ME/CFS Science
@mecfsskeptic.bsky.social
In-depth analysis of research on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Formerly known as ME/CFS Skeptic.
https://mecfsscience.org/
https://mecfsscience.org/
Could be but don't remember reading this in the paper. Thought the 33% percentage was about recovery at the last follow-up.
January 21, 2026 at 1:11 PM
Could be but don't remember reading this in the paper. Thought the 33% percentage was about recovery at the last follow-up.
8) Link to the paper:
Prashar et al. Trajectory, healthcare utilisation and recovery in 3590 individuals with long covid: a 4-year prospective cohort analysis.
Prashar et al. Trajectory, healthcare utilisation and recovery in 3590 individuals with long covid: a 4-year prospective cohort analysis.
Trajectory, healthcare utilisation and recovery in 3590 individuals with long covid: a 4-year prospective cohort analysis
Objective To characterise long-term trajectory of recovery in individuals with long covid.
Design Prospective cohort.
Setting Single-centre, specialist post-COVID service (London, UK).
Participants Individuals aged ≥18 years with long covid (hospitalised and non-hospitalised) from April 2020 to March 2024.
Main outcome measures Routine, prospectively collected data on symptoms, quality of life (including Fatigue Assessment Scale (FAS) and EuroQol 5 Dimensions (EQ-5D), return to work status and healthcare utilisation (investigations, outpatient and emergency attendances). The primary outcome was recovery by self-reported >75% of ‘best health’ (EQ-5D Visual Analogue Scale) and was assessed using Cox proportional hazards regression models over 4 years. Linked National Health Service England registry data provided secondary care healthcare utilisation and expenditure.
Results We included 3590 individuals (63.3% female, 73.5% non-hospitalised, median age 50.0 years, 71.9% with ≥2 doses of COVID-19 vaccination), who were followed up for a median of 136 (0–346) days since first assessment and 502 (251–825) days since symptom onset. At first assessment, 33.2% of employed individuals were unable to work. Dominant symptoms were fatigue (78.7%), breathlessness (68.1%) and brain fog (53.5%). 33.4% of individuals recovered to >75% of best health prior to clinic discharge (recovery occurred median 202 (94–468) days from symptom onset). Vaccinated individuals were more likely to recover faster (pre: HR 2.93 (2.00–4.28) and post: HR 1.34 (1.05–1.71) COVID-19 infection), whereas recovery hazard was inversely associated with FAS (HR 0.37 (0.33–0.42)), myalgia (HR 0.59 (0.45–0.76)) and dysautonomic symptoms (HR 0.46 (0.34–0.62)). There was high secondary care healthcare utilisation (both emergency and outpatient care). Annual inpatient and outpatient expenditure was significantly lower in hospitalised individuals while under the service. When compared with the prereferral period, emergency department attendances were reduced in non-hospitalised patients with long covid, but outpatient costs increased.
Conclusions In the largest long covid cohort from a single specialist post-COVID service to date, only one-third of individuals under follow-up achieved satisfactory recovery. Fatigue severity and COVID-19 vaccination at presentation, even after initial COVID-19 infection, was associated with long covid recovery. Ongoing service provision for this and other post-viral conditions is necessary to support care, progress treatment options and provide capacity for future pandemic preparedness. Research and clinical services should emphasise these factors as the strongest predictors of non-recovery.
No data are available.
bmjopen.bmj.com
January 21, 2026 at 8:56 AM
8) Link to the paper:
Prashar et al. Trajectory, healthcare utilisation and recovery in 3590 individuals with long covid: a 4-year prospective cohort analysis.
Prashar et al. Trajectory, healthcare utilisation and recovery in 3590 individuals with long covid: a 4-year prospective cohort analysis.
7) The authors mention that the EQ-5D VAS severity seen in their cohort is similar to ME/CFS and "worse than in some cohorts with chronic conditions such as heart failure and chronic obstructive pulmonary disease."
January 21, 2026 at 8:56 AM
7) The authors mention that the EQ-5D VAS severity seen in their cohort is similar to ME/CFS and "worse than in some cohorts with chronic conditions such as heart failure and chronic obstructive pulmonary disease."
6) The median quality of life score measured with the EQ-5D visual analogue scale changed from 45 to 50 points, a very small effect size (Cohen's d=0.188). A score of 50 is pretty poor, it's in between the best possible and worst possible health.
January 21, 2026 at 8:56 AM
6) The median quality of life score measured with the EQ-5D visual analogue scale changed from 45 to 50 points, a very small effect size (Cohen's d=0.188). A score of 50 is pretty poor, it's in between the best possible and worst possible health.
5) Nonetheless the data seems quite bleek. The VAS fatigue scale changed from 33 points at first appointment to 31 at the last assessment, barely any improvement.
The authors see severity of fatigue as a potential marker for poor prognosis.
The authors see severity of fatigue as a potential marker for poor prognosis.
