Preprint: Chronic COVID-19 Syndrome and Chronic Fatigue Syndrome (ME/CFS) following the first pandemic wave in Germany.., Kedor et al, 2021

Andy

Andy

Retired committee member
Full title: Chronic COVID-19 Syndrome and Chronic Fatigue Syndrome (ME/CFS) following the first pandemic wave in Germany: a first analysis of a prospective observational study
Objective: Characterization of the clinical features of patients with persistent symptoms after mild to moderate COVID-19 infection and exploration of factors associated with the development of Chronic COVID-19 Syndrome (CCS).

Methods: Setting: Charite Fatigue Center with clinical immunologists and rheumatologist, neurologists and cardiologists at Charite University hospital.

Participants: 42 patients who presented with persistent moderate to severe fatigue six months following a mostly mild SARS-CoV-2 infection at the Charite Fatigue Center from July to November 2020.

Main outcome measures: The primary outcomes were clinical and paraclinical data and meeting diagnostic criteria for Chronic Fatigue Syndrome (ME/CFS). Relevant neurological and cardiopulmonary morbidity was excluded.

Results: The median age was 36.5, range 22-62, 29 patients were female and 13 male. At six months post acute COVID-19 all patients had fatigue (Chalder Fatigue Score median 25 of 33, range 14-32), the most frequent other symptoms were post exertional malaise (n=41), cognitive symptoms (n=40), headache (n=38), and muscle pain (n=35). Most patients were moderately to severely impaired in daily live with a median Bell disability score of 50 (range 15-90) of 100 (healthy) and Short Form 36 (SF36) physical function score of 63 (range 15-80) of 100. 19 of 42 patients fulfilled the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These patients reported more fatigue in the Chalder Fatigue Score (p=0.006), more stress intolerance (p=0.042) and more frequent and longer post exertional malaise (PEM) (p= 0.003), and hypersensitivity to noise (p=0.029), light (p=0.0143) and temperature (0.024) compared to patients not meeting ME/CFS criteria. Handgrip force was diminished in most patients compared to healthy control values, and lower in CCS/CFS compared to non-CFS CCS (Fmax1 p=0.085, Fmax2, p=0.050, Fmean1 p=0.043, Fmean2 p=0.034, mean of 10 repeat handgrips, 29 female patients). Mannose-binding lectin (MBL) deficiency was observed frequently (22% of all patients) and elevated IL-8 levels were found in 43% of patients.

Conclusions: Chronic COVID-19 Syndrome at months 6 is a multisymptomatic frequently debilitating disease fulfilling diagnostic criteria of ME/CFS in about half of the patients in our study. Research in mechanisms and clinical trials are urgently needed.
Click to expand...
https://www.medrxiv.org/content/10.1101/2021.02.06.21249256v1
 
MP and scientist Karl Lauterbach shared this study on Twitter and Facebook as well. Good to see this. Hopefully it will be published in a big journal

Curious about the significance of the objective measures like Mannose-binding lectin deficiency and elevated IL-8 levels. Although this is prospective we don't know if this MBL deficiency was already present beforehand. Very interesting though.

 
Last edited:
Disappointing that they use CFQ (it encourages its continued usage) but at least they asked about more symptoms than usual. Bit weird to ask about painful lymph nodes, rather than, say, enlarged. Mine are never painful but usually enlarged, and often tingly. It would be really important to devise the list and range of symptoms so that studies don't have to make arbitrary decisions.

The symptoms distribution suggest a much higher % that should meet the CCC. Really not sure about that:
Most CCS patients (18 of 23) did not fulfill ME/CFS criteria due to a duration of PEM less than 14 hours.
Click to expand...
91% of CCS had PEM, but it was determined not to count pretty much arbitrarily. Certainly as single points in time. That's always an issue given the wide variability.
 
Sounds interesting but there are some big caveats. What I would like to see is a big study that follows up on a large group of patients with a confirmed COVID-19 diagnosis of which only a small group will go on to develop long term symptoms. That would provide a representative sample of the population and a test of coronacrisis leads to an increase of ME/CFS.

This study, however, simply recruited patients who already had long-term symptoms following COVID-19. The paper writes for example:
Patients were selected based on a screening questionnaire, specifying COVID-19 diagnosis and symptoms including mild to moderate COVID-19 according to WHO criteria and persistent symptoms. Inclusion criteria were symptoms of moderate to severe fatigue and exertion intolerance, neurocognitive impairment, and pain six months post-infection in the absence of relevant respiratory, neurological or psychiatric comorbidity
Click to expand...
The inclusion criteria sound a lot like ME/CFS.

It also seems that they recruited patients through the website of a log COVID Facebook group:
The German facebook group of patients with long COVID contacted us first in July 2020 sharing their observations (https://c19langzeitbeschwerden.de/). The study design was developed based on frequency, type and severity of symptoms reported and discussed with the patient group. The possibility for local patients to participate in our study was communicated on their website.
Click to expand...
So there is a large risk of selection bias: we don't know how representative those 44 patients in the study where of patients who get COVID-19.
 
Not a bad start (but whose dumb idea was the CFQ?!).

This bit puzzles me though. They say all but one person in the cohort of 42 had PEM but only 19 had ME (CCC). They say themselves more people would have qualified for an ME label had they used IOM or Fukuda instead of CCC. But if all but one person really had ME-type PEM anyway, insisting on CCC seems to create an artificial division here between the Chronic Covid with ME and the Chronic Covid without ME groups. More likely those supposedly without ME were just milder cases.

But. Thing is it's not clear if the PEM definition they used was ME-type PEM. Sigh. Why do researchers insist on being so vague with their reporting of PEM? Saying it lasted more than 14 hours is neither here nor there. What were the symptoms, was increased fatigue and breathlessness enough to qualify as PEM? When did it start, with a delay or not? What did they look at here, ordinary exertion intolerance or ME-PEM? How are we supposed to know?

This isn't to say people without PEM but whose symptoms otherwise look similar to ME or people with ordinary exertion intolerance shouldn't be studied. In fact it's a good idea to study them - to compare with ME-PEM and to see what similarities and/or differences there are. Just... pleeeease describe who or what you're studying and don't throw everyone into a single melting pot.

This habit has bedevilled ME for far too long and we really, really shouldn't make the same mistake all over again with long Covid.
 
It is the way they use symptoms we talk about but have no understanding of what they are. It is infuriating the number of people who say PEM but actually mean prolonged fatigue or fatigue after exercise which are common to many things.

The problems we have after exercise are different, even talking about an increase in symptoms does not mean it is PEM as people with lung damage will feel breathless but they will not get swollen glands or the other ways PEM causes symptoms not related to the exercise involved nor will they take weeks to recover :)
 
rvallee said:
The symptoms distribution suggest a much higher % that should meet the CCC. Really not sure about that:
91% of CCS had PEM, but it was determined not to count pretty much arbitrarily. Certainly as single points in time. That's always an issue given the wide variability.
Click to expand...

Yep, I think they mentioned this under Limitations of Study:
Secondly, it is unclear, if the distinction into subgroups based on the criterion of the length of PEM indicates differences in mechanisms or merely reflect the variance of the disease spectrum.
Click to expand...
 
You must log in or register to reply here.
Back
Top Bottom