Jennifer Caldwell was active and energetic, working two jobs and caring for her daughter and parents when she developed a bacterial infection that left her with severe light-headedness, fatigue and memory problems.
That was a decade ago, and since then she has struggled with a condition known as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, or ME/CFS. Ms. Caldwell, 56, of Hillsborough, N.C., said she likes to stay in bed most of the time between skiing, dancing and working two jobs as a clinical research coordinator and caterer.
“I haven’t been right since, and I haven’t worked a day,” said Miss Caldwell, whose symptoms include extreme dizziness when her legs are not elevated.
The situation “concerns me,” she said. “I can’t read and understand something, I can’t remember new things. It’s like being in a state of limbo. That’s how I describe it, lost in shock.”
Seven years ago, the National Institutes of Health began a study of ME/CFS patients, and Ms. Caldwell was one of 17 participants who underwent a series of tests and assessments of their blood, body and brain.
Findings from The studyThe study, published Wednesday in the journal Nature Communications, showed significant physiological differences in the immune system, cardiorespiratory function, gut microbiome and brain activity of ME/CFS patients compared to a group of 21 healthy study participants.
Clinicians said the study was a snapshot of a small number of patients, but it was important, in part because ME/CFS has long been dismissed or misdiagnosed. “It’s biological, not psychological,” said Dr. Avindra Nath, director of nervous system infections at the National Institute of Neurological Disorders and Stroke, who led the study.
The findings may have implications for patients with chronic covid, which often includes the same or similar symptoms as ME/CFS. Although the study participants were recruited before the outbreak, all had a pre-infectious form of ME/CFS, just as the virus was preceded by a coronavirus infection.
“Anything we learn from ME/CFS will benefit long-term Covid patients, and I think anything we learn from long-term Covid will benefit ME/CFS patients,” said Dr. Nath. (He never had Lyme disease; Mrs. Caldwell’s C. infection was the exception.)
Dr. Anthony Komaroff, a professor of medicine at Harvard Medical School, who was not involved in the research but served as a reviewer for the journal, said that immune system differences were among the most telling findings. “They found chronic activity of the immune system, as if the immune system was engaged in a long war against foreign microbes, a war that it could not completely win, and therefore had to continue fighting,” he said.
Dr. Nath said his thinking is that with long-term covid and post-infectious ME/CFS, “either you have bits and pieces of that pathogen driving this thing around” or “the pathogen is gone, but whatever it does, the immune system is re- It didn’t stop.
Another unique finding was that when the participants were asked to perform tasks that measured grip strength, the part of their brain involved in coordinating and directing actions showed a decrease in activity – while in healthy people, it showed an increase in activity.
That area of the brain, the right temporal-parietal junction, “tells the legs to move, to open the mouth and to eat — it says do something,” says Dr. Komarf. “If it’s not lit properly, it’s very difficult to get the body to make that effort,” the NIH researchers said.
Experts caution that the results of the small study may not reflect the experiences of many people with ME/CFS.
The disease can also occur in people who are not infected with the disease. And while ME/CFS is often characterized by severe energy depletion after physical or cognitive activity (a phenomenon known as post-exercise stress disorder), study participants had to be functional enough to undergo a high-risk assessment during their visit to the NIH in Maryland.
“They chose healthy patients,” said Dr. Carmen Schebanbogen, professor of immunology at the Institute of Medical Immunology at Charité Hospital in Berlin, who was not involved in the study. I think there are a lot of interesting findings, it’s just unfortunate because that was a large approach and they chose an underrepresented patient population.
Beth Polk, a research scientist at the Massachusetts Institute of Technology, said that four of the 17 patients recovered spontaneously in the years following their participation, which is “not typical of ME/CFS.”
Both she and Dr. Schiebenbogen noted that the study missed some of the medical signatures documented in other studies. For example, it was not found that patients did more poorly on cognitive tests or had neurological disorders.
“These are well-established diseases and they’re central to ME/CFS,” Ms. Pollack said, “so this doesn’t put it all together and it goes against some of what we know.”
According to Dr. Schebenbogen, the most important finding is that the condition is caused by a disorder of the immune system, and the researchers clearly stated that the physiological condition is “not a psychosomatic disease.”
Experts say the study, the NIH’s first detailed look at ME/CFS, should be considered just one step in understanding the condition, its severity and potential solutions. “We need to advance the field for medical research,” said Ms. Pollack.
For Ms. Caldwell, some aspects of being a research participant were boring. and a sense of security.
She says her main hope for the study is to encourage doctors and others to recognize ME/CFS and take it more seriously.
“We’re at a stage where we’re trying to understand, so this study is a big deal,” she says. She added: “For so long I’ve been hurt, dismissed, rejected, put down, so the validation is huge for me.”