ME/CFS Research Published 18 – 24 September 2021

October 1, 2021

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).

All research relating to ME/CFS can be located in the ME Association: Index of ME/CFS Published Research. It is a FREE resource, available to anyone, and updated at the beginning of each month.

The Index provides an A-Z of published research studies, selected key documents and articles, listed by subject matter, on myalgic encephalomyelitis, myalgic encephalopathy, and/or chronic fatigue syndrome (ME/CFS).

You can use it to easily locate and read any research that you might be interested in regard to, e.g., epidemiology, infection, neurology, post-exertional malaise etc.

You can also find the Research Index in the Research section of the website together with a list of Research Summaries that provide more detailed lay explanations of the more interesting work that has been published to date.

Five new research studies on ME/CFS but eleven studies on Long Covid. We highlight two on ME/CFS from the selection below: 

The first paper (1) despite in my opinion having a slightly misleading title, looks at infectious triggers leading to the onset of ME/CFS. This study looked at data from several countries, with an impressive 1773 diagnosed individuals.  

The study found that over 60% report a variety of infections for some time before the onset of ME/CFS (we do not have access to the full journal to see the time scales studied). Mononucleosos infections (also known as the kissing disease, involving the Epstein-Barr virus which is spread through saliva) occurred in 30% of infectious cases. It is probably unsurprising to most of us that the authors conclude “the findings suggest that many infectious agents might be associated with the onset of ME/CFS.” 

The fifth paper (5) is a journal pre-proof, and is currently “in press”, this means the paper has been peer-viewed and accepted for publication, it  just needs to undergo further editing (more about pre-journal proofs can be read here). 

This paper looks at cerebral blood flow (blood flow to the brain) which often can cause orthostatic symptoms (i.e. light headedness and dizziness). This study looked into the “prevalence and risk factors for delayed recovery of cerebral blood flow in ME/CFS patients.”  

The study found that:  

  • Cerebral blood flow in ME/CFS patients remains abnormal 5 minutes post-tilt test. 
  • Post cerebral blood flow abnormalities are most severe in more severely diseased ME/CFS patients. 
  • A significant difference was found in the degree of abnormal cerebral blood flow reduction in the supine post-test in mild, moderate, and severe ME/CFS patients. 
  • Cardiac index (an assessment of the cardiac output value based on the patient's size) declined significantly during the tilt test in all 3 severity groups, with no significant differences between the groups.  

The findings from this research study are significant as they show that disease severity greatly influences reductions in the cerebral blood flow, which may have implication on how energy is managed after a stressor.  

ME/CFS Research References and Abstracts  

1Patient perceptions of infectious illnesses preceding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome 

Jason LA, Yoo S, Bhatia S.  

Chronic Illn. 2021 Sep 20:17423953211043106. [Epub ahead of print.] 


Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is often reported to be caused by an infectious agent. However, it is unclear whether one infectious agent might be the cause or whether there might be many different infectious agents. The objective of this study was to identify self-reported infectious illnesses associated with the onset of ME/CFS. 

Methods: The present study involved data from multiple sites in several countries. 1773 individuals diagnosed with either ME, CFS or ME/CFS provided qualitative data concerning infectious triggers which were coded and classified for analysis. 

Results: 60.3% of patients report a variety of infectious illnesses some time before onset of ME/CFS. The most frequently reported infectious illness was Mononucleosis, which occurred in 30% of infections. However, over 100 other infectious illnesses were mentioned. 

Discussion: The findings suggest that many infectious agents might be associated with the onset of ME/CFS. 

2Long COVID and Chronic Fatigue Syndrome: A survey of elderly female survivors in Egypt 

Aly MA, Saber HG.  

Int J Clin Pract. 2021 Sep 19:e14886. [Epub ahead of print.]   


Objectives: This study aimed to investigate post COVID 19 symptoms amongst elderly females and whether they could be a risk factor for developing Chronic Fatigue Syndrome (CFS) later on. 

Methods: This was a retrospective cross-sectional study, in the form of an online survey. A total of 115 responses were finally included. 

