Nature: A prospective observational study of post-COVID-19 CFS following the first pandemic wave in Germany... Scheibenbogen et al, 2022

[Kalliope]

Full title: A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity


Abstract

A subset of patients has long-lasting symptoms after mild to moderate Coronavirus disease 2019 (COVID-19). In a prospective observational cohort study, we analyze clinical and laboratory parameters in 42 post-COVID-19 syndrome patients (29 female/13 male, median age 36.5 years) with persistent moderate to severe fatigue and exertion intolerance six months following COVID-19.

Further we evaluate an age- and sex-matched postinfectious non-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome cohort comparatively.

Most post-COVID-19 syndrome patients are moderately to severely impaired in daily live. 19 post-COVID-19 syndrome patients fulfill the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome.

Disease severity and symptom burden is similar in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome and non-COVID-19/myalgic encephalomyelitis/chronic fatigue syndrome patients.

Hand grip strength is diminished in most patients compared to normal values in healthy.

Association of hand grip strength with hemoglobin, interleukin 8 and C-reactive protein in post-COVID-19 syndrome/non-myalgic encephalomyelitis/chronic fatigue syndrome and with hemoglobin, N-terminal prohormone of brain natriuretic peptide, bilirubin, and ferritin in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome may indicate low level inflammation and hypoperfusion as potential pathomechanisms.

 

[Kalliope]

Quote:

Taken together, our study provides evidence that patients following mild COVID-19 develop a chronic syndrome fulfilling diagnostic criteria of ME/CFS in a subset.

By defining and characterizing subgroups of PCS patients we could identify associations of HGS with biomarkers which may indicate hypoperfusion and inflammation as potential pathomechanisms.

We must anticipate that this pandemic has the potential to dramatically increase the number of ME/CFS patients. At the same time, it offers the unique chance to identify ME/CFS patients in a very early stage of disease and apply interventions such as pacing and coping early with a better therapeutic prognosis.

Further, it is an unprecedented opportunity to understand the underlying pathomechanism and characterize targets for specific treatment approaches.

 

[rvallee]

We must anticipate that this pandemic has the potential to dramatically increase the number of ME/CFS patients

It needs to be said but should be said differently, anticipating something means seeing it in advance, preparing, "pre": before. We are 2.5 years into this and a full century into the issue in general with decades of non-stop "controversy" and pseudoscience sucking up all the oxygen. There is no talk of anticipating anything at this point, the medical profession isn't even reacting to it yet. The horse has loooong left the barn, any talk of closing the gate is just silly at this point.

The best case scenario with expertise is to be able to anticipate and deal with problems before they become disastrous. The patient community warned about this and the experts did not react, did not anticipate, are still clearly waiting for the issue to stop being talked about.

It has to be said that this was anticipated by many, should have been anticipated by the medical profession, while in reality they are still not even reacting. The continuing inability of medicine to self-criticize is one of its biggest weaknesses, it's basically self-induced yes-manning.

 

[Jaybee00]

First, this is Nature Communications, which is not the same journal as Nature (same publisher).

Second, this abstract is poorly written and filled with typos, which is never a good sign.

 

[Andy]

The authors, "We sort of used CCC". My bolding.

"Several diagnostic criteria have been proposed for use in ME/CFS, of which CCC are recommended for diagnosis confirmation in secondary care and in research30. Severity and duration of PEM is a key diagnostic criterion of the CCC. In contrast to the original minimum length of 24 h of PEM required by the CCC, we set the duration criterion at 14 h as shown by others to yield the highest diagnostic sensitivity and specificity to discriminate patients with ME/CFS from patients with fatigue due to other chronic illnesses10,14.

Strikingly, while all PCS patients suffered from moderate to severe fatigue and exertion intolerance, a subset did not fulfill the CCC criteria for ME/CFS mostly due to a shorter PEM lasting <14 h. We have not seen such a symptom constellation in other chronic postinfectious syndromes so frequently. The previously widely used Fukuda or CDC-1994 criteria do not require PEM for the diagnosis of ME/CFS thus most PCS/non-ME/CFS patients from our study would have been classified as ME/CFS31,32. Fukuda criteria are, however, no longer recommended to be used for ME/CFS diagnosis as they do not require PEM, the key symptom of ME/CFS12,13. The IOM (Institute of Medicine) criteria do not define the length of PEM but require that it should occur at least half of the time with moderate to severe intensity. Thus many patients not classified as ME/CFS in our study would not have fulfilled the IOM criteria either30"

 

[Andy]

From reference 10, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165517/, Jason et al, my bolding,

"Results for the two time periods did vary and setting the criterion at PEM duration of 14 or more hours (including responses of both ‘14–23 h’ and ‘24 h or more’) would include the majority (87.5%) of patients with ME and CFS in the screening process, while discriminating out a large number (77.8%) of patients with other chronic illnesses. Setting the criterion at 24 h or more would include a smaller subset of patients with ME and CFS (70.3%) but exclude a greater proportion of patients with other chronic illnesses (88.6%). Using the robust criterion of 14–23 h could be thought of as a clinical criterion, which is broader than a research criterion that could be 24 h or more. Further research is needed to assess whether those in these two time frames actually are different in terms of levels of disability or reductions in functioning."

and I see nothing in reference 14, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817848/, Jason et al, that supports reducing the duration requirement for PEM, although I may have missed something.

 

[Sid]

Nature Communications (garbage open access journal), not Nature. Big difference.

 

[BrightCandle]

I think I am on the lower end of that scale, I tend to get PEM the next day after an exertion the prior afternoon, so around 14-16 hours. But I also get a pretty good predictor when I try to sleep and can't and that will happen just hours after an exertion. I do wonder if getting to sleep disruption is something others notice on the day of exertions or if its common enough normally that is not a clear signal for others.

