ME/CFS and Long Covid Research: 08 – 14 March 2022

March 18, 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 Katrina Pears

ME/CFS Research Published 8 – 14 March 2022 

It’s been another busy week for research, with six new ME/CFS studies and seventeen studies on Long Covid.  

We have highlighted two of the studies below:  

Paper one (1) is a review of evidence for the clinical similarities between ME/CFS and chronic intensive care unit patients, who have for example severe trauma, burns, infections and do not recover (i.e. something keeps them unwell). The authors find that the terms used to describe these patients are also similar, i.e. flat batteries. For this reason the lead researcher (Dominic Stanculescu) looked into the pathological mechanisms researchers have found in these “chronic ICU patients.”  

The principal researcher initially found literature describing that the pulsatility of the pituitary hormone release (i.e., frequency & amplitude) is altered in these patients but that this is very hard to detect (requires blood analysis every 10 min for 24 hours). In addition the thyroid hormone function is depressed (equally hard to detect because this takes place at cellular level). These findings through literature reviews have led the author to write a series of papers, starting with prolonged recovery of ICU patients (see here). This current paper covers the already reported findings relating to pituitary and thyroid hormone dysfunctions and includes findings related to gut injury, endotoxemia, endothelial dysfunction, hypoperfusion, etc. from critical illness and notes similar findings in ME/CFS (it is worth looking at the summary table in this research which lists the similarities). The authors conclude that there are a lot of overlaps between ME/CFS and chronic ICU patients (especially it should be noted for severe ME/CFS), and hope that the critical illness literature can help us understand ME/CFS.  

I am personally impressed with the principal author leading this review, as he is an independent researcher with no relevant scientific background who is looking for hope for his very severely ill wife. We have previously featured one of his other papers in our round-ups on heat stroke. I do feel much of the same conclusion could be applied here while these findings could be applied to a wide range of other medical conditions. The triggers of ME/CFS (viral infection is the most well reported) and critical illness differ, and for that reason I feel there are probably many more biological differences. We cannot know for certain without more biomedicial research and finding biomarkers for ME/CFS. 

Paper two (2) while not strictly on ME/CFS does cover the illness in the discussion, which is on the role of creatine supplementation in conditions involving mitochondrial dysfunction. ME/CFS has been widely reported to involve mitochondrial dysfunction (see the references cited in our index of published research) so lies perfectly in the emit of this research which has a section dedicated to ME/CFS and long-covid (section 9 of the paper).  

Disappointingly, in reviewing the previously published literature the authors only find one study (see here), which finds benefits of taking creatine resulting in higher muscle creatine-phosphate levels and better oxidative capacity but no significant improvement of fatigue symptoms. Due to the lack of studies it is hard to full evaluate the true benefit to ME/CFS but this research shows the benefits in other mitochondria dysfunction illness where more research has been conducted.  

You may also be interested in reading papers three (3) and four (4) in this roundup which further show the similarities between ME/CFS and Long Covid. Paper five (5) may also be of interest which finds no neuroinflammation in women with ME/CFS, although this is a very small study. 

ME/CFS Research References and Abstracts  

1. Perspective: Drawing on Findings From Critical Illness to Explain Myalgic Encephalomyelitis/Chronic Fatigue Syndrome 

Dominic Stanculescu and Jonas Bergquist 
Frontiers in Medicine 


We propose an initial explanation for how myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) could originate and perpetuate by drawing on findings from critical illness research.  

Specifically, we combine emerging findings regarding (a) hypoperfusion and endotheliopathy, and (b) intestinal injury in these illnesses with our previously published hypothesis about the role of (c) pituitary suppression, and (d) low thyroid hormone function associated with redox imbalance in ME/CFS.  

Moreover, we describe interlinkages between these pathophysiological mechanisms as well as “vicious cycles” involving cytokines and inflammation that may contribute to explain the chronic nature of these illnesses.  

This paper summarizes and expands on our previous publications about the relevance of findings from critical illness for ME/CFS.  

New knowledge on diagnostics, prognostics and treatment strategies could be gained through active collaboration between critical illness and ME/CFS researchers, which could lead to improved outcomes for both conditions. 

2. Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review 

Marshall RP, Droste JN, Giessing J, Kreider RB 
Nutrients. 2022 Jan 26;14(3):529.  


Creatine monohydrate (CrM) is one of the most widely used nutritional supplements among active individuals and athletes to improve high-intensity exercise performance and training adaptations. However, research suggests that CrM supplementation may also serve as a therapeutic tool in the management of some chronic and traumatic diseases.  

Creatine supplementation has been reported to improve high-energy phosphate availability as well as have antioxidative, neuroprotective, anti-lactatic, and calcium-homoeostatic effects. These characteristics may have a direct impact on mitochondrion's survival and health particularly during stressful conditions such as ischemia and injury.  

