Trial By Error: And Now–No Surprise–CBT for Post-Covid Fatigue

By David Tuller, DrPH

Old habits die hard. So do bad ideas. Especially when these old habits and bad ideas have formed the basis for prominent academic and medical careers in the UK and the Netherlands.

In the UK, Professor Trudie Chalder of King’s College London has advised patients with prolonged fatigue after an acute bout of Covid-19 that they should get back to regular activities quickly and avoid resting too much. The effort from the UK National Health Service called “Your COVID Recovery” promotes a course of increasing exercise based on what appears to be a deconditioning model–despite lack of evidence that the exhaustion experienced by many post-Covid patients is mainly the result of deconditioning.

In the Netherlands, the Dutch health research agency ZonMw has proposed a welcome and long-overdue investment of almost $30 million (25 million Euros) over ten years in biomedical research into ME/CFS (more about that later). At the same time, the agency has also announced support for another effort by Professor Hans Knoop in his longstanding campaign to promote cognitive behavior therapy. His new study, highlighted along with dozens of others about Covid-19 on the ZonMw website, is called: ReCOVer: Can Cognitive Behavioral Therapy via the Internet prevent the fatigue symptoms of COVID-19 patients from becoming chronic? A controlled and randomized trial

Here we go again.

Professor Knoop, a psychologist at Amsterdam University, demonstrated his willingness to make preposterous claims with a co-authored commentary published alongside the 2011 PACE trial report in The Lancet. Professor Knoop and his co-author falsely claimed that 30 percent of those who received CBT or graded exercise therapy met a “strict criterion” for recovery. The commentary was disinformation–I documented its Trumpian misrepresentations and misstatements a few years ago. It remains an embarrassment to the medical literature, as does the PACE trial itself.

So I’m not surprised Professor Knoop would propose a course of CBT to prevent post-Covid fatigue from becoming chronic. I’m somewhat more surprised that Dutch funders are falling for the same sort of biopsychosocial babble all over again. Perhaps they needed to allow Professor Knoop to save face after the decision to throw their weight behind the biomedical research effort.


Here’s the description of the Professor Knoop’s study on the ZonMw site:

A substantial subgroup of COVID-19 patients is expected to develop chronic fatigue, that is, severe fatigue persisting for more than 6 months with associated adverse effects on the patient’s health, functioning and social participation. It is hypothesized that the timely provision of internet-based cognitive behavioral therapy (iCBT) for fatigue leads to a significant and clinically relevant reduction in fatigue severity after the intervention.

The study consists of a randomized, controlled study, in patients with fatigue symptoms 3 to 6 months after discharge from the hospital or after the diagnosis of COVID-19. One group is treated with iCBT and the other group in the regular manner.

The trial rests on a questionable notion: that CBT will prevent fatigue from becoming chronic. The available information does not elaborate on the hypothesis behind the study. Based on Professor Knoop’s history, the idea is likely to be that people recovering from acute Covid-19 will need therapeutic encouragement and psychological intervention to get back to their regular activities–that for a range of reasons they will be less willing or able to do so without professional assistance. In selling the premise, Professor Knoop perhaps cited the PACE trial, his own FITNET trial and/or other methodologically challenged studies from the CBT/GET ideological brigades.

The basis of such an assumption, especially in the case of a completely new viral disease, is not clear. Many, many people are suffering from overwhelming exhaustion and a range of other symptoms as part of post-covid syndrome. Perhaps it is true that, after the awful experience of the acute illness, some are mis-interpreting normal deconditioning as an excuse not to test the bounds of their capacities. Perhaps they will need psychotherapy to convince them to get moving again.

However, in the many accounts of post-Covid syndrome being posted online and discussed in news articles, I have seen little to suggest that patients’ reported exhaustion and other symptoms are related to unhelpful beliefs about their state of health or an irrational fear of engaging in activities they enjoy. Most of them sound desperate to get back to their lives. So the CBT approach does not sound promising to me, although it would be helpful to have more information.

In any event, the premise is likely not far from the animating concept behind the CBT/GET treatment paradigm for what these investigators prefer to call chronic fatigue syndrome. So it makes sense that Professor Knoop would like to apply the same template to post-Covid syndrome patients. But reanalyses of the PACE data have demonstrated that the interventions produced either null results or self-reported benefits well within the range of a placebo response. Moreover, all the reported benefits had dissipated by the follow-up study. Despite inflated claims of treatment efficacy, other methodologically challenged CBT studies of CFS have yielded similarly unimpressive results.

I assume that, like most of these studies, Professor Knoop’s new research will rely on subjective outcomes of fatigue and other indicators. Subjective or self-reported outcomes are not a problem when participants and clinicians are blinded to treatment assignment. But when interventions cannot be blinded, as in this case, subjective responses are likely to be fraught with bias. They are essentially uninterpretable.

That will be the situation with this study. The investigators will claim success anyway, if past is any guide. The question is whether anyone will believe them this time around.

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