ME/CFS and Long Covid Research: 18 December 2021 – 03 January 2022

January 7, 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.

ME/CFS Research Published 18 December 2021 – 3 January 2022 

The papers we have highlighted in this roundup from over the Christmas period cover a slightly longer interval. Despite expecting research to be quiet in this period, there have been eight new research studies on ME/CFS but fourteen studies on Long Covid this week.  

We have highlighted two from the selection below:  

Paper one (1) is on the similarities in ME/CFS patients and long COVID patients in orthostatic(upright positions)  symptoms and reductions in cerebral blood flow (blood flow to the brain in a given time). This was a small study but had some key findings: 

  • Long COVID patients developed postural tachycardia syndrome (POTS) during the tilt test, 
  • Cerebral blood flow reduction was larger in the long COVID patients, 
  • Investigation further shows the similarities between these two sets of patients, 
  • Results suggest that SARS-CoV-2 infection acts as a trigger for the development of ME/CFS. 

This paper concludes that deconditioning does not play a part in long COVID patients who go on to develop POTS, which is interesting as the role of deconditioning is frequently debated in ME/CFS. However, the authors themselves acknowledge that this study is limited by having selected patients with already known orthostatic symptoms and the small sample size. 

You may also be interested in reading paper four (4) in this roundup which is by the same research group (van Campen et al.) on the use of compression stockings

Paper two (2) looks at the use of Oxygen-Ozone Autohemotherapy (O2-O3-AHT) as a potential treatment option. Oxygen therapies are thought to improve fatigue by helping to treat oxidative stress, which may play a part in ME/CFS pathology as well as help moderate immunity.   

In comparison to most research studies, this paper was a fairly large study looking at fatigue levels in 200 ME/CFS patients treated with Oxygen-Ozone Autohemotherapy. The results from this study were positive, showing improvements in fatigue with no side effects. However, this study was not very detailed, there is no detail of the exact ME criteria used and the outcomes used are self-reported fatigue. Therefore, a more rigorous study is needed before this potential treatment option can be further considered. 

You may also be interested in reading papers seven (7) and eight (8) in the ME/CFS Research reference section, which were published the week before, but details have only just become available. In the Long COVID reference section, you may be interest in papers six (6), seven (7) and ten (10) in the Long COVID reference section. 

ME/CFS Research References and Abstracts  

1. Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long-Haul COVID-19 Patients: Similarities with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome 

van Campen, C.M.C.; Rowe, P.C.; Visser, F.C.  

Medicina2022, 58, 28. 


Background and Objectives: Symptoms and hemodynamic findings during orthostatic stress have been reported in both long-haul COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but little work has directly compared patients from these two groups. To investigate the overlap in these clinical phenotypes, we compared orthostatic symptoms in daily life and during head-up tilt, heart rate and blood pressure responses to tilt, and reductions in cerebral blood flow in response to orthostatic stress in long-haul COVID-19 patients, ME/CFS controls, and healthy controls.  

Materials and Methods: We compared 10 consecutive long-haul COVID-19 cases with 20 age- and gender-matched ME/CFS controls with postural tachycardia syndrome (POTS) during head-up tilt, 20 age- and gender-matched ME/CFS controls with a normal heart rate and blood pressure response to head-up tilt, and 10 age- and gender-matched healthy controls. Identical symptom questionnaires and tilt test procedures were used for all groups, including measurement of cerebral blood flow and cardiac index during the orthostatic stress.  

Results: There were no significant differences in ME/CFS symptom prevalence between the long-haul COVID-19 patients and the ME/CFS patients. All long-haul COVID-19 patients developed POTS during tilt. Cerebral blood flow and cardiac index were more significantly reduced in the three patient groups compared with the healthy controls. Cardiac index reduction was not different between the three patient groups. The cerebral blood flow reduction was larger in the long-haul COVID-19 patients compared with the ME/CFS patients with a normal heart rate and blood pressure response.  

