Review Interventions for the management of long covid post-covid condition: living systematic review, 2024, Zeraatkar, Flottorp, Garner, Busse+

[Joan Crawford]

I'm away from home an with limited WiFi so not has opportunity to read.

I'm wondering if they referred to the ReCover trial?

I had the following critical letter published. Kuut et al 2023.

"Issues with Expectation Bias, Absence of Data Relating to Objective Trial Outcome Measures, the Use of Low Quality Trial Design Methods and Choice of Flawed Psychological Model in ReCOVer Trial for Prolonged Fatigue Post Covid-19 Infection"

I'm guessing the authors didn't reference me......

 

[Sean]

Both CBT and physical activity have long been shown to improve health and quality of life for people living with other chronic diseases.

Irrelevant. Particularly given the distinctive, maybe even unique, feature of PEM in ME/CFS.

Notably, both graduated physical activity and CBT have been found effective for myalgic encephalomyelitis (chronic fatigue syndrome or ME/CFS)

Lie.

CBT and graduated physical activity are offered to patients with long covid and ME/CFS based on the observation that patients often reduce activity in response to their symptoms.

So what? Would they make that observation about a patient with a broken leg? Of course not, it would be obvious, circular, and trivial.

Reduced activity in response to symptoms is consistent with patients having a pathophysiology that restricts activity capacity.

The only difference between the two cases is that the cause of the reduced activity is unknown in ME/CFS.

Consequently, patients may become physically deconditioned, develop disrupted sleep-wake patterns, and hold unhelpful beliefs about fatigue.

Interventions such as CBT and supervised physical activity which gradually reintroduce patients to activity may help with reconditioning, regularising patterns of activity, optimising rest and sleep, and addressing patients’ unhelpful beliefs about fatigue and activity.

What is the evidence for deconditioning, and for it being a significant factor (not a postulated one)?

If patients are deconditioned then why do they not re-condition and resume normal activity levels after exercise therapy? Re-conditioning in otherwise healthy deconditioned people takes 2-4 weeks at most.

In PACE, after a year of GET, patients could still only manage an increase on the 6MWT of 35m, and coming off a very low base, and no patients showed improvement on the Self-Paced Step test. Either patients are not deconditioned, or conventional re-conditioning doesn't work and may even be harmful.

Disrupted sleep-wake patterns could be a result of pathophysiology.

How is it determined that a belief is "unhelpful"? That requires that the belief is empirically demonstrated to be false or at least unproductive, not merely postulated to be so because it is convenient for the hypothetical model.

Despite supporting evidence, the role of exercise and CBT for long covid and other post-viral fatigue syndromes remains contentious, with some interpreting their success as evidence that the condition is “not real.”

WTF does that even mean?

We emphasise that the effectiveness of CBT and physical rehabilitation for long covid neither indicates the condition is psychological...

So holding "unhelpful beliefs about fatigue and activity" is not a psychological phenomenon now, let alone a critical feature of your causal model?

...nor negates a possible somatic cause. It is possible that CBT and physical rehabilitation only offer patients mechanisms to cope with symptoms from biological causes.

So get to researching biological causes properly, and stop wasting patients' lives with this cruel endless flood of shabby superficial psycho-behavioural speculation and studies. Like this one.

May, may, may, possibly, irrelevant and trivial observations, unjustified inferences...

They got nothing. Just the same inconsistent evidence-free fairy-tale they have been spinning for nearly four decades.

 

[Campanula]

It's interesting that these authors conclude that there's no compelling evidence for HBOT as a treatment for LC. Another systematic review that was just published came to the opposite conclusion:

Most studies found that HBOT can improve quality of life, fatigue, cognition, neuropsychiatric symptoms, and cardiopulmonary function. Although HBOT has shown some benefits for long COVID symptoms, further rigorous large-scale RCTs are required to establish precise indications, protocols, and post-treatment evaluations.

https://www.mdpi.com/2075-1729/14/4/438

 

[Robert 1973]

So if Garner is being endorsed by Toby Young, one could presume he might be part of the Freespeech Union.

For those not familiar with Young, he has quite a high media profile in the UK but he is not someone whose views are taken seriously by those who care about the truth. He and Garner are a good match.

See Controversies: https://en.m.wikipedia.org/wiki/Toby_Young

 

[Campanula]

For those not familiar with Young, he has quite a high media profile in the UK but he is not someone whose views are taken seriously by those who care about the truth. He and Garner are a good match.

