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

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.

Source: Bárbara Silva-Passadouro, Arnas Tamasauskas, Omar Khoja, Alexander J. Casson, Ioannis Delis, Christopher Brown, Manoj Sivan. A systematic review of quantitative EEG findings in Long COVID, Fibromyalgia and Chronic Fatigue Syndrome. medRxiv [Preprint] https://www.medrxiv.org/content/10.1101/2023.11.06.23298171v1.full-text (Full text)

Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis

Abstract:

Background: Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness without a medically explained cause. Recently during COVID-19 pandemic, many studies have confirmed the symptoms similar to ME/CFS in the recovered individuals. To investigate the virus-related etiopathogenesis of ME/CFS, we conducted a systematic assessment of viral infection frequency in ME/CFS patients.

Methods: We conducted a comprehensive search of PubMed and the Cochrane Library from their inception through December 31, 2022, using selection criteria of viral infection prevalence in ME/CFS patients and controls. Subsequently, we performed a meta-analysis to assess the extent of viral infections’ contribution to ME/CFS by comparing the odds ratio between ME/CFS patients and controls (healthy and/or diseased).

Results: Finally, 64 studies met our eligibility criteria regarding 18 species of viruses, including a total of 4971 ME/CFS patients and 9221 control subjects. The participants included healthy subjects and individuals with one of 10 diseases, such as multiple sclerosis or fibromyalgia. Two DNA viruses (human herpes virus (HHV)-7 and parvovirus B19, including their co-infection) and 3 RNA viruses (borna disease virus (BDV), enterovirus and coxsackie B virus) showed odds ratios greater than 2.0 compared with healthy and/or diseased subjects. Specifically, BDV exceeded the cutoff with an odds ratio of ≥ 3.47 (indicating a “moderate association” by Cohen’s d test) compared to both healthy and diseased controls.

Conclusion: This study comprehensively evaluated the risk of viral infections associated with ME/CFS, and identified BDV. These results provide valuable reference data for future studies investigating the role of viruses in the causation of ME/CFS.

Source: Hwang, JH., Lee, JS., Oh, HM. et al. Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis. J Transl Med 21, 763 (2023). https://doi.org/10.1186/s12967-023-04635-0 https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04635-0 (Full text)

Complementary and alternative medicine for long COVID: a systematic review of randomized controlled trials

Abstract:

Background: Complementary and alternative medicine (CAM) interventions are growing in popularity as possible treatments for long COVID symptoms. However, comprehensive analysis of current evidence in this setting is still lacking.

Objective: This study aims to review existing published studies on the use of CAM interventions for patients experiencing long COVID through a systematic review.

Design: Systematic review of randomized controlled trials (RCTs).

Methods: A comprehensive electronic literature search was performed in multiple databases and clinical trial registries from September 2019 to January 2023. RCTs evaluating efficacy and safety of CAM for long COVID were included. Methodological quality of each included trial was appraised with the Cochrane ‘risk of bias’ tool. A qualitative analysis was conducted due to heterogeneity of included studies.

Results: A total of 14 RCTs with 1195 participants were included in this review. Study findings demonstrated that CAM interventions could benefit patients with long COVID, especially those suffering from neuropsychiatric disorders, olfactory dysfunction, cognitive impairment, fatigue, breathlessness, and mild-to-moderate lung fibrosis. The main interventions reported were self-administered transcutaneous auricular vagus nerve stimulation, neuro-meditation, dietary supplements, olfactory training, aromatherapy, inspiratory muscle training, concurrent training, and an online breathing and well-being program.

Conclusion: CAM interventions may be effective, safe, and acceptable to patients with symptoms of long COVID. However, the findings from this systematic review should be interpreted with caution due to various methodological limitations. More rigorous trials focused on CAM for long COVID are warranted in the future.

