MEA Research Roundup

ME/CFS and Long Covid Research: 23 – 29 August 2022


The ME Association maintains a comprehensive index of published research on ME/CFS and Long Covid that is free to use and updated weekly.

Audio Commentary by Dr Katrina Pears

ME/CFS Research Published 23 – 29 August 2022

There have been six new ME/CFS studies and sixteen studies on Long Covid, however, there are few studies which caught our interest this week.

We have highlighted two studies below which both look into Long Covid:

Paper five (5) looks at comparing and characterising pain, fatigue and function between the three overlapping conditions: Long Covid, fibromyalgia (FM) and CFS (ME) through the use of surveys. This is one of the few studies which has been conducted which looks at all three overlapping conditions and surveyed 707 participants.

Unsurprisingly, all three conditions reported increased levels of pain, fatigue, anxiety, depression, catastrophizing (assuming the worse will happen), and kinesiophobia (fear of pain due to movement), additionally the impact on physical and cognitive function was similar. However, interestingly, lower pain and fatigue was reported in Long Covid compared to the other two conditions. Individuals with Long Covid as well as ME/CFS or FM reported even higher levels of the indicators studied (pain and fatigue).

It is disappointing that we cannot access the full study due to it being behind a paywall, as it is a large study so it is difficult to comment on the full strength of the research. However, it would have been beneficial if this was combined with some sort of biological analysis, i.e. looking at a range of substances in the blood.

Paper six (6) is another paper researching the clinical overlap between Long covid and ME/CFS, with 42 Long Covid patients with matched age and sex ME/CFS patients. The study looked at symptom severity, hand grip strength, autonomic dysfunction and a range of blood markers.

Of the 42 Long Covid patients, 19 of them fulfilled the Canadian Consensus Criteria (CCC) definition of ME/CFS, providing further evidence that following mild Covid-19 infection a subset of patients can develop symptoms meeting ME/CFS criteria. The authors stress that the number of ME/CFS patients is likely to dramatically increase.

The study also found diminished Hand Grip Strength (HGS) in all patients, and this was associated with different blood levels of biomarkers whether or not the patients had Long Covid with ME/CFS. The biomarkers which were analysed in the blood were indicators of muscle fatigue and had roles in oxygen supply, inflammation and vasoregulation. The results showed correlation (both positive and negative) between certain biomarkers and patients groups, such as:

  • Long Covid without ME/CFS: haemoglobin (endothelial function or muscle oxygen supply), interleukin 8 (IL8- inflammation) and C-reactive protein (CRP- inflammation). 
  • Long Covid with ME/CFS: haemoglobin (endothelial function or muscle oxygen supply), N-terminal prohormone of brain natriuretic peptide (NT- proBNP- marker of heart failure (but no evidence of this)), bilirubin (vasodilation and antioxidant), and ferritin (iron).
  • The authors hypothesise that the levels of biomarker substances in blood may indicate hypoperfusion (reduction in blood flow) and inflammation as potential pathomechanisms, although further investigation is needed to prove this hypothesis.

Unfortunately, this study is not well written with a number of typos throughout, and it would have been useful to assess a control group who did not have lasting symptoms after a Covid-19 infection. However, I would like to see more comprehensive studies like this which use a range of surveys, physical tests and link these to biomarkers within the blood.

ME/CFS Research References and Abstracts 

1. Chronic Fatigue Syndrome in Patients with Deteriorated Iron Metabolism

Świątczak M, Młodziński K, Sikorska K, Raczak A, Lipiński P, Daniłowicz-Szymanowicz L.

Diagnostics. 2022; 12(9):2057.


Fatigue is a common, non-specific symptom that often impairs patients’ quality of life. Even though fatigue may be the first symptom of many serious diseases, it is often underestimated due to its non-specific nature.

Iron metabolism disorders are a prominent example of conditions where fatigue is a leading symptom. Whether it is an iron deficiency or overload, tiredness is one of the most common features.

Despite significant progress in diagnosing and treating iron pathologies, the approach to chronic fatigue syndrome in such patients is not precisely determined.

Our study aims to present the current state of knowledge on fatigue in patients with deteriorated iron metabolism.

