Post-COVID Fatigue Signal ME/CFS Exercise Intolerance

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A new study provides even more evidence that a significant subset of people who suffer from persistent fatigue and exercise intolerance after COVID-19 will meet the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome ( ME/CFS).

Data from the prospective observational study of 42 patients with ‘post-COVID-19 syndrome (PCS)’, including persistent fatigue and exercise intolerance, suggest that a large proportion will meet diagnostic criteria stringent for ME/CFS, including characteristic post-exertional malaise (PEM). Still others may experience a similar disability but do not have the duration and/or severity requirements for diagnosis.

Additionally, disease severity and symptom burden were found to be similar in people with ME/CFS after COVID-19 and in a group of 19 age- and sex-matched people with ME/CFS. CFS that were not associated with COVID-19.



Doctor Carmen Scheibenbogen

“The key finding is that ME/CFS is indeed part of the post-COVID syndrome spectrum and is very similar to the ME/CFS we experience after other infectious triggers,” said lead author Carmen Scheibenbogen. , MD, acting director of the Institute for Medical Immunology at the Medical Campus of Charité University Virchow-Klinikum, Berlin, Germany, said Medscape Medical News.

Importantly, from a clinical perspective, decreased hand grip strength (HGS) and orthostatic intolerance were common in all patient groups, as were several lab values, Claudia Kedor , MD, and his Charité colleagues report in the article, published online August 30 in Nature Communication.

Of the 42 people with PCS, including persistent fatigue and exercise intolerance lasting at least 6 months, 19 met the stringent Canadian Consensus Criteria (CCC) for ME/CFS, established in 2003, which require PEM, as well as sleep dysfunction, significant persistent fatigue, pain, and several other symptoms of neurological/cognitive, autonomic, neuroendocrine, and immune categories that persist for at least 6 months.

Of the 23 who did not meet the CCC criteria, 18 still underwent PEM, but for less than the required 14 hours set by the authors based on recent data. The original CCC had suggested 24 hours as the PEM duration. Eight subjects met all Canadian criteria except for neurological/cognitive symptoms. None of the 42 had signs of severe depression.

The previously widely used “Fukuda” 1994 criteria for ME/CFS are no longer recommended because they do not require PEM, which is now considered a key symptom. The most recent criteria from the 2015 Institute of Medicine (now the Academy) do not define the duration of EMP, the authors note in the paper.

Scheibenbogen said: “Post-COVID has a range of syndromes and conditions. We find that a subset of patients have similar symptoms of ME/CFS but do not meet the CCC, although they may meet to less stringent criteria. We believe this is of relevance for diagnostic markers and therapy development, as there may be different pathomechanisms between subsets of post-COVID patients.

She pointed to other studies from her group suggesting that inflammation is present early in post-COVID (not yet published), while in the subset that transitions to ME/CFS, autoantibodies or endothelial dysfunction play a more important role. “At the moment it’s quite complex, and I don’t think we’ll end up with just one pathomechanism, so I think we’ll have to develop various treatment strategies.”



Doctor Anthony Komaroff

Asked to comment on the new data, Anthony L. Komaroff, MD, professor of medicine at Harvard Medical School, chief medical officer at Brigham and Women’s Hospital in Boston and editor of the Harvard Health LetterTold Medscape Medical News“This article adds to the evidence that disease with symptoms that meet criteria for ME/CFS may follow COVID-19 in nearly half of patients who have persistent symptoms. This may occur even in people who initially have only mild symptoms of COVID -19, although it is more likely to occur in the sickest people when they first get COVID-19. ‘EM/CFS have been severely impaired in their ability to function, [both] at work and at home.”

But, Komaroff also warned, “the study does not help determine what fraction of all people infected with SARS-CoV-2 go on to develop a disease like ME/CFS, or how long that disease will last. It is crucial that we get answers to these questions, because the impact on the economy, the health system and the disability system could be considerable.”

He pointed to a recent Brookings Institution report concluding that “the long COVID may be a major contributor to the shortage of job candidates plaguing many companies.”

Biomarkers include hand grip strength, orthostatic intolerance, and laboratory measurements

Hand grip strength, assessed by 10 repeated grips at maximal force and repeated after 60 minutes, was lower for all those fulfilling the ME/CFS criteria, compared to healthy controls. Hand grip strength parameters were also positively correlated with laboratory hemoglobin measurements in both PCS groups that met and did not meet the Canadian ME/CFS criteria.

A total of three patients with PCS who did not meet criteria for ME/CFS and seven patients with PCS who met criteria for ME/CFS had seated blood pressure greater than 140 mm Hg systolic and/or greater than 90 mm Hg diastolic. Five patients with PCS—four who met ME/CFS criteria and one who did not—met criteria for postural orthostatic tachycardia syndrome. Orthostatic hypotension was diagnosed in a total of seven with PCS, including one who did not meet the criteria for ME/CFS and the others who did.

Among the significant laboratory findings, mannose-binding lectin deficiency, which is associated with increased susceptibility to infections and found in only about 6% of historical controls, was found more frequently in both PCS cohorts (17% of those with ME/CFS and 23% of those without) than it has been in the past in those with ME/CFS compared to historical controls (15%).

There was only a slight elevation in C-reactive protein, the most commonly measured marker of inflammation. However, another marker indicating inflammation in the past 3-4 months, interleukin 8 assessed in erythrocytes, was above normal in 37% of patients with PCS and ME/CFS and in 48 % of patients with PCS who did not meet criteria for ME/CFS.

Elevated antinuclear antibodies, anti-thyroid peroxidase antibodies, vitamin D deficiencies, and folic acid deficiencies have all been observed in a small number of patients with SCP. Angiotensin-converting enzyme 1 (ACE1) levels were below normal in 31% of all patients.

“We must anticipate that this pandemic has the potential to dramatically increase the number of patients with ME/CFS,” Kedor and colleagues write. “At the same time, it offers the unique chance to identify patients with ME/CFS at a very early stage of the disease and to apply interventions such as early stimulation and adaptation with a better therapeutic prognosis. Moreover, it is an unprecedented opportunity to understand the underlying pathomechanism and characterize targets for specific treatment approaches.”

Scheibenbogen and Komaroff reported no relevant financial relationship.

Communication Nature. Published online August 30, 2022. Full text

Miriam E. Tucker is a freelance journalist based in the Washington, DC area. She is a regular contributor to Medscape, with other work published in The Washington Post, NPR’s Shots blog, and Diabetes Forecast magazine. She’s on Twitter @MiriamETucker.

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Post-COVID Fatigue Signal ME/CFS Exercise Intolerance

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