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 from Dr Katrina Pears
ME/CFS Research Published 6 – 13 September 2022
We have definitely seen a lull in research this week ahead of the new academic year starting. There have been two new ME/CFS studies (with only one of these directly on ME/CFS) and fifteen studies on Long Covid.
We have also listed the research which was published in the previous week (30th August to 5th September), where three new ME/CFS studies were published.
We have highlighted two studies below:
Paper one (1) is a very complex preprint study (the science in this paper has not been peer-viewed and therefore it has not been verified) on the genetic risk factors for ME/CFS. The research identifies 14 genes being associated with ME/CFS as well as further evidence for subgroups within ME/CFS. The genes identified were associated with autoimmunity, energy metabolism, sleep and infection.
Steve Gardener and colleagues also presented this research at the M.E. Genetic Research Symposium which was held on the 14th September 2022 (recordings from Action for ME will hopefully be available in the next few days), allowing a better understanding of this research. The technique used in this research is patented by the company PrecisionLife who undertook this study so we cannot dive into the specifics of their analysis, but they used combinatorial analysis to look at combinations of genes (SNP- DNA building blocks) instead of looking at every single gene.
This research is novel and has provided some interesting initial findings, but has a few limitations:
- Patient recruitment: ME/CFS patients used in this study were recruited from the UK Biobank, where the diagnosis was self-reported after filling in the pain questionnaire which was completed when samples were originally recruited. This led to the genotype of 2,382 patients with ME/CFS being analysed along with 4,764 controls (these numbers are small for genetic studies). Therefore, the diagnosis of ME/CFS was not verified, and also the demographics of the sample differ from the typical ME/CFS population, with average age of 69 and just over 70% women. (NB. These samples therefore differ from those collected by the UK ME/CFS biobank (UKMEB), which the MEA supports the running of.)
- Replication: these findings need to be verified through replication, which was attempted in this study by interviewing a separate group, but not all the same 14 genes were identified.
If the findings from this study can be verified, there could be potential for new treatments in which specific genes could be targeted. If you would like to read more on this study, Simon McGrath has also published a blog of this research which explains this study in more detail. There have also been several news articles published on this paper, such as here.
Paper two (2) in the Long Covid reference section which was actually published back in July may also be of interest as it looks at the use of hyperbaric oxygen therapy (HBOT). In this study, patients either received 40 sessions of HBOT (for 37 patients) or sham (for 36 patients, session with no pressurisation in HBOT chamber and normal air). This study reported significant improvements in damaged brain tissue and cognitive function including pain, sleep and fatigue from receiving HBOT therapy.
Despite these findings looking promising, some caution needs to be taken, due to the commercial interest in this treatment where this research was undertaken by a team employed by the Hyperbaric centre with no independent verification. Secondly, with 40 sessions in a two-month period you would hope for more differences between the controls (sham) and those receiving HBOT. Furthermore, it is difficult to replicate a study like this on larger scale due to the due costs involved.
Nevertheless, this is not the first paper showing the benefit of HBOT in Long Covid, we have seen a few studies of late, such as studies by Robbins et al., 2021 and Kjellberg et al., 2022. Therefore, hopefully there is the potential for more studies in this area, especially seeing as with ME/CFS this area of research has been very limited, with one study using 16 patients showing the decrease in symptoms severity (Akarsu et al., 2013). Dr Charles Shepherd has also provided a medical matters blog on the use of hyperbaric oxygen therapy and the current lack of research in this area.
On a personal note, I am interested in this research as I have tried mild hyperbaric oxygen therapy (mHBOT), with a number of sessions spread over a month. However, I did not see any benefits from this treatment (in fact I always felt much worse after a session than beforehand), but this may have been due to the milder pressurisation conditions used, whereas I know others who benefitted from the use of normal HBOT.
ME/CFS Research References and Abstracts (6 – 13 September)
1. Genetic Risk Factors for ME/CFS Identified using Combinatorial Analysis
Sayoni Das, Krystyna Taylor, James Kozubek, Jason Sardell, Steve Gardner
medRxiv [Preprint]
Abstract
Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease that lacks known pathogenesis, distinctive diagnostic criteria, and effective treatment options. Understanding the genetic (and other) risk factors associated with the disease would begin to help alleviate some of these issues for patients.
Methods: We applied both GWAS and the PrecisionLife combinatorial analytics platform to analyze ME/CFS cohorts from UK Biobank, including the Pain Questionnaire cohort, in a case-control design with 1,000 cycles of fully random permutation. The results from this study were supported by a series of replication and cohort comparison experiments, including use of a disjoint Verbal Interview cohort also derived from UK Biobank, and results compared for reproducibility.
Results: Combinatorial analysis revealed 199 SNPs mapping to 14 genes, that were significantly associated with 91% of the cases in the ME/CFS population. These SNPs were found to stratify by shared cases into 15 clusters (communities) made up of 84 high-order combinations of between 3-5 SNPs. p-values for these communities range from 2.3 × 10−10 to 1.6 × 10−72.
Many of the genes identified are linked to the key cellular mechanisms hypothesized to underpin ME/CFS, including vulnerabilities to stress and/or infection, mitochondrial dysfunction, sleep disturbance and autoimmune development. We noted similarities with genes associated with multiple sclerosis and long COVID, which share some symptoms and potentially a viral infection trigger with ME/CFS.
Conclusions: This study provides the first detailed genetic insights into the pathophysiological mechanisms underpinning ME/CFS and offers new approaches for better diagnosis and treatment of patients.
Ohashi, Y., Fukushima, K., Uchida, K. et al.
Sci Rep 12, 15327 (2022).Sci Rep 12, 15327 (2022).
Abstract
We investigated the differences in outcomes after total hip arthroplasty (THA) for hip osteoarthritis (HOA) between patients with and without central sensitivity syndromes (CSSs) other than fibromyalgia (FM).
After excluding two patients with FM, we compared the clinical data of 41 patients with CSSs and 132 patients without CSSs.
Clinical data included scores on the central sensitization inventory, visual analog scale for pain (VAS pain), and Japanese Orthopedic Association Hip Disease Evaluation Questionnaire (JHEQ).
VAS pain was significantly higher at 3 and 6 months after THA in patients with CSSs than in those without CSSs (3 and 6 months, P < 0.001).
Satisfaction, pain, and mental JHEQ scores were lower in patients with CSSs than in those without CSSs (satisfaction, P < 0.001; pain, P = 0.011; mental, P = 0.032).
Multiple regression analyses indicated that one and ≥ 2 CSS diagnoses significantly impacted the satisfaction score (one CSS, β = − 0.181, P = 0.019; ≥ 2 CSSs, β = − 0.175, P = 0.023).
Two or more CSSs were the only factor influencing the pain score (β = − 0.175, P = 0.027).
Pain in patients with CSSs reflects central sensitization, which may adversely affect post-operative outcomes. Surgeons should pay attention to patients with a history of CSSs diagnoses who undergo THA for HOA.
ME/CFS Research References (30 August – 5 September)
Long-COVID Research References (6 – 13 September)
Dr Katrina Pears,
Research Correspondent.
The ME Association.
