Cognitive behavioural therapy for severe fatigue following COVID-19 in adolescents: a serial single-case observational study... 2025 Knoop et al

[Andy]

Full title: Cognitive behavioural therapy for severe fatigue following COVID-19 in adolescents: a serial single-case observational study of five consecutively referred patients

Abstract

Background:
Severe fatigue following COVID-19 is a debilitating symptom in adolescents for which no treatment exists currently.

Aims:
The aim of this study was to determine the effectiveness and feasibility of cognitive behavioural therapy (CBT) for severe fatigue following COVID-19 in adolescents.

Method:
A serial single-case observational design was used. Eligible patients were ≥12 and <18 years old, severely fatigued and ≥6 months post-COVID-19. Five patients, consecutively referred by a paediatrician, were included. The primary outcome was a change in fatigue severity, assessed with the fatigue severity subscale of the Checklist Individual Strength, 12 weeks after the start of CBT, tested with a permutation distancing two-phase A-B test. Secondary outcomes were the presence of severe fatigue, difficulty concentrating and impaired physical functioning directly post-CBT as determined with questionnaires using validated cut-off scores. Also, the frequency of post-exertional malaise (PEM) and absence from school directly post-CBT determined with self-report items were evaluated.

Results:
All five included patients completed CBT. Twelve weeks after starting CBT for severe post-COVID-19 fatigue, three out of five patients showed a significant reduction in fatigue severity. After CBT, all five patients were no longer severely fatigued. Also, four out of five patients were no longer physically impaired and improved regarding PEM following CBT. All five patients reported no school absence post-CBT and no difficulties concentrating.

Conclusion:
This study provides a first indication for the effectiveness and feasibility of CBT among adolescents with post-COVID-19 fatigue.

Open access

 

[Andy]

They don't explain exactly how they characterised PEM, and the link to the Supplementary Material is just the link to the main article.

 

[Grigor]

"They all reported PEM, the frequency ranged from ‘every day’ to ‘few times a week’. They all reported school absence ranging from ‘several times a week’ to ‘few times a month’."

Whoot? What kind of PEM is that? Several times a week. For me PEM takes a couple of days. They probably measured fatigue after exertion?

 

[Andy]

They probably measured fatigue after exertion?

Yes, that would be my suspicion as well.

 

[Utsikt]

In adults, a beneficial effect of cognitive behavioural therapy (CBT) in reducing fatigue following COVID-19 in a subgroup of patients was demonstrated in a randomised controlled trial (RCT) (Kuut et al., Reference Kuut, Müller, Csorba, Braamse, Aldenkamp, Appelman, Assmann-Schuilwerve, Geerlings, Gibney, Kanaan, Mooij-Kalverda, Hartman, Pauëlsen, Prins, Slieker, van Vugt, Keijmel, Nieuwkerk, Rovers and Knoop2023). In chronic fatigue syndrome (ME/CFS), a syndrome with substantial overlap in symptomatology with long COVID, CBT has also been found effective in reducing severe fatigue in adults and adolescents, with adolescents benefiting most (Albers et al., Reference Albers, Nijhof, Berkelbach van der Sprenkel, van de Putte, Nijhof and Knoop2021; Kuut et al., Reference Kuut, Buffart, Braamse, Csorba, Bleijenberg, Nieuwkerk, Moss-Morris, Müller and Knoop20

How does cherry picking like this get past peer review?

 

[Utsikt]

Study design
A single-case observational design was used. This design can help to better understand for whom and under what circumstances CBT is effective.

The design can’t assess effectiveness at all.

Patients
Eligible patients were referred by a paediatrician after physical examination. They did not have somatic or psychiatric co-morbidity that could explain their fatigue. They were ≥12 and <18 years old and severely fatigued, operationalised as scoring ≥40 on the fatigue severity subscale of the Checklist Individual Strength (CIS-fatigue) (see Supplementary material). They had a symptomatic, laboratory-confirmed SARS-CoV-2 infection. Fatigue started with the onset of symptoms of COVID-19, as reported by patients and confirmed by their paediatrician. In all patients, fatigue lasted ≥6 months since COVID-19 at the time of inclusion.

