Trial Report [Abstract] - Individualised aerobic and resistance exercise training improves exercise tolerance in individuals with [LC]: [PERCEIVE], 2025, Howden+

forestglip

forestglip

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Individualised aerobic and resistance exercise training improves exercise tolerance in individuals with Long COVID: findings from the PERCEIVE randomised controlled trial

E Howden, L Burnham, J Smith, K Whitmore, K Morrison, R Hoare, Y Sata, Q Huynh, T Marwick

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Background
"Long COVID" is reported to occur in about 10% of people after COVID-19 infection, with predominant symptoms of exercise intolerance and fatigue. Exercise training is an effective treatment for these symptoms in other settings, but may have adverse sequelae in chronic fatigue syndrome, which overlaps with Long COVID. The efficacy of training in Long COVID is unknown.

Purpose
To evaluate the effect of a multidisciplinary exercise intervention (MExT) including medical management of left ventricular (LV) dysfunction and a 6-month personalized supervised aerobic and resistance exercise training program in an randomised control trial (RCT) comparison with usual care (UC) in people with long COVID.

Method
In this multicenter, two-arm, parallel, RCT we enrolled adults who were experiencing ongoing symptoms (>12 weeks) and a reduced VO2 peak (< age-sex-predicted) following acute COVID-19. Participants were randomised (stratified by age [40-64; >65] and hospitalization status) to MExT (personalised exercise training + medical management of LV dysfunction and CV risk factors) vs UC for 6-months, with baseline and follow-up cardiopulmonary exercise testing (CPET). The primary outcome was change in peak oxygen uptake (VO2peak). Secondary outcomes included change in quality of life (AQoL-8D) and mood (PHQ-9). Exercise prescription and adherence were monitored via heart monitors.

Results
In total 133 participants (mean age, 53±9 years; 87 females (65%) and 46 males (35%)) were randomised 1:1 to MExT (n=66) or UC (67) between October 2022 – May 2024, 11 [5-29] months post-acute infection and 57 MExT and 60 UC participants completed follow-up testing. The MExT group completed a median of 53 aerobic (range 2-225) and median of 68 resistance (range 1-68 sessions) exercise sessions over the 6-month period and received CV risk factor optimization (50%) or initiation of cardioprotective therapy (27%).

The CPETs results are summarised in the table. At 6 months, there were between group differences in indexed VO2 peak of 1.74 mL kg-1 min-1(95% confidence interval (CI): 0.71, 2.76) p= 0.001), absolute VO2 of 0.14 L.min-1(95% CI: 0.05, 0.22; p value =0.003) and peak watts of 11.5w (95%CI: 4.3, 18.7, p=0.002).

Other CPET parameters were not statistically different at 6-months (Ve/VCO2 slope, RER), except for peak HR which was ~6 beats lower in UC.

There was no significant effect of the intervention on mood (PHQ-9 between group difference 0.60 (-0.82, 2.02; p = 0.40) or quality of life (AQoL-8D score 0.01(-0.04, 0.06; p =0.72).

Conclusion
These results suggest that a carefully supervised and individualised exercise program improves cardiorespiratory fitness in individuals with long COVID.

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Web | PDF | European Heart Journal | Abstract only
 
Yann04 said:
Especially considering Long COVID probably includes majoritarily people who don’t have PEM.
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I think even if it was only people with PEM, you should expect that their VO2 and peak power will improve with exercise.

I don't think we have evidence that muscles don't become stronger or the cardiovascular system doesn't become more efficient with training in pwME as opposed to healthy people. It's just that the training happens to cause bad symptoms.

Edit: I think the conclusion should be something like "These results suggest that improving cardiorespiratory fitness does not improve quality of life in individuals with long COVID."

Instead it spins this as a positive result and doesn't mention the part that's actually important:
These results suggest that a carefully supervised and individualised exercise program improves cardiorespiratory fitness in individuals with long COVID.
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forestglip said:
I think even if it was only people with PEM, you should expect that their VO2 and peak power will improve with exercise.

I don't think we have evidence that muscles don't become stronger or the cardiovascular system doesn't become more efficient with training in pwME as opposed to healthy people. It's just that the training happens to cause bad symptoms.
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I exercised for thrice this time and initially became stronger. Didn’t stop me from becoming bedbound eventually. Anecdotal, of course.
forestglip said:
Edit: I think the conclusion should be something like "These results suggest that improving cardiorespiratory fitness does not improve quality of life in individuals with long COVID."

Instead it spins this as a positive result and doesn't mention the part that's actually important:
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They leave the QoL to the BPS crowd that can work holistically and individually tailored in multidisciplinary rehabilitation teams.

Edit: or maybe they didn’t do it for long enough.
 
forestglip said:
It's just that the training happens to cause bad symptoms.
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Anecdotally for me the training caused me to go from exercising 3 times a week walking 10’000 steps a day to being bedridden.

But I cannot prove causality and I dont think we will be able to know for sure until we figure out a way to quantify the biology.