Results: The mean age was 73.18±6.42. Eighty-nine reported symptoms in the post recovery period; of these 54 had no symptoms of CFS, 60 were possible, and only 1 was probable. Fatigue was reported by 66, musculoskeletal symptoms by 56, and sleep problems by 73. Twenty-nine patients visited a doctor's office as a result. Post recovery symptoms were significantly related to stress, sadness and sleep disturbances. Also, stress, sadness, sleep disturbances, fatigue, cognitive impairment, and recurrent falls were all significantly associated with CFS like symptoms. 

Conclusions: From our findings the presence of fatigue, cognitive impairment, stress, sadness, sleep disturbances, and recurrent falls in the post-recovery period were all significantly associated with CFS like symptoms. To conclude it would be reasonable to screen for Long COVID and consider the potential for developing CFS later on. Whether it can be a risk factor for developing CFS like other viral infections will need more larger scale studies to confirm this. 

3. The ‘medically unexplained symptoms' syndrome concept and the cognitive-behavioural treatment model 

Scott MJ, Crawford JS, Geraghty KJ, Marks DF.  

J Health Psychol. 2021 Sep 23:13591053211038042. [Epub ahead of print.] 


The American Psychiatric Association's, 2013 DSM-5 abandoned the use of the term ‘medically unexplained symptoms' for non-neurological disorders.  

In the UK, treatments for various medical illnesses with unexplained aetiology, such as chronic fatigue syndrome, irritable bowel syndrome and fibromyalgia, continue to fall under an MUS umbrella with cognitive behavioural therapy promoted as a primary therapeutic approach.  

In this editorial, we comment on whether the MUS concept is a viable diagnostic term, the credibility of the cognitive-behavioural MUS treatment model, the necessity of practitioner training and the validity of evidence of effectiveness in routine practice. 

4. Central sensitisation in chronic fatigue syndrome and fibromyalgia; a case control study 

Bourke JH, Wodehouse T, ClarkLV, Constantinou E, Kidd BL,Langford R, Mehta V, White PD 

Journal of Psychosomatic Research: 110624. [In press, Journal pre-proof] 


  • Central sensitisation (CS) was assessed using quantitative sensory tests (QST). 
  • Dynamic QST showed complete agreement in all subjects regarding the presence of CS. 
  • The large majority of CFS and fibromyalgia cases demonstrated CS. 
  • This could be either a cause or an effect of these conditions. 


Introduction: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are both complex conditions that are challenging to treat. This may be related to an incomplete understanding of their pathophysiology, itself obfuscated by their heterogeneity. The symptomatic overlap between them and their common comorbidity suggests a shared vulnerability, which might be explained by central sensitisation. 

Methods: 19 CFS cases, 19 FM cases and 20 age and sex matched healthy controls (HC) were recruited primarily from secondary care clinics in London. Those with other pain disorders, psychiatric diagnoses and those taking centrally acting or opiate medications were excluded. Participants were asked to abstain from alcohol and over the counter analgaesia 48 h prior to assessment by static and dynamic quantitative sensory tests, including measures of temporal summation (TS) and conditioned pain modulation (CPM). 

Results: CS, as defined by the presence of both enhanced TS and inefficient CPM, was present in 16 (84%) CFS cases, 18 (95%) FM cases, and none of the HC (p < 0.001). Pressure pain thresholds were lower in CFS (Median222kPaIQR 146–311; p = 0.04) and FM cases (Median 189 kPa; IQR 129–272; p = 0.003) compared to HC (Median 311 kPa; IQR 245–377). FM cases differed from HC in cold-induced (FM = 22.6 °C (15.3–27.7) vs HC = 14.2 °C (9.0–20.5); p = 0.01) and heat-induced (FM = 38.0 °C (35.2–44.0) vs HC = 45.3 °C (40.1–46.8); p = 0.03) pain thresholds, where CFS cases did not. 

Conclusion: Central sensitisation may be a common endophenotype in chronic fatigue syndrome and fibromyalgia. Further research should address whether central sensitisation is a cause or effect of these disorders. 

