8 ) Link to the (open-access) paper: Jothi et al. Long COVID and chronic fatigue syndrome/myalgic encephalitis share similar pathophysiologic mechanisms of exercise limitation.
In-depth analysis of research on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Formerly known as ME/CFS Skeptic. https://mecfsscience.org/
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8 ) Link to the (open-access) paper: Jothi et al. Long COVID and chronic fatigue syndrome/myalgic encephalitis share similar pathophysiologic mechanisms of exercise limitation.
7) Caveats are that this was a small study (15 PASC patients, 11 ME/CFS patients, and 11 controls). And some of the control data seem to be taken from another study.
6) Results were similar to the preload failure that David Systrom's group reported. The authors found a reduced cardiac index relative to controls and "in keeping with the lack of a rise in right atrial pressure with exercise, this may be considered 'preload insufficiency'”
5) Instead, the authors suspect that the results point to an "abnormal peripheral neuromuscular response" to exercise. Five out of six patients tested had findings consistent with small fiber neuropathy.
4) The researchers don't think it's just deconditioning: "While deconditioning can reduce cardiac output, the dysautonomia and preload insufficiency observed in PASC and CFS/ME appear mechanistically distinct."
3) The authors note that cardiac filling pressures or pulmonary artery pressure were normal, indicating that heart failure is an unlikely cause. Standard hemodynamics parameters at rest were also similar between patients and controls.
2) The authors used O2 pathway analysis, which breaks down oxygen transport into independent parameters. In ME/CFS and Long Covid patients, the problem seems to lie in the DM parameter, which stands for muscle diffusion capacity (moving oxygen from blood to muscle cells).
1) A research team from Arizona university used Invasive cardiopulmonary exercise testing (iCPET) in ME/CFS and Long Covid patients. They found that muscle oxygen diffusion was the most impaired parameter.
5) The full declaration and list of signees can be viewed on the website of the German ME/CFS Research Foundation:
4) The Declaration has been signed by leading experts such as Akiko Iwasaki, Carmen Scheibenbogen, Ian Lipkin, Anthony Komaroff, Øystein Fluge, Lucinda Bateman, Leonard Jason, Chris P. Ponting, Karl Johan Tronstad and many others.
3) It also highlights the need for medical education about ME/CFS, patient partnership, a global expansion of clinical trials and the involvement of pharmaceutical and biotech companies.
2) The declaration states that "Governments, health ministries, and international bodies must designate ME/CFS and Long COVID as high-priority conditions for dedicated funding, comparable to other chronic diseases with similar or lower disease burden and prevalence."
1) On May 12 2025, a group of researchers signed an International Declaration stating that "there is a moral, medical, economic and scientific imperative to invest robustly in international and collaborative research into the pathophysiology of ME/CFS and Long COVID."
6) Link to the Canadian study (open-access): Azimi et al. 2025. Circulating FGF-21 as a Disease-Modifying Factor Associated with Distinct Symptoms and Cognitive Profiles in Myalgic Encephalomyelitis and Fibromyalgia
5) FGF-21 is a metabolic stress hormone and increased levels have been found in conditions such as obesity, mitochondrial myopathies, and type 2 diabetes. Perhaps it's a subtle signal that points to an underlying metabolic issue or a compensation mechanism in ME/CFS.
4) In a later publication (Hoel et al. 2025) it seemed that the Norwegian group replicated these results in a larger sample of more than 200 patients from the Cure ME/CFS Biobank. Reference: www.medrxiv.org/cont...
6) Link to the Canadian study (open-access): Azimi et al. 2025. Circulating FGF-21 as a Disease-Modifying Factor Associated with Distinct Symptoms and Cognitive Profiles in Myalgic Encephalomyelitis and Fibromyalgia www.mdpi.com/1422-0067/26...
