Trial Report Functional Limitations and Exercise Intolerance in Patients With Post-COVID Condition A Randomized Crossover Clinical Trial, 2024, Tryfonos et al

Importance Many patients with post-COVID condition (PCC) experience persistent fatigue, muscle pain, and cognitive problems that worsen after exertion (referred to as postexertional malaise). Recommendations currently advise against exercise in this population to prevent symptom worsening; however, prolonged inactivity is associated with risk of long-term health deterioration.

Objective To assess postexertional symptoms in patients with PCC after exercise compared with control participants and to comprehensively investigate the physiologic mechanisms underlying PCC.

Design, Setting, and Participants In this randomized crossover clinical trial, nonhospitalized patients without concomitant diseases and with persistent (≥3 months) symptoms, including postexertional malaise, after SARS-CoV-2 infection were recruited in Sweden from September 2022 to July 2023. Age- and sex-matched control participants were also recruited.

Interventions After comprehensive physiologic characterization, participants completed 3 exercise trials (high-intensity interval training [HIIT], moderate-intensity continuous training [MICT], and strength training [ST]) in a randomized order. Symptoms were reported at baseline, immediately after exercise, and 48 hours after exercise.

Main Outcomes and Measures The primary outcome was between-group differences in changes in fatigue symptoms from baseline to 48 hours after exercise, assessed via the visual analog scale (VAS). Questionnaires, cardiopulmonary exercise testing, inflammatory markers, and physiologic characterization provided information on the physiologic function of patients with PCC.

Results Thirty-one patients with PCC (mean [SD] age, 46.6 [10.0] years; 24 [77%] women) and 31 healthy control participants (mean [SD] age, 47.3 [8.9] years; 23 [74%] women) were included. Patients with PCC reported more symptoms than controls at all time points. However, there was no difference between the groups in the worsening of fatigue in response to the different exercises (mean [SD] VAS ranks for HIIT: PCC, 29.3 [19.5]; controls, 28.7 [11.4]; P = .08; MICT: PCC, 31.2 [17.0]; controls, 24.6 [11.7]; P = .09; ST: PCC, 31.0 [19.7]; controls, 28.1 [12.2]; P = .49). Patients with PCC had greater exacerbation of muscle pain after HIIT (mean [SD] VAS ranks, 33.4 [17.7] vs 25.0 [11.3]; P = .04) and reported more concentration difficulties after MICT (mean [SD] VAS ranks, 33.0 [17.1] vs 23.3 [10.6]; P = .03) compared with controls. At baseline, patients with PCC showed preserved lung and heart function but had a 21% lower peak volume of oxygen consumption (mean difference: −6.8 mL/kg/min; 95% CI, −10.7 to −2.9 mL/kg/min; P < .001) and less isometric knee extension muscle strength (mean difference: −37 Nm; 95% CI, −67 to −7 Nm; P = .02) compared with controls. Patients with PCC spent 43% less time on moderate to vigorous physical activity (mean difference, −26.5 minutes/d; 95% CI, −42.0 to −11.1 minutes/d; P = .001). Of note, 4 patients with PCC (13%) had postural orthostatic tachycardia, and 18 of 29 (62%) showed signs of myopathy as determined by neurophysiologic testing.

Conclusions and Relevance In this study, nonhospitalized patients with PCC generally tolerated exercise with preserved cardiovascular function but showed lower aerobic capacity and less muscle strength than the control group. They also showed signs of postural orthostatic tachycardia and myopathy. The findings suggest cautious exercise adoption could be recommended to prevent further skeletal muscle deconditioning and health impairment in patients with PCC.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2817149

 

And here is an accompanying commentary that concludes with a hint that exercise therapy should be prescribed for ME/CFS (though they somehow omit any discussion of the vast literature on ME/CFS and exercise therapy). Tiresome.

https://jamanetwork.com/journals/ja...y's findings,–COVID-19 rehabilitation service.

 

Inability to question absurd results is one hell of a problem. They have some discussion of PEM, minimal, it's listed as a required criterion, and find that exercise is well-tolerated in people who have PEM. This is obviously nonsensical. Not everyone with LC has PEM or intolerance to exercise. In those, say in people who have lost their ability to smell or other issues, it's expected that it would be well-tolerated, but then exercise makes no sense as a treatment anyway.

Plus it doesn't even produce meaningful benefits, all they report is that they find people with exercise intolerance who tolerate exercise, therefore it should be used as a treatment. This is several layers of not making sense.

But to find that people who have intolerance to exercise tolerate high-intensity exercise is blatantly absurd. It's a complete contradiction, simply cannot be true. It's like finding a group of people who are more thirsty after drinking plenty of water.

This really looks more like an advert, a trial designed to produce a desired result, and the accompanying commentary only adds to this.

 

This is from accelerometer data from 7 days:

Obviously not.

SF-36 shows quite significant physical impairment, and yet the 6 MWT shows only a slight difference. I don't know how total physical activity, sedentary behavior and 6-MWT can be similar to controls in a group with an average of 13 in SF-36 physical function.

Table 2 shows quite significant differences and worsening, in fact zero worsening for controls and a significant worsening for patients, but in Supplemental data they disappear those difference, showing deltas of 0:

Those figures do not reflect the data above:

Those graphs are supposed to show no differences. OK, then:

I don't know what the hell is going on here. But managing to publish an advert in JAMA will no doubt lead to solid evidence-based evidence, or whatever. What an incredible disaster this industry is.

