ME Association Index Of Published Research

ME/CFS and Long Covid Research: 06 – 15 November 2023

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).

RESEARCH INDEX

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

It’s been another busy week for research. There have been twelve new ME/CFS studies and twenty-four new Long Covid studies this week.

We have highlighted one of the ME/CFS studies in more detail below:

Paper four (4) looks into small intestinal bacterial overgrowth (SIBO). SIBO is defined as the presence of excessive bacteria in the small intestine, and is frequently implicated as the cause of chronic diarrhoea and malabsorption. Patients with SIBO may also suffer from unintentional weight loss, nutritional deficiencies, and osteoporosis.

Irritable bowel syndrome (IBS) is found to be a common comorbidity and is reported to be present in approximately 60% of patients with ME/CFS, while the prevalence of small intestinal bacterial overgrowth (SIBO) in IBS is approximately 40%. This study aimed to determine the prevalence of SIBO in patients with ME/CFS with and without IBS symptoms.

The common test used to diagnosis SIBO is a breath test- this is a noninvasive test that measures the amount of hydrogen or methane that is breathed out after drinking a mixture of glucose and water. A rapid rise in exhaled hydrogen or methane may indicate bacterial overgrowth in the small intestine.

This study reviewed 479 ME/CFS patients that were referred for a hydrogen or methane breath test.

The study found that SIBO is highly prevalent in patients with ME/CFS, with older age and comorbid IBS diagnosis predicting increased odds of positive breath test. Further findings included:

  • Of the 479 patients studied, 367 have completed a breath test with usable results.
  • Of the available data for the 367 patients, 152 (41%) had positive SIBO breath test results, 164 (45%) a negative SIBO breathe test and a further 78 (21%) had inconclusive results.
  • In ME/CFS patients with conclusive breath test results, further testing was conducted with 48% testing positive for SIBO, and the diagnosis of IBS was present in 186/316 (59%).
  • There was no difference in the prevalence of IBS between the SIBO positive versus the SIBO negative group.
  • Age, unknown race, and IBS diagnosis were all found to significantly predict increased odds of having a positive breath test.
  • Surprisingly, taking proton pump inibitor (PPI) medication (which reduces stomach acid) was associated with decreased odds of a positive breath test. (This medication has had prior implications as a possible risk factor for SIBO.)
  • Due to the high prevalence of IBS in the cohort and the association between IBS and SIBO, an analysis was performed excluding patients with IBS diagnosis. When excluding patients with IBS, unknown race and tricyclic antidepressant (TCA) use were associated with increased odds of positive breath test, while diarrhoea, hypothyroidism, PPI, and naltrexone use were associated with decreased odds.

This study was published in The American Journal of Gastroenterology, however, unfortunately, it is not a full length paper so we cannot fully analyse the interesting results that are presented in a large ME/CFS cohort. It would be interesting to know where such a large data set was collected from and the diagnosis criteria used. It should be noted, however, that the authors only use the term Chronic Fatigue Syndrome/ CFS, which previous experience has shown us often means a poorly defined cohort and knowledge.

Nevertheless, in the information available, some interesting findings and interactions were investigated. Further research is needed to explore the mechanisms causing the overlap between ME/CFS, IBS and SIBO, which may help to establish suitable therapies.

Recently, in relation to this study, we have also seen research into the use of Amitriptyline doubling IBS improvement (see here). Interestingly, in the study above, increased odds of SIBO were found in patients without IBS with use tricyclic antidepressant (TCA), which includes Amitriptyline. The MEA have leaflets covering Amitriptyline and Irritable Bowel and Stomach Symptoms.

In the Long Covid reference section this week, Paper thirteen (13) also explores what we know about Post-Covid syndrome and IBS.

ME/CFS Research References

1. Integrated ‘omics analysis for the gut microbiota response to moxibustion in a rat model of chronic fatigue syndrome

Chaoran LI, Yan Y, Chuwen F, Heng LI, Yuanyuan QU, Yulin W, Delong W, Qingyong W, Jing G, Tianyu S, Xiaowei S, Xue W, Yunlong H, Zhongren S, Tiansong Y.

