Epstein-Barr virus (EBV) infection is commonly reported at the onset of ME/CFS, but could antibodies against EBV serve as biomarkers of the disease?
No differences in antibody responses were found between blood samples from 92 ME/CFS patients and 50 healthy control subjects.
However, when analysing only patients with a reported infectious onset of disease, antibody responses against two EBV-related antigens were stronger in the patient group; these results need confirmation.
Research abstract:
Infections by the Epstein-Barr virus (EBV) are often at the disease onset of patients suffering from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, serological analyses of these infections remain inconclusive when comparing patients with healthy controls (HCs). In particular, it is unclear if certain EBV-derived antigens eliciting antibody responses have a biomarker potential for disease diagnosis.
With this purpose, we re-analyzed a previously published microarray data on the IgG antibody responses against 3,054 EBV-related antigens in 92 patients with ME/CFS and 50 HCs. This re-analysis consisted of constructing different regression models for binary outcomes with the ability to classify patients and HCs. In these models, we tested for a possible interaction of different antibodies with age and gender. When analyzing the whole data set, there were no antibody responses that could distinguish patients from healthy controls.
A similar finding was obtained when comparing patients with non-infectious or unknown disease trigger with healthy controls. However, when data analysis was restricted to the comparison between HCs and patients with a putative infection at their disease onset, we could identify stronger antibody responses against two candidate antigens (EBNA4_0529 and EBNA6_0070).
Using antibody responses to these two antigens together with age and gender, the final classification model had an estimated sensitivity and specificity of 0.833 and 0.720, respectively. This reliable case-control discrimination suggested the use of the antibody levels related to these candidate viral epitopes as biomarkers for disease diagnosis in this subgroup of patients.
To confirm this finding, a follow-up study will be conducted in a separate cohort of patients.
Research authors & location:
Nuno Sepúlveda, João Malato, Franziska Sotzny, Anna D Grabowska, André Fonseca, Clara Cordeiro, Luís Graça, Przemyslaw Biecek, Uta Behrends, Josef Mautner, Francisco Westermeier, Eliana M Lacerda, Carmen Scheibenbogen inFront Med (Lausanne). 2022 Jun 24;9:921101 [doi: 10.3389/fmed.2022.921101] eCollection 2022.
Whilst we are cognisant that the pandemic has brought with it unprecedented demand on all health and social services, two years hence, the situation for people living with neurological conditions in Wales is now at crisis point and they feel abandoned [WNA]
8,510 people living with or affected by neurological conditions across the UK completed the My Neuro Survey, 503 from Wales. Results are now available in the Wales Neurological Alliance (WNA) report: My Neuro Survey Wales.
People living with neurological conditions in Wales continue to report substantial barriers to accessing the treatment, services and support that they need from health and social care services. [WNA]
Survey aim?
To understand the demand for and impact of services for people living with neurological
conditions in Wales
Who?
Of those who completed the questionnaire, 93% (n=462) lived with a neurological
condition; 7% were carers, friends or family members of a person with a neurological
condition.
The most reported conditions were:
Multiple sclerosis 23.1%
Other 22.3% (includes people with ME)]
Dystonia 10.7%
Epilepsy 9.1%
Migraine 7.6%
Parkinson’s 7.6%
Myasthenia 7.6%
Huntington’s 4.4%
Results
There were several themes emerging from the My Neuro Survey, these include:
The Wales Neurological Alliance’s response:
Urgent action is now required by those who plan, commission and deliver our services to address the shortcomings and ensure that people living with neurological conditions are not left behind in the post COVID recovery planning.
1 in 6 people in the UK live with a neurological condition, but there simply isn’t the workforce or services in place to support them.
From delays to lifechanging treatment and care, to a lack of mental health support, we need Governments across the UK to back the 1 in 6, and set up a Neuro Taskforce to deliver real change. Sign our petition today!
WAMES (and the WNA) are also in discussions with the Welsh Government Neuro / ME lead, exploring ways to help Health Boards improve healthcare for people with ME and #ImplementNICEmecfs. You can help by sharing with us your recent experiences of health and social care so we are up to date with any changes that are (or are not) bring made.