Source: Yang J, Lim KH, Lim KT, Woods JT, Mohabbat AB, Wahner-Roedler DL, Ganesh R, Bauer BA. Complementary and alternative medicine for long COVID: a systematic review of randomized controlled trials. Ther Adv Chronic Dis. 2023 Oct 11;14:20406223231204727. doi: 10.1177/20406223231204727. PMID: 37841213; PMCID: PMC10571674. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571674/ (Full text)

A Systematic Analysis of the Effectiveness of Mitochondrial-Based Therapies for the Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Background: This study aimed to compile and analyze an assortment of research findings concerning potential therapeutic strategies for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The understanding of the multifaceted nature of ME/CFS and the need for varied and personalized therapeutic approaches were central to this investigation.

Methods: A comprehensive review and analysis of various studies conducted on ME/CFS was undertaken. These studies covered a wide array of interventions, including pharmacological treatments, nutritional supplements, dietary changes, physical therapies, and lifestyle modifications. The analysis pertained to the effectiveness of these interventions, potential physiological and biochemical markers, and the response of ME/CFS patients to different treatment strategies.

Results: The 22 selected papers investigated demonstrated varied responses to the multitude of interventions. While some interventions showed significant improvement in fatigue and biochemical parameters, others found no significant differences between the treated and control groups. Potential physiological and biochemical markers for ME/CFS, such as impaired T cell metabolism, reduced flow-mediated dilation, and decreased work rate at the ventilatory threshold, were highlighted.

Conclusion: The findings underscored the complexity of ME/CFS and the need for personalized treatment strategies. Despite mixed results and several limitations, these studies collectively contributed to understanding ME/CFS’s complex pathophysiology and treatment, laying the groundwork for future research towards more effective therapeutic strategies for this debilitating disease.

Source: Keferstein, L.G. A Systematic Analysis of the Effectiveness of Mitochondrial-Based Therapies for the Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Preprints 2023, 2023100637. https://doi.org/10.20944/preprints202310.0637.v1 https://www.preprints.org/manuscript/202310.0637/v1 (Full text available as PDF)

Post-COVID-19 cholangiopathy: Systematic review

Abstract:

Background: The coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on global health, primarily characterized by severe respiratory illness. However, emerging evidence suggests that COVID-19 can also lead to secondary sclerosing cholangitis (SC), referred to as post-COVID-19 cholangiopathy.

Aim: To synthesize currently reported cases to assess the current state of knowledge on post-COVID-19 cholangiopathy.

Methods: Medical Subject Headings and Health Sciences Descriptors were used to retrieve relevant studies, which were combined using Boolean operators. Searches were conducted on electronic databases including Scopus, Web of Science, and MEDLINE (PubMed). Studies published in English, Spanish, or Portuguese were included, with no restrictions on the publication date. Additionally, the reference lists of retrieved studies were manually searched. Simple descriptive analyses were used to summarize the results. Then the data were extracted and assessed based on Reference Citation Analysis (https://www.referencecitationanalysis.com/).

Results: The initial search yielded a total of 192 articles. After screening, 85 articles were excluded due to duplication, leaving 107 articles for further review. Of these, 63 full-length articles met the inclusion criteria and were included in the analyses. Most of the patients were male and exhibited elevated liver function tests (93.8%). Magnetic resonance imaging revealed duct thickening with contrast enhancement (47.7%), as well as beading of the intrahepatic ducts (45.7%) with peribiliary contrast enhancement on diffusion (28.7%). Liver biopsy results confirmed SC in most cases (74.4%). Sixteen patients underwent liver transplantation, with three experiencing successful outcomes.

Conclusion: Post-COVID-19 cholangiopathy is a serious condition that is expected to become increasingly concerning in the coming years, particularly considering long COVID syndromes. Although liver transplantation has been proposed as a potential treatment option, more research is necessary to establish its efficacy and explore other potential treatments.

