syndrome (POTS) and PEM severity (eg, via the functional capacity questionnaire).2

To me, that makes it sound ubiquitous. You're supposed to quantify its severity.

I don't know how reliable the data we have on the prevalence of POTS in long covid or ME/CFS post-SARS-CoV-2 infection is. But Newton's team did some studies on the prevalence of POTS in CFS, which was, at the time, defined by Fukuda criteria.

In Hoad et al. 2008 Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome, participants were selected like this:

Subjects with CFS/ME (Fukuda Criteria6) were identified via the patient support group ‘ME NorthEast’. Subjects had been diagnosed with CFS/ME in a specialist CFS/ME service within 2 years of assessment in the autonomic laboratory. Controls were recruited via notices placed within the hospital.

and they found 29% had POTS.

In a study of their own service, 2.5% (4/157) of those referred and diagnosed with CFS 2008-2009 were found to have POTS. I note that 20% were reported to have CFS "precipitated by an infective episode" which seems unusually low.

The team came back in 2012 and did another study, Lewis et al. 2012 Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatictachycardia syndrome, where patients were selected like this:

A total of 179 consecutive patients who had attended the Northern Regional Department of Health-funded CFS Clinical Service (Newcastle upon Tyne, UK) between November 2008 and June 2011 with a diagnosis of CFS according to the 1994 Centers for Disease Control and Prevention (CDC) criteria [3] were included in this study. All patients with secondary causes of fatigue (such as hypothyroidism or diabetes) or who fulfilled the 1994 CDC exclusion criteria were excluded from the study (n = 23). [bolding added]

and they found 13% had POTS.

Newton's team's interest in POTS, and orthostatic intolerance more generally, was big news in the UK ME/CFS world at the time. So the 13% is likely to be inflated by selection bias.

I don't know if we have reliable data on the prevalence of POTS in ME/CFS defined according to Canadian Consensus Criteria. We might speculate that POTS might be more common in that group, but in Lewis et al. 2012 (linked above) those with POTS do not sound more severe:

Amongst the POTS-CFS subgroup, there were fewer subjects with depression (14%, n = 3 vs. 35%, n = 51; P = 0.05). There was no difference in the anxiety domain of the HADS test between these two groups. Patients in the POTS-CFS subgroup were significantly less fatigued according to the Chalder fatigue scale in both the physical and mental domains, and also reported significantly lower levels of daytime sleepiness (Fig. 1a). The presence of orthostatic symptoms was significantly more likely in the POTS-CFS group, with two thirds (n = 8) of patients scoring >9 on the OGS (Fig. 1b). Finally, there were no differences in functional domains (SF-36 and self-efficacy), cognitive impairment (CFQ) and pain ratings between the two subgroups. [bolding added]

I know that in another paper by Newton's team they mentioned that their subgroup with POTS did better/were more likely to recover, but I cannot find that right now. I will add the reference when/if I find it.

In my view, the problem with overestimating the prevalence of POTS in ME/CFS and long covid would be that it takes the focus off areas that should be focussed on in order to actually solve ME/CFS. Another issue would be patients potentially being seen as less credible if they test negative for POTS, even though most will test negative, and this may be associated with worse, not better, prognosis.

 

[Evergreen]

Here's another study relevant to prevalence of POTS in CFS: Roerink et al. 2016 Postural orthostatic tachycardia is not a useful diagnostic marker for chronic fatigue syndrome. I've created a thread for it here.