J Tradit Chin Med. 2023 Oct;43(6):1176-1189.

Abstract

Objective: To observe the efficacy of moxibustion in the treatment of chronic fatigue syndrome (CFS) and explore the effects on gut microbiota and metabolic profiles.

Methods: Forty-eight male Sprague-Dawley rats were randomly assigned to control group (Con), CFS model group (Mod, established by multiple chronic stress for 35 d), MoxA group (CFS model with moxibustion Shenque (CV8) and Guanyuan (CV4), 10 min/d, 28 d) and MoxB group (CFS model with moxibustion Zusanli (ST36), 10 min/d, 28 d).

Open-field test (OFT) and Morris-water-maze test (MWMT) were determined for assessment the CFS model and the therapeutic effects of moxibustion.16S rRNA gene sequencing analysis based gut microbiota integrated untargeted liquid chromatograph-mass spectrometer (LC-MS) based fecal metabolomics were executed, as well as Spearman correlation analysis, was utilized to uncover the functional relevance between the potential metabolites and gut microbiota.

Results: The results of our behavioral tests showed that moxibustion improved the performance of CFS rats in the OFT and the MWMT. Microbiome profiling analysis revealed that the gut microbiomes of CFS rats were less diverse with altered composition, including increases in pro-inflammatory species (such as Proteobacteria) and decreases in anti-inflammatory species (such as Bacteroides, Lactobacillus, Ruminococcus, and Prevotella). Moxibustion partially normalized these changes in the gut microbiota.

Furthermore, CFS was associated with metabolic disorders, which were effectively ameliorated by moxibustion. This was demonstrated by the normalization of 33 microbiota-related metabolites, including mannose (P = 0.001), aspartic acid (P = 0.009), alanine (P = 0.007), serine (P = 0.000), threonine (P = 0.027), methionine (P = 0.023), 5-hydroxytryptamine (P = 0.008), alpha-linolenic acid (P = 0.003), eicosapentaenoic acid (P = 0.006), hypoxanthine (P = 0.000), vitamin B6 (P = 0.000), cholic acid (P = 0.013), and taurocholate (P = 0.002).

Correlation analysis showed a significant association between the perturbed fecal microbiota and metabolite levels, with a notable negative relationship between LCA and Bacteroides.

Conclusions: In this study, we demonstrated that moxibustion has an antifatigue-like effect. The results from the 16S rRNA gene sequencing and metabolomics analysis suggest that the therapeutic effects of moxibustion on CFS are related to the regulation of gut microorganisms and their metabolites. The increase in Bacteroides and decrease in LCA may be key targets for the moxibustion treatment of CFS.

2. Post Viral Pain, Fatigue, and Sleep Disturbance Syndromes: Current knowledge and Future Directions

Caleb Tackey, P. Maxwell Slepian, Hance Clarke & Nimish Mittal.

Canadian Journal of Pain.

Abstract

Post-viral pain syndrome, also known as post-viral syndrome (PVS), is a complex condition characterized by persistent pain, fatigue, musculoskeletal pain, neuropathic pain, neurocognitive difficulties, and sleep disturbances1,2 that can occur after an individual has recovered from a viral infection.

Much remains unknown regarding the pathophysiology of post-viral syndromes and few studies have provided a comprehensive summary of the condition, agents that cause it, and successful treatment modalities. With the COVID-19 pandemic continuing to affect millions of people worldwide, the need for understanding the etiology of post-viral illness and how to help individuals cope with the sequalae is paramount.2 

This narrative review provides a summary of the sequelae of post-viral syndromes, viral agents that cause it, the pathophysiology, treatment, and future considerations for research and targeted therapies.

3. The economic burden of myalgic encephalomyelitis/chronic fatigue syndrome in Australia

Ting Zhao, Ingrid Cox , Hasnat Ahmed, Julie Campbell, Martin Hensher, Andrew Palmer, Ryan Kelly, Melissa Rogerson, Karen Wills, Barbara de Graaff.

Journal of the Australian Healthcare & Hospitals Association: AH23106

Abstract

Objective: Estimate costs of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to patients, government, and Australian society.

