MEA Research Roundup

ME/CFS and Long Covid Research: 22 – 28 November 2022 

The weekly research round-up includes recent publications about ME/CFS and Long Covid. We highlight the studies that have particularly caught our interest and follow these with the full list of publications together with their abstracts (summaries).


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 22 – 28 November 2022 

There have been only four new ME/CFS studies but it’s been another extremely busy week for Long Covid research with twenty-four new studies. 

Similar to the previous weeks, there is mounting evidence for the similarities between ME/CFS and Long Covid. This week there has also been a letter published to the editor of the Spanish Rheumatology Journal, which presents a clear table showing the similarities and difference of Long Covid and ME/CFS. While this is not a research study, it is interesting to see researchers coming together on this topic. 

There are a few unusual ME/CFS studies this week, which really questions the authors knowledge and understanding of what ME/CFS is, including typos of the acronym CFS, these include Papers one (1), three (3) and four (4). 

We have highlighted two of the ME/CFS studies and listed some of the interesting Long Covid research below: 

Paper one (1) is of a slightly different nature as it looks at those patients who have developed ME/CFS following exposure to humidifier disinfectants (HDs) which used to contain numerous harmful chemicals in Korea. Therefore, this is a small subset of patients with a known onset.  

This study investigated the use of two-day cardiopulmonary exercise tests (CPETs) to provoke and assess post-exertional malaise (PEM) as well as to distinguish between differing fatigue conditions. Two CPET were used separated by 24 hours, including a variety of other measurements, such as peak oxygen consumption (VO2peak). This study enrolled 29 participants who had been exposed to HDs with CFS symptoms. 

Unsurprisingly, significant differences were found between the majority of parameters measured for test-1 and test-2, for example, decrease in peak oxygen consumption (VO2peak), showing the inability to reproduce the same test results on the second day of exercise testing.  

This is obviously not our usual sort of ME/CFS study due to the subset of patients used, so it is unclear how findings would translate to an ME/CFS population without HD exposure. Even though this is the first study to look at CPET testing in a ME/CFS HD exposed cohort, I don’t really think this expands on our knowledge. A few other things stand out about this study: 

  • it’s small scale, 
  • no healthy control group, which limits the application of these results, especially where the authors say these results can differentiate between fatigue conditions, 
  • use of the Fukuda criteria for diagnosis, which is heavily criticised in its use to diagnosis ME/CFS, especially when used in research. For example, problems with the Fukuda criteria include: post-exertional malaise (PEM) is not compulsory which leads to misdiagnosis, and it is not easy to use on a clinical level (a review on the contrasting case definitions has been written by Brown et al., 2013).  

The authors say that the inability to reproduce the same exercise response on a second day of exercise testing could be used diagnostically as an objective indicator of an abnormal post-exertion response, as it can differentiate between fatigue conditions. However, personally I would not be willing to participate in vigorous exercise testing at the risk of worsening my condition! Fortunately, the long-lasting relapse of symptoms is acknowledged as potentially unethical by the authors. Let’s hope that eventually a biological biomarker for PEM can be found in studies that provoke PEM. 

We cannot unfortunately read the full content of paper two (2)  as it is behind a paywall, however, this study involves patient agreement on which other illnesses (i.e. those overlapping) should be excluded in reaching an ME/CFS diagnosis. The lead author of this research is Leonard Jason from DePaul University, who has published a number of studies this year on a range of different topics from biological studies on cytokine expression to demographic studies looking at ME/CFS in different ethnicities (such as; Jason and Torres, 2022; Jason et al., 2022a; Jason et al., 2022b; Jason et al., 2022c). 

The specific aim of this study is to enhance future reproductivity in studies so that a more uniform population can be selected, which in the future could help to find more  significant answers from research. However, to me, there is some concern that these exclusionary illnesses would have a role in ME/CFS diagnosis and illness progression, for example, they develop because of ME/CFS. Despite this there is a need to tighten criteria for research, once more definite answers have been found, other conditions can be included. 