See Controversies: https://en.m.wikipedia.org/wiki/Toby_Young

Reading about him it makes perfect sense that he and Paul Garner found each other. The subheading of "Covid 19 pandemic" under Controversies is especially enlightening.

 

[ME/CFS Skeptic]

I'm also curious how they rated the synbiotic study (thread here) as lower quality of evidence. Not that I believe it has any value in the treatment of LC (the authors didn't report any meaningful data and the LC classifications were nonsense), but it was at least a double blind placebo controlled trial with a "positive outcome".

Yes according to their standards, this should have at least the same certainty of evidence. But they downgraded it twice, once for selective reporting and the second time because the reviewers believed there is no plausible mechanism:

We also rated down the certainty of evidence as the trial reported a large effect on fatigue, concentration, and dyspnoea, and other symptoms such as hair loss, for which there is no plausible mechanism of action. Furthermore, this formulation of synbiotics, SIM01, has not been independently tested or shown to be effective for long covid or other conditions, except by its named innovators and patent holders.

 

[rvallee]

Toby Young: Director of freespeechunion.org Editor-in-Chief of Daily Sceptic (dailysceptic.org) Associate Editor of the Spectator
Currently with just the 67 followers on Bluesky.

(See previous S4ME comments about Young here)



Links to an article on DailySceptic.org which simply quotes the Daily Mail article and is titled: "Only Psychological Therapy Could Cure Long Covid, Major BMJ Study Finds".

So he's not simply jumped the shark, he's gone back to the Pliocene and vaulted over the nearest megalodon.

We're so far beyond the biased review of the biased studies as aptly described by Brian Hughes, that even the article talking about the article talking about the biased review has managed to take the idea that "CBT and exercise might possibly maybe help some people maybe maybe if we ignore the fact that it doesn't" and headline that it's a) a cure and b) the cure.

https://bsky.app/profile/toadmeister.bsky.social/post/3lc2dd4wets2p

Exactly what happened with PACE. This has always been the process: the lies amplified, massively overhyped, on page A1, the slow gradual debunking that simply gets ignored nowhere to be found, even years down the line. The asymmetry of bullshit in action.

It's really like an amplification process. Nowhere is there any evidence suggesting this treats anything, but out come loud assertions that this is a 100% safe and effective cure. Nothing's changed, this is how this scam industry thrives.

 

[rvallee]

Incidentally, I was listening to Skeptics with a K (podcast for the Merseyside Sceptics Society) recently, and almost fell off my chair, when they said Professor Paul Garner had talked at one of Toby Young's events about science. I didn't know much about Toby Young or the paper The Spectator, but they appear to be climate change deniers and antivaxxers. The podcast definitely outlines the alternate views this group of people have about health, science and "free speech".
https://www.merseysideskeptics.org.uk/podcasts/skeptics-with-a-k/episode-377

Of course they also are not sceptical as I would understand the term. So if Garner is being endorsed by Toby Young, one could presume he might be part of the Freespeech Union. Garner does like to publicise his views and talk about cancel culture...and perhaps he got his mate Toby to disseminate his flawed paper.

Oh the overlap between both grifter groups is obvious. It comes from a deep-rooted disdain for disabled people that is very popular in these political circles. No surprise there.

We're seeing the same thing with the more general pandemic deniers that will dominate US medicine in the next few years. They are all deeply associated with, and often funded by, corporate groups pushing far right politics.

It's stuff that would be super popular on platformed BS like Joe Rogan. It plays very well with the conspiracy crowds, so this is where they get the warmest reception. They understand where the politics of this stand, and where the money is coming from.

 

[EndME]

Yes according to their standards, this should have at least the same certainty of evidence. But they downgraded it twice, once for selective reporting and the second time because the reviewers believed there is no plausible mechanism:

Interesting, that one can do that in a systematic review, i.e. use a system such as GRADE, but then also move outside of said system and judge certain studies according to your own criteria without specifying what these criteria even are, since "plausibility assessment" wouldn't seem to be part of the bias 2.0 tool.

 

[SNT Gatchaman]

It's interesting that these authors conclude that there's no compelling evidence for HBOT as a treatment for LC. Another systematic review that was just published came to the opposite conclusion

There's also Hyperbaric oxygen effectively addresses the pathophysiology of long COVID: clinical review (2024, Frontiers in Medicine) which came out around the same time as the review you quoted. I haven't got round to reading any of these yet, but this review concluded —

These published studies, including case series and randomized trials, demonstrate that utilizing HBO provided significant improvement in patients with long COVID.