Methods: Australian ME/CFS patients and their carers were recruited using convenience sampling. Patients completed an online retrospective cost diary, providing ME/CFS-related direct medical, non-medical and indirect costs. Informal care costs were collected directly from carers.

Data from the Pharmaceutical Benefits Scheme and Medicare Benefits Schedule were linked to participant survey data. Annual per/patient and total societal costs were estimated, and broken down by category, and presented in 2021AUD. Factors associated with higher costs were investigated using generalized linear models.

Results: 175 patients (mean/SD age of 49/14 years, 79.4% female) completed the cost diary. Estimated total annual societal costs of ME/CFS in Australia ranged between $1.38 and $10.09billion, with average annual total costs of $63,400/patient. Three-quarters of these costs were due to indirect costs ($46,731). Disability severity was the key factor associated with higher costs, particularly for indirect costs (being 2.27-fold higher for severe disability than no/mild disability).

Conclusions: ME/CFS poses a significant economic burden in Australia, owing mainly to high indirect and informal care costs.

4. Prevalence and Predictive Factors of Small Intestinal Bacterial Overgrowth in Patients With Chronic Fatigue Syndrome

Karhu, Elisa; Neshatian, Leila; Fass, Ofer; Sonu, Irene; Nguyen, Linda Anh.

The American Journal of Gastroenterology 118(10S):p S1351-S1352, October 2023.

Abstract

Introduction: Chronic fatigue syndrome (CFS) is a poorly understood illness, characterized by fatigue and related symptoms including cognitive dysfunction, headaches, joint pains, and gastrointestinal distress. Irritable bowel syndrome (IBS) is common and present in approximately 60% patients with CFS while the prevalence of small intestinal bacterial overgrowth (SIBO) in IBS is approximately 40%.

Our study aimed to 1) Determine the prevalence of SIBO in patients with CFS with and without IBS symptoms 2) Identify factors associated with increased risk of SIBO.

Methods: A retrospective chart review of 479 patients with CFS referred for hydrogen/methane breath testing. Clinical documentation was reviewed to identify positive breath test result diagnosing SIBO. Statistical analysis was conducted with 2-proportions z test and logistic regression analysis to identify predictive variables of SIBO diagnosis.

Results: 479 patients with CFS referred for glucose or lactulose breath testing were identified. Three hundred sixty-seven of those patients completed a breath test with available result: 152(41%) SIBO+ (mean age (SD) 50 (17)), 164(45%) SIBO- (mean age SD 46 (15)), and 78(21%) equivocal results. In CFS patients with conclusive breath test result, 48% tested positive for SIBO, and the diagnosis of IBS was present in 186/316 (59%). There was no difference in the prevalence of IBS between the SIBO+ vs SIBO-group [98/152 (64%) vs 88/164 (53%), P < 0.05].

Using multiple logistic regression analysis, age, unknown race, and IBS diagnosis all significantly predicted increased odds of having a positive breath test (Table 1). Conversely, PPI use was associated with decreased odds of a positive breath test.

Due to the high prevalence of IBS in our cohort and the association between IBS and SIBO, an analysis was performed excluding patients with IBS diagnosis. When excluding patients with IBS, unknown race and TCA use were associated with increased odds of positive breath test, while diarrhea, hypothyroidism, PPI, and naltrexone use were associated with decreased odds (P< 0.05).

Conclusion: SIBO is highly prevalent in patients with CFS referred for breath testing. Older age and comorbid IBS diagnosis predict increased odds of positive breath test.

Surprisingly, PPI use predicted decreased odds despite its prior implication as a possible risk factor for SIBO. Further studies are needed to explore the underlying mechanism causing the overlap between CFS, IBS and SIBO which may provide insights into potential therapies for CFS.

5. Increased risk of chronic fatigue syndrome following infection: a 17-year population-based cohort study

Chang H, Kuo CF, Yu TS, Ke LY, Hung CL, Tsai SY.

J Transl Med. 2023 Nov 11;21(1):804. 

