The weekly research round-up includes recent publications about ME/CFS and Long Covid. We highlight the studies that have particularly caught our interest and follow these with the full list of publications together with their abstracts (summaries).
The ME Association maintains a comprehensive index of published research on ME/CFS and Long Covid that is free to use and updated weekly.
Audio commentary form Katrina Pears
ME/CFS Research Published 1 – 7 February 2022
There have been five new ME/CFS studies and thirteen studies on Long Covid this week.
We have had a range of different topics this week, however, none of these particularly caught our interest or added to our understanding of ME/CFS.
We have highlighted two of the studies below:
Paper one (1) despite being behind a paywall is a commonly occurring topic in ME/CFS research, which looks into herpes viruses 6 and 7 (HHV-6, HHV-7). This paper doesn’t cover the other well-known herpes viruses which are talked about in relation to ME/CFS such as Epstein Barr virus (EBV). There are a number of studies suggesting that this set of viruses play an important part in the development of chronic illnesses.
This study compared the use of three different treatments: valaciclovir (familiar name in commonly used cold sore treatment), valganciclovir (antiviral medication used frequently to treat HIV/AIDS or organ transplant patients), and artesunate (frequently used to treat malaria).
The study showed that Artesunate was by far the best treatment. However, the reported success of these treatments was low when measuring the viral presence after treatment (reported results are typically under 50% for virus presence). This study was fairly large for ME/CFS research, using 255 ME/CFS patients. However, the abstract does not suggest any improvements in symptoms or if this was even researched. Furthermore, I am confused how this paper only has one author for a reportedly large study which questions the strength of the study.
Paper five (5) is a study which was published back in June, which evaluated mitochondria function in six patients. While this paper does not tell us anything new, concluding that the mitochondria in people with ME/CFS have a decreased ability to fulfil their cellular energy demands, it does add to the growing evidence on mitochondria dysfunction.
It is a great shame that the study was so small, needing a large amount of replication. Furthermore, the exact mechanisms for mitochondria dysfunction between studies seems to vary. This study indicated a decrease in ATP production (the energy carrying molecule) in people with ME/CFS, whereas other studies have shown no difference compared to controls (e.g. Tomas et al. 2017). Therefore, there is a need for large studies using one technique to study mitochondria dysfunction as the different methods used could be causing the different results.
ME/CFS Research References and Abstracts
Microbiol Immunol. 2022 Jan 31. [Epub ahead of print.]
The study aimed to compare the efficacy of valaciclovir, valganciclovir, and artesunate in treating chronic reactivated HHV-6 and HHV-7 associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
From 255 patients with reactivated HHV-6 and HHV-7 infections (blood leukocyte PCR) in 192 cases, valaciclovir, valganciclovir, or artesunate were administered at a dose of 3,000, 900, and 100 mg per day, respectively, for 3 months (study group).
The control group consisted of similar 63 ME/CFS patients not taking any antiviral drugs.
The significance of differences was evaluated by Student's T-test and the non-parametric criterion – the number of Z-signs. Negative PCR results in HHV6 and HHV-7 treated with valaciclovir was achieved in 26% and 23% (first), 34%, and 28% (second), 37% and 34% of cases (third month), respectively (p<0.05; Z<Z0.05 ).
The same results with valganciclovir were obtained in 35% and 33% (first), 44% and 39% (second), 48% and 45% (third month), but with artesunate – in 44% and 41% (first), 57% and 53% (second), 68% and 63% of cases (third month), respectively (p<0.05; Z<Z0.05 ).
Artesunate is more effective than valganciclovir and valacyclovir in ME/CFS patients with reactivated HHV-6 and HHV-7 infections.
Clery P, Royston A, Driver K, Bailey J, Crawley E, Loades M.
BMJ Open. 2022 Jan 31;12(1):e051358.
Objectives: Children with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) experience a higher prevalence of depression and anxiety compared with age-matched controls. Our previous systematic reviews in 2015/16 found little evidence for effective treatment for children with CFS/ME with comorbid depression and/or anxiety. This review updates these findings.
Design: A systematic review. We searched Cochrane library, Medline, Embase and PsycINFO databases from 2015 to 2020. We combined the updated results with our previous reviews in a narrative synthesis.
Participants: Inclusion criteria: <18 years old; diagnosed with CFS/ME (using Centers for Disease Control and Prevention, National Institute for Health and Care Excellence or Oxford criteria); validated measures of depression and/or anxiety.
Interventions: Observational studies or randomised controlled trials.
Comparison: Any or none.
Outcomes: Studies with outcome measures of anxiety, depression or fatigue.
Results: The updated review identified two studies. This brings the total number of paediatric CFS/ME studies with a measure of anxiety and/or depression since 1991 to 16. None of the studies specifically targeted depression, nor anxiety. One new study showed the Lightning Process (in addition to specialist care) was more effective at reducing depressive and anxiety symptoms compared with specialist care alone. Previous studies evaluated cognitive-behavioural therapy (CBT); pharmacological interventions and behavioural approaches. CBT-type interventions had most evidence for improving comorbid anxiety and/or depressive symptoms but varied in delivery and modality. Other interventions showed promise but studies were small and have not been replicated.