And just recently is Is there a rationale for hyperbaric oxygen therapy in the patients with Post COVID syndrome? (2024, European Archives of Psychiatry and Clinical Neuroscience) with abstract concluding —

up to this date HBO is the only scientifically proven treatment in a prospective randomized controlled trial to be effective for cognitive improvement, regeneration of brain network and improvement of cardiac function.

Hyperbaric oxygen for treatment of long COVID-19 syndrome HOT-LoCO: protocol for a randomised, placebo-controlled, double-blind, phase II clinical trial (2022, BMJ Open) appears to have completed in June 24 but not yet reported. See https://www.clinicaltrials.gov/study/NCT04842448

 

[Hutan]

Risk factors for the development of long covid include female sex, greater comorbidity, and patient reported psychological distress.19 20 21

On misrepresentation, this sentence, which I discussed in a post above, is an example of the bias of the authors. They make it seem that three references all found that female sex, greater comorbidity and patient reported psychological distress are risk factors. If you are convinced that psychological distress is a risk factor, then therapy to fix the psychological distress can seem like a good idea.

But, ref 19 and ref 20 are reviews of multiple studies and neither review said that patient reported psychological distress was a risk factor. Ref 21 is the only one of the three references that mentioned psychological distress at baseline as a risk factor and it's just a single flawed study. The placement of the reference citations adds false credibility to the authors' contention that Long Covid is a psychological problem fixed by psychological therapies - but the incorrect placement has plausible deniability.

 

[rvallee]

Interesting, that one can do that in a systematic review, i.e. use a system such as GRADE, but then also move outside of said system and judge certain studies according to your own criteria without specifying what these criteria even are, since "plausibility assessment" wouldn't seem to be part of the bias 2.0 tool.

It's truly the perfect method to greenlight fashionable establishment pseudoscience while still gatekeeping, correctly, other forms of perfectly equivalent pseudoscience. Basically it's almost entirely arbitrary, but it has the pretense of being somewhat scientific. Exactly the definition and process of pseudoscience: using the tools and language of science to sanewash beliefs and opinions lacking any credible evidence.

They're even showing the perfect application in pushing establishment pseudoscience by performing a more rigorous application of bias concerns for pharmaceutical/supplement treatments while arbitrarily upgrading the reliability rating of behavioral interventions, despite being subject to far more inherent bias. It couldn't be more blatant, but put this in front of 100 so-called skeptics, even professional ones, and all 100 will say this is a great review.

IMO it's the most extreme example of how expertise can fail, and it's precisely because experts see nothing wrong with it that it's so extreme. The death of expertise. Why they are delivering less and less over time, and losing trust and credibility while being oblivious that it's almost entirely self-inflicted.

 

[Nightsong]

Notably, both graduated physical activity and CBT have been found effective for myalgic encephalomyelitis (chronic fatigue syndrome or ME/CFS)—a condition with a striking resemblance to long covid that often emerges after viral infection. 120-122

These references are:

120 Komaroff AL, Lipkin WI. ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature. Front Med (Lausanne) 2023;10:1187163. doi:10.3389/ fmed.2023.1187163
121 Larun L, Brurberg KG, Odgaard-Jensen J, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev 2019;10:CD003200.
122 Kim DY, Lee JS, Park SY, Kim SJ, Son CG. Systematic review of randomized controlled trials for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). J Transl Med 2020;18:7. doi:10.1186/ s12967-019-02196-9

The Komaroff-Lipkin paper does not seem to suggest that graduated physical activity and CBT have been found effective, the Larun review is supposed to be being replaced, and the abstract of the Kim et al paper states that while a number of interventions reached statistical significance "there was no definitely effective intervention with coherence and reproducibility".

I'm puzzled about some of the determinations they have made. They use the broad WHO definition but exclude anosmia/hyposmia trials. Moderate certainty classifications are assigned even when trials don't seem to warrant it. They also don't seem to say how the TRACT flagged issues were addressed? (I don't think there's a specific cutoff/threshold score for TRACT but it would have been useful to have more detail on this; the per-trial determinations can be found in the spreadsheet).

While the trial reports a large effect for alleviation of fatigue, concentration, and dyspnea, there is no plausible mechanism of action for these effects, particularly for concentration and dyspnea.