Conclusions: The symptoms of long-haul COVID-19 are similar to those of ME/CFS patients, as is the response to tilt testing. Cerebral blood flow and cardiac index reductions during tilt were more severely impaired than in many patients with ME/CFS. The finding of early-onset orthostatic intolerance symptoms, and the high pre-illness physical activity level of the long-haul COVID-19 patients, makes it unlikely that POTS in this group is due to deconditioning. These data suggest that similar to SARS-CoV-1, SARS-CoV-2 infection acts as a trigger for the development of ME/CFS.  

2. Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Greatly Improved Fatigue Symptoms When Treated with Oxygen-Ozone Autohemotherapy 

Tirelli, U.; Franzini, M.; Valdenassi, L.; Pandolfi, S.; Berretta, M.; Ricevuti, G.; Chirumbolo, S.  

J. Clin. Med.2022, 11, 29.  


(1) Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic syndrome characterized by fatigue as its major and most outstanding symptom. Previous evidence has supported the ability of ozone to relief ME/CFS related fatigue in affected patients  

(2) Methods: A number of 200 ME/CFS previously diagnosed patients, (mean age 33 ± 13 SD years) were consecutively treated with oxygen-ozone autohemotherapy (O2-O3-AHT). Fatigue was evaluated via an FSS 7-scoring questionnaire before and following 30 days after treatment.  

(3) Results: Almost half (43.5%) of the treated patients evolved their FSS scale from the worst (7) to the best (1) score, assessing the highest improvement from being treated with O2-O3-AHT. Furthermore 77.5% of patients experienced significant ameliorations of fatigue, of 4–6 delta score. No patient showed side effects, yet experienced long lasting fatigue disappearance, by three months follow up  

(4) Conclusions: Treatment with O2-O3-AHT greatly improves ME/CFS related fatigue, aside from sex and age distribution. 

3. Detection of herpes viruses in patients with myalgic encephalomyelitis /chronic fatigue syndrome in Belarus 

Orlova S, Rudjko G, Orlova O, Dakukina T 

Polish Journal of Applied Sciences, [S.l.], v. 6, n. 2, p. 50-53, dec. 2021.  


Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifactorial chronic disease. The etiology and pathogenesis of ME/CFS are unknown . There are many theories for the occurrence of this disease. but the most convincing is the infectious or viral theory of the emergence of CFS. 

The aim of this study is to detect of herpes viruses 6, 7 types and Epstein-Barr  to examine the prevalence HHV-6, HHV-7 and EBV infections in Belarus CFS patients . 

We examined 30 patients with CFS in whom fatigue during  more than 2 years (7), more than 1 year (11) and more than 6 months (12). The diagnosis was made on clinical grounds using the Fukuda criteria. 

The presence of markers the active forms  infection HHV-6 and HHV-7 in CFS patients with a long period of fatigue  were detected in 16.6% and 26.6% respectively. IgM  antibodies to HHV-6 and EBV. positive, in 16.6% and 6.7% respectively in patients with long-term illness. Detection of IgG antibodies indicates a quiet carrier state, latent phase. 

4. Compression Stockings Improve Cardiac Output and Cerebral Blood Flow during Tilt Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients: A Randomized Crossover Trial 

van Campen, C.M.C.; Rowe, P.C.; Visser, F.C.  

Medicina2022, 58, 51. 

Background and Objectives: Orthostatic intolerance (OI) is a clinical condition in which symptoms worsen upon assuming and maintaining upright posture and are ameliorated by recumbency. OI has a high prevalence in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).  

Limited data are available to guide the treatment of OI in ME/CFS patients. We and others have previously described patient-reported subjective improvement in symptoms using compression stockings. We hypothesized that these subjective reports would be accompanied by objective hemodynamic improvements.  