People with chronic invisible illnesses like POTS, CFS/ME, EDS, MCAS, and fibromyalgia have numerous and often severe somatic symptoms related to their illness that may over-inflate their depression scores on many common screening instruments. This leads to the possible over-diagnosis of depression in this community, further hindering individuals with chronic invisible illness when seeking treatment.
Research abstract
Background
Depression screening instruments are commonly used in research and the clinic.
Aim:
This study seeks to determine whether several common depression scales might be contaminated by somatic symptoms, thus overestimating depression in people with chronic invisible illness.
Method:
685 chronically ill women with postural orthostatic tachycardia syndrome, chronic fatigue syndrome/myalgic encephalomyelitis, mast cell activation syndrome, Ehlers-Danlos syndrome and/or fibromyalgia took the Beck Depression Inventory-II (BDI-II). For a broader look at major self-report scales that assess depression in adults, we also investigated seven additional instruments listed on the American Psychological Association webpage.
Results:
In this sample, 38.5% appeared to have major depression as measured by the BDI-II, but this number decreased to 8% when somatic symptoms were removed. Further, there was a 31.2% increase in the number of participants in the minimal depression category of the BDI-II-Mood.
Finally, 75% of the adult depression scales that we assessed had at least 40% of the score related to somatic symptoms.
Conclusion:
Care must be taken when assessing depression in people with chronic invisible illnesses to prevent artificial over-inflation of scores based on somatic complaints.
Our findings provide the first metabolomic evidence of peroxisomal dysfunction, and are consistent with dysregulation of lipid remodeling and the tricarboxylic acid cycle. These findings, if validated in other cohorts, could provide new insights into the pathogenesis of ME/CFS and highlight the potential use of the plasma metabolome as a source of biomarkers for the disease.
Peroxisomes are small structures (organelles) inside a cell that perform specific functions to keep that cell alive. Mitochondria is an organelle which makes energy. Peroxisome regulates biochemical pathways that involve oxidation. (Study.com)
Research abstract:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease characterized by unexplained physical fatigue, cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems.
Persoxisome
People with ME/CFS often report a prodrome consistent with infections. Using regression, Bayesian and enrichment analyses, we conducted targeted and untargeted metabolomic analysis of plasma from 106 ME/CFS cases and 91 frequency-matched healthy controls.
Subjects in the ME/CFS group had significantly decreased levels of plasmalogens and phospholipid ethers (p<0.001), phosphatidylcholines (p<0.001) and sphingomyelins (p<0.001), and elevated levels of dicarboxylic acids (p=0.013). Using machine learning algorithms, we were able to differentiate ME/CFS or subgroups of ME/CFS from controls with area under the receiver operating characteristic curve (AUC) values up to 0.873.
Metabolomics is the screening for characteristic substances in body fluids and tissue, which serve as direct marker of biochemical activity
Xiaoyu Che, Christopher R Brydges, Yuanzhi Yu, Adam Price, Shreyas Joshi, Ayan Roy, Bohyun Lee, Dinesh K Barupal, Aaron Cheng, Dana March Palmer, Susan Levine, Daniel L Peterson, Suzanne D Vernon, Lucinda Bateman, Mady Hornig, Jose G Montoya, Anthony L Komaroff, Oliver Fiehn, W Ian Lipkin
by Suzanne D Vernon, Sherlyn Funk, Lucinda Bateman, Gregory J Stoddard, Sarah Hammer, Karen Sullivan, Jennifer Bell, Saeed Abbaszadeh, W Ian Lipkin, Anthony L Komaroff inFront Med (Lausanne). 23 Jun 2022 [doi: 10.3389/fmed.2022.917019]
Research abstract conclusions:
A test of orthostatic stress easily performed in an office setting reveals different symptomatic, hemodynamic and cognitive abnormalities in people with Long COVID and ME/CFS, compared to healthy control subjects.