Abstract

Background: Previous serological studies have indicated an association between viruses and atypical pathogens and Chronic Fatigue Syndrome (CFS). This study aims to investigate the correlation between infections from common pathogens, including typical bacteria, and the subsequent risk of developing CFS. The analysis is based on data from Taiwan's National Health Insurance Research Database.

Methods: From 2000 to 2017, we included a total of 395,811 cases aged 20 years or older newly diagnosed with infection. The cases were matched 1:1 with controls using a propensity score and were followed up until diagnoses of CFS were made.

Results: The Cox proportional hazards regression analysis was used to estimate the relationship between infection and the subsequent risk of CFS. The incidence density rates among non-infection and infection population were 3.67 and 5.40 per 1000 person-years, respectively (adjusted hazard ratio [HR] = 1.5, with a 95% confidence interval [CI] 1.47-1.54). Patients infected with Varicella-zoster virus, Mycobacterium tuberculosis, Escherichia coli, Candida, Salmonella, Staphylococcus aureus and influenza virus had a significantly higher risk of CFS than those without these pathogens (p < 0.05). Patients taking doxycycline, azithromycin, moxifloxacin, levofloxacin, or ciprofloxacin had a significantly lower risk of CFS than patients in the corresponding control group (p < 0.05).

Conclusion: Our population-based retrospective cohort study found that infection with common pathogens, including bacteria, viruses, is associated with an increased risk of developing CFS.

6. Dry eye symptoms and signs in United States Gulf War era veterans with myalgic encephalomyelitis/chronic fatigue syndrome

Sanchez V, Kim CK, Locatelli EVT, Cohen AK, Cabrera K, Aenlle K, Klimas NG, O'Brien R, Galor A.

Clin Exp Ophthalmol. 2023 Nov 12. [Epub ahead of print.]

Abstract

Background: To examine ocular symptoms and signs of veterans with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) diagnosis, ME/CFS symptoms, and controls.

Methods: This was a prospective, cross-sectional study of 124 South Florida veterans in active duty during the Gulf War era. Participants were recruited at an ophthalmology clinic at the Miami Veterans Affairs Hospital and evaluated for a diagnosis of ME/CFS, or symptoms of ME/CFS (intermediate fatigue, IF) using the Canadian Consensus criteria. Ocular symptoms were assessed via standardised questionnaires and signs via comprehensive slit lamp examination. Inflammatory blood markers were analysed and compared across groups.

Results: Mean age was 55.1 ± 4.7 years, 88.7% identified as male, 58.1% as White, and 39.5% as Hispanic. Ocular symptoms were more severe in the ME/CFS (n = 32) and IF (n = 48) groups compared to controls (n = 44) across dry eye (DE; Ocular Surface Disease Index [OSDI]: 48.9 ± 22.3 vs. 38.8 ± 23.3 vs. 19.1 ± 17.8, p < 0.001; 5 item Dry Eye Questionnaire [DEQ-5]: 10.8 ± 3.9 vs. 10.0 ± 4.6 vs. 6.6 ± 4.2, p < 0.001) and pain-specific questionnaires (Numerical Rating Scale 1-10 [NRS] right now: 2.4 ± 2.8 vs. 2.4 ± 2.9 vs 0.9 ± 1.5; p = 0.007; Neuropathic Pain Symptom Inventory modified for the Eye [NPSI-E]: 23.0 ± 18.6 vs. 19.8 ± 19.1 vs. 6.5 ± 9.0, p < 0.001). Ocular surface parameters and blood markers of inflammation were generally similar across groups.

Conclusion: Individuals with ME/CFS report increased ocular pain but similar DE signs, suggesting that mechanisms beyond the ocular surface contribute to symptoms.

7. Yeast Beta-Glucan Supplementation with Multivitamins Attenuates Cognitive Impairments in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

Lacasa M, Alegre-Martin J, Sentañes RS, Varela-Sende L, Jurek J, Castro-Marrero J.

Nutrients. 2023 Oct 24;15(21):4504.

Abstract

This research aimed to examine the potential alleviative effects of beta-glucan administration on fatigue, unrefreshing sleep, anxiety/depression symptoms and health-related quality of life in ME/CFS.

