1) 🩸 New paper by the team of Ronald Davis.

They found that red blood cells from ME/CFS patients are slower and less responsive to low oxygen levels in a lab device that mimics small blood vessels. 2) Previous studies suggested that red blood cells change their shape more easily when oxygen is low. That allows them to move faster through small blood vessels (capillaries) and deliver oxygen where it is needed.

1) Interesting experiment on fatiguability of arm muscles that might be useful as an objective test.

During repeated handgrip tasks, researchers found that "the neuromuscular system experienced changes earlier than the actual behavior" 2) The experiment used multiple fatigue measures during the task:

– EMG = tiny electrical signals in the forearm muscles
– EEG = brain waves at the scalp
– fMRI = brain activity through blood oxygenation levels
– contraction force of the muscle
– a subjective fatigue scale.

1) In a new preview video, Dr. Yarred Younger from the University of Alabama says he found evidence that ME/CFS patients have more microglia cell activation in their brains than healthy controls.

His theory is that chronic brain inflammation is driving symptoms in ME/CFS. 2) A short recap of the evidence:

In a 2014 paper researchers, Japanese researchers reported neuro-inflammation in ME/CFS using PET-scans.
pubmed.ncbi.nlm.nih.gov/24665088/

A Dutch 2022 paper, however, found no difference between patients and controls
pubmed.ncbi.nlm.nih.gov/34815320/

1) In a new pre-print, the lab of Bhupesh Prusty reports that antibodies (IgG) from ME/CFS patients cause mitochondrial fragmentation in endothelial cells.

This was not seen in antibodies from MS patients or healthy controls. 2) Their experiments were inspired by two studies finding ME/CFS and long COVID-like symptoms in mice after transferring IgG from patients.

One from the Dutch team of Eijkelkamp/Den Dunnen:
biorxiv.org/content/10.110…

And one from the US group of Iwasaki:
biorxiv.org/content/10.110…

1) Saw some skepticism about DecodeME, asking if it is overhyped.

As an account that focuses on dissecting and critically analyzing research (our name was 'ME/CFS Skeptic' for a reason!), we think it’s the real deal.

Here are a couple of reasons why it stands out. 🧵 2) First, there is the sample size: 15.000 participants dwarfs any other ME/CFS study in comparison. Try finding biomedical ME/CFS studies with more than 1000 participants: there are almost none...

1) The DecodeME study compared DNA of ca. 15,000 ME/CFS patients and 250,000 controls and found significant differences in 8 regions of our genome.

The Manhattan plot below shows the genes and chromosomes involved.

Let’s unpack the results 🧵 2) A first major finding is that the results for females and males were very similar.

This was a surprise, as some had expected the biological pathways behind ME/CFS to differ between males and females. Not so!

1) Spanish researchers exposed muscle cells to serum of ME/CFS and Long Covid patients and found:

- reduction in muscle contraction strength

- upregulation of genes involved in protein translation

- elevated oxygen consumption 2) It looks like the 'something in the blood' hypothesis is back on the table: serum of patients caused cellular stress that serum of healthy controls did not.

The sample size was really small though: serum of only 4 ME/CFS patients and 5 Long Covid patients was used.

1) Hilda Bastian wrote a new article on the Cochrane review for ME/CFS.

"There are many people who care about the harm this outdated review can do, and won’t let it go – myself included."

"Not retiring influential out-of-date reviews is a ticking time bomb." 2) She points out that this review one exercise therapy for ME/CFS is still frequently being cited and often misinterpreted as being up to date.

In reality, the evidence was last updated in May 2014.

1) In a large international sample of more than 2000 ME/CFS patients, researchers found that neurocognitive complaints consists of two factors:

- one involving classical memory and concentration symptoms

- the other involving sensory overload phenomena 2) The researchers did a factor analysis using the DePaulSymptom Questionnaire. 13 questions loaded into two factors.

The first factor explain 47% of common variance, the second (including sensitivity to light, noise and smells) only 7%.

1) This fact sheet is one of the best resources for explaining what post-exertional malaise (PEM) is.

The vague name ‘malaise’ isn’t very clear...

https://twitter.com/TomKindlon/status/1950609412852183304

2) Core aspects of PEM are:

- Symptoms get much worse (new symptoms may appear)

- Severity is out of proportion to the exertion trigger

- Loss of functional capacity

- Onset of PEM is often delayed

- Prolonged recovery

1) Had a closer look at the BioMapAI paper in Nature Medicine that is getting a lot of media coverage.