Thus, an orthostatic challenge easily performed in an office setting, and the use of a smart phone app to assess cognition, can provide objective confirmation of the orthostatic intolerance and brain fog reported by patients with Long COVID and ME/CFS.
Background:
Some patients with acute COVID-19 are left with persistent, debilitating fatigue, cognitive impairment (“brain fog”), orthostatic intolerance (OI) and other symptoms (“Long COVID”). Many of the symptoms are like those of other post-infectious fatigue syndromes and may meet criteria for myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). Common diagnostic laboratory tests are often unrevealing.
Methods:
We evaluated whether a simple, standardized, office-based test of OI, the 10-min NASA Lean Test (NLT), would aggravate symptoms and produce objective hemodynamic and cognitive abnormalities, the latter being evaluated by a simple smart phone-based app.
Participants:
People with Long COVID (N = 42), ME/CFS (N = 26) and healthy control subjects (N = 20) were studied just before, during, immediately after, 2 and 7 days following completion of the NLT.
Results:
The NLT provoked a worsening of symptoms in the two patient groups but not in healthy control subjects, and the severity of all symptoms was similar and significantly worse in the two patient groups than in the control subjects (p < 0.001). In the two patient groups, particularly those with Long COVID, the NLT provoked a marked and progressive narrowing in the pulse pressure. All three cognitive measures of reaction time worsened in the two patient groups immediately following the NLT, compared to the healthy control subjects, particularly in the Procedural Reaction Time (p < 0.01).
Since H2 ameliorates mitochondrial dysfunction, we herein reviewed the literature for the anti-fatigue effects of H2 in animal studies and human clinical trials. The findings of the literature review suggested that H2 exerts anti-fatigue effects, and that these effects may involve not only the direct scavenging of mitochondria-generated ROS by H2, but also its antioxidant and anti-inflammatory effects through the regulation of gene expression.
Molecular hydrogen =H2 = dihydrogen = hydrogen gas
Since mitochondrial dysfunction is also involved in the etiology of ME/CFS, the literature review also suggested that the anti-fatigue effects of H2 in animal and human clinical studies indicate a possible ameliorative effect of H2 on ME/CFS. Since “long COVID” or “post COVID,” the “sequelae” of COVID-19, may be similar to ME/CFS, there is an urgent need to develop precise therapies and substances for ME/CFS. H2 gas may be an effective medical gas for the treatment of ME/CFS.
A possible mechanism by which H2 ameliorates mitochondrial dysfunction in ME/CFS patients.
Review abstract:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disorder that is characterized by fatigue that persists for more than 6 months, weakness, sleep disturbances, and cognitive dysfunction. There are multiple possible etiologies for ME/CFS, among which mitochondrial dysfunction plays a major role in abnormal energy metabolism.
The potential of many substances for the treatment of ME/CFS has been examined; however, satisfactory outcomes have not yet been achieved. The development of new substances for curative, not symptomatic, treatments is desired. Molecular hydrogen (H2) ameliorates mitochondrial dysfunction by scavenging hydroxyl radicals, the most potent oxidant among reactive oxygen species. Animal experiments and clinical trials reported that H2 exerted ameliorative effects on acute and chronic fatigue.
Therefore, we conducted a literature review on the mechanism by which H2 improves acute and chronic fatigue in animals and healthy people and showed that the attenuation of mitochondrial dysfunction by H2 may be involved in the ameliorative effects.
Although further clinical trials are needed to determine the efficacy and mechanism of H2 gas in ME/CFS, our literature review suggested that H2 gas may be an effective medical gas for the treatment of ME/CFS.
Cwm Taf Morgannwg UHB is “aware of the revised ME/CFS NICE guideline”
WAMES has been asking Health Boards in Wales what plans they have to implement NICE guidelines, whether they intend to consult with patients and how they think their long COVID service might benefit people with ME.
Cwm Taf Morgannwg University Health Board’s Chief Executive Paul Mears asked their Executive Director of Therapies and Health Sciences to respond. Lauren Edwards shares her overview with WAMES:
“Your email raised queries in regard to our Health Board’s response to the recent publication of updated NICE ME/CFS Guidelines and I have linked in with key colleagues on this matter.