A 36-week unicenter, randomized, double-blind, placebo-controlled trial was conducted in 65 ME/CFS patients, who were randomly allocated to one of two arms to receive four capsules each one of 250 mg beta-glucan, 3.75 µg vitamin D3, 1.05 mg vitamin B6, and 7.5 mg zinc (n = 35), or matching placebo including only microcrystalline cellulose as an excipient (n = 30) once daily.

The findings showed that the beta-glucan supplementation significantly improved cognitive fatigue (assessed with FIS-40 scores) after the 36-week treatment compared to the baseline (p = 0.0338). Taken together, this study presents the novel finding that yeast-derived beta-glucan may alleviate cognitive fatigue symptoms in ME/CFS. Thus, it offers valuable scientific insights into the potential use of yeast beta-glucan as a nutritional supplement and/or functional food to prevent or reduce cognitive dysfunction in patients with ME/CFS.

Further interventions are warranted to validate these findings and also to delve deeper into the possible immunometabolic pathomechanisms of beta-glucans in ME/CFS.

8. Therapeutic Potential of Indian Medicinal Herbs and Current Therapeutic Approach used to Mitigate the Symptoms of Chronic Fatigue Syndrome: A Review

Singh, Nisha; Sharma, Rahul K.; Kushwah, Ajay Singh; Kumar, Manish.

Current Traditional Medicine, Volume 10, Number 4, 2024, pp. 115-128(14).

Abstract

Chronic fatigue syndrome (CFS) is a complex condition marked by severe exhaustion that lasts at least 6 months. The global prevalence of CFS ranging between 0.4% and 2.5% is growing. Women are affected by CFS more often than men. It is considered a common condition in developed countries.

There is no approved treatment for CFS but symptoms can be managed and controlled persistent exhaustion causes significant impairment in daily routine activities. Lowered ATP synthesis, mitochondrial impairment, decreased oxidative phosphorylation, disruption of the hypothalamic–pituitary–adrenal (HPA) axis, and an imbalance of brain neurotransmitters play a major role in the pathophysiology of CFS.

The purpose of the present study is to figure out the several plants that are used as a source of medication in chronic fatigue syndrome (CFS) and its current therapeutic approach. The Indian medicinal herbs described in this article are very efficacious in the management of chronic fatigue syndrome symptoms due to the presence of phytochemicals.

This review article also covers the current therapeutic approach for chronic fatigue syndrome in a concise form that comprises CBT (Cognitive based therapy), GET (Graded exercise therapy), usage of immunoglobins, psychodynamic counseling, and yoga therapy that includes isometric yoga and yoga nidra are very beneficial in alleviating the symptoms of chronic fatigue syndrome.

Antidepressants, immunomodulatory agents, and corticosteroids come under conventional medication for CFS. This article explores different Indian medicinal herbs, their pharmacological properties, and their potential role and current treatments for reducing the severity of symptoms of chronic fatigue syndrome.

9. Brain-targeted autoimmunity is strongly associated with Long COVID and its chronic fatigue syndrome as well as its affective symptoms

Abbas F. Almulla, Michael Maes, Bo Zhou, Hussein K. Al-Hakeim, Aristo Vojdani.

medRxiv [Preprint]

Asbtract

Background: Autoimmune responses contribute to the pathophysiology of Long COVID, affective symptoms and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Objectives: To examine whether Long COVID, and its accompanying affective symptoms and CFS are associated with immunoglobulin (Ig)A/IgM/IgG directed at neuronal proteins including myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), synapsin, α+β-tubulin, neurofilament protein (NFP), cerebellar protein-2 (CP2), and the blood-brain-barrier-brain-damage (BBD) proteins claudin-5 and S100B.

Methods: IgA/IgM/IgG to the above neuronal proteins, human herpes virus-6 (HHV-6) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were measured in 90 Long COVID patients and 90 healthy controls, while C-reactive protein (CRP), and advanced oxidation protein products (AOPP) in association with affective and CFS ratings were additionally assessed in a subgroup thereof.