Materials and Methods: We performed a randomized crossover trial in 16 ME/CFS patients. Each underwent two 15-min head-up tilt table tests, one with and one without wearing knee-high compression stockings that provided 20–25 mm Hg compression. The order of the tests was randomized.  

We measured heart rate and blood pressure as well as cardiac output and cerebral blood flow (CBF) using extracranial Doppler of the internal carotid and vertebral arteries.  

Results: There were no differences in supine measurements between the 2 baseline measurements. There were no differences in heart rate and blood pressure at either end-tilt testing period. Compared to the test with the stockings off, the mean percentage reduction in cardiac output during the test with compression stockings on was lower, 15 (4)% versus 27 (6)% (p < 0.0001), as was the mean percentage CBF reduction, 14 (4)% versus 25 (5)% (p < 0.0001).  

Conclusion: In ME/CFS patients with orthostatic intolerance symptoms, cardiac output and CBF are significantly reduced during a tilt test. These abnormalities were present without demonstrable heart rate and blood pressure changes and were ameliorated by the use of compression stockings. 

5. New guidance for ME and CFS to improve understanding of these largely misunderstood conditions 

Palmer SJ 

Practice Nursing 2022 33:1, 34-36 


The National Institute for Health and Care Excellence has published new guidelines on myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Sarah Jane Palmer looks at the key changes made 

6. An Open-Label, Pilot Trial of HRG80™ Red Ginseng in Chronic Fatigue Syndrome, Fibromyalgia, and Post-Viral Fatigue 

Teitelbaum, J.; Goudie, S.  

Pharmaceuticals2022, 15, 43. 


Chronic fatigue syndrome and fibromyalgia (CFS/FMS) affect 2.1% of the world’s population and ~10–25% of people who have had COVID-19.  

Previous clinical data suggested that a unique Panax ginseng (C.A. Meyer, family Araliaceae) root extract (HRG80™ Red Ginseng) often resulted in marked improvement.  

We aimed to study this hydroponic form of red ginseng root, containing high levels of rare ginsenosides, for improving energy, cognition, and stamina.  

This open-label prospective study included participants with severe CFS/FMS who took a daily supplement of HRG80 capsules (200–400 mg) or tablets (100–200 mg) for one month. A total of 188 subject patients completed the one-month treatment trial.  

Of these, 60.1% rated themselves as improved, with 13.3% rating themselves as being much better.  

In this group, the mean composite score improved from 11.9 to 18.8 (p < 0.001), with a 67% average increase in energy, 44% average increase in overall well-being, 48% average improvement in mental clarity, 58% average composite improvement in the previous three measurements (primary outcome measure), 46% average improvement in sleep, 33% average decrease in pain, and 72% average increase in stamina.  

Our study showed that HRG80 red ginseng root powder resulted in a marked improvement in people with CFS and fibromyalgia. This included the subgroup with post-viral CFS/FMS. 

7. Brainstem Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Scoping Review and Evaluation of Magnetic Resonance Imaging Findings 

Nelson T, Zhang LX, Guo H, Nacul L, Song X.  

Front Neurol. 2021 Dec 17;12:769511.  


Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multisystem medical condition with heterogeneous symptom expression. Currently, there is no effective cure or treatment for the standard care of patients. A variety of ME/CFS symptoms can be linked to the vital life functions of the brainstem, the lower extension of the brain best known as the hub relaying information back and forth between the cerebral cortex and various parts of the body.  

Objective/Methods: Over the past decade, Magnetic Resonance Imaging (MRI) studies have emerged to understand ME/CFS with interesting findings, but there has lacked a synthesized evaluation of what has been found thus far regarding the involvement of the brainstem. We conducted this study to review and evaluate the recent MRI findings via a literature search of the MEDLINE database, from which 11 studies met the eligibility criteria.  