Whilst we do not have a dedicated ME/CFS service within CTMUHB, I have received assurance from colleagues within our core services that they are aware of the revised guideline. As you are aware, the guideline makes it clear that any programme based on fixed incremental increases in physical activity or exercise, for example graded exercise therapy (GET), should not be recommended in the management of ME/CFS.
Cwm Taf Morgannwg University Health Board provides primary, community, hospital and mental health services to the 450,000 people living in three County Boroughs: Bridgend, Merthyr Tydfil and Rhondda Cynon Taf. [CTUHB]
CTMUHB’s Long-Covid Rehabilitation Service (LCRS)
Your email quite rightly highlights the overlap in symptoms between ME/CFS and long-Covid. Within CTMUHB’s Long-Covid Rehabilitation Service (LCRS), we support and coach people with fatigue management through activity diaries and various strategies to help manage their energy levels throughout the day. We specifically do not include a physical rehabilitation element within our service, based upon our awareness of post-exertional malaise amongst the people that we see in our LCRS.
Welsh Government support request
In co-ordination with other Health Boards across Wales delivering long-Covid services, our CTMUHB LCRS submitted a case to Welsh Government earlier this year outlining how the services could be expanded to support people experiencing other post-viral syndromes and the additional resource that this would require. On this occasion, additional resource was not allocated to expand the remit of the LCRSs across Wales for 2022/23 but please be assured that this remains our ambition for 2023/24.
As you point out, the Health Minister has commented upon the possible expansion of community models to treat and support people with other long-term conditions and so we are hopeful that Welsh Government will be able to support this approach for the future.
Thank you once again for making contact on this important matter.”
WAMES would like to hear from anyone with ME/CFS in the CTMUHB area about the service they have received since the publication of the revised ME/CFS NICE guideline in October 2021. Please let us know if your GPs are aware of the new guideline and understand exercise intolerance and PEM, so we can continue to work for service improvement. #ImplementNICEmecfs Contact jan@wames.org.uk
WAMES has been asking Health Boards in Wales what plans they have to implement NICE guidelines, whether they intend to consult with patients and how they think their long COVID service might benefit people with ME.
Swansea Bay University Health Board (formerly ABMU) covers Neath Port Talbot and Swansea areas. Responsibility for providing healthcare services in the Bridgend County Borough Council area passed from ABMU to the new Cwm Taf Morgannwg UHB in 2019. [SBUHB]
Swansea Bay University Health Board’s Chief Executive Mark Hackett shares their current and future plans for healthcare services for ME with WAMES:
Thank you for your email requesting information about changes people can expect from NHS services since the publication of the updated NICE ME/CFS guideline in October 2021. I’m happy to respond as follows:
Access, diagnosis and referral
Swansea Bay UHB
GPs will identify signs and symptoms of ME/CFS and will initiate relevant investigations to exclude any other causes. Patients with suspected ME/CFS are diagnosed by GPs using (since 2018) a diagnostic tool developed in conjunction with the Rheumatology Consultants in our Rheumatology Occupational Therapy Service. This tool has been amended in view of the updated guideline and the NICE implementation statement published on 12th May 2022, and should soon be available to GPs on the Welsh Clinical Communications Gateway.
Rheumatology is the study of rheumatism, arthritis, and other disorders of the joints, muscles, and ligaments. (OED)
As this diagnosis can have lifelong implications for patients, GPs often refer patients for confirmation of diagnosis and for reablement, rehabilitation, complex needs and ongoing management or to social care services. Our Rheumatology Occupational Therapy Service currently accepts referrals from consultants and primary care GPs for adults with a confirmed diagnosis of ME/CFS. Rheumatology colleagues’ advice, discussion and education enhances confidence among GPs in diagnosing ME/CFS, avoiding delays.