This narrative review discusses current scientific evidence for use or supplemental CrM as a therapeutic agent during conditions associated with mitochondrial dysfunction.  

Based on this analysis, it appears that CrM supplementation may have a role in improving cellular bioenergetics in several mitochondrial dysfunction-related diseases, ischemic conditions, and injury pathology and thereby could provide therapeutic benefit in the management of these conditions. However, larger clinical trials are needed to explore these potential therapeutic applications before definitive conclusions can be drawn. 

3. Diagnosis of Chronic Fatigue Syndrome in Adolescents 

Tarjei Tørre Asprusten 
PhD thesis 


Diagnostic labels such as Chronic Fatigue Syndrome (CFS), Myalgic Encephalomyelitis (ME) and Systemic Exertion Intolerance Disease (SEID) represent different approaches to the enigmatic phenomenon of long-lasting unexplained fatigue.  

More than 20 case definitions/diagnostic criteria for CFS/ME/SEID exist. All are based on subjective symptom reports, and the details of symptom requirement vary considerably. No one has been thoroughly validated.  

The present thesis shows that adolescent CFS patients fulfilling the Canadian Consensus Criteria (CCC) or SEID-criteria do not differ from adolescent CFS patients diagnosed according to broad diagnostic criteria regarding neuroendocrine, cardiovascular, inflammatory, infectious or cognitive variables.  

Furthermore, there appears to be no distinct subgroups within the overarching CFS label, but rather a continuum of subjective symptom experiences and pathophysiological aberrations.  

These findings question the descriptive, predictive and construction validity of the CCC and SEID-criteria, and more fundamentally question the rationale of sub-classifying chronically fatigued patients based on clinical symptoms.  

Rather, the results seem to suggest that all patients with an unexplained chronic fatigue may be seen as one entity in a qualitative sense, albeit with individual, quantitative differences regarding symptom severity and functional impairments. 

3. Individualizing medical treatment in chronic fatigue syndrome/ myalgic encephalomyelitis: Evidence for effective medications and possible relevance to “Long-Hauler Syndrome” in Covid-19 affected patients 

Levine PH, Ajmera KM, Bjorke B, Peterson D.  
J Clin Images Med Case Rep. 2022; 3(1): 1681 


Large controlled studies of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) have shown no effective medical treatment for this disorder. There are individual patients, however, with dramatic responses to some medications.  

We report two patients with clear responses to rintatolimid and galantamine characterized by rapid reduction of symptoms on starting treatment and return of symptoms on withdrawal.  

As in cancer, CFS/ME is a heterogeneous disorder but unlike most cancers, such as melanoma, breast cancer, and B-cell lymphoma, CFS/ME has no known biological marker that can distinguish between subtypes.  

We suggest an approach to medical treatment of CFS/ME that could be utilized by primary caregivers that offer the possibility of more rapid and complete recovery from this debilitating disorder.  

Current studies indicate that prolonged symptomatic recovery from infection with Covid-19 (“long hauler syndrome” or PASC, for post-acute sequelae of Covid-19) represents a severe form of CFS/ME and thus may also be amenable to personalized medicine with specific medications. 

4. Long-Term COVID 19 Sequelae in Adolescents: the Overlap with Orthostatic Intolerance and ME/CFS 

Morrow, A.K., Malone, L.A., Kokorelis, C. et al.  
Curr Pediatr Rep (2022). 


Purpose of Review: To discuss emerging understandings of adolescent long COVID or post-COVID-19 conditions, including proposed clinical definitions, common symptoms, epidemiology, overlaps with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and orthostatic intolerance, and preliminary guidance on management. 

Recent Findings: The recent World Health Organization clinical case definition of post-COVID-19 condition requires a history of probable or confirmed SARS-CoV-2 infection, with symptoms starting within 3 months of the onset of COVID-19. Symptoms must last for at least 2 months and cannot be explained by an alternative diagnosis.  

Common symptoms of the post-COVID-19 condition include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction. These symptoms generally have an impact on everyday functioning.  

The incidence of prolonged symptoms following SARS-CoV-2 infection has proven challenging to define, but it is now clear that those with relatively mild initial infections, without severe initial respiratory disease or end-organ injury, can still develop chronic impairments, with symptoms that overlap with conditions like ME/CFS (profound fatigue, unrefreshing sleep, post-exertional malaise, cognitive dysfunction, and orthostatic intolerance). 

Summary: We do not yet have a clear understanding of the mechanisms by which individuals develop post-COVID-19 conditions. There may be several distinct types of long COVID that require different treatments.  

At this point, there is no single pharmacologic agent to effectively treat all symptoms. Because some presentations of post-COVID-19 conditions mimic disorders such as ME/CFS, treatment guidelines for this and related conditions can be helpful for managing post-COVID-19 symptoms. 