Findings: Data showed that MRI studies frequently reported structural changes in the white and gray matter. Abnormalities of the functional connectivity within the brainstem and with other brain regions have also been found. The studies have suggested possible mechanisms including astrocyte dysfunction, cerebral perfusion impairment, impaired nerve conduction, and neuroinflammation involving the brainstem, which may at least partially explain a substantial portion of the ME/CFS symptoms and their heterogeneous presentations in individual patients.  

Conclusions: This review draws research attention to the role of the brainstem in ME/CFS, helping enlighten future work to uncover the pathologies and mechanisms of this complex medical condition, for improved management and patient care. 

8. Submaximal Exercise Provokes Increased Activation of the Anterior Default Mode Network During the Resting State as a Biomarker of Postexertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome 

Rayhan RU, Baraniuk JN.  

Frontiers in Neuroscience. 2021 Dec 15;15:748426.  


Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by disabling fatigue and postexertional malaise. We developed a provocation paradigm with two submaximal bicycle exercise stress tests on consecutive days bracketed by magnetic resonance imaging, orthostatic intolerance, and symptom assessments before and after exercise in order to induce objective changes of exercise induced symptom exacerbation and cognitive dysfunction.  

Method: Blood oxygenation level dependent (BOLD) scans were performed while at rest on the preexercise and postexercise days in 34 ME/CFS and 24 control subjects. Seed regions from the FSL data library with significant BOLD signals were nodes that clustered into networks using independent component analysis. Differences in signal amplitudes between groups on pre- and post-exercise days were determined by general linear model and ANOVA.  

Results: The most striking exercise-induced effect in ME/CFS was the increased spontaneous activity in the medial prefrontal cortex that is the anterior node of the Default Mode Network (DMN). In contrast, this region had decreased activation for controls. Overall, controls had higher BOLD signals suggesting reduced global cerebral blood flow in ME/CFS.  

Conclusion: The dynamic increase in activation of the anterior DMN node after exercise may be a biomarker of postexertional malaise and symptom exacerbation in CFS. The specificity of this postexertional finding in ME/CFS can now be assessed by comparison to post-COVID fatigue, Gulf War Illness, fibromyalgia, chronic idiopathic fatigue, and fatigue in systemic medical and psychiatric diseases. 

Long-COVID Research References   

  1. Post-Covid-19 Syndrome: Improvements in Health-Related Quality of Life Following Psychology-Led Interdisciplinary Virtual Rehabilitation 
  1. Intravenous immunoglobulin as an important adjunct in the prevention and therapy of coronavirus 2019 disease 
  1. Levocetirizine and montelukast in the COVID-19 treatment paradigm 
  1. Year-long COVID-19 infection reveals within-host evolution of SARS-CoV-2 in a patient with B cell depletion 
  1. Biomedical Perspectives of Acute and Chronic Neurological and Neuropsychiatric Sequelae of COVID-19 
  1. Multisystem Involvement in Post-acute Sequelae of COVID-19 (PASC) 
  1. Prevalence of Long-term Post COVID-19 Symptom and Blood Group Correlation 
  1. Disturbances in sleep, circadian rhythms and daytime functioning in relation to coronavirus infection and Long-COVID – A multinational ICOSS study 
  1. Impaired systemic oxygen extraction long after mild COVID-19: potential perioperative implications 
  1. Endothelial dysfunction is the key of long COVID-19 symptoms: The results of TUN-EndCOV study 
  1. Sulodexide in the treatment of patients with long COVID 19 symptoms and endothelial dysfunction: The results of TUN-EndCOV study 
  1. Relationship Between Myocardial Injury During Index Hospitalization for SARS-CoV-2 Infection and Longer-Term Outcomes 
  1. Fatigue and Cognitive Impairment in Post-COVID-19 Syndrome: A Systematic Review and Meta-Analysis 
  1. Combined triple treatment of brain amyloid micro clots and platelet pathology in individuals with Long COVID/ Post-Acute Sequelae of COVID-19 (PASC) can resolve their persistent symptoms 

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent



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