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
ME/CFS Research Published 13 – 19 September 2022
It’s been another quiet week in research as the new academic year begins. There have been three new ME/CFS studies and fourteen studies on Long Covid.
We have highlighted two studies below:
Paper two (2) is a genetic study which works towards proving the link between Long Covid and ME/CFS. This study does not collect any samples itself, and uses pre-existing gene databases (three of these) to find the connection between these two illnesses.
The study found links between the two illnesses, with: nine common genes, five common protein-protein interactions (PPI) and the prediction of 10 chemical compounds. This revealed similarities in infection, neuroinflammation, energetic metabolic dysfunction, and impaired immune function. The full paper has some useful images explaining their analysis and results which are worth a look at.
Image taken from the paper, showing a Venn diagram with 9 genes found as common genes from 49 related genes of long COVID and 1023 related genes of ME/CFS.
It goes without saying, that the methodology used will limit the results found by the study:
- There is no clarification on the diagnostic criteria for ME/CFS, i.e. Canadian Consesus Criteria (CCC) or Fukuda etc.
- One of the databases used was disgenet.org, which lists the FURIN gene, but this is also known as a PACE gene, which has resulted in the database linking this to the PACE trial which is not relevant to genetics. If the untrained eye can spot problems like this, we would hope that the authors have carefully screened the database but we have no way of knowing.
- Lack of available data available to date on Long Covid.
- Using data already collected is limited by the previous study design, which may have large shortcomings in their methods for example.
In my opinion, this research would be a lot stronger if coupled with some primary data collection, as at the moment it is limited by the protocols used by previous studies. Although it does further support the overlap between ME/CFS and Long Covid.
Paper three (3) is on continuous activity monitoring using off-the shelf activity monitors and comparing this to symptom variability with patient reported outcome measures (PROMs). This study used the Fitbit Charge 3 in 27 patients with varying symptom severity for a six-month period. The authors also compared these results to the SenseWear device which they have previously used in other studies.
The results showed unsurprisingly average steps decrease with symptom severity, with:
- mild- 5566 steps per day,
- moderate- 4991 steps per day,
- severe- 1998 steps per day.
The study also found:
- a large day-to-day variation in steps of 47%,
- an increase in steps seen in the last three months of the trial particularly in mild patients,
- steps per day were correlated to physical and social function, and symptoms.
One of the reasons that the authors conducted this feasibility study was as part of wider research to help them validate findings in other studies looking at outcome measures, so that not only patient reported symptoms are used. The authors particularly noted that this would be useful in treatment involving the anti-CD20 B-cell depleting antibody rituximab or the cytotoxic drug cyclophosphamide.
Findings from this study do not surprise me, although I would have expected a lower number of steps from the severe group studied. It is disappointing that a larger cohort was not researched, seeing as the study randomly selected patients from a possible cohort of 92, therefore, I hope there is potential to expand this study on a larger scale. The small scale of this study limited the conclusions the authors could draw when linking activity to symptoms, therefore, there is the potential to gain much more from a study like this. Furthermore, there is no control group, so we do not know how these numbers of steps compare to a sedentary population.
I am personally interested in this study having used a Fitbit activity tracker over the past seven years. I have always found the use of an activity tracker crucial to my pacing, where I can monitor the number of steps I am doing to make sure I’m not going over my personal daily limit. Furthermore, it is also reassuring to see that my daily steps are also in line with the findings in this study for differing symptom severity.
(N.B. The ME Association is funding a new study on Pacing with a heart rate monitor, see here.)
ME/CFS Research References and Abstracts (6 – 13 September)
Prylińska-Jaśkowiak, Monika & Kożuchowski, Marcin.
Journal of Education, Health and Sport [online]. T. 12, nr 9, s. 712–719.
Abstract
Chronic Fatigue Syndrome (CFE) is a severe and disabling disease whose etiology has not yet been elucidated. This implies the lack of a specific biomarker for the diagnosis of PE, and no causal treatment.
There are a number of diagnostic criteria that facilitate the diagnosis of PE, but it is still a diagnosis with exclusion. This chapter reviews the scientific literature systematically, summarizing the available knowledge about the probable etiology of Chronic Fatigue Syndrome.