2. Effectiveness of Electroacupuncture in Patients with Chronic Fatigue Syndrome: A Systematic Review and Meta-analysis

Jaewoo Yang 1, Donghoon Shin 1, Jihoon Oh 1, Jinwoong Lim

Journal of Acupuncture Research 39(3):170-181


This review evaluated the efficacy of electroacupuncture (EA) for chronic fatigue syndrome. Randomized controlled trials (RCTs) using EA as an intervention for patients with chronic fatigue syndrome were identified in 6 databases (PUBMED, EMBASE, CNKI, J-STAGE, KMBASE, OASIS).

Fatigue indicators were used as the primary outcome measures. The quality-of-life index, efficiency rate, and level of pain were used as secondary outcome measures.

There were 408 patients from seven RCTs included in this study.

Meta-analysis showed that EA was significantly associated with fatigue relief compared with the control group (n = 141 SMD = -1.55, 95% CI: -2.58 – -0.52, p = 0.003, I² = 92%).

In addition, EA had a statistically significant improvement in quality of life compared with the control group (n = 176, SMD = -2.29, 95% CI: -3.68 – -0.90, p = 0.001, I² = 96%).

One study reported ten cases of bleeding, however, no serious adverse events were reported in any of the included studies.

This review determined that EA may have a greater clinical effect than the control group for fatigue relief and improved quality of life. However, there were several risks of bias identified.

Not all of the RCTs accurately reported the research method, all studies were conducted in 1 country (China), and the number of studies included were small.

3. The Significance of Pain Drawing as a Screening Tool for Cervicogenic Headache and Associated Symptoms in Chronic Fatigue

Bernhoff G , Huhmar HMRasmussen-Barr EBunketorp Käll L

Journal of Pain Research 15: 2547–2556


Purpose: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with a broad spectrum of symptoms, including headache. A simple, yet powerful tool – the pain drawing identifies essential aspects such as pain distribution.

The aim with this study was to:

 1) evaluate the significance of pain drawing as a screening tool for cervicogenic headache using a predefined C2 pain pattern,

2) assess whether there was an association between dizziness/imbalance and a C2 pain pattern, and

3) compare subgroups according to the pain drawing with respect to pain characteristics and quality of life.

Patients and Methods: Pain drawings and clinical data from 275 patients investigated for ME/CFS were stratified into:

1) cervicogenic headache as determined by a C2 pain pattern,

2) headache with no C2 pain pattern, and

3) no headache.

For inference logistic regression presented with odds ratios (OR) and 95% confidence intervals (95% CI) and Kruskal–Wallis test were applied.

Results: One hundred sixteen participants (42%) were stratified to the group for which the pain drawing corresponded to the C2 pain pattern, thus indicating putative cervicogenic origin of the headache.

Dizziness/imbalance was strongly associated with a C2 pain pattern; OR 6.50 ([95% CI 2.42–17.40] p ˂ 0.00), whereas this association was non-significant for patients with headache and no C2 pain pattern.

Those demonstrating a C2 pain pattern reported significantly higher pain intensity (p = 0.00) and greater pain extent (p = 0.00) than the other groups, and lower health-related quality of life (p = 0.00) than the group with no headache.

Conclusion: For patients with chronic fatigue who present with a C2 pain pattern (interpreted as cervicogenic headache) the pain drawing seems applicable as a screening tool for signs associated with neuropathic and more severe pain, dizziness and reduced quality of life as detection of these symptoms is essential for targeted treatment.

4. A Comparative Study of Antifatigue Effects of Taurine and Vitamin C on Chronic Fatigue Syndrome

Shin-Hee Kim, Hyun-Jin Kim, Semi Kim, Ju-Seop Kang, Young Tae Koo, Sang Hun Lee, Dong-Hyun Paik

Pharmacology & Pharmacy, 13, 300-312


Vitamin C and taurine (TR) are well known as active components for fatigue recovery. However, the mechanism of the anti-fatigue effects of vitamin C and TR is still unclear.

Our study was designed to evaluate the anti-fatigue activities of vitamin C and TR in an animal test for fatigue and to compare the activities between vitamin C and TR.

Materials and Methods: Vitamin C, TR or their combination were orally administrated to mice once daily for 15 days, and then metabolic activities such as blood glucose, triglyceride (TG), lactate, and lactate dehydrogenase (LDH) as well as antioxidant activities such as malondialdehyde (MDA) and superoxide dismutase (SOD) were determined (evaluated) after forced swimming test (FST).

Results: Compared with the control group, C100, C200, and T50 showed a tendency to decrease mobility in FST. Moreover, TG (C100, C200, T200), LDH (C200), lactic acid (C100) and MDA (C50, C100, C200) levels were inhibited by vitamin C and TR.