The research group of Derya Unutmaz (@DeryaTR_) and Julia Oh at The Jackson Laboratory created an impressive rich dataset and analyzed it using a deep neural network. @DeryaTR_ 2) They tracked 153 ME/CFS patients and 96 age- and gender-matched controls over a period of 4 years.

The dataset includes:

- 48 standard blood parameters
- mass spectrometry of 958 metabolites in plasma
- immune cell profiling
- gut metagenomics of stool samples

1) An impressive dataset on ME/CFS was just published by the research team of Ian Lipkin.

They tested multiple proteins and metabolites in 56 ME/CFS patients and 51 controls before and after exercise and cytokines in response to mimics of viral, bacterial, and yeast infection. 2) Let's start with the cytokine response. The researchers measured this after exposure to antigens that mimic:

- a fungal infection (HKCA)
- a bacterial infection (LPS)
- a viral infection (poly I:C)
- superantigens (SEB) which triggers a nonspecific T-cell response

1) The Dutch research agency ZonMw announced a list of new Long Covid studies that will receive funding. The total budget was approximately €6 million.

There are some interesting projects that will also be relevant to #MECFS. 2) A study led by dr. Rob Wüst from Amsterdam University will study immune cell infiltration on muscle tissue and mast cell activation during post-exertional malaise. Focus is on how immune cells affect muscle recovery.

1) The Canadian research group of Alain Moreau published a big study on Sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B) as a potential biomarker for ME/CFS.

Unfortunately, it seems that the results could simply be due to sex differences and contraception use... 2) As a recap, here are their main findings.

Figure 2.A shows that SMPDL3B levels in plasma were significantly elevated in the Canadian ME cohort of 249 patients compared to 63 healthy controls.

1) A research team at the University of Surrey are studying the electrical properties of white blood cells in ME/CFS.

They reported that after salt treatment, these proporties change differently in ME/CFS donors compared to healthy controls and patients with multiple sclerosis. 2) This research followed up on the famous nanoneedle findings. In 2019, the team of Ron Davis found spectacular differences between ME/CFS patients and controls in the electrical impedance of white bloods cells. The effect was clearest after 1.5 hours.

1) Finally had a look at the new trial of Rapamycin, an FDA-approved drug that is used an immunosuppressant to prevent organ rejection.

86 ME/CFS patients were included in a pilot trial and received a low dose of rapamycin of 6 mg once per week. 2) How did the Simmaron Researchers came to Rapamycin?

They first found that ME/CFS subjects had elevated levels of the early autophagy protein ATG13 and that these were heavily phosphorylated.

1) A new Norwegian study tested more than 6000 proteins in the serum using aptamers (small pieces of DNA or RNA that can bind with specific targets such as proteins).

751 proteins showed a significant difference between ME/CFS patients and controls. 2) This aptamer method has been tried before in two ME/CFS studies but these had small sample size of 20 patients or less.

This Norwegian study had 54 ME/CFS patients who were recruited from the Rituximab and Cyclophosphamide trials.

1) A fascinating new hypothesis on ME/CFS by prof. Emeritus Jonathan Edwards and colleagues.

Well worth a read as it provides some fundamental thinking about what we know about ME/CFS and what might explain the syndrome. 2) Age profile: Edwards et al. note that the incidence of ME/CFS rises steeply in teenage years. Onset rarely occurs under the age of 10.

This steep early rise reminds them of seronegative spondyloarthropathies (likely T cell-mediated) and systemic lupus (autoantibody-mediated).

1) This new paper by Van Campen & Visser shows an impressive separation between two groups of ME/CFS patients with POTS. 2) Cardiac output and cerebral blood flow (CBF) were measured using doppler flow velocity during a tilt test.

The biggest group (2/3rds of patients) had moderate heart rate increases but showed a strong relation between CBF reduction and the reduction in cardiac output.

1) One of the most interesting ME/CFS studies of 2025 this far, from the research teams of Hanson (Cornell) and Snyder (Stanford). 👇

A neural network on rare genetic variants, found 115 ME/CFS risk genes. 2) The authors used 3 cohorts in this study: one from Stanford, one from the UK ME/CFS biobank (CureME) and one from Cornell.

The first two were used as discovery cohort (247 ME/CFS cases, 192 controls), the latter as testing cohort (36 cases, 21 controls).

1) Another interesting study Gemma Samms and Chris Ponting.

They looked closely at data on ME/CFS in the UK biobank and found that some of these may not be very reliable. 2) Take for example self-reported diagnoses. Participants to the biobank could report serious illnesses in a verbal interview with ‘chronic fatigue syndrome’ as one of the recorded options.