ME-pedia on the CIS-scale:

The CIS consists of 20 statements on fatigue-related problems respondents might have experienced in the past 2 weeks.[2] A Likert scoring scheme is used. With each statement respondents have to indicate a score from 1 to 7, indicating either “yes, that is true” or “no, that is not true.” Examples of statements are: “I feel tired”, “I have trouble concentrating” or “, I don’t do much during the day” etc.[3] Almost half of the questions are inverted, meaning the statements indicate fitness instead of fatigue and the scoring system is reversed. “Yes, that is true” would then indicate a score of 1 instead of 7. Examples of such statements are: “. I feel fit, “I feel rested” or “I am full of plans”.[4]

It does not seem like it’s a good scale.

 

[Utsikt]

Intervention
CBT for post-COVID-19 fatigue was originally developed for and tested in adult patients with post-COVID-19 fatigue. It is based on a cognitive behavioural model of fatigue, which assumes that COVID-19 triggers fatigue while cognitive behavioural variables contribute to its perpetuation (Hulme et al., Reference Hulme, Hudson, Rojczyk, Little and Moss-Morris2017).

The seven perpetuating factors addressed are (1) a disrupted sleep–wake pattern; (2) unhelpful beliefs about fatigue; (3) a low or unevenly distributed activity level; (4) perceived low social support; (5) problems with psychological processing of COVID-19; (6) fears and worries regarding COVID-19; and (7) poor coping with pain.

It sounds like the intended to put most of the blame on the children.

In CBT for adolescents, parents are actively involved during the treatment. The aims of the therapy take the specific developmental tasks of adolescents into account and return to full-time education is one of the treatment goals (see also Supplementary material).

I really fear for the safety of the children if their parents are gaslighted as well.

 

[Utsikt]

Characteristics of the patients
From November 2021 to January 2023, six consecutively referred patients were assessed for eligibility and fulfilled our inclusion criteria. One patient refused to participate in the study; five patients were included and completed treatment. One patient (case 3) stopped completing the weekly assessments because she found them too demanding. She continued CBT and completed the post-CBT questionnaires. In one patient (case 4) only 12 observations were collected, making it possible that the PDT did not have sufficient statistical power to detect changes in fatigue. Because only two patients completed the daily fatigue assessments, these results are not presented. The patients were treated by three therapists.

What a complete mess. 3/5 not completing the assessments.

 

[Utsikt]

Figure 1. Results 12 weeks after starting CBT. CIS-fatigue is the Fatigue severity subscale of the Checklist Individual Strength. The green line indicates the period of CBT delivery. Cases 1, 2 and 5, show significant improvement in weekly assessed fatigue severity after 12 weeks (primary outcome). Case 3 stopped completing weekly assessments.

Case 1 and 2 were already on a downwards trend.
Case 3 and 4 has too much missing data.
Case 5 did not change much and was still severely fatigued.

 

[Utsikt]

They don't explain exactly how they characterised PEM, and the link to the Supplementary Material is just the link to the main article.

I eventually found the supplementary file. There’s a collapsable menu at the top:

The file does not explain how they characterised PEM. But it has this as an inclusion criteria:

Met 2003 revised U.S. Centers for Disease Control and Prevention (CDC) case definition of ME/CFS according to their referring paediatrician.

 

[rvallee]

Severe fatigue following COVID-19 is a debilitating symptom in adolescents for which no treatment exists currently.

I guess Knoop hasn't read Knoop's research? In which he has been claiming this. He is even claiming this here, on the basis of a very cheap anecdote where you have to "just trust him, bro".

It's a good sign of a serious professionals with years of academic and clinical experience promoting a treatment paradigm that has established itself as a fully curative treatment model that they resort to anecdotes / case studies of that treatment. That's how you know these people are serious. They totally could swing a hole-in-one, they just prefer to putt on the practice turfs with no one watching then send you a video titled "trust me bro, I nailed it, hole-in-one wooot!". Got it.

 

[Arvo]

I eventually found the supplementary file. There’s a collapsable menu at the top:
[photo]
The file does not explain how they characterised PEM. But it has this as an inclusion criteria:

>>Met 2003 revised U.S. Centers for Disease Control and Prevention (CDC) case definition of ME/CFS according to their referring paediatrician.<<

Spoiler: Deleted as confused CDC with CCC criteria

Very interesting, as the CCC are way more elaborate and precise than mere fatigue.

Spoiler: This also raises a question.

(This also raises a question. They used "severity of fatigue" as their primary outcome and they "target" the subjective reporting of fatigue, as per their usual approach following the CB model Knoop and Bleijenberg have been using for decades.