5) FGF-21 is a metabolic stress hormone and increased levels have been found in conditions such as obesity, mitochondrial myopathies, and type 2 diabetes. Perhaps it's a subtle signal that points to an underlying metabolic issue or a compensation mechanism in ME/CFS.
4) In a later publication (Hoel et al. 2025) it seemed that the Norwegian group replicated these results in a larger sample of more than 200 patients from the Cure ME/CFS Biobank. Reference: medrxiv.org/content/10.1...
3) But FGF-21 has been found to be increased before in ME/CFS, most notably by the Norwegian group (Hoel et al. 2021). They speculated that this might reflect a metabolic compensation mechanism in response to tissue hypoxia. Reference: pubmed.ncbi.nlm.nih....
2) Here's the data from the new Canadian study. There were 49 patients with fibromyalgia (FM), 99 with ME/CFS, 104 with both ME/CFS and FM, and 54 healthy controls. As you can see, the difference is not large with lots of overlap between groups.
1) A new paper found slight increase of Fibroblast growth factor 21 (FGF-21) in ME/CFS patients compare to controls. FGF-21 is a hormone-like protein that helps to regulate metabolism and has been found to be increased in previous ME/CFS studies.
Thanks!
10) Link to the (open-access) study: Moezzi et al. Haptoglobin phenotypes and structural variants associate with post-exertional malaise and cognitive dysfunction in myalgic encephalomyelitis.
9) Caveats are that this was an exploratory study where most proteins didn't show a significant difference, while the Hp changes weren't based on direct comparison with controls. In ME/CFS patients, the corrected p-value for the change in Hp was barely significant (q = 0.04).
8 ) The authors wonder if their results are related to reported vascular and hematological abnormalities in ME/CFS, such as impaired red blood cell deformability.
7) Lastly, the authors report that Soluble Plasma LRP-1 (sLRP-1), a receptor that helps to clear a wide range of molecules from circulation, was increased in ME/CFS versus controls, especially in those with the Hp2-1 phenotype.
6) The authors found that the Hp2-2 and Hp2-1 phenotypes had more Hp tetramer and pentamer forms, which correlated with PEM severity and declines in cognitive performance.
5) Next, they found differences in the phenotype distribution of the haptoglobin gene. Fewer ME/CFS patients had the Hp1-1 phenotype compared to controls (ca. 10% versus 20%). HP-1 is considered the more efficient form of haptoglobin at binding free hemoglobin.
4) They then tested Hp levels and found that these were lower in the most severely affected subgroup and that lower plasma Hp levels at baseline were associated with greater cognitive dysfunction.
3) Few proteins were significantly changed after the cuff test, but Haptoglobin stood out. It was decreased in ME/CFS patients after the cuff test (1.84-fold change, p = 0.007), but not in healthy controls.
2) To trigger post-exertional malaise (PEM), the authors didn't use an exercise test but an inflatable cuff that gives pulsatile compressions to the patient's forearm. (we have some doubts if this really triggers PEM).
1) 🇨🇦 In a new ME/CFS study, the research team of Alain Moreau reports that haptoglobin (Hp) might be a potential biomarker of PEM severity and cognitive impairment. Its main function is to bind free hemoglobin that is released after the breakdown of red blood cells.
Thanks not sure what went wrong. Noticed it too late, so keeping both up.
Not that I know of but I suspect the biobanks will recruit patients from multiple locations, possibly also Maastricht. You can register for the NMCB here: nmcb.eu/doe-mee/
10) The announcement with an overview of all the projects can be found here:
9) All of the projects are linked to either the Lifelines cohort or the Dutch ME/CFS Cohort and Biobank consortium (NMCB) or both. The budget for projects isn't provided but it was previously announced that this call would have a total budget of € 3,5 million.
10) The announcement with an overview of all the projects can be found here:
9) All of the projects are linked to either the Lifelines cohort or the Dutch ME/CFS Cohort and Biobank consortium (NMCB) or both. The budget for projects isn't provided but it was previously announced that this call would have a total budget of € 3,5 million.