Source: Rasheed MA, Ballotin VR, Bigarella LG, Soldera J. Post-COVID-19 cholangiopathy: Systematic review. World J Methodol. 2023 Sep 20;13(4):296-322. doi: 10.5662/wjm.v13.i4.296. PMID: 37771872; PMCID: PMC10523251. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10523251/ (Full text)

Is there a role for traditional and complementary medicines in managing chronic fatigue? A systematic review of randomized controlled trials

Abstract:

Introduction: Chronic fatigue syndrome (CFS) is an increasingly common condition that is challenging to treat due to unclear etiology and a lack of consensus on clinical diagnosis and treatment guidance. Many affected people resorted to using traditional and complementary medicines (T&CMs). However, the evidence for T&CMs for CF has been inconclusive and continues to evolve. The study aims to identify, summarize and assess the most recent evidence on the efficacy and safety of T&CMs for CFS.

Methods: Randomized controlled trials (RCTs) investigating T&CMs for CFS published in English of Chinese between 1 January 2013 and 31 December 2022 were searched from 7 databases. RCTs comparing T&CMs with no treatment, placebo, or pharmacological medicine were included, irrespective of language or blinding.

The Consolidated Standards of Reporting Trials Statement extensions for Chinese herbal medicine Formulas (CONSORT-CHM) and the Cochrane Collaboration’s Risk of Bias tool were used to evaluate the quality and risk of bias of included studies.

Results: A total of 62 RCTs investigating 43 types of T&CMs and involving 5,231 participants with CFS were included in this review. The primary outcome measures mainly included the scoring of fatigue symptoms using the validated tool Fatigue Scale-14 (FS-14) or the TCM syndrome score.

The main interventions showing overall efficacy were Chaihu Guizhi Decoction and Buzhong Yiqi combined with Xiao Chaihu Decoction, and 148 ingredients were identified, including Astragali Radix, Glycyrrhizae Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, and Bupleuri Radix.

The most significant effect was the improvement of fatigue, followed by TCM-diagnosed symptoms and other psychological conditions. No serious adverse effect had been reported. However, the quality of the RCTs included RCTs were found to be suboptimal, and the risk of bias remained uncertain.

Conclusions: Some evidence from RCTs supported the efficacy and safety of T&CM in CFS. However, given the methodological and quality heterogenicity of the included studies, the recommendations of T&CMs in treating CFS remain inconclusive. To develop better quality evidence about T&CMs for CFS, future studies should employ more objective diagnosis standards and outcome measurements, larger sample size, and better bias control, and ensure the compliance with the corresponding reporting guidelines.

Source: Yuxiao Li, Jingya Yang, Chi Ian Chau, Junnan Shi, Xianwen Chen, Hao Hu, Carolina Oi Lam Ung. Is there a role for traditional and complementary medicines in managing chronic fatigue? A systematic review of randomized controlled trials. Frontiers in Pharmacology, Volume 14, 2023. https://www.frontiersin.org/articles/10.3389/fphar.2023.1266803/abstract

Identifying, synthesising and appraising existing evidence relating to myalgic encephalomyelitis/chronic fatigue syndrome and pregnancy: a mixed-methods systematic review

Abstract

Objectives: To identify, synthesise and appraise evidence relating to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and pregnancy.

Design: Mixed-methods systematic review, using convergent segregated design.

Data sources: MEDLINE, EMBASE, Scopus, PsycINFO, CINAHL, MedRxiv, PROSPERO and grey literature sources through 6 August 2023.

Eligibility criteria: We included original research studies, expert opinion and grey literature reporting on ME/CFS and pregnancy/post partum (up to 2 years), risk of pregnancy outcomes with ME/CFS or experiences during pregnancy for mother, partner or health and social care professionals following ME/CFS during pregnancy, all where the evidence was relevant to a confirmed ME/CFS diagnosis prior to pregnancy.

Data extraction and synthesis: Three independent reviewers completed all screening, data extraction and quality assessment. Risk of bias was assessed using the mixed-methods appraisal tool V.2018. Qualitative and quantitative literature was analysed separately using thematic and descriptive syntheses. Findings were integrated through configuration.

