How many Long COVID patients develop ME/CFS? by Art Mirin (August 20, 2022)

[Tom Kindlon]

Art has kindly given me permission to share this

How many Long COVID patients develop ME/CFS? Art Mirin, 8/20/22

Overview: Of the 5 studies of Long COVID patients below, 4 of them addressed ME/CFS onset (per case definition); the other looked at ME/CFS symptoms. Two of them used CCC, one used NAM, and the other Fukuda. The two that used CCC might not have been independent cohorts, as they were from the same facility in Germany with overlapping co-authors. Two of the four studies used patients with persistent moderate to severe fatigue and exertion intolerance for more than six months after mild to moderate COVID-19. A third used patients with shortness of breath. The only study that did not control for symptoms (Bonilla, Stanford) used a cohort of 134 people and found 36% to satisfy the ME/CFS case definition.

Kedor C, Freitag H, Meyer-Arndt L, et al. 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. MedRxiv, Preprint 2021. Doi: 10.1101/2021.02.06.21249256.

Charite University Hospital 42 patients 45% ME/CFS (CCC) However, cohort is described as: “persistent moderate to severe fatigue and exertion intolerance for more than six months after mild to moderate COVID-19”. That is, this is not a random sample of LC patients.

Haffke M, Freitag H, Rudolf G, et al. Endothelial dysfunction and altered endothelial biomarkers in patients with post-COVID-19 syndrome and chronic fatigue syndrome (ME/CFS). J Transl Med 2022; 20(138). Doi: 10.1186/s12967-022-03346-2.

Charite University Hospital 30 patients 47% ME/CFS (CCC) Is this cohort separate from that of Kedor, et al (2021), which was published as a preprint? Kedor, et al. cites study evaluation period July-Nov 2020. Cannot find corresponding information here. Note too that the cohort is described as: “persistent moderate to severe fatigue and exertion intolerance for more than six months after mild to moderate COVID-19”. That is, this is not a random sample of LC patients.

Mancini DM, Brunjes DL, Lala A, et al. Use of Cardiopulmonary Stress Testing for Patients with Unexplained Dyspnea Post-Coronavirus Disease. JACC: Heart Failure, 2021; 9(12):927-937. Doi: 10.1016/j.jchf.2021.10.002.

Mt Sinai 41 patients 46% ME/CFS (Fukuda) “This was a prospective study of patients who had been reverse transcription polymerase chain reaction positive for SARS-CoV-2 and who developed new and persistent shortness of breath for >3 months after recovery.” That is, this was not a random sampling of LC patients.

Bonilla H, Quach TC, Tiwari A, et al., Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) is common in post-acute sequelae of SARS-CoV-2 infection (PASC): results from a post-COVID-19 multidisciplinary clinic. BMJ Yale Preprint, 2022. Doi: 10.1101/2022.08.03.22278363.

Stanford 134 patients 36% ME/CFS (NAM) Original cohort had 140 patients, but 6 excluded. 105 patients had symptoms longer than 6 months; of those, 46% satisfied ME/CFS case definition.

Twomey R, DeMars J, Franklin K, et al. Chronic Fatigue and Postexertional Malaise in People Living with Long COVID: An Observational Study. Phys. Ther. 2022; 102(4) pzac005. Doi: 10.1093/ptj/pzac005.

University of Calgary 213 patients Did not evaluate using ME/CFS case definition 71% had chronic fatigue, 59% PEM

 

[BrightCandle]

Is notable that still no one is managing to reach the severe patients to assess their condition. They obviously can't be coming into clinics for care and nothing has been learnt from the exclusion of these patients in ME/CFS research either. They just aren't appearing in any of the research and the consequences are likely biasing the data because I suspect those severe patients are lot more likely to be suffering ME/CFS symptoms.

 

[Peter T]

Is notable that still no one is managing to reach the severe patients to assess their condition. They obviously can't be coming into clinics for care and nothing has been learnt from the exclusion of these patients in ME/CFS research either. They just aren't appearing in any of the research and the consequences are likely biasing the data because I suspect those severe patients are lot more likely to be suffering ME/CFS symptoms.

This very worrying, given there are little or no relevant services for people with severe or very severe ME, failure to also recognise the existence of severe Long Covid patients will mean they also will be missed in planning new services.