Any other health and social needs are being managed within primary care and referred into appropriate specialities/pathways. Some aspects of these patients’ needs e.g. lifestyle advice, nutrition, weight management, symptom control, given possible similar symptom presentation, are guided by Welsh Government to sit within Health Boards’ Long Covid services.
The SBUHB Rheumatology Occupational Therapy Service
The Occupational Therapy service is our only specific service for those with a diagnosis of ME/CFS. This is an adults-only uni-professional service, provided by a team which also sees a range of rheumatological conditions e.g. fibromyalgia, osteoarthritis, rheumatoid arthritis and hypermobility.
Occupational Therapy intervention ensures holistic, meaningful and realistic goals are established. The risks and benefits of physical activity and exercise are discussed with patients who want to incorporate or increase this in their daily routine.
Specific occupational therapy intervention is provided to address functional limitations through a focus on daily activities, roles and responsibilities meaningful to the individual, using a person- centred, self-management approach. Interventions are co-produced in line with patient- identified values, aims and activity tolerance limits.
Various options are available for people to access appointments, including phone calls or virtual and face-face meetings, and we are supportive and flexible in offering an alternative appointment when needed. If employment or education needs are identified, the individual is signposted to SBUHB work-based initiatives and third sector organisations that can support work and training needs. The service operates a waiting list but consistently meets the Welsh Government Referral to Treatment target of 14 weeks.
An occupational therapist helps people of all ages overcome challenges completing everyday tasks or activities – what we call ‘occupations’. Everything is focused on increasing independence and wellbeing. (RCOT)
There is no specialist clinical lead or team for physiotherapy provision, therefore no multidisciplinary team assessments for ME/CFS are conducted, nor care and support plans completed. However, all members of the Occupational Therapy Team are aware of the recommendation for establishing an individual’s baseline and working within their energy parameters without attempting to exceed their limits. In the event of a patient’s evident psychological distress, they will be signposted to psychological medicine or mental health services as there is no specialist provision for psychological therapies for those with ME/CFS. Supporting families and carers’ needs are addressed as required.
Our other therapy services accept referrals for patients with this condition but they are managed within generic caseloads within multiple services e.g. persistent pain service, neurology or musculoskeletal physiotherapy outpatients. For example, the persistent pain service has accepted referrals for people with ME/CFS for a multidisciplinary service, however clinicians are not specifically trained in ME/CFS – they have relevant skills from working in pain services and can support people who have ongoing pain as part of their presentation.
The SBUHB Long Covid Service
This service has been developed in response to the needs of and demand from our local population. It involves several approaches with rehabilitation and self-management at the core, delivered through virtual group consultations, webinars, face-to-face rehabilitation meetings and/or via online resources.
Under the ’Adferiad’ programme, resources have been developed for Long Covid which may have value for other patient cohorts due to the nature of shared symptoms. These include a chronic fatigue workbook which will be made available to Secondary Care specialities and Primary Care. The funding of this programme is time-limited, with adverse implications for service development for other chronic conditions. We are currently not offering a combined referral pathway for ME/CFS and Long Covid as NICE distinguishes these as separate conditions.
Nevertheless, there have been discussions regarding the ME/CFS client group and others with post-viral and fatigue-related conditions, and possible integration with the Long Covid Service within our pulmonary rehabilitation and wellbeing services. For example, we are aware of the evidence with regard to PEM/PESE, and while it is noted that this is not mentioned in the list of symptoms, assessment and treatment from the Long Covid Service is tailored accordingly.
Service developments
The following service developments are in progress:
our training resources are being reviewed to ensure they reflect the NICE ME/CFS guideline and implementation statement
we are adopting flexible case-by-case support for ME/CFS patients who did not attend or were unable to attend appointments
the Occupational Therapy Team may currently refer patients to the out-patient physiotherapy service for exercise planning or to the National Exercise Referral Scheme, and will consider dietician referral where appropriate. Plans to further develop this referral pathway to dietetics are underway and resource identified, however there is no specialist provision in this development for the ME/CFS patient group
within the Long Covid Service we continue to develop educational resources, group consultations and webinars for common symptoms such as fatigue, breathlessness, muscle ache and low mood, and lifestyle advice on weight management, exercise, nutrition, mental health etc. We expect to widen referral to these resources to ME/CFS patients and others who present with these symptoms.”