The current topic of the influence of SARS-Cov-2 virus infection on the development of symptoms of IPC was also taken into account in particular.
A clear explanation of the etiology of PE is necessary for the further development of scientific knowledge about the Chronic Fatigue Syndrome.
Lv Y, Zhang T, Cai J, Huang C, Zhan S and Liu J
Front. Immunol. 13:952987
Abstract
Background: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global crisis. Although many people recover from COVID-19 infection, they are likely to develop persistent symptoms similar to those of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) after discharge.
Those constellations of symptoms persist for months after infection, called Long COVID, which may lead to considerable financial burden and healthcare challenges. However, the mechanisms underlying Long COVID and ME/CFS remain unclear.
Methods: We collected the genes associated with Long COVID and ME/CFS in databases by restricted screening conditions and clinical sample datasets with limited filters.
The common genes for Long COVID and ME/CFS were finally obtained by taking the intersection.
We performed several advanced bioinformatics analyses based on common genes, including gene ontology and pathway enrichment analyses, protein–protein interaction (PPI) analysis, transcription factor (TF)–gene interaction network analysis, transcription factor–miRNA co-regulatory network analysis, and candidate drug analysis prediction.
Results: We found nine common genes between Long COVID and ME/CFS and gained a piece of detailed information on their biological functions and signaling pathways through enrichment analysis. Five hub proteins (IL-6, IL-1B, CD8A, TP53, and CXCL8) were collected by the PPI network.
The TF–gene and TF–miRNA coregulatory networks were demonstrated by NetworkAnalyst. In the end, 10 potential chemical compounds were predicted.
Conclusion: This study revealed common gene interaction networks of Long COVID and ME/CFS and predicted potential therapeutic drugs for clinical practice.
Our findings help to identify the potential biological mechanism between Long COVID and ME/CFS. However, more laboratory and multicenter evidence is required to explore greater mechanistic insight before clinical application in the future.
Rekeland IG, Sørland K, Bruland O, Risa K, Alme K, Dahl O, Tronstad KJ, Mella O, Fluge Ø.
PLoS One. 2022 Sep 19;17(9):e0274472.
Abstract
Introduction: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease with no validated specific and sensitive biomarker, and no standard approved treatment.
In this observational study with no intervention, participants used a Fitbit activity tracker. The aims were to explore natural symptom variation, feasibility of continuous activity monitoring, and to compare activity data with patient reported outcome measures (PROMs).
Materials and methods: In this pilot study, 27 patients with mild to severe ME/CFS, of mean age 42.3 years, used the Fitbit Charge 3 continuously for six months. Patients wore a SenseWear activity bracelet for 7 days at baseline, at 3 and 6 months. At baseline and follow-up they completed the Short Form 36 Health Survey (SF-36) and the DePaul Symptom Questionnaire-Short Form (DSQ-SF).
Results: The mean number of steps per day decreased with increasing ME/CFS severity; mild 5566, moderate 4991 and severe 1998. The day-by-day variation was mean 47% (range 25%-79%).
Mean steps per day increased from the first to the second three-month period, 4341 vs 4781 steps, p = 0.022.
The maximum differences in outcome measures between 4-week periods (highest vs lowest), were more evident in a group of eight patients with milder disease (baseline SF-36 PF > 50 or DSQ-SF < 55) as compared to 19 patients with higher symptom burden (SF-36 PF < 50 and DSQ-SF > 55), for SF-36 PF raw scores: 16.9 vs 3.4 points, and for steps per day: 958 versus 479 steps.
The correlations between steps per day and self-reported SF-36 Physical function, SF-36 Social function, and DSQ-SF were significant. Fitbit recorded significantly higher number of steps than SenseWear. Resting heart rates were stable during six months.
Conclusion: Continuous activity registration with Fitbit Charge 3 trackers is feasible and useful in studies with ME/CFS patients to monitor steps and resting heart rate, in addition to self-reported outcome measures.
Long-COVID Research References
Dr Katrina Pears,
Research Correspondent.
The ME Association.