January 21, 2026 at 8:56 AM
5) Nonetheless the data seems quite bleek. The VAS fatigue scale changed from 33 points at first appointment to 31 at the last assessment, barely any improvement.
The authors see severity of fatigue as a potential marker for poor prognosis.
The authors see severity of fatigue as a potential marker for poor prognosis.
4) One possible reason for the poor numbers is a high drop-out rate (approximately 32%) for the long-term follow up. Patients who fully recovered might have been less willing to participate or in need for health care.
January 21, 2026 at 8:56 AM
4) One possible reason for the poor numbers is a high drop-out rate (approximately 32%) for the long-term follow up. Patients who fully recovered might have been less willing to participate or in need for health care.
3) Risk factors that predicted poor recovery were ME/CFS-like symptoms such as fatigue, myalgia and postural symptoms/dysautonomia.
Being vaccinated and symptoms such as vertigo and skin rash were associated with a higher chance of improvement.
Being vaccinated and symptoms such as vertigo and skin rash were associated with a higher chance of improvement.
January 21, 2026 at 8:56 AM
3) Risk factors that predicted poor recovery were ME/CFS-like symptoms such as fatigue, myalgia and postural symptoms/dysautonomia.
Being vaccinated and symptoms such as vertigo and skin rash were associated with a higher chance of improvement.
Being vaccinated and symptoms such as vertigo and skin rash were associated with a higher chance of improvement.
2) Median follow-up was 502 days. 63% of patients were female, median age was 50 years.
Approximately, three-quarters of the sample were Long Covid patients who were not hospitalised. They had an even lower recovery rate (28%) than those that were hospitalized (47%).
Approximately, three-quarters of the sample were Long Covid patients who were not hospitalised. They had an even lower recovery rate (28%) than those that were hospitalized (47%).
January 21, 2026 at 8:56 AM
2) Median follow-up was 502 days. 63% of patients were female, median age was 50 years.
Approximately, three-quarters of the sample were Long Covid patients who were not hospitalised. They had an even lower recovery rate (28%) than those that were hospitalized (47%).
Approximately, three-quarters of the sample were Long Covid patients who were not hospitalised. They had an even lower recovery rate (28%) than those that were hospitalized (47%).
Not sure, don't remember reading about that in the paper.
January 19, 2026 at 3:52 PM
Not sure, don't remember reading about that in the paper.
Not an expert but seems unlikely, as methylation in the promotor region usually means less expression of the gene.
January 19, 2026 at 1:50 PM
Not an expert but seems unlikely, as methylation in the promotor region usually means less expression of the gene.
9) Link to the paper:
Wyns et al. 2026. Hypermethylation of OPRM1: Deregulation of the Endogenous Opioid Pathway in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia.
Wyns et al. 2026. Hypermethylation of OPRM1: Deregulation of the Endogenous Opioid Pathway in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia.
Hypermethylation of OPRM1: Deregulation of the Endogenous Opioid Pathway in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are debilitating disorders with overlapping symptoms such as chronic pain and fatigue. Dysregulation of the endogenous opioid system, particularly µ-opioid receptor function, may contribute to their pathophysiology. This study examined whether epigenetic modifications, specifically µ-opioid receptor 1 gene (OPRM1) promoter methylation, play a role in this dysfunction. Using a repeated-measures design, 28 ME/CFS/FM patients and 26 matched healthy controls visited the hospital twice within four days. Assessments included blood sampling for epigenetic analysis, a clinical questionnaire battery, and quantitative sensory testing (QST). Global DNA (hydroxy)methylation was quantified via liquid chromatography–tandem mass spectrometry, and targeted pyrosequencing was performed on promoter regions of OPRM1, COMT, and BDNF. ME/CFS/FM patients reported significantly worse symptom outcomes. No differences in global (hydroxy)methylation were found. Patients showed significantly higher OPRM1 promoter methylation, which remained after adjusting for symptom severity and QST findings. Across timepoints, OPRM1 methylation consistently correlated with BDNF Promoter I and Exon III methylation. This is, to the best of our knowledge, the first study examining OPRM1 methylation in ME/CFS/FM. Increased OPRM1 methylation in patients, independent of symptoms or pain sensitivity measures, supports the hypothesis of dysregulated opioidergic signaling in these conditions.
www.mdpi.com
January 19, 2026 at 9:04 AM
9) Link to the paper:
Wyns et al. 2026. Hypermethylation of OPRM1: Deregulation of the Endogenous Opioid Pathway in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia.
Wyns et al. 2026. Hypermethylation of OPRM1: Deregulation of the Endogenous Opioid Pathway in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia.
8) Another limitation (which the authors acknowledge) is that the study only looked at methylation of DNA, assuming that this would lead to less expression of the gene and thus less opioid receptors.
They didn't actually measure RNA or proteins to check if this was the case.
They didn't actually measure RNA or proteins to check if this was the case.
January 19, 2026 at 9:04 AM
8) Another limitation (which the authors acknowledge) is that the study only looked at methylation of DNA, assuming that this would lead to less expression of the gene and thus less opioid receptors.