 

Of those included following initial physiological characterisation, 5 out of the 31 PCC patients dropped out. 3 after the first exercise session, 1 after the second (and 1 before the first session). 2 HCs dropped out, both after the second session.

 

PCCs are 13 minutes more sedentary per day than HCs (571 vs 558), with 11 minutes more total physical activity per day (317 vs 306).

 

Cidrap No need to avoid exercise with long-COVID diagnosis, researchers say

quotes:

Surprisingly, there were no differences in the two groups on self-ratings of fatigue. Patients with PCC had greater exacerbation of muscle pain after HIIT, however.

"What we can generally see is that the post-COVID patients do just as well as the controls, even though they had more symptoms to begin with. By equally well, I mean that they did not worsen their symptoms or negatively affect their body during the 48 hours we observed them," said Andrea Tryfonos, PhD, first author of the study, in a press release from the Karolinska Institutet.

....

In a commentary on the study, Peter Ladlow, PhD; Alexander Bennett, PhD; and Oliver O’Sullivan, MBChB; all United Kingdom-based researchers, said the findings are reassuring and should help guide clinicians treating post-COVID patients.

"The ability of individuals with PCC to tolerate various exercise activities, particularly hard-intensity activities … without major escalation of symptoms, fatigue, or exercise capacity is important for advancing rehabilitation," they write.

 

@rvallee the PCC SF 36 PF score is 49.9, I think you've quoted the Physical role score below

 

Professor Karl Lauterbach, the German Minister of Health comments the study on X:

Neue Studie aus Stockholm zu Exercise mit Post-COVID Symptomen ist sehr relevant. Eine Studie kann Frage der gezielten Belastung #Post-COVID nicht beantworten. Trotzdem ein wichtiger Hoffnungsschimmer. Werden wir mit Experten ⁦@BMG_Bund besprechen

Auto translation:
New study from Stockholm on exercise with post-COVID symptoms is very relevant. A study cannot answer the question of targeted exercise #Post -COVID. Nevertheless, an important glimmer of hope. We will discuss it with experts ⁦@BMG_Bund

⁩

 

This sort of mess just emphasises how utterly pointless it is to go on treating everyone who comes under the umbrella of Long Covid as if they had the same needs and conditions. Ridiculous categorical pronouncements that mean absolutely nothing to individuals in practice.

 

exactly! - and even these sick people were capable of repeatedly doing enough tiring physical exercise to be included in the study, while other Long Covid patients can't even leave their beds. Yet these researchers think they've "comprehensively investigate[d] the physiologic mechanisms underlying PCC."

 

Professor Carmen Scheibenbogen on X:

Solche methodisch unsauberen Studien zu verallgemeinern ist für Erkrankte mit #MECFS und #PCS mit #PEM sehr gefährlich. Diese Patienten hatten offensichtlich keine #PEM!

Auto translation:

Generalizing such methodologically flawed studies is very dangerous for patients with #MECFS and #PCS with #PEM . These patients obviously had no #PEM !

 

16% (5/31) of PCC dropped out of the study after the initial CPET (1), first (3) or second (1) exercise sessions. In comparison 2 HCs (6%) dropped out after the second exercise session. The paper does not tell us why they dropped out. If it was due to exertion intolerance or PEM crash that needed to be reported as an outcome, otherwise this data is meaningless. It might simply be saying if we ignore the people with PEM, no-one has PEM.

 

The body of the report also glosses over the first drop-out occurring after physiologic characterisation including bicycle ergometer CPET. They write —

Continuing —

However "all participants" doesn't actually seem to mean "all participants" as for PCC there are data for 27, 28 and 27, so not 31 (or even 30). So it seems to mean that all participants that did the exercises reached the targeted intensity.

But 31 PCC didn't do the three exercise sessions: eTable 2 says 27 did. However fig 1 says only 26 did all 3.

 

Editorial on this.

Free fulltext:
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2817151
Invited Commentary
Physical Medicine and Rehabilitation
April 4, 2024
Exercise Therapy for Post–COVID-19 Condition—Does No Harm
Peter Ladlow, PhD1,2; Alexander N. Bennett, PhD1,3; Oliver O’Sullivan, MBChB1,4
Article Information

• 1Academic Department of Military Rehabilitation, Defence Medical Rehabilitation Centre (DMRC) Stanford Hall, Loughborough, United Kingdom
• 2Department for Health, University of Bath, Bath, United Kingdom
• 3National Heart and Lung Institute, Imperial College London, London, United Kingdom
• 4Academic Unit of Injury, Recovery and Inflammation Science, School of Medicine, University of Nottingham, Nottingham, United Kingdom

JAMA Netw Open. 2024;7(4):e246959. doi:10.1001/jamanetworkopen.2024.6959

 

Invited commentary largely referencing their own prior work and opinions.

Exercise tolerance, fatigue, mental health, and employment status at 5 and 12 months following COVID-19 illness in a physically trained population (2023, Journal of Applied Physiology)

Use of symptom-guided physical activity and exercise rehabilitation for COVID-19 and other postviral conditions (2023, BMJ Mil Health)

The latter opinion piece contained —

Concluding with —

(Article also noted in Ravi's post #2).