Some of the papers of interest in the Long Covid Reference section include: 

  • Paper two (2) is on symptoms following infection with different variants of the Covid-19 virus (SARS-CoV-2), the review shows that the prevalence of Long Covid is higher with the historical variants and those infected with Omicron seem to have the smallest prevalence, however, long term data is still needed. 
  • Papers three (3) and four (4) are similar studies, using the same methodology (the Long Covid Stigmas scale) looking into the stigmas associated with Long Covid in the UK.  
  • Paper five (5) shows that suffering with insomnia increases the likelihood of experiencing more chronic longer lasting covid symptoms, and has wider implications showing that insomnia and sleep have a role on the immune system functioning. 
  • Paper six (6) is a feasibility study looking into the use of online Forest Bathing therapy to reduce Long Covid symptoms, particularly cognitive and mental health symptoms. Forest bathing is a Japanese relaxation technique of finding calm and quiet amongst trees and observing nature, similar to those practices of mindfulness. The pilot study found significant improvements in symptoms with this accessible and inexpensive therapy which can be conducted online. 
  • Paper seven (7) is a review on acupuncture treatment for Long Covid, which supports acupuncture as effective and safe. 

ME/CFS Research References and Abstracts  

1. A 2-day cardiopulmonary exercise test in chronic fatigue syndrome 

Jong-Han Leem, Hyoung-Eun Jeon, Hun Nam, Hwan-Cheol Kim, Kyung-Lim Joa. 

Environmental Analysis Health and Toxicology 2022;37(4):e2022033-0 


Some survivors of humidifier disinfectants (HDs) complain of chronic, inexplicable fatigue, and post-exertional malaise (PEM). Two-day cardiopulmonary exercise tests (CPETs) performed 24 hours apart (2-day CPET protocol) are increasingly employed to evaluate PEM and related disabilities among individuals with chronic fatigue syndrome (CFS).  

The purpose of this study was to assess the reproducibility of CPET variables in individuals who had been exposed to HD and to show that 2-day CPET is an objective means of differentiating between fatigue conditions in people with CFS symptoms who have been exposed to HDs. Twenty-nine HD survivors with CFS symptoms were enrolled in this study.  

To document and assess PEM in CFS, a 2-day CPET was conducted to measure baseline functional capacity (CPET1) and provoke PEM. Twenty-four hours later, a second CPET assessed changes in related variables, focusing on PEM effects on functional capacity.  

This CPET also measured changes in energy production and physiological function, objectively documenting PEM effects. In the 2-day CPET, the peak oxygen consumption (VO2peak), VO2 at ventilatory threshold (VO2@VT), time to reach VO2peak, and time to reach VO2@VT were significantly decreased (p<0.001).  

The peak O2 pulse and O2 pulse at VT also decreased significantly (p<0.001). A 6-minute walk test revealed significantly decreased distance (p<0.01).  

This is the first study to conduct a 2-day consecutive CPET in previously exposed HD participants with CFS symptoms.  

Our results confirm previous work that demonstrated abnormal responses to PEM in CFS patients. Therefore, a 2-day CPET is an objective measure to differentiate fatigue conditions in people with CFS symptoms who have been exposed to HDs. 

2. Establishing a consensus on ME/CFS exclusionary illnesses 

Leonard A. Jason, Suvetha Ravichandran, Ben Z. Katz, Benjamin H. Natelson & Hector Fabio Bonilla. 

Fatigue: Biomedicine, Health & Behavior. 


Introduction: The diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is generally reached based on meeting the criteria of a case definition and eliminating other conditions that could be causing the patient’s symptoms. Investigators in the ME/CFS field are currently confronted with 139 medical exclusionary conditions listed among the various ME/CFS case definitions. There is a need to standardize the illnesses/diagnoses that should be excluded. 

Methods: Exclusionary conditions were listed for several prominent ME/CFS case definitions. From this list, symptoms were also identified as exclusionary by several physicians with experience in diagnosing ME/CFS. Input was also solicited from representatives from the patient community for a consensus list of exclusionary comorbid conditions. 

Results: Once overlapping illnesses were eliminated, a consensus was reached on a briefer set of exclusionary conditions. The final set of exclusionary conditions is divided into 14 categories with 53 specific examples. 

Conclusions: It is important for ME/CFS researchers to select uniform medical conditions to exclude from their studies so that samples across different studies are consistent and generate generalizable ME/CFS findings. This list can be applied to ME/CFS case definitions in order to enhance the reproducibility of identifying patients with ME/CFS for research studies. 

3. Relation of Urinary Mercury Level to Chronic Fatigue Syndrome among Workers of Artisanal and Small-scale Gold Mining: A Study of 3 Districts in West Nusa Tenggara Province and Lebak District of Banten Province, Indonesia 

Adi N P, Hardjono AW, Kekalih A, Wahyuningsih A, Ilyas M, Mubin M, Isbayuputra M.  

Acta Med Philipp 2022 Nov.29; 56(19). 