Conclusions: These results suggest that vitamin C and TR have anti-fatigue activities in mice, with vitamin C providing a stronger effect.

5. A comparison of pain, fatigue, and function between post-COVID-19 condition, fibromyalgia, and chronic fatigue syndrome: a survey study

Haider S, Janowski AJ, Lesnak JB, Hayashi K, Dailey DL, Chimenti R, Frey-Law LA, Sluka KA, Berardi G.

Pain. 2022 Jun 29


A growing number of individuals report prolonged symptoms following acute Coronavirus-19 (COVID-19) infection, known as post-COVID-19 condition (post-COVID-19).

While studies have emerged investigating the symptom sequelae of post-COVID-19, there has been limited investigation into the characterization of pain, fatigue, and function in these individuals, despite initial reports of a clinical phenotype similar to fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME).

This study aimed to characterize multiple symptom domains in individuals reporting post-COVID-19 and compare its clinical phenotype with those with FMS and CFS.

A total of 707 individuals with a single or comorbid diagnosis of post-COVID-19, FMS, and/or CFS completed multiple surveys assessing self-reported pain, fatigue, physical and cognitive function, catastrophizing, kinesiophobia, anxiety, depression, dyspnea, and sleep quality.

In all 3 diagnoses, elevated pain, fatigue, anxiety, depression, catastrophizing, and kinesiophobia were reported.

Physical and cognitive function were similarly impacted among individuals with post-COVID-19, FMS, and CFS; however, individuals with post-COVID-19 reported lower pain and fatigue than FMS and CFS.

The comorbid diagnosis of post-COVID-19 with FMS and/or CFS further exacerbated pain, fatigue, and psychological domains when compared with post-COVID-19 alone.

In summary, individuals with post-COVID-19 report a symptom phenotype similar to FMS and CFS, negatively impacting cognitive and physical function, but with less severe pain and fatigue overall. These findings may help direct future investigations of the benefit of a biopsychosocial approach to the clinical management of post-COVID-19.

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

Kedor C, Freitag H, Meyer-Arndt L, Wittke K, Hanitsch LG, Zoller T, Steinbeis F, Haffke M, Rudolf G, Heidecker B, Bobbert T, Spranger J, Volk HD, Skurk C, Konietschke F, Paul F, Behrends U, Bellmann-Strobl J, Scheibenbogen C.

Nat Commun. 2022 Aug 30;13(1):5104.


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.

Long-COVID Research References  

  1. Impact of COVID-19 vaccination on the risk of developing long-COVID and on existing long-COVID symptoms: A systematic review
  2. Association between Parents Experiencing Ongoing Problems from Covid-19 and Adolescents Reporting Long Covid Six Months after a Positive or Negative Sars-Cov-2 Pcr-Test: Prospective, National Cohort Study in England
  3. Long-COVID Clinical Features and Risk Factors: A Retrospective Analysis of Patients from the STOP-COVID Registry of the PoLoCOV Study
  4. Post-COVID-19 Syndrome is Rarely Associated with Damage of the Nervous System: Findings from a Prospective Observational Cohort Study in 171 Patients
  5. Coenzyme Q10 + alpha lipoic acid for chronic COVID syndrome
  6. Cardiac impairments in postacute COVID-19 with sustained symptoms: A review of the literature and proof of concept
  7. Possible long COVID healthcare pathways: a scoping review
  8. Autonomic and neuropathic complaints of long-COVID objectified: an investigation from electrophysiological perspective
  9. Hyperbaric Oxygen Therapy for Long COVID (HOTLoCO), an interim safety report from a randomised controlled trial
  10. Recent developments in the immunopathology of COVID-19
  11. Gastrointestinal manifestations of long COVID: A systematic review and meta-analysis
  12. Somatic symptom disorder in patients with post-COVID-19 neurological symptoms: a preliminary report from the somatic study (Somatic Symptom Disorder Triggered by COVID-19)
  13. A pilot randomized controlled trial of supervised, at-home, self-administered transcutaneous auricular vagus nerve stimulation (taVNS) to manage long COVID symptoms
  14. Post COVID-19 ongoing symptoms and health related quality of life: does rehabilitation matter? Preliminary evidence
  15. Exposure to phenytoin associates with a lower risk of post-COVID cognitive deficits: a cohort study
  16. Microbiota and COVID-19: Long-term and complex influencing factors

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent
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