5. Cerebral blood flow remains reduced after tilt testing in myalgic encephalomyelitis/chronic fatigue syndrome patients 

Van Campen CMC, Rowe PC, Visser FC 

Clinical Neurophysiology Practice [In press, Journal pre-proof] 


  • Cerebral blood flow in ME/CFS patients remains abnormal 5 minutes post-tilt test. 
  • Post cerebral blood flow abnormalities do not depend on hemodynamic results and on end-tidal carbon dioxide pressures during the tilt-test. 
  • Post cerebral blood flow abnormalities are most severe in more severely diseased ME/CFS patients. 


Objective: Orthostatic symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may be caused by an abnormal reduction in cerebral blood flow. An abnormal cerebral blood flow reduction was shown in previous studies, without information on the recovery pace of cerebral blood flow. This study examined the prevalence and risk factors for delayed recovery of cerebral blood flow in ME/CFS patients. 

Methods: 60 ME/CFS adults were studied: 30 patients had a normal heart rate and blood pressure response during the tilt test, 4 developed delayed orthostatic hypotension, and 26 developed postural orthostatic tachycardia syndrome (POTS) during the tilt. Cerebral blood flow measurements, using extracranial Doppler, were made in the supine position pre-tilt, at end-tilt, and in the supine position at 5 minutes post-tilt. Also, cardiac index measurements were performed, using suprasternal Doppler imaging, as well as end-tidal PCO2 measurements. The change in cerebral blood flow from supine to end-tilt was expressed as a percent reduction with mean and (SD). Disease severity was scored as mild (approximately 50% reduction in activity), moderate (mostly housebound), or severe (mostly bedbound). 

Results: End-tilt cerebral blood flow reduction was -29 (6)%, improving to -16 (7)% at post-tilt. No differences in either end-tilt or post-tilt measurements were found when patients with a normal heart rate and blood pressure were compared to those with POTS, or between patients with normocapnia (end-tidal PCO2 ≥30 mmHg) versus hypocapnia (end-tidal PCO2 <30 mmHg) at end-tilt. A significant difference was found in the degree of abnormal cerebral blood flow reduction in the supine post-test in mild, moderate, and severe ME/CFS: mild: cerebral blood flow: -7 (2)%, moderate: -16 (3)%, and severe :-25 (4)% (p all <0.0001). Cardiac index declined significantly during the tilt test in all 3 severity groups, with no significant differences between the groups. In the supine post-test cardiac index returned to normal in all patients. 

Conclusions: During tilt testing , extracranial Doppler measurements show that cerebral blood flow is reduced in ME/CFS patients and recovery to normal supine values is incomplete, despite cardiac index returning to pre-tilt values. The delayed recovery of cerebral blood flow was independent of the hemodynamic findings of the tilt test (normal heart rate and blood pressure response, POTS, or delayed orthostatic hypotension), or the presence/absence of hypocapnia, and was only related to clinical ME/CFS severity grading. We observed a significantly slower recovery in cerebral blood flow in the most severely ill ME/CFS patients. 

Significance: The finding that orthostatic stress elicits a post-stress cerebral blood flow reduction and that disease severity greatly influences the cerebral blood flow reduction may have implications on the advice of energy management after a stressor and on the advice of lying down after a stressor in these ME/CFS patients. 

Long-COVID Research References   

  1. Large study will probe Long Covid 
  1. Long COVID: long-term symptoms and morphological/radiological correlates 
  1. Brain Stress Mapping in COVID-19 Survivors Using MR Spectroscopy: New Avenue of Mental Health Status Monitoring 
  1. Should we be vaccinating children against COVID-19 in high-income countries? 
  1. Electrophysiological and olfactometric evaluation of long-term COVID-19 
  1. Conceptualising Long COVID as an episodic health condition 
  1. Gut Microbiome Alterations in COVID-19 
  1. Altered smell and taste: Anosmia, parosmia and the impact of long Covid-19 
  1. Longitudinal Neurocognitive and Pulmonological Profile of Long Covid: the COVIMMUNE-Clin Study Protocol 
  1. Mast cell activation symptoms are prevalent in Long-COVID 
  1. Understanding Long Covid: Nosology, Social Attitudes and Stigma 

Katrina Pears, Research Correspondent, ME Association  

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