1) The Australian team of Christopher Armstrong wrote a paper on how Metformin might be useful as a treatment for ME/CFS and Long Covid.

They focus on the multiple pathways it impacts such as mTOR signalling. 2) Metformin is mostly known as a drug for type 2 diabetes as it lowers sugar levels in the blood.

In the 1950s, however, it was also used to treat Influenza because of its assumed anti-inflammatory properties.

1) Interesting interview of Prof. Ian Lipkin by David Tuller (@davidtuller1).

They not only talk about Lipkin's recent study showing heightened innate immunity in ME/CFS but also about past and future studies.

A brief summary 🧵 @davidtuller1 2) Lipkin explained that in the 1990s, his team looked at whether Bornavirus might be the cause of ME/CFS. They found no evidence of that, but they did see immune activation (nonspecific polyclonal B-cell activation) in a majority of patients.

1) ME Research UK and the ME Association are funding more research on the electrical abnormalities found in blood cells of ME/CFS patients.

This builds on the work on the nanoneedle by Ron Davis and his team in 2019. 2) Funding goes to Dr Fatima Labeed (United Arab Emirates University), who authored the initial research, and Dr Jacqueline Cliff, who will host the work in her laboratory at Brunel University of London.

1) 🇳🇴 A new Norwegian study reports that ME/CFS patients have different DNA variants of killer cell immunoglobulin-like receptors (KIR) compared to controls.

According to the authors, this points to the involvement of natural killer cells in ME/CFS. 2) Natural Killer (NK) cells are a type of immune cell and have been implicated in ME/CFS for more than 30 years. The most consistent finding is reduced cytotoxicity of NK cells; their ability to destroy other cells.

Here's a recent review about this:
frontiersin.org/journals/immun…

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. 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) 🇨🇦 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. 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) 🇦🇺 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. 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) 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. 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) Very preliminary data but Dutch researchers report that antibodies of Long Covid patients caused more cultured muscles cells to die. 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) 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. 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) 🩸 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