It’s Not “All in Your Head”: Scientists Develop Revolutionary Blood Test for Chronic Fatigue Syndrome

A 96% accurate blood test for ME/CFS could transform diagnosis and pave the way for future long COVID detection.

Researchers from the University of East Anglia and Oxford Biodynamics have created a highly accurate blood test capable of diagnosing Chronic Fatigue Syndrome, also known as Myalgic Encephalomyelitis (ME/CFS).

This long-term and debilitating condition affects millions of people around the world, including more than 400,000 in the UK, yet it remains poorly understood and has lacked reliable diagnostic methods for decades.

Achieving an accuracy rate of 96 percent, the new test provides renewed hope for patients who have often faced years of uncertainty, misdiagnosis, or dismissal of their symptoms.

And it is hoped that the breakthrough could pave the way for a similar blood test to diagnose Long COVID.

Lead researcher Prof Dmitry Pshezhetskiy, from UEA's Norwich Medical School, said: "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."

How the discovery was made

The researchers used Oxford BioDynamics' advanced EpiSwitch® 3D Genomics technology (AIM:OBD) to examine how DNA folds within blood samples collected from 47 individuals with severe ME/CFS and 61 healthy participants.

Inside each human cell lies about two meters of DNA, intricately packed and folded in three dimensions. These folds are not random; rather, millions of them are precisely arranged to create a regulatory code that controls when genes are switched on or off, ensuring normal cellular function.

OBD Chief Scientific Officer, Alexandre Akoulitchev, 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 knowledge base, 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."

DNA folding patterns reveal key disease markers

This approach using EpiSwitch has previously shown success in identifying disease-specific blood markers in highly complex inflammatory and neurological conditions such as fast ALS (amyotrophic lateral sclerosis), rheumatoid arthritis, and certain cancers. This includes the EpiSwitch PSE test, which is a blood test with world-leading accuracy for prostate cancer already used in the UK and US.

The team discovered a unique pattern that appears consistently in people with ME/CFS that is not seen in healthy people.

Using a different approach, this work looked beyond the linear DNA sequence investigated by a previously published DecodeME study, the largest genetic investigation of ME/CFS to date.

By examining 3D genomic folds, UEA and Oxford BioDynamics revealed hundreds of additional changes, including five of the eight sites identified by DecodeME, which can now provide a deeper understanding of the disease.

The analysis showed remarkable accuracy – with 92 percent sensitivity in identifying ME/CFS, which indicates how well the test identifies those who have the disease (a show of true positives) and 98 percent specificity, which indicates how well it identifies those who do not have the disease.

The researchers also found signs of immune system and inflammation pathways involved in the disease, which may help guide future treatments and identify patients more likely to respond to specific therapies.

A vital tool for diagnosis and treatment

"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."

Reference: "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" by Ewan Hunter, Heba Alshaker, Oliver Bundock, Cicely Weston, Shekinah Bautista, Abel Gebregzabhar, Anya Virdi, Joseph Croxford, Ann Dring, Ryan Powell, Dominik Vugrinec, Caroline Kingdon, Carol Wilson, Sarah Dowrick, Jayne Green, Alexandre Akoulitchev and Dmitri Pchejetski, 8 October 2025, Journal of Translational Medicine.
DOI: 10.1186/s12967-025-07203-w