They didn't actually measure RNA or proteins to check if this was the case.
They didn't actually measure RNA or proteins to check if this was the case.
7) Another caveat is that they analysed only three potential methylation sites (CpG sites) in the OPRM1 promotor region, while there are approximately 50. In other words, of the 50 potential switches to silence the gene, they only looked at 3.
January 19, 2026 at 9:04 AM
7) Another caveat is that they analysed only three potential methylation sites (CpG sites) in the OPRM1 promotor region, while there are approximately 50. In other words, of the 50 potential switches to silence the gene, they only looked at 3.
6) The main results are given in Table 2 below. There was more methylation in the OPRM1 gene in patients than controls but the difference was only slightly significant and the study does not seem to correct for multiple comparisons.
January 19, 2026 at 9:04 AM
6) The main results are given in Table 2 below. There was more methylation in the OPRM1 gene in patients than controls but the difference was only slightly significant and the study does not seem to correct for multiple comparisons.
5) The authors suspect that ME/CFS and fibromyalgia might cause something similar, so that natural opioids and pain relief no longer work that well. They tested this in 28 patients and 26 controls whose DNA and pain measurements were collected almost 10 years ago.
January 19, 2026 at 9:04 AM
5) The authors suspect that ME/CFS and fibromyalgia might cause something similar, so that natural opioids and pain relief no longer work that well. They tested this in 28 patients and 26 controls whose DNA and pain measurements were collected almost 10 years ago.
4) In chronic overuse of opioids, there's a downregulation of these opioid receptors and researchers see increased methylation in the region where the OPRM1 gene is located. This might explain why people become desensitised to opioids.
January 19, 2026 at 9:04 AM
4) In chronic overuse of opioids, there's a downregulation of these opioid receptors and researchers see increased methylation in the region where the OPRM1 gene is located. This might explain why people become desensitised to opioids.
3) In the current study, Andrea Polli and his colleagues looked at OPRM1, the gene that provides instructions for building µ-opioid receptors. These are the receptors for both your body’s natural painkillers (endorphins) and prescription painkillers (like morphine).
January 19, 2026 at 9:04 AM
3) In the current study, Andrea Polli and his colleagues looked at OPRM1, the gene that provides instructions for building µ-opioid receptors. These are the receptors for both your body’s natural painkillers (endorphins) and prescription painkillers (like morphine).
2) This paper focuses on epigenetics: how our genes are switched on or off. This is done by adding methyl groups to specific pieces of DNA, making it less likely that a gene will be expressed.
The genetic code remains exactly the same but it becomes harder to acces and read.
The genetic code remains exactly the same but it becomes harder to acces and read.
January 19, 2026 at 9:03 AM
2) This paper focuses on epigenetics: how our genes are switched on or off. This is done by adding methyl groups to specific pieces of DNA, making it less likely that a gene will be expressed.
The genetic code remains exactly the same but it becomes harder to acces and read.
The genetic code remains exactly the same but it becomes harder to acces and read.
7) More background about the call can be found in this document on Cluster 1 - Health, page 69:
ec.europa.eu/info/fu...
ec.europa.eu/info/fu...
January 18, 2026 at 8:30 AM
7) More background about the call can be found in this document on Cluster 1 - Health, page 69:
ec.europa.eu/info/fu...
ec.europa.eu/info/fu...
6) Proposals should come from an international team with at least 3 partner organisations from 3 different EU or associated countries. More info:
rea.ec.europa.eu/hor...
The United Kingdom, Norway and Switzerland are among the associated countries.
ec.europa.eu/info/fu...
rea.ec.europa.eu/hor...
The United Kingdom, Norway and Switzerland are among the associated countries.
ec.europa.eu/info/fu...
Horizon Europe – Who should apply
Who should apply
rea.ec.europa.eu
January 18, 2026 at 8:30 AM
6) Proposals should come from an international team with at least 3 partner organisations from 3 different EU or associated countries. More info:
rea.ec.europa.eu/hor...
The United Kingdom, Norway and Switzerland are among the associated countries.
ec.europa.eu/info/fu...
rea.ec.europa.eu/hor...
The United Kingdom, Norway and Switzerland are among the associated countries.
ec.europa.eu/info/fu...
5) The call has a total budget of 39.3 million euros and aims to fund approximately 5 projects with 6-8 million each.
These Horizon Europe calls have a low chance of success but given that the scope fits ME/CFS research quite well, it seems worth submitting an application.
These Horizon Europe calls have a low chance of success but given that the scope fits ME/CFS research quite well, it seems worth submitting an application.
January 18, 2026 at 8:30 AM
5) The call has a total budget of 39.3 million euros and aims to fund approximately 5 projects with 6-8 million each.
These Horizon Europe calls have a low chance of success but given that the scope fits ME/CFS research quite well, it seems worth submitting an application.
These Horizon Europe calls have a low chance of success but given that the scope fits ME/CFS research quite well, it seems worth submitting an application.