Trial Report There Is No Established Connection Between Long-COVID and Chronic Fatigue Syndrome, 2025, Kouyoumdjian et al

[John Mac]

https://www.preprints.org/manuscript/202506.2016/v1

Abstract​

Fatigue is the most common symptom of Long-COVID (LC), characterized by persistent or new symptoms occurring at least three months after the initial SARS-CoV-2 infection, with no other identifiable cause.
This study aims to assess the prevalence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) as a condition associated with LC.
The study included 37 adult controls without SARS-CoV-2 infection and 32 cases with a history of infection, categorized into two groups: LC-yes and LC-no.
ME/CFS was diagnosed using the International Consensus Criteria. The most frequent symptoms of LC included post-exertional malaise (PEM), neurosensory, perceptual, or motor disturbances, cognitive impairments, sleep disturbances, pain, loss of thermoregulatory stability, and flu-like symptoms, with significant differences compared to the other groups. PEM was reported in all LC-yes cases.
ME/CFS was diagnosed in 18.8% of the LC-yes group, 6.7% of the LC-no group, and 10.8% of controls, with no significant differences.
Experiencing more than six symptoms during acute infection—such as tiredness, loss of taste, fatigue, loss of smell, headache, fever, cough, myalgia, sore throat, dyspnea, rhinorrhea, and diarrhea—doubled the likelihood of developing LC.
Experiencing at least six symptoms during the acute infection further increased the likelihood of developing LC. A high proportion of LC cases exhibited PEM, neurosensory, perceptual, or motor disturbances, cognitive impairments, and sleep disturbances, with significant differences compared to the control and LC-no groups. However, only 18.8% of LC cases met the ICC criteria for ME/CFS diagnosis, showing no significant difference from the LC-no and control groups.

I don't understand the studies headline with the following finding.
"ME/CFS was diagnosed in 18.8% of the LC-yes group, 6.7% of the LC-no group"
Wouldn't this point to ME/CFS being 3 times more likely to be prevalent in Long Covid?
Is this not considered significant?
Also "PEM was reported in all LC-yes cases." Wouldn't this point to all LC-yes cases having ME/CFS?

Doesn't the 10.8% of the non-Covid control group being diagnosed with ME/CFS seem very high?
I thought ME/CFS prevalence (in the UK) was about 0.25%, nowhere near 10%?

 

[Eleanor]

Tiny numbers, and the non-covid controls were also "randomly selected" patients at the teaching hospital but I can't see if the paper includes details on what their health conditions were.

 

[InitialConditions]

This must be the most bizzare abstract I've read for many, many years.

 

[Eleanor]

In the LC-yes group, PEM was present in 100% of cases. Yet, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), as defined by the ICC [8], was diagnosed in only 18.8%.

Table 2 shows 29.7% of the control group experiencing "PEM".

 

[InitialConditions]

Wouldn't this point to ME/CFS being 3 times more likely to be prevalent in Long Covid?
Is this not considered significant?

It's not significant if your error bars are longer than a giraffe's neck.

 

[ME/CFS Skeptic]

Doesn't the 10.8% of the non-Covid control group being diagnosed with ME/CFS seem very high?
I thought ME/CFS prevalence (in the UK) was about 0.25%, nowhere near 10%?

Yes that seems about 10-20 times too large.

 

[BrightCandle]

They have the definitions of PEM wrong completely, its defined as tiredness/fatigue/pain immediately after exercise. I don't know how they managed to butcher the ICC criteria so badly but they have completely misunderstood. Fatigue being defined as tiredness that doesn't resolve from rest, which also isn't right either.

When your tiredness/fatigue in your apparently health group is 62.5% you have got something badly wrong. They have so many of the LC-no and control groups having PEM its kind of ridiculous but given how they defined it this makes a lot of sense, who doesn't feel a bit tired after a big workout? But that isn't what PEM is and its certainly not how the CCC or ICC defines PEM.

 

[Kiristar]

Should Sci4ME point out the PEM error to the author or is it a waste of time?

 

[InitialConditions]

Should Sci4ME point out the PEM error to the author or is it a waste of time?

I don't even know where you'd start with this crap. Probably a lost cause.

 

[Kitty]

Our main building was once evacuated for five hours, so we couldn't get on with our work. We got so bored that some of us decided to swap jobs – I had to plot a scene into a touring lighting board, and the LX tech had to draft my advertising copy.

It went a lot like this.

 

[InitialConditions]

Will be interesting to see if this gets published. I have no doubt given scientific publishing and peer review standards that they'll find a home for it.

 

[Kiristar]

Will be interesting to see if this gets published. I have no doubt given scientific publishing and peer review standards that they'll find a home for it.

So depressing. The more PEM gets transmuted into fatigue like this by ignorant professionals, the harder it is to make our case.

 

[InitialConditions]

So depressing. The more PEM gets transmuted into fatigue like this by ignorant professionals, the harder it is to make our case.

It really seems to be a big problem now, made much worse by poor long covid research.

 

[rvallee]

There's lab work, and then there's lab work.

 

[Trish]

Maybe someone could send them a link to our PEM fact sheet.

 

[SNT Gatchaman]

Tiredness is a nonspecific term that refers to a subjective feeling of lacking energy or experiencing exhaustion. It can stem from various physiological, psychological, or environmental causes. Fatigue is a persistent and subjective sensation of physical, mental, or emotional exhaustion that is disproportionate to recent activity and is not relieved by rest. Unlike tiredness, it often indicates an underlying medical, psychological, or physiological condition. However, in clinical anamnesis, it appears to be the same. We consider fatigue when there is no relief from rest.

As above they've completely misunderstood PEM. What's wrong with defining tiredness as simply "wanting to sleep"?

Spoiler: For some reason these Genesis lyrics came to mind

I must have dreamed a thousand dreams
Been haunted by a million screams

Now, did you read the news today?
They say the danger has gone away

Can't you see this is the land of confusion?

There's too many men, too many people
Making too many problems

This is the world we live in
And these are the hands we're given

Tell me why this is the land of confusion