Also, as with ME, this increases the risk of poorly designed research ending up recommending inappropriate or even harmful rehabilitation for those that have the core ME symptom of PEM. With severe or very severe patients displaying PEM any rehabilitation aimed at increasing activity levels is self evidently a non starter, whereas mild or moderate patients may have some capacity to undertake rehabilitation over a fixed term intervention period, especially if also reducing activity in other areas, before PEM catastrophically kicks in.

 

[Tom Kindlon]

Not quite same but there was also this study:
Post-Acute COVID-19 Symptoms, a Potential Link with [ME/CFS]: A 6-Month Survey in a Mexican Cohort, 2021, González-Hermosillo et al
https://www.s4me.info/threads/post-...-cohort-2021-gonzález-hermosillo-et-al.20913/

There is a large discrepancy in the prevalence of ME/CFS as a result of using different definitions. The more specific the exclusion criteria in the definition, the smaller the number of patients diagnosed with ME/CFS.

Based on the original criteria of ME/CFS proposed by the Centers for Disease Control and Prevention (CDC) Fukuda definition of 1994 [13], the only mandatory feature of ME/CFS is unexplained chronic fatigue, which must be accompanied by at least four out of eight minor symptoms related to neurological, cognitive, sleep, autonomic, gastrointestinal, and genitourinary disturbances, plus pain. In our survey, 23 (17.6%) patients met this case definition criteria.

The Canadian clinical case definition [14] specifies that post exertional malaise (a vague feeling of discomfort or fatigue) must occur with a loss of physical or mental stamina, muscle, or cognitive fatigability. In addition, there need to be two or more neurological/cognitive manifestations, (unrefreshing sleep or poor sleep quality), as well as a significant degree of arthralgia and/or myalgia. Finally, there needs to be at least one symptom from two of the following categories: autonomic manifestations (neurally mediated hypotension, postural orthostatic tachycardia, lightheadedness, palpitations with or without arrhythmias), neuroendocrine manifestations (recurrent feelings of feverishness and cold extremities), and immune manifestations (recurrent sore throats). Therefore, in our cohort, 20 (15.3%) patients met these criteria.

Compared with the International Consensus Criteria of 2011 [15], where a patient has to report at least eight (one mandatory: post-exertional neuroimmune exhaustion, and seven variable symptoms) to meet the diagnosis of ME, while autonomic, sensory and cognitive dysfunctions are not compulsory; 25 (19.2%) of our patients met the diagnosis criteria.

The Institute of Medicine [16], recently proposed a new case definition that included the following 4 symptoms: substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities; post-exertional malaise, unrefreshing sleep; and at least one of the two following symptoms: cognitive impairment or orthostatic intolerance. According to this definition, the presence of other illnesses should not preclude patients from receiving a diagnosis of ME/CFS (SEID) except in the event that all the symptoms can be accounted for by these other illnesses. Following the SEID case definition in our cohort, only 17 (13%) patients met the criteria for ME/CFS.

 

[rvallee]

Is notable that still no one is managing to reach the severe patients to assess their condition. They obviously can't be coming into clinics for care and nothing has been learnt from the exclusion of these patients in ME/CFS research either. They just aren't appearing in any of the research and the consequences are likely biasing the data because I suspect those severe patients are lot more likely to be suffering ME/CFS symptoms.

Most likely simply not seen in clinics and most are overflowing with demand so they obviously don't bother seeking them out. I've seen many of the usual "too sick for this clinic, discharged" we see in ME. The clinics only want the easy cases, makes them look good even though they're useless.

 

[RedFox]

Not quite same but there was also this study:
Post-Acute COVID-19 Symptoms, a Potential Link with [ME/CFS]: A 6-Month Survey in a Mexican Cohort, 2021, González-Hermosillo et al
https://www.s4me.info/threads/post-acute-covid-19-symptoms-a-potential-link-with-me-cfs-a-6-month-survey-in-a-mexican-cohort-2021-gonzález-hermosillo-et-al.20913/

Their numbers make me wonder if something's up with their methodology. 23 people met Fukuda, but 25 met the much more restrictive ICC? And only 17 met the fairly inclusive IOM criteria?