Breakthrough blood test finally confirms Chronic Fatigue Syndrome

The condition, which causes long-term and often debilitating exhaustion, affects millions of people around the world, including more than 400,000 individuals in the UK. Despite its prevalence, ME/CFS has remained poorly understood and notoriously difficult to diagnose.

This new test, which demonstrates 96 percent accuracy, offers renewed hope to patients who have struggled for recognition and reliable answers. Researchers believe the discovery could also lead to a similar test for identifying long Covid.

Validating an Illness Long Dismissed

Lead researcher Prof Dmitry Pshezhetskiy of UEA's Norwich Medical School explained, "ME/CFS is a serious and often disabling illness characterized by extreme fatigue that is not relieved by rest.

"We know that some patients report being ignored or even told that their illness is 'all in their head'. With no definitive tests, many patients have gone undiagnosed or misdiagnosed for years.

"We wanted to see if we could develop a blood test to diagnose the condition -- and we did!

"Our discovery offers the potential for a simple, accurate blood test to help confirm a diagnosis, which could lead to earlier support and more effective management."

"Post-Covid syndrome, commonly referred to as long Covid, is one example of ME/CFS, where a similar cluster of symptoms is triggered by the Covid-19 virus, rather than by other known causes such as glandular fever. We therefore hope that our research will also help pave the way for a similar test to accurately diagnose long Covid."

Using DNA Folding to Detect Disease

To develop the test, researchers employed Oxford BioDynamics' advanced EpiSwitch® 3D Genomics technology, which examines how DNA is folded within cells. The study analyzed blood samples from 47 people with severe ME/CFS and compared them to 61 healthy volunteers.

Each human cell contains around two metres of DNA, intricately folded in three dimensions. These folds are not random; they form deliberate patterns that help control how genes are activated or silenced, keeping the body functioning properly.

Alexandre Akoulitchev, Chief Scientific Officer at Oxford BioDynamics, said, "Chronic Fatigue Syndrome is not a genetic disease you're born with. That's why using EpiSwitch 'epigenetic' markers -- which can change during a person's life, unlike fixed genetic code -- was key to reaching this high level of accuracy.

"The EpiSwitch platform behind this test, together with OBD's vast 3D Genomic knowledgebase, has already been proven to deliver practical, rapid blood diagnostics accessible at scale.

"With this breakthrough, we are proud to enable a first-in-class test that can address an unmet need for a quick and reliable diagnostic for a complex, challenging-to-identify illness."

Proven Technology Behind the Discovery

EpiSwitch technology has previously helped identify blood-based biomarkers for other complex conditions, including fast-progressing ALS (amyotrophic lateral sclerosis), rheumatoid arthritis, and several cancers. It also underpins the EpiSwitch PSE prostate cancer test, which delivers world-leading accuracy and is already in clinical use across the UK and US.

In the ME/CFS study, researchers found a distinctive genomic pattern present only in affected individuals and absent in healthy participants. This work looked beyond the linear DNA sequence explored in the large DecodeME study, which was the most extensive genetic investigation of ME/CFS to date.^[1]

By examining the 3D architecture of DNA, the UEA and Oxford BioDynamics team uncovered hundreds of additional biological differences, including five of the eight genetic regions previously identified by DecodeME. This deeper insight could advance scientific understanding of the illness.

Uncovering Biological Clues for Future Treatments

The new analysis demonstrated exceptional precision, achieving 92 percent sensitivity (correctly identifying those with ME/CFS) and 98 percent specificity (correctly identifying those without it).

Researchers also observed signs of immune system involvement and inflammation pathways, suggesting potential biological targets for future therapies. These findings may help determine which patients are most likely to benefit from specific treatments.

Toward More Accurate Diagnosis and Personalized Care

"This is a significant step forward," said UEA's Prof Pshezhetskiy. "For the first time, we have a simple blood test that can reliably identify ME/CFS -- potentially transforming how we diagnose and manage this complex disease."

"Additionally, understanding the biological pathways involved in ME/CFS opens the door to developing targeted treatments and identifying which patients might benefit most from specific therapies.

"We hope that the Episwitch® CFS test could become a vital tool in clinical settings, paving the way for more personalized and effective care."

Notes

1. Genetics Discovery Team, et al (2025). Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome. medRxiv, Preprint. https://doi.org/10.1101/2025.08.06.25333109

This research was led by UEA and Oxford BioDynamics in collaboration with The London School of Hygiene & Tropical Medicine and Royal Cornwall Hospitals NHS Trust.

'Development and validation of blood-based diagnostic biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) using EpiSwitch® 3-dimensional genomic regulatory immuno-genetic profiling' is published in the Journal of Translational Medicine.