8 ) The last project will study orthostatic intolerance (OI). It will use advanced brain scan techniques (MRI with Lower Body Negative Pressure) to investigate how reduced blood flow to the brain might explain OI.
7) The 6th project will look at the activity of viruses (B19, EBV, HCMV, HHV-6, HHV-7) in the gut and how this affects the composition of the microbiome. The researchers suspect this leads to deterioration of the gut barrier and inflammation. projecten.zonmw.nl/n...
6) The next project aims to replicate abnormalities found in muscle tissue but also looks at non-invasive techniques, such as MRI, MRS, and NIRS for assessing muscle structure, mitochondrial function, and oxygen uptake, and how these are related to PEM.
8 ) The last project will study orthostatic intolerance (OI). It will use advanced brain scan techniques (MRI with Lower Body Negative Pressure) to investigate how reduced blood flow to the brain might explain OI.
5) The fourth project focuses on the gut flora and will use the i-screen and InTESTine™ models. These allow them to study how bacteria react to e.g., probiotics and prebiotics, and how bacteria influence the intestinal wall.
4) In a third project, researchers from Tilburg University will compare brain imaging, blood tests, and the results of several short cognitive tests that measure thinking ability. It will compare how these different measures are related to each other.
3) A second project focuses on severe ME/CFS and will use a mobile laboratory to carry out examinations at patients' homes. The researchers will measure inflammatory cells and bioactive peptides with a special focus on the enzyme neprilysin.
7) The 6th project will look at the activity of viruses (B19, EBV, HCMV, HHV-6, HHV-7) in the gut and how this affects the composition of the microbiome. The researchers suspect this leads to deterioration of the gut barrier and inflammation. projecten.zonmw.nl/n...
2) The first project is led by Prof. Huitinga and will use single-nucleus RNA sequencing (snRNA-seq) to study changes in the brain. It will use tissue samples from the Dutch brain bank. It will also look at microglia, the immune cells within the brain.
6) The next project aims to replicate abnormalities found in muscle tissue but also looks at non-invasive techniques, such as MRI, MRS, and NIRS for assessing muscle structure, mitochondrial function, and oxygen uptake, and how these are related to PEM.
1) 7 new ME/CFS projects have received funding from the Dutch research agency ZonMw. All projects look high-quality and focus on different aspects such as the brain, muscle, microbiome, viruses, orthostatic intolerance, and the immune system. A brief overview 🧵
5) The fourth project focuses on the gut flora and will use the i-screen and InTESTine™ models. These allow them to study how bacteria react to e.g., probiotics and prebiotics, and how bacteria influence the intestinal wall.
4) In a third project, researchers from Tilburg University will compare brain imaging, blood tests, and the results of several short cognitive tests that measure thinking ability. It will compare how these different measures are related to each other.
3) A second project focuses on severe ME/CFS and will use a mobile laboratory to carry out examinations at patients' homes. The researchers will measure inflammatory cells and bioactive peptides with a special focus on the enzyme neprilysin.
2) The first project is led by Prof. Huitinga and will use single-nucleus RNA sequencing (snRNA-seq) to study changes in the brain. It will use tissue samples from the Dutch brain bank. It will also look at microglia, the immune cells within the brain.
1) 7 new ME/CFS projects have received funding from the Dutch research agency ZonMw. All projects look high-quality and focus on different aspects such as the brain, muscle, microbiome, viruses, orthostatic intolerance, and the immune system. A brief overview 🧵
Yes true, thanks.
Yes, but we prefer to use OI as referring to symptoms (needing to lie down, dizziness, symptoms worsen when sitting or standing upright, etc.) instead of mechanisms (POTS, NMH, etc). So with that interpretation, the direction CBF -> OI makes more sense.
It could mean that the orthostatic intolerance patients experience is (partly) due to a lack of blood flow to the brain.