WAMES would like to hear from anyone who has accessed healthcare for ME/CFS in the SBUHB area since the publication of the revised ME/CFS NICE guideline. We want to hear about the successes and the failures, so we can continue to work for service improvement. #ImplementNICEmecfs
Most of the research about Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has focused on ambulant patients who are able to attend clinics.
It is estimated that 25% of people with ME/CFS are severely, or very severely, affected and are housebound or bedbound; some require tube feeding. Due to the severity of their illness, these patients have largely been excluded from research and are often described as ‘hard to reach.’
A questionnaire was devised to gather data about their experiences of accessing tube feeding. By making the necessary reasonable adjustments, such as direct outreach and the option to complete the questionnaire by telephone or texting, very severely affected patients were enabled to participate and provided invaluable contributions. This study aimed to act as a model for future researchers.
Conclusions:
Although patients with severe ME/CFS have often been excluded from previous research, due to being regarded as ‘hard to reach’, this study showed that if people with very severe ME/CFS are made aware that research is being undertaken, and the necessary support is provided, without time constraints, they can make invaluable contributions to research.
Recommendations to ensure high quality research in the form of a checklist for future researchers to follow:
Utilise organisations, charities and support groups, both locally and nationally, who know the demographics of their patients, or members.
Contact charities and other organisations to publicise an invitation to take part in research, both online and in print.
Liaise with charities to find out when they send members printed documents, such as magazines, and place advertisements in these, allowing sufficient time for potential participants to see the advertisement and respond to it.
When designing a survey, use simple language. Aim for a reading age of nine.
Ensure software is used which has a ‘save’ function to enable participants to complete and return the document, as and when their health permits.
Offer paper copies of surveys/questionnaires.
Offer assistance to complete the survey/questionnaire by telephone and, if possible, by text.
Look to recruit people with knowledge of severe ME/CFS to assist with completing documentation by telephone.
Speak slowly and softly when talking to people with severe ME/CFS and avoid having them repeat themselves. Read the participants’ responses back to them for confirmation that they are correct.
Make funders aware of the need for extended deadlines.
Article inHealthcare 2022, 10(7), 1278; [doi.org/10.3390/healthcare10071278]
Published: 10 July 2022 (This article belongs to the Collection Why Some Patients Never Fully Recover: Post Active Phase of Infection Syndromes (PAPIS))
It has been great to receive enquiries asking how people can donate money to WAMES.
We would like be able to say that we can accept it in any format. In practice we would struggle to know what to do with cryptocurrency and we have just discovered our online donation service has ceased operation!
We are exploring how to expand our options and currently suggest:
The online donation service we used in the past no longer operates so we are looking for a new one.
Please Gift Aid your donation
If you are a UK taxpayer, every £1 you give will be worth 25p more to us, at no extra cost to you, if you Gift Aid it. You can download the Gift Aid form.
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By bank transfer or standing order. Account name:
Welsh Association of ME & CFS
Account Number: 76392081
Sort Code: 09-01-55
We are exploring other possible donation methods, such us FB, twitter, texting but it will take time to set those up – maybe you can help us do that?
Infections by the Epstein-Barr virus (EBV) are often at the disease onset of patients suffering from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, serological analyses of these infections remain inconclusive when comparing patients with healthy controls (HCs). In particular, it is unclear if certain EBV-derived antigens eliciting antibody responses have a biomarker potential for disease diagnosis.
WAMES, as part of the WNA, are backing the:
This study seeks to determine whether several common depression scales might be contaminated by somatic symptoms, thus overestimating depression in people with chronic invisible illness.
A test of 
Cwm Taf Morgannwg University Health Board’s Chief Executive 
Most of the research about Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has focused on ambulant patients who are able to attend clinics.
It has been great to receive enquiries asking how people can donate money to WAMES.