Results: Long COVID is associated with significant increases in IgG directed at tubulin (IgG-tubulin), MBP, MOG and synapsin; IgM-MBP, MOG, CP2, synapsin and BBD; and IgA-CP2 and synapsin. IgM-SARS-CoV-2 and IgM-HHV-6 antibody titers were significantly correlated with IgA/IgG/IgM-tubulin and -CP2, IgG/IgM-BBD, IgM-MOG, IgA/IgM-NFP, and IgG/IgM-synapsin. Binary logistic regression analysis shows that IgM-MBP and IgG-MBP are the best predictors of Long COVID.

Multiple regression analysis shows that IgG-MOG, CRP and AOPP explain together 41.7% of the variance in the severity of CFS. Neural network analysis shows that IgM-synapsin, IgA-MBP, IgG- MOG, IgA-synapsin, IgA-CP2, IgG-MBP and CRP are the most important predictors of affective symptoms due to Long COVID with a predictive accuracy of r=0.801.

Conclusion: Brain-targeted autoimmunity contributes significantly to the pathogenesis of Long COVID and the severity of its physio-affective phenome.

10. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (Me/Cfs): The Biology of a Neglected Disease

Hayley Arron, Benamin Marsh, M. Asad Khan, Beate Jaeger, Douglas Kell, Etheresia Pretorius.

Heliyon [Preprint]

Abstract

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic disease with debilitating symptoms that impact all aspects of life. The diverse symptom presentation indicates that ME/CFS is likely to have a multifactorial origin. However, it is an extremely understudied disease with no standardised diagnostic criteria or proven treatment avenues.

It is hypothesised that environmental insults (such as acute infection, mainly viral) or stress in genetically susceptible individuals may trigger the development of ME/CFS. These insults result in acute inflammatory responses, along with aberrant immune activation. A spiralling disruption of homeostasis promotes subsequent patho-mechanisms including gut dysbiosis and systemic inflammation, and eventually a pathological clotting system, chronic endothelialitis, vasoconstriction, and hypoxia.

Additionally, dysfunctional energy metabolism including oxidative stressis also present in the development of ME/CFS. Since the exact pathophysiology of ME/CFS remains unclear, additional research is required to reveal further insight into this “neglected” disease.

11. Case report: Recurrent cervical spinal stenosis masquerading as myalgic encephalomyelitis/chronic fatigue syndrome with orthostatic intolerance

Charles C. Edwards III, Charles C. Edwards II, Scott Heinlein, Peter C. Rowe.

Frontiers in Neurology, Volume-14- 2023.

Abstract

Introduction: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, chronic, multi-system disorder that is characterized by a substantial impairment in the activities that were well tolerated before the illness.

In an earlier report, we had described three adult women who met criteria for ME/CFS and orthostatic intolerance, and had congenital or acquired cervical spinal stenosis. All three experienced substantial global improvements in their ME/CFS and orthostatic intolerance symptoms after recognition and surgical treatment of the cervical stenosis. After a several year period of improvement, one of the individuals in that series experienced a return of ME/CFS and orthostatic intolerance symptoms.

Main Symptoms and Clinical Findings: Radiologic investigation confirmed a recurrence of the ventral compression of the spinal cord due to a shift of the disc replacement implant at the involved cervical spinal level.

Therapeutic Intervention: Decompression of the spinal cord with removal of the implant and fusion at the original C5-C6 level was once again followed by a similar degree of improvement in function as had been observed after the first operation.

This recapitulation of the outcomes after surgical management of cervical stenosis provides further evidence in support of the hypothesis that cervical spinal stenosis can exacerbate pre-existing or cause new orthostatic intolerance and ME/CFS. Especially for those with refractory symptoms and neurological signs, surgical interventions may offer relief for selected patients with this complex condition.

12. A systematic review of quantitative EEG findings in Long COVID, Fibromyalgia and Chronic Fatigue Syndrome

Bárbara Silva-Passadouro, Arnas Tamasauskas, Omar Khoja, Alexander J. Casson, Ioannis Delis, Christopher Brown, Manoj Sivan.

medRxiv [Preprint]

Abstract

Long COVID (LC) is a multisymptom clinical syndrome with similarities to Fibromyalgia Syndrome (FMS) and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). All these conditions are believed to be associated with centrally driven mechanisms such as central sensitisation.