7) The study was supported by the Open Medicine Foundation (@OpenMedF) Link to the paper (open-access): Christopoulos et al. Mapping cerebral blood flow in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and orthostatic intolerance...
6) Most of the studies compared patients to healthy controls. It would be good to have a replication study that uses other patient groups such as depression, rheumatoid arthritis or MS.
5) The Dutch studies by Van Campen and Visser that stand out by their enormous sample size (we suspect that the samples from their studies overlap). They used extracarnial Doppler ultrasound, which focuses on the arteries in the neck rather than the head itself.
4) The studies also used different measurement techniques, which made it difficult to conduct a meta-analysis. While ME/CFS studies mostly used varioius MRI and SPECT scans, studies on OI mainly used transcranial Doppler ultrasound.
3) Below is a graph that we made ourselves using the 26 studies on ME/CFS alone. The number of ME/CFS participants was < 50 in all but three: an old SPECT study from 1992 (Ichise et al.) and then the two big studies by Van Campen and Visser.
2) There were a lot more ME/CFS studies that measured CBF than we expected: 26 on ME/CFS alone and 11 in both ME/CFS and OI. Unfortunately, the sample sizes were quite small.
1) 🇦🇺 The Australian research group of Christopher Armstrong just published a review on cerebral blood flow (CBF) in ME/CFS and orthostatic intolerance. About half of the ME/CFS studies reported a significant CBF decrease.
5) This review found that "OLFM4 expression is upregulated in many viral and bacterial infections, as well as in malaria. OLFM4 appears to play an important role in regulating host innate immunity against bacterial infection." academic.oup.com/ofi...
4) The DecodeME graph below shows that OLFM4 is the only protein-coding gene in the region on chromosome 13 that was associated with post-infectious ME/CFS.
3) Interestingly, OLFM4 isn't an inflammatory protein. It reduces the antibacterial and inflammatory responses of neutrophils. It does so by binding to the neutrophils cationic proteins and neutralizing their ability to kill bacteria and form immunogenic complexes with DNA.
2) OLFM4 is expressed in gut epithelial cells and is stored in the granules of neutrophils, the most common type of white blood cells. These granules are like storage spaces that contain enzymes, and antimicrobial molecules that neutrophils release during infection.
1) Suppose this isn't a coincidence: - Olfactomedin 4 (OLFM4) Is a Biomarker for the severity of infectious diseases. - OLFM4 is also one of the few DecodeME hits for patients with an infectious onset.
6) The presentation is from the International ME/CFS Conference 2025 and can be viewed here:
5) Lastly, the researchers are exploring three treatment: - immune adsorption: taking out the antibodies - Sonlicromanol: a drug that boost mitochondrial activity - An inhibitor of the enzyme IDO-2, which seems activated in LC
4) They also found antibodies in Long Covid patients that they don’t see in healthy controls, so they are working on a diagnostic test: a Luminex panel of a set of Long-COVID specific autoantibodies.
3) They are exploring a connection with their autoantibody results and the muscle abnormalities and necrosis that the team of Rob Wust found in Long Covid patients.
2) This comes from the research group of Jeroen Den Dunnen, whose preprint showed that transfer of antibodies (IgG) from Long COVID patients induces symptoms in mice. Similar findings were reported by the group of Iwasaki and a Belgian team from Namur.
1) Very preliminary data but Dutch researchers report that antibodies of Long Covid patients caused more cultured muscles cells to die.
9) Here's the link to the study (open-access): Azcue et al. Plasma Neurofilament Light Chain: A Potential Biomarker for Neurological Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
8) Thought this was interesting, as the genetic evidence found in DecodeME mostly points to the brain. Perhaps this could be further tested using samples from the Cure ME biobank (@mecfsbiobank), which offers samples from ME/CFS patients and MS controls.
7) Increased neurofilament light chain has also been reported in Long Covid and Fibromyalgia. References: www.nature.com/artic... onlinelibrary.wiley....