Introduction. Chronic Fatigue Syndrome (CFS) is a collection of symptoms from a substantial reduction in the ability to engage in preillness levels of occupational, educational, social, or personal activities that persists for more than six months and is accompanied by fatigue, post-exertional malaise, and unrefreshing sleep. One of the effects of heavy metal exposure is the occurrence of CFS among workers. Artisanal and Small-scale Gold Mining (ASGM) workers used mercury in their work, and this leads to a higher risk of chronic mercury poisoning. One of the health problems dueto mercury exposure is the occurrence of CFS and this has not been studied among ASGM workers. 
Objective. This study intended to discover the prevalence of CFS among ASGM workers and the factors associated with it. 
Method. This study used a cross-sectional design to find the relationship between independent variables such as age, sex, working period as a miner, type of work activities in ASGM, and cumulative urinary mercury levels with CFS in ASGM workers in West Nusa Tenggara and Banten province. CFS was measured using standardized questionnaire on effect on mercury released by WHO-UNEP, and creatinine-corrected urinary mercury levels. 
Results. The prevalence of CFS in ASGM workers in West Nusa Tenggara and Banten provinces was 17.9%. Based on the results, the factors of age, sex, work period, type of work, province of origin and cumulative urinary mercury levels did not have a statistically significant relationship with CFS (p> 0.05). 
Conclusion. There was no significant relationship between age, sex, work period, type of work, urinary mercury level and cumulative urinary mercury levels with CFS in ASGM workers. 

4. A case of post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome characterized by post-exertional malaise and low serum acylcarnitine level 

Ryuhei Jinushi; Sho Nishiguchi; Sakue Masuda; Akiko Sasaki; Kazuya Koizumi; Shomei Ryozawa. 

Authorea. November 29, 2022. [Preprint] 


COVID-19 afflicts patients with acute symptoms and longer-term sequelae. One of the sequelae is myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which is often difficult to diagnose, having no established tests. In this article, we synthesize information from literature reviews on patients with ME/CSF that developed after recovery from COVID-19. 

Long-COVID Research References  

  1. Clinical features, therapeutic outcomes and recovery period of long COVID 
  1. Long-COVID Symptoms in Individuals Infected with Different SARS-CoV-2 Variants of Concern: A Systematic Review of the Literature 
  1. Long Covid stigma: Estimating burden and validating scale in a UK-based sample 
  1. The prevalence of stigma in a UK community survey of people with lived experience of long COVID 
  1. Insomnia symptoms predict longer COVID-19 symptom duration 
  1. The Feasibility and Impact of Practising Online Forest Bathing to Improve Anxiety, Rumination, Social Connection and Long-COVID Symptoms: A Pilot Study 
  1. Acupuncture Treatment of Long-COVID: A Narrative Review of Selected Case Studies and Review Articles 
  1. Intravenous immunoglobulins in the treatment of post-COVID: A case-control study 
  1. A Multimodal Approach in the Treatment of Persistent Post-COVID 
  1. Autoantibodies against SUMO1-DHX35 in long-COVID 
  1. The Adaptive Force as potential biomechanical parameter in the recovery process of patients with long COVID 
  1. Metabolic Profile of Patients With Long Covid: a Cross-sectional Study 
  1. Persistent symptoms among post-COVID-19 survivors: A systematic review and meta-analysis 
  1. The Effect of Long COVID-19 Infection and Vaccination on Male Fertility; A Narrative Review 
  1. Long COVID – Six months of prospective follow-up of changes in symptom profiles of non-hospitalised children and young people after SARS-CoV-2 testing: a national matched cohort study. (The CLoCK study) 
  1. Is SARS-CoV-2 the only cause of long-COVID? 
  1. Post-COVID-19 Syndrome: Retinal Microcirculation as a Potential Marker for Chronic Fatigue 
  1. Mental Fatigue, Activities of Daily Living, Sick Leave and Functional Status among Patients with Long COVID: A Cross-Sectional Study 
  1. Long COVID at Different Altitudes: A Countrywide Epidemiological Analysis 
  1. Hospital admission and vaccination as predictive factors of long COVID-19 symptoms 
  1. One-year temporal changes in long COVID prevalence and characteristics: a systematic review and meta-analysis 
  1. Predictive model for long COVID in children 3 months after a SARS-CoV-2 PCR test 
  1. Prevalence, pathophysiology, prediction and health-related quality of life of long COVID: study protocol of the longitudinal multiple cohort CORona Follow Up (CORFU) study 
  1. Emerging Roles of Type-I Interferons in Neuroinflammation, Neurological Diseases, and Long-Haul COVID 

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent
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