Results: Searches identified 3675 articles, 16 met the inclusion criteria: 4 quantitative (1 grey), 11 qualitative (9 grey) and 1 grey mixed-methods study. Of the four quantitative studies that reported on ME/CFS severity during pregnancy, two suggested pregnancy negatively impacted on ME/CFS, one found most women had no change in ME/CFS symptoms and one found ME/CFS improved; this difference in symptom severity across studies was supported by the qualitative evidence. The qualitative literature also highlighted the importance of individualised care throughout pregnancy and birth, and the need for additional support during family planning, pregnancy and with childcare. Only one quantitative study reported on pregnancy outcomes, finding decreased vaginal births and higher rates of spontaneous abortions and developmental and learning delays associated with pregnancies in those with ME/CFS.

Conclusions: Current evidence on ME/CFS in pregnancy is limited and findings inconclusive. More high-quality research is urgently needed to support the development of evidence-based guidelines on ME/CFS and pregnancy.

Source: Slack E, Pears KA, Rankin J, Newton JL, Pearce M. Identifying, synthesising and appraising existing evidence relating to myalgic encephalomyelitis/chronic fatigue syndrome and pregnancy: a mixed-methods systematic review. BMJ Open. 2023 Oct 5;13(10):e070366. doi: 10.1136/bmjopen-2022-070366. PMID: 37798026. https://bmjopen.bmj.com/content/13/10/e070366 (Full text)

Post-COVID-19 Symptoms in Adults with Asthma—Systematic Review

Abstract:

Background: Research on the longer-term sequelae of COVID-19 in patients with asthma is limited. Objective: To assess the frequency and severity of long-term symptoms of COVID-19 in the population of asthma patients.
Methods: A systematic review of the published literature was conducted in accordance with the recommendations of the PRISMA statement. EMBASE, MEDLINE/PubMed, Web of Science, CINAHL, and Scopus Scholar were searched for terms related to asthma and post or long COVID-19, and for systematic reviews related to specific questions within our review, up to June 2022.
Results: Data from 9 references publications included in the review were extracted. A total of 1466 adult asthmatic patients with COVID-19 infection were described in all the publications mentioned above. Of the long-term symptoms reported after COVID-19, patients indicated: lower respiratory symptoms, fatigue, cognitive symptoms, psychological problems, and other such as skin rashes, gastrointestinal disorders, tachycardia, palpitations, ocular disorders, ageusia/hypogeusia, anosmia/hyposmia, and poor sleep quality. These symptoms in similar intensity were observed in the comparison groups without a diagnosis of asthma.
Conclusions: The published data neither confirm nor deny that long-term COVID-19 symptoms in patients with asthma diagnosis are different in strength and frequency from patients without asthma diagnosis. To indicate associations between asthma and COVID-19 infection and severity, as well as the frequency of long-term symptoms of COVID-19, more longitudinal research is needed in chronic asthma patients with different phenotypes, intensity of treatment, and degree of asthma control.
Source: Kaszuba M, Madej N, Pilinski R, Sliwka A. Post-COVID-19 Symptoms in Adults with Asthma—Systematic Review. Biomedicines. 2023; 11(8):2268. https://doi.org/10.3390/biomedicines11082268 https://www.mdpi.com/2227-9059/11/8/2268 (Full text)

DNA methylation signatures of functional somatic syndromes: Systematic review

Abstract:

Objective: Functional somatic syndromes (FSS) are highly prevalent across all levels of healthcare. The fact that they are characterised by medically unexplained symptoms, such as fatigue and pain, raises the important question of their underlying pathophysiology. Psychosocial stress represents a significant factor in the development of FSS and can induce long-term modifications at the epigenetic level. The aim of this review was to systematically review, for the first time, whether individuals with FSS are characterised by specific alterations in DNA methylation.

Methods: MEDLINE and PsycINFO were searched from the first available date until September 2022. The inclusion criteria were: 1) adults fulfilling research diagnostic criteria for chronic fatigue syndrome, fibromyalgia syndrome, and/or irritable bowel syndrome, 2) healthy control group, and 3) candidate-gene or genome-wide study of DNA methylation.

