As more research emerges about long COVID, some experts are noticing that its trigger factors, symptoms, and causative mechanisms overlap with myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS).
By Annie Lennon
Extracts
ME/CFS is characterised by severe fatigue that does not improve with rest, in addition to pain and cognitive problems. One in four patients are bed- or house-bound with severe forms of the condition, sometimes experiencing atypical seizures, and speech and swallowing difficulties.
Despite affecting around 250,000 people in the UK and around 2 million people in the European Union (EU), it is a relatively poorly funded disease research area. Increased research into long COVID is thus providing a much-needed boost to ME/CFS research.
What we already know about the possible causation of ME/CFS is helping research into the causes of long COVID. At the same time, research into long COVID is opening up new avenues of research that may also be relevant to ME/CFS. It is becoming a two-way process.
Dr Charles Shepherd, Honorary Medical Adviser to the ME Association, told Medscape News UK.
He continues: While funding remains an issue, promising research is currently underway in the UK to improve diagnosis, treatment, and understanding of the pathology of ME/CFS.
Viral Reactivation
Dr David Newton is research director at ME Research UK. “Viral infection is commonly reported as a trigger for [ME/CFS, meaning that the disease] may be caused by reactivation of latent viruses, including human herpes viruses and enteroviruses,” he said.
Herpes viruses can lie dormant in their host’s immune system for long periods of time. They can be reactivated by factors including infections, stress, and a weakened immune system, and may cause temporary symptoms or persistent disease.
A 2021 pilot study found that people with ME/CFS have a higher concentration of human herpesvirus 6B (HHV-6B) DNA in their saliva, and that concentration correlates with symptom severity. HHV-6B is a common virus typically contracted during infancy and childhood.
A continuation of this research is now underway at Brunel University to improve understanding of HHV-6B’s role in the onset and progression of ME/CFS, and to support the development of diagnostic and prognostic markers, as well as therapeutics such as antiviral therapies.
Mitochondrial Dysfunction
Shepherd explained that there is now sound evidence demonstrating that biochemical abnormalities in ME/CFS affect how mitochondria produce energy after physical exertion. Research is thus underway to see if treating mitochondrial dysfunction improves ME/CFS symptoms.
A phase 2a placebo-controlled clinical trial from 2023 found that AXA1125, a drug that works by modulating energy metabolism, significantly improved symptoms of fatigue in patients with fatigue-dominant long COVID, although it did not improve mitochondrial respiration.
[The findings suggest] that improving mitochondrial health may be one way to restore normal functioning among people with long COVID, and by extension CFS.
Study Author Betty Raman, associate professor of cardiovascular medicine at the University of Oxford
Gut Dysbiosis
Many studies have found that people with ME/CFS have altered gut microbiota, which suggests that changes in gut bacteria may contribute to the condition. Researchers at the Quadram Institute will thus conduct a clinical trial called RESTORE-ME to see whether faecal microbiota transplants (FMT) can treat the condition.
Our FMT studies, if effective, could provide a longer lasting or even permanent relief of ME/CFS, as restoring the gut microbial composition wouldn’t require continuous medication.
Rik Haagmans, research scientist and PhD candidate at the Quadram Institute.
Biobank and Biomarkers
Europe’s first ME/CFS-specific biobank is in the UK and is called UKMEB. It now has more than 30,000 blood samples from patients with ME/CFS, multiple sclerosis, and healthy controls. Uniquely, it includes samples from people with ME/CFS who are house- and bed-bound.
Caroline Kingdon, RN, MSc, a research fellow and biobank lead at the London School of Hygiene and Tropical Medicine (LSTHM), told Medscape News UK that samples and data from the UKMEB have been provided to research groups all over the world and have contributed to widely cited literature.
One group making use of these samples is led by Dr Fatima Labeed, senior lecturer in human biology at the University of Surrey. Labeed and her team are developing a diagnostic test for ME/CFS based on electrical properties in white blood cells.
To date, studies of ME/CFS have focused on the biochemical behaviour of cells: the amount and type of proteins that cells use. We have taken a different approach, studying the electrical properties.
Dr Fatima Labeed, senior lecturer in human biology at the University of Surrey.
Genetic Test
Another promising avenue for diagnostics comes from a research team at the University of Edinburgh led by Professor Chris Ponting at the university’s Institute of Genetics and Cancer. They are currently working on DecodeMe, a large genetic study of ME using data from more than 26,000 people.
We are studying blood-based biomarkers that distinguish people with ME from population controls. We’ve found a large number – including some found previously in other studies – and are writing these results up for publication.
Decode ME research team at the University of Edinburgh led by Professor Chris Ponting
The Future
In 2022, the UK government announced its intention to develop a cross-government interim delivery plan on ME/CFS for England, however publication of the final plan has been delayed numerous times.
Shepherd agreed that increased funding is crucial for progress to be made. He said the biggest help to ME/CFS research would be to end the disparity in government research funding for the disease, and match what is given for many other disabling long-term conditions.
It's not fair to continue to rely on the charity sector to fund almost all of the biomedical research into ME/CFS here in the UK.
Dr Charles Shepherd, Honorary Medical Adviser to the ME Association
Dr Charles Shepherd,
Trustee and Hon. Medical Adviser to the ME Association.
Member of the 2018-2021 NICE Guideline Committee.
Member of the 2002 Independent Working Group on ME/CFS.