While it is true that there is no plausible mechanism of action for "synbiotics" I wonder what the authors would say if someone did a GRADE-style review and downgraded all of the CBT studies on the grounds that they did not find the cognitive-behavioural model at all plausible? Tools like GRADE are surely just useless if the authors of reviews can simply substitute their own judgment on a selective basis?

Don't have the energy to look at this further but hope someone does.

 

[Hutan]

Tools like GRADE are surely just useless if the authors of reviews can simply substitute their own judgment on a selective basis?

GRADE
A tool that judges the body of evidence as a whole. It's structured into five domains that might introduce bias into the result.
Cochrane risk of bias tool
A tool that assesses the risk of bias in individual studies. The Cochrane risk of bias tool covers six domains of bias: selection bias, performance bias, detection bias, attrition bias, reporting bias, and other bias.

There's a lot in what you say @Nightsong, but actually I think the benefit of GRADE, which is admittedly limited, is that it provides a structure to evaluation and helps with the documentation of decision-making processes. Authors of reviews, even authors who are trying their best to not be biased, will inevitably use their judgement, possibly in ways that a different set of unbiased authors would.

GRADE doesn't prevent individual studies or the whole evidence base being found to be so flawed that they tell us nothing reliable. It's hard to make very cut and dried rules about where the line of 'too flawed' is drawn. For example, even studies with only subjective outcomes might actually provide some useful evidence if the reported improvement over a prolonged period was very large, or very small/negative, or they might be useful when assessing harms. I think the problem is not so much with the tools, as with the users of the tools.

 

[Snow Leopard]

They've done the same ignore the high risk of bias and rate it as "moderate strength" evidence anyway trick seen in the Cochrane review...

 

[Nightsong]

One more point - the authors say of PEM that:

This symptom, frequently reported by patients with long covid and ME/CFS, involves worsening fatigue after physical or mental exertion. 43-45

Ref 43 is a New Scientist article; ref 44 is a Dave Tuller blog and ref 45 is the Vink paper "Could Cognitive Behavioural Therapy Be an Effective Treatment for Long COVID and Post COVID-19 Fatigue Syndrome?". On this basis they define PEM as "worsening fatigue after physical or mental exertion", which proves that they don't understand what it is at all; the references they cite also don't define PEM in this way.

 

[SNT Gatchaman]

They use those same references in the discussion/implications section.

However, both CBT and physical and mental health rehabilitation require active patient engagement, which may be challenging owing to some patient groups expressing concerns about the safety and efficacy of these approaches and that the effectiveness of CBT and rehabilitation implies that long covid is not “real” but “psychological.”43-45

 

[InitialConditions]

Print article in the Telegraph — complete with a terribly misquoted pull quote stating:“The effectiveness of CBT and rehabilitation implies that long COVID is not real but psychological.”

I guess this is the icing on the cake. Can't see Garner and co being in any rush to call the Telegraph.

 

[ME/CFS Skeptic]

Noticed that the protocol says this about conflicts of interest (my bolding):

Conflicts of interest
Systematic reviews necessitate subjective judgments about the magnitudes of benefits and harms of interventions and the certainty of the evidence. To ensure such judgments are not unduly influenced, we will screen all co-authors and members of our team for financial and intellectual conflicts of interest using a standardized procedure developed by the BMJ (142).

Financial conflicts will include stocks, grants, research contracts, royalties, and speaking fees and travel accommodations and intellectual conflicts will include academic publications or statements on social or traditional media that could make reviewers attached to a particular intervention or point of view. We will exclude individuals with financial conflicts and restrict intellectual conflicts to no more than 25% of the team. Only reviewers completely free of both financial and intellectual conflicts of interest will be involved with screening search records, data extraction, risk of bias assessments, data analysis, and the assessment of the certainty of evidence.

 

[Robert 1973]

Print article in the Telegraph — complete with a terribly misquoted pull quote stating:“The effectiveness of CBT and rehabilitation implies that long COVID is not real but psychological”

I guess this is the icing on the cake. Can't see Garner and co being in any rush to call the Telegraph.

I wouldn’t be at all surprised to see a letter from them protesting that psychological illnesses like LC and ME/CFS are real. PR manipulation at its best/worst.

SW and co will no doubt be raising a cheer – a truly dreadful piece of research, which doesn’t provide any reliable evidence in support of its claims about CBT and rehab, has passed peer-review and been published in the BMJ. Now the Telegraph is using it to write headlines which are not even supported by the false claims in the BMJ paper.

“War is peace, freedom is slavery, ignorance is strength.”