Apart from the mess, unreliableness through incomplete data, and normal healing occurence of LC, they imply that their patients got "normal physical functioning" and "were no longer physically impaired" because of the CBT - so, what then happened to the rest of the CCC required symptoms? They all went poof?)

It's The Netherlands, so due to ignorance and decades of dominant psychosomatic narrative, I doubt wheter the average paediatrician knows what PEM means, I expect them to just translate that as "feeling fatigued after doing stuff". (Even more so if they were pediaetricians in close contact with Knoop's medical psychology department at the same hospital, as he is the *cough* expert.)

They don't explain exactly how they characterised PEM, and the link to the Supplementary Material is just the link to the main article.

"They all reported PEM, the frequency ranged from ‘every day’ to ‘few times a week’. They all reported school absence ranging from ‘several times a week’ to ‘few times a month’."

Whoot? What kind of PEM is that? Several times a week. For me PEM takes a couple of days. They probably measured fatigue after exertion?

Probably. Also, Knoop has a track record of distorting the meaning of words to fit his purpose, he did it with "recovery". Since a short while he's started to claim that CBT has an effect on PEM as well as fatigue (I'd reckon that is because he can't escape it anymore if he wants to continue to claim effectiveness on ME/CFS & Long Covid) and I'd find it on brand if he was messing about with PEM's definition and meaning to do that.

A reminder that for the referred-to previous CBT study he did on Long Covid, with almost the same team and funded by ZonMw with the impression that CBT would improve fatigue and with it influence patients’ work ability and physical and social functioning, they left the actigraphy info out of the paper which found no result for increase of activity (David Tuller's piece on it here.)

"A reduction of fatigue will not necessarily lead to increased levels of objective physical activity or vice versa. Also, reduced fatigue levels do not necessarily concur with improved aerobic capacity. In our study there was no significant difference between the conditions in the increase in physical activity assessed with actigraphy."

Also, PEM was not a selection criterium there, nor was it even mentioned in the paper.
But still, at a Long Covid symposium in Amsterdam Knoop claimed that the study had found "improved physical functioning" and "less often PEM (increase of complaints after exertion)". (And that it was a "safe treatment") Exactly the claims he makes in this paper.

This also may illustrate how he may have "defined" PEM for the study: as a simple "increase of complaints after exertion" which can so easily be distorted, including for it to apply to people without PEM, or healthy people even.

(Which is of course bollocks, PEM is a state, a worsening of the illness, which includes bodily dysfunction & -discomfort and hitting a "wall" in functioning ability, and which gets induced by -regularly absurdly- disproportionate/inappropriate exertion to cause it, and takes some time to peter out again, if it even does. It's not simply feeling worse or getting symptoms after exertion, although that is a part of it, but that feels nothing like a normal effect of e.g. fatigue or sore muscles people without PEM get after e.g jogging.

Spoiler: Deleted as confused CDC with CCC criteria

As per the CCC, it's: "inappropriate loss of physical and mental stamina, rapid muscular and cognitive fatigability, post-exertional malaise and/or post-exertional fatigue and a tendency for other associated symptoms within the patient’s cluster of symptoms to worsen." (Canadian Consensus Criteria - MEpedia)

(Like with the previous study I also have questions again regarding the funding and its application (again ZonMw -dutch public money- and the NKCV), but am unable to look at it more.)

 

[Utsikt]

Very interesting, as the CCC are way more elaborate and precise than mere fatigue.

Are the CDC criteria the same as the CCC criteria?

It seems to me like they might have a typo, because there is a 2005 CDC version by Reeves.

Source

And CDC 2005 used Fukuda:
https://pmc.ncbi.nlm.nih.gov/articles/PMC1334212/

Edit: there are no references for the criteria at all.

 

[Arvo]

Are the CDC criteria the same as the CCC criteria?

Nope! Brain glitch.

I will adjust my post.

(Edited to add: 2003 = CCC, so hence the mistake.)

 

[Arvo]

Are the CDC criteria the same as the CCC criteria?

It seems to me like they might have a typo, because there is a 2005 CDC version by Reeves.

Source

And CDC 2005 used Fukuda:
https://pmc.ncbi.nlm.nih.gov/articles/PMC1334212/

Edit: there are no references for the criteria at all.

Would not be the first time the Dutch psychosomatic movement is vague about criteria, using CDC which means Fukuda. Rosmalen repeatedly stated they were using the "CDC criteria" for Lifelines, implying they were using the most recent ones without being clear that it was Fukuda 1994.

(See e.g. here.)