 

[Mij]

I do wonder if getting to sleep disruption is something others notice on the day of exertions or if its common enough normally that is not a clear signal for others.

I do not experience any sleep disruptions just before, during or after PEM.

Sleep isn't a factor for me.

 

[Kalliope]

First, this is Nature Communications, which is not the same journal as Nature (same publisher).

huh, I didn't know that. Thought it was the same thing. Thanks for pointing it out.

 

[RedFox]

I think I am on the lower end of that scale, I tend to get PEM the next day after an exertion the prior afternoon, so around 14-16 hours. But I also get a pretty good predictor when I try to sleep and can't and that will happen just hours after an exertion. I do wonder if getting to sleep disruption is something others notice on the day of exertions or if its common enough normally that is not a clear signal for others.

I think this discussion is around how long PEM lasts, not how long it's delayed.

 

[Amw66]

I think this discussion is around how long PEM lasts, not how long it's delayed.

Delay could be interesting too, as is when " peak PEM " is and link to severity , and also type of disease onset Cognitive v physical v both in terms of inducing - does this differ ( yes here)
For a defining feature it's both poorly defined and woefully underesearched

 

[RedFox]

Delay could be interesting too, as is when " peak PEM " is and link to severity , and also type of disease onset Cognitive v physical v both in terms of inducing - does this differ ( yes here)
For a defining feature it's both poorly defined and woefully underesearched

There's so much potential here. Messing around with symptom data from a cohort of thousands of pwME could yield fascinating insights. My mind buzzes with possibilities. Hopefully Solve ME/CFS will have something like this.

 

[Amw66]

We need machine learning applied . This seems a systems condition , it dosn't seem remotely linear .
" Both and " not binary , a complete Schroedinger condition.

It's very like climate science with feedback loops and tipping points - how do we get these kind of scientists interested?
since physicists got involved in cancer research and " quantum biology" gained traction , more progress seems to have been made .

 

[Tom Kindlon]

Press release
https://www.eurekalert.org/news-releases/963385

Twitter thread with a few extracts from press release:

.

 

[Dolphin]

Protocol:
Studying the pathophysiology of coronavirus disease 2019: a protocol for the Berlin prospective COVID‑19 patient cohort (Pa‑COVID‑19)
https://link.springer.com/epdf/10.1...PpoF7Qd0KgM5xmttzdwhvhqvATBk4F8B3Vwb9HWz1vUs=

 

[Kalliope]

Medscape Post-COVID Fatigue, Exercise Intolerance Signal ME/CFS by Miriam Tucker


quotes:

"The major finding is that ME/CFS is indeed part of the spectrum of the post-COVID syndrome and very similar to the ME/CFS we know after other infectious triggers," senior author Carmen Scheibenbogen, MD, acting director of the Institute for Medical Immunology at the Charité University Medicine Campus Virchow-Klinikum, Berlin, Germany, told Medscape Medical News.

...

"This paper adds to the evidence that an illness with symptoms that meet criteria for ME/CFS can follow COVID-19 in nearly half of those patients who have lingering symptoms. This can occur even in people who initially have only mild symptoms from COVID-19, although it is more likely to happen in the people who are sickest when they first get COVID-19. And those who meet criteria for ME/CFS were seriously impaired in their ability to function, [both] at work and at home."


But, Komaroff also cautioned, "the study does not help in determining what fraction of all people who are infected with SARS-CoV-2 go on to develop a condition like ME/CFS, nor how long that condition will last. It is crucial that we get answers to these questions, as the impact on the economy, the healthcare system, and the disability system could be substantial."

 

[Trish]

Thread on a webinar to be given on this research:
Webinar: COVID-19 as a Trigger for ME/CFS: Severity Biomarkers and Underlying Mechanisms with Dr Carmen Scheibenbogen

 

[forestglip]

Notable lab findings

n= 19 PCS/ME/CFS and 23 PCS/non-ME/CFS (Some participants were not tested for some of the following markers.)

Remarkably, mannose binding lectin (MBL) deficiency, which is associated with enhanced susceptibility to infections and was found previously more frequently in ME/CFS (15%) than in a historical control group (6%)28, was also more frequent in both PCS patient cohorts with 17% and 23%28.

While C-reactive protein (CRP) was slightly elevated in two PCS patients only, another marker of inflammation interleukin 8 (IL8), which we assessed in erythrocytes, was above the normal value in 37% and 48% of PCS/ME/CFS and PCS/non-ME/CFS patients, respectively, indicating inflammation during the last 3–4 months29.

Elevated antinuclear antibodies (ANA) of 1:160–1:1280 were found in eight patients.

Four patients (two of each group) showed elevated anti-thyroid peroxidase (TPO) antibodies with normal thyroid stimulating hormone (TSH) and free triiodothyronine/thyroxine (fT3/fT4).

Deficiencies of vitamin D were found in 11% and 22% of PCS/ME/CFS and PCS/non-ME/CFS patients, respectively, and folic acid deficiencies in 19% of all patients.

N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was slightly elevated in three patients.

ACE1 levels were below the normal range in 31% of all patients.

Hand grip strength (HGS) correlations with lab markers

HGS parameters showed a positive correlation with levels of hemoglobin in both PCS/non-ME/CFS and PCS/ME/CFS. Further we observed a negative correlation of Fmax1 with IL8 in erythrocytes and of Fmean2 with CRP and a positive correlation with ACE2 levels in the PCS/non-ME/CFS cohort. In the PCS/ME/CFS cohort there was a positive correlation of HGS parameters with bilirubin and ferritin and a negative correlation with NT-proBNP levels. In non-COVID ME/CFS patients we observed a similar correlation of bilirubin with HGS which was not significant after BH correction.