There is a lack of consensus on quantitative EEG (qEEG) changes observed in these conditions. This review aims to synthesise and appraise the literature on resting-state qEEG in LC, FMS and CFS/ME, to help uncover possible mechanisms of central sensitisation in these similar clinical syndromes.

A systematic search of MEDLINE, Embase, CINHAL, PsycINFO and Web of Science databases for articles published between December 1994 and September 2023 was performed. Following screening for predetermined selection criteria and out of the initial 2510 studies identified, 17 articles were retrieved that met all the inclusion criteria, particularly of assessing qEEG changes in one of the three conditions compared to healthy controls. All studies scored moderate to high quality on the Newcastle-Ottawa scale.

There was a general trend for decreased low frequency EEG band activity (delta, theta, and alpha) and increased high-frequency EEG beta activity in FMS, whereas an opposite trend was found in CFS/ME. The limited LC studies included in this review focused mainly on cognitive impairments and showed mixed findings not consistent with patterns seen in FMS and CFS/ME.

Further research is required to explore whether there are phenotypes within LC that have EEG signatures similar to FMS or CFS/ME. This could inform identification of reliable diagnostic markers and possible targets for neuromodulation therapies.

Long-COVID Research References

  1. From aging to long COVID: exploring the convergence of immunosenescence, inflammaging, and autoimmunity
  2. Correlations of Long COVID Symptoms and Inflammatory Markers of Complete Blood Count (CBC): A cross-sectional study
  3. The cost of primary care consultations associated with long COVID in non-hospitalised adults: a retrospective cohort study using UK primary care data
  4. Decreased Pulmonary Blood Flow and Airway Volumes in Patients With Long COVID Syndrome Assessed by Functional Respiratory Imaging
  5. Several De-Regulated Chemokine Pathways Characterize Long COVID Syndrome
  6. Association between SARS-CoV-2 variants and post COVID-19 condition: findings from a longitudinal cohort study in the Belgian adult population
  7. Remission of severe forms of long COVID following monoclonal antibody (MCA) infusions: A report of signal index cases and call for targeted research
  8. Beyond the acute illness: Exploring long COVID and its impact on multiple organ systems
  9. Autonomic Manifestations of Long-COVID Syndrome
  10. Allergic diseases as risk factors for Long-COVID symptoms: Systematic review of prospective cohort studies
  11. Long COVID with Persistent High Fever as the Main Manifestation: A Case Report
  12. Analysis of the Correlation between Heart Rate Variability and Palpitation Symptoms in Female Patients With Long COVID
  13. Post-COVID-19 and Irritable Bowel Syndrome: A Literature Review
  14. Nirmatrelvir/ritonavir and risk of long COVID symptoms: a retrospective cohort study
  15. Role of Tau protein in long COVID and potential therapeutic targets
  16. Determinants of the onset and prognosis of the post-COVID-19 condition: a 2-year prospective observational cohort study
  17. Insights into the epidemiology and clinical aspects of post-COVID-19 conditions in adult
  18. Pharmacological evaluation of vitamin D in COVID-19 and long COVID-19: recent studies confirm clinical validation and highlight metformin to improve VDR sensitivity and efficacy
  19. Substantial differences in perception of disease severity between post COVID-19 patients, internists, and psychiatrists or psychologists: the Health Perception Gap and its clinical implications
  20. Long COVID and Physical Therapy: A Systematic Review
  21. Risk Factors for Long COVID in Older Adults
  22. Effectiveness of an amygdala and insula retraining program combined with mindfulness training to improve the quality of life in patients with long COVID: a randomized controlled trial protocol
  23. The pathophysiology and diagnostics of post-acute SARS COVID-19 infection of the CNS

Physical exertion worsens symptoms in patients with post-COVID condition : Post-exertional malaise in patients with post-COVID condition

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent
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