Conclusion: Very few paediatric CFS/ME intervention studies have been conducted. This review update does not significantly add to what is known from previous reviews. The evidence is of poor quality and insufficient to conclude which interventions are effective at treating comorbid anxiety and/or depression in paediatric CFS/ME.
Siberry VGR, Rowe PC.
Pediatr Infect Dis J. 2022 Feb 4. Epub ahead of print
No Abstract available– Full commentary available online
Ann Clin Med Case Rep. 2022; V8(7): 1-4
Chronic fatigue syndrome characterized by severe disabling fatigue, prolonged post-exertional malaise, and unrefreshing sleep markedly reduces the activities of daily living and impairs the quality of life.
Central nervous system dysfunction associated with myalgic encephalomyelitis (ME) has been postulated as the main cause of chronic fatigue syndrome.
Recently, oral minocycline therapy has been reported to exert favorable therapeutic effects in some patients with ME, especially in the initial stage of the disease, although many patients discontinued treatment in the first few days because of acute adverse effects such as nausea and/or dizziness.
Minocycline appeared to exert a variety of biologic actions against neural inflammation that are independent of their anti-microbial activity, including anti-inflammatory, immunomodulatory, and neuroprotective effects.
In recent years, it has been noted that COVID-19 disease may cause persistent signs and symptoms described as post-COVID syndrome or long COVID, in which the clinical presentation is remarkably similar to those seen in patients with ME.
A wide range of infectious agents have been suggested to trigger the development of ME, and one of such pathogens may be the COVID-19 virus.
Recently, I had a valuable experience of a 22-year-old female patient with a 14-month duration of long COVID who completely recovered from ME-like symptoms after treatment with minocycline. This case suggests that oral minocycline could be an effective first-line therapy for long COVID-19, although a large scale of trial is obviously needed to justify the therapy.
O’Boyle S, Nacul L, Nacul FE, Mudie K, Kingdon CC, Cliff JM, Clark TG, Dockrell HM and Lacerda EM
Front. Med. 8:688159
We propose a framework for the treatment, rehabilitation, and research into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) using a natural history of disease approach to outline the distinct disease stages, with an emphasis on cases following infection to provide insights into prevention.
Moving away from the method of subtyping patients based on the various phenotypic presentations and instead reframing along the lines of disease progression could help with defining the distinct stages of disease, each of which would benefit from large prospective cohort studies to accurately describe the pathological mechanisms taking place therein. With a better understanding of these mechanisms, management and research can be tailored specifically for each disease stage.
Pre-disease and early disease stages call for management strategies that may decrease the risk of long-term morbidity, by focusing on avoidance of further insults, adequate rest to enable recovery, and pacing of activities.
Later disease stages require a more holistic and tailored management approach, with treatment—as this becomes available—targeting the alleviation of symptoms and multi-systemic dysfunction.
More stringent and standardised use of case definitions in research is critical to improve generalisability of results and to create the strong evidence-based policies for management that are currently lacking in ME/CFS.
Fernandez-Guerra, P.; Gonzalez-Ebsen, A.C.; Boonen, S.E.; Courraud, J.; Gregersen, N.; Mehlsen, J.; Palmfeldt, J.; Olsen, R.K.J.; Brinth, L.S.
Biomolecules 2021, 11, 961
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous, debilitating, and complex disease. Along with disabling fatigue, ME/CFS presents an array of other core symptoms, including autonomic nervous system (ANS) dysfunction, sustained inflammation, altered energy metabolism, and mitochondrial dysfunction.
Here, we evaluated patients’ symptomatology and the mitochondrial metabolic parameters in peripheral blood mononuclear cells (PBMCs) and plasma from a clinically well-characterised cohort of six ME/CFS patients compared to age- and gender-matched controls.
We performed a comprehensive cellular assessment using bioenergetics (extracellular flux analysis) and protein profiles (quantitative mass spectrometry-based proteomics) together with self-reported symptom measures of fatigue, ANS dysfunction, and overall physical and mental well-being.
This ME/CFS cohort presented with severe fatigue, which correlated with the severity of ANS dysfunction and overall physical well-being. PBMCs from ME/CFS patients showed significantly lower mitochondrial coupling efficiency.
They exhibited proteome alterations, including altered mitochondrial metabolism, centred on pyruvate dehydrogenase and coenzyme A metabolism, leading to a decreased capacity to provide adequate intracellular ATP levels.
Overall, these results indicate that PBMCs from ME/CFS patients have a decreased ability to fulfill their cellular energy demands.
Long-COVID Research References
- Functional gastrointestinal and somatoform symptoms five months after SARS-CoV-2 infection: A controlled cohort study
- Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis
- Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: A systematic review and meta-analysis
- Outcomes in post-acute sequelae of COVID-19 (PASC) at 6 months post-infection Part 1: Cognitive functioning
Dr Katrina Pears
The ME Association.