6) The NfL levels of ME/CFS patients also correlated with performances on cognitive tests, while this was not (or much less) the case in controls.
5) The authors highlight that this evidence "does not support categorizing ME/CFS as a degenerative disease." But the slight increase suggests that there is increased neuroaxonal damage in ME/CFS, from perhaps a more subtle brain pathology.
4) The graph below shows the main findings in picograms per milliliter (pg/mL). The difference isn't large. Only 7.5% of patients had levels above 20 pg/mL, which is seen as pathological.
3) NfL is usually measured in the cerebrospinal fluid, but newer methods, such as the chemiluminescence analyzer used here, can pick up on small amounts in the blood as well.
2) Neurofilament light chain (NfL) is a structural protein that is part of the cytoskeleton of neurons. When neurons are damaged, NfL is released and ends up in the cerebrospinal fluid and blood plasma. It's increased in neurological disorders such as Alzheimer's or MS.
1) Re-reading this Spanish paper from last year. It found slightly increased levels of neurofilament light chain (a marker of neural damage) in ME/CFS patients compared to controls.
If you'd like to support the researchers behind #DecodeME with other projects eg #SequenceME www.clinicalresearchnewsonline.com/cln/pressrel..., here's donation link www.decodeme.org.uk/support-us/ Alternatively donate directly to Prof Ponting's #MECFS research donate.ed.ac.uk/support/ME-C... #CFS
8) There's more info about this research in the talk by group leader Rob Wüst: www.youtube.com/watc... Big thanks to Zaphereus and Anil for highlighting these findings to us.
7) The presentation by Ph.D researcher Anouk Slaghekke can be viewed on the website of the ME Research Foundation (@MECFSResearch). events.mecfs-researc... Her poster presentation is available here: mecfs-research.org/w...
6) There was not a lot of overlap between patients and controls on these markers, so the researchers are exploring if they have potential as a biomarker or diagnostic test. They are looking for validation cohorts from other groups to see if they see similar things there.
5) Using electron microscopy the researchers could zoom in even further. This confirmed basement membrane thickening as well as membrane reduplications and signs of endothelial activation. The endothelial cells were full of vesicles, excreting things into the circulation.
4) They also found that the lumen space (the open space inside a blood vessel where blood actually flows) was reduced. This may affect the perfusion of oxygen and nutrients to the muscle site.
3) The Dutch researchers found that the basement membrane was thicker in patients. This is the supportive layer of proteins around the capillaries. It consists of proteins such as Collagen IV. Too much of it can stiffen the capillary walls.
2) They zoomed in on the muscle capillaries, the tiny blood vessels that are so small that red blood cells need to move through them one by one.
1) Interesting presentation by Anouk Slaghekke at the 2025 Berlin conference. This Dutch team found that small blood vessels of patients with ME/CFS and Long Covid are clocked up with Collagen IV.
5) Link to the announcement: ME Research UK (MERUK). Investigating the genetic and cellular clues to understand why ME/CFS affects more women than men.
4) Dr Manousaki states that: “Understanding the molecular differences in how ME/CFS affects men and women could be key to unlocking its underlying biology."
3) Dr Manousaki’s research will test the idea that, in ME/CFS, X chromosome inactivation is not being maintained correctly. This could lead to abnormal levels of X-linked genes, which may increase susceptibility to ME/CFS.
2) Females have two X chromosomes, while males only have one. To avoid that the two do a double job and activate too much of the same genes, one of the female X chromosomes is inactivated.
1) In a new genetics project supported by @MEResearchUK, Dr Alkisti Manousaki from the University of Leicester will study X chromosome inactivation in ME/CFS. This could help clarify why females are approximately 4 times more likely to develop ME/CFS than males.
8) One limitation is that diagnoses were self-reported. Link to the paper: Buchner et al. 2025. "Have you considered that it could be burnout?" —psychologization and stigmatization of self-reported long COVID or post-COVID-19 vaccination syndrome