Results: Sixteen studies (N = 957) were included. In candidate-gene studies, specific sites within NR3C1 were identified, which were hypomethylated in individuals with chronic fatigue syndrome compared to healthy controls. In genome-wide studies in chronic fatigue syndrome, a hypomethylated site located to LY86 and hypermethylated sites within HLA-DQB1 were found. In genome-wide studies in fibromyalgia syndrome, differential methylation in sites related to HDAC4 , TMEM44 , KCNQ1 , SLC17A9 , PRKG1 , ALPK3 , TFAP2A , and LY6G5C was found.

Conclusions: Individuals with chronic fatigue syndrome and fibromyalgia syndrome appear to be characterised by altered DNA methylation of genes regulating cellular signalling and immune functioning. In chronic fatigue syndrome, there is preliminary evidence for these to be implicated in key pathophysiological alterations, such as hypocortisolism and low-grade inflammation, and to contribute to the debilitating symptoms these individuals experience.

Preregistration PROSPERO identifier: CRD42022364720.

Source: Fischer S, Kleinstäuber M, Fiori LM, Turecki G, Wagner J, von Känel R. DNA methylation signatures of functional somatic syndromes: Systematic review. Psychosom Med. 2023 Aug 21. doi: 10.1097/PSY.0000000000001237. Epub ahead of print. PMID: 37531610. https://pubmed.ncbi.nlm.nih.gov/37531610/

The demographic features of fatigue in the general population worldwide: a systematic review and meta-analysis

Abstract:

Background: Fatigue is one of the most common subjective symptoms that impairs daily life and predict health-related events. This study aimed to estimate the prevalence of fatigue in the global population.

Methods: PubMed and the Cochrane Library were used to search for relevant articles from inception to December 31, 2021. Studies with prevalence data of fatigue in the general population were selected and reviewed by three authors independently and cross-checked. Regarding subgroups, adults (≥18 years), minors (<18 years), and specific occupation population (participants in each study being limited to a specific occupational group), and fatigue types and severity, meta-analysis was conducted to produce point estimates and 95% confidence intervals (95% CI).

Results: From the initial 3,432 studies, 91 studies accounting for 115 prevalence data points (623,624 participants) were finally selected. The prevalence of general fatigue (fatigue lasting < 6 months, or fatigue of unspecified duration) was 20.4% (95% CI, 16.7–25.0) in adults, 11.7% (95% CI, 5.2–26.6) in minors, and 42.3% (95% CI, 33.0–54.2) in specific occupations. Chronic fatigue (fatigue lasting more than 6 months) affected 10.1% (95% CI, 8.2–12.5) of adults, 1.5% (95% CI, 0.5–4.7) of minors, and 5.5% (95% CI, 1.4–21.6) of subjects in specific occupations. There was an overall female-predominant prevalence for all subgroup analyses, with a total odds ratio of 1.4 (95% CI, 1.3–1.6).

Regarding the severity and presence of medical causes, the total prevalence of moderate fatigue [14.6% (95% CI, 9.8–21.8)] was 2.4-fold that of severe fatigue [6.1% (95% CI, 3.4–11.0)], while unexplained fatigue (fatigue experienced by individuals without any underlying medical condition that can explain the fatigue) was ~2.7-fold that of explained fatigue (fatigue experienced by individuals with a medical condition that can explain the fatigue); as proportion of 40.0% of physical, 8.6% of mental, and 28.4% of mixed cause.

Conclusions: This study has produced the first comprehensive picture of global fatigue prevalence in the general population, which will provide vital reference data contributing to fatigue-related research, including the prevention of diseases.

Source: Yoon JH, Park NH, Kang YE, Ahn YC, Lee EJ, Son CG. The demographic features of fatigue in the general population worldwide: a systematic review and meta-analysis. Front Public Health. 2023 Jul 28;11:1192121. doi: 10.3389/fpubh.2023.1192121. PMID: 37575103; PMCID: PMC10416797. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10416797/ (Full text)