But I think there is strong anecdotal evidence to suggest exercise training might actually worsen some pwME’s exertion capacity in the long term.

Which is also why seeing PEM conceptually as both an increase in symptoms and decrease in function is more true to the illness I have, or atleast my experience thereof.
 
Yann04 said:
Anecdotally for me the training caused me to go from exercising 3 times a week walking 10’000 steps a day to being bedridden.

But I cannot prove causality and I dont think we will be able to know for sure until we figure out a way to quantify the biology.

But I think there is strong anecdotal evidence to suggest exercise training might actually worsen some pwME’s exertion capacity in the long term.
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I have little doubt that exercise does causally worsen exertion capacity. But I think it's because exercise causes symptoms, so the person chooses/is forced not to exert.

If a healthy person and a person with ME/CFS do identical amounts of exercise, I think their objective markers of physical fitness like muscle mass and VO2 will likely still improve similar amounts. If not, it sounds like a straightforward biomarker that would have been measured by now.

But larger muscle mass and higher VO2 don't prevent the symptoms that end up leading to being bedbound.
 
I don’t conceive myself as being bedridden by symptoms. While I think you do. Hence our different views.

My experience leads me to conceive myself as bedridden because of the fact my “threshold” to trigger PEM is so low I couldn’t leave my bed without triggering it.

And the key part of PEM here isn’t symptoms, I can bare the symptoms, it’s that when in PEM the threshold to trigger more of it, and therefore my capacity, lowers. Oftentimes it never goes back to what it was before.
forestglip said:
If a healthy person and a person with ME/CFS do identical amounts of exercise, I think their objective markers of physical fitness like muscle mass and VO2 will likely still improve similar amounts.
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In the short term (days weeks months) quite possibly, I agree, otherwise 2D CPET and similar would be far more definitive, in the long term, my anecdotal experience is quite the opposite.

The physio I saw for a year in Austria said I came to her with more endurance than I left her with. She was puzzled that my exercise capacity seemed to decrease over the long term despite me exercising more.

In the study it seems 9 people dropped out of the exercise group, 13%. I reckon it’s possible some of those had little to no improvement, or even worsening in their capacity. After all the ± in the improvement seems to have an overlap going lower than baseline.
 
Yann04 said:
My experience leads me to conceive myself as bedridden because of the fact my “threshold” to trigger PEM is so low I couldn’t leave my bed without triggering it.

And the key part of PEM here isn’t symptoms, I can bare the symptoms, it’s that when in PEM the threshold to trigger more of it, and therefore my capacity, lowers. Oftentimes it never goes back to what it was before.
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Very well said. I can completely relate to this description.
 
What you're saying about the spiralling trap of PEM makes sense. Maybe a different version of what @forestglip said is that exercise seems to lead to *worse underlying disease* even if studies show it also narrowly improves fitness in the short term.

E.g. we could imagine what it would look like if exercise worsened the underlying pathology in some other disease like MS. In the short term encouraging patients to exercise might very well improve their fitness and in the long term leave them totally debilitated and unable to exercise.
 
I don't think one even has to go as far as argue that a possibility could exist where exercise worsens the underlying pathology, whatever that may be. There's no evidence that it has any worthwhile benefits and there's simply no point in making people feel horrible if those benefits don't even exist.
 
The MExT group completed a median of 53 aerobic (range 2-225) and median of 68 resistance (range 1-68 sessions) exercise sessions over the 6-month period
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"median of 68 resistance (range 1-68 sessions)" can't be right, can it?

Anyhow, it's clear from that sentence that adherence was extremely variable - some participants doing almost no exercise and others doing more than 1 session per day for 6 months - and yet the results are phrased as if the (limited) benefits apply universally?
 
The paper said:
These results suggest that a carefully supervised and individualised exercise program improves cardiorespiratory fitness in individuals with long COVID.
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Given the number of sessions over this period of time, no, it does not, and this is not the problem anyway. Those differences pretty much make it clear that it doesn't even achieve that, and it does nothing else. Plus, who even decides whether the supervision is 'careful', when it clearly simply means boxes were checked? I've never seen any such supervision being assessed as anything but careful, and if all supervision is careful, which it clearly isn't here, then none of them are.

I have been doing one-leg balance exercises for 2 years. I mean to write something on the forum about it. Over those 2 years, I have become better at balancing on one leg. And that's it. I am slightly better at doing the thing, but I can't do more of the thing. In a trial like this, this would be hailed as a success, even though it's meaningless.

I so don't care about desperate people spreading biobabble when this kind of junk is praised.
 
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forestglip said:
As long as more than half the group did exactly 68 sessions, and anyone else did less. Could be a mistake, but it's not impossible that's right.
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That would be the mode, the most common data point.

Shame it's abstract only, can't really correct them on it, but obviously they made a mistake somewhere.

The 1-255 range of aerobic sessions is wiiiiild.
 
I was still able to run during the first 8 months of sudden viral onset ME. Physically I felt ok, but the lack of endorphins and feeling flat after was very odd. I didn't have delayed PEM back then.
 
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