5. No Signs of Neuroinflammation in Women With Chronic Fatigue Syndrome or Q Fever Fatigue Syndrome Using the TSPO Ligand [ 11 C]-PK11195 

Raijmakers R, Roerink M, Keijmel S, Joosten L, Netea M, van der Meer J, Knoop H, Klein H, Bleeker-Rovers C, Doorduin J.  
Neurol Neuroimmunol Neuroinflamm. 2021 Nov 23;9(1):e1113.  


Background and objectives: The pathophysiology of chronic fatigue syndrome (CFS) and Q fever fatigue syndrome (QFS) remains elusive.  

Recent data suggest a role for neuroinflammation as defined by increased expression of translocator protein (TSPO).  

In the present study, we investigated whether there are signs of neuroinflammation in female patients with CFS and QFS compared with healthy women, using PET with the TSPO ligand 11C-(R)-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carbox-amide ([11C]-PK11195). 

Methods: The study population consisted of patients with CFS (n = 9), patients with QFS (n = 10), and healthy subjects (HSs) (n = 9).  

All subjects were women, matched for age (±5 years) and neighborhood, aged between 18 and 59 years, who did not use any medication other than paracetamol or oral contraceptives, and were not vaccinated in the last 6 months.  

None of the subjects reported substance abuse in the past 3 months or reported signs of underlying psychiatric disease on the Mini-International Neuropsychiatric Interview. All subjects underwent a [11C]-PK11195 PET scan, and the [11C]-PK11195 binding potential (BPND) was calculated. 

Results: No statistically significant differences in BPND were found for patients with CFS or patients with QFS compared with HSs. BPND of [11C]-PK11195 correlated with symptom severity scores in patients with QFS, but a negative correlation was found in patients with CFS. 

Discussion: In contrast to what was previously reported for CFS, we found no significant difference in BPND of [11C]-PK11195 when comparing patients with CFS or QFS with healthy neighborhood controls. In this small series, we were unable to find signs of neuroinflammation in patients with CFS and QFS. 

6. Recursive Debility: Symptoms, Patient Activism, and the Incomplete Medicalization of ME/CFS 

Rogers, E.L.  
Medical Anthropology Quarterly. 


This article examines the contestation of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Lacking consistent diagnostic definitions, agreed-on biological indicators, or approved treatments, ME/CFS is an incompletely medicalized condition. It is defined by intractable and debilitating exhaustion after any form of exertion.  

Through an ethnographic exploration of an American ME/CFS patient activist group, I develop the concept of “recursive debility.”  

Symptoms form the very basis for disease activist groupings in the absence of biomarkers, but they also present a significant barrier to traditional forms of activism.  

Ironically, then, debilitation blocks the means through which debilitation might end. Patients contest systems of knowledge but always in bodies that experience exhaustion without end.  

This article presents a disability studies intervention in suggesting that the recursivity of debility demonstrates the profound interdependence of the bodily aspects of impairment and the sociopolitical aspects of disability. 

Long-COVID Research References   

  1. Post-acute COVID-19 syndrome presented as a cerebral and systemic vasculitis: a case report 
  1. A systematic review and meta-analysis of Long COVID symptoms 
  1. The immunology and immunopathology of COVID-19 
  1. Long-COVID and the Autonomic Nervous System: The journey from Dysautonomia to Therapeutic Neuro-Modulation, Analysis of 152 Patient Retrospectives   
  1. Long-term outcomes of pediatric infections: from traditional infectious diseases to long Covid 
  1. Early clues regarding the pathogenesis of long-COVID 
  1. Characteristics and impact of Long Covid: Findings from an online survey 
  1. Enhancing the management of long COVID in general practice: a scoping review 
  1. Long COVID and episodic disability: advancing the conceptualisation, measurement and knowledge of episodic disability among people living with Long COVID – protocol for a mixed-methods study 
  1. Toward Unbiased Evaluation of Postacute Sequelae of SARS-CoV-2 Infection: Challenges and Solutions for the Long Haul Ahead 
  1. The effectiveness of pulmonary rehabilitation for Post-COVID symptoms: A rapid review of the literature 
  1. Serial Changes of Long COVID Symptoms and Clinical Utility of Serum Antibody Titers for Evaluation of Long COVID 
  1. The Role of Nutrients in Prevention, Treatment and Post-Coronavirus Disease-2019 (COVID-19) 
  1. Number of initial symptoms is more related to long COVID-19 than acute severity of infection: a prospective cohort of hospitalized patients 
  1. On the single and multiple associations of COVID-19 post-acute sequelae: 6-month prospective cohort study 
  1. Neurocognitive and psychiatric post-coronavirus disease 2019 conditions: pathogenic insights of brain dysfunction following severe acute respiratory syndrome coronavirus 2 infection 
  1. Mechanisms of coronavirus infectious disease 2019-related neurologic diseases 

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent



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