For decades, [ME/CFS] was considered a women’s condition, and patients were told it was in their heads. Now research leaves no doubt: ME/CFS is a disease with clear biological hallmarks.
STAT News, by Isabella Cueto, 21 February 2024.
Extracts
A new, detailed study from the National Institutes of Health takes the most rigorous look yet inside the bodies of patients with the condition. The 70-page manuscript, published in Nature Communications on Wednesday, took almost eight years and over $8 million to complete. It has more than 70 authors from 15 of the 27 NIH institutes.
For a disease that just decades ago was relegated to a dusty corner of science — and reduced to an issue women made up — the paper is a milestone, albeit one based on a small sample of patients. Using many different analyses, researchers confirmed that there are clear biological markers of illness. Namely, there’s a protracted immune response that exhausts T cells. No matter how much the body tries to fight whatever bug is in its system, it can’t win.
This inflammation is what makes people feel like they’re constantly battling a flu, researchers say. ME/CFS patients also had abnormal functioning in a part of their brain that governs effort. “When they are asked to exert themselves, it doesn’t light up as much,” said Anthony Komaroff, a professor of medicine at Harvard Medical School and Brigham and Women’s Hospital. “It’s like trying to swim against a current.”
Such changes in the brain make it so ME/CFS patients have a different tolerance for physical and mental exertion, and a different perception of fatigue. Every decision is made knowing that, if a sick person pushes their body too far, it takes them longer to recover.
“That is not something that a person can wish on themselves or imagine that they have. It’s there. It’s real,” said Komaroff, who helped screen participants for ME/CFS but said he was otherwise not involved in the study. He has researched ME/CFS since the 1980s, when very little was known about these patients.
Other researchers in the field told STAT they also found some of the findings compelling, with the caveat that just 17 ME/CFS patients were included.
“This is really a tour de force,” said Mady Hornig, a physician-scientist who has studied ME/CFS and was not involved in the research. “There are clues that I think are really worthy of pursuit.”
Findings about the effect of ME/CFS on the autonomic nervous system, which controls unconscious processes, could be further probed to see what link it might have to the immune system, Hornig said. And more study is needed on connections to the gut microbiome, she said, which in its mysterious diversity helps shape the immune system and could factor into disease progression. (Hornig has long Covid and is a patient representative in the NIH’s RECOVER study, and she contributes to study manuscripts in that role.)
Because of the low headcount, some things could’ve been missed. Any similarities to people with long Covid, for example, will need to be studied separately. “We need to know at the molecular and biochemical level, how similar are pre-pandemic ME/CFS patients to people with long Covid? We don’t know that. There’s an assumption that they’re the same,” said Maureen Hanson, a professor and ME/CFS researcher at Cornell University who wasn’t involved in the study.
And certain suggestions in the paper come with a large grain of salt, including a theory that drugs used to help cancer patients’ bodies destroy tumor cells could also help people with ME/CFS finally beat their infections. The study didn’t point to any new therapeutic targets.
Most importantly, the work still doesn’t answer what is arguably the single most important question: What is causing ME/CFS, and how can it be treated?
Researchers in the field think certain people may have a genetic predisposition that makes it more difficult for their body to clear an infection, so that could play a part. But if the disease can crop up after many different kinds of bugs, then what is the antigen — the molecule, protein, or thing — that’s driving an unrelenting immune response for months to years afterward? And why do some people get better, like the few study participants who had a spontaneous recovery, while many others don’t?
“This is such an important paper and one I am so pleased to see come out,” said Prof Karl Morten, who researches ME/CFS at the John Radcliffe hospital, University of Oxford, and was not involved in the latest work. “We’ve had lots of little studies showing there might be a problem with this cell or that cell, but no one has really looked at everything in one patient before.”
The Guardian
More media stories
- Expert reaction to study of deep phenotyping of patients with post-infectious ME/CFS | Science Media Centre
- Brain Dysfunction, Immune Abnormalities Seen in Post-Infectious Chronic Fatigue | MedPageToday
- Study offers clues into chronic fatigue syndrome | Pulse
- Scientists find link between brain imbalance and chronic fatigue syndrome | The Guardian
- Study offers clues about the cause of chronic fatigue syndrome post infection | Independent
- Brain Dysfunction May Be at Root of Chronic Fatigue Syndrome | WebMD
- Sweeping chronic fatigue study brings clues but not clarity to mysterious syndrome | Science
- People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome May Have an “Exhausted” Immune System | Scientific American
- Study of patients with a chronic fatigue condition may offer clues to Long Covid | New York Times
- Study offers clues about the cause of chronic fatigue syndrome post infection | The Herald
- Study offers new clues into the causes of post-infectious chronic fatigue syndrome | Medical Xpress
- Is chronic fatigue syndrome all in your brain? | Harvard Health
- ME/CFS experts express dismay at aspects of NIH study | Medscape