Trial By Error: The Usual Suspects Promote a Psychosocial “Research Agenda” for Long Covid

By David Tuller, DrPH

In what could be described as a form of epistemic land grab, core members of the graded exercise therapy/cognitive behavior therapy (GET/CBT) ideological brigades have proposed a “research agenda” for long Covid that reflects the premises of their crumbling treatment paradigm for ME/CFS. This is not surprising. It has been clear from the early reports of continuing symptoms after Covid-19 that this powerful cabal would seek to colonize the field and devour a large share of the long Covid funding pie.

“A research agenda for post-COVID-19 fatigue,” published as an editorial by the Journal of Psychosomatic Research, is from a group known as the Collaborative on Fatigue Following Infection (COFFI). The round-up of authors includes some of the usual suspects in this domain of inquiry, such as Rona Moss-Morris, Andrew Lloyd, Simon Wessely, Vegard Wyller, and Hans Knoop. (I have written about shoddy work conducted by each of these authors.) This paper represents the most recent step in the effort to extend their discredited psycho-behavioral strategy for ME/CFS patients to those suffering from long Covid.

To be fair, in this new paper the authors do advocate for the collection of basic biomedical data in longitudinal studies of long Covid. In light of all the unknowns about SARS-CoV-2 and the flood of emerging discoveries about the neurological and other impacts of infection, it would have been difficult if not impossible to publish a “research agenda” that omitted such a call. In this context, however, it comes across mostly as a nod to the reality of the circumstances rather than as an indication of serious concern about biomedical aspects.

Their actual interests—and the true point of this “research agenda”—appear to lie elsewhere. While they understand that biomedical research will be conducted, they are staking a claim for the same kind of investigations they have pursued for years into the illness they have preferred to call CFS. In their research, they have favored the “psychosocial” in their much-touted “biopsychosocial” framework over the “bio.” While they acknowledge that an initial viral or other infection could trigger the syndrome, their decades-long project has involved denying any role for ongoing pathophysiological processes.

The premise of their favored interventions is that patients who don’t buy into these “psychosocial” theories but do believe in the “bio” aspects of ME/CFS are harboring “unhelpful” and “dysfunctional” illness beliefs that lead to sedentary behavior and deconditioning. These beliefs and behaviors, per the authors, are the factors that generate and prolong the classic CFS symptoms. Within this context, patients need either CBT to alleviate them of their abnormal “illness beliefs” and/or GET to get them back into shape through a steady increase in activity.

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So many flaws, so little time

So with this long Covid “research agenda,” where to begin?

One major problem is that these authors have generally reduced the entire spectrum of post-viral or post-infection illness to the domain of fatigue, despite the range of symptoms reported by many patients with these conditions. They do so again here, as the title indicates.

Given this fatigue-centric focus, the article does not mention the core ME/CFS symptom of post-exertional malaise (PEM), or post-exertional symptom exacerbation, as it has been called. Many long Covid patients have similarly reported experiencing PEM. The article also does not mention cognitive deficits and dysautonomia, and in particular postural orthostatic tachycardia syndrome (POTS). These are central complaints in both ME/CFS and long Covid.

To interpret everything in terms of the vague construct of fatigue represents a myopic perspective. However, some of the authors have built careers on these concepts, so it is understandable they are resistant to change and eager to defend their beleaguered turf—even at the risk of appearing foolish and a bit desperate to others.

The article includes some questionable passages. Here’s one:

“Previous research has shown that psychosocial factors, such as distressing life events, may predispose to developing PIFS, whereas symptoms of depression or anxiety, cognitive factors (i.e., illness beliefs) and behavioural factors (i.e., changes in activity patterns) may act as perpetuating factors. It is therefore unfortunate that there seems to be opposition to research into psychosocial predisposing and perpetuating factors that play a role in PIFS… It would be a shortcoming if we were to exclude research areas.“

Let’s be clear. The main evidence for the purported “predisposing” and “perpetuating” factors comes from studies that find associations between such cognitive and behavioral patterns and worse illness outcomes. These experts have a tendency to assume that such associations represent causal pathways in the direction supporting their hypothesis—that is, they believe these cognitive and behavioral patterns directly lead to the poor results. In making these assumptions, they overlook an equally if not more plausible and rational explanation–that the causality runs in the other direction.

In other words, people’s cognitive and behavioral patterns are likely to reflect the reality of their condition. Patients with worse physical health are more likely to believe—with reason—that they have an organic disease, and if they have an organic disease they are of course also likely to have more negative outcomes. People who experience PEM are more likely to reduce their behavior patterns—a smart move if they want to avoid repeated crashes. Of course these patients have a fear of doing too much! That is not a function of harboring “unhelpful“ beliefs about illness but of learning from past experience. In the presence of PEM, a treatment like GET is contra-indicated.

These concepts are not hard to understand. It requires willful stupidity to overlook them. Yet the GET/CBT ideologues seem unable to entertain these interpretations as legitimate possibilities. This is reflected in the current paper’s citations. The authors cite none of the major research that has refuted their perspective, such as the 2015 report from the US Institute of Medicine and last year’s new ME/CFS guideline from Britain’s National Institute for Health and Care Excellence (NICE), which repudiated the agency’s previous recommendations in support of the GET/CBT paradigm.

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Should psycho-behavioral treatments be offered to long Covid patients?

The “research agenda” authors make an oblique but peevish reference to the international rebellion against the treatments they have championed, declaring it “unfortunate” that there is opposition to their research strategy. Given the lack of evidence for their claims, the “unfortunate” aspect of this whole affair is that these authors and other self-important pooh-bahs have amassed so much influence and control over the public health purse strings. They have promised government agencies and other funders that their interventions can get people back to work and health—yet their trials routinely fail to document such results.

Nonetheless, based on meaningless findings from poorly designed studies, the authors assert boldly in their section on “interventions” that their psycho-behavioral treatments “should be available to patients with post-COVID-19 fatigue.” Interestingly, they do not cite the PACE trial. Perhaps Wessely no longer stands by his previous claim that PACE was “a thing of beauty”? Or perhaps they would then have felt forced to cite as well the 2018 re-analysis that rebuts all the main PACE results? (Disclosure: I was a co-author of that paper.)

The flimsiness of their overall argument is evident from the reference for this statement: “Exercise therapy was previously found to be effective in chronic fatigue syndrome.” The citation is of a 2019 Cochrane review called “Exercise therapy for chronic fatigue syndrome”–the subject of much controversy due to its unacceptable methodological flaws. (I have participated somewhat in this controversy, but my friend and colleague Caroline Struthers, a self-described citizen scientist and “health research enthusiast,” has rigorously pursued the Cochrane issue and has documented her meticulous efforts on her blog, Healthy Control.)

Cochrane published a comment alongside the 2019 review, which was an update of an earlier version. The comment noted that the new review “places more emphasis [than the previous version] on the limited applicability of the evidence to definitions of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) used in the included studies, the long-term effects of exercise on symptoms of fatigue, and acknowledges the limitations of the evidence about harms that may occur.”

The comment also included this acknowledgement of the review’s serious limitations from Cochrane editor-in-chief Karla Soares-Weiser: “This amended review is still based on a research question and a set of methods from 2002, and reflects evidence from studies that applied definitions of ME/CFS from the 1990s.”

Translation of these Cochrane statements into standard English: This review is unreliable.

Cochrane has launched an effort to create a completely new guideline. That the “research agenda” authors consider this pathetic document to be reliable evidence for GET demonstrates a troubling lack of scientific acumen and integrity.

The “research agenda” does not mention the most recent statement on the issue—the new ME/CFS guidelines from NICE, published last October. A review accompanying these guidelines found that the quality of the evidence for the effectiveness of GET and CBT was either “very low” or merely “low.” The agenda authors do not have to agree with this conclusion. But it is unacceptable to ignore these very recent and very salient assessments from an authoritative and widely respected arbiter like NICE—however unpleasant or unwarranted these determinations might seem to the authors.

In any event, we are already seeing some of the early fruits of this “research agenda.” Knoop, the senior author, is conducting a trial of CBT to prevent severe fatigue among long Covid patients. I have already criticized this study and its protocol. Since it is unblinded and relies solely on subjective outcomes, it is designed in a way that maximizes the possibility of positive findings.

In response to recent questions from patient advocates about the absence of objective measures in the study, Knoop indicated that he avoids them because in the past the results have contradicted the findings from the subjective measures he prefers. That’s certainly an unusual rationale for abandoning objective outcomes.

But what about Knoop’s call in the new “research agenda” that psycho-behavioral interventions for long Covid should “be evaluated using both psychological and biological data in relation to response to